Keywords: Malaria
Equatorial Guinea’s high-tech push to end malaria by 2030
35501Ronald Musoke, The Independent, 2026-03-10 09:39:41.
In the humid equatorial belt of Central Africa; where dense forests, heavy rains and winding rivers create ideal breeding grounds for mosquitoes, malaria has long been a stubborn public health adversary. For Equatorial Guinea, the disease has shaped health outcomes, economic prospects and daily life for decades. Now the small oil-rich nation is attempting something few countries in malaria-endemic regions have managed: complete elimination. Speaking during a virtual press briefing held on Feb. 26, hosted by the Addis Ababa-based Africa Centres for Disease Control and Prevention, Equatorial Guinea’s Minister of Health, Social Welfare and Health Infrastructure, Mitoha Ondo’o Ayekaba, laid out an ambitious national strategy known as Vision 2030. The goal is simple but formidable—eradicate malaria across the country within the next five years. The plan builds on two decades of progress on Bioko Island and introduces a new phase of intervention combining vaccines, advanced surveillance, cutting-edge vector control and emerging technologies such as genetically modified mosquitoes. “This is a historic transition from advanced malaria control to full national elimination,” Ayekaba said. But the path from control to eradication will test the limits of science, policy and community engagement.
Liverpool School of Tropical Medicine joins the Target Malaria Consortium
35499Dr. Tony Nolan, Target Malaria: News, 2026-03-10 09:34:21.
Target Malaria has so far been working on the three widespread vectors of the Anopheles gambiae species complex: An. coluzzii, An. gambiae, and An. arabiensis. As members of a species complex, these three species are morphologically indistinguishable. Together, they are among the most important malaria vectors in sub-Saharan Africa. Although they are distinct species, they can occasionally inter-breed. In addition, Anopheles funestus is a widespread vector across sub-Saharan Africa. It is more distantly related to the gambiae species complex and is not capable of hybridising with those species. An. funestus has distinct ecological characteristics and is a highly efficient vector of malaria – its species name, funestus, means “deadly”. In some areas, it is the dominant contributor to malaria transmission. Modelling indicates that achieving the full public health impact of gene drive will require trageting of An. funestus, as malaria transmission in many regions is shared between multiple vector species. Anopheles funestus is particularly challenging to colonise and maintain in the laboratory. Our team at the Liverpool School of Tropical Medicine was among the first to demonstrate stable genetic modification of An. funestus, establishing the technical foundation required to explore gene drive approaches in this species. Through joining Target Malaria, we will extend gene drive research beyond the gambiae complex and support the development of multi-species gene drive strategies for malaria control.
Compound effector genes suppress malaria parasite infections in gene-drive population modification strains of the African malaria mosquitoes, Anopheles gambiae and Anopheles coluzzii
35494Rebeca Carballar-Lejarazú, Yuemei Dong, Thai Binh Pham, et al., G3 Genes|Genomes|Genetics, 2026-03-09 10:43:52.
Malaria remains a major global health burden and is caused by protozoan parasites in the genus Plasmodium. Parasites are transmitted to humans during blood feeding by anopheline mosquitoes, and members of the Anopheles gambiae species complex are important vectors in sub-Saharan Africa. Gene-drive technologies offer promising options for disease control by enabling the spread of genetic traits through mosquito populations that block parasite transmission. We report here the development and characterization of four population modification gene-drive strains in Anopheles gambiae s.s. and An. coluzzii carrying compound effector genes. We sought to enhance the effectiveness of existing gene-drive strains to block Plasmodium transmission, thereby reducing vector competence and minimizing the opportunities for selection of resistant parasites. Two compound effector gene modules, TP24 and TP43, were introduced using Cas9 endonuclease and dual guide RNAs into TP13-based gene-drive strains to produce the An. gambiae AgTP24 and AgTP43 strains. The gene-drive cassettes were then introgressed into An. coluzzii to produce AcTP24 and AcTP43. Gene-drive dynamics, gene conversion, and inheritance were high in all strains, with 95% to 100% inheritance of the gene-drive constructs. Life table analyses showed mixed impacts on fitness dependent on the species and copy number (hemi- or homozygosity) of the gene-drive systems. The compound effector molecule gene complexes significantly reduced both parasite prevalence and infection intensities in An. gambiae and An. coluzzii following challenge assays with the human malaria parasite, P. falciparum. These findings highlight the potential of compound effector strategies in gene-drive systems to achieve durable malaria transmission control.
Evaluating paratransgenesis using engineered symbiotic bacteria for Plasmodium inhibition in mosquito vectors: A systematic review
35538Cleanclay WD, Kernyuy FB, Kintung IF, et al, PLoS Neglected Tropical Diseases, 2026-02-12 16:54:19.
Malaria is one of the key world health problems, especially in sub-Saharan Africa, where the rising resistance to insecticides and antimalarial drugs is posing a threat to the current control mechanisms. New strategies are urgently needed to break the cycle of the spread of Plasmodium parasites by the Anopheles mosquito. A potential solution is paratransgenesis, which involves the genetic modification of naturally occurring mosquito-associated microbes to produce molecules that prevent the development of parasites in the gut of the mosquito. In this systematic review, we examined experimental studies that investigated paratransgenesis as a malaria control measure. Using the PRISMA guideline, we identified ten eligible studies that had engineered bacterial or fungal symbionts to express antiplasmodial effector proteins. These studies showed that feeding mosquitoes a sugar meal containing engineered microbes resulted in a stable colonization of the mosquito midgut. Several of the molecules tested were highly effective in reducing parasite development, with scorpine consistently showing strong transmission-blocking activity, achieving parasite inhibition rates greater than 90% in different experimental systems. Inhibitory effects were also further augmented by the combination of several effector molecules. Overall, the finding suggests that paratransgenesis has strong potential as an additional malaria control measure. Nevertheless, contests concerning ecological safety, microbial stability, and field implementation will need to be solved before large-scale implementation can be done.
Assessing the population genetic structure and demographic history of Anopheles gambiae and Anopheles arabiensis at island and mainland sites in Uganda: implications for testing novel malaria vector control approaches
35384Mwima, R., Hui, TY.J., Lukyamuzi, E. et al., Malar J, 2026-01-20 13:40:12.
Despite substantial investments in malaria control, the disease remains a major burden in sub-Saharan Africa, particularly Uganda. Novel tools such as gene drive systems are being developed to suppress malaria vector populations, but their deployment requires detailed knowledge of mosquito population genetics. The genetic structure, diversity, and demographic history of Anopheles gambiae and Anopheles arabiensis were assessed at six sites in Uganda: three islands in Lake Victoria and three mainland sites. A total of 2918 An, gambiae and 173 An. arabiensis were genotyped using targeted amplicon sequencing of 62 loci across coding and non-coding regions of the genome. Population structure analyses revealed clear separation between the two species but little differentiation within each species across sites. Pairwise FST values among An. gambiae populations were low (0.00054–0.028) but often statistically significant, with mainland populations showing higher connectivity and island populations exhibiting greater isolation. Anopheles arabiensis mainland populations showed no statistically significant differentiation, suggesting panmixia. Principal component analysis and Bayesian clustering similarly distinguished species-level structure but no obvious substructure within sites. Mainland An. gambiae populations displayed higher nucleotide diversity than island populations, while An. arabiensis showed the lowest diversity overall. Tajima’s D values were negative across sites, consistent with recent population expansions. Effective population size estimates indicated small populations at the islands (146–249) compared to large mainland populations (4054–8190). These findings demonstrate strong genetic differentiation between An. gambiae and An. arabiensis, and subtle but meaningful structure between island and mainland An. gambiae populations. The reduced diversity and small effective population sizes at island sites suggest stronger genetic drift and limited gene flow, in contrast to the highly connected mainland populations. This study highlights how geographic and ecological factors shape mosquito population structure and provides critical evidence for the design and monitoring of genetic-based vector control interventions, including the planning and evaluation of field trials.
Beyond the static lab: environmental variability in genetically modified mosquito target gene identification for malaria control
35371Luna Dael, Maria L. Simões, Current Opinion in Insect Science, 2026-01-17 15:23:28.
As malaria remains a critical public health challenge causing hundreds of thousands of deaths annually, novel methods to combat it are urgently needed. Genetically modified mosquitoes (GMMs) offer a promising innovative approach to reduce malaria transmission. However, the foundational research to identify the target gene candidates for genetic modification is typically conducted under static laboratory conditions. These standardized insectary settings of constant temperature and humidity do not reflect the dynamic environmental and climatic variability that mosquitoes and the pathogens they carry encounter in nature. This review argues that this “lab-to-field” discrepancy represents a significant knowledge gap. We highlight that natural variations in environmental factors influence Anopheles and Plasmodium biology, and mosquito innate immunity responses, with consequences for vector competence and malaria transmission. Insufficient consideration of environmental variability during the initial gene discovery phase risks developing GMMs where the intended function of the genetic modification may be compromised by environmental stress. We emphasize the need to incorporate realistic environmental variability into the upstream GMM development, particularly in the face of escalating climate change.
Gene drives tested against real-world malaria diversity
35377Marchal, I, Nature Biotechnology, 44. 2026-01-16 16:30:43.
Gene drive technology, which uses genetic engineering to propagate selected genes throughout a population, is a potential strategy for blocking the spread of malaria, either by suppressing mosquito populations or by making them unable to transmit the disease. However, gene drive mosquitos have mainly been tested in laboratory settings with decade-old Plasmodium parasite strains, and it is unknown whether they can block the transmission of genetically diverse Plasmodium now in circulation. In an important step toward application, Habtewold et al. now report in Nature the adaptation of a previously developed gene drive strategy to an African context.
The symbiotic Wolbachia in Anopheles and its role in reducing the transmission of Plasmodium: updates and prospects
35359Nehra, R., Dhanda, S., Singh, K. et al., Archives of Microbiology, 208. 2026-01-14 11:49:05.
Reducing malaria transmission and the prospects for vector control include multi-pronged strategies, such as interrupting the parasite cycle in both vectors and mosquitoes. Effective vector control remains essential to prevent malaria transmission. This is all the more important as problems such as resistance to insecticides and the lack of a highly effective malaria vaccine remain. New generation vector control measures and optimised products are essential to address the public health needs for malaria eradication. Strategies to reduce malaria transmission include the use of insecticide-treated nets (ITNs), indoor residual spraying (IRS) and other measures. Recent studies have shown that Wolbachia pipientis, a bacterium that acts as an intracellular endosymbiotic in host cells, is becoming increasingly popular as a new method of control for Anopheles mosquitoes, both for cytoplasmic incompatibility and for pathogen blocking. Anopheles gambiae, the infection rate ranged from 8 to 24% in the wild population of the same study in the case of An. coulzzi (WAnga) in Ghana, with a prevalence of 4%. Various studies have successfully identified Wolbachia in several species of Anopheles. A highly infected Anopheles species A population in the Democratic Republic of the Congo (DRC) showed a 91% infection rate (strain wAnsA). Broader surveys list additional species hosting natural Wolbachia, including An. funestus, An. moucheti, An. melas, An. nili, An. coustani, An. dirus, An. baimaii, An. hyrcanus, and An. sinensis, among others, totalling around 31 Anopheles species. In Anopheles stephensi, researchers achieved stable maternal transmission of the wPip strain with a 100% infection frequency in the transinfected line across generations. The infection caused nearly complete cytoplasmic incompatibility (CI) and moderate fitness costs. Previous experimental infections using the wAlbB strain in An. stephensi similarly established CI and partial protection against Plasmodium infection. Wolbachia has been detected naturally at low prevalence (~ 1.4%) in field-collected An. culicifacies samples in India. However, these infections are often rare and may not lead to a high blocking effect of the pathogens. Despite the notable progress in demonstrating the CI and moderate inhibitory effect of the pathogen in several Anopheles trans-infected lines, the remaining setbacks include persistent, mother-transmitted infection with a high population replacement or suppression potential that will be relevant for widespread use. This comprehensive evaluation identified the need for further research on host-symbiotic interactions, improved genetic engineering tools and comprehensive long-term field evaluations to fully realise the potential of Wolbachia as a vector control tool for malaria.
Wolbachia for malaria control
35347Zhang, Xinmi et al., Trends in Parasitology, 2026-01-08 10:34:56.
Malaria remains a major public health concern, and traditional vector control methods face growing challenges, underscoring the need for novel strategies. The success of Wolbachia-based dengue control, together with the establishment of Plasmodium-blocking Wolbachia transinfections in Anopheles, highlights the potential of a new tool for malaria control. This review discusses the main experimental systems for studying Wolbachia–Anopheles interactions, emphasizing the challenges of generating Wolbachia transinfected Anopheles gambiae strains. Experiments utilizing Plasmodium parasite challenge in transiently and stably infected Anopheles demonstrated that Wolbachia-induced Plasmodium suppression is feasible. Building on insights from Wolbachia–Aedes–arborvirus systems – and with current evidence from Anopheles systems – we also address mechanisms of Plasmodium suppression. Finally, we outline challenges and opportunities for translating these findings from proof-of-concept to field application.
From song to stories: assessing the impact of exposure to arts-based community engagement tools in shaping knowledge, attitudes, and acceptability toward the Sterile Insect Technique for malaria control in South Africa
35319Manana, P.N., Jewett, S. & Munhenga, G., Malaria Journal, 24. 2026-01-05 11:31:18.
Community engagement (CE) is essential for public health interventions. This is particularly important when introducing novel technologies, such as the Sterile Insect Technique (SIT), that require strong community understanding and acceptance. Against this background, arts-based CE strategies, including music, drama, and radio short stories, were developed and piloted, but their effectiveness remained unevaluated. This study assessed whether exposure to arts-based CE approaches influenced community knowledge, attitudes, and acceptance of the SIT in uMkhanyakude District, KwaZulu-Natal, South Africa. A cross-sectional survey to understand the influence of arts-based CE approaches was conducted in the Jozini municipality, uMkhanyakude District, after community exposure to these CE productions. Structured interviews were conducted with randomly sampled community members. Data were collected on CE exposure and SIT-related knowledge, attitudes, and acceptance. A chi-square test and a stepwise ordinal logistic regression were used to analyze the data after adjusting for sociodemographic factors. Among 614 participants, only 26.2% (n = 161) were exposed to arts-based CE approaches. Those exposed were more likely to correctly identify that female mosquitoes feed on blood as compared to the unexposed (95.0% vs. 85.8%, p = 0.008), and to express support for SIT (e.g., 98.1% vs. 89.4% agreed with upcoming releases, p = 0.003). Exposure remained a significant predictor of SIT acceptance in multivariate models (OR 0.65, 95% CI 0.45–0.94). Positive attitudes and accurate knowledge also independently predicted greater acceptance. Arts-based CE tools were effective in supporting the introduction of SIT by improving knowledge and acceptance. However, limited exposure suggests the need for more sustained and widely accessible engagement strategies to maximize reach and long-term impact. These findings suggest that artistic productions, especially when delivered through culturally relevant, multimodal formats, play a meaningful role in shaping community receptiveness to novel vector control methods like the SIT.
The ‘mosquito factory’ breeding genetically-engineered insects to fight malaria
35321Rachel Schraer, The Independent, 2025-12-28 11:31:52.
A British company breeding mosquitoes whose offspring cannot spread malaria is set to start releasing the insects into Djibouti city by the end of the year. Genetically-engineered male mosquitoes hatched in boxes placed around the East African capital will produce female babies with genes that cause them to die before they reach adulthood. Only female mosquitoes bite and spread disease. The scheme is designed to slash the number of mosquitoes to reduce cases of malaria, which currently infects up to 10 per cent of the country a year. Malaria is among the world’s biggest killers of children under five. “So much has been achieved with existing tools,” like bed nets and insecticide spraying, says Neil Morrison, chief strategy officer at Oxitec, the British biotech company which produces the altered mosquitoes. “But progress is stalling” as resistance is being built up. As global funding to fight malaria reduces, thanks to cuts by the US, UK and a number of other nations, Morrison adds: “We just need to get a bit smarter in terms of how we think about controlling mosquitoes.”A piece of code is inserted into the genetic material of the mosquitoes at a research facility in the UK, before the “friendly” mosquitoes are transported to a “mosquito factory” in Djibouti, Morrison explains. A chemical antidote is then given to the mosquitoes to “switch off” the code, allowing them to survive and breed within that “factory”.
New Gene Drive Stops the Spread of Malaria—Without Killing Any Mosquitoes
35343Shelly Fan, SingularityHub, 2025-12-18 11:51:00.
Mosquitoes are an uncomfortable, itchy nuisance. But for people in sub-Saharan Africa, a bite could mean death. The pests are living incubators for the parasite that causes malaria. Roughly 600,000 people are killed by the disease each year, with most being children under five years of age. Insecticides, malaria drugs, and mosquito nets saved a million lives globally in 2024 alone. But their efficacy is waning. Mosquitoes and the malaria parasite are becoming resistant to chemical inhibitors. And consistent, perfect use of physical barriers is hard to manage for years on end, especially for children. Realizing this, scientists have turned to a drastic solution: Gene drives, a technology that skews the rules of inheritance. Rather than nature’s fifty-fifty chance of an offspring inheriting a gene from either parent, gene drives raise the possibility of a gene’s inheritance to over 90 percent—if not higher. The tweak allows a gene to rapidly spread across entire populations. In lab tests encoding gene drives that reduce female mosquito fertility, mosquito populations have collapsed. Other experimental gene drives encoding genes that block parasite reproduction have suggested they could replace a natural population with one unable to carry malaria in just a few generations.
Out-of-the-Box Innovations Against Malaria
35287Foreign Policy, 2025-11-06 17:34:40.
Malaria kills nearly 600,000 people every year, with 95 percent of deaths occurring in Africa. Most of them are children under the age of 5. While progress on curbing malaria has flattened in recent years, new scientific breakthroughs may bring the world closer than ever not only to controlling malaria outbreaks but potentially also to eradicating the disease. In this episode, we focus on the best mosquito control strategies to eliminate malaria. Host Henry Bonsu interviews Fredros Okumu, a professor at the University of Glasgow in Scotland and a scientist at Ifakara Health Institute in Tanzania. His research evaluates many of the latest tools to combat malaria, including next-generation insecticide bed nets, indoor residual sprays, and spatial repellants, also known as spatial emanators. Then, reporter Paul Adepoju talks to scientists from the U.K.- and Tanzania-based Transmission Zero project. They have developed genetically modified mosquitoes that could dramatically reduce the transmission of malaria. Adepoju speaks with Dickson Wilson Lwetoijera, a leading entomologist also at the Ifakara Health Institute, as well as Nikolai Windbichler from Imperial College London, who leads the molecular genetics side of the Transmission Zero project.
The nanosd integral gene drive enables population modification of the malaria vector Anopheles gambiae
35269Pei-Shi Yen, Sebald A N R Verkuijl, Paolo Capriotti, et al., G3 Genes|Genomes|Genetics, 2025-11-02 17:38:52.
The modification of mosquito populations at scale through CRISPR-Cas9-mediated homing gene drives is a promising route for malaria vector control. Integral gene drives (IGDs) are designed to utilise the regulatory sequences of endogenous genes to reduce the size of the modification required for nuclease and effector expression. In this study, we describe the creation and characterisation of the nanosd IGD, which targets and is inserted into the nanos gene of the malaria vector Anopheles gambiae, and show that it achieves high rates of gene drive (98.4% in females, 99.5% in males). We find that homozygous nanosd females but not males show impaired fecundity and exhibit variable degrees of ovary underdevelopment. Transcriptomic analysis of ovaries points to decreased transcript levels of the nanos gene when harbouring Cas9 and changes to other fertility-related genes. As a minimal genetic modification, nanosd does not induce widespread transcriptomic perturbations that would affect vector competence, and we show that its susceptibility to Plasmodium spp. and O’nyong nyong virus infection remains similar to wild-type mosquitoes. Importantly, we find that nanosd propagates efficiently in caged mosquito populations and is maintained as a source of Cas9 after the emergence of drive-resistant alleles, whilst also mobilising a non-autonomous antiparasitic effector modification. The nanosd gene drive shows promise as a genetic tool for malaria vector control via population modification, and we outline steps towards its further optimisation.
Highlight: Self-limiting gene drive suppresses malaria mosquitoes
35263Gorm Palmgren, CRISPR Medicine News, 2025-11-02 17:22:29.
Malaria claimed over 600,000 lives in 2022, with Anopheles gambiae serving as one of the most efficient vectors in sub-Saharan Africa, where approximately 96% of malaria deaths occur. The emergence of insecticide resistance threatens progress in disease control, prompting the development of genetic strategies to address it. CRISPR-homing gene drives have emerged as the most studied self-sustaining approaches, whilst various self-limiting methods that require repeated releases continue to be explored. The research team developed a system, termed Male-Drive Female-Sterile (MDFS), that exploits CRISPR-Cas9 to simultaneously perform two distinct functions (see Figure 1). The genetic construct contains an eCFP fluorescent marker, a Cas9 endonuclease under the control of the germline vasa2 promoter, and a guide RNA targeting the female-specific exon 5 of the doublesex gene. The construct was integrated into the doublesex locus at the intron 4–exon 5 boundary using recombinase-mediated cassette exchange.
Malaria Know More: Behind the Science of Gene Drive with Krystal Birungi
35271Malaria No More, 2025-10-29 17:39:23.
Congratulations on being named a 2025 Goalkeepers Champion by the Gates Foundation! What does this acknowledgement mean to you personally and professionally as an advocate for malaria elimination? BIRUNGI: It was pretty exciting and also very validating. Malaria has been around for so long that, for many people, it can seem like it’s no longer a big deal. It’s incredible how it can be glossed over that we’re losing over half a million people a year to a disease that we’ve been fighting for decades. You don’t often get recognized for work in this field, so it means a lot to have something I’m working towards be acknowledged. I was also delighted that this brought such a large platform to the fight against malaria. It has helped draw more attention to what we’re doing, why we’re doing it, and the potential it holds to defeat the disease. This year’s Goalkeepers event and being named a champion, is something I’m incredibly grateful for – not just for myself, but for the impact that it can have for malaria.
Innovation under pressure: bold ideas for a changing malaria landscape
35253Epstein, A., Tangena, JA., BMC Glob. Public Health, 3. 2025-10-27 10:36:07.
Innovation has never been more urgent. Encouragingly, the malaria research community is responding. Next-generation insecticide-treated nets (ITNs) [1], new indoor residual sprays (IRS) [2], and spatial emanators are reaching communities [3]. Vaccines such as R21 and RTS,S are moving from trials into wider use [4, 5]. On the treatment front, the pipeline now includes long-lasting antimalarials [6], triple combination therapies (TACTs) [7], and single-dose drugs like tafenoquine [8]. Novel approaches such as ivermectin, recently shown to reduce malaria incidence when deployed in mass drug administration campaigns, are also gaining traction [9]. Looking further ahead, early breakthroughs in gene drive in mosquitoes to bias inheritance of a specific genetic trait (like sterility or resistance to malaria) is passed on to offspring, and monoclonal antibodies, which point to bold new frontiers [10, 11]. Together, these advances represent the most significant broadening of the malaria toolkit in decades. But innovation alone will not be enough. The momentum is colliding with deep structural challenges. Funding cuts threaten to derail the rollout of new tools. Resistance is mounting: mosquitoes have developed resistance to most insecticides used for vector control, and parasites are showing reduced sensitivity to artemisinin and even lumefantrine, a key partner drug to control artemisinin resistance, in East Africa [12]. Climate change is redrawing the risk map by shifting mosquito habitats. Health systems remain fragile, weakened by COVID-19, extreme weather, and political unrest. Even when technologies are available, their potential can be weakened by regulatory delays, fragmented governance, or inequities in access and limited community trust. The path forward requires more than breakthroughs in science. Sustained progress will depend equally on the strength of delivery systems, stable financing, and governance that can translate innovation into equitable impact.
UC Malaria Initiative Expands Activities to Equatorial Guinea
35209Andy Fell, UC Davis, 2025-10-01 14:52:44.
The University of California Malaria Initiative, which includes researchers at UC Davis, will partner in the Republic of Equatorial Guinea’s Vision 2030 strategy to eliminate malaria from the Central African country. The plan, which also includes Oxford University, Tsinghua University and a MCD Global Health, was announced Sept. 24 during the United Nations General Assembly in New York. Vision 2030 builds on 20 years of experience in malaria control on Bioko island, Equatorial Guinea. This effort has led to a 78 percent reduction in malaria transmission and eliminated two major mosquitoes that transmit the disease. The program will include R21, a malaria vaccine developed at Oxford. It will also include a range of proven malaria control measures and health interventions. UCMI is focused on using genetically modified mosquitoes to eliminate malaria transmission. It is led by Professor Anthony James, Donald Bren and Distinguished Professor of Microbiology and Molecular Genetics at UC Irvine. Professor Gregory Lanzaro, Department of Pathology, Microbiology and Immunology at UC Davis School of Veterinary Medicine, is leading the translational component of this program and established a field site in the Democratic Republic of São Tomé and Príncipe, and island nation off the coast of Central Africa, where he and his team have been working since 2018. They will now expand this work in Equatorial Guinea. “We are pleased to partner with the Government of Equatorial Guinea in their pioneering malaria elimination program," Lanzaro in a news release. "Our mission is to support countries in achieving malaria elimination through responsible science, deep collaboration, and genuine community engagement. Together, we can help build a future where malaria is no longer a threat to families and communities across the region."
Advances in population-based interventions to control falciparum malaria
35153Samuel E Glossop, Thomas J Peto, Bipin Adhikari, Transactions of The Royal Society of Tropical Medicine and Hygiene, 2025-09-22 10:26:25.
Malaria is a complex disease and transmission can be prevented in multiple ways. A range of interventions to achieve this became widely available from the year 2000, and cases continually declined, but progress has plateaued since 2015. This review aims to cover the population-level prevention strategies responsible for this and those that could continue this progress, focusing on how they can be successfully integrated. Insecticide-treated nets (ITNs) made the most substantial contribution to reducing malaria mortality, but their distribution, access and use remains suboptimal while development of insecticide resistance requires continuous adaptation. Chemoprevention provides protections to tens of millions of people, primarily children in sub-Saharan Africa, but is also threatened by the emergence and spread of drug resistance. These strategies may have reached a point of saturation for reducing morbidity and mortality, thus calling for innovative developments to build upon more basic approaches such as accurate early diagnosis, appropriate treatment and improved housing. The R21/Matrix-M vaccine is a significant improvement over the RTS,S/AS01 vaccine, with greater efficacy, lower cost and scalable mass production. Field trials of current monoclonal antibodies (mAbs) suggest that next-generation mAbs could be a promising tool for seasonal chemoprophylaxis. Furthermore, gene drives may have the potential to eradicate entire populations of malaria-transmitting mosquitoes. A multifaceted approach combining these new strategies with traditional approaches (ITNs and chemoprevention) offers a framework to reinvigorate progress towards malaria elimination.
Governance Landscape of Gene Drive for Malaria
35069GeneConvene Global Collaborative, 2025-08-28 10:24:11.
This infographic presents a hypothetical example of how real governance mechanisms could work to make decisions about gene drive field trials.
Genetic control strategies for population suppression in the Anopheles gambiae complex: a review of current technologies
35055Alekos Simoni, Ignacio Tolosana, Federica Bernardini, Current Opinion in Insect Science, 2025-08-25 20:42:10.
Malaria continues to pose a critical public health threat, with mosquitoes from the Anopheles gambiae complex acting as the main vectors of the disease in sub-Saharan Africa, where approximately 95% of malaria-related deaths occur. Despite significant advancements in vector control, such as insecticide-treated bed nets and indoor spraying, the effectiveness of these interventions is increasingly compromised by various challenges, including rising levels of insecticide and pathogen resistance, mosquito behavioural adaptations, and persistent funding gaps. In this context, genetic vector control strategies have shown considerable promise, primarily based on findings from controlled laboratory studies. This review explores the development of these genetic approaches within the Anopheles gambiae complex and outlines future directions for their advancement and potential integration into malaria control efforts.
RESEARCH GROUP PUSHES GENE DRIVE TECHNOLOGY TO END MALARIA IN AFRICA || NEWS UPDATE
35049IDEA TV, YouTube, 2025-08-24 18:23:33.
Tanzania’s bold step toward malaria elimination
35079Guardian Correspondent, IPP Media, 2025-08-20 12:44:23.
It is both mind-boggling and frustrating that an insect with an average lifespan of just two weeks can cause so much sickness and even deaths. Today, on World Mosquito Day, 20th August, the Ifakara Health Institute (IHI) honours Sir Ronald Ross, whose landmark discovery in 1897 confirmed that mosquitoes transmit malaria. His finding not only transformed medical science but also highlighted the profound impact mosquitoes have on public health. For more than a century, his discovery—made while serving with the Indian Medical Services—has continued to remind the world that defeating malaria requires a deep understanding of parasites and efficient mosquito vectors in order to make a real impact in preventing the disease. Globally, vector control has been instrumental in saving millions of lives, mainly through Long-lasting Insecticidal Nets (LLINs) and Indoor Residual Spraying (IRS). These measures prevented more than 78 million malaria cases between 2000 and 2015.
The buzz stops here
35057Bill Gates, Gates Notes, 2025-08-19 20:44:24.
I've been working on malaria for over two decades. I’ve talked with researchers in labs and parents who’ve lost children to a mosquito bite. I’ve seen promising new tools and surprising setbacks. But I’ve rarely been as excited about a new innovation as I am about this one. In a lab in Tanzania, researchers are studying something incredible: a mosquito that can’t give you malaria. It looks and behaves like any other mosquito. It flies, bites, and breeds. But what it doesn’t do is transmit one of the deadliest diseases on the planet—which means it could save hundreds of thousands of lives a year. This mosquito was developed in 2023 by a team of African scientists at the Ifakara Health Institute in partnership with Imperial College London. It’s the first transgenic mosquito ever created on African soil—meaning that scientists have made a small, targeted change to its DNA. It was both a major scientific milestone and a major moment of African leadership in the global health space. The project is called Transmission Zero, and its goal is as ambitious as its name: to eliminate malaria not by killing mosquitoes, but by making them unable to transmit it to humans.
Driving a protective allele of the mosquito FREP1 gene to combat malaria
34980Li, Z., Dong, Y., You, L. et al., Nature, 2025-07-24 09:46:46.
Malaria remains a substantial global health challenge, causing approximately half a million deaths each year1. The mosquito fibrinogen-related protein 1 (FREP1) is required for malaria parasites to infect the midgut epithelium2. The naturally occurring FREP1Q allele has been reported to prevent parasite infection, while supporting essential physiological functions in the mosquito3. Here we generate congenic strains of Anopheles stephensi, edited to carry either the parasite-susceptible FREP1L224 or the putative-refractory FREP1Q224 alleles. The FREP1Q224 allele confers robust resistance to infection by both human and rodent malaria parasites, with negligible fitness costs. The protective FREP1Q224 allele can be efficiently driven into FREP1L224 mosquito populations using a novel linked allelic-drive system that selectively replaces the L224 codon with the parasite-refractory Q224 allele, thereby rendering populations refractory to parasite infection. This antimalaria drive system provides a novel genetic approach to aid in malaria elimination efforts.
Controversial ‘gene-drive’ strategy could make mosquitoes hostile to malaria parasites
34977Mitch Leslie, Science, 2025-07-24 09:37:48.
To fight malaria and the mosquitoes that spread it, people have drained swamps, showered their homes with insecticides, slathered themselves in noxious repellents, hidden under netting at night, and invented the gin and tonic—as a palatable way to take the bitter antimalarial quinine. Now, researchers report in Nature that they have borrowed a weapon from the mosquitoes themselves. The team genetically engineered mosquitoes to be resistant to parasites that cause malaria by inserting a version of a gene naturally found in some of the insects. They also enlisted a genetic trick known as gene drive to speed the gene variant's spread through mosquito populations in the lab. The strategy is not ready for field testing, researchers caution. But the experiments "are elegantly designed and sound, really showing great proof of principle for driving natural variants of mosquito genes into a population," says functional geneticist Tony Nolan of the Liverpool School of Tropical Medicine, who wasn't connected to the study.
Lethal malaria parasite’s weaknesses revealed
34975Nature, 553. 2025-07-24 09:33:54.
A sweeping genomic analysis of the most deadly malaria parasite has revealed targets for more resilient drugs against the pathogen. The parasite Plasmodium falciparum has evolved resistance to every licensed drug. To aid the search for compounds that present higher barriers to resistance, a team led by Elizabeth Winzeler at the University of California, San Diego, exposed 262 strains of P. falciparum to a range of antimalarial agents. By analysing the genomes of strains that evolved resistance to the chemicals, the researchers identified the mutations that were most- and least-often linked to the parasite’s ability to survive an onslaught of antimalarial drugs. The team reasoned that genes with infrequent mutations would make good drug targets, because they seem less likely to adapt to new antiparasitic agents. Some of those genes code for enzymes, which can be targeted by drugs that are easier to administer than other types of therapy.
A genetic tweak could prevent mosquitoes from transmitting malaria
34987Jonathan Lambert, NPR, 2025-07-23 10:40:28.
Each year, 263 million people get malaria. But from the parasite's perspective, infecting humans is harder than you might think, and requires completing an epic journey within the tiny body of a mosquito. First, the mosquito must suck the blood of an individual infected with malaria — bringing the Plasmodium parasite into the insect's gut. Then the parasite must travel to the critter's salivary glands, where it's poised to be injected into the mosquito's next victim via a bite. Now a team of researchers have found a way to interrupt this crucial journey. By using gene editing to make a tiny tweak to the mosquito's genome — one that changes just a single amino acid — parasites were largely prevented from reaching their final destination. The change effectively rendered laboratory mosquitoes highly resistant to spreading malaria, researchers report Wednesday in Nature. "The idea that you could change just one amino acid and not have the parasite transmitted is a pretty big deal," says Fred Gould, an entomologist at North Carolina State University who wasn't involved in the study. "It's really exciting." That tiny tweak could be spread through a whole mosquito population using a gene drive, a genetic technology that breaks the normal 50-50 rules of inheritance. Gene drives are sequences of DNA that can be inserted into the genome of an individual and cause a specific mutation or gene to be passed on to virtually all offspring, instead of just 50%.
Genetic tweak in mosquitoes blocks malaria transmission without affecting insect health
34978University of California - San Diego, Phys.org, 2025-07-23 09:38:04.
Mosquitoes kill more people each year than any other animal. In 2023, the blood-sucking insects infected a reported 263 million people with malaria, leading to nearly 600,000 deaths, 80% of which were children. Recent efforts to block the transmission of malaria have been stalled because mosquitoes have adapted resistance to insecticides and the parasites within mosquitoes that cause malaria have become resistant to drugs. These setbacks have been amplified by the COVID-19 pandemic, which impeded ongoing anti-malarial efforts. Now, researchers at the University of California San Diego, Johns Hopkins University, UC Berkeley and the University of São Paulo have developed a new method that genetically blocks mosquitoes from transmitting malaria. Their work appears in Nature. Biologists Zhiqian Li and Ethan Bier from UC San Diego, along with Yuemei Dong and George Dimopoulos from Johns Hopkins University, created a CRISPR-based gene-editing system that changes a single molecule within mosquitoes, a minuscule but effective change that stops the malaria-parasite transmission process. Genetically altered mosquitoes are still able to bite those with malaria and acquire parasites from their blood, but the parasites can no longer be spread to other people. The new system is designed to genetically spread the malaria resistance trait until entire populations of the insects no longer transfer the disease-causing parasites. "Replacing a single amino acid in mosquitoes with another naturally occurring variant that prevents them from being infected with malarial parasites—and spreading that beneficial trait throughout a mosquito population—is a game-changer," said Bier, a professor in the UC San Diego Department of Cell and Developmental Biology (School of Biological Sciences). "It's hard to believe that this one tiny change has such a dramatic effect."
CRISPR technologies for the control and study of malaria-transmitting anopheline mosquitoes
34964Smidler, A.L., Akbari, O.S., Parasites Vectors, 18. 2025-07-08 13:44:43.
Malaria is one of the deadliest diseases on the planet, killing approximately 600,000 people annually, and is transmitted by the bite of an anopheline mosquito. Anophelines, and the diseases they transmit, have changed the course of history and the fate of nations, and their successful control promises to end the transmission of malaria. With the advent of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technologies, the study and control of these deadly pests have been revolutionized. As the release of genetically modified anophelines is being considered, here we outline the advances in CRISPR/Cas9 technologies and how they have revolutionized the study of anopheline basic biology and the development of innovative vector control strategies. We outline the major findings of CRISPR-based basic biological research into traits relevant for vector control including, but not limited to, olfaction, chemosensation, neurobiology, and reproduction. Further, we summarize the advancements in CRISPR-based innovative vector control strategies, such as the precision-guided sterile insect technique (pgSIT), inherited female elimination by genetically encoded nucleases to interrupt alleles (IFEGENIA), X-shredder, Y-linked editors, and gene drives. All in all, this review summarizes the basic biological and vector control research undertaken using CRISPR since its advent approximately a decade ago.
Assessing the impact of the Wolbachia-based control of malaria
34962Zhuolin Qu, Lauren M. Childs, Mathematical Biosciences, 2025-07-08 13:34:58.
Malaria remains a significant infectious disease globally, causing hundreds of thousands of deaths each year. Traditional control methods, such as disease surveillance and mosquito control, along with the development of malaria vaccines, have made strides in reducing the disease’s impact, but new control methods are urgently needed. Wolbachia is a natural bacterium that can infect mosquitoes and reduce their ability to transmit diseases. While initially used to control dengue fever, recent research explored its potential for malaria control. In this study, we develop and analyze a novel mathematical model to assess the potential use of Wolbachia-based strategies for malaria control. The model describes the complex Wolbachia transmission dynamics among mosquitoes and incorporates key features of malaria transmission in humans with dynamical immunity feedback. We derive the basic reproduction number of the malaria disease transmission, which depends on the prevalence of Wolbachia in mosquitoes. Our findings reveal bifurcations in both Wolbachia transmission among mosquitoes and malaria transmission in humans, suggesting the potential for malaria elimination through Wolbachia-based interventions. The sensitivity analysis identifies the important parameters for the basic reproduction number and for malaria reduction and elimination. We numerically explore the integration of Wolbachia and other malaria controls. When control focuses on reducing the malaria burden in humans, there is a substantial rebound in malaria prevalence following the intervention in humans, and our results suggest post-Wolbachia malaria control leads to the greatest reduction in total days of infection. When Wolbachia release is integrated with pre-release mosquito control, there is a comparably large reduction in total days of infection if pre-release mosquito control occurs only a few days before Wolbachia release.
Dynamical analysis of a nonlocal delays spatial malaria model with Wolbachia-infected male mosquitoes release
34960Liping Wang, Runqi Liu, Yangyang Shi, Electronic Research Archive, 33:3177-3200. 2025-07-08 13:27:46.
Malaria continues to pose a considerable threat to global health. This study investigates the use of releasing Wolbachia-infected male mosquitoes as a method to mitigate the spread of malaria. We have formulated a reaction-diffusion model with nonlocal delays that includes the Wolbachia release strategy. The basic reproduction number R0 is defined within our model framework, serving as a critical threshold parameter that dictates the dynamic behavior of the model. A thorough dynamic analysis of the model reveals that when R0<1, a globally attractive infection-free steady state is established. In contrast, if R0>1, the disease persists uniformly. Numerical simulations are conducted to validate the theoretical results and to further illustrate the effectiveness of the Wolbachia release strategy on transmission and control of malaria. These simulations underscore the potential of using Wolbachia-infected male mosquitoes to significantly reduce spread of malaria.
The goal of eliminating malaria by 2030 is in jeopardy
34937African Media Agency, African Newspage, 2025-06-24 08:50:49.
Africa could see 554,000 additional malaria deaths due to climate change, unless urgent action is taken. The goal of eliminating malaria by 2030 is in jeopardy, as climate change, population growth, and funding shortfalls converge to reverse hard-won gains over the past decade. “Shifting temperature and rainfall patterns are expanding and altering malaria risk zones, which will continue to disproportionately affect vulnerable populations, especially children under five,” says Dr. Patric Epopa, researcher at the Health Sciences Research Institute (IRSS) and Field Entomology Coordinator at Target Malaria Burkina Faso. According to a climate impact model developed by Boston Consulting Group and the Malaria Atlas Project to predict changes in extreme weather events and to estimate their impact on malaria deaths to the year 2049, the increase in extreme weather events is reshaping malaria risk. The findings indicate: Between 2030 and 2049, climate change is expected to cause 554,000 more malaria deaths than if today’s climate remained unchanged. This is despite some regions seeing reduced transmission rates. Extreme weather events will drive 92% of these additional deaths. Stepping up malaria control with current tools could reduce the additional deaths, but climate change may weaken their impact by up to 17%, making progress fragile. By 2050, climate change will make malaria eradication harder for 75% of sub-Saharan Africa’s population,equating to 1.3 billion people. “Extreme weather is one of the biggest drivers of malaria spikes,” says the researcher. “Displaced communities are often left unprotected without mosquito nets, indoor spraying, or access to early diagnosis and treatment.”
Gene Drive Mosquitoes: Can We End Malaria?
34930The Curious Scholarette, YouTube, 2025-06-19 14:56:01.
What if we could genetically modify mosquitoes to stop malaria in its tracks? In this episode of The Curious Scholarette, we explore the groundbreaking world of gene-drive technology — a powerful tool that could eliminate malaria-carrying mosquitoes by altering their DNA. But with great power comes great ethical debate. 🔬 In this video, we break down: What gene drives are and how they work How scientists are using CRISPR to disrupt mosquito reproduction or malaria transmission Evidence from field trials and lab experiments The potential risks: ecological disruption, irreversible changes, and bioethical concerns Perspectives from global health experts, bioethicists, and community leaders 📍 Why it matters: Malaria kills over 600,000 people each year, mostly in sub-Saharan Africa. Could gene-drive mosquitoes be the silver bullet? Or are we playing with fire? 🧪 Sources Cited: WHO Malaria Report
Battle of the mosquitoes
34911Adepoju, P, Nature Medicine, 2025-06-11 19:05:47.
The mosquito was frozen in place. Its tiny body, no longer buzzing, lay still on the cold metal surface, caught in a moment of stasis. A few minutes earlier, it had been active, darting around Oxitec’s research facility, a modified version of nature’s most dangerous killer. “We put them on ice because that slows them down”, an Oxitec scientist explained, adjusting the microscope. “It makes our job easier”. This laboratory in Abingdon, England, is where an ambitious mosquito control project is unfolding. The work being done here — modifying Anopheles stephensi mosquitoes to fight malaria—has implications not just for Djibouti, where the genetically modified insects are being released, but for the entire African continent. Outside, it’s a chilly 7 °C, but the lab is surprisingly warm and humid: a digital thermometer plugged in beside the microscope reads 21.1 °C — perfectly mimicking a mosquito’s natural habitat. Large cages fill a section, each holding different generations of modified mosquitoes, bred with a self-limiting gene that ensures that only male offspring survive when they mate with wild females. On one side of the lab, scientists peer into microscopes, searching for a tiny fluorescent marker inside the mosquitoes’ bodies — a glowing signature that confirms the genetic modification was successful. Each mosquito is carefully examined (Fig. 1), its fate decided under the magnifying glass.
Influence of genetic factors of humans, mosquitoes and parasites, on the evolution of Plasmodium falciparum infections, malaria transmission and genetic control methods: a review of the literature
34903Nikiema, S., Soulama, I., Ampofo, G.D. et al., BMC Medical Genomics, 18. 2025-06-06 08:52:12.
Despite significant progress, malaria remains a public health problem in many regions, particularly in sub-Saharan Africa. This situation is partly explained by the mosquito’s resistance to insecticides and the emergence of parasite resistance to antimalarial drugs. Indeed, in spite of the various vectors’ controls, insecticide resistance emerges from multi-generational selection and poses worldwide concern. In parallel, artemisinin resistance unfortunately emerged independently in multiple countries in eastern Africa. Since 2014, artemisinin resistance has been observed in 6 countries in Africa and, more concerningly, the evidence from longitudinal molecular surveys in these countries suggests that it is spreading. While phenotypic evidence of treatment failure is still limited, the increasing reports of validated artemisinin resistance mutations are alarming. Unlike the emergence of artemisinin resistance in South-East Asia, our understanding of the genetic determinants of artemisinin resistance and our ability to sequence and map the spread of resistance are significantly greater. In addition to mosquito and parasite genetics affecting malaria evolution, many human individual variants have been identified that are associated with malaria protection, but the most important of all relates to the structure or function of red blood cells, the classical polymorphisms that causes sickle cell trait, α-thalassaemia, G6PD deficiency, and the major red cell blood group variants. In that biological complex context, there is a need to characterize the various genetic factors in Plasmodium falciparum, humans and mosquitoes that are potentially associated with resistance to antimalarial drugs and insecticides, and their involvement in the evolution, severity and transmission of malaria. In this direction, A comprehensive literature review was conducted to capture the objectives highlighted above. The advances in genomic surveillance and emerging genetic control strategies, such as gene drive technology were also considered in this review. We used search engines such as PubMed and Google scholar to retrieve articles useful to the objective of this paper and information on the knowledge of genetic factors and methods that contributed to malaria control were synthesized.
Paratransgenesis: Overview, Current Perspectives, and Future Research Needs for Malaria Control
34874Oziegbe, O., Okeke, C.C., Esho, D.O., Springer, Cham., 2025-05-26 21:52:21.
Malaria is an insect-borne disease (IBD) that is responsible for significant human mortality and morbidity globally. Several effective vector and parasite control strategies have been considered to control malaria. However, paratransgenesis is a strategy targeted towards parasite development disruption rather than vector elimination which can potentially address insecticide resistance in mosquitoes. Genetically modified symbionts such as bacteria, fungi, or viruses secrete anti-plasmodial effector molecules that kill or inhibit the development of Plasmodium species without affecting the vector or the microorganism. Various anti-plasmodial effector molecules have been identified such as scorpin, a peptide from scorpion venom that acts by lysing the parasite, enolase- plasminogen interaction peptide (EPIP) which acts by inhibiting midgut invasion, A protein kinase (Akt) that acts by activating innate immune responses, and salivary gland and midgut peptide 1 (SMI) that acts by preventing binding to the parasite surface proteins. For this strategy to be successful, the selected symbiotic microorganism should be easy to culture and genetically manipulate, stable, as well as capable of producing effector molecules with anti-plasmodial activity while colonizing a wide range of the host species. Paratransgenesis presents a promising future for malaria control globally. However, its efficacy and safety as a malaria control strategy should be experimented with in large outdoor settings with more elaborate and collaborative studies carried out to sustain the approach in malaria-endemic countries.
Assessing the population genetic structure and demographic history of Anopheles gambiae and An. arabiensis at island and mainland populations in Uganda: Implications for testing novel malaria vector control approaches
34868Rita Mwima, Tin-Yu J. Hui, Edward Lukyamuzi, et al, bioRxiv, 2025-05-26 21:26:56.
This study collected 2918 Anopheles gambiae and 173 Anopheles. arabiensis across six populations from both the islands on Lake Victoria and mainland Uganda for amplicon sequencing. Large pairwise FST values were observed between the two species, indicating their divergence. We observed low but often significant FST values between the 6 An. gambiae populations, while between the An. arabiensis mainland populations, FST values were not significant. Principal Component Analysis also revealed strong genetic structure between the two species but did not provide a clear picture between populations within each species. We also found that mainland An. gambiae populations had higher within population genetic diversity than the islands’, while An. arabiensis had the lowest nucleotide diversity. Tajima’s D values were all negative, suggesting a recent population expansion. The islands An. gambiae populations had very low contemporary effective population sizes in the tens and hundreds, as estimated from linkage disequilibrium, while the mainland population sizes were consistently higher, in the thousands.
Unstable laboratory Wolbachia strain w-Anga is negatively correlated with Plasmodium falciparum in wild malaria vectors
34856Estelle, D.L., Jacques, G.E., Issiaka, S. et al., Scientific Reports, 15. 2025-05-26 20:48:59.
Spread of insecticides resistance threatens the control of malaria. In this context, biological control using an endosymbiotic bacterium Wolbachia is being explored as a complementary method for its control. However, for optimal use of this bacterium in biocontrol strategies, it is imperative to characterize it. So, Anopheles gambiae complex mosquitoes were collected, morphologically identified, then blood fed and gravid female mosquitoes oviposited individually. After oviposition, the species of parent was molecularly determined, along with their w-Anga infection status. Additionally, we performed 16SrRNA gene sequencing of w-Anga-positive mosquitoes to determine their phylogeny. Finally, we amplified gene encoding the circumsporozoite protein to determinate their Plasmodium falciparum infection status and assessed the stability of w-Anga transmission of positive females and their offspring. From the results obtained, our w-Anga strains cluster with other Wolbachia Supergroup B strains. However, the prevalence of Plasmodium falciparum infection was lower in Wolbachia-infected females (4.59%) than in those uninfected (22.02%). Furthermore, the transmission frequency of this bacterium in infected Anopheles coluzzii females of the F0 generation to F1 offspring was 10.64% and 16.67% from infected females of the F1 generation to F2 offspring. This study results will serve as preliminary data for the possible use of Wolbachia in malaria control.
Nanobody-mediated targeting of Plasmodium falciparum PfPIMMS43 can block malaria transmission in mosquitoes
34819Ukegbu, C.V., Mohamed, M., Hoermann, A. et al., Communications Biology, 8. 2025-05-04 18:21:46.
The transition from ookinete to oocyst is a critical step in the Plasmodium falciparum lifecycle and an important target for malaria transmission-blocking strategies. PfPIMMS43, a surface protein of P. falciparum ookinetes and sporozoites, is critical for this transition and aids the parasite in evading mosquito immune responses. Previous studies demonstrated that polyclonal PfPIMMS43 antibodies reduced P. falciparum infection in Anopheles mosquitoes. Here, building on these findings, we have developed high-affinity single-domain VHH antibodies (nanobodies) derived from llama heavy-chain-only antibodies. We have shown that these nanobodies bind both recombinant and endogenous PfPIMMS43 produced by P. falciparum ookinetes in the mosquito midgut. Importantly, they significantly reduce infection intensity and prevalence of laboratory and field strains of P. falciparum in An. coluzzii and An. gambiae, respectively. Epitope mapping has revealed that the nanobodies target conserved regions in the second half of PfPIMMS43, with homology modelling confirming epitope accessibility. These findings establish PfPIMMS43 as a promising transmission-blocking target. To enhance malaria control and elimination efforts, we propose an innovative strategy in which genetically modified mosquitoes express PfPIMMS43-specific nanobodies in their midguts and spread this trait in wild mosquito populations via gene drive technology.
Gene drive could reshape the malaria fight and young people must be at the centre
34803Dr. Phillip Chigiya, African Leaders Malaria Alliance, 2025-04-25 12:04:22.
The only time I was ever admitted overnight in hospital was when I was five years old. I had malaria. I still remember the strange chill of the sheets, the IV line taped to my small hand, and my mother at my bedside, watching me breathe. That moment has never left me. Since then, I have moved from patient to practitioner. I have worked in clinics and hospitals across Africa, and malaria has never been far away. I have diagnosed it in children too young to speak, in teenagers missing school, and in pregnant women arriving in labour wards with dangerously low haemoglobin. Sometimes treatment is routine. Sometimes it is a race against time. It is easy to be swept up by bold declarations, especially on World Malaria Day. But we must be honest. The progress we once celebrated is stalling. In 2023, there were over 263 million new malaria cases and an estimated 597,000 deaths, most of them in Africa. One child dies every minute. Behind every number is a name, a family, and a future lost too soon.
Optimization of SgRNA expression with RNA pol III regulatory elements in Anopheles stephensi
34801Gonzalez, E., Anderson, M.A.E., Ang, J.X.D. et al., Scientific Reports, 15. 2025-04-23 11:08:06.
Anopheles stephensi, a major Asian malaria vector, is invading Africa and has been implicated in recent outbreaks of urban malaria. Control of this species is key to eliminating malaria in Africa. Genetic control strategies, and CRISPR/Cas9-based gene drives are emerging as promising species-specific, environmentally friendly, scalable, affordable methods for pest control. To implement these strategies, a key parameter to optimize for high efficiency is the spatiotemporal control of Cas9 and the gRNA. Here, we assessed the ability of four RNA Pol III promoters to bias the inheritance of a gene drive element inserted into the cd gene of An. stephensi. We determined the homing efficiency and examined eye phenotype as a proxy for non-homologous end joining (NHEJ) events in somatic tissue. We found all four promoters to be active, with mean inheritance rates up to 99.8%. We found a strong effect of the Cas9-bearing grandparent (grandparent genotype), likely due to maternally deposited Cas9.
Uganda grapples with malaria burden amidst promising innovations
34795Innocent Lawrence Okima, The Independent, 2025-04-23 10:42:44.
According to the report, Uganda, with a population of close to fifty million people, accounts for 5% of the world’s malaria cases and 3% of malaria-related deaths. Astonishingly, according to page 151 of the report, Uganda leads the East and Southern African countries with 23% of malaria cases and high transmission rates, beating even Mozambique, which comes in second at 19%. It’s not exactly the kind of competition anyone wants to win. Malaria’s economic toll is just as staggering. Families lose loved ones, and resources that could have contributed to building roads, schools, create jobs are diverted to fight malaria. Children – the main victims of malaria – lose access to education and young children often die (80% of malaria deaths are children under five). Pregnant women are at high risk of losing their babies and their lives because malaria in pregnancy puts them in grave danger. Uganda’s government, together with partners like WHO, has declared a fight against malaria. This includes distributing insecticide-treated mosquito nets (ITNs), spraying homes with indoor residual insecticides (IRS), and ensuring early diagnosis through rapid diagnostic tests (RDTs). Treatment relies heavily on artemisinin-based combination therapies (ACTs), which remain a mainstay in the battle against the disease. While these measures have shown results—malaria prevalence has declined slightly over the last decade—progress is hampered by challenges like insecticide resistance, inadequate healthcare in remote areas, and insufficient funding. Not to mention the eternal struggle of getting children to sleep under the mosquito net and fishermen not to use it as one of their equipment to trap silverfish locally known as “Mukene”. Amid these challenges, hope emerges in the form of a genetic technology called “gene drive”, currently under development, and championed by Target Malaria at the Uganda Virus Research Institute in Entebbe. This cutting-edge approach involves genetic modifications to the Anopheles gambiae mosquito, the main malaria carrier in Uganda.
World Malaria Day: Renewing our commitment to end malaria in Africa
34791Damaris Matoke-Muhia, Outreach Network for Gene Drive Research, 2025-04-23 10:14:29.
As the world marks World Malaria Day this week, we are reminded that malaria remains one of the oldest and deadliest diseases in human history. Despite decades of global effort, it continues to claim half a million lives each year. The overwhelming majority of these deaths occur in sub-Saharan Africa, where it is estimated that one person dies of the disease every minute. This year’s World Malaria Day theme: Malaria Ends with Us: Reinvest, Reimagine, Reignite is a reminder that we must renew our commitment to end malaria and rethink our approach to fighting the disease. The malaria burden in Africa remains unacceptably high. The impact of the disease extends beyond health. Malaria strains healthcare systems, reduces productivity, and hinders economic development. In many African countries, malaria-related absenteeism and healthcare costs place a significant burden on families and communities. Over the past two decades, significant progress has been made in the fight against malaria. Control programs involving the distribution of insecticide-treated bed nets, indoor residual spraying, and artemisinin-based combination therapies have resulted in a decline in malaria infections and deaths. But several challenges now threaten these gains. Insecticide resistance is rising, making it harder to control mosquito populations with the tools we have relied on for decades. Antimalarial drug resistance is emerging in some regions, complicating treatment. Urban malaria is becoming a growing concern, in part due to the spread of species such as Anopheles stephensi, a mosquito native to parts of South Asia and the Arabian Peninsula, which has been detected in several African countries. Climate change is shifting transmission dynamics, altering mosquito habitats and infection patterns, bringing malaria to new areas and intensifying the burden of the disease in regions where it was already present. By the 2030s, it is estimated that an additional 147 to 171 million additional Africans could be at risk of malaria.
Problem formulation for a small-scale field study of non-gene drive, genetically modified, male bias mosquitoes in Burkina Faso
34758Hayes, K. R., & Hosack, G. R., Human and Ecological Risk Assessment: An International Journal, 2025-04-10 09:17:32.
This article documents the problem formulation step of a risk assessment for a proposed small-scale field release in Burkina Faso of genetically modified (GM) An. coluzzii mosquitoes that carry a Paternal Male Bias (PMB) construct. These mosquitoes are part of the pathway developed by Target Malaria to provide a new cost-effective control strategy for malaria vectors in Africa. The problem formulation describes 7 potentially harmful outcomes that might occur through 19 pathways to harm and identifies 22 types of desk-based analysis, 6 laboratory tests, and 5 field observations that can be used to test the risk hypotheses associated with these pathways. The problem formulation forms the basis of a prerelease risk assessment that meets the standards stipulated under the Cartagena Protocol and guidance provided by the World Health Organization, the African Union Development Authority, and the European Food Safety Authority. The Problem Formulation reflects the concerns expressed about the proposed field release by relevant stakeholders, although stated concerns are not always specific enough to be unambiguously associated to a single pathway. The presentation of the pathways to harm emphasizes the types of evidence that supports the steps within each pathway, and so portrays the speculative nature of some pathways.
Challenges in developing a split drive targeting dsx for the genetic control of the invasive malaria vector Anopheles stephensi
34659Larrosa-Godall, M., Ang, J.X.D., Leftwich, P.T. et al., Parasites & Vectors, 18. 2025-03-25 09:18:22.
Anopheles stephensi is a competent malaria vector mainly present in southern Asia and the Arabian Peninsula. Since 2012, it has invaded several countries of eastern Africa, creating an emerging risk of urban transmission. Urgent efforts are required to develop novel and more efficient strategies for targeted vector control. CRISPR/Cas9-based homing gene drives have been proposed as attractive alternative strategies. Gene drives have the potential to spread a desired trait through a population at higher rates than via normal Mendelian inheritance, even in the presence of a fitness cost. Several target genes have been suggested and tested in different mosquito vector species such as Anopheles gambiae and Aedes aegypti. Several promising suppression drives have been developed in An. gambiae that target the sex determination gene doublesex (dsx). In this study, a geographically confineable gene drive system targeting dsx was developed (dsxgRNA). Here, a transgenic line which expresses Cas9 under the control of the endogenous zpg promoter was generated. Separately a transgenic line which expresses a gRNA targeting the female specific exon of dsx was inserted into that same target site. The reproductive fitness of males and females heterozygous and homozygous for this element was determined. A series of experimental crosses was performed to combine the two elements and assess the homing rate of the dsx element in a split drive system. The drive was able to home in a super-Mendelian rate comparable to those obtained by an autonomous drive in this species. Although inheritance rates as high as 99.8% were observed, potentially providing very potent gene drive, dominant effects on male and female fertility were observed, which would be sufficient to hinder spread of such a drive. Molecular analysis indicated that the gRNA expressing insertion disrupted normal splicing of dsx. These results should be considered when proposing the viability of dsx as a target gene for a population suppression gene drives in Anopheles stephensi. Although high homing rates were observed, the fitness defects found in both males and females carrying the transgene would likely prohibit this drive from functioning in the field.
Exploring the ecology of malaria mosquitoes in São Tomé and Príncipe
34636Lisa Chamberland, Outreach Network for Gene Drive Research, 2025-03-21 14:28:58.
As part of our work to develop new genetic approaches for malaria control, the University of California Malaria Initiative (UCMI) is studying mosquito movement and breeding patterns in São Tomé and Príncipe. In a study published last year, we investigated the dispersal dynamics of Anopheles coluzzii – the only malaria vector on this island nation. Our recent study examines how environmental factors influence A. coluzzii breeding sites and shape mosquito dispersal across São Tomé and Príncipe. Understanding movement and interactions between mosquito populations is key to designing malaria control strategies. The data collected will also offer key insights that will guide the design of potential field evaluations of the technology we are working to develop. To determine the most suitable habitats for A. coluzzii, we used computer modeling to analyze environmental conditions such as temperature, elevation, and human population density. Our results show that the northeastern regions of both São Tomé and Príncipe islands provide the most suitable conditions for A. coluzzii larval development, with lower elevations and higher human population densities likely contributing to greater habitat availability. Interestingly, our climate modeling suggests that the mosquito’s geographic distribution on the islands will remain largely unchanged under current climate projections, even without additional interventions.
Ghana committed to exploring gene drive to combat malaria – Minister
34638Ghana News Agency, 2025-03-20 14:31:41.
Ghana has expressed interest in exploring gene drive technology as a new approach to combatting malaria. The country is open to adopting technology that is cost-effective, efficient, harmless and has the potential to significantly reduce malaria transmission, especially in areas where traditional control methods have failed. Dr. Ibrahim Murtala Muhammed, the Minister of Environment, Science, and Technology gave the assurance in an interview with journalists after opening the Second Global Genetic Biocontrol Congress in Accra. Scientists, researchers, and stakeholders from 25 institutions drawn from 15 countries are participating in the conference on the theme: “Harnessing genetic biocontrol potential solutions in changing climate.” Describing Malaria as a “serious threat,” Dr. Muhammed said the burden of malaria on Africa’s economy was high as the continent spent millions of dollars on malaria control. He said Ghana would adopt emerging technologies to help support disease prevention including those that affect crops “as long as it does not affect our survival as human beings.” People who are against GMO have several cultural issues and social issues. But the question is, is it the way to go now?
Inside the lab breeding malaria resistant GM mosquitoes
34618Reuters, YouTube, 2025-03-18 12:02:59.
An international team of scientists are developing genetically modified mosquitoes that can slowly convert the entire wild population of mosquitoes resistant to transmitting malaria, the world’s most deadly disease.
Gene drive modified mosquitoes offer new tool for malaria elimination efforts
34615Conrad Duncan, Imperial, 2025-03-13 11:59:36.
Transmission Zero, a research team from Imperial College London in partnership with the Ifakara Health Institute and the National Institute of Medical Research in Tanzania, has developed genetic technology which renders a mosquito unable to transmit the malaria parasite and has a gene drive that ensures that future generations are also resistant to the parasite. The technology could significantly reduce the malaria burden in high-risk countries, saving hundreds of thousands of lives each year, especially among children – who are disproportionately at risk from the disease. The work of Transmission Zero has been highlighted in a new Global Development Hub STEM for Development Impact Memo authored by Professor George K. Christophides, Professor of Infectious Disease and Immunity at Imperial, Dr Nikolai Windbichler, Reader in Genetics at Imperial, and Dr Dickson Wilson Lwetoijera, Principal Research Scientist at Ifakara Health Institute in Tanzania. Professor Christophides from Imperial’s Department of Life Sciences said: “The solutions we currently have for malaria are not enough – we need something new. “Our technology is equitable, it offers hope in the fight against malaria and doesn’t present economic or social barriers to malaria intervention access.”
2nd Edition Report: Gene Drives for Malaria Control and Elimination in Africa
34579African Union High-Level Panel on Emerging Technologies, APET Secretariat, 2025-03-12 16:43:52.
Malaria continues to impose a significant economic and public health burden on Africa. In 2021, the continent accounted for 95% of the global 247 million new malaria cases and 96% of the 619,000 malaria-related deaths. Notably, over three-quarters (77%) of these deaths occurred among children under the age of five. At present, ten countries—Burkina Faso, Cameroon, the Democratic Republic of the Congo, Ghana, Mali, Mozambique, Niger, Nigeria, Uganda, and the United Republic of Tanzania—have been classified as High Burden, High Impact (HBHI) nations, collectively contributing to 68% of all malaria cases and 70% of malaria-related fatalities globally. Furthermore, approximately 1,031,000,000 individuals across Africa are estimated to be at risk of contracting malaria. Extensive studies have consistently demonstrated a strong correlation between economic development rates and the burden of malaria, underscoring malaria’s role as a critical impediment to economic progress. The direct economic costs of malaria are substantial, placing immense strain on the limited resources of the affected African nations. Countries severely burdened by malaria exhibit Gross Domestic Products (GDPs) that are up to five times lower than those of malaria-free nations. The annual economic growth loss in endemic countries is estimated at 1.3%, equating to as much as US$12 billion in lost productivity. Moreover, malaria contributes to between 5-8% of school absenteeism among African children and causes an additional 2.4 to 6.5 days of absenteeism per student. The costs associated with malaria prevention and treatment further highlight the economic challenge. The annual cost of protecting one individual against malaria ranges from US$1.18 to US$5.97 through vector control measures. Diagnosis costs have a median of US$6, while treatment costs for each case vary depending on severity, ranging from US$9 to US$89.93. As such, malaria remains the foremost public health priority in Africa, with the costs of treatment and disease prevention far exceeding the financial capacities of most African governments. A further pressing concern is the recent introduction and establishment of Anopheles stephensi, a species of mosquito that poses a significant threat to the Horn of Africa and beyond. This invasive species, which tends to bite outdoors, could exacerbate the existing malaria burden and undermine the gains made in malaria control over the past two decades. The global response to malaria control heavily relies on donor funding, which is currently only sufficient to meet half of the required global funding targets. This reliance on external financing is unsustainable and highly vulnerable to shifts in political priorities in donor countries. Approximately a quarter of the global malaria funding is directed to Africa for the provision of insecticide-treated nets, rapid diagnostic tests, and medicines, while national funding should cover the operating costs of the broader health sector. Existing malaria control measures, including the use of Long-Lasting Insecticidal Nets (LLINs), Indoor Residual Spraying (IRS), and Larval Source Management (LSM), have demonstrated limited effectiveness, especially against the newly introduced invasive mosquito species. This underscores the necessity for the development and adoption of innovative mosquito control approaches, such as Attractive Targeted Sugar Bait (ATSB), Endocticides, Improved Housing, Sterile Insect Technique (SIT), and Paratransgenesis. Research into these methods is ongoing, and their potential for improving malaria control strategies is considerable. To supplement existing malaria control efforts, innovative technologies like Gene Drive present promising long-term solutions to protect the most vulnerable populations and address the malaria burden in Africa. The African Union (AU) has recognised the potential of Gene Drive technology and has endorsed its development, with support from the African Union Development Agency (AUDA-NEPAD). This initiative aims to foster conducive environments for research, develop regulatory frameworks, and engage stakeholders across African Union Member States, ensuring a collaborative approach to the ongoing fight against malaria.
Gene drive: communication, hype, and the publics
34577Boëte, C., Journal of Medical Entomology, 2025-03-12 16:35:04.
Engineered gene drive (EGD) systems are probably the most high-tech approach considered for their potential role in the control of vector-borne diseases. Interestingly, the rhetoric around it often goes along with a negative presentation of the current “conventional” tools and exaggerated promises about EGD themselves, leading to a situation of hype.
Uganda expands genetically modified mosquito survey in Mukono, Kalangala islands
34600David Ssekayinga, Monitor, 2025-02-05 10:38:42.
The Uganda Virus Research Institute (UVRI) has extended its research on the behaviour of genetically modified mosquitoes to more islands on Lake Victoria. The two islands where similar research will be conducted are Sselinya in Kalangala District and Koome in Mukono District. Gene drive mosquitoes are among the anti-malarial strategies the Ugandan government has embarked on since 2016 under the Africa Target Malaria Project, seeking to reduce fatalities resulting from the disease in the country. Scientists say they aim to develop sterile male mosquitoes that wouldn't be capable of fertilizing the female Anopheles mosquitoes which spread malaria and also intend to reduce the population of female malaria-spreading mosquitoes by having them lay fewer eggs compared to the 300 eggs that a natural female Anopheles mosquito lays. According to Krystal Birungi, the field entomologist coordinator for the Target Malaria Uganda Project, differing results from the first research in villages on the mainland and the smaller islands prompted them to explore results on the larger islands.
Generating sterile Anopheles mosquitoes to combat malaria transmission
34492Xu, X. and Champer, J., Research Communities by Springer Nature, 2025-02-04 17:49:08.
Malaria remains a deadly disease, claiming hundreds of thousands of lives worldwide every year. The primary vectors of malaria are Anopheles mosquitoes, including Anopheles gambiae and Anopheles stephensi. Controlling mosquito populations is crucial for stopping malaria transmission. Gene drive technology represents a promising alternative to traditional chemical-based control methods, offering a species-specific and eco-friendly approach. However, key challenges in developing gene drives include resistance formation due to end-joining repair after Cas9/gRNA cleavage and the fitness costs associated with drive heterozygotes. One of the most successful gene drive designs to date targets the doublesex (dsx) gene in Anopheles gambiae, as reported by Kyrou et al. (2018). The dsx gene plays a crucial role in sex differentiation, with distinct isoforms expressed in males and females. Disrupting the female-specific isoform results in female sterility. Ideally, only homozygous females exhibit sterility due to a male-like intersex phenotype, while male homozygous and heterozygous mosquitoes of both sexes remain fertile. This makes it a suitable target for a suppression gene drive aimed at reducing the number of fertile females and ultimately eliminating the population.
Life-history traits of a fluorescent Anopheles arabiensis genetic sexing strain introgressed into South African genomic background
34435Nonhlanhla L. Ntoyi, Thabo Mashatola, Jérémy Bouyer, Carina Kraupa, Hamidou Maiga, Wadaka Mamai, Nanwintoum, Bimbile‑Somda, Thomas Wallner, Danilo O. Carvalho, Givemore Munhenga and Hanano Yamada, Malaria Journal, 21. 2025-02-03 06:44:24.
South Africa has set a mandate to eliminate local malaria transmission by 2023. In pursuit of this objective a Sterile Insect Technique programme targeting the main vector Anopheles arabiensis is currently under development. Significant progress has been made towards operationalizing the technology. However, one of the main limitations being faced is the absence of an efficient genetic sexing system. This study is an assessment of an An. arabiensis (AY‑2) strain carrying the full Y chromosome from Anopheles gambiae, including a transgenic red fluorescent marker, being introgressed into a South African genetic background as a potential tool for a reliable sexing system. Adult, virgin males from the An. arabiensis AY‑2 strain were outcrossed to virgin females from the South African, Kwazulu‑Natal An. arabiensis (KWAG strain) over three generations. Anopheles arabiensis AY‑2 fluorescent males were sorted as first instar larvae (L1) using the Complex Object Parametric Analyzer and Sorter (COPAS) and later screened as pupae to verify the sex. Life history traits of the novel hybrid KWAG‑AY2 strain were compared to the original fluorescent AY‑2 strain, the South African wild‑type KWAG strain and a standard laboratory An. arabiensis (Dongola reference strain). Results: The genetic stability of the sex‑linked fluorescent marker and the integrity and high level of sexing efficiency of the system were confirmed. No recombination events in respect to the fluorescent marker were detected over three rounds of introgression crosses. KWAG‑AY2 had higher hatch rates and survival of L1 to pupae and L1 to adult than the founding strains. AY‑2 showed faster development time of immature stages and larger adult body size, but lower larval survival rates. Adult KWAG males had significantly higher survival rates. There was no significant difference between the strains in fecundity and proportion of males. KWAG‑AY2 males performed better than reference strains in f light ability tests. The life history traits of KWAG‑AY2, its rearing efficiency under laboratory conditions, the preservation of the sex‑linked fluorescence and perfect sexing efficiency after three rounds of introgression crosses, indicate that it has potential for mass rearing. The potential risks and benefits associated to the use of this strain within the Sterile Insect Technique programme in South Africa are discussed.
Integrating malaria vaccine and CRISPR/Cas9 gene drive: a comprehensive strategy for accelerated malaria eradication
34374Abraham, I.C., Aboje, J.E., Ukoaka, B.M. et al., Malaria Journal, 24. 2025-01-28 15:04:09.
Malaria remains a significant public health challenge, particularly in low- and middle-income countries, despite ongoing efforts to eradicate the disease. Recent advancements, including the rollout of malaria vaccines, such as RTS,S/AS01 and R21/Matrix-M™, offer new avenues for prevention. However, the rise of resistance to anti-malarial medications necessitates innovative strategies. This review explores the potential integration of CRISPR/Cas9 gene drive technology with malaria vaccination efforts to enhance vector control and reduce transmission. By employing gene drive mechanisms for population suppression and replacement of malaria-transmitting Anopheles mosquitoes, combined with the immunogenic properties of vaccines, a synergistic approach can be established. This paper discussed the need for integrated strategies to address the biological complexities of malaria and socio-economic factors influencing its prevalence. Challenges such as regulatory hurdles, community acceptance, ecological impacts, and sustainable funding are examined, alongside strategies for implementation within existing malaria control programmes. This integrated approach could significantly contribute to achieving the World Health Organization's targets for malaria reduction by 2030, ultimately enhancing public health outcomes and supporting broader socio-economic development.
Gene Drive Technology Offers Hope For Malaria Vector Control
34365Evrim Ağacı, The Pinnacle Gazette, 2025-01-28 13:46:11.
A team of scientists has developed an innovative gene drive targeting Anopheles stephensi mosquitoes, a key malaria vector in urban areas. Their strategy uses CRISPR technology to disrupt the doublesex (dsx) gene, crucial for female fertility, thereby reducing mosquito populations. The gene drive, called HSDdsx, showed promising results in suppressing mosquito reproduction with minimal resistance, indicating long-term effectiveness. This approach could help control malaria transmission and reduce reliance on pesticides. The research also opens doors for future advancements in pest control, with potential applications against other disease vectors, marking a significant step toward environmentally friendly solutions.
For the Sake of 600,000 Children, Science Must Be Bold
34053Laurie Zoloth, The New York Times, 2024-12-16 14:36:13.
Bold ideas in science research used to thrill us; now they seem pretty threatening. When I have written about the ethics of genetically engineered mosquitoes to combat malaria, many of my friends have expressed alarm. “What if it goes badly wrong?” they ask. What if there are unintended consequences that ripple across ecosystems? What if this is one of those technologies that cross the line from innovative to utterly world-destroying And yet, one could also ask, what if we do nothing? For that question, at least we have an answer. A report last week from the World Health Organization reveals that 597,000 people died of malaria last year, overwhelmingly children under age 5, and an estimated 263 million people were sickened. Thousands of families cradled a baby dying from a preventable fever; thousands of pregnancies ended in stillbirth or maternal death. For a time in the early 2000s, it seemed as if the world was gaining ground against malaria, but progress has stalled, cases have risen and the hopes for its near-elimination by 2030 have been scuttled. Global warming, armed conflict and lack of funding are all factors. And while new vaccines certainly will help, they are limited in their effectiveness (they reduce the risk of severe malaria by 30 percent and require four separate clinic visits). For much of the world’s poor, we still rely on the 19th-century technology of bed nets and insecticide. For the past two decades, scientists have explored whether a new technology known as a gene drive might hold the tantalizing promise of eliminating malaria by targeting the mosquitoes that carry the deadly parasite. The reason the gene drive is so potentially revolutionary — but disturbing — is that it uses genetic engineering to introduce changes in mosquitoes that do not stop with one generation, but are preferentially inherited by all future generations.
Assessing the Efficacy of Gene-Drive Technology in Reducing Malaria Transmission in Sub-Saharan Africa: Current Progress and Future Prospects
33876Bizimana Rukundo T., IAA Journal of Applied Sciences, 12(1):1-5. 2024-12-10 16:43:06.
Malaria continues to pose a significant public health challenge in Sub-Saharan Africa, necessitating innovative solutions to combat its transmission. This review examined the efficacy of gene-drive technology as a novel approach to reducing malaria transmission through genetic modifications of Anopheles mosquitoes. Utilizing a comprehensive literature review and analysis of experimental studies and pilot projects, we assessed the mechanisms of gene drives, including population suppression and replacement strategies. The findings indicated that gene-drive technology has the potential to significantly alter mosquito populations, thereby diminishing the burden of malaria. However, challenges such as ecological concerns, regulatory complexities, and public acceptance must be addressed for successful implementation. The integration of gene drives with existing malaria control measures, collaborative research efforts, and robust ethical governance is crucial for maximizing effectiveness and ensuring sustainable outcomes. Furthermore, monitoring and evaluation systems are essential for assessing the safety and efficacy of gene-drive initiatives. This review underscored the transformative potential of gene-drive technology in malaria prevention, advocating for continued dialogue among stakeholders to navigate the complexities associated with its application in Sub-Saharan Africa.
Exploring The Dynamics of Gene Drive Mosquitoes Within Wild Populations Using an Agent-Based Simulation
33614S. Wickramasooriya, I. Mahmood, et al., IEEE Xplore, 2024-11-12 13:33:12.
Gene drive technology is emerging as a potentially powerful tool in combating vector-borne diseases – notably malaria. This study introduces an agent-based model (ABM) focused on the deployment of genetically engineered mosquitoes with gene drive (GEM) in Príncipe Island, Republic of São Tomé and Príncipe, an island nation in the Gulf of Guinea, West Africa. Grounded in empirical data from laboratory and field studies, our model forecasts the dynamics of mosquito populations central to devising efficacious GEM release strategies. The core objective is to evaluate the time required for GEMs to constitute 90% of the mosquito population and to elucidate their dispersal throughout the island. This research is instrumental in understanding GEM potential in controlling malaria vectors.
GeneConvene Global Collaborative | Considerations for the First Field Trials of Gene Drive for Malaria
33388GeneConvene Global Collaborative, YouTube, 2024-11-04 17:19:36.
A webinar organized by the GeneConvene Global Collaborative discussed the potential first field trials of gene drive technology for malaria control. This genetic modification approach aims to alter mosquito populations to reduce their ability to transmit malaria. While laboratory results are promising, no field trials have been conducted yet. Experts convened to explore key considerations for trial design, including efficacy, safety, and stakeholder perceptions. The challenges of indefinite spread associated with low-threshold gene drives complicate trial logistics, necessitating a phased testing approach recommended by the WHO. Key factors for site selection include regulatory structures, existing health data, and the need for isolated mosquito populations. The session aimed to share insights and foster discussion on the future of gene drive applications in malaria control.
Exploring The Dynamics of Gene Drive Mosquitoes Within Wild Populations Using an Agent-Based Simulation
34602S. Wickramasooriya, I. Mahmood, A. Calinescu, M. Wooldridge and G. Lanzaro, 2024 Annual Modeling and Simulation Conference, Washington, D.C.:1-14. 2024-10-29 10:38:49.
Gene drive technology is emerging as a potentially powerful tool in combating vector-borne diseases – notably malaria. This study introduces an agent-based model (ABM) focused on the deployment of genetically engineered mosquitoes with gene drive (GEM) in Príncipe Island, Republic of São Tomé and Príncipe, an island nation in the Gulf of Guinea, West Africa. Grounded in empirical data from laboratory and field studies, our model forecasts the dynamics of mosquito populations central to devising efficacious GEM release strategies. The core objective is to evaluate the time required for GEMs to constitute 90% of the mosquito population and to elucidate their dispersal throughout the island. This research is instrumental in understanding GEM potential in controlling malaria vectors.
Using genomics to find solutions to malaria
32714Morgan Morris, Nature Africa, 2024-10-22 17:47:10.
Joel Odero’s experiences of malaria is wide and deep. Growing up in a village in Kenya, he not only contracted the disease numerous times, but was all too familiar with the relentless daily regimen of spraying insecticides and checking malaria nets were not ripped. Decades later, as a research scientist with the Ifakara Health Institute in Tanzania, he witnessed firsthand how, for many, that daily grind is still ongoing. As part of the institute’s teams that, between 2018 and 2022, spread out across the country to capture a range of malaria-transmitting mosquitoes for studying, he would collect samples from homes where people had to spray and check their nets every day. Odero is part of a generation of scientists trying to break the stranglehold of the Anopheles mosquitoes that transmit the disease-causing parasite. Their weapon of choice is genomics. It’s a challenge taken up by organizations like Target Malaria, a not-for-profit international research consortium featuring teams in Africa, the US and Europe, and funded by, among others, the Bill & Melinda Gates Foundation and Open Philanthropy. There, researchers’ game plan is simple: reduce the population numbers of the mosquitoes, specifically those of three related species responsible for most malaria transmissions in Africa – Anopheles gambiae, Anopheles coluzzii and Anopheles arabiensis. To do so, they are looking to capitalize on a naturally occurring phenomenon, gene drive. Often described as “selfish genetic elements”, taking the form of bits of DNA code, genes are ‘driven’ when a gene that has a favorable effect becomes more prevalent in successive generations. Typically, with both humans and mosquitoes, offspring inherit two copies of any gene, one from each parent. As a result, there is a 50/50 chance of either of the two copies being passed on to later generations. Using gene drives, researchers are manipulating the bias that is introduced to that rate of inheritance so that a specific trait is nearly 100% guaranteed to be passed on. Gene-drive malaria research takes on many forms. Two of the most popular are known as ‘population replacement’ and ‘population suppression’. With population replacement, the aim is to modify the mosquitoes so that they are no longer vectors, aka transmitters, of the malaria parasite. With population suppression – which the work of Target Malaria falls under – the goal is to reduce the mosquito population. Target Malaria’s strategy is to sterilise and reduce the number of female mosquitoes. The females transmit the malaria-causing parasite known as Plasmodium falciparum to humans, and whose numbers typically determine the size of a mosquito population. The gene drive approach would be a game changer, says Target Malaria’s Abdoulaye Diabaté, head of medical entomology and parasitology at Burkina Faso’s Research Institute in Health Sciences in Bobo-Dioulasso. “It’s clear that the tools that we have today are not the ones that can take us to malaria elimination,” says Diabaté. It is the failure of these ageing tools, or the fear that they might fail, that is driving the gene-based approach to malaria research in Africa and elsewhere.
The potential of gene drives in malaria vector species to control malaria in African environments
32702Hancock, P.A., North, A., Leach, A.W. et al., Nature Communications, 15. 2024-10-22 14:44:25.
Gene drives are a promising means of malaria control with the potential to cause sustained reductions in transmission. In real environments, however, their impacts will depend on local ecological and epidemiological factors. We develop a data-driven model to investigate the impacts of gene drives that causes vector population suppression. We simulate gene drive releases in sixteen ~ 12,000 km2 areas of west Africa that span variation in vector ecology and malaria prevalence, and estimate reductions in vector abundance, malaria prevalence and clinical cases. Average reductions in vector abundance ranged from 71.6–98.4% across areas, while impacts on malaria depended strongly on which vector species were targeted. When other new interventions including RTS,S vaccination and pyrethroid-PBO bednets were in place, at least 60% more clinical cases were averted when gene drives were added, demonstrating the benefits of integrated interventions. Our results show that different strategies for gene drive implementation may be required across different African settings.
Gene Drive and Symbiont Technologies for Control of Mosquito-Borne Diseases
32504Guan-Hong Wang, Ary Hoffmann, and Jackson Champer, Annual Review of Entomology, 70. 2024-10-08 09:05:08.
Mosquito-borne diseases, such as dengue and malaria, pose a significant burden to global health. Current control strategies with insecticides are only moderately effective. Scalable solutions are needed to reduce the transmission risk of these diseases. Symbionts and genome engineering–based mosquito control strategies have been proposed to address these problems. Bacterial, fungal, and viral symbionts affect mosquito reproduction, reduce mosquito lifespan, and block pathogen transmission. Field tests of endosymbiont Wolbachia-based methods have yielded promising results, but there are hurdles to overcome due to the large-scale rearing and accurate sex sorting required for Wolbachia-based suppression approaches and the ecological impediments to Wolbachia invasion in replacement approaches. Genome engineering–based methods, in which mosquitoes are genetically altered for the modification or suppression of wild populations, offer an additional approach for control of mosquito-borne diseases. In particular, the use of gene drive alleles that bias inheritance in their favor is a potentially powerful approach. Several drives are frequency dependent, potentially giving them broadly similar population dynamics to Wolbachia. However, public acceptance and the behavior of released drives in natural mosquito populations remain challenges. We summarize the latest developments and discuss the knowledge gaps in both symbiont- and gene drive–based methods.
Stable introduction of Wolbachia wPip into invasive Anopheles stephensi for potential malaria control
32022Yongkang Liang, Julian Liu, et al., PLoS Neglected Tropical Diseases, 2024-10-01 16:23:02.
Recent efforts have successfully utilized the endosymbiotic bacterium Wolbachia to control mosquito-transmitted viral diseases like dengue in multiple countries. However, similar initiatives have been limited in combating malaria, the most devastating and deadly mosquito-borne disease, which claims over half a million lives each year. This is primarily due to the difficulty in establishing a stable, maternally inheritable Wolbachia infection in Anopheles, the mosquito vector responsible for malaria transmission. A significant concern in malaria control is the invasion of the urban malaria vector Anopheles stephensi into Africa, where malaria burden is highest, and over 40% of the population resides in urban areas. Building on the previous breakthrough of establishing Wolbachia strain wAlbB in An. stephensi, the author has now achieved a second stable infection by transferring the wPip strain from Culex pipiens into this mosquito species using embryonic microinjection. The resultant transinfected HP1 line induces nearly complete cytoplasmic incompatibility when crossed with wild mosquitoes, displays robust fitness and male mating competitiveness, and exhibits strong resilience against heat stress. These advantageous traits position the HP1 line as a promising candidate for further development in malaria control.
10 myths and misconceptions around modified mosquitoes
31627Milliam Murigi, k24, 2024-09-23 21:32:42.
In the fight against mosquito-borne diseases, scientists have turned to groundbreaking genetic technologies to reduce disease transmission. However, Genetically Modified (GM) mosquitoes have raised concerns and sparked myths and misconceptions around it. Abraham Isah, OFAB Project officer, Nigeria demystifies them. There have been allegations that scientists have secret agendas, and that is why they’re pushing for the release of Genetically Modified (GM) mosquitoes. However, the truth, releasing GM is intended to control populations of disease-carrying mosquitoes, such as Aedes aegypti, which spread malaria, dengue, and Zika virus. These mosquitoes are engineered to either reduce the population or make it less capable of transmitting diseases. This approach has been thoroughly tested and regulated by authorities like the Environmental Protection Agency (EPA) and the World Health Organisation (WHO) to ensure safety and efficacy. The primary goal is to reduce disease burden and improve public health, not to impose a hidden agenda.
The ultra-selfish gene
31608Mathias Kirk Bonde, Works in Progress, 2024-09-18 20:59:37.
Almost every cell in our bodies contains 23 pairs of chromosomes, which are packages of the DNA and genes that provide the code for producing living things. Sperm and egg cells, however, each contain only one set of chromosomes. This set of chromosomes has been recombined from their parents’ chromosomes, meaning it contains a random mixture of segments from the parents. When a sperm and egg cell fuse, the resulting cell has a pair of each chromosome once again, resulting in 23 pairs. Because the sections of each chromosome to be passed on were selected randomly, any specific gene in a parent has only a 50 percent chance of making it to the next generation. A gene that helps organisms to have more surviving offspring will gradually become more widespread in the population. But some genes have found ways of overriding this process. For example, what if a gene makes the sperm or egg more likely to inherit the section of DNA where the gene itself is located? In that case, the selection process is no longer random, and the gene can spread across the population even if the gene carries no advantage to the animal’s fitness.
Bill Gates’ Efforts To Eradicate Malaria And The Economic Impact Of Ridding The Globe Of This Disease
31585Kaili Killpack, Yahoo Finance, 2024-09-17 10:18:40.
In a compelling drive to eradicate one of the world’s deadliest diseases, Bill Gates is leveraging his substantial influence and resources to tackle malaria with renewed vigor. His foundation's recent initiatives are centered around a multi-faceted approach that blends cutting-edge technology with grassroots interventions. Gates highlights the strategic investment in next-generation mosquito control methods, such as genetically modified insects that target and disrupt malaria transmission. This ambitious endeavor is complemented by an increased focus on innovative treatments and vaccines, aiming to outpace the disease's adaptability. Gates’ commitment underscores a broader global effort to turn the tide against malaria, demonstrating that through a combination of scientific innovation and dedicated funding, the fight against this ancient scourge is on the brink of a transformative breakthrough.
Is Kenya ready to turn to technology to finally defeat malaria?
31451Brygettes Ngana, Nation, 2024-09-04 21:31:11.
For decades, researchers have tested and refined dozens of methods to combat malaria, striving to outmaneuver the resilient mosquito. From deploying bed nets to developing indoor residual spraying, these strategies have formed the frontline defense against this persistent parasite. Over the years, tactics like sleeping under a treated mosquito net and destroying mosquito breeding areas have become ingrained in our daily lives. Yet, malaria remains one of the deadliest diseases in Africa, claiming nearly 600,000 lives annually, the majority of whom are children under the age of five. The disease is transmitted by the parasite Plasmodium falciparum, found in the female Anopheles mosquito, and thrive in the warm, tropical climates found across much of the continent. The World Health Organization (WHO) indicates that 249 million cases of malaria occurred in just 85 malaria-endemic countries in 2022. Nine out of 10 of these deaths occurred in Africa. Despite the development of new vaccines, and antimalarial drugs, progress in reducing malaria transmission, WHO says, has slowed. Even in some developed countries where it was once a distant memory, the disease is making a comeback.
A model-informed target product profile for population modification gene drives for malaria control
31339Agastya Mondal, Héctor M. Sánchez C., John M. Marshall, medRxiv, 2024-09-03 18:44:21.
As reductions in malaria transmission in sub-Saharan Africa stagnate, gene drive-modified mosquitoes represent one of the most promising novel tools for continued disease control. In order to advance from the laboratory to the field, gene drives will be assessed against target product profiles, planning tools that list minimum criteria products should satisfy as they progress through the development pipeline. Here, we use an eco-epidemiological model to investigate parameter values for population modification gene drives that satisfy two previously-discussed target outcomes: a 50% reduction in clinical malaria incidence for a duration (window-of-protection) of at least three years, and a time-to-impact of less than one year. We consider two African settings, Burkina Faso and Kenya, where gene drive mosquitoes are currently being researched, and consider three transmission intensities at each. For the gene drive product, we explore rates of homing and resistance allele generation, fitness costs associated with gene drive and non-functional resistance alleles, and the efficacy of the effector gene(s) at reducing mosquito-to-human transmission. We find that when the window-of-protection criterion is satisfied, the time-to-impact criterion also is. Target outcomes are most influenced by the fitness cost associated with the gene drive allele and effector gene efficacy. Resistance allele parameters are also highly influential on target outcomes, and determine how long the gene drive allele persists in the population after most available wild-type alleles have been cleaved. Low rates of functional resistance allele generation are preferred, while costly non-functional resistance alleles will allow the drive allele to outcompete them. Homing rates already achieved for Anopheles gene drives do not need to be improved upon. A conundrum exists whereby the most important product parameters for predicting field efficacy are those that can only be reliably measured in the field, which presents a challenge for assessment of product readiness.
World Mosquito Day: Gene Drives and CRISPR Technology
31205Public Health On Call, YouTube, 2024-08-27 14:16:24.
About this episode: World Mosquito Day, observed annually on August 20th, commemorates British doctor Sir Ronald Ross's discovery in 1897 that female Anopheles mosquitoes transmit malaria to humans. More than a century later, major advancements like genetically modifying mosquitoes—AKA gene drives—have the potential to reduce malaria cases and deaths dramatically, but not without hurdles. This special episode is an extended version of Malaria Minute, a podcast from the Johns Hopkins Malaria Research Institute.
Scientists want to use mosquito stomach bacteria to end malaria
31201Chia-Yu Chen & Shüné Oliver, Alliance for Science, 2024-08-27 14:05:18.
The months of September to May are an unfortunate season in South Africa: malaria season. The mosquito-borne disease is found in the north-eastern districts of KwaZulu-Natal, Mpumalanga and Limpopo provinces. There are fewer malaria cases in South Africa compared to other African countries. The World Health Organization estimated there were over 10 million cases of malaria in Mozambique in 2022. South Africa, that country’s neighbor, recorded 5,183 malaria cases between September 2022 and August 2023. Its relatively low case numbers may be a result of South African health authorities’ excellent work in controlling the disease (control efforts began more than 120 years ago). The last major malaria outbreak in South Africa was in 2000, when more than 60,000 cases were recorded. Also notable was the 2017 outbreak, with 28,264 cases. This combination of control efforts and low numbers may mean that South Africans think malaria is not something they need to worry about unless they travel to provincial hotspots in the months of September to May. But it remains a disease of concern – not just within the country’s borders, but in the broader southern African region. Many researchers like ourselves are working towards eliminating or even, one day, totally eradicating the disease. “Elimination” doesn’t mean there will be no malaria in the region at all. Instead, it would mean that local mosquitoes no longer spread the disease in South Africa. The reason that South Africa has not fully eliminated malaria is precisely because its local mosquito populations are still transmitting the disease. In fact, in 2023, about 17 percent of people who got sick from malaria had caught it in South Africa and not from travelling to neighboring African countries. Scientists are using and developing many different “weapons” in the fight against malaria. Our approach involves using mosquitoes’ own gut bacteria to prevent them from spreading malaria. This is a form of biocontrol, which involves the use of living organisms or natural substances to control harmful pests. The groundwork we’re laying with this ongoing research will, we believe, allow us and other scientists to create a powerful malaria-beating tool.
Malaria & Dengue; distinguishing mosquito-borne diseases
31178Grace Matheka, HapaKenya, 2024-08-25 20:26:45.
World Mosquito Day is commemorated every year on the 20th of August. The day brings an opportunity to raise awareness on the dangers posed by mosquito-borne diseases like malaria and dengue, and the ongoing efforts to combat them. Both malaria and dengue are transmitted by female mosquitoes and cause severe illness in humans. The two diseases have some similarities, and mosquito species are often confused by patients and medical personnel. Malaria is a leading cause of death in the world, with 200 million cases reported every year worldwide, leading to 600,000 deaths. Most of these deaths happen in Africa, affecting children and pregnant women most. In 2022, WHO reported that Africa was home to 94% of malaria cases at 233 million and 95% at 580 000 of malaria deaths. Children under five accounted for about 78% of all malaria deaths.
Scientists’ novel technology to conserve mosquitoes
31459Milliam Murigi, People Daily, 2024-08-20 09:24:48.
As the world celebrates World Mosquito Day today, scientists have introduced a revolutionary technology that could conserve mosquitoes instead of killing them while eliminating some of the diseases transmitted by mosquitos. Known as gene drive technology, this innovative approach promises to eliminate malaria one of the diseases that is transmitted by mosquitos without harming the mosquito population a crucial aspect that could make this solution both effective and environmentally sustainable. “Gene drives have been successfully tested in laboratory settings to reduce mosquito fertility and spread resistance genes against the malaria parasite. There are field trials and pilot studies underway to test the effectiveness and safety of gene drives in real-world environments,” says Dr Willy Tonui. Tonui, the Chairman and Executive Director at Environmental Health Safety (EHS Consultancy Ltd) also doubles up as the Founder and Head of the Secretariat at the African Genetic Biocontrol Consortium.
FILMS: Gene drive mosquitoes for malaria control
30894Sarah Hartley and Tom Law, Gene Drive Governance, 2024-07-09 08:50:21.
Gene drive mosquitoes for malaria control is a short documentary film that is beautifully shot in Uganda and explores Ugandan stakeholders’ hopes for gene drive mosquitoes – a radical new tool that offers a way to eliminate or change the mosquitoes that cause malaria. Uganda is one of the first countries in the world preparing for field trials for gene drive mosquitoes and malaria is the main cause of death in Uganda, so the stakes are high. The film builds on social science research at the University of Exeter in the UK and Makerere University in Uganda and shows how complex it is to govern gene drive.
Assessing CRISPR/Cas9 potential in SDG3 attainment: malaria elimination—regulatory and community engagement landscape
30888Snuzik, A., Malaria Journal, 23. 2024-07-07 21:42:05.
Elimination of malaria has become a United Nations member states target: Target 3.3 of the sustainable development goal no. 3 (SDG3). Despite the measures taken, the attainment of this goal is jeopardized by an alarming trend of increasing malaria case incidence. Globally, there were an estimated 241 million malaria cases in 2020 in 85 malaria-endemic countries, increasing from 227 million in 2019. Malaria case incidence was 59, which means effectively no changes in the numbers occurred, compared with the baseline 2015. Jennifer Doudna—co-inventor of CRISPR/Cas9 technology—claims that CRISPR holds the potential to lessen or even eradicate problems lying in the centre of SDGs. On the same note, CRISPR/Cas9-mediated mosquito-targeting gene drives (MGD) are perceived as a potential means to turn this trend back and put momentum into the malaria elimination effort. This paper assessed two of the critical elements of the World Health Organization Genetically modified mosquitoes (WHO GMM) Critical Pathway framework: the community and stakeholders’ engagement (inability to employ widely used frameworks, segmentation of the public, ‘bystander’ status, and guidelines operationalization) and the regulatory landscape (lex generali, ‘goldilocks dilemma’, and mode of regulation) concerning mosquito-oriented gene drives (MGD) advances. Based on the assessment findings, the author believes that CRISPR/Cas-9-mediated MGD will not contribute to the attainment of SDG3 (Target 3.3), despite the undisputable technology’s potential. This research pertains to the state of knowledge, legal frameworks, and legislature, as of November 2022.
New Global Malaria Programme operational strategy calls to accelerate the development and introduction of new tools
30874Lodney Nazaré, Outreach Network for Gene Drive Research, 2024-07-02 12:43:13.
The World Health Organization (WHO) recently published its Global Malaria Programme operational strategy 2024–2030. The document builds on the previously adopted Global technical strategy for malaria 2016-2030, and sets out priorities and key activities needed to support achievement of its ambitious goals. Progress in the fight against malaria has stalled in recent years, and the world is currently off track to meet the GTS 2030 targets. The new operational strategy recognizes that a “business as usual” approach to malaria will not be enough and that “changing the trajectory of current malaria trends will require urgent and concerted efforts across the malaria ecosystem”. Progress has particularly levelled-off in high-burden countries in sub-Saharan Africa, where young children and pregnant women living in poverty are most vulnerable. Existing interventions and tools are facing the risk of reduced effectiveness due to quality concerns and biological threats, such as drug and insecticide resistance. These threats are compounded by funding shortfalls and the impacts of climate change, which is affecting the geographical range, seasonality and transmission of malaria.
The race against time to defeat mosquito-borne diseases
30858Michael Peel, Financial Times, 2024-06-28 15:51:06.
Deep in the bowels of Imperial College London’s main campus is a facility known as the insectary. The journey to it, via basement corridors and an entrance that sounds an alarm upon opening, feels like something out of a horror film. Beyond two sets of double doors lies the reason for the security: thousands of the Anopheles mosquito that has long been humanity’s deadliest animal threat. The insects in these temperature-controlled chambers are central to pioneering efforts to use genetic engineering to stop them passing on life-threatening malaria. Federica Bernardini, a research associate, places a hand close to the white mesh sides of a box housing the biting bugs. “I am not going to put it there for long,” Bernardini says, quickly pulling back from the tiny creatures. The Imperial work is part of a global struggle against the intensifying threat of mosquitoes and the destructive pathogens they carry. The first malaria vaccination campaign is being rolled out this year, while researchers are exploring ways to stem disease that are both ingenious and — in the case of genetic engineering — controversial to some. It is part of a wider public health battle against various infectious diseases that have surged in recent years due to environmental change, the Covid-19 pandemic and other factors. The mosquito campaign is a race against the clock. The insects are becoming more resistant to traditional prevention methods, while the climate crisis has opened up new regions where they can thrive.
Eliminating malaria vectors with precision-guided sterile males
30852Reema A. Apte, Andrea L. Smidler, James J. Pai, et al, Applied Biological Sciences, 121. 2024-06-28 12:20:46.
Controlling the principal African malaria vector, the mosquito Anopheles gambiae, is considered essential to curtail malaria transmission. However, existing vector control technologies rely on insecticides, which are becoming increasingly ineffective. Sterile insect technique (SIT) is a powerful suppression approach that has successfully eradicated a number of insect pests, yet the A. gambiae toolkit lacks the requisite technologies for its implementation. SIT relies on iterative mass releases of nonbiting, nondriving, sterile males which seek out and mate with monandrous wild females. Once mated, females are permanently sterilized due to mating-induced refractoriness, which results in population suppression of the subsequent generation. However, sterilization by traditional methods renders males unfit, making the creation of precise genetic sterilization methods imperative. Here, we introduce a vector control technology termed precision-guided sterile insect technique (pgSIT), in A. gambiae for inducible, programmed male sterilization and female elimination for wide-scale use in SIT campaigns. Using a binary CRISPR strategy, we cross separate engineered Cas9 and gRNA strains to disrupt male-fertility and female-essential genes, yielding >99.5% male sterility and >99.9% female lethality in hybrid progeny. We demonstrate that these genetically sterilized males have good longevity, are able to induce sustained population suppression in cage trials, and are predicted to eliminate wild A. gambiae populations using mathematical models, making them ideal candidates for release. This work provides a valuable addition to the malaria genetic biocontrol toolkit, enabling scalable SIT-like confinable, species-specific, and safe suppression in the species.
Mosquito population structure and gene-drive
30499Heredity Podcast, 2024-06-04 20:59:37.
Gene-drives hold great potential for the control of biological pests, but first they need to be thoroughly tested under appropriate conditions. In this episode we discuss some new work assessing whether mosquito populations in Northern Australia could be used to test a gene-drive targeting malaria mosquitoes.
Investigating the ecological role of malaria mosquitoes
30358Talya D. Hackett, Outreach Network for Gene Drive Research, 2024-05-21 20:22:50.
A team of entomologists and ecologists at the University of Ghana have been working with colleagues from the University of Oxford and the Centre for Biodiversity Genomics at the University of Guelph on a groundbreaking project to investigate the potential ecological consequences of reducing the population of the malaria mosquito Anopheles gambiae. This research is a key part of our work at Target Malaria, a not-for-profit research consortium whose aim is to develop new tools to reduce malaria transmission. The “ecological observatory project” studies the ecological interactions between An.gambiae and other species in the local ecosystem, including its larval competitors and predators, adult predators, and plant species that it might visit for sugar meals. By collecting data on the community ecology surrounding these mosquitoes, we can predict the effect, if any, that reducing their numbers could have on the ecosystem.
Curing mosquitoes with genetic approaches for malaria control
30356Mary Kefi, Victor Cardoso-Jaime, Sally A. Saab, George Dimopoulos, Trends in Parasitology, 2024-05-21 19:48:52.
Malaria remains a persistent global public health challenge because of the limitations of current prevention tools. The use of transgenic mosquitoes incapable of transmitting malaria, in conjunction with existing methods, holds promise for achieving elimination of malaria and preventing its reintroduction. In this context, population modification involves the spread of engineered genetic elements through mosquito populations that render them incapable of malaria transmission. Significant progress has been made in this field over the past decade in revealing promising targets, optimizing genetic tools, and facilitating the transition from the laboratory to successful field deployments, which are subject to regulatory scrutiny. This review summarizes recent advances and ongoing challenges in ‘curing’ Anopheles vectors of the malaria parasite.
Where gene drive fits into WHO’s new Global Malaria Programme operational strategy
30354Mouhamed Drabo, Target Malaria, 2024-05-21 19:35:24.
On the 23rd of April 2024, WHO published an updated operational strategy for its Global Malaria Programme for the years 2024-2030. The Global Malaria Programme was initially guided by a strategy intended to cover the years 2016-2030, which served as a framework and guide for efforts to reduce the global malaria incidence and mortality rates by at least 90% within that period. Since then, a stall in progress has indicated that a different, more intensive approach needs to be taken. WHO’s updated operational strategy, notes that ‘In 2022, there were an estimated 249 million new cases of malaria worldwide, compared to 231 million in 2015.’, indicating that current efforts towards malaria elimination are not effective enough, and that the current framework, which was last revised in 2021, required for a new update.
A Y chromosome-linked genome editor for efficient population suppression in the malaria vector Anopheles gambiae
30350Ignacio Tolosana, Katie Willis, Austin Burt, Matthew Gribble, Tony Nolan, Andrea Crisanti, Federica Bernardini, bioRxiv, 2024-05-21 18:59:24.
Genetic control – the deliberate introduction of genetic traits to control a pest or vector population – offers a powerful tool to augment conventional mosquito control tools that have been successful in reducing malaria burden but that are compromised by a range of operational challenges. Self-sustaining genetic control strategies have shown great potential in laboratory settings but hesitancy due to their invasive and persistent nature may delay their implementation. Here instead we describe a self-limiting strategy, designed to have geographically and/or temporally restricted effect, based on a Y chromosome-linked genome editor (YLE). The YLE comprises a CRISPR-Cas9 construct that is always inherited by males yet generates an autosomal dominant mutation that is transmitted to over 90% of the offspring and results in female-specific sterility. Males are unaffected. To our knowledge, our system represents the first engineering of the Y chromosome to generate a genetic control strain for mosquitoes. Mathematical modelling shows that this YLE technology is up to 8 times more efficient for population suppression than optimal versions of other self-limiting strategies.
Gene drive mosquitoes designed to eliminate malaria – but governance is complex, new film shows
29897Russell Parton, University of Exeter, 2024-05-07 16:59:05.
A radical new biotechnology could eliminate the mosquitoes that cause malaria, but in Uganda – where malaria is the leading cause of death – a lack of information and debate is undermining public debate on the issue. Professor Sarah Hartley’s new research documentary Gene Drive Mosquitoes for Malaria Control, which will be screened at Exeter Phoenix on 29 April, looks at this potentially game-changing technology through conversations with Ugandan stakeholders and explores the complexities of governance. Gene drive mosquitoes are being researched in Uganda by scientists at the Ugandan Virus Research Institute, and could soon be trialled in the wild – making Uganda one of the first countries to do so. Gene drive targets the particular genes in the malaria-transmitting female mosquito, making it unable to reproduce or transmit malaria. But unlike in other forms of genetic modification, the altered gene is inherited by more than 95% of offspring, which means the trait increases over time – allowing it to spread through a whole population. This means we could change the mosquito at a scale never seen before. Gene drive offers the possibility of controlling malaria, but the decision to release gene drive mosquitoes into the wild hinges not only on the science but on social, political and environmental issues and the support of the public.
How could genetic approaches be integrated in the malaria toolkit?
29889Damaris Matoke-Muhia, Outreach Network for Gene Drive Research, 2024-05-07 16:29:20.
The Outreach Network for Gene Drive Research organized a symposium on the margins of the Multilateral Initiative on Malaria (MIM Society)’s 8th Pan-African Malaria Conference held last week in Kigali, Rwanda. The event explored how novel genetic approaches could be integrated into the malaria toolkit and contribute to end malaria. I had the pleasure of participating in the Network’s symposium “Integrating genetic approaches in the malaria toolkit” as a panellist alongside Lucy Okell, Imperial College London and Isabelle Coche, Secretariat of the Outreach Network for Gene Drive Research. The session was chaired by El Hadji Amadou Niang, Pan-African Mosquito Control Association (PAMCA). Speakers discussed the potential of genetic approaches such as gene drive technologies to offer a sustainable, long term and cost-effective solution that could, in the context of integrated approaches to malaria control, contribute to the elimination of the disease. Presentations emphasized the need for collaboration, effective governance, multi-stakeholder engagement and strategic planning to support the effective integration of gene drive technologies into malaria control strategies.
Wolbachia infection-responsive immune genes suppress Plasmodium falciparum infection in Anopheles stephensi
29565Vandana V, Dong S, Sheth T, Sun Q, Wen H, Maldonado A, et al., PLoS Pathogens, 20. 2024-04-25 18:04:55.
Wolbachia, a maternally transmitted symbiotic bacterium of insects, can suppress a variety of human pathogens in mosquitoes, including malaria-causing Plasmodium in the Anopheles vector. However, the mechanistic basis of Wolbachia-mediated Plasmodium suppression in mosquitoes is not well understood. In this study, we compared the midgut and carcass transcriptomes of stably infected Anopheles stephensi with Wolbachia wAlbB to uninfected mosquitoes in order to discover Wolbachia infection-responsive immune genes that may play a role in Wolbachia-mediated anti-Plasmodium activity. We show that wAlbB infection upregulates 10 putative immune genes and downregulates 14 in midguts, while it upregulates 31 putative immune genes and downregulates 15 in carcasses at 24 h after blood-fed feeding, the time at which the Plasmodium ookinetes are traversing the midgut tissue. Only a few of these regulated immune genes were also significantly differentially expressed between Wolbachia-infected and non-infected midguts and carcasses of sugar-fed mosquitoes. Silencing of the Wolbachia infection-responsive immune genes TEP 4, TEP 15, lysozyme C2, CLIPB2, CLIPB4, PGRP-LD and two novel genes (a peritrophin-44-like gene and a macro domain-encoding gene) resulted in a significantly greater permissiveness to P. falciparum infection. These results indicate that Wolbachia infection modulates mosquito immunity and other processes that are likely to decrease Anopheles permissiveness to Plasmodium infection.
African health ministers commit to concerted action to end malaria deaths
29556Felista Tarimo, Outreach Network for Gene Drive Research, 2024-04-25 17:39:16.
On March 6, health ministers from African countries with the highest burden of malaria met in Yaoundé, Cameroon, and signed a declaration committing to the fundamental principle “that no one should die from malaria.” The Declaration for Accelerated Malaria Mortality Reduction in Africa signals a unified commitment to achieving a future free from malaria deaths on the continent. Despite advances made in the fight against the disease over the last two decades, the World Health Organization (WHO) African Region still accounts for over 90% of malaria cases and deaths worldwide. The 11 signatory countries to the document, which are classified as High burden High Impact (HBHI) countries — and include the United Republic of Tanzania, where I live and work — account alone for 70% of the global malaria burden. The declaration underscores the urgency of addressing several emerging and persistent challenges hindering progress in the fight against malaria, such as inadequate funding, growing biological threats — including insecticide and drug resistance — as well as low access to and insufficient quality of health services. It outlines a comprehensive plan built on four pillars: stronger political will, data-driven strategies, best practices in action, and multisectoral collaboration. Central to the Yaoundé Declaration is Point 6, which emphasizes the pivotal role of research and innovation in the quest to end malaria deaths. The fight against malaria requires constant adaptation, and this declaration acknowledges the importance of developing new tools and technologies specifically tailored to the high-burden African context. The focus on research and innovation aligns perfectly with our work at Transmission Zero. Our international research programme — that brings together collaborators from several institutions in Tanzania, the United Kingdom and Switzerland — is working to develop new genetic technologies which could reduce malaria transmission by disrupting mosquitoes’ ability to transmit the malaria parasite to humans. If proven safe and effective, this approach could complement existing tools to achieve the vision of a world free from malaria.
Genetically modified mosquitoes could one day end malaria
29553Alexis Akwagyiram, Semafor, 2024-04-25 17:31:43.
Abdoulaye Diabaté, a scientist from Burkina Faso, is at the vanguard of efforts to eliminate malaria by editing the genetic makeup of male mosquitoes and releasing them in the wild to prevent the reproduction of female mosquito species that transmit malaria. The technique is known as “gene drive” technology. Malaria kills more than 600,000 people every year, most of whom are children in Africa. Research by Diabaté, who heads medical entomology and parasitology at Burkina Faso’s Research Institute in Health Sciences, earned him the 2023 Falling Walls Prize for Science and Innovation Management. He spoke to Semafor Africa ahead of a Ted Talk on ending malaria. Gene drive offers great promises as a vector control tool. The fact that it is self-sustaining, meaning that a relatively small release of modified mosquitoes are able to spread within a population and induce suppression. It allows targeting a large area in a cost effective and self-sustaining manner, reaching areas that are difficult to control with conventional methods.
Group trains Nigerian journalists on “gene drives” controversies
29550Tosin Omoniyi, Premium Times, 2024-04-25 17:23:47.
The Renevlyn Development Initiative (RDI) held a training for Nigerian journalists on the controversies surrounding the ‘gene drives’ research organisations that allegedly target Africans as “guinea pigs.” The training, the organisers said, was aimed at equipping journalists to understand the issues and be able to report the controversies robustly. The Executive Director of RDI, Philip Jakpor, in his opening remarks, said in conceiving the training, the organisation realised that the media is key not only in keeping the public informed but also in “exposing and interrogating initiatives and innovations that are extraneous to Africans and African culture as part of its watchdog role”. Gene drive is a technology that allows a chosen set of genes to alter an animal’s biology in certain ways, such as making them produce sterile offspring. The inability to reproduce then sweeps through a population, upending the “laws of inheritance.” Specifically, the genes copy themselves exponentially from generation to generation, rapidly coming to dominate the whole population. Potentially, scientists argue that their careful use might save millions of lives by making, for instance, mosquitoes unable to transmit malaria or by eliminating the insects entirely. The possibility of a definitive solution to major infectious diseases makes a compelling case for such a technology.
Bacterial warriors fight mosquito-borne diseases
29114Alejandra Manjarrez, Drug Discovery News, 2024-04-16 21:12:48.
Every time a mosquito bites a person, multiple feasts take place. As in most animals, a meal provides nutrients to the mosquito as well as to the troop of bacteria that inhabits its gut. Occasionally, the mosquito may also ingest a parasite: a Plasmodium protozoan responsible for malaria in humans, or an arbovirus, which can cause dengue, chikungunya, Zika, or yellow fever. The pathogen is just along for the ride, but those first hours after being ingested are crucial for its survival. The parasite develops in the insect’s midgut lumen, and any interference during this period may hamper its future survival and transmission. When the mosquito ingests blood, the number of bacteria in its midgut increases dramatically. “That’s easy to understand because they use the nutrients of the blood to multiply,” noted Marcelo Jacobs-Lorena, a malaria researcher at the Johns Hopkins Bloomberg School of Public Health. “You have a few parasites surrounded by a huge number of bacteria.” These bacteria become promising targets for intervening in the development of parasites during their most vulnerable stages, either by competing for resources or directly attacking the threat. In the ongoing battle against mosquito-borne diseases that kill more than a million people each year, scientists like Jacobs-Lorena increasingly turn to mosquito microbiota as allies in disease prevention (1). Delving into the guts and other bacteria-inhabited parts of mosquitoes is beginning to bear fruit. The performance of these bacteria in laboratory and semi-field experiments is promising. Releasing mosquitoes armed with a virus-fighting bacterium in cities affected by dengue significantly decreased its incidence in those locations. While these interventions don’t offer a silver bullet against mosquito-borne diseases, they appear to be a game-changer in the fight against those deadly parasites.
Africa’s Champion Against Malaria, Professor Abdoulaye Diabaté on stage at TED2024
29112Nelly Gachanja, African Media Agency, 2024-04-16 21:07:37.
TED2024, a hallmark event celebrating 40 years of innovation, ingenuity, creativity, courage, and generosity, taking place in Vancouver, Canada from 15-19 April, will feature Africa’s esteemed, and leading champion against malaria, Prof. Abdoulaye Diabaté as a speaker. In his Talk, titled “How to End Malaria”, Prof. Diabaté aims to catalyse transformative change in global health. Hailing from Burkina Faso, Prof. Diabaté is Head of Medical Entomology and Parasitology at the Research Institute in Health Sciences (Institut de Recherche en Sciences de la Santé – IRSS), in Bobo-Dioulasso. His acclaimed research work as Principal Investigator of Target Malaria Burkina Faso has earned him global recognition, including prestigious speaking engagements at Harvard University, interviews by several prestigious international and national media, including the CNN, BBC, Netflix, The New York Times, the National TV channels of Burkina Faso. Prof. Diabaté was recently honoured as one of the 10 global winners of the esteemed Falling Walls Science and Innovation Prize 2023. This recognition underscores his pioneering efforts in eradicating malaria through innovative gene drive mosquito technology, which holds the promise of being a self-sustaining and cost-effective method to reduce the population of malaria mosquitoes – offering hope to millions worldwide.
High-Stakes Decision Making for World-Changing Technologies
29077TEDx Talks, YouTube, 2024-04-02 19:48:16.
We have important decisions to make that require rigorous and inclusive decision-making models that can be applied on a broad scale to a growing number of emerging challenges.
African researchers committed to ending malaria
29075African Media Agency, 2024-04-02 19:38:40.
The need to encourage more young African girls to pursue careers in science cannot be overemphasized.
Uganda and Djibouti seek Friendly mosquitoes to fight malaria
29066Richard Wetaya, Alliance for Science, 2024-04-02 11:40:33.
According to Oxitec CEO Grey Frandsen, the Friendly technology platform was ideally equipped to produce a safe, sustainable solution to manage the Anopheles stephensi mosquito vector based on years of experience creating and deploying other Oxitec solutions at scale.
Flight Against Infections: The Role of Genetically Engineered Mosquitoes, with Dr. Stephanie James
28997EeKs on Health, YouTube, 2024-03-11 10:40:20.
In this episode of Causes or Cures, Dr. Eeks chats with Dr. Stephanie James about the potential use of genetically modified mosquitoes (GMMs) to fight diseases that mosquitoes carry and spread, such as Malaria and Dengue Fever. In the podcast, Dr. James provides an overview on GMMs, as well as what something called Gene Drive Modified Mosquitoes (GDMMs) are. She talks about the current state of research, testing, and describes the GeneConvene Global Collaborative "GeneConvene", which was created to advance best practices and informed decision making for developing GMMs and GDMMs. She talks about the potential benefits versus the potential risks, how they are conducting risk assessments, how they plan to test GMMs, the ethical and safety concerns, and how local communities will be included in the decision-making process.
CRISPR-mediated germline mutagenesis for genetic sterilization of Anopheles gambiae males
28970Smidler, A.L., Marrogi, E., Kauffman, J. et al., Scientific Reports, 14. 2024-03-05 13:54:40.
Rapid spread of insecticide resistance among anopheline mosquitoes threatens malaria elimination efforts, necessitating development of alternative vector control technologies. Sterile insect technique (SIT) has been successfully implemented in multiple insect pests to suppress field populations by the release of large numbers of sterile males, yet it has proven difficult to adapt to Anopheles vectors. Here we outline adaptation of a CRISPR-based genetic sterilization system to selectively ablate male sperm cells in the malaria mosquito Anopheles gambiae. We achieve robust mosaic biallelic mutagenesis of zero population growth (zpg, a gene essential for differentiation of germ cells) in F1 individuals after intercrossing a germline-expressing Cas9 transgenic line to a line expressing zpg-targeting gRNAs. Approximately 95% of mutagenized males display complete genetic sterilization, and cause similarly high levels of infertility in their female mates. Using a fluorescence reporter that allows detection of the germline leads to a 100% accurate selection of spermless males, improving the system. These males cause a striking reduction in mosquito population size when released at field-like frequencies in competition cages against wild type males. These findings demonstrate that such a genetic system could be adopted for SIT against important malaria vectors.
Biotech Mosquitoes Can Help to Regain Ground in Fight Against Malaria
28932Florence Banoba, East News, 2024-02-27 17:59:07.
In response to the recent opinion articles that ran in the National print and online media in the last couple of days (1st and 5th February, 2024), regarding the use of GMO technology as a tool in the fight against malaria, I wish to address the writer’s broad-brush dismissal of the significance of genetic modification technologies in combating malaria. It is crucial, from the outset, to clarify a fundamental distinction overlooked in the article between Gene-drive and Self-limiting technologies in addressing this global health challenge. As rightly stated in that article, gene-drive technology refers to a genetic engineering technique that aims to spread a particular gene throughout a population at an accelerated rate. The primary objective would be to either suppress a mosquito population or reduce its ability to transmit malaria. Under this method, the introduced mosquitoes are designed to stay in the environment for long. In contrast, self-limiting technology involves the introduction of genetically modified organisms which possess traits designed to limit their population growth. This technology focuses on controlling or suppressing the modified organisms themselves.
Maui ‘ground zero’ for release of billions of biopesticide lab-altered mosquitoes
28929Michael Nevradakis, LifeSite, 2024-02-27 16:57:41.
Up to 775,992,000 bacteria-infected mosquitoes could be released in Maui every week for the next 20 years, according to Hawaii Unites, an environmental advocacy group that last month lost its bid to require the state to conduct an environmental impact statement before allowing the controversial project to proceed. Hawaii Unites in May 2023 sued the state in the Circuit Court of the First Circuit in Hawaii. The group’s president and founder, Tina Lia, told The Defender: "These biopesticide lab-altered mosquitoes are already being released in East Maui. Hawaii Unites has taken the state to court seeking a ruling to require an environmental impact statement for the project and comprehensive studies of the risks". She said Hawaii Unites describes itself as “a 501(c)(3) non-profit organization dedicated to the conservation and protection of our environment and natural resources,” with a focus on “protecting the health of Hawai‘i’s people, wildlife, and the ‘āina from the State of Hawaii’s biopesticide bacteria-infected mosquito experiment.”
SPOTLIGHT: Gene Drives for Malaria Elimination in Africa
28916Ifakara Health Institute, YouTube, 2024-02-20 20:05:51.
This SPOTLIGHT Series features Dr. Marceline Finda, a distinguished Research Scientist at Ifakara Health Institute. The insightful 20-minute discussion centered around the topic: "Gene Drives for Malaria Elimination in Africa."
Intra-lineage microevolution of Wolbachia leads to the emergence of new cytoplasmic incompatibility patterns
28889Namias A, Ngaku A, Makoundou P, Unal S, Sicard M, Weill M, PLoS Biology, 2024-02-13 20:25:15.
Mosquitoes of the Culex pipiens complex are worldwide vectors of arbovirus, filarial nematodes, and avian malaria agents. In these hosts, the endosymbiotic bacteria Wolbachia induce cytoplasmic incompatibility (CI), i.e., reduced embryo viability in so-called incompatible crosses. Wolbachia infecting Culex pipiens (wPip) cause CI patterns of unparalleled complexity, associated with the amplification and diversification of cidA and cidB genes, with up to 6 different gene copies described in a single wPip genome. In wPip, CI is thought to function as a toxin-antidote (TA) system where compatibility relies on having the right antidotes (CidA) in the female to bind and neutralize the male’s toxins (CidB). By repeating crosses between Culex isofemale lines over a 17 years period, we documented the emergence of a new compatibility type in real time and linked it to a change in cid genes genotype. We showed that loss of specific cidA gene copies in some wPip genomes results in a loss of compatibility. More precisely, we found that this lost antidote had an original sequence at its binding interface, corresponding to the original sequence at the toxin’s binding interface. We showed that these original cid variants are recombinant, supporting a role for recombination rather than point mutations in rapid CI evolution. These results strongly support the TA model in natura, adding to all previous data acquired with transgenes expression.
Gene driver flies and quantum finance: News from Imperial
28872Bryony Ravate, Hayley Dunning, Imperial College London, 2024-02-13 16:54:58.
Researchers have created the first gene drive for the Mediterranean fruit fly (medfly), a global agricultural pest affecting food production. The team was led by Dr Nikolai Windbichler and Dr Angela Meccariello at Imperial's Department of Life Sciences, and included researchers from the University of East Anglia and the Hebrew University of Jerusalem. Gene drives are genetic modifications that preferentially spread throughout a species, and which are designed to reduce the population. No gene drives have been released in the wild yet, but versions in malaria-carrying mosquitos have been shown to be highly effective in the lab. This success prompted the researchers to look at other pest species that could be susceptible to similar interventions. The team were able to target the process of sex determination in medflies, creating a gene drive that transforms genetic females into fertile but harmless XX males. The proof-of-concept demonstrates how gene drives can be applied to insect pests in the same group as medflies. Dr Meccariello said: “Our results demonstrate the untapped potential for gene drives to tackle agricultural pests in an environmentally friendly and economical way.”
Scientists create first transgenic mosquito strain in Africa
28847CGTN Africa, 2024-01-28 13:15:53.
Scientists in Tanzania have created the first transgenic mosquito strain in Africa. This genetically modified strain aims to prevent malaria transmission.
Gene drives, mosquitoes, and ecosystems: An interdisciplinary approach to emerging ethical concerns
28778Ricardo D. Moreno, Luca Valera, Cristián Borgoño, Juan Carlos Castilla, José Luis Riveros, Frontiers in Environmental Science, 11. 2023-12-28 22:14:12.
Gene drives are genetic elements that in sexually reproducing organisms spread faster than those transmitted through a Mendelian fashion. Since gene drives can be engineered to modify different aspects of physiology and reproduction, they have been proposed as a new and revolutionary tool to control vector-borne diseases, particularly those transmitted by the genera Anopheles and Aedes (Culicidae), such as malaria, Dengue and Zika virus. This approach may impact on human health by lowering the transmission of such devastating diseases. However, the release of genetically modified mosquitos (or other species) into the environment raises a series of questions related to the still incipient technology and our present understanding of the complex structure and dynamics of terrestrial and aquatic ecosystems. Moreover, there are ethical concerns about human interventions in natural ecosystems that may eventually impact our way of living or the ecosystems themselves. This work is an interdisciplinary approach that analyzes from a biological, philosophical, and theological perspective the potential ecological impacts on natural environments of the release of genetically modified species, focusing on gene drive-modified mosquitos. It includes theological approach from a Catholic point of view (although it could be easily shared by other Christians) because we hold that world religions give valuable insights even though not everyone may share their groundings. We conclude that the focal problem is the relationship between humans and nature, and the release of genetically modified species may change this relationship unpredictably. However, given the complex interactions in ecosystems, new approaches such as Earth Stewardship principles could provide new and more widely accepted answers involving biological, philosophical, and theological concepts that will help engaging all relevant actors to make a better world.
Communicating Creatively About Genetically Modified Mosquitoes
28748Lorraine Gibson, Target Malaria, 2023-12-21 15:27:14.
In 2018, the Target Malaria team at Imperial College London published a landmark paper in Nature Biotechnology. The study demonstrated how gene drive mosquitoes successfully suppressed a population of wild-type malaria mosquitoes, marking a significant milestone for gene drive technology as a tool for malaria elimination. In our communications team working across Burkina Faso, Ghana, Uganda and the UK, we are exploring different, creative ways to explain the technology and its progress to the general public. By continually expanding our toolkit of science communications tools and embracing innovative approaches, we hope to bridge the gap between scientific advancements and the general public, in particular communities most affected by malaria, fostering understanding and support for our mission to combat malaria.
African scientist could wipe out malaria by editing mosquito DNA
28731Nimi Princewill, CNN, 2023-12-19 13:03:40.
Malaria is a leading cause of death in Burkina Faso, where nearly all of the West African nation’s 22 million inhabitants, especially children, are at risk of the disease, according to the World Health Organization. Malaria killed nearly 19,000 people in Burkina Faso in 2021, the most recent data from the WHO regional office for Africa showed. The disease is also one of the main causes of death in the wider African region, which shoulders the world’s largest malaria burden. Abdoulaye Diabate faced a life-threatening bout of malaria when he was just five years old. Diabate narrowly survived the mosquito-borne disease, but cousins ages three and four were not as fortunate. Diabate, who now heads medical entomology and parasitology at Burkina Faso’s Research Institute in Health Sciences, is developing an innovative technique that could potentially wipe out malaria-transmitting mosquito species by altering their genes.
To End Malaria In Africa, a Scientist From Africa Invented Gene Drive Technology.
28728Salman Ahmad, CTN News, 2023-12-19 12:41:22.
Abdoulaye Diabate, a scientist from Africa, is currently working on a groundbreaking technology called ‘gene drive’ that has the potential to eradicate malaria or the mosquitoes that cause it from the continent. Diabate, who received the prestigious 2023 Falling Walls Prize for Science and Innovation Management, is developing an ingenious technique that can eliminate female mosquitoes responsible for transmitting malaria by modifying their genes. Using gene drive technology, the reproduction of female mosquitoes is hindered by releasing genetically modified male mosquitoes into the environment. This approach would result in a significant reduction in the number of female mosquitoes, thereby combating malaria throughout the continent.
Gene Drive Technology Unlocks Innovative Potential Solutions At The Intersection Of Climate Change And Public Health
28705Krystal Birungi, African Media Agency, 2023-12-12 17:23:52.
The inaugural ‘Day of Health’ at the UN Climate Conference (COP-28) highlighted the dramatic impact of climate change on health, diseases and in particular on malaria. Heads of State and climate experts converged in Dubai to emphasise the indisputable link between climate and health, echoing WHO Director-General Dr. Tedros Adhanom Ghebreyesus’s statement that climate change is a pressing public health issue. As we grapple with the harsh reality of half a million lives lost annually to malaria, including a child succumbing every minute in Africa, it is imperative to integrate innovative solutions that address both the disease and its broader public health implications exacerbated by climate change.
Germline transformation of the West Nile Virus and avian malaria vector Culex quinquefasciatus Say using the piggyBac transposon system
28653Katherine Nevard, Rajdeep Kaur, Tim Harvey-Samuel, bioRxiv, 2023-12-05 11:04:04.
Culex quinquefasciatus Say is a mosquito which acts as a vector for numerous diseases including West Nile Virus, lymphatic filariasis and avian malaria, over a broad geographical range. As the effectiveness of insecticidal mosquito control methods declines, the need has grown to develop genetic control methods to curb the spread of disease. The piggyBac transposon system - the most widely used genetic transformation tool in insects, including mosquitoes - generates quasi-random insertions of donor DNA into the host genome. However, despite the broad reported species range of piggyBac, previous attempts to use this tool to transform Culex quinquefasciatus mosquitoes have failed. Here we report the first successful transformation of Culex quinquefasciatus with the piggyBac transposon system. Using commercially synthesised piggyBac mRNA as a transposase source, we were able to generate three independent insertions of a ZsGreen fluorescent marker gene, with transformation efficiencies of up to 5%. Through this work, we have expanded the genetic toolkit available for the genetic manipulation of Culex mosquitoes and thus removed a barrier to developing novel genetic control methods in this important disease vector.
Anopheles gambiae on remote islands in the Indian Ocean: origins and prospects for malaria elimination by genetic modification of extant populations
28597Ditter, R.E., Campos, M., Crepeau, M.W. et al., Scientific Reports, 13. 2023-11-29 16:40:50.
The mosquito Anopheles gambiae s.s. is a primary malaria vector throughout sub-Saharan Africa including the islands of the Comoros archipelago (Anjouan, Grande Comore, Mayotte and Mohéli). These islands are located at the northern end of the Mozambique Channel in eastern Africa. Previous studies have shown a relatively high degree of genetic isolation between the Comoros islands and mainland populations of A. gambiae, but the origin of the island populations remains unclear. Here, we analyzed phylogenetic relationships among island and mainland populations using complete mitochondrial genome sequences of individual A. gambiae specimens. This work augments earlier studies based on analysis of the nuclear genome. We investigated the source population of A. gambiae for each island, estimated the number of introductions, when they occurred and explored evidence for contemporary gene flow between island and mainland populations. These studies are relevant to understanding historical patterns in the dispersal of this important malaria vector and provide information critical to assessing their potential for the exploration of genetic-based vector control methods to eliminate this disease. Phylogenetic analysis and haplotype networks were constructed from mitogenome sequences of 258 A. gambiae from the four islands. In addition, 112 individuals from seven countries across sub-Saharan Africa and Madagascar were included to identify potential source populations. Our results suggest that introduction events of A. gambiae into the Comoros archipelago were rare and recent events and support earlier claims that gene flow between the mainland and these islands is limited. This study is concordant with earlier work suggesting the suitability of these oceanic islands as appropriate sites for conducting field trial releases of genetically engineered mosquitoes (GEMs).
Mosquito modification programme aiming to eliminate malaria receives US$15m
28402Hayley Dunning, Imperial College London, 2023-11-14 15:15:02.
Half of the world’s population is at risk of contracting malaria, a disease caused by parasites that are transmitted from one person to another through bites from Anopheles mosquitoes. In 2021 alone, there were over 247 million cases and 619,000 deaths from malaria, mostly children under five years old in sub-Saharan Africa. With current measures failing to halt disease transmission, new ways to control the spread of malaria are desperately needed. Transmission Zero is a global programme led by scientists at Imperial College London (Imperial) and the Ifakara Health Institute (IHI) of Tanzania, in partnership with the Tanzanian National Institute of Medical Research (NIMR), which aims to modify specific species of mosquitoes so that they are unable to transmit the disease.
Inside Gates Foundation’s $15M effort to release gene-hacked mosquitoes that end malaria with ‘killer sex’
28407Jona Jaupi, The U.S. Sun, 2023-11-14 10:26:29.
Malaria is a mosquito-borne disease caused by parasites and poses a significant threat to nearly half of the world's population. In 2021, an estimated 247 million people contracted malaria, with a staggering 619,000 deaths, per Imperial College. Most of those deaths affected children under five in sub-Saharan Africa. Because current methods for fighting malaria are falling short, innovative approaches are required – enter Transmission Zero. The program's end goal is to genetically modify specific mosquito species to make them incapable of transmitting the disease. The way this works is that the gene-modified mosquitoes get sent out into the world to breed with wild mosquitoes. The result is a new generation of mosquitoes that are born with an antimalarial modification.
What are gene drives?
28374Anonymous, MalariaGEN, 2023-11-09 09:43:47.
Among the new generation of technological tools being developed to combat malaria, there is a lot of buzz around gene drives. This is a method for genetically modifying malaria-spreading mosquitoes and ultimately reducing or replacing their populations. But how exactly do gene drives work? And how can genomic surveillance data produced by the MalariaGEN community help gene drive researchers achieve their goals safely and effectively?
Bill Gates Talks Gene Drives, mRNA, and U.S.$40m in Science Funding
28314N. Mlambo, allAfrica, 2023-10-31 08:32:46.
In 2003, the Bill and Melinda Gates Foundation launched the Grand Challenges initiative in order to find scientific solutions to these health challenges. Initially, the initiative focused on 14 scientific challenges including focusing on creating effective single-dose vaccines that can be used soon after birth, discovering drugs and delivery systems that minimise the likelihood of drug-resistant micro-organisms, creating therapies that can cure latent infection, and developing needle-free delivery systems. "We started Grand Challenges with two goals. In a narrow sense, we wanted to spur specific advances we thought could lead to breakthroughs. In 2003, we listed ... priorities like creating therapies that could cure latent TB infection - and supported researchers who had exciting ideas in those areas. In a broader sense, we hoped to inspire more brilliant scientists to share big ideas about transforming health in low-income countries. We hoped to create a scientific community that was supported to sustain R&D (Research and Development) for the benefit of billions of people who had been neglected," said co-chair of the Bill & Melinda Gates Foundation Bill Gates during his opening remarks at the Grand Challenges meeting held in Dakar, Senegal.
Conceptual risk assessment of mosquito population modification gene-drive systems to control malaria transmission: preliminary hazards list workshops
28220A. Kormos, G. Dimopoulos, E. Bier, G. C. Lanzaro, J. M. Marshall and A. A. James, Frontiers in Bioengineering and Biotechnology, 11. 2023-10-26 14:54:57.
The field-testing and eventual adoption of genetically-engineered mosquitoes (GEMs) to control vector-borne pathogen transmission will require them meeting safety criteria specified by regulatory authorities in regions where the technology is being considered for use and other locales that might be impacted. Preliminary risk considerations by researchers and developers may be useful for planning the baseline data collection and field research used to address the anticipated safety concerns. Part of this process is to identify potential hazards (defined as the inherent ability of an entity to cause harm) and their harms, and then chart the pathways to harm and evaluate their probability as part of a risk assessment. The University of California Malaria Initiative (UCMI) participated in a series of workshops held to identify potential hazards specific to mosquito population modification strains carrying gene-drive systems coupled to anti-parasite effector genes and their use in a hypothetical island field trial. The hazards identified were placed within the broader context of previous efforts discussed in the scientific literature. Five risk areas were considered i) pathogens, infections and diseases, and the impacts of GEMs on human and animal health, ii) invasiveness and persistence of GEMs, and interactions of GEMs with target organisms, iii) interactions of GEMs with non-target organisms including horizontal gene transfer, iv) impacts of techniques used for the management of GEMs and v) evolutionary and stability considerations. A preliminary hazards list (PHL) was developed and is made available here. This PHL is useful for internal project risk evaluation and is available to regulators at prospective field sites. UCMI project scientists affirm that the subsequent processes associated with the comprehensive risk assessment for the application of this technology should be driven by the stakeholders at the proposed field site and areas that could be affected by this intervention strategy.
How Genetically Modified Mosquitos can end malaria in Africa – Dr. Santos
28165S. Akioye, The Star, 2023-10-23 12:15:51.
With over 200 million cases every year and nearly 700,000 deaths, Malaria is currently one of Africa’s most dreaded sicknesses. While there have been efforts at finding different drugs for treatment, scientists are working on an innovative solution using genetically modified mosquitoes to eradicate malaria spreading mosquitoes in Africa. In this interview with Dr. Michael Santos of GeneConvene Global Collaborative, SEUN AKIOYE finds out how it will work.
This Burkinabe researcher wants his groundbreaking work to wipe out malaria, altogether
28154B. Orucho and M. Ndengar, The African Mirror, 2023-10-10 11:49:04.
ABDOULAYE Diabaté and his team are betting on gene technology to protect children like his own from malaria. Along with a clutch of brand-new vaccines, the technology could help the world end malaria for good.
Genetically modified mosquitoes will be ready by 2033 – scientists
28096D. Sekayinga, MONITOR, 2023-10-10 07:43:26.
The Uganda Virus Research Institute (UVR[) has announced that genetically modified mosquitoes will be ready within a decade. Gene-drive mosquitoes are among the anti-malarial strategies the government under the Africa Target Malaria project has embarked on since 2016, to reduce the number of malaria deaths in the country. ''If the non -Gene-drive (sterilised) mosquitoes respond positively at every stage. we shall possibly be able to have the Gene-drives 10 years from now," Dr Jonathan Kayondo, one of the researchers, made the revelation during an anti-malarial training for journalists in Kalangala District last week. Dr Kayondo said every level of research will help in information flow, especially in places where research is conducted like the island of Jaana in Bubeke Sub-county in Kalangala District and Nsazi Island in Koome Sub-county. Mukono District. The two islands have high malaria cases. He added that researchers are yet to receive some Ugandan mosquito species whose genes have beenengineered at a laboratory in the USA for trial lease. "Ne are currently looking at developing sterile male mosquitoes that wouldn't be capable offertilising the female anopheles mosquitoes that spread malaria before introducing gene-drives to thecommunity," he said.
Expansions to the MGDrivE suite for simulating the efficacy of novel gene-drive constructs in the control of mosquito-borne diseases
28003J. B. Bennett, S. L. Wu, P. R. Chennuri, K. M. Myles and M. L. Ndeffo-Mbah, BMC Research Notes, 16:258. 2023-10-05 08:39:23.
The MGDrivE (MGDrivE 1 and MGDrivE 2) modeling framework provides a flexible and expansive environment for testing the efficacy of novel gene-drive constructs for the control of mosquito-borne diseases. However, the existing model framework did not previously support several features necessary to simulate some types of intervention strategies. Namely, current MGDrivE versions do not permit modeling of small molecule inducible systems for controlling gene expression in gene drive designs or the inheritance patterns of self-eliminating gene drive mechanisms. Here, we demonstrate a new MGDrivE 2 module that permits the simulation of gene drive strategies incorporating small molecule-inducible systems and self-eliminating gene drive mechanisms. Additionally, we also implemented novel sparsity-aware sampling algorithms for improved computational efficiency in MGDrivE 2 and supplied an analysis and plotting function applicable to the outputs of MGDrivE 1 and MGDrivE 2.
The Gamble: Can Genetically Modified Mosquitoes End Disease?
27985S. Nolen, New York Times, 2023-09-29 08:00:43.
The malaria situation in São Tomé and Príncipe, an African island nation with a population of 200,000, epitomizes the current challenge in the global struggle against the disease. The country is among the world’s least developed, and it has depended on foreign aid to fight malaria. Various campaigns over the past 50 years drove cases down, only to have them resurge worse than ever when the benefactor moved on. Over the past 18 years, with nearly $21 million from the Global Fund to Fight AIDS, Tuberculosis and Malaria, São Tomé has used a package of tools — including insecticide-treated bed nets; new and better drugs; killing larvae in bodies of water; and indoor spraying of homes — to stunning effect. No one has died of malaria here in the past five years. These countries need a way to fight the disease that is permanent and does not require continuous investment. Greg Lanzaro, a molecular geneticist at the University of California, Davis, who leads the malaria team, believes his grouphas that solution. “We’ve been working on this for 30 years, and from the beginning we said, ‘It has to work, but it also has to be inexpensive,and it has to be sustainable,’” he said as he watched the mosquitoes being released in a Santo Antonio park. “And we believewe have it.” But genetic modification is a controversial endeavor. Governments are hesitant, and few in Africa have laws to regulate theuse of the technology. Its risks lie in the unknowns: Could the modified mosquito evolve in some way that has harmfuleffects on the rest of the ecosystem? Could it prompt a dangerous mutation in the malaria parasite, which will find a new way to spread to survive? It is, in essence, the Jurassic Park question: Could meddling in genetic code have catastrophic consequences that no oneanticipates?
Could a new gene-editing technique be a major breakthrough in the battle against malaria?
27888B. Cottam, GEOGRAPHICAL, 2023-09-23 07:58:35.
The idea is that since female mosquitoes typically only mate once, the mass release of the sterile male mosquitoes should prevent wild females from producing future generations. Insect populations can and have already been successfully suppressed by the release of sterilised males that have been irradiated with gamma or x-rays, a technique that was originally trialled in the USA as a way to control agricultural pests such as fruit flies and screwworms. However, that method of sterilisation has a detrimental impact on the fitness of male mosquitoes, which then struggle to compete for mates with the wild males. That’s why sterilisation needs to be done genetically.
Measuring the Impact of Genetic Heterogeneity and Chromosomal Inversions on the Efficacy of CRISPR-Cas9 Gene Drives in Different Strains of Anopheles gambiae
27837Pescod, Poppy Bevivino, Giulia Anthousi, Amalia Shelton, Ruth Shepherd, Josephine Lombardo, Fabrizio Nolan, Tony, The CRISPR Journal, 2023-09-13 09:06:32.
The human malaria vector Anopheles gambiae is becoming increasingly resistant to insecticides, spurring the development of genetic control strategies. CRISPR-Cas9 gene drives can modify a population by creating double-stranded breaks at highly specific targets, triggering copying of the gene drive into the cut site (?homing?), ensuring its inheritance. The DNA repair mechanism responsible requires homology between the donor and recipient chromosomes, presenting challenges for the invasion of laboratory-developed gene drives into wild populations of target species An. gambiae species complex, which show high levels of genome variation. Two gene drives (vas2-5958 and zpg-7280) were introduced into three An. gambiae strains collected across Africa with 5.3?6.6% variation around the target sites, and the effect of this variation on homing was measured. Gene drive homing across different karyotypes of the 2La chromosomal inversion was also assessed. No decrease in gene drive homing was seen despite target site heterology, demonstrating the applicability of gene drives to wild populations.
Buzzing breakthrough: genetic engineering gives mosquito control an upgrade
27841Sivasubbu, Sridhar Scaria, Vinod, The Hindu, 2023-09-10 09:28:26.
Throughout human history, mosquitoes have constantly buzzed in the background of human existence, irritating us with their incessant bites and occasionally wreaking havoc by transmitting deadly diseases. The earliest known mosquitoes from the fossil record date back at least 70 million years, and evidence of mosquito-borne diseases like malaria dates back to Egyptian mummies from 2000 BC. Apart from malaria, which claims the lives of over half a million people every year and infects close to 250 million, mosquitoes serve as vectors for various other diseases. These include dengue, Zika, lymphatic filariasis, and yellow fever. Understandably, our relationship with these tiny, blood-sucking insects has been far from cordial.
A recombinant Aspergillus oryzae fungus transmitted from larvae to adults of Anopheles stephensi mosquitoes inhibits malaria parasite oocyst development
27665L. Kianifard, A. M. Rafiqi, O. Akcakir, A. S. I. Aly, P. F. Billingsley and S. Uysal, Scientific Reports, 13:12177. 2023-08-25 06:27:41.
The control of malaria parasite transmission from mosquitoes to humans is hampered by decreasing efficacies of insecticides, development of drug resistance against the last-resort antimalarials, and the absence of effective vaccines. Herein, the anti-plasmodial transmission blocking activity of a recombinant Aspergillus oryzae (A. oryzae-R) fungus strain, which is used in human food industry, was investigated in laboratory-reared Anopheles stephensi mosquitoes. The recombinant fungus strain was genetically modified to secrete two anti-plasmodial effector peptides, MP2 (midgut peptide 2) and EPIP (enolase-plasminogen interaction peptide) peptides. The transstadial transmission of the fungus from larvae to adult mosquitoes was confirmed following inoculation of A. oryzae-R in the water trays used for larval rearing. Secretion of the anti-plasmodial effector peptides inside the mosquito midguts inhibited oocyst formation of P. berghei parasites. These results indicate that A. oryzae can be used as a paratransgenesis model carrying effector proteins to inhibit malaria parasite development in An. stephensi. Further studies are needed to determine if this recombinant fungus can be adapted under natural conditions, with a minimal or no impact on the environment, to target mosquito-borne infectious disease agents inside their vectors.
Can Gene-Drives Combat Vector-Borne Diseases?
27636Anonymous, tomorrow.bio, 2023-08-18 07:40:46.
Scientists, technophiles, and the medical community are abuzz with a topic that sounds like science fiction: gene-drives. Given the growing fear of vector-borne diseases, wouldn’t it be marvelous if we could meddle with genetics to drive vectors like mosquitoes to extinction? Sounds too good to be true? Let’s dive into it! Understanding Gene-Drives To comprehend how gene-drives might revolutionize disease control, we first need to understand what they are. Think of gene-drives as inherently selfish genes that ensure their own propagation throughout a population, bypassing traditional inheritance rules of mother nature. Quite enjoyably sneaky, isn't it?
How genetically modifying mosquitoes could strengthen the world’s war on malaria
27634S. Oliver and J. Raman, The Conversation, 2023-08-18 07:35:58.
Mosquitoes can be genetically modified through two different technologies. The first method, paratransgenesis, involves infecting mosquitoes with bacteria that prevent them from transmitting malaria. This doesn’t harm the mosquito. It is important not to eliminate or harm mosquitoes because they pollinate many plants and are food for animals like bats, birds and reptiles. Scientists are excited about this method following the recent discovery of a bacterium that occurs naturally in mosquitoes’ guts and appears to prevent the malaria parasite from developing inside the mosquito. The second method involves genetically modifying the mosquitoes themselves. This approach centres on gene drives: genetic systems that ensure genes of interest are inherited by all offspring in every generation. There are two types of gene drive. One aims to reduce the vector population size and is known as population suppression. The other aims to prevent the mosquito from transmitting malaria; it is known as population modification.
British super mosquitoes being deployed to wipe out malaria from the planet
27622J. Lawton, Daily Star, 2023-08-15 10:00:16.
The Brit-made mosquitoes are all male and carry a special gene to prevent female offspring from surviving into adulthood.Only females bite and spread malaria. Released into the wild Oxitec’s genetically-modified males mate with wild females. All the female offspring then die. Males - which do not bite or spread the disease - survive and go on to mate with other wild females `dramatically’ reducing the world’s mosquito population and the "spread of malaria". according to Gates. Tests have shown the super mozzies pose no risk to the environment or humans. More than one billion have so far been released worldwide with "no negative impacts", Bill wrote in an online blog. In Brazil the Brit buzzers are helping eliminate dengue fever - another mosquito-transmitted disease which kills up to 40,000-a-year. They will be introduced to Djibouti in east Africa next year to stop a rise in the number of malaria cases from 27 in 2012 to 73,000 in 2020.
Genetically modified Brit mosquitoes could stamp out malaria with Bill Gates’ backing
27619K. Williams, Mirror, 2023-08-15 09:49:13.
British super mosquitoes could be deployed worldwide to eradicate malaria. Billionaire Bill Gates is backing the British effort to send the country’s mosquitoes across the world in an effort to stamp out the deadly disease. This would work because the super mozzies, created by UK biotech firm Oxitec, are capable of killing off their disease-ridden rivals that spread the illness responsible for over half a million deaths a year.Oxitec genetically modifies insects to use them as biological insecticides. They work by the British mozzies being entirely male only and they carry a special gene that stops female offspring from surviving into adulthood. This is key because only the females bite and spread malaria. So Oxitec’s all-male mosquitoes are released into the wild and mate with the wild females, whose female offspring all die off. However, the male offspring survive and, unable to bite and spread the disease, go off into the world and mate with other wild females.
A mosquito symbiont takes down malaria
27667A. Taglialegna, Nature Reviews Microbiology, 2023-08-14 06:27:59.
Malaria, a parasitic infection transmitted by Anopheles mosquitoes, is globally prevalent. Control strategies for malaria include insecticides and antiparasitic drugs, which target the mosquito vector or the parasite in the human host, respectively. The effectiveness of these methods can be undermined by resistance; hence, new containment approaches are needed. In this study, Huang et al. discover Delftia tsuruhatensis TC1, a mosquito symbiotic bacterium that inhibits parasite development via the secretion of a small molecul
Baker: New tools can change mosquitoes’ DNA, but should it be done?
27597K. Baker, Fremont News Messenger, 2023-08-09 06:54:53.
Suppose Sauron — or perhaps Gandalf — were to offer you a magical golden ring with the power to rid the world of mosquitoes once and for all. And with their demise, to save countless human lives from the many diseases for which mosquitoes are the sole or primary vectors: Malaria, dengue, West Nile virus, chikungunya, yellow fever, filariasis, tularemia, encephalitis, Zika fever, Keystone Virus, Rift Valley Fever…And not just mosquitoes. From within the folds of his cloak the wizard draws out an array of equally luminous rings with the power to cure genetic disorders like cystic fibrosis, hemophilia, and Down’s syndrome, to rid cities of mice and rats, and free the world’s farms of weeds and insect pests without the use of pesticides. Would you take them? Those rings exist and are now being refined and tested in the Elvin forges of academic, commercial, and government research facilities around the world. They go by various names, but collectively may be referred to as CRISPR-Cas Genome Editing Systems.
Malaria’s latest foe? Bacteria.
27592M. Coulson, Johns Hopkins, 2023-08-07 06:38:09.
In a new paper published in Science, Marcelo Jacobs-Lorena, PhD, professor emeritus in Molecular Microbiology and Immunology, and his colleagues, in collaboration with researchers at GSK Global Health Medicines R&D, show that a naturally occurring bacterium and a chemical it secretes inhibit the malaria parasite’s development in mosquitoes—meaning they can’t transmit the parasite to humans. The method has distinct advantages: It’s low-tech, easily reproducible, and uses no genetic modification techniques. And, Jacobs-Lorena says, it can work in perfect concert with existing effective control strategies.
A naturally occurring bacteria can stop the malaria parasite right in a mosquito’s gut
27573A. Bhattacharya, Quartz, 2023-08-04 07:55:34.
Scientists at a GlaxoSmithKline (GSK) research facility in Spain discovered that a strain of Delftia tsuruhatensis bacterium, named Tres Cantos 1 (TC1), inhibits the malaria parasite in mosquitoes, known as Plasmodium. Researchers suspected something was going on when the mosquitoes they were using to study malaria were resisting Plasmodium infections. As noted in the study published in the peer-reviewed journal Science yesterday (Aug. 3), TC1 secretes a molecule called harmane that attacks the Plasmodium parasite, which is transmitted to humans by the bite of a mosquito.When the researchers fed the existing strain to other malaria-spreading Anopholes mosquitoes—without any human tinkering like with the genetically-modified microbes—they found the bacteria “drastically reduces malaria parasite burden in the mosquito, potentially reducing transmission to humans significantly,” GSK said in an Aug. 3 press release.
Delftia tsuruhatensis TC1 symbiont suppresses malaria transmission by anopheline mosquitoes
27565W. Huang, J. Rodrigues, E. Bilgo, J. R. Tormo, J. D. Challenger, C. De Cozar-Gallardo, I. Pérez-Victoria, F. Reyes, P. Castañeda-Casado, E. J. Gnambani, D. F. d. S. Hien, M. Konkobo, B. Urones, I. Coppens, A. Mendoza-Losana, L. Ballell, A. Diabate, T. S., Science, 381:533-540. 2023-08-04 07:30:48.
Malaria control demands the development of a wide range of complementary strategies. We describe the properties of a naturally occurring, non?genetically modified symbiotic bacterium, Delftia tsuruhatensis TC1, which was isolated from mosquitoes incapable of sustaining the development of Plasmodium falciparum parasites. D. tsuruhatensis TC1 inhibits early stages of Plasmodium development and subsequent transmission by the Anopheles mosquito through secretion of a small-molecule inhibitor. We have identified this inhibitor to be the hydrophobic molecule harmane. We also found that, on mosquito contact, harmane penetrates the cuticle, inhibiting Plasmodium development. D. tsuruhatensis TC1 stably populates the mosquito gut, does not impose a fitness cost on the mosquito, and inhibits Plasmodium development for the mosquito?s life. Contained field studies in Burkina Faso and modeling showed that D. tsuruhatensis TC1 has the potential to complement mosquito-targeted malaria transmission control. Malaria mosquitoes can act as hosts to several microorganisms, including commensal bacterial species. Huang et al. noticed that some laboratory colonies of anopheline mosquitoes were incapable of transmitting malaria parasites. These insects also harbored a few cells of a bacterium called Delftia tsuruhatensis TC1, which produces a toxic alkaloid called harmane. Bacteria-produced harmane inhibited the development of female Plasmodium parasite gametes in the mosquito gut. Harmane was found to be a contact poison that could also cross the mosquito cuticle to kill developing malaria parasites. Contained field trials in Burkina Faso, coupled with modeling studies, showed that the bacterium has the potential to be deployed in mosquito breeding sites as a component of malaria control. ?Caroline Ash A naturally occurring bacterium of anopheline mosquitoes produces an alkaloid that arrests the development of co-occurring Plasmodium oocytes
Microbe stops mosquitoes from harboring malaria parasite
27567C. Offord, Science, 2023-08-03 07:31:08.
Researchers have tried to use microbes to control mosquito-borne diseases before. The virus-fighting bacterium Wolbachia pipientis has shown particular promise against dengue fever in recent clinical trials and is already used in some areas of the world. But most methods for blocking malaria-causing Plasmodium parasites, which are transmitted by different mosquito species from dengue, have relied on genetically modified bacteria. That’s a major obstacle to regulatory and public acceptance, Barillas-Mury notes, given the unknowns of releasing edited organisms into the wild. The latest news, commentary, and research, free to your inbox daily The bacterium in the new study, published today in Science, inhibits the malaria parasite without any genetic tinkering by humans. Janneth Rodrigues, a scientific lead in global health medicines R&D at GlaxoSmithKline, and colleagues stumbled across the microbe at a GSK research center in Spain, after noticing the mosquitoes they were using for malaria research were getting harder to infect with Plasmodium.
Cost-effectiveness of Precision Guided SIT for Control of Anopheles gambiae in the Upper River Region, The Gambia
27060G. William, R. Robyn, M. Agastya, M. S. C. Hector, S. Andrea, Z. David, G. I. Patrick, D. Umberto, Alessandro, M. M. John and A. Omar, bioRxiv, 2023.07.20.549762. 2023-07-22 06:41:45.
Precision-guided sterile insect technique (pgSIT) is an extremely promising vector control intervention that can reduce and potentially eliminate the unacceptable malaria burden, particularly in sub-Saharan Africa. Here we explore the cost effectiveness of using this approach in Africa using mathematical modeling and economical analysis. Overall, we find that pgSIT represents a cost-effective and promising approach to A. gambiae control in The Gambia, with the potential to deliver significant economic and social benefits.Competing Interest StatementThis work was supported by funding from an Open Philanthropy award (309937-0001). The views, opinions, and/or findings expressed are those of the authors and should not be interpreted as representing the official views or policies of the U.S. government. Figures were created using www.BioRender.com.
Mosquitoes spread malaria. These researchers want them to fight it instead
26948G. Brumfiel, NPR, 2023-07-20 08:45:44.
Mosquitoes carry malaria, which kills hundreds of thousands of people each year. Now some researchers are trying to use genetic engineering to make the pesky insects into allies in the fight against the disease. The approach is a radical departure from traditional ways of controlling malaria. For years, public health officials have tried to limit the disease by controlling mosquito populations. But that approach is temporary, says Anthony James, a professor of molecular biology and genetics at the University of California, Irvine. Because mosquitoes are extremely tough little insects, and their populations can quickly rebound. "To try to get rid of them, I don't think it's possible," he says. Instead, James and his colleagues want to try a different approach: making mosquitoes themselves into malaria-fighting warriors.
Mosquito-friendly gene drive may lead to a malaria-free future
26945Anonymous, LIFE TECHNOLOGY, 2023-07-19 08:23:51.
A gene drive is a genetic mechanism that allows a particular gene to spread rapidly through a population. In the case of malaria, scientists are working on developing a gene drive that would make mosquitoes resistant to the parasite that causes the disease. This would reduce the number of mosquitoes that can transmit the disease to humans. However, there are concerns about the use of gene drives. One potential issue is that the gene drive could spread beyond the intended population of mosquitoes and affect other species. Another concern is that the gene drive could have unintended consequences, such as creating new diseases or disrupting ecosystems. To address these concerns, scientists are developing a new type of gene drive that is "mosquito-friendly." This means that the gene drive would only affect mosquitoes that carry the malaria parasite, rather than all mosquitoes. This would reduce the risk of unintended consequences and help to ensure that the gene drive is effective in reducing the spread of malaria.
Engineered Gut Symbiotic Bacterium-Mediated RNAi for Effective Control of Anopheles Mosquito Larvae
27559J. J. Ding, C. L. Cui, G. D. Wang, G. Wei, L. Bai, Y. F. Li, P. L. Sun, L. Dong, Z. C. Liu, J. Q. Yun, F. Li, K. Li, L. He and S. B. Wang, Microbiology Spectrum, 2023-07-17 06:46:02.
Anopheles mosquitoes are the primary vectors for the transmission of malaria parasites, which poses a devastating burden on global public health and welfare. The recent invasion of Anopheles stephensi in Africa has made malaria eradication more challenging due to its outdoor biting behavior and widespread resistance to insecticides. To address this issue, we developed a new approach for mosquito larvae control using gut microbiota-mediated RNA interference (RNAi). We engineered a mosquito symbiotic gut bacterium, Serratia fonticola, by deleting its RNase III gene to produce double-stranded RNAs (dsRNAs) in the mosquito larval gut. We found that the engineered S. fonticola strains can stably colonize mosquito larval guts and produce dsRNAs dsMet or dsEcR to activate RNAi and effectively suppress the expression of methoprene-tolerant gene Met and ecdysone receptor gene EcR, which encode receptors for juvenile hormone and ecdysone pathways in mosquitoes, respectively. Importantly, the engineered S. fonticola strains markedly inhibit the development of A. stephensi larvae and leads to a high mortality, providing an effective dsRNA delivery system for silencing genes in insects and a novel RNAi-mediated pest control strategy. Collectively, our symbiont-mediated RNAi (smRNAi) approach offers an innovative and sustainable method for controlling mosquito larvae and provides a promising strategy for combating malaria.IMPORTANCE Mosquitoes are vectors for various diseases, imposing a significant threat to public health globally. The recent invasion of A. stephensi in Africa has made malaria eradication more challenging due to its outdoor biting behavior and widespread resistance to insecticides. RNA interference (RNAi) is a promising approach that uses dsRNA to silence specific genes in pests. This study presents the use of a gut symbiotic bacterium, Serratia fonticola, as an efficient delivery system of dsRNA for RNAi-mediated pest control. The knockout of RNase III, a dsRNA-specific endonuclease gene, in S. fonticola using CRISPR-Cas9 led to efficient dsRNA production. Engineered strains of S. fonticola can colonize the mosquito larval gut and effectively suppress the expression of two critical genes, Met and EcR, which inhibit mosquito development and cause high mortality in mosquito larvae. This study highlights the potential of exploring the mosquito microbiota as a source of dsRNA for RNAi-based pest control. Mosquitoes are vectors for various diseases, imposing a significant threat to public health globally. The recent invasion of A. stephensi in Africa has made malaria eradication more challenging due to its outdoor biting behavior and widespread resistance to insecticides.
Dual effector population modification gene-drive strains of the African malaria mosquitoes, Anopheles gambiae and Anopheles coluzzii
26580R. Carballar-Lejarazú, Y. Dong, T. B. Pham, T. Tushar, R. M. Corder, A. Mondal, H. M. Sánchez C, H.-F. Lee, J. M. Marshall, G. Dimopoulos and A. A. James, Proceedings of the National Academy of Sciences, 120:e2221118120. 2023-07-11 05:52:31.
Proposed genetic approaches for reducing human malaria include population modification, which introduces genes into vector mosquitoes to reduce or prevent parasite transmission. We demonstrate the potential of Cas9/guide RNA (gRNA)?based gene-drive systems linked to dual antiparasite effector genes to spread rapidly through mosquito populations. Two strains have an autonomous gene-drive system coupled to dual anti-Plasmodium falciparum effector genes comprising single-chain variable fragment monoclonal antibodies targeting parasite ookinetes and sporozoites in the African malaria mosquitoes Anopheles gambiae (AgTP13) and Anopheles coluzzii (AcTP13). The gene-drive systems achieved full introduction within 3 to 6 mo after release in small cage trials. Life-table analyses revealed no fitness loads affecting AcTP13 gene-drive dynamics but AgTP13 males were less competitive than wild types. The effector molecules reduced significantly both parasite prevalence and infection intensities. These data supported transmission modeling of conceptual field releases in an island setting that shows meaningful epidemiological impacts at different sporozoite threshold levels (2.5 to 10 k) for human infection by reducing malaria incidence in optimal simulations by 50 to 90% within as few as 1 to 2 mo after a series of releases, and by ≥90% within 3 mo. Modeling outcomes for low sporozoite thresholds are sensitive to gene-drive system fitness loads, gametocytemia infection intensities during parasite challenges, and the formation of potentially drive-resistant genome target sites, extending the predicted times to achieve reduced incidence. TP13-based strains could be effective for malaria control strategies following validation of sporozoite transmission threshold numbers and testing field-derived parasite strains. These or similar strains are viable candidates for future field trials in a malaria-endemic region.
Mosquitoes made immune to malaria could help stamp out the disease
26614C. Wilson, NewScientist, 2023-07-10 13:29:44.
Mosquitoes have been gene edited so they are immune to the parasites that cause malaria. If released into the wild, the genetic modification should spread through a population of mosquitoes because it contains a sequence known as a “gene drive”, which means all the modified insects’ offspring would inherit the immunity. This approach could slash the numbers of malaria cases in people. Malaria is one of the world’s leading causes of death and ill health, taking a particular toll on young children in sub-Saharan Africa. Two vaccines have recently been developed, but they only give partial immunity. Other high-tech strategies against mosquito-borne diseases are under investigation, including gene drives that kill all mosquitoes in a targeted area. But these could have unpredictable effects on ecosystems, says Anthony James at the University of California, Irvine.
Routes of Introduction of Anopheles gambiae Into Remote Islands in the Indian Ocean
26612R. E. Ditter, M. Campos, M. W. Crepeau, J. Pinto, A. Toilibou, Y. Amina, Y. Lee, A. J. Cornel and G. C. Lanzaro, 2023-07-07 13:23:28.
The malaria vector Anopheles gambiae s.s., is a primary malaria vector throughout sub-Saharan Africa including the islands of the Comoros archipelago (Anjouan, Grande Comore, Mayotte and Mohéli). These islands are located at the northern end of the Mozambique Channel in eastern Africa. Previous studies have shown a relatively high degree of genetic isolation between island and mainland populations of A. gambiae, but the origin of the island populations remains unclear. Here, we analyzed phylogenetic relationships among island and mainland populations using complete mitochondrial genome sequences of individual A. gambiae specimens. We investigated the source population of A. gambiaefor each island, determined the number of introductions and estimated when they occurred, and explored evidence for contemporary gene flow between island and mainland populations. Phylogenetic analysis and haplotype networks were constructed from mitogenome sequences of 258 A. gambiae from the four islands. In addition, 112 individuals from seven countries across sub-Saharan Africa and Madagascar were included to identify potential source populations. Our results suggest that introduction events of A. gambiae into the Comoros archipelago were rare and recent events and that there is no evidence of contemporary migration between the islands and mainland Africa. This study further supports the suitability of these oceanic islands as appropriate sites for conducting field trial releases of genetically engineered mosquitoes (GEMs).
Unleashing the swarm: Battling the global mosquito menace and defending public health
26467J. Entine and S. Moxon, Genetic Literacy Project, 2023-07-05 07:47:22.
There is one solution embraced by global health experts that should be pursued aggressively, if with some caution. Scientists in real-world trials have altered the genomes of entire animal populations, including mosquitoes, to thwart the vectoring of diseases and control pests — an innovation called gene drives. Emerging gene drive technologies offer enormous potential and have already shown their value in test projects in many parts of the world. More recently, the application of CRISPR/Cas9 tools has dramatically accelerated their effectiveness. But implementation on a wider scale is progressing at a snail’s pace. Why? For the most part, it is restrained by controversy, misunderstanding and the political opposition of activist environmental groups in Europe and North America.
Malaria Cases In U.S. Trigger Unfounded Claims About Bill Gates, Mosquito Project
26378B. Y. Lee, Forbes, 2023-07-01 07:03:59.
When the U.S. Centers for Disease Control and Prevention (CDC) issued an alert about finding four malaria cases in Florida and one malaria case in Texas, it created quite a buzz. After all, these were the first reported cases of people actually catching malaria in the U.S. since 2003. Finding these five cases has raised questions about whether malaria may return to the U.S. after being largely absent for many years and whether climate change may be opening the gates for Anopheles mosquitoes to spread in the U.S. That would kind of suck since the females of certain Anopheles mosquito species can carry and transmit malaria-causing parasites. This news also opened the gates in another way—allowing a flood of even more conspiracy theories about billionaire philanthropist Bill Gates to be spread across social media. This included claims that Gates was somehow responsible for these new malaria cases via a project that has released genetically-modified mosquitoes in the U.S. However, such claims really provided zzzzzero supporting evidence and, in fact, detracted from what’s really happened.
How genetically modified mosquitoes could eradicate malaria
26308S. Jones, Nature, 2023-06-28 07:16:33.
Malaria is caused by Plasmodium parasites that are transmitted from person to person by Anopheles mosquitoes — often Anopheles gambiae, the primary vector in sub-Saharan Africa. Many approaches to malaria control focus on mosquitoes. Insecticide-treated mosquito nets and indoor spraying of insecticides, for instance, have played a massive part in malaria reduction. But still it persists. “We’ve had great success over the past 20 years, using the bed nets and spraying, but those tools are not going to be enough to eliminate malaria,” says Gregory Lanzaro, director of the Vector Genetics Laboratory at the University of California, Davis. Many researchers, including Lanzaro, are hopeful that part of the solution lies in altering the genomes of Anopheles mosquitoes. Scientists around the world are exploring how to make lasting changes to mosquito DNA that impair the insects’ ability to transmit malaria — either by making them less hospitable hosts to Plasmodium, or by interfering with their reproduction to reduce or eliminate mosquito populations. Interventions of this kind have been in development for decades, but their use in the wild could be now just years away. Ecological and ethical concerns, however, about how these modified mosquitoes will be monitored, and by whom, remain the subject of active and contentious conversation.
MGSurvE: A framework to optimize trap placement for genetic surveillance of mosquito population
26616C. H. Sánchez, D. L. Smith and J. M. Marshall, bioRxiv, 2023-06-23 13:35:51.
Genetic surveillance of mosquito populations is becoming increasingly relevant as genetics-based mosquito control strategies advance from laboratory to field testing. Especially applicable are mosquito gene drive projects, the potential scale of which leads monitoring to be a significant cost driver. For these projects, monitoring will be required to detect unintended spread of gene drive mosquitoes beyond field sites, and the emergence of alternative alleles, such as drive-resistant alleles or non-functional effector genes, within intervention sites. This entails the need to distribute mosquito traps efficiently such that an allele of interest is detected as quickly as possible - ideally when remediation is still viable. Additionally, insecticide-based tools such as bednets are compromised by insecticide-resistance alleles for which there is also a need to detect as quickly as possible. To this end, we present MGSurvE (Mosquito Gene SurveillancE): a computational framework that optimizes trap placement for genetic surveillance of mosquito populations such that the time to detection of an allele of interest is minimized. A key strength of MGSurvE is that it allows important biological features of mosquitoes and the landscapes they inhabit to be accounted for, namely: i) resources required by mosquitoes (e.g., food sources and aquatic breeding sites) can be explicitly distributed through a landscape, ii) movement of mosquitoes may depend on their sex, the current state of their gonotrophic cycle (if female) and resource attractiveness, and iii) traps may differ in their attractiveness profile. Example MGSurvE analyses are presented to demonstrate optimal trap placement for: i) an Aedes aegypti population in a suburban landscape in Queensland, Australia, and ii)an Anopheles gambiae population on the island of São Tomé, São Tomé and Príncipe. Further documentation and use examples are provided in project's documentation. MGSurvE is freely available as an open-source Python package on pypi ( https://pypi.org/project/MGSurvE/ ). It is intended as a resource for both field and computational researchers interested in mosquito gene surveillance. AUTHOR SUMMARY: Mosquito-borne diseases such as malaria and dengue fever continue to pose a major health burden throughout much of the world. The impact of currently-available tools, such as insecticides and antimalarial drugs, is stagnating, and gene drive-modified mosquitoes are considered a novel tool that could contribute to continuing reductions in disease transmission. Gene drive approaches are unique in the field of vector control in that they involve transgenes that could potentially spread on a wide scale, and consequently, surveillance is expected to be a major cost driver for the technology. This is needed to monitor for unintended spread of intact drive alleles, and the emergence of alternative alleles such as homing-resistance alleles and non-functional effector genes. Additionally, surveillance of insecticide-resistance alleles is of interest to support the impact of insecticide-based tools such as bednets. Here, we present MGSurvE, a computational framework that optimizes trap placement for genetic surveillance of mosquito populations in order to minimize the time to detection for an allele of interest. MGSurvE has been tailored to various features of mosquito ecology, and is intended as a resource for researchers to optimize the efficiency of limited surveillance resources.
Draft environmental assessment released for using modified mosquitoes to save native birds on Kauaʻi
26244Anonymous, Big Island NOW, 2023-06-23 07:24:12.
Today, the draft environmental assessment was made public for the use of Wolbachia-based incompatible male mosquitoes on Kauaʻi to stop the spread of avian malaria that is decimating native forest bird populations. The public has 31 days — from June 23 until July 24 — to comment on the draft, which was released by the U.S. Fish and Wildlife Service and the State of Hawaiʻi Division of Forestry and Wildlife. Hawaiʻi’s forest birds are facing an extinction crisis, with avian malaria a major factor. It is transmitted by non-native mosquitoes and just a single bite from an infected mosquito can be deadly. Of Kauaʻi’s 16 native honeycreepers, 10 have gone extinct and three are listed under the Endangered Species Act as threatened or endangered.
World malaria report 2023
34046Geneva: World Health Organization, Licence: CC BY-NC-SA 3.0 IGO. 2023-06-15 00:00:00.
Requirements for market entry of gene drive-modified mosquitoes for control of vector-borne diseases: analogies to other biologic and biotechnology products
26281S. L. James, H. Quemada, M. Q. Benedict and B. Dass, Frontiers in Bioengineering and Biotechnology, 11:1205865. 2023-06-08 10:56:02.
Gene drive-modified mosquitoes (GDMMs) are proposed as new tools for control and elimination of malaria and other mosquito-borne diseases, and promising results have been observed from testing conducted in containment. Although still at an early stage of development, it is important to begin now to consider approval procedures and market entry strategies for the eventual implementation of GDMMs in the context of disease control programs, as these could impact future research plans. It is expected that, as for other types of new products, those seeking to bring GDMMs to market will be required to provide sufficient information to allow the regulator(s) to determine whether the product is safe and effective for its proposed use. There already has been much emphasis on developing requirements for the biosafety components of the "safe and effective" benchmark, largely concerned with their regulation as genetically modified organisms. Other potential approval requirements have received little attention, however. Although GDMMs are expected to be implemented primarily in the context of public health programs, any regulatory analogies to other public health products, such as pharmaceuticals, vaccines, or chemical pesticides, must take into account the characteristics of live mosquito products. Typical manufacturing standards related to product identity, potency or quality will need to be adapted to GDMMs. Valuable lessons can be drawn from the regulatory approval processes for other whole organism and genetically modified (GM) organism products. Supply chain requirements, such as scale of production, location and design of production facilities, and methods of distribution and delivery, will be dependent upon the characteristics of the particular GDMM product, the conditions of use, and the region to be served. Plans for fulfilling supply chain needs can build upon experience in the development of other live insect products for use in public health and agriculture. Implementation of GDMMs would benefit from additional research on enabling technologies for long-term storage of mosquito life stages, efficient mass production, and area-wide delivery of GDMMs. Early consideration of these practical requirements for market entry will help to mitigate downstream delays in the development of these promising new technologies.
Generation game: gene-edited mosquitos to fight malaria
25551J. Opara, Sci Dev Net, 2023-06-07 08:44:49.
Population-level changes in the genetic make-up of one of the world’s deadliest animals could provide a key in the fight against malaria, proponents of a radical new technology argue. So-called gene drive technology, where genetic changes are passed down through generations, could rein in mosquito populations, or prevent them from passing on malaria.“Through genetic engineering, researchers have modified mosquitoes to favour the inheritance of genes that either will reduce the size of the population of those mosquitoes or stop them from transmitting the malaria parasite,” Michael Santos, senior vice-president and chief population health sciences officer at the US-based charity the Foundation for the National Institutes of Health (FNIH), tells SciDev.Net. “In other words, [it is about] using mosquitoes to control mosquitoes.” Malaria is one of the world’s “big three” deadly diseases, killing over half a million people in 2021, the vast majority in Africa.
The optimal strategy of incompatible insect technique (IIT) using Wolbachia and the application to malaria control
25203T. Matsufuji and S. Seirin-Lee, Journal of Theoretical Biology, 569:111519. 2023-05-29 09:18:33.
For decades, techniques to control vector population with low environmental impact have been widely explored in both field and theoretical studies. The incompatible insect technique (IIT) using Wolbachia, based on cytoplasmic incompatibility, is a technique that Wolbachia-infected male mosquitoes are incapable of producing viable offspring after mating with wild-type female mosquitoes. While the IIT method experimentally ensured its effectiveness in several field works, the failure of female mosquito population control by replacement owing to the accidental contamination of Wolbachia-infected female mosquitoes has been a concern and an obstacle in implementing the IIT method in nature. In this study, we develop a population-based IIT mathematical model using cytoplasmic incompatibility and evaluate the effectiveness of the IIT method in scenarios where contamination is present or absent. In addition, by extending the model to assess the disease infection status of the human population with malaria, we evaluate the optimal release strategy and cost for successful disease control. Our study proves that IIT could be a promising method to control mosquito-borne diseases without perfect suppression of vector mosquito population regardless of contamination.
Holobiont perspectives on tripartite interactions among microbiota, mosquitoes, and pathogens
25208R. Zheng, Q. Wang, R. Wu, P. N. Paradkar, A. A. Hoffmann and G. H. Wang, ISME, 2023-05-25 13:32:28.
Mosquito-borne diseases like dengue and malaria cause a significant global health burden. Unfortunately, current insecticides and environmental control strategies aimed at the vectors of these diseases are only moderately effective in decreasing disease burden. Understanding and manipulating the interaction between the mosquito holobiont (i.e., mosquitoes and their resident microbiota) and the pathogens transmitted by these mosquitoes to humans and animals could help in developing new disease control strategies. Different microorganisms found in the mosquito's microbiota affect traits related to mosquito survival, development, and reproduction. Here, we review the physiological effects of essential microbes on their mosquito hosts; the interactions between the mosquito holobiont and mosquito-borne pathogen (MBP) infections, including microbiota-induced host immune activation and Wolbachia-mediated pathogen blocking (PB); and the effects of environmental factors and host regulation on the composition of the microbiota. Finally, we briefly overview future directions in holobiont studies, and how these may lead to new effective control strategies against mosquitoes and their transmitted diseases.
The boundary problem: Defining and delineating the community in field trials with gene drive organisms
25098N. de Graeff, I. Pirson, R. van der Graaf, A. L. Bredenoord and K. R. Jongsma, Bioethics, 2023-05-03 10:11:03.
Despite widespread and worldwide efforts to eradicate vector-borne diseases such as malaria, these diseases continue to have an enormous negative impact on public health. For this reason, scientists are working on novel control strategies, such as gene drive technologies (GDTs). As GDT research advances, researchers are contemplating the potential next step of conducting field trials. An important point of discussion regarding these field trials relates to who should be informed, consulted, and involved in decision-making about their design and launch. It is generally argued that community members have a particularly strong claim to be engaged, and yet, disagreement and lack of clarity exist about how this "community" should be defined and delineated. In this paper, we shed light on this "boundary problem": the problem of determining how boundaries of inclusion and exclusion in (GDT) community engagement should be drawn. As our analysis demonstrates, the process of defining and delineating a community is itself normative. First, we explicate why it is important to define and delineate the community. Second, we demonstrate that different definitions of community are used and intermingled in the debate on GDTs, and argue in favor of distinguishing geographical, affected, cultural, and political communities. Finally, we propose initial guidance for deciding who should (not) be engaged in decision-making about GDT field trials, by arguing that the definition and delineation of the community should depend on the rationale for engagement and that the characteristics of the community itself can guide the effective design of community engagement strategies.
In The Face Of Nigerian Mosquito Nets, Westerners’ Gene Editing Offers Hope
24964O. Onwumere, The Nigerian Voice, 2023-04-10 10:42:21.
In Nigeria, the utilization of mosquito nets is prevalent, while in the Western world, optimism is associated with the implementation of gene editing technology. In this article, ODIMEGWU ONWUMERE reports that malaria could soon be eradicated in Nigeria. According to US scientists, Anopheles mosquitoes have been genetically modified to resist the malaria-causing parasite by incorporating various anti-malaria molecules that target different stages of the parasite's lifecycle. Nevertheless, the article highlights a lack of information on the knowledge and overall viewpoint of Nigerian scientists concerning GMMs
First transgenic mosquito made in Africa by Transmission Zero
24962H. Dunning, Imperial College London, 2023-04-04 10:33:04.
Transmission Zero, a global scientific programme led by scientists at Imperial College London and the Ifakara Health Institute (IHI) of Tanzania, in partnership with the Tanzanian National Institute of Medical Research (NIMR), announces the generation of the first transgenic mosquito strain ever to be made in Africa.This strain carries in its genome genetic modifications that will allow scientists in the future to render mosquitoes unable to transmit malaria. This major scientific achievement is a pivotal milestone in the renewed international efforts to rid Africa of malaria. Half of the world’s population is at risk of contracting malaria, a disease caused by parasites that are transmitted from one person to another through mosquito bites. In 2021 alone, there were over 247 million cases and 619,000 deaths from malaria, mostly children under five years old in sub-Saharan Africa.
The Promise and Challenge of Genetic Biocontrol Approaches for Malaria Elimination
24901S. James and M. Santos, Tropical Medicine and Infectious Disease, 2023-03-29 07:50:09.
Malaria remains an ongoing public health challenge, with over 600,000 deaths in 2021, of which approximately 96% occurred in Africa. Despite concerted efforts, the goal of global malaria elimination has stalled in recent years. This has resulted in widespread calls for new control methods. Genetic biocontrol approaches, including those focused on gene-drive-modified mosquitoes (GDMMs), aim to prevent malaria transmission by either reducing the population size of malaria transmitting mosquitoes or making the mosquitoes less competent to transmit the malaria parasite. The development of both strategies has advanced considerably in recent years, with successful field trials of several biocontrol methods employing live mosquito products and demonstration of the efficacy of GDMMs in insectary-based studies. Live mosquito biocontrol products aim to achieve area-wide control with characteristics that differ substantially from current insecticide-based vector control methods, resulting in some different considerations for approval and implementation. The successful field application of current biocontrol technologies against other pests provides evidence for the promise of these approaches and insights into the development pathway for new malaria control agents. The status of technical development as well as current thinking on the implementation requirements for genetic biocontrol approaches are reviewed, and remaining challenges for public health application in malaria prevention are discussed.
Gene Drives Are Coming
24887D. Lowe, Science, 2023-03-23 08:26:31.
Consider the “gene drive” idea - there are a lot of variations, but the general idea is that you introduce a genetic sequence into an organism that can bias (drive) its own inheritance into the next generation. This is a thumb-on-the-scale unnatural selection if ever there was one, because that biased inheritance is outside of any fitness advantage that the new sequence might bring with it. In fact, a number of gene drive ideas have the opposite sign, conferring catastrophic unfitness in order to wipe out pathogens and disease-vector organisms.Gene drives of various kinds show up in nature, though, when a gene has some sort of ability to control its own transmission. These are the so-called “selfish genes”, and some of these have no fitness advantage (or even some disadvantage) in the organisms themselves. There are a lot of potential mechanisms for this (see that link for a good review), but what you don’t see are the total-wipeout forms just mentioned, which is what we has humans might like to do to (say) mosquitos or tsetse flies. The advent of CRISPR-Cas9 technology has really brought a lot more attention to these ideas, because they make them far more possible, for better or worse.
Modeling Sustained Transmission of Wolbachia among Anopheles Mosquitoes: Implications for Malaria Control in Haiti
24916D. Florez, A. J. Young, K. J. Bernabé, J. M. Hyman and Z. Qu, Trop Med Infect Dis, 8. 2023-03-09 12:09:17.
Wolbachia infection in Anopheles albimanus mosquitoes can render mosquitoes less capable of spreading malaria. We developed and analyzed a mechanistic compartmental ordinary differential equation model to evaluate the effectiveness of Wolbachia-based vector control strategies among wild Anopheles mosquitoes in Haiti. The model tracks the mosquito life stages, including egg, larva, and adult (male and female). It also accounts for critical biological effects, such as the maternal transmission of Wolbachia through infected females and cytoplasmic incompatibility, which effectively sterilizes uninfected females when they mate with infected males. We derive and interpret dimensionless numbers, including the basic reproductive number and next-generation numbers. The proposed system presents a backward bifurcation, which indicates a threshold infection that needs to be exceeded to establish a stable Wolbachia infection. The sensitivity analysis ranks the relative importance of the epidemiological parameters at baseline. We simulate different intervention scenarios, including prerelease mitigation using larviciding and thermal fogging before the release, multiple releases of infected populations, and different release times of the year. Our simulations show that the most efficient approach to establishing Wolbachia is to release all the infected mosquitoes immediately after the prerelease mitigation process. Moreover, the model predicts that it is more efficient to release during the dry season than the wet season.
Gene Drives and Vector-Borne Diseases: A Comparative Perspective Using Malaria as a Case Study
24818S. Todi, The Takshashila Institution, 2023-03-07 15:51:15.
Gene drives are an emerging technological application to reduce the prevalence of vector-borne diseases, crop pests, and non-native invasive species. This method for vector control is currently at the research stage, with parallel community engagement programmes being carried out in African countries to raise awareness for its adoption. Yet, the risks associated with using gene drives may go beyond the communities they are deployed in. Hence, it is critical for India to understand the relevance of gene drive application in India and its neighboring countries to create effective policy measures for achieving control of vector-borne diseases. Using malaria as a case study, we argue that India currently does not require the use of gene drives to achieve control of mosquito-borne diseases. However, India should invest in research for gene drives and vaccines, while continuing with current efforts to curb vector-borne diseases. Further, India will need strong data monitoring systems to identify if any gene drive mosquitoes deployed by other countries make their way to India.
Hybrid incompatibilities in the anopheles gambiae species complex
24968A. Kriezis, Imperial College London, 2023-03-01 10:47:20.
Malaria is an infectious disease caused by parasites of the genus Plasmodium which is responsible for approximately 400,000 deaths annually, primarily in sub-Saharan Africa. Malaria is transmitted by mosquitoes belonging to the Anopheles gambiae species complex. While progress has been made to reduce the incidence of malaria, the emergence of insecticide resistance necessitates the development of novel vector control strategies. Gene drive technologies have seen significant advances in recent years, providing hope for their implementation in the near future. While gene flow has been identified between sibling species of the An. gambiae species complex, they are reproductively isolated by both pre- and post-zygotic isolation mechanisms. Interspecific crosses between most member species produce sterile hybrid males, in accordance with Haldane’s rule of speciation. The aim of this project was to support the development of gene drive technologies by investigating hybrid incompatibilities between two of the most significant vector species, Anopheles gambiae and Anopheles arabiensis. The potential for the introgression of genomic regions from one species into the genetic background of the other was investigated to help inform models regarding the spread of gene drives between sibling species. In addition, the identification of genetic elements involved in hybrid male sterility could provide potential targets for vector control strategies. Large autosomal regions were found to introgress and persist in interspecific genomes without a detectable fertility cost. In addition, the introduction of distinct autosomal regions of conspecific DNA into otherwise heterospecific genomes of hybrid males was found to overcome hybrid incompatibilities and partially restore fertility. While no specific genetic factors involved in hybrid incompatibilities could be identified, the results indicate that such factors are present at least on the X chromosome. Furthermore, the evidence suggests that asynapsis between interspecific homologous autosomes during gametogenesis plays a role in the manifestation of hybrid male sterility.
Alleviating the burden of malaria with gene drive technologies? A biocentric analysis of the moral permissibility of modifying malaria mosquitoes
24800N. de Graeff, K. R. Jongsma and A. L. Bredenoord, Journal of Medical Ethics, 2023-02-28 08:33:28.
Gene drive technologies (GDTs) have been proposed as a potential new way to alleviate the burden of malaria, yet have also raised ethical questions. A central ethical question regarding GDTs relates to whether it is morally permissible to intentionally modify or eradicate mosquitoes in this way and how the inherent worth of humans and non-human organisms should be factored into determining this. Existing analyses of this matter have thus far generally relied on anthropocentric and zoocentric perspectives and rejected an individualist biocentric outlook in which all living organisms are taken to matter morally for their own sake. In this paper, we reconsider the implications of taking a biocentric approach and highlight nuances that may not be evident at first glance. First, we shortly discuss biocentric perspectives in general, and then outline Paul Taylor's biocentric theory of respect for nature. Second, we explore how conflicting claims towards different organisms should be prioritised from this perspective and subsequently apply this to the context of malaria control using GDTs. Our ethical analysis shows that this context invokes the principle of self-defence, which could override the pro tanto concerns that a biocentrist would have against modifying malaria mosquitoes in this way if certain conditions are met. At the same time, the case study of GDTs underlines the relevance of previously posed questions and criticism regarding the internal consistency of Taylor's egalitarian biocentrism.
Will new genetic engineering tech finally eliminate malaria?
24747Anonymous, Business Daily, 2023-02-20 19:03:20.
Richard Mukabana, a senior research and policy analyst at African Institute for Development Policy, says the technology which employs the principle of sending a thief to catch a thief may yet prove the most effective. “It is only a mosquito that knows where another mosquito is and it’s easier for it to search for others and kill them through suppression,” says Prof Mukabana. In gene drive technologies, an artificial gene is introduced into the malaria-transmitting mosquito population. This then disrupts reproduction by either distorting sex chromosome inheritance such that most offspring are males, or by knocking out female fertility genes such that they no longer lay eggs. Experts argue that the current technology used in fighting malaria, which comprises vector control and drug therapy has not been sufficiently adequate to eliminate the disease on the continent, hence the need to embrace new technologies.
Gene Drives Could Fight Malaria and Other Global Killers but Might Have Unintended Consequences
24460M. Cobb, Scientific American, 2023-01-13 08:22:55.
Every year more than 600,000 people die from mosquito-transmitted malaria, most of them children under age five. Some insects that are disease vectors, such as mosquitoes, are currently expanding their range around the world, bringing new threats. Genetic engineering can fix this by permanently altering insect genes through what is known as a gene drive. This technology allows a chosen set of genes to alter an animal’s biology in some way, such as making them produce sterile offspring. The inability to reproduce then sweeps through a population, upending the laws of inheritance. The genes copy themselves exponentially from generation to generation, rapidly coming to dominate the whole population. Potentially, their careful use might save millions of lives by making mosquitoes unable to transmit malaria or by eliminating the insects entirely. The possibility of a definitive solution to major infectious diseases makes a compelling case for a such a techno fix.
Genetically modified mosquitoes … could CRISPR gene editing end malaria?
24315D. Wells, SelectScience, 2022-12-22 08:44:13.
Despite being a preventable and treatable disease, malaria is currently affecting the lives of more than 200 million people.1 This results in over half a million deaths per year, with 80% of this mortality occurring in children under the age of 5.2 In addition to the tragic social and humanitarian considerations, the economic losses to Africa attributed to malaria equate to around $12 billion a year.3 Hence, the public health burden of malaria is huge, and continued efforts in malaria control, elimination strategies, and case management are crucial to minimizing the devastation that malaria has on at-risk communities. In this article, we explore the innovative use of genetically modified mosquitoes as a means of fighting this devastating disease.
East Maui project hopes mosquito v. mosquito mating battle will save endangered birds
24173K. Cerizo, MAUINOW, 2022-12-11 11:03:34.
Bioinformatic and literature assessment of toxicity and allergenicity of a CRISPR-Cas9 engineered gene drive to control the human malaria mosquito vector Anopheles gambiae
24161A. Qureshi and J. B. Connolly, Malaria Journal, 2022-12-06 07:52:06.
Population suppression gene drive is currently being evaluated, including via environmental risk assessment (ERA), for malaria vector control. One such gene drive involves the dsxFCRISPRh transgene encoding (i) hCas9 endonuclease, (i) T1 guide RNA (gRNA) targeting the doublesex locus, and (iii) DsRed fluorescent marker protein, in genetically modified mosquitoes (GMMs). Problem formulation, the first stage of ERA, for environmental releases of dsxFCRISPRh previously identified nine potential harms to the environment or health that could occur, should expressed products of the transgene cause allergenicity or toxicity. Amino acid sequences of hCas9 and DsRed were interrogated against those of toxins or allergens from NCBI, UniProt, COMPARE and AllergenOnline bioinformatic databases and the gRNA was compared with microRNAs from the miRBase database for potential impacts on gene expression associated with toxicity or allergenicity. PubMed was also searched for any evidence of toxicity or allergenicity of Cas9 or DsRed, or of the donor organisms from which these products were originally derive While Cas9 nuclease activity can be toxic to some cell types in vitro and hCas9 was found to share homology with the prokaryotic toxin VapC, there was no evidence of a risk of toxicity to humans and other animals from hCas9. Although hCas9 did contain an 8-mer epitope found in the latex allergen Hev b 9, the full amino acid sequence of hCas9 was not homologous to any known allergens. Combined with a lack of evidence in the literature of Cas9 allergenicity, this indicated negligible risk to humans of allergenicity from hCas9. No matches were found between the gRNA and microRNAs from either Anopheles or humans. Moreover, potential exposure to dsxFCRISPRh transgenic proteins from environmental releases was assessed as negligible.Bioinformatic and literature assessments found no convincing evidence to suggest that transgenic products expressed from dsxFCRISPRh were allergens or toxins, indicating that environmental releases of this population suppression gene drive for malaria vector control should not result in any increased allergenicity or toxicity in humans or animals. These results should also inform evaluations of other GMMs being developed for vector control and in vivo clinical applications of CRISPR-Cas9.
Determining the landscape of resistance to gene drives in the malaria mosquito
27631I. Morianou, Imperial College London, 2022-12-01 10:17:51.
Gene drives are engineered selfish genetic elements with the potential to spread throughout entire insect populations for sustainable vector control. Recently, a gene drive was shown to eliminate caged populations of the malaria mosquito by targeting the highly conserved female-specific exon of the doublesex gene. This caused females, homozygous for the gene drive, to develop as sterile intersex individuals, leading to the observed population crash. However, target site resistant alleles that block gene drive activity, whilst encoding a functional copy of the target gene, may halt gene drive spread in the wild. These may be naturally occurring or generated by the gene drive itself. This thesis presents a pipeline for the discovery, genetic engineering, and testing of putative drive-resistant variants. First, to investigate the potential for natural resistance, existing population genomics data were interrogated for the presence of natural single nucleotide polymorphisms (SNPs) at the highly conserved gene drive target region. To investigate the potential for drive-induced resistance, a high-throughput assay was designed to generate a high volume of mutations at the gene drive target site and screen them for their ability to restore dsx function. These methods yielded three putatively resistant SNPs: one natural polymorphism and two rare Cas9-induced mutations. These were engineered in the mosquito genome for testing, using a novel method termed CRISPR-mediated cassette exchange (CriMCE). It was confirmed that all three polymorphisms are functional and offer full, partial or no resistance to gene drive. Importantly, partial resistance to gene drive is being demonstrated for the first time. To mitigate observed resistance, gene drive systems targeting multiple sites simultaneously were developed. These showed improved drive dynamics and caused rapid elimination of caged mosquito populations within 7-8 generations. The experimental pipeline described here can be applied to pre-empt and mitigate resistance against any gene drive strategy, prior to field testing.
A comprehensive overview of the existing microbial symbionts in mosquito vectors: An important tool for impairing pathogentransmission
24088V. Vandana, M. P. Kona, J. Kumar, O. P. Singh and K. C. Pandey, Experimental Parasitology, 243. 2022-11-30 09:06:12.
The emergence of drug-resistant parasites and/or insecticide-resistant mosquito vectors necessitates developing alternative tools that either supplement or replace the conventional malaria control strategies. Trans-infecting the mosquito vector with symbionts that can either compete with a targeted pathogen or manipulate the host biology by reducing its vectorial capacity could be a promising and innovative biological approach for the control of infectious diseases This idea could be utilized to develop a novel and efficient vector control strategy; symbionts are dispersed into vector populations to reduce their ability to transmit human pathogens. Here, we reported the natural existence of Microsporidian (an obligate fungus) in the field-collected An. stephensi mosquito. However, laboratory-reared An. stephensi and An. culicifacies did not exhibit microsporidian infection. Similarly, 16s rRNA PCR identified -1kb amplicons in laboratory-reared An. stephensi and An. culicifacies, indicating the presence of naturally residing different bacterial species. DNA sequencing of these amplicons revealed the identities of different bacteria which are not well-characterized in terms of plasmodia-interaction activity in the Indian malaria vector. This article summarizes an overview of the previously studied microbial symbionts for their role in Plasmodium transmission along with a list of new or unexplored symbionts in the disease transmitting mosquito vectors. The summarized information could be utilized to explore such microbial symbionts for their role in Plasmodium-transmission biology in-depth and implementation in the malaria control interventions globally.
Should we use a genetic weapon against mosquitoes carrying malaria?
23988T. H. Saey, ScienceNewsExplores, 2022-11-17 08:58:08.
In a large laboratory cage, a male mosquito carries a genetic weapon that could launch the destruction of his species. That loss could also mean the end of the parasite that causes malaria. The weapon? A self-replicating bit of DNA known as a gene drive. It’s one of the most anticipated tools being developed to stop mosquitoes from spreading diseases like malaria to humans. It’s also one of the most controversial. The gene drive interferes with the insects’ ability to reproduce. In one small lab study, it wiped out captive populations of mosquitoes in just eight to 12 generations. A larger study in outdoor cages in Terni, Italy, worked too. Within as little as five to 10 years, this gene drive could be ready to test in the wild. Researchers are eyeing Africa for the first test release. There, malaria takes a huge toll. In 2020, it sickened close to 241 million people on the continent. And most of the globe’s 670,000 malaria deaths that year were in Africa. About eight in every 10 were children, the World Health Organization says. Many tools have been made to fight the disease. There are preventive drugs, insecticide-treated bed nets and even vaccines. These efforts are helping. But mosquitoes are developing resistance to insecticides. And some anti-malaria drugs may no longer work well. “To go toward zero [cases], we need to have something that is transformational,” says Fredros Okumu. By that, he means a completely new type of strategy. Okumu is a mosquito biologist. He directs science programs at Ifakara Health Institute in Tanzania, a country in East Africa. Gene drives might be the big change people are looking for. This technology was first devised in 2015. Researchers are still refining and testing it. Other types of genetically altered mosquitoes have been released in Brazil, the United States and elsewhere. But so far, those altered genes spread slowly among wild populations. Gene drives could potentially spread to nearly every member of a species quickly. In this way, they could forever alter the species. Or even wipe it out.
Health experts meet in Dar over use of GMO mosquitoes to fight Malaria
23991M. Chelangat, NATION, 2022-11-16 09:03:01.
Regional health think thanks led by the African Institute for Development and Policy (AFIDEP), East African Community(EAC) Health department, East African Health Research Commission and Ifakara health institute will be meeting in Dar es Salaam, Tanzania for three day starting tomorrow to discuss the development of genetically modified mosquitoes to help in controlling and eliminating malaria.The experts will also be discussing regulatory reforms and policies, given that regulatory frameworks of many African countries do not provide clear guidance on how to develop and test genetically modified mosquitoes. According to the Centers for Disease Control and Prevention (CDC), genetically modified mosquitoes are mass produced in a laboratory to carry two types of genes.
Combining transgenesis with paratransgenesis to fight malaria
23802W. Huang, J. Vega-Rodriguez, C. Kizito, S.-J. Cha and M. Jacobs-Lorena, eLife, 11:e77584. 2022-10-25 06:30:55.
Malaria is among the deadliest infectious diseases, and Plasmodium, the causative agent, needs to complete a complex development cycle in its vector mosquito for transmission to occur. Two promising strategies to curb transmission are transgenesis, consisting of genetically engineering mosquitoes to express antimalarial effector molecules, and paratransgenesis, consisting of introducing into the mosquito commensal bacteria engineered to express antimalarial effector molecules. Although both approaches restrict parasite development in the mosquito, it is not known how their effectiveness compares. Here we provide an in-depth assessment of transgenesis and paratransgenesis and evaluate the combination of the two approaches. Using the Q-system to drive gene expression, we engineered mosquitoes to produce and secrete two effectors – scorpine and the MP2 peptide – into the mosquito gut and salivary glands. We also engineered Serratia, a commensal bacterium capable of spreading through mosquito populations to secrete effectors into the mosquito gut. Whereas both mosquito-based and bacteria-based approaches strongly reduced the oocyst and sporozoite intensity, a substantially stronger reduction of Plasmodium falciparum development was achieved when transgenesis and paratransgenesis were combined. Most importantly, transmission of Plasmodium berghei from infected to naïve mice was maximally inhibited by the combination of the two approaches. Combining these two strategies promises to become a powerful approach to combat malaria.
Target Malaria’s scientists are working to rid Africa of an ancient plague
23783D. Matthews, Vox, 2022-10-20 07:12:04.
This could very well be the last century in human history when people die from malaria. If and when we do eradicate the disease, the team at Target Malaria will probably deserve a big share of the credit. Their plan to use gene drive technology to wipe out species of mosquitoes carrying the parasitic illness represents the most promising path to eradicating a disease that killed on the order of 150 million to 300 million people over the 20th century, and still kills hundreds of thousands each year. Malaria used to be broadly common across most of the populated world, covering much of North America, Europe, Japan, and Australia, in addition to its current locations in Africa, Latin America, and South Asia. As the researchers Max Roser and Hannah Ritchie note, “poet Friedrich Schiller contracted the disease in Mannheim, Oliver Cromwell in Ireland, and Abraham Lincoln in Illinois.” Malaria no longer exists in those areas due to decades of public health measures like the drainage of mosquito breeding sites and use of pesticides like DDT, as well as economic development that gave residents resources to prevent and treat the disease.
Driving down malaria transmission with engineered gene drives
23780W. T. Garrood, P. Cuber, K. Willis, F. Bernardini, N. M. Page and R. E. Haghighat-Khah, Frontiers in Genetics, 13. 2022-10-19 07:08:43.
The last century has witnessed the introduction, establishment and expansion of mosquito-borne diseases into diverse new geographic ranges. Malaria is transmitted by female Anopheles mosquitoes. Despite making great strides over the past few decades in reducing the burden of malaria, transmission is now on the rise again, in part owing to the emergence of mosquito resistance to insecticides, antimalarial drug resistance and, more recently, the challenges of the COVID-19 pandemic, which resulted in the reduced implementation efficiency of various control programs. The utility of genetically engineered gene drive mosquitoes as tools to decrease the burden of malaria by controlling the disease-transmitting mosquitoes is being evaluated. To date, there has been remarkable progress in the development of CRISPR/Cas9-based homing endonuclease designs in malaria mosquitoes due to successful proof-of-principle and multigenerational experiments. In this review, we examine the lessons learnt from the development of current CRISPR/Cas9-based homing endonuclease gene drives, providing a framework for the development of gene drive systems for the targeted control of wild malaria-transmitting mosquito populations that overcome challenges such as with evolving drive-resistance. We also discuss the additional substantial works required to progress the development of gene drive systems from scientific discovery to further study and subsequent field application in endemic settings.
Mosquito Gene Drives and the Malaria Eradication Agenda
23731Editor: R. Carballar-Lejarazu,, Jenny Stanford Publishing, 2022-10-17 06:37:46.
Malaria is one of most serious infectious diseases today and has afflicted humankind for thousands of years. A significant number of people still die from this mosquito-borne disease, despite the use of various malaria prevention and control methods over hundreds of years and more than a century of coordinated global control efforts using modern tools, together with research into and development of new strategies for prevention, diagnosis, and disease treatment. Genetic approaches that focus on the vector mosquitoes to prevent malaria parasite transmission have been considered for many decades. Genetic control strategies received a significant boost with the successful development of gene-drive systems, genetic methods for rapidly spreading beneficial genes and phenotypes through mosquito populations. This book reviews some concepts of gene drive systems and describes pioneering applications to control mosquito populations and prevent parasite transmission.
Combating Mosquito-Borne Diseases with CRISPR
23701N. Spahich, The Scientist, 2022-10-11 08:06:34.
Female mosquitoes are some of the deadliest organisms in the world due to their ability to spread infectious diseases through a simple bite. Mosquito-borne diseases such as yellow fever, Zika, Dengue fever, and malaria kill millions of humans every year, and there are limited therapeutics for their prevention and treatment. While in college, Omar Akbari worked as a public service intern testing the local mosquito population for human pathogens and eradicating these insects with chemicals. During this experience, he felt dissatisfied with the insecticide-based method of controlling mosquito population and wanted to find a better way to tackle the problem of mosquito-borne disease spread. With a multidisciplinary team in his laboratory at the University of California, San Diego, he now develops tools through genetic engineering techniques such as CRISPR to solve the world’s insect control problems.
Research: Scientists Modify Mosquitoes That Can’t Spread Malaria
23775N. Kharbanda, Onlymyhealth, 2022-10-07 07:00:18.
According to a research, scientists have found a way to genetically engineer mosquitoes with the capability to slow down the multiplication of malaria-causing parasites in their gut. This is an advance study, that can help in preventing the infecting of the disease in humans. The disease spreads in people because of a female mosquito when it bites someone infected with the malaria parasite. The parasite grows into the next stage in the mosquito’s gut and transports to its salivary glands, to infect the next human it bites. These modified mosquitoes produce compounds which interfere in the growth of malaria-causing parasites, which are then not able to reach the mosquitoes’ salivary glands and be passed on in a bite before the insects are dead. The team of researchers from the Institute for Disease Modeling at the Bill and Melinda Gates Foundation have created a model which can analyse the effect of such changes if used in various African settings. They also found that the modification of these mosquitoes could be helpful even in locations where the transmission rate is high.
Explained: How Scientists Are Genetically modifying Mosquitoes To Reduce Malaria
23772Anonymous, Outlook, 2022-10-07 06:57:17.
he Delhi High Court on Friday asked the state government to inform it within two weeks of the proposal of increasing the fine amount in mosquito breeding cases. The court last year took suo moto cognizance of the issue of large-scale mosquito breeding in the city, resulting in the spread of vector-borne diseases With a sudden increase in malaria cases across the country, a recent research might provide some respite. Scientists have genetically modified mosquitoes to slow the growth of malaria-causing parasites in their guts — an advancement that can help prevent transmission of the disease to humans. Though only around 10 per cent of mosquitoes live long enough for the infectious parasite to develop, malaria remains one of the most devastating diseases globally, putting at risk about half of the world’s population. In 2021, it infected 241 million people and killed 627,000 people.
Explained: How scientists engineered mosquitoes that cannot spread malaria
23670FP Explainers, Firstpost, 2022-10-06 08:14:50.
The world of science is reaching new heights. Scientists have now developed mosquitoes that will bite you but not cause malaria. The study was conducted by a team of researchers called Transmission: Zero at the Imperial College of London. The results of the research were published in the Science Advances journal. Genetically modified mosquitoes have the ability to slow the growth of malaria-causing parasites in their gut, an innovation that can help prevent transmission of the disease to humans. Owing to the devastating effects of Malaria, which is putting about half of the world’s population at risk, scientists came up with this new method in the hope to deter the growth of the parasite.
Malaria Gene Drives: A Battle Of Wit Between The Government And Stakeholders
23650O. Onwumere, The Nigerian Voice, 2022-10-03 08:29:30.
Through the National Biosafety Management Agency (NBMA), guidelines for gene editing, primarily in agriculture, were approved by the Nigerian Federal Government in December 2020. As the first country in Africa, the government was praised for taking the momentous step of establishing guidelines for gene editing. The government sees science and technology as major drivers of agricultural productivity, as stated in the approved guidelines. This is due to the fact that the technology is guaranteed to be safe and won't harm the environment or human health. Scientists and non-governmental organizations have nonetheless refused to support the use of genetically engineered bacteria to eradicate malaria-carrying mosquitoes despite the government's actions. The reason was that a doctor from Nigeria who didn't want his name published said that gene-editing technology needs to be looked at carefully because there have been failed reports in some African countries, like Burkina Faso, where modified mosquitoes were released and people got bit by them
Malaria-free mosquito engineered by scientists
23697GNA, MODERN GHANA, 2022-10-03 07:54:35.
Scientists have genetically modified the main malaria-carrying species of mosquito in sub-SaharanAfrica to slow the growth of malaria-causing parasites in their gut, preventing transmission of thedisease to humans. When the Anopheles gambiae takes a blood meal, it produces two molecules called antimicrobialpeptides in its guts, according to the scientists. These peptides, which were originally isolated from honeybees and African clawed frogs, impair themalaria parasite's development. Now researchers from the Transmission Zero team at Imperial College London have come up with adesign that can be combined with existing “gene drive” technology to spread the modification anddrastically cut malaria transmission. Collaborators from the Institute for Disease Modelling at the Bill and Melinda Gates Foundation,which funded the research, also developed a model that, for the first time, can assess the impact ofsuch modifications if used in a variety of African settings. They found that the modification developed by the Imperial team could be a powerful tool forbringing down cases of malaria even where transmission is high.
Gene drive used to make all female mosquitoes sterile
23653Akfire1, TechiLink, 2022-10-01 08:45:17.
We have long known that we can limit malaria infections by controlling the mosquitoes that transmit them. But that knowledge has not translated into auditing efforts that have always been completely successful. Many of the approaches we have used to control mosquitoes have caused environmental problems, and mosquito populations are large enough that they have developed resistance to many of our pesticides. That made the development of so-called ‘gene drive’ constructs exciting (albeit a little scary). They have the potential to quickly spread genes across a population, including a mosquito population. But the prospect of modern genetic control of mosquito populations faces the very old problem of evolution, as gene drives often grind to a halt due to genetic changes that allow mosquito populations to escape their impact. Now a team has come up with a way to potentially avoid this problem: use gene drive to target a gene fundamental to mosquito development as male or female. By doing so, the females become sterile and, at least in the lab, the mosquito populations collapse.
Justifying an Intentional Species Extinction: The Case of Anopheles gambiae
23662D. E. Callies and Y. Rohwer, Environmental Values, 31:193-210. 2022-10-01 06:16:34.
Each year, over 200 million people are infected with the malaria parasite, nearly half a million of whom succumb to the disease. Emerging genetic technologies could, in theory, eliminate the burden of malaria throughout the world by intentionally eradicating the mosquitoes that transmit the disease. In this paper, we offer an ethical examination of the intentional eradication of Anopheles gambiae, the main malaria vector of sub-Saharan Africa. In our evaluation, we focus on two main considerations: the benefit of alleviating the malaria burden, and the loss of value that would accompany the eradication of the species. We outline a typology of the different ways in which species are valued or could be valuable, then use that typology to appraise the value of the species in question. We argue that Anopheles gambiae has minor (and redundant) instrumental value, little final subjective value and no objective final value.
How We’re Reducing Disease With Genetically Modified Mosquitoes
23667V. Wise, HealthMatch, 2022-09-29 08:07:21.
We all know mosquitoes as those annoying insects we swat away from our faces. They carry diseases, so we don’t want them anywhere near us. There are over 200 types of wild mosquitoes bugging us across America and the U.S. territories. Approximately 12 types can spread disease, but most are “nuisance” mosquitoes, which don’t spread germs. Obviously, it’s hard to identify a tiny flying creature, so we need to keep them all away from us just in case. Aedes aegypti¹ is one of the most common mosquitoes in the U.S. that can spread disease. One of the best-known mosquito-borne diseases is malaria, but Aedes aegypti is associated with 54 viruses². West Nile virus, Zika, and dengue are just three diseases these mosquitoes transmit around the U.S With 1 in 150 people becoming seriously ill due to West Nile virus, sometimes fatally, what can we do to prevent mosquito bites?
Scientists stunt parasite growth to tackle malaria
23769RSS24.news, RSS24.NEWS, 2022-09-29 06:52:01.
Loss of life, loss of livlihoods and homelessness have already afflicted these flood marooned refugees in Pakistan. Now these living conditions means they also face sickness and and without protection malaria is a major threat. Health agencies try to protect people against infection with sprays, nets and a vaccine for children, there are also preventative medicines. But despite all these, there were 241 million cases of malaria in 2020 and an estimated 627,000 deaths according to the latest malaria report from the World Health Organization (WHO). The WHO says these strategies, which are also used for other mosquito borne diseases such as Zika and dengue, are only partially effective. In the meantime the insects are becoming inceasingly resistant to insecticides. Scientists have for many years been investigating whether they can control the life cycle of mosquitoes by manipulating their DNA, thereby creating genetically modified mosquitoes. The disease is spread by a parasite Plasmodium falciparum which grows and reaches maturation inside the female Anopheles mosquito.
Scientists are manipulating the DNA of mosquitoes to fight the spread of malaria
23766R. Min, EURONEWS.NEXT, 2022-09-29 06:48:00.
Scientists say they have managed to genetically modify mosquitoes so that they are unable to spread malaria, a disease that kills well over half a million people each year. The changes cause mosquitoes to live shorter lives, while the parasites inside them, which cause the fatal infection, develop more slowly. This slashes the chances of mosquitoes living long enough to carry fully grown parasites – and transmit the disease to the humans they bite.Malaria is spread by the parasite Plasmodium falciparum, which grows and reaches maturation inside the female Anopheles mosquito. The average mosquito survives on average seven to 10 days in the wild. "By prolonging the developmental time that the parasite needs inside the mosquito to become infectious, this 10 per cent becomes now much smaller".
Scientists engineer mosquitoes that cannot spread malaria
23601J. Dalton, Independen, 2022-09-22 14:30:39.
Scientists have engineered mosquitoes that cannot give humans malaria, saying their work could potentially eliminate the disease. Researchers at Imperial College London genetically modified the insects so that the growth of malaria-causing parasites in their guts was slowed.
Scientists Engineer Mosquitoes That Can’t Transmit Malaria
23598C. Murez, US News, 2022-09-22 14:21:57.
The fight against malaria could hinge on genetically engineered mosquitoes that have something called "gene drive."Researchers from the Transmission: Zero team at Imperial College London report that they have engineered mosquitoes that slow the growth in their gut of the parasites that cause malaria. This delay would mean the mosquito would reach its natural life span before the parasite would reach the mosquitoes' salivary glands. So a bite wouldn't spread the disease. In the lab, this dramatically reduced the spread of malaria. "Since 2015, the progress in tackling malaria has stalled. Mosquitoes and the parasites they carry are becoming resistant to available interventions such as insecticides and treatments, and funding has plateaued. We need to develop innovative new tools," study co-author Tibebu Habtewold said in a college news release. He's a researcher from the college's Department of Life Sciences. Last year, malaria infected 241 million people, killing 627,000 of them, mostly children younger than age 5 in sub-Saharan Africa.
Mosquitoes that can’t spread malaria engineered by scientists
235842022-09-22 14:04:19.
Scientists have engineered mosquitoes that slow the growth of malaria-causing parasites in their gut, preventing transmission of the disease to humans The genetic modification causes mosquitoes to produce compounds in their guts that stunt the growth of parasites, meaning they are unlikely to reach the mosquitoes' salivary glands and be passed on in a bite before the insects die. So far, the technique has been shown to dramatically reduce the possibility of malaria spread in a lab setting, but if proven safe and effective in real-world settings it could offer a powerful new tool to help eliminate malaria.The innovation, by researchers from the Transmission:Zero team at Imperial College London, is designed so it can be coupled with existing 'gene drive' technology to spread the modification and drastically cut malaria transmission. The team is looking towards field trials, but will thoroughly test the safety of the new modification before combining it with a gene drive for real-world tests. Collaborators from the Institute for Disease Modeling at the Bill and Melinda Gates Foundation also developed a model that, for the first time, can assess the impact of such modifications if used in a variety of African settings. They found that the modification developed by the Transmission:Zero team could be a powerful tool for bringing down cases of malaria even where transmission is high.
Scientists engineer mosquitoes that can’t spread malaria
23581S. Varshney, Gamacher Central, 2022-09-22 13:58:18.
Scientists have engineered mosquitoes that slow the growth of malaria-causing parasites in their gut, preventing transmission of the disease to humans. The genetic modification causes mosquitoes to produce compounds in their guts that stunt the growth of parasites, meaning they are unlikely to reach the mosquitoes’ salivary glands and be passed on in a bite before the insects die. So far, the technique has been shown to dramatically reduce the possibility of malaria spread in a lab setting, but if proven safe and effective in real-world settings it could offer a powerful new tool to help eliminate malaria.
Mosquitoes with honeybee DNA could tame malaria
23579R. Blakely, The Times, 2022-09-22 13:53:23.
A new form of genetically engineered mosquito could reduce the spread of malaria in Africa, a study suggests. The addition of DNA from a honeybee and genetic material from the African clawed frog prompt the new mosquitoes to produce compounds to stunt the growth of the parasite that causes malaria. This means that the parasite, and therefore the disease, is less likely to be passed on to human victims via mosquito bite. To be useful in the real world this would have to be coupled with an existing technology known as a gene drive, a controversial genetic tool that would force the new characteristic through populations of mosquitoes as they reproduce. For malaria to spread, a female mosquito must bite someone infected with the malaria
Genetically Engineered Mosquitoes Prevented the Growth of Malaria-causing Parasites in Their Gut
23576P. Mozter, Nature World News 2022, 2022-09-22 13:45:51.
Abstract: Scientists have created mosquitoes that inhibit the development of malaria-causing parasites in their stomachs, therefore decreasing disease transmission to people. The genetic change allows mosquitoes to create substances in their intestines that inhibit parasite development, making parasites less likely to reach the mosquitoes' salivary glands and be transmitted in a bite before the insects die, as per ScienceDaily. The Transmission: Zero team at Imperial College London developed the breakthrough so that it may be used with current "gene drive" technologies to distribute the alteration and substantially reduce malaria transmission. The team is planning field experiments, but first, they will rigorously verify the new modification's safety before merging it with a gene drive for real-world testing.
Mosquitoes are being genetically modified so they can’t spread malaria
23596M. Le Page, New Scientist, 2022-09-21 14:17:06.
Gene editing mosquitoes so they die before malaria parasites can develop inside them could stop the spread of the deadly parasite entirely,
Genetically-modified mosquitoes could ‘help wipe out malaria’
23594S. Knapton, The Telegraph, 2022-09-21 14:11:56.
Mosquitoes that cannot spread malaria have been genetically engineered by British scientists, in a breakthrough that could help eliminate the disease. ...
Scientists engineer mosquitoes that can’t spread malaria
23572Imperial College London, Phys Org, 2022-09-21 13:32:19.
Scientists have engineered mosquitoes that slow the growth of malaria-causing parasites in their gut, preventing transmission of the disease to humans. The genetic modification causes mosquitoes to produce compounds in their guts that stunt the growth of parasites, meaning they are unlikely to reach the mosquitoes' salivary glands and be passed on in a bite before the insects die. So far, the technique has been shown to dramatically reduce the possibility of malaria spread in a lab setting, but if proven safe and effective in real-world settings it could offer a powerful new tool to help eliminate malaria. The innovation, by researchers from the Transmission:Zero team at Imperial College London, is designed so it can be coupled with existing "gene drive" technology to spread the modification and drastically cut malaria transmission. The team is looking towards field trials, but will thoroughly test the safety of the new modification before combining it with a gene drive for real-world tests. Collaborators from the Institute for Disease Modeling at the Bill and Melinda Gates Foundation also developed a model that, for the first time, can assess the impact of such modifications if used in a variety of African settings. They found that the modification developed by the Transmission:Zero team could be a powerful tool for bringing down cases of malaria even where transmission is high.
Humans Have a Long History of Making ‘Very Bad Decisions’ to Save Animals
23627T. McDonnell, The New York Times, 2022-09-17 07:17:21.
Environmental reporter Tim McDonnell on the potential negative consequences of animal conservation efforts. McDonnell highlights Target Malaria’s research on gene drive to “eliminate malaria-carrying mosquitos” and quotes New Zealand researcher Philipp Messer saying that the world is “ill-prepared” for a "real-life gene drive.” The article also quotes MIT biologist Kevin Esvelt saying that misuse of the technology would cause the public and policymakers to halt gene drive research and would set the field back by a decade. The article notes that there is no international regulation to “prevent the premature deployment of gene drive in the wild” and states that “individual governments, powerful funding organizations like the Bill and Melinda Gates Foundation, and scientists themselves” are responsible for balancing the prevention of risky interventions with the need to support basic research. Esvlet is also quoted saying that the WHO needs to “establish a registry for all gene drive experiments that requires scientists to detail safeguards and find a local community who agrees to guide the research before experiments begin.”
Life-history traits of a fluorescent Anopheles arabiensis genetic sexing strain introgressed into South African genomic background
23550N. L. Ntoyi, T. Mashatola, J. Bouyer, C. Kraupa, H. Maiga, W. Mamai, N. S. Bimbile-Somda, T. Wallner, D. O. Carvalho, G. Munhenga and H. Yamada, Malaria Journal, 21:12. 2022-09-05 06:11:50.
Background South Africa has set a mandate to eliminate local malaria transmission by 2023. In pursuit of this objective a Sterile Insect Technique programme targeting the main vector Anopheles arabiensis is currently under development. Significant progress has been made towards operationalizing the technology. However, one of the main limitations being faced is the absence of an efficient genetic sexing system. This study is an assessment of an An. arabiensis (AY-2) strain carrying the full Y chromosome from Anopheles gambiae, including a transgenic red fluorescent marker, being introgressed into a South African genetic background as a potential tool for a reliable sexing system. Methods Adult, virgin males from the An. arabiensis AY-2 strain were outcrossed to virgin females from the South African, Kwazulu-Natal An. arabiensis (KWAG strain) over three generations. Anopheles arabiensis AY-2 fluorescent males were sorted as first instar larvae (L1) using the Complex Object Parametric Analyzer and Sorter (COPAS) and later screened as pupae to verify the sex. Life history traits of the novel hybrid KWAG-AY2 strain were compared to the original fluorescent AY-2 strain, the South African wild-type KWAG strain and a standard laboratory An. arabiensis (Dongola reference strain). Results The genetic stability of the sex-linked fluorescent marker and the integrity and high level of sexing efficiency of the system were confirmed. No recombination events in respect to the fluorescent marker were detected over three rounds of introgression crosses. KWAG-AY2 had higher hatch rates and survival of L1 to pupae and L1 to adult than the founding strains. AY-2 showed faster development time of immature stages and larger adult body size, but lower larval survival rates. Adult KWAG males had significantly higher survival rates. There was no significant difference between the strains in fecundity and proportion of males. KWAG-AY2 males performed better than reference strains in flight ability tests. Conclusion The life history traits of KWAG-AY2, its rearing efficiency under laboratory conditions, the preservation of the sex-linked fluorescence and perfect sexing efficiency after three rounds of introgression crosses, indicate that it has potential for mass rearing. The potential risks and benefits associated to the use of this strain within the Sterile Insect Technique programme in South Africa are discussed.
An evaluation of fusion partner proteins for paratransgenesis in Asaia bogorensis
24274C. Grogan, M. Bennett and D. J. Lampe, Plos One, 17:18. 2022-09-01 14:11:14.
Mosquitoes transmit many pathogens responsible for human diseases, such as malaria which is caused by parasites in the genus Plasmodium. Current strategies to control vector-transmitted diseases are increasingly undermined by mosquito and pathogen resistance, so additional methods of control are required. Paratransgenesis is a method whereby symbiotic bacteria are genetically modified to affect the mosquito's phenotype by engineering them to deliver effector molecules into the midgut to kill parasites. One paratransgenesis candidate is Asaia bogorensis, a Gram-negative bacterium colonizing the midgut, ovaries, and salivary glands of Anopheles sp. mosquitoes. Previously, engineered Asaia strains using native signals to drive the release of the antimicrobial peptide, scorpine, fused to alkaline phosphatase were successful in significantly suppressing the number of oocysts formed after a blood meal containing P. berghei. However, these strains saw high fitness costs associated with the production of the recombinant protein. Here, we report evaluation of five different partner proteins fused to scorpine that were evaluated for effects on the growth and fitness of the transgenic bacteria. Three of the new partner proteins resulted in significant levels of protein released from the Asaia bacterium while also significantly reducing the prevalence of mosquitoes infected with P. berghei. Two partners performed as well as the previously tested Asaia strain that used alkaline phosphatase in the fitness analyses, but neither exceeded it. It may be that there is a maximum level of fitness and parasite inhibition that can be achieved with scorpine being driven constitutively, and that use of a Plasmodium specific effector molecule in place of scorpine would help to mitigate the stress on the symbionts.
A confinable female-lethal population suppression system in the malaria vector, Anopheles gambiae
23500A. L. Smidler, J. J. Pai, R. A. Apte, H. M. Sánchez C, R. M. Corder, E. J. Gutiérrez, N. Thakre, I. Antoshechkin, J. M. Marshall and O. S. Akbari, bioRxiv, 2022.08.30.505861. 2022-08-30 19:10:47.
Malaria is among the world’s deadliest diseases, predominantly affecting sub-Saharan Africa, and killing over half a million people annually. Controlling the principal vector, the mosquito Anopheles gambiae, as well as other anophelines, is among the most effective methods to control disease spread. Here we develop an innovative genetic population suppression system termed Ifegenia (Inherited Female Elimination by Genetically Encoded Nucleases to Interrupt Alleles) in this deadly vector. In this bicomponent CRISPR-based approach, we disrupt a female-essential gene, femaleless (fle), demonstrating complete genetic sexing via heritable daughter gynecide. Moreover, we show that Ifegenia males remain reproductively viable, and can load both fle mutations and CRISPR machinery to induce fle mutations in subsequent generations, resulting in sustained population suppression. Through modeling, we demonstrate that iterative releases of non-biting Ifegenia males can act as an effective, confinable, controllable, and safe population suppression and elimination system.
What do we mean by “Target Organism” in Target Malaria’s gene drive research?
23336J. B. Connolly, Target Malaria, 2022-07-27 08:46:32.
In the wild and in laboratory settings, sibling mosquito species can successfully mate to produce viable offspring, regardless of whether they are vectors or not. Importantly, females, but not males, of these offspring can be fertile. Nonetheless, the likelihood of finding such hybrid mosquitoes in field samples varies greatly between different combinations of species. According to some field studies, typically, only about 0.1% of mosquito collected in the wild could be An. gambiae s.s./An. coluzzii hybrids. In addition, some species that do not overlap geographically, and therefore would not come into direct contact, cannot produce hybrids in the field. This includes An. melas, which is found along the coast of West Africa, and An. bwambae, which is restricted to hot springs in the Toro District of Uganda. This means that the gene drive could eventually transfer to all sibling species of the complex, both by direct hybridisation between geographically-overlapping species and, indirectly, by transferring from one species to another overlapping ones like stepping-stones until the gene drive was transferred to all species of the complex, including to the likes of An. melas and An. bwambae
Population replacement gene drive characteristics for malaria elimination in a range of seasonal transmission settings: a modelling study
23307S. Leung, N. Windbichler, E. A. Wenger, C. A. Bever and P. Selvaraj, Malaria Journal, 21:226. 2022-07-26 07:49:07.
BACKGROUND: Gene drives are a genetic engineering method where a suite of genes is inherited at higher than Mendelian rates and has been proposed as a promising new vector control strategy to reinvigorate the fight against malaria in sub-Saharan Africa. METHODS: Using an agent-based model of malaria transmission with vector genetics, the impacts of releasing population-replacement gene drive mosquitoes on malaria transmission are examined and the population replacement gene drive system parameters required to achieve local elimination within a spatially-resolved, seasonal Sahelian setting are quantified. The performance of two different gene drive systems-"classic" and "integral"-are evaluated. Various transmission regimes (low, moderate, and high-corresponding to annual entomological inoculation rates of 10, 30, and 80 infectious bites per person) and other simultaneous interventions, including deployment of insecticide-treated nets (ITNs) and passive healthcare-seeking, are also simulated. RESULTS: Local elimination probabilities decreased with pre-existing population target site resistance frequency, increased with transmission-blocking effectiveness of the introduced antiparasitic gene and drive efficiency, and were context dependent with respect to fitness costs associated with the introduced gene. Of the four parameters, transmission-blocking effectiveness may be the most important to focus on for improvements to future gene drive strains because a single release of classic gene drive mosquitoes is likely to locally eliminate malaria in low to moderate transmission settings only when transmission-blocking effectiveness is very high (above ~ 80-90%). However, simultaneously deploying ITNs and releasing integral rather than classic gene drive mosquitoes significantly boosts elimination probabilities, such that elimination remains highly likely in low to moderate transmission regimes down to transmission-blocking effectiveness values as low as ~ 50% and in high transmission regimes with transmission-blocking effectiveness values above ~ 80-90%. CONCLUSION: A single release of currently achievable population replacement gene drive mosquitoes, in combination with traditional forms of vector control, can likely locally eliminate malaria in low to moderate transmission regimes within the Sahel. In a high transmission regime, higher levels of transmission-blocking effectiveness than are currently available may be required.
Operationalizing stakeholder engagement for gene drive research in malaria elimination in Africa-translating guidance into practice
23281L. Pare Toe, B. Dicko, R. Linga, N. Barry, M. Drabo, N. Sykes and D. Thizy, Malaria Journal, 21:225. 2022-07-23 10:16:04.
Gene drive mosquitoes are increasingly considered a potential transformational tool for vector control of malaria mosquitoes. As part of efforts to promote responsible research in this field, a number of guidance documents have been published by the World Health Organization, National Academies and expert groups. While virtually all recent guidance documents on gene drive research stress the importance of stakeholder engagement activities, no specific guidelines on implementing them have been established. Target Malaria, a not-for-profit research consortium developing a vector-control gene drive approach to eliminate malaria, has reflected on how its stakeholder engagement strategy translates engagement guidance documents into practice. The project analysed and addressed the tension between the context specificities and the international recommendations. The engagement strategy combines published recommendations for responsible gene drive research, information collected from the local context where the project operates and a set of principles guiding the choices made. This strategy was first developed during the early phases of the project's research, years ahead of any activities with gene drive mosquitoes in those countries of operations. These earlier activities, and their related engagement, allow the project to develop and adapt an engagement strategy appropriate for potential gene drive research in its field site countries. This paper offers a description of a stakeholder engagement strategy operationalization based on (1) adaptation to stakeholder preferences, (2) inclusiveness and (3) empowerment and accountability. The authors hope to offer concrete examples to support other projects with the development and implementation of their engagement strategies with particular attention to the co-development principle.
Gene drives and Africa’s battle against malaria
23154Annonymous, Africa Verified, 2022-07-08 09:43:10.
As malaria cases rise, and the effectiveness of current methods begins to fall, the WHO’s target of reducing the global malaria burden by 90% by 2030 will not be met. It is critical for new and resilient treatment, prevention, and control methods to be developed and integrated into current strategies. Target Malaria is a not-for-profit research consortium aiming to develop ‘cost-effective and sustainable genetic technologies to modify mosquitoes and reduce malaria transmission’ that would work alongside current anti-malaria efforts. They are pioneering research into genetically programmed mosquitoes, which when released into the wild to mate, reproduce offspring that either produce fewer female mosquitoes or are unable to transmit malaria parasites.
A population modification gene drive targeting both Saglin and Lipophorin disables Plasmodium transmission in Anopheles mosquitoes
23150E. I. Green, E. Jaouen, D. Klug, R. P. Olmo, A. Gautier, S. A. Blandin and E. Marois, bioRxiv, 2022.07.08.499187. 2022-07-08 09:32:53.
Lipophorin is an essential, highly expressed lipid transporter protein that is secreted and circulates in insect hemolymph. We hijacked the Anopheles gambiae Lipophorin gene to make it co-express a single-chain version of antibody 2A10, which binds sporozoites of the malaria parasite Plasmodium falciparum. The resulting transgenic mosquitoes show a markedly decreased ability to transmit Plasmodium berghei expressing the P. falciparum circumsporozoite protein. To force the spread of this anti-malarial transgene in a mosquito population, we designed and tested several CRISPR/Cas9-based gene drives. One of these is installed in, and disrupts, the pro-parasitic gene Saglin and also cleaves wild type Lipophorin, causing the anti-malarial modified Lipophorin version to hitch-hike together with the Saglin drive. Although producing drive-resistant alleles, the Saglin-based gene drive reached high levels in caged mosquito populations and efficiently promoted the simultaneous spread of the antimalarial Lipophorin::Sc2A10 allele. This combination is expected to affect parasite transmission by two different mechanisms. This work contributes to the design of novel strategies to spread antimalarial transgenes in mosquitoes, and illustrates some expected and unexpected outcomes encountered when establishing a population modification gene drive.Competing Interest StatementThe authors have declared no competing interest.
Larval mosquito management and risk to aquatic ecosystems: A comparative approach including current tactics and gene-drive Anopheles techniques
23152R. K. D. Peterson and M. G. Rolston, Transgenic Research, 2022-07-07 09:39:09.
Genetic engineering of mosquitoes represents a promising tactic for reducing human suffering from malaria. Gene-drive techniques being developed that suppress or modify populations of Anopheles gambiae have the potential to be used with, or even possibly obviate, microbial and synthetic insecticides. However, these techniques are new and therefore there is attendant concern and uncertainty from regulators, policymakers, and the public about their environmental risks. Therefore, there is a need to assist decision-makers and public health stewards by assessing the risks associated with these newer mosquito management tactics so the risks can be compared as a basis for informed decision making. Previously, the effect of gene-drive mosquitoes on water quality in Africa was identified as a concern by stakeholders. Here, we use a comparative risk assessment approach for the effect of gene-drive mosquitoes on water quality in Africa. We compare the use of existing larvicides and the proposed genetic techniques in aquatic environments. Based on our analysis, we conclude that the tactic of gene-drive Anopheles for malaria management is unlikely to result in risks to aquatic environments that exceed current tactics for larval mosquitoes. As such, these new techniques would likely comply with currently recommended safety standards.
Gene Drives: A Potentially New Weapon Against Mosquitoes
22905M. Sherman, Times Union Online, 2022-06-13 06:36:32.
Scientists have studied gene drives for more than 50 years, and to most of us this has been a well-kept secret. The development of a powerful genome editing tool in 2012, CRISPR/Cas9,1 led to recent breakthroughs in gene drive research that built on that half century’s worth of knowledge, and stimulated new discussions of the potential applications and implications of gene drive technologies. Just prior to the beginning of this study and since the committee was first convened, scientists published four proofs of concept — one in yeast, one in fruit flies, and two in different species of mosquitoes — that demonstrate the successful development of gene drives in the laboratory, at least in these organisms.Proposed applications for gene-drive modified organisms for basic research, conservation, agriculture, public health and other purposes will likely continue to expand as gene editing tools become more refined. Gene-drive modified organisms are on the horizon. With mosquitoes, the gene drive interferes with the insect’s ability to reproduce. It wiped out captive populations in eight or 12 generations. The first experimental release could be rolled out in Burkina Faso, Mali, Ghana or Uganda.
Active genetics comes alive
22888V. M. Gantz and E. Bier, BioEssays, 2022-06-09 09:28:52.
Abstract Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based ?active genetic? elements developed in 2015 bypassed the fundamental rules of traditional genetics. Inherited in a super-Mendelian fashion, such selfish genetic entities offered a variety of potential applications including: gene-drives to disseminate gene cassettes carrying desired traits throughout insect populations to control disease vectors or pest species, allelic drives biasing inheritance of preferred allelic variants, neutralizing genetic elements to delete and replace or to halt the spread of gene-drives, split-drives with the core constituent Cas9 endonuclease and guide RNA (gRNA) components inserted at separate genomic locations to accelerate assembly of complex arrays of genetic traits or to gain genetic entry into novel organisms (vertebrates, plants, bacteria), and interhomolog based copying systems in somatic cells to develop tools for treating inherited or infectious diseases. Here, we summarize the substantial advances that have been made on all of these fronts and look forward to the next phase of this rapidly expanding and impactful field.
Who decides whether to use gene drives against malaria-carrying mosquitoes?
22730T. H. Saey, ScienceNews, 2022-06-03 08:12:18.
The gene drive interferes with the insects’ ability to reproduce. It wiped out captive populations of mosquitoes in eight to 12 generations (SN: 10/27/18, p. 6) in a small lab study. In 2021, the technology worked in the large cages in Terni, Italy, too. Within as little as five to 10 years, this gene drive could be ready to test in the wild. The first experimental release could be rolled out in Burkina Faso, Mali, Ghana or Uganda. In those locations, researchers are working with a nonprofit research consortium called Target Malaria to develop the gene drive carriers along with other genetically engineered mosquitoes to fight malaria. This research is driven by the idea that every tool available must be used to fight malaria, which sickened close to 241 million people in 2020 and killed 670,000 worldwide, mostly in Africa. Children 5 years old and younger accounted for about 80 percent of the continent’s malaria deaths, the World Health Organization says. Because of malaria’s huge toll, large investments have been made to fight the disease, yielding preventive drugs, insecticide-treated bed nets and even malaria vaccines — one was recently recommended for use in sub-Saharan Africa (SN: 12/18/21 & 1/1/22, p. 32). These efforts are helping. But mosquitoes are developing resistance to insecticides, and some anti-malaria drugs may no longer work well.
Testing non-autonomous antimalarial gene drive effectors using self-eliminating drivers in the African mosquito vector Anopheles gambiae
22689D. A. Ellis, G. Avraam, A. Hoermann, C. A. S. Wyer, Y. X. Ong, G. K. Christophides and N. Windbichler, PLOS Genetics, 18:e1010244. 2022-06-02 14:26:57.
Author summary Gene drive is a method that allows the genetic modification of entire populations of harmful organisms. Their application to tackle invasive species, agricultural pests or insect disease vectors has been suggested. For example, they could reduce the capacity of malaria mosquitoes to transmit this deadly disease to humans by producing effector molecules inhibiting the development of the Plasmodium parasite in the mosquito vector. We describe a strategy to modularize and test multiple transgenes destined for release, and to introduce only the minimal set of modifications needed into a mosquito population. We show how some elements, once no longer needed, can be made to self-eliminate from populations and we also study how several independent gene drive traits, located in different parts of the genome, can interact and propagate at the level of mosquito cage populations.
Modifying mosquitoes to suppress disease transmission: Is the long wait over?
22854J. R. Powell, Genetics, 2022-06-02 08:31:17.
For more than 50 years it has been a dream of medical entomologists and public health workers to control diseases like malaria and dengue fever by modifying, through genetics and other methods, the arthropods that transmit them to humans. A brief synopsis of the history of these efforts as applied to mosquitoes is presented; none proved to be effective in reducing disease prevalence. Only in the last few years have novel approaches been developed or proposed that indicate the long wait may be over. Three recent developments are particularly promising: CRISPR-Cas9 driven genetic modification, shifting naturally occurring allele frequencies, and microbe-based modifications. The last is the furthest along in implementation. Dengue fever incidence has been reduced between 40% and 96% in 4 different regions of the world where Wolbachia-infected Aedes aegypti have been established in the field. It is not yet clear how sustainable such control programs will prove to be, but there is good reason for optimism. In light of this, the time is ripe for reinvigorated research on vectors, especially genetics. Vector-borne diseases primarily affect under-developed countries and thus have not received the attention they deserve from wealthier countries with well-developed and funded biomedical research establishments.
Unfolding the Next Frontier of Innovation in Malaria: The Way Forward
22699ETHealthWorld, ET Healthworld, 2022-05-30 14:53:17.
Malaria innovation is on the verge of a challenging yet exciting frontier. Therefore, to ramp up current innovatins and expand effective therapeutic and prevenitive methods, the governments, international organizations, and the private sector must work together. Additionally, malaria eradication calls for multiple innovative approaches.
Recommendations for environmental risk assessment of gene drive applications for malaria vector control
22586J. B. Connolly, J. D. Mumford, D. C. M. Glandorf, S. Hartley, O. T. Lewis, S. W. Evans, G. Turner, C. Beech, N. Sykes, M. B. Coulibaly, J. Romeis, J. L. Teem, W. Tonui, B. Lovett, A. Mankad, A. Mnzava, S. Fuchs, T. D. Hackett, W. G. Landis, J. M. Marshall, Malar J, 21:152. 2022-05-25 09:36:02.
Building on an exercise that identified potential harms from simulated investigational releases of a population suppression gene drive for malaria vector control, a series of online workshops identified nine recommendations to advance future environmental risk assessment of gene drive applications.
Gene Drives: The advanced science fiction technology used to fight malaria mosquitoes explained
22563Anonymous, NewsBeezer, 2022-05-23 08:42:27.
Scientists are using the most advanced form of genetic engineering to eradicate a population of malaria-carrying mosquitoes by rendering the females infertile. Scientists introduced a lab-tweaked gene (a gene created using Gene Drive) into an organism that automatically replicates itself and targets a specific natural gene to destroy it. The potential of the gene drive was explored back in 2003 by Austin Burt, a professor at Imperial College London. Burt studied “selfish genes” that can copy themselves into a specific target DNA sequence. As research continues to develop, Burt said this technology has great potential, for example it could be used to eliminate a population of malaria-carrying mosquitoes.
The sci-fi technology tackling malarial mosquitos
22560Anonymous, The Star, 2022-05-23 08:30:39.
Environmental campaigner Liz O'Neill doesn't mince her words about gene drives - the next generation of genetic modification (GM) technology. "It is extremely worrying," says the director of UK anti-GM pressure group, GM Freeze. "To release something that has been specifically created in a laboratory in order to outfight nature, and spread without exception within wild populations, is extraordinary arrogant. "And once the genie is out of the bottle, you cannot put it back in." The way gene drives work sounds like something from a science fiction novel, but they are already being used in laboratory tests. It is complicated stuff, but here is a simple explanation.
The fight against malaria
22445F. Ammache, Year 2049, 2022-05-06 08:51:20.
Malaria is a disease we’ve been dealing with for thousands of years. Traces of the malaria parasite have been found in the remains of Egyptian mummies. Hippocrates described the fevers caused by malaria in Ancient Greece. The mosquito-filled Pontine Marshes protected Ancient Rome from invaders. Back then, we thought the disease was caused by people breathing “bad air”, or “mal aria”. The relationship between mosquitoes and malaria was unknown. Plasmodium falciparum, the deadliest form of malaria, was introduced by a new breed of mosquitoes around the 5th century. Some historians speculate that P. falciparum played a key role in the fall of the Roman Empire. It wasn’t until 1897 that we understood that mosquitoes transmitted malaria. Sir Ronald Ross, a British doctor based in India, found the malaria parasite in the blood of Anopheles mosquitoes which proved a hypothesis that was first put forward by his predecessor Alphonse Laveran.
New weapons to fight malaria transmission: A historical view
22487W. Huang, S.-J. Cha and M. Jacobs-Lorena, Entomological Research, 2022-05-02 07:19:32.
The stagnation of our fight against malaria in recent years, mainly due to the development of mosquito insecticide resistance, argues for the urgent development of new weapons. The dramatic evolution of molecular tools in the last few decades led to a better understanding of parasite?mosquito interactions and coalesced in the development of novel tools namely, mosquito transgenesis and paratransgenesis. Here we provide a historical view of the development of these new tools and point to some remaining challenges for their implementation in the field.
The Financialisation of Malaria in Africa: Burkina Faso, rogue capital & GM/gene drive mosquitoes
22066S. Mentz-Lagrange and S. Swanepoel, African Centre for Biodiversity, 2022-04-28 07:02:28.
This paper seeks to understand the financialisation of malaria as a vehicle for rogue capital in a context of a weakened state (through capture, corruption and coups) and the power that limits effective interventions. It shows how malaria, along with other diseases, is increasingly financialised – financial markets, institutions, actors and motives play a pivotal role in disease response. Country and donor funds are invested into research and development non-profit organisations, for example, that partner with market actors (such as pharmaceutical companies) to bring the product to market. Patents are sought and royalties procured from the sale of the product to country governments. These royalties are then accumulated by the research and development company, using vehicles such as endowment funds, for example. It show cases Burkina Faso as a real-world example of how rogue capital can enter a country and experiment with patented products, with impunity and no fear of accountability. It also illustrates how both historical and modern factors create conducive conditions for philanthrocapitalists such as the Bill and Melinda Gates Foundation and the companies they fund, to exploit Africa as a living laboratory. The outcomes of risky experimental research such as genetically modified (GM) and gene drive mosquitoes is not yet known. What is known is that it is Africans who bear the consequences – not the owners of the technologies foisted on the continent.
Genetically altered mosquitoes to close gaps in malaria fight
22248M. Murigi, People Daily, 2022-04-25 09:00:48.
In 2020, nearly 6.9 million cases of malaria and about 742 deaths were confirmed in Kenya according to the Kenya Malaria Indicator Survey (KMIS) 2020. Although the number of reported infections declined from 10.9 million in 2018, the disease is still one of the main health issues in the country despite being a largely preventable and treatable disease. Kenya is not the only country suffering from the burden of this life-threatening disease. According to World Health Organisation (WHO) latest world malaria report, there were an estimated 241 million malaria cases and 627,000 malaria deaths worldwide in 2020. This represents about 14 million more cases in 2020 compared to 2019, and 69,000 more deaths. The high number of malaria cases continues to be registered even though several efforts have been put in place towards malaria eradication. It is for this reason scientists and researchers are assessing the use of new tools to edit the genes of malaria-transmitting mosquitoes as they try to come up with a long-lasting solution towards control and elimination of this disease. “The war against malaria has been ongoing for decades. It has led to the development of several interventions strategies, such as antimalarial drugs, insecticide-treated nets, and vaccines among others. However, despite all the interventions, the disease has not been eradicated because there are increased cases of insecticide resistance in mosquitoes, which pose a significant public health concern,” says Dr Willy Kiprotich Tonui, EBS, the Chairman and Executive Director at the Environmental Health Safety (EHS) Consultancy Limited who also doubles up as the Founder and Head of Secretariat to African Genetic Biocontrol Consortium.
Role of CRISPR Technology in Gene Editing of Emerging and Re-emerging Vector Borne Disease
21811K. K. Mahto, P. Prasad, M. Kumar, H. Dubey and A. Ranjan, Recent Advances in Pathogen Interactions, Immunity, and Vector Control Strategies, 2022-04-23 05:49:18.
Vector borne diseases are rampant across the world. Due to spread and estab-lishment of vector species in different geographical areas, vector adaptation and resistance towards many insecticides the only option left is vector control for vari-ous vector borne diseases. Recent advancement in the field of genome editing have provided a variety of tools like, CRISPR, a novel genome editing techniques which can be applied for the control and prevention of many deadly diseases like dengue, chikungunya, filariasis, Japanese encephalitis and Zika. The present chapter is aimed to discuss the recent advancement in genome editing tools such as, their applica-tion, challenges, and limitations in vector control. Additionally, this chapter would potentially be advantageous to understand the hurdles, knowledge gaps in eliminating vector borne disease.
New frontiers in vector control
21717WHO, World Health Organization, 2022-04-11 09:17:11.
Ever since Sir Ronald Ross discovered malaria parasites in an Anopheles mosquito in 1897, controlling insect vectors has played an increasingly important role in reducing the burden of the disease. For decades after World War II, indoor residual spraying (IRS) with insecticides was the only weapon against mosquitoes and proved a blunt and reasonably effective instrument for protecting people inside their homes. Then, beginning in the early 2000s, insecticide-treated nets (ITNs) became a new addition to countries’ vector control strategies. Thanks, in part, to the wide deployment of these 2 WHO-recommended interventions, the world made remarkable gains against malaria in the period 2000–2015. But progress plateaued, and this troubling slowdown was exacerbated by COVID-19. According to WHO’s latest World malaria report, 2020 saw a rise in the global burden of malaria, with an estimated 627 000 deaths and 241 million new cases of the disease. Getting back on track, and meeting WHO’s targets of a 90% reduction in malaria case incidence and mortality rates by 2030, will require renewed global attention, increased funding, and continued research and development of new interventions, among other actions. In the field vector control, researchers are working on several innovations that aim to enhance efforts to combat the disease.
Podcast: How do you solve a problem like malaria?
21655A. Jha, The Economist, 2022-04-05 15:01:14.
SQUASHING MALARIA could, over the next three decades, save as many lives as covid-19 has taken. We explore new ways to fight infections: from the introduction of the first malaria vaccines, to genetically modified mosquitoes
Expanding the flexibility of genome editing approaches for population control of the malaria mosquito
22226N. Kranjc, Imperial College London-PhD, 2022-04-01 15:50:55.
Discovery and adaptation of CRISPR-Cas systems for genome editing have allowed us to gain an efficient and yet simple tool for genetic manipulation in various fields of molecular biology and biotechnology. One of the most promising applications is the use of CRISPR-Cas9 endonuclease for gene drive systems as a population control strategy for various insect pests of medical and agricultural importance. Use of CRISPR-Cas9 endonuclease in gene drive applications has shown great promise in the laboratory, particularly for the control of Anopheles gambiae, the major vector of malaria. However, the performance of such gene drives can be limited by the range of available target sequences and by a propensity of existing endonuclease formulations to generate resistant mutations that hinder the gene drive’s efficiency. To expand the flexibility of gene drive systems, computational analysis was performed to identify additional Cas9 orthologs and their specificities that could usefully augment the targeting range of endonuclease-based gene drives. Two alternative variants of CRISPR-Cas endonucleases found in the bacterial species Lactobacillus rhamnosus and Bacteroides fragilis were assessed for their potential to expand the targeting space in the genome Anopheles gambiae. In addition, a computational tool was developed that evaluates neighbouring sequences to the target site to measure both its likely functional constraint and its likely propensity for DNA repair that could generate in-frame alleles. Using this approach we were able to generate a prioritized list of Anopheles gambiae target sites for gene drive applications that are less likely to be compromised by resistant alleles.
Squashing malaria could save as many lives as covid-19 has taken
21012Anonymous, The Economist, 2022-03-19 06:25:31.
When it comes to covid-19 vaccines, poor countries in Africa have been stuck at the back of the queue. However, the continent’s long wait for another immunological miracle appears to be drawing to a close. Later this year, the world’s first malaria vaccine is scheduled for a roll-out. Although the current version leaves much to be desired—it requires four doses, is hard to manufacture at scale and reduces severe infections by a mere 30%—better alternatives may be on the way. A jab developed by scientists at Oxford has shown 77% effectiveness. If clinical trials go well, they aim to apply for pre-qualification from the World Health Organisation in September. Production at a rate of up to 200m doses per year could follow swiftly.
Should we kill every mosquito on Earth?
20519J. Phelan, LiveScience, 2022-02-28 08:05:44.
Before you grab that can of bug spray, know this: While some mosquitoes are dangerous to us, not all are. Even those that are sometimes harmful tend not to feed on humans, preferring honeydew, plant sap and nectar, according to Mosquito Joe, a mosquito control company. There are around 3,500 mosquito species, but "only around 100 will potentially bite and spread disease to humans," Steven Sinkins, a professor in microbiology and tropical medicine at the Centre for Virus Research at the University of Glasgow in Scotland, told Live Science in an email. For instance, Culiseta mosquitoes often bite humans, but are not known to carry any debilitating diseases, while Toxorhynchites, which are common the world over and tend to live in forests, prefer nectar sugars to blood, according to Entomology Today. Therefore, it probably wouldn't be necessary to get rid of every mosquito species. Instead, we could target the more problematic ones, such as Aedes aegypti, which carry diseases such as yellow fever and Zika. A. aegypti is now ubiquitous, but it wasn't always this way. The species first spread out of Africa during the slave trade between the 15th and 19th centuries, through trade with Asia in the 18th and 19th centuries, and via troop movements during World War II, according to the World Mosquito Program, a nonprofit based in Australia.
A UC malaria initiative program receives grant for work researching genetically engineered mosquitoes
20483S. Slater, The California Aggie, 2022-02-23 08:39:35.
Malaria, a mosquito-borne infectious disease, was discovered in 1880, and has remained widespread in tropical regions around the equator including parts of Africa, Asia and Latin America, resulting in thousands of deaths and a significant blow to economic development in these regions. Many of the attempted strategies to eliminate malaria in the past have planned to do so by eliminating mosquitoes entirely — but according to a recent press release, the Vector Genetics Laboratory (VGL) at UC Davis, in collaboration with a UC malaria initiative program that originally started at UC Irvine, and with the financial support of a $10.2 million grant from Open Philanthropy, is taking a different approach. “Mosquitoes are a part of the ecosystem,” Greg Lanzaro, project principal investigator and director at VGL, said. “Our strategy does not eliminate mosquitoes. The mosquitoes will still be there, they’ll just be incapable of transmitting malaria. In every sense these mosquitoes are normal mosquitoes, except for the fact that they can’t transmit malaria.” The idea is called a “population modification strategy,” Lanzaro said, explaining that groups at UC Irvine and Johns Hopkins University genetically engineered mosquitoes that are incapable of transmitting the malaria parasite. “The way that malaria is transmitted is that the mosquito bites a person who has malaria and it picks up the parasite in the blood that it feeds on,” Lanzaro said. “Then the parasite develops in the mosquito so that when the mosquito bites the next person, they spread the parasite. Our mosquitoes have been engineered with a couple of genes that kill the parasite inside of the mosquito, so they’re not able to transmit.”
Regulation of genetically engineered (GE) mosquitoes as a public health tool: a public health ethics analysis
20480Z. Meghani, Globalization and Health, 18:21. 2022-02-21 08:33:18.
In recent years, genetically engineered (GE) mosquitoes have been proposed as a public health measure against the high incidence of mosquito-borne diseases among the poor in regions of the global South. While uncertainties as well as risks for humans and ecosystems are entailed by the open-release of GE mosquitoes, a powerful global health governance non-state organization is funding the development of and advocating the use of those bio-technologies as public health tools.
Evaluation of anti-malaria potency of wild and genetically modified Enterobacter cloacae expressing effector proteins in Anopheles stephensi
20485H. Dehghan, S. H. Mosa-Kazemi, B. Yakhchali, N. Maleki-Ravasan, H. Vatandoost and M. A. Oshaghi, Parasites and Vectors, 15:63. 2022-02-19 08:43:23.
Malaria is one of the most lethal infectious diseases in tropical and subtropical areas of the world. Paratransgenesis using symbiotic bacteria offers a sustainable and environmentally friendly strategy to combat this disease. In the study reported here, we evaluated the disruption of malaria transmission in the Anopheles stephensi-Plasmodium berghei assemblage using the wild-type (WT) and three modified strains of the insect gut bacterium, Enterobacter cloacae.
Gene drive mosquitoes can aid malaria elimination by retarding Plasmodium sporogonic development
20447A. Hoermann, T. Habtewold, P. Selvaraj, G. Del Corsano, P. Capriotti, M. G. Inghilterra, K. M. Temesgen, G. K. Christophides and N. Windbichler, bioRxiv, 2022.02.15.480588. 2022-02-17 09:41:11.
Gene drives hold promise for the genetic control of malaria vectors. The development of vector population modification strategies hinges on the availability of effector mechanisms impeding parasite development in transgenic mosquitoes. We augmented a midgut gene of the malaria mosquito Anopheles gambiae to secrete two exogenous antimicrobial peptides, Magainin 2 and Melittin. This small genetic modification, capable of efficient non-autonomous gene drive, hampers oocyst development in both Plasmodium falciparum and Plasmodium berghei. It delays the release of infectious sporozoites while it simultaneously reduces the lifespan of homozygous female transgenic mosquitoes. Modeling the spread of this modification using a large-scale agent-based model of malaria epidemiology reveals that it can break the cycle of disease transmission across a range of endemic settings.Competing Interest StatementThe authors have declared no competing interest.
C-type lectin 4 regulates broad-spectrum melanization-based refractoriness to malaria parasites
20489M. L. Simões, Y. Dong, G. Mlambo and G. Dimopoulos, PLOS Biology, 20:e3001515. 2022-02-13 08:53:42.
Anopheles gambiae melanization-based refractoriness to the human malaria parasite Plasmodium falciparum has rarely been observed in either laboratory or natural conditions, in contrast to the rodent model malaria parasite Plasmodium berghei that can become completely melanized by a TEP1 complement-like system-dependent mechanism. Multiple studies have shown that the rodent parasite evades this defense by recruiting the C-type lectins CTL4 and CTLMA2, while permissiveness to the human malaria parasite was not affected by partial depletion of these factors by RNAi silencing. Using CRISPR/Cas9-based CTL4 knockout, we show that A. gambiae can mount melanization-based refractoriness to the human malaria parasite, which is independent of the TEP1 complement-like system and the major anti-Plasmodium immune pathway Imd. Our study indicates a hierarchical specificity in the control of Plasmodium melanization and proves CTL4 as an essential host factor for P. falciparum transmission and one of the most potent mosquito-encoded malaria transmission-blocking targets.
Gene-drive mosquitoes, a prospect for future malaria control
21770S. A. Monawwer, A. O. I. Alzubaidi, F. Yasmin, S. M. Q. Haimour, S. M. I. Shay and I. Ullah, Pan African Medical Journal, 41:2-6. 2022-02-08 07:58:25.
Despite major developments in malaria control over the past two decades, the disease continues to scourge the human population across the globe. Rising concerns such as insecticide resistance amongst vector mosquitoes are a cause of huge fear amongst healthcare providers and policymakers. Amidst such dire circumstances, a recent development may form the blueprint for future malaria control as for the first time ever researchers were able to decimate an entire mosquito population using gene-drive technology within a span of one year in a multi-generation, ecologically challenging study. Despite some concerns, the technology displayed a high potential of becoming a powerful tool in malaria control.
Could Crispr Flip the Switch on Insects’ Resistance to Pesticides?
20288E. Mullin, WIRED, 2022-02-02 11:53:17.
WHILE THE COVID-19 pandemic raged across the world in 2020, another disease was quietly infecting more than 220 million people on the continent of Africa: malaria. That year, the disease led to more than 600,000 deaths, most of them children. Caused by the parasite Plasmodium, the illness is spread through the bites of infected female Anopheles mosquitoes. Insecticide-treated bed nets and indoor spraying have long been some of the most effective strategies for combating the disease. But decades of using these chemicals has lessened their potency. It happens like this: Insecticides kill off most of the mosquitoes in an area. But a small number may survive because something about their genetic makeup makes them unaffected by the pesticide. Mosquitoes within that small population mate with each other and pass on their genes to their offspring, breeding more resistant mosquitoes. In some cases, resistance has built up just a few years after the introduction of an insecticide. It makes fighting deadly mosquitoes a constant game of whack-a-mole. Insecticides remain the frontline in fighting malaria, because interventions like building mosquito-resistant housing are still experimental, and the effort to develop a vaccine has taken decades. Last summer the World Health Organization recommended Mosquirix, the first anti-parasitic vaccine, for African children under age 5, but it is only 30 percent effective at preventing serious disease, and will take many years to achieve approval and distribution among individual nations.
Crisp Genes
20283J. Mckenna, The Simple Science, 2022-01-29 11:44:36.
Imagine we had the power to use genetic technologies to stop one of humanity’s most dangerous predators. What is that predator? Sharks? Crocodiles? Snakes? Think far, far smaller. It is in fact, the mosquito.Mosquitos cause all sorts of nasty diseases like the Zika Virus, Dengue Fever, Yellow Fever, and malaria. While nobody really wants to contract any of those diseases, and they’ll all make you pretty miserable, they’re nothing compared to the frankly hellacious malaria being one of the single biggest killers of humans in history. Well, plot twist, we actually do have the technology and it comes in the form of some genetic machinery discovered in bacteria: CRISPR-Cas9 (or CRISPR for short).
Scientists find transmission chain-breaker, give new hope for fight against malaria
20473ANI, ANI, 2022-01-27 08:09:19.
A recent study, published online in 'PLoS Biology', has revealed that blocking a key protein found in Anopheles gambiae mosquitoes -- the principal vector for malaria transmission to humans in Africa could thwart infection with malaria parasites and thus prevent them from transmitting the parasites to humans. The study was undertaken by Johns Hopkins Malaria Research Institute at the Johns Hopkins Bloomberg School of Public Health. In a lab experiment, the researchers used CRISPR/Cas9 gene-editing technology to delete the gene for a protein called CTL4 from Anopheles gambiae mosquitoes. This deletion made the mosquitoes highly resistant to the malaria parasite. The researchers found that disrupting the CTL4 protein brought a 64 percent decrease in infection prevalence. The researchers believe that targeting the CTL4 protein could be the basis for new strategies to control malaria in regions where it is still endemic.
CRISPR Technology Can Eliminate Disease-Spreading Mosquitoes
20133S. Krishana, Now, 2022-01-19 13:10:41.
Scientists have uncovered a new technique they call the “precision-guided sterile insect technique,” or pgSIT. While most CRISPR procedures affect organisms that spread diseases by passing a gene change down generations, this system is more limited. It targets male mosquito genes that are linked to fertility. As a result of changing these genes, any offspring these mosquitoes have would be infertile. “pgSIT is a new scalable genetic control system that uses a CRISPR-based approach to engineer deployable mosquitoes that can suppress populations,” said Omar Akbari, one of the study’s authors. “Males don’t transmit diseases, so the idea is that, as you release more and more sterile males, you can suppress the population without relying on harmful chemicals and insecticides.” But it’s the female population that spreads diseases, so pgSIT targets them, as well. According to the study, the CRISPR technology treatment renders female mosquitoes unable to fly or hold their wings up. It also makes them slower and more lethargic in their movements. Combined, these effects lower the chances that these female mosquitoes will mate or successfully find a blood source and attach to it to spread disease.
Genetic Strategy Reverses Insecticide Resistance
20108H. Tasoff, The Current, 2022-01-18 17:08:09.
University of California biologists have now developed a method that reverses insecticide resistance using CRISPR/Cas9 technology. A team including UC Santa Barbara researchers Craig Montell(link is external) and Menglin Li(link is external), UC San Diego researchers Bhagyashree Kaduskar, Raja Kushwah and Professor Ethan Bier of UCSD’s Tata Institute for Genetics and Society (TIGS) used the genetic editing tool to replace an insecticide-resistant gene in fruit flies with the normal insecticide-susceptible form. Their achievement, described in Nature Communications(link is external), could significantly reduce the amount of insecticides used. “This strategy could be used to reverse the resistance of mosquito disease vectors that spread devastating diseases that impact hundreds of millions of people each year,” said Craig Montell, a professor of molecular, cellular and developmental Biology at UC Santa Barbara.
Reversing insecticide resistance with allelic-drive in Drosophila melanogaster
20085B. Kaduskar, R. B. S. Kushwah, A. Auradkar, A. Guichard, M. Li, J. B. Bennett, A. H. F. Julio, J. M. Marshall, C. Montell and E. Bier, Nature Communications, 13:291. 2022-01-12 09:16:33.
A recurring target-site mutation identified in various pests and disease vectors alters the voltage gated sodium channel (vgsc) gene (often referred to as knockdown resistance or kdr) to confer resistance to commonly used insecticides, pyrethroids and DDT. The ubiquity of kdr mutations poses a major global threat to the continued use of insecticides as a means for vector control. In this study, we generate common kdr mutations in isogenic laboratory Drosophila strains using CRISPR/Cas9 editing. We identify differential sensitivities to permethrin and DDT versus deltamethrin among these mutants as well as contrasting physiological consequences of two different kdr mutations. Importantly, we apply a CRISPR-based allelic-drive to replace a resistant kdr mutation with a susceptible wild-type counterpart in population cages. This successful proof-of-principle opens-up numerous possibilities including targeted reversion of insecticide-resistant populations to a native susceptible state or replacement of malaria transmitting mosquitoes with those bearing naturally occurring parasite resistant alleles.
The Need for a Tiered Registry for US Gene Drive Governance
20003K. L. Warmbrod, A. L. Kobokovich, R. West, G. K. Gronvall and M. Montague, Health Security, 2022-01-10 10:08:26.
A great deal of attention has been focused on the potential risks of gene drives, the kinds of biosafety protections they may require, and how they may be reversed; however, less attention has been paid to the systems that would be useful to have in place in the future, when multiple gene drives may be fielded in multiple species, environments, and countries.4-7 The need for coordinated governance of these technologies will become more pressing as gene drive technologies advance and more drives are created to address other vector-borne diseases like the West Nile virus, agricultural pest management, or invasive species. Gene drives carry different inherent risks compared with other genetically modified organisms (GMOs). Existing governance mechanisms for traditional GMOs are insufficient for oversight of gene drives, which require different systems to assess their usefulness and safety. To address the needs for enhanced oversight, we propose a tiered registry system, similar to the clinical trials databases, which can provide government officials, researchers, biotechnology companies, and the public with useful information about ongoing gene drive research or previously released gene drives. Such a resource would enable scientists to confirm that new gene drives would not interfere with existing drives, provide the public with the information needed to make informed decisions concerning consent for release of gene drives, provide researchers with technical information needed to prevent collisions of independent projects modifying the same organism, and provide regulators with information critical for effective oversight. We propose that the US government should implement such a registry for gene drives in the United States, which does not have a robust gene drive regulatory system in place and is not party to the international treaty most relevant for international gene drive regulation, the Convention on Biological Diversity.8 In this commentary, we describe current efforts to safely regulate gene drive and similar genetic technologies worldwide and how the United States could build a tiered registry database that is specifically designed to regulate such technologies throughout a drive's life cycle.
Preparing an Insectary in Burkina Faso to Support Research in Genetic Technologies for Malaria Control
20042C. Guissou, M. M. Quinlan, R. Sanou, R. K. Ouédraogo, M. Namountougou and A. Diabaté, Vector-Borne and Zoonotic Diseases, 2022-01-06 09:53:59.
The Institut de Recherche en Sciences de la Santé (IRSS) of Burkina Faso, West Africa, was the first African institution to import transgenic mosquitoes for research purposes. A shift from the culture of mosquito research to regulated biotechnology research and considerable management capacity is needed to set up and run the first insectary for transgenic insects in a country that applied and adapted the existing biosafety framework, first developed for genetically modified (GM) crops, to this new area of research. The additional demands arise from the separate regulatory framework for biotechnology, referencing the Cartagena Protocol on Biosafety, and the novelty of the research strain, making public understanding and acceptance early in the research pathway important. The IRSS team carried out extensive preparations following recommendations for containment of GM arthropods and invested efforts in local community engagement and training with scientific colleagues throughout the region. Record keeping beyond routine practice was established to maintain evidence related to regulatory requirements and risk assumptions. The National Biosafety Agency of Burkina Faso, Agence Nationale de Biosécurité (ANB), granted the permits for import of the self-limiting transgenic mosquito strain, which took place in November 2016, and for conducting studies in the IRSS facility in Bobo-Dioulasso. Compliance with permit terms and conditions of the permits and study protocols continued until the conclusion of studies, when the transgenic colonies were terminated. All this required close coordination between management and the insectary teams, as well as others. This article outlines the experiences of the IRSS to support others undertaking such studies. The IRSS is contributing to the ongoing development of genetic technologies for malaria control, as a partner of Target Malaria (https://targetmalaria.org). The ultimate objective of the innovation is to reduce malaria transmission by using GM mosquitoes of the same species released to reduce the disease-vectoring native populations of Anopheles gambiae s.l.
Driving the Self-Destruction of Malaria-Transmitting Mosquitos
19948H. Aliouche, News Medical Life Sciences, 2021-12-22 09:36:57.
Self-destruction of malaria-transmitting mosquitoes can be driven by gene drives deployed to manipulate natural populations. In particular, they can be used to reduce the number of individuals in a population or to modify their composition; this is particularly useful when such species are vectors of disease. The use of genetic engineering tools is becoming increasingly widespread and enables the deployment of natural and synthetic gene drivers that can propagate a particular subset of genetic expressions population through the biasing of Mendelian inheritance laws.
Integrated Management of Malaria Vectors in Africa
19971R. Mbabazi, K. Maredia, B. B. El-Sayed, A. K. Babumba, M. Savadogo and O. Akinbo, Genetically Modified and other Innovative Vector Control Technologies, 2021-12-21 11:36:56.
Malaria disease is a major public health burden in Africa. The control of malaria vectors is a critical component for prevention, management, and eradication of malaria disease. This chapter presents information on the current status of malaria vector control in Africa with emphasis on integrated vector management (IVM) programs. The chapter highlights innovative and emerging technologies such as sterile insect technique, gene drive, Wolbachia-based biological control, and other technologies for malaria vector control in Africa which can be integrated into IVM programs. The chapter also provides global resources on malaria vector management programs.
Measuring Public Attitudes to Releases of Transgenic Mosquitoes for Disease Control, with Special Reference to Dengue and Malaria
19958L. A. De Las Llagas and M. S. T. Gunigundo, Genetically Modified and other Innovative Vector Control Technologies, 2021-12-21 11:10:05.
Since the advent of DDT in public health and agriculture, science leaped forward with revolutionary technology such as gene drive or editing, thus making it possible to develop alternative approaches to address vector-borne diseases. However, their utilization and sustenance in public life are dependent on public attitude, i.e., societal awareness and social acceptance. In the face of strong skepticism against genetically modified organisms in both developed and developing countries, public acceptance is therefore a requirement (Boete and Beisel 2013, and Bohannon 2002, as cited in De Souza et al. Understanding the requirements and factors necessary for the acceptance of genetically modified mosquitoes as a potential malaria control tool in Ghana: a questionnaire survey, AsPac J Biol Biotechnol 21(3):76–88, 2013).
Safe Application of Genetically Modified Mosquito (GMM) to Combat Dengue and Chikungunya Depends on Socioeconomic Status and Social Acceptance in the Developing Countries: A Comprehensive Analysis
19898M. N. Islam, Genetically Modified and other Innovative Vector Control Technologies, 2021-12-21 08:16:32.
The emerging and re-emerging vector-borne diseases are a serious public health problem throughout the world. It has been observed that more than 100 countries and approximately half of the world’s population are at risk on vector-borne diseases (VBDs). The global burden of the vector-borne diseases is unacceptably high. It alludes toward their functional inappropriateness, untimeliness, and irrelevance in controlling vectors and vector-borne diseases. Modern technologies, coupled with other appropriate ones within the precincts of integrated vector management (IVM), can tide over this situation posed by conventional, mostly insecticide-based, methodologies. A lot of challenges, obstacles, and interruptive factors have warranted urgent deployment of new approaches for the control of VBDs keeping in mind the inbuilt ethical, social, and regulatory issues. Genetically modified mosquito (GMM) technology is a complex and highly sophisticated biotechnological intervention for suppression of vector populations. Wolbachia-associated sterile insect technique (SIT) has been proved highly significant and effective for replacement of mosquito populations. Adopting a highly sophisticated GMM technology to suppress or replace the mosquito populations’ density is a big question in developing countries because their priority is directed to foremost fulfill the basic human rights to sustain. Yet, notwithstanding foreseeable bottlenecks, of paramount importance is the need to deploy GMM technology with due consideration to socioeconomic factors and availability of advanced biotechnological facilities during the application of GMM in the developing countries.
Malaria vector control tools in emergency settings: What do experts think? Results from a DELPHI survey
19785C. Boete, S. Burza, E. Lasry, S. Moriana and W. Robertson, Conflict and Health, 15:11. 2021-12-20 14:16:22.
Background The use and implementation of novel tools for malaria control such as long lasting impregnated bednets (LLINs) and Indoor Residual Spraying (IRS) over the last decade has contributed to a substantial reduction in malaria burden globally. However numerous challenges exist particularly in relation to vector control in emergency settings. This study seeks to explore expert opinion on the utility of existing tools within the emergency context setting and to better understand the attitude towards emerging and innovative tools (including Genetically Modified Mosquitoes) to augment current approaches. Methods 80 experts in the field of malaria and vector control were invited to participate in a two-round Delphi survey. They were selected through a combination of literature (academic and policy publications) review and snowball sampling reflecting a range of relevant backgrounds including vector control experts, malaria programme managers and emergency response specialists. The survey was conducted online through a questionnaire including the possibility for free text entry, and concentrated on the following topics: Utility and sustainability of current vector control tools, both in and outside emergency settings Feasibility, utility and challenges of emerging vector control tools, both in and outside emergency settings Current and unmet research priorities in malaria vector control and in malaria control in general. Results 37 experts completed the first round and 31 completed the second round of the survey. There was a stronger consensus about the increased utility of LLIN compared to IRS in all settings, while insecticide-treated covers and blankets ranked very high only in emergency settings. When considering the combination of tools, the ones deemed most interesting always involved LLINs and IRS regardless of the setting, and the acceptability and the efficacy at reducing transmission are essential characteristics. Regarding perceptions of tools currently under development, consensus was towards improvement of existing tools rather than investing in novel approaches and the majority of respondents expressed distrust for genetic approaches. Conclusion Malaria vector control experts expressed more confidence for tools whose efficacy is backed up by epidemiological evidence, hence a preference for the improvement rather than the combination of existing tools. Moreover, while several novel tools are under development, the majority of innovative approaches did not receive support, particularly in emergency settings. Stakeholders involved in the development of novel tools should involve earlier and raise awareness of the potential effectiveness amongst a wider range of experts within the malaria community to increase acceptability and improve early adoption once the evidence base is established.
Gene Drives For Malaria Control And Elimination
19693Annonymous, Health Tech, 2021-12-16 19:01:30.
There is notable ongoing research and prioritization of gene drive technology in Africa for Malaria control and elimination. Currently, there is ongoing gene drive mosquito research in Burkina Faso, Ghana, Mali and Uganda led by the Target Malaria consortium. While laboratory research has demonstrated that gene drive techniques are effective in altering the Anopheles mosquito populations so that they can no longer transmit Malaria parasites and crashing entire mosquito populations, this research still has a long way to go in testing the effectiveness of gene drive mosquitoes in controlling Malaria. Initiated in 2018, Target Malaria’s work in Uganda is led by the Uganda Virus Research Institute (UVRI). The work in Uganda is still in early stages, focusing on entomological mosquito collections from field sites on islands within Lake Victoria and mainland sites. In Burkina Faso, Target Malaria’s initiated exploratory gene drive research in in 2012, led by the Institut de Recherche en Sciences de la Santé (IRSS) in Bobo-Dioulasso. In 2019, the team released genetically modified sterile male mosquitoes in Bana village. The mosquitoes were genetically-modified to be sterile, which means they died without any offspring. These were not gene drive mosquitoes, and their release was not to test these as a vector control tool.
Modeling impact and cost-effectiveness of driving-Y gene drives for malaria elimination in the Democratic Republic of the Congo
19594N. Metchanun, C. Borgemeister, G. Amzati, J. von Braun, M. Nikolov, P. Selvaraj and J. Gerardin, Evolutionary Applications, 2021-12-07 17:59:09.
Malaria elimination will be challenging in countries that currently continue to bear high malaria burden. Sex-ratio distorting gene drives, such as driving-Y, could play a role in an integrated elimination strategy if they can effectively suppress vector populations. Using a spatially explicit, agent-based model of malaria transmission in eight provinces spanning the range of transmission intensities across the Democratic Republic of the Congo, we predict the impact and cost-effectiveness of integrating driving-Y gene drive mosquitoes in malaria elimination strategies that include existing interventions such as insecticide-treated nets and case management of symptomatic malaria. Gene drive mosquitoes could eliminate malaria and were the most cost-effective intervention overall if the drive component was highly effective with at least 95% X-shredder efficiency at relatively low fertility cost, and associated cost of deployment below 7.17 $int per person per year. Suppression gene drive could be a cost-effective supplemental intervention for malaria elimination, but tight constraints on drive effectiveness and cost ceilings may limit its feasibility.
The economic value of genetically engineered mosquitoes as a Malaria control strategy depends on local transmission rates
19788K. Lacy, K. A. Schaefer, D. P. Scheitrum and E. Y. Klein, Biotechnology Journal, 10. 2021-12-06 14:26:13.
This paper assesses the economic value of genetically engineered (GE) Anopheles gambiae mosquitoes as a malaria control strategy. We use an epidemiological-economic model of malaria transmission to evaluate this technology for a range of village-level transmission settings. In each setting, we evaluate public health outcomes following introduction of GE mosquitoes relative to a "status quo" baseline scenario. We also assess results both in contrast to-and in combination with-a Mass Drug Administration (MDA) strategy. We find that-in low transmission settings-the present value (PV) public health benefits of GE mosquito release are substantial, both relative to status quo dynamics and MDA. In contrast, in high transmission settings, the release of GE mosquitoes may increase steady-state infection rates. Our results indicate that there are substantial policy complementarities when GE mosquito release is combined with local MDA-the combined control strategy can lead to local eradication.
Scientists eye gene drive technology to combat malaria
19496S. Buguzi, Sci Dev Net, 2021-12-03 16:55:44.
Scientists are hoping that adoption of gene drive technology could reduce mosquito populations as they call for new innovations in the fight against malaria, a fatal disease widespread in Sub-Saharan Africa. The World Health Organization (WHO) says the Africa region accounted for around 94 per cent of all global malaria cases and deaths in 2019. Over two-thirds of deaths were among children under the age of five. Gene drive technology — genetic engineering that modifies malaria mosquitoes so they can pass their genes on to large mosquito populations — could potentially contribute to malaria elimination in Africa, according to Krystal Birungi, a field entomology coordinator at the not-for-profit research consortium Target Malaria, Uganda. “There is a sense in which our best tools today are also our oldest, which implies that innovation needs to be scaled up.” Fredros Okumu, entomologist and director of science, Ifakara Health Institute, Tanzania “It is a cost-effective way to cut down malaria vectors, and is simple to implement because the mosquitoes themselves do the work,” said Birungi during a Roll Back Malaria Partnership virtual boot camp on malaria control innovation on 15 November. Although the technology is not on the market, and is yet to gain public acceptance, if rolled out it could complement existing malaria interventions such as insecticide-treated nets and indoor residual spray, helping reduce malaria cases, according to Birungi.
Podcast: Malaria Gene Drive
19474S. Hartley, S. Neema and C. Opesen, University of Exeter Business School, 2021-11-25 15:15:30.
Professor Sarah Hartley and her two colleagues in Uganda, Stella Neema and Chris Opesen discuss gene drive research for malaria control. Funded by British Academy and Wellcome trust, their work is to understand the social science challenges around the development of this kind of technology and to consider how governance and ethics should be managed when dealing with a scientific breakthrough such as this.
Gene drives in malaria control: what we need to know
19289R. Mudziwapasi, M. C. Changara, A. Ndudzo, T. Kaseke, F. Godobo, F. L. Mtemeli, R. Shoko, F. Songwe, S. Ndlovu and S. Sandra Mlambo, Biotechnology and Biotechnological Equipment, 35:1623-1631. 2021-11-15 13:42:40.
Gene drives are being used to enhance a DNA sequence?s likelihood of passing between generations via sexual reproduction. Gene drives can be deployed to manipulate natural populations. They can be used to suppress populations by reducing the number of individuals in a population or to modify populations. There are more than 3000 mosquito species in the world, some of which are vectors of diseases. Malaria is a typical disease whose vectors are mosquitoes. It affects mostly tropical countries. It kills many people annually, many of whom are children. Interventions currently in use, such as indoor residual spraying and mosquito nets, are proving insufficient to eradicate malaria. Gene drives can be used in different ways to control mosquito populations or to eliminate mosquito species, thereby reducing malaria cases and deaths. This can occur through population replacement or suppression. However, before the elimination of any mosquito species for malaria control, it is necessary to consider the effects of such an action. Additionally, there is a need to review the options available for the control of mosquitoes and to create awareness of the benefits and risks of such an action. This paper, therefore, looks at the role of mosquitoes in the environment, the methods of controlling mosquitoes and malaria and necessary considerations when using gene drives inter alia.
Two years of laboratory studies on the non gene drive genetically modified sterile male mosquitoes concluded successfully in Mali
19224M. Coulibaly, Target Malaria, 2021-11-09 21:44:38.
The Target Malaria Mali team at the Malaria Research and Training Centre (MRTC) based at the University of Sciences, Techniques and Technologies of Bamako (USTTB) is proud to have been the first Malian research team to work on non gene drive genetically modified sterile male mosquitoes. The team has just published the results of the two years we spent studying these mosquitoes in our laboratory. Thanks to this research, we have gained new knowledge and developed cutting-edge skills in the areas of entomology, molecular biology and genetics, allowing us to sustain a colony containing both local and genetically modified mosquitoes. This research was made possible thanks to an authorisation from the Malian Ministry of Environment, Sanitation and Sustainable Development (MEADD) issued on 21 June 2019 to import a strain of non gene drive genetically modified sterile male mosquitoes and study them in a contained environment. Initially designed at Imperial College London1, the genetically modified mosquitoes were then tested at Polo d’Innovazione di Genomica, Genetica e Biologia (PoloGGB) in Terni, Italy, before being transported to Mali. The mosquito eggs arrived by plane on 4 September 2019. They were kept in the insectarium renovated by the Target Malaria project.
Malaria modeling and optimal control using sterile insect technique and insecticide-treated net
19230L. Cai, L. Bao, L. Rose, J. Summers and W. Ding, Applicable Analysis, 2021-11-05 21:55:36.
We investigate a malaria transmission model with SEIR (susceptible-exposed-infected-recovered) classes for the human population, SEI (susceptible-exposed-infected) classes for the wild mosquitoes and an additional class for the sterile mosquitoes. The basic reproduction number of the disease transmission is obtained, and a release threshold of the sterile mosquitoes is provided. We formulate an optimal control problem in which the goal is to minimize both the infected human populations and the cost to implement two control strategies: the release of sterile mosquitoes and the usage of insecticide-treated nets to reduce the malaria transmission. Adjoint equations are derived, and the characterization of the optimal controls is established. Finally, we quantify the effectiveness of the two interventions aimed at limiting the spread of malaria transmission. A combination of both strategies leads to more rapid elimination of the wild mosquito population that can suppress malaria transmission. Numerical simulations are provided to illustrate the results.
Will freeing ourselves (forever) from mosquitoes soon be a realizable “dream”? Pros and cons of an epochal turning point – breaking latest news
19160Annonymous, Breaking Latest News, 2021-11-05 14:34:10.
Also true for a dangerous insect like the mosquito: due to the pathologies of which vector, such as the malaria, the dengue o la yellow fever, every year in the world about 800 thousand people die. There are therefore quite a few reasons to want to get rid of it, not just the itchy summer bites, and thanks to the technique developed by Professor Crisanti it would seem possible, in a not too distant future. It starts from a premise: Not that we want to get rid of all mosquitoes. There are around 3,500 species of mosquitoes and fortunately only a few transmit parasitic diseases such as malaria or others that cause diseases such as zika and dengue. So if I want to get rid of malaria I have to attack malaria. Traditionally this has been done with insecticides which have shown all their limits and dangers. These measures, which are apparently simple, require sustainability over time, require resources and political continuity. All this is missing today. Hence biotechnology, the idea of making mosquitoes themselves do this job. If we manage to modify the genetic characteristics of mosquitoes, we can theoretically create mosquitoes that do not reproduce or that do not transmit the infection.
Population replacement gene drive characteristics for malaria elimination in a range of seasonal transmission settings: a modeling study
19134S. Leung, N. Windbichler, E. Wenger, C. Bever and P. Selvaraj, bioRxiv, 2021.11.01.466856. 2021-11-03 14:42:23.
Genetically engineering mosquitoes is a promising new vector control strategy to reinvigorate the fight against malaria in Sub-Saharan Africa. Using an agent-based model of malaria transmission with vector genetics, we examine the impacts of releasing population-replacement gene drive mosquitoes on malaria transmission and quantify the gene drive system parameters required to achieve local elimination within a spatially-resolved, seasonal Sahelian setting. We evaluate the performance of two different gene drive systems: "classic" and "integral". Various transmission regimes (low, moderate, and high - corresponding to annual entomological inoculation rates of 10, 30, and 80 infectious bites per person) and other simultaneous interventions, including deployment of insecticide-treated nets (ITNs) and passive healthcare seeking, are also simulated. Local elimination probabilities decreased with pre-existing population target site resistance frequency, increased with transmission-blocking effectiveness of the introduced antiparasitic gene and drive efficiency, and were context dependent with respect to fitness costs associated with the introduced gene. Of the four parameters, transmission-blocking effectiveness may be the most important to focus on for improvements to future gene drive strains because a single release of classic gene drive mosquitoes is likely to locally eliminate malaria in low to moderate transmission settings only when transmission-blocking effectiveness is very high (above approximately 80-90‰). However, simultaneously deploying ITNs and releasing integral rather than classic gene drive mosquitoes significantly boosts elimination probabilities, such that elimination remains highly likely in low to moderate transmission regimes down to transmission-blocking effectiveness values as low as approximately 50‰ and in high transmission regimes with transmission-blocking effectiveness values above approximately 80-90‰. Thus, a single release of currently achievable population replacement gene drive mosquitoes, in combination with traditional forms of vector control, can likely locally eliminate malaria in low to moderate transmission regimes within the Sahel. In a high transmission regime, higher levels of transmission-blocking effectiveness than are currently available may be required.Competing Interest StatementThe authors have declared no competing interest.
Small-scale release of non-gene drive mosquitoes in Burkina Faso: from engagement implementation to assessment, a learning journey
18910L. Pare Toe, N. Barry, A. D. Ky, S. Kekele, W. Meda, K. Bayala, M. Drabo, D. Thizy and A. Diabate, Malaria Journal, 20:395. 2021-10-11 14:50:37.
This study provides a review of engagement activities relevant to field trials on non-gene drive genetically-modified mosquitoes as well as an assessment framework-using both qualitative and quantitative studies as well as an audit procedure. The latter was implemented to evaluate whether the release activities could proceed with the appropriate level of agreement from the community. RESULTS: This paper shows the importance of this first phase of work to innovate and learn about engagement processes for responsible research in the field of genetic approaches for malaria vector control. The function of these assessments is crucial for the learning agenda. The assessments demonstrated ways to increase understanding and ensure effective progress with field studies and, therefore, the pathway for responsible research.
Fighting the world’s most deadly animal: the mosquito
19227M. Rozenbaum, Understanding Animal Research, 2021-10-09 21:50:46.
n the first, sterile male mosquitos are mass produced and released into the wild. These sterile males mate with wild females who then lay sterile eggs which will not hatch. This approach has been shown to reduce wild populations by as much as 90% in trials with Aedes aegypt. The second approach is to introduce a gene that, if inherited, results in the death of the female, but not the male. Genetically modified males are mass produced and released. Only male offspring from matings between the modified males and wild females survive. They go on to breed, further spreading the female-killing gene and reducing the overall mosquito population. Genetically modified mosquitoes have been successfully used in parts of Brazil, the Cayman Islands, Panama, and India to control Ae. aegypti mosquitoes. Since 2019, over one billion GM mosquitoes have been released. When genetically modified mosquitoes stop being released into an area, the Ae. aegypti mosquito population slowly returns to normal levels, so control requires regular release of modified mosquitos.
Gene drive revolution: How genetically tweaked mosquitoes could tip the balance in the battle to contain malaria
18903F. Okumu, Genetic Literacy Project, 2021-10-06 14:24:37.
In 2016, a World Health Organisation (WHO) panel concluded that even with the best use of current approaches, there would still be 11 million malaria cases in 2050. What’s needed are longer-term integrated strategies to complement current methods. These may include large-scale environmental management to reduce Anopheles breeding, mosquito-proof homes, stronger health systems and public education focusing on disease prevention. Fortunately, new technologies are also being developed which could complement these strategies at lower cost and less effort. One particularly exciting example is the release of genetically programmed mosquitoes, which we call “protector mosquitoes”. Upon mating with wild mosquitoes they produce offspring that are either incapable of any further reproduction or unable to transmit malaria parasites.
Stakeholders call for adoption of emerging technologies to fight Malaria
18869C. Muchira, KBC, 2021-10-05 19:08:06.
Health stakeholders are calling for adoption of innovative and emerging technologies such as gene drive to change the focus of the war on malaria from just controlling its spread to actual elimination. The African Institute for Development Policy and other stakeholders have urged the government to allocate adequate resources to boost initiatives by institutions in fighting malaria and improve health.According to a 2020 World Health Organization report, in 2019, 229 million people were infected with Malaria in 87 malaria endemic countries. The African Region recorded an estimated 215 million cases in 2019 which accounted for about 94% of cases including Nigeria (27%), the Democratic Republic of the Congo (12%), Uganda (5%), Mozambique (4%) and Niger (3%) accounted for about 51% of all cases globally. Although milestones have been made, the persisting high rates of illnesses and deaths have called for concerted efforts towards malaria elimination.
Microsporidia MB is found predominantly associated with Anopheles gambiae s.s and Anopheles coluzzii in Ghana
18931J. Akorli, E. A. Akorli, S. N. A. Tetteh, G. K. Amlalo, M. Opoku, R. Pwalia, M. Adimazoya, D. Atibilla, S. Pi-Bansa, J. Chabi and S. K. Dadzie, Scientific Reports, 11:5. 2021-09-20 19:43:33.
A vertically transmitted microsporidian, Microsporidia MB, with the ability to disrupt Plasmodium development was reported in Anopheles arabiensis from Kenya, East Africa. To demonstrate its range of incidence, archived DNA samples from 7575 Anopheles mosquitoes collected from Ghana were screened. MB prevalence was observed at 1.8%. An. gambiae s.s constituted 87% of positive mosquitoes while the remaining were from An. coluzzii. Both sibling species had similar positivity rates (24% and 19%; p = 0.42) despite the significantly higher number of An. gambiae s.s analysed (An. gambiae s.s = 487; An. coluzzii = 94; p = 0.0005). The microsporidian was also more prevalent in emerged adults from field-collected larvae than field-caught adults (p < 0.0001) suggestive of an efficient vertical transmission and/or horizontal transfer among larvae. This is the first report of Microsporidia MB in Anopheles mosquitoes in West Africa. It indicates possible widespread among malaria vector species and warrants investigations into the symbiont's diversity across sub-Saharan Africa.
Mosquito transgenesis for malaria control
18284S. Dong, Y. Dong, M. L. Simões and G. Dimopoulos, Trends in Parasitology, 2021-09-02 14:42:32.
Malaria is one of the deadliest diseases. Because of the ineffectiveness of current malaria-control methods, several novel mosquito vector-based control strategies have been proposed to supplement existing control strategies. Mosquito transgenesis and gene drive have emerged as promising tools for preventing the spread of malaria by either suppressing mosquito populations by self-destructing mosquitoes or replacing mosquito populations with disease-refractory populations. Here we review the development of mosquito transgenesis and its application for malaria control, highlighting the transgenic expression of antiparasitic effector genes, inactivation of host factor genes, and manipulation of miRNAs and lncRNAs. Overall, from a malaria-control perspective, mosquito transgenesis is not envisioned as a stand-alone approach; rather, its use is proposed as a complement to existing vector-control strategies.
Genetically changed mosquitoes could transform Africa’s long fight against malaria
18258L. Singh, ForumIAS, 2021-08-30 13:13:44.
In nature, there’s a phenomenon called gene drive which operates in the process of reproduction. This is when a genetic element is able to increase the chance that it will be inherited by offspring. The general underlying principle of all gene drives is an organism that will produce offspring similar to themselves. Some characteristics are randomly passed on from parents to the next generation. However, gene drive forces a different type of inheritance that ensures a specific characteristic is always present in the next generation. Scientists engineer gene drive using various molecular tools. Gene drive is not just a human invention; some occur naturally in insects. Unlike traditional genetic modification, gene drives enable extremely rapid spread of the desired characteristics.
Africa must not rest until Malaria rests: What is the role of emerging technologies?
18165R. Oronje, AFIDEP, 2021-08-20 14:42:16.
As we mark the World Mosquito Day today, it is a sad reminder that Malaria still kills hundreds of thousands of people every year, majority of these people in Africa. According to the World Health Organisation (WHO), Malaria killed 409,000 people in 2019, and 94% of these deaths were in Africa. For those who survive the disease, they have many horrifying tales to tell because many get Malaria every so often, especially for those living in Malaria endemic regions. I have many horrifying tales of my experience with Malaria because I grew up in the Malaria-endemic region of Western Kenya. One of these tales is when I passed out in school when I was in Primary-4 because I had refused to take the very bitter Quinine tablets. My Mum was called to take me to hospital and by the time she arrived, I was in “hallucination mode” because all I remember is seeing two Mums lifting me up; and the next time I woke up, I was in a nearby health facility. My parents still live in this region, which means I visit them often and so every time I visit Western Kenya without taking prophylaxis, I can be sure I will come back with Malaria. But this blog is not about my horrifying Malaria tales, so I will not delve much more into that. Although many people in sub-Saharan Africa have suffered from Malaria, many are not aware of ongoing efforts to develop and test new tools with potential to eliminate Malaria. In a recent study by the African Institute for Development Policy (AFIDEP) on the “Landscape and Political Economy Analysis of Emerging Health Technologies in Sub-Saharan Africa”, we found that apart from the researchers developing these new tools and their funding agencies, other stakeholders including journalists, civil society actors, and policymakers know little, if anything, about the ongoing research on emerging health technologies, including those technologies being developed with potential to eliminate Malaria.
The Complex Lives of Mosquitoes: The Key for Malaria Control
18216F. Okumu, ISGlobal, 2021-08-19 15:19:27.
Mosquitoes spread diseases to millions of people around the world, yet they remain poorly understood by most. Studying their biology and behaviours can help us combat, and eventually eliminate, dangerous diseases such as malaria and dengue fever.There are nearly 3,500 species of mosquitoes. About 400 belong to a family called Anopheles, and of these, only about 50-70 can actually transmit malaria to humans. In Africa, where the malaria burden is highest, the most important are Anopheles gambiae, Anopheles funestus, Anopheles arabiensis and Anopheles colluzzi. Often, only one or two of these dominate malaria transmission in any country. Effective malaria control can therefore be achieved by simply identifying, understanding and then targeting just the one or two dominant Anopheles species instead of trying to kill all mosquitoes.A female Anopheles lays about 500 eggs in her lifetime, usually in standing fresh waters, although some breed along rivers or in brackish waters. The eggs weigh just 4 micrograms each and float like little pontoons on the water surfaces
Mobilizing Mutant Mosquitoes to Fight Malaria
18227D. Mclaughlin and J. Recht, United Nations Foundation, 2021-08-18 15:49:29.
World Mosquito Day today marks the 1897 discovery by Sir Ronald Ross that female Anopheles mosquitoes spread malaria. Since that breakthrough, the world has fought this deadly disease through scientific research and new technology. While astounding progress has been made against the ancient disease, more than 400,000 people died from malaria in 2019, two-thirds of them children under 5, the vast majority in Africa.Existing malaria controls such as spraying insecticides indoors or sleeping beneath long-lasting insecticidal bed nets work by blocking mosquitoes from biting people and transmitting malaria. Such tools have helped halve malaria in many countries throughout sub-Saharan Africa. Yet this remarkable progress is in jeopardy as mosquitoes develop resistance to these insecticides. As the dangerous mosquito continues to adapt, health interventions must continue evolving to protect families from this disease and move us closer to a malaria-free world. Now, there is a promising new tool, seemingly ripped from the pages of a science fiction novel, to stop malaria’s spread: genetically modified mosquitoes.
Identifying Sites for Testing Modified Mosquitoes as a Strategy to Eradicate Malaria
18222A. Fell, UC Davis News, 2021-08-18 15:34:12.
In a newly published article in the journal Evolutionary Applications Professor Greg Lanzaro and his team at the Vector Genetics Laboratory, UC Davis School of Veterinary Medicine, set forth a framework for the selection of field sites in Africa best suited for testing genetically engineered mosquitoes (GEMs).“We followed earlier recommendations from the National Academy of Sciences and the World Health Organization that argued that a physical island would be a logical place to initiate early field trials of a GEM that uses gene drive technology,” Lanzaro said.n this paper, they establish a set of criteria including geographic and genetic isolation, biological complexity, island size, and topography and apply these criteria to a set of 22 potential island sites located off the coast of Africa. Their goal is to identify sites that maximize prospects for success, minimize risk, and serve as a fair, valid and convincing test of the efficacy and impacts of a GEM product intended for large-scale deployment in Africa.
New mosquito control tools are critical
18148L. Braack, Open Access Government, 2021-08-17 17:38:18.
Globally, we are making slow headway in the fight against malaria, but there has been progress, nonetheless. Since 2000, 39 countries and territories have managed to rid themselves of malaria; the most recent is China. Existing tools can achieve local elimination, but the battle is becoming harder and mosquitoes and parasites are able to change their defences, which is why we too have to constantly adapt and respond with better tools and strategies. We should also be on high alert; malaria has been distracting our attention from what will be our next global public health threat: mosquito-borne arboviruses such as Dengue, Chikungunya, Zika, Yellow Fever, West Nile Virus, Usutu, and a host of others few people have heard of. These arboviruses are spreading across the globe, each year more abundant. The mosquitoes that transmit them pose a different set of challenges, as most of them bite by day, with very different breeding habits. We must increase public awareness of the rising threat and invest much greater research effort to find ways to combat these viruses and mosquitoes.
Scientists eradicate malaria-transmitting mosquitos using genetic engineering which make females infertile in new study which takes one step closer to wiping out the disease worldwide.
18078C. Ciaccia, Daily Mail, 2021-07-30 17:09:51.
Malaria kills nearly 500,000 people globally every year, but scientists have now figured out a way to use CRISPR gene-editing technology to make female mosquitoes infertile, described as a 'game-changer' for ending the deadly disease. Researchers from Imperial College London, Genomics Genetics and Biology, and the Liverpool School of Tropical Medicine were able to use a gene drive for the first time to not only show that blocking female reproduction worked in a lab setting, but natural-like setting as well. The researchers targeted the mosquito species Anopheles gambiae, which is responsible for the majority of malaria transmissions in sub-Saharan Africa. The gene-drives targets the gene known as 'doublesex' in these mosquitoes.
Breakthrough in non-GMO malaria control
17914C. Robinson and J. Matthews, GM Watch, 2021-07-29 15:27:47.
A just-published study carried out in a high-security lab claims to show that a CRISPR gene drive (a way of forcing a heritable genetic modification through a whole species or population) can crash populations of malaria-spreading mosquitoes. But why crash mosquito populations with a risky experimental technology if you can completely stop them spreading malaria naturally? A naturally occurring biocontrol agent – a microbe – that inhibits the development of the malaria parasite in the mosquito Anopheles arabiensis, which spreads malaria in Sub-Saharan Africa, has recently been reported in the journal Nature Communications. Among the notable features of this approach are: • The microbe doesn’t seem to harm the mosquitoes in any way • Because it doesn’t kill the mosquitoes or cut their numbers, it should not have an impact on ecosystems dependent on them for food • The microbe seems to give the mosquitoes lifelong protection from malaria infection. The researchers are based at the International Centre of Insect Physiology and Ecology (ICIPE), Kenya, and in the UK. The microbe featured in their recent publication is a microsporidian. Microsporidia are unicellular spore-forming parasites that are now recognised as fungi, or as being related to fungi. All major animal groups harbour them, particularly insects. They spread horizontally, via spores that are ingested by a new host, but many also undergo vertical transmission to the next generation, via infected eggs (known as transovarial transmission).
Genetic engineering may rid world of malaria-transmitting mosquitoes
18163Y. Steinbuch, New York Post, 2021-07-29 14:35:51.
Scientists have eradicated a population of malaria-transmitting mosquitoes by using genetic engineering to make the females infertile — in what the lead researcher called a possible “game-changer in bringing about malaria elimination.” A team of researchers — led by scientists at Imperial College London, Italy’s Polo Genomics Genetics and Biology, and the Liverpool School of Tropical Medicine — used the “gene drive” technology for the study, which was published in Nature Communications. “Gene drive is a self-sustaining and fast-acting technology that can work alongside existing tools such as bed nets, insecticides and vaccines — and could be a game-changer in bringing about malaria elimination,” Andrew Hammond, a molecular biologist at Imperial College London, told the Guardian. Using the technology, scientists may circumvent natural selection by providing genetic instructions that will spread through a mosquito population and pass on a particular trait — in this case, infertility — much faster than could be attained through regular selective breeding, the outlet said.
Gene-Drive Technology Could Decimate Malaria-Carrying Mosquitoes–Scientists Use CRISPR to Modify the Insects’ Genes
17925J. Henry, Tech Times, 2021-07-28 17:53:43.
Gene-drive technology can now suppress the growing numbers of mosquitoes that carry malaria. A group of researchers discovered that this gene-editing technique can eradicate the vectors that could rapidly populate in a particular environment. A mosquito (Anopheles albimanus) is prepared to be studied in a laboratory at the Center for Scientific Research Caucaseco in the outskirts of Cali, Colombia, on April 25, 2012, during the World Day for the fight against malaria. After Colombian physician Manuel Elkin Patarroyo developed a vaccine against malaria in 1986, Colombian scientists keep researching for another immunization for the illness, which in 2010 caused over 855.000 deaths all over the world. A team of 40 scientists is preparing to begin the second phase of chemical tests for a synthetic vaccine against malaria. Malaria is caused by the Plasmodium vivax and Plasmodium falcitarum parasites, and is transmitted by mosquitoes. In a study entitled "Gene-drive suppression of mosquito populations in large cages as a bridge between lab and field" published on Wednesday, July 28 on Nature.com, scientists used genetic engineering to create a special class of mosquitoes that would exterminate those that carry malaria.According to the researchers, their main aim is to develop a weapon that would lessen or wipe out the malaria-spreading mosquitoes. Most importantly, they applied the DNA sequence called "gene drive" to the male mosquitoes. Ruth Muller, one of the researchers who is an entomologist at PoloGGB, said that what they did was a "big breakthrough" in science. Somehow, the scientists are also thinking of freeing the genetically modified mosquitoes someday, but it would take some time to ensure that it is applicable.
Malaria-carrying mosquitoes could be bred out of existence using ‘gene drive’ technology
17923A. Wilkins, METRO, 2021-07-28 17:49:56.
Malaria-carrying mosquitoes have been eliminated using ‘gene drive’ technology in a nature-like environment, in a world-first study. By altering a gene that blocks female mosquito reproduction, and allowing that gene to spread, researchers found they could ensure complete mosquito population collapse within one year of the experiment’s start. It’s the first time so-called ‘gene drive’ technology has been shown to be effective in challenging ecological conditions over a long time scale. The results of the study, published in Nature Communications today, could be a key tool in battling the hundreds of millions of cases of malaria infections that happen each year. ‘The challenges facing malaria elimination have intensified in recent years, due in part to the spread of insecticide resistance and large gaps in funding for parts of sub-Saharan Africa,’ said co-lead author of the study Dr. Drew Hammond. ‘Sadly, researchers estimate that Covid-19 related disruptions may have doubled mortality from malaria in 2020, threatening a setback of several decades. ‘Gene drive is a self-sustaining and fast acting technology that can work alongside existing tools such as bed nets, insecticides and vaccines – and could be a game-changer in bringing about malaria elimination.’
Scientists reveal controversial genetically modified mosquitoes in high-security lab
17920The Frontier Post, The Frontier Post, 2021-07-28 17:44:04.
Many years of additional research will be needed to prove the approach works and the mosquitoes would be safe to release into the wild. The project would also require regulatory approval and agreement by local residents in areas where those mosquitoes live, mostly in sub-Saharan Africa and parts of Asia. Despite years of efforts, malaria remains a major health problem. The mosquito-borne parasitic disease sickens more than 200 million people every year and kills more than 400,000, many of whom are children. So Muller and her colleagues decided to use CRISPR, a technique that enables scientists to easily make very precise changes in DNA to genetically modify the Anopheles gambiae species of mosquito, which spreads malaria in sub-Saharan Africa. The modification consisted of a mutation in a gene known as “doublesex,” which female mosquitoes need for normal development. The mutation deforms their mouths, making them unable to bite and spread the parasite. It also deforms their reproductive organs, rendering them unable to lay eggs. The mutation is combined with a gene drive, “effectively a selfish type of genetic element that spreads itself in the mosquito population,” says Tony Nolan of the Liverpool School of Tropical
Genetic engineering test with mosquitoes ‘may be game changer’ in eliminating malaria
17918L. Geddes, The Guardian, 2021-07-28 17:38:58.
Scientists have successfully wiped out a population of malaria-transmitting mosquitoes by using a radical form of genetic engineering to render the females infertile – in the most advanced and largest ever test of use of the technology to fight the disease. As well as bringing fresh hope in the fight against one of the world’s biggest killers, the study lays the foundations for further trials of gene-drive technology, which could mean self-destroying mosquitoes being released into the wild within 10 years. “This is a very exciting development,” said Dr Thomas Price, a senior lecturer in evolution, ecology and behaviour at the University of Liverpool, who was not involved in the research. “There are still lots of ethical and regulatory questions that need answering. But none of those really matter if it is impossible to build gene drives that are effective in the field. This is a major step towards achieving that.” Despite the reduction in malaria over recent decades there were still 229m cases of the disease in 2019, and 409,000 deaths. Dr Drew Hammond, at Imperial College London, who led the new research, said: “Gene drive is a self sustaining and fast acting technology that can work alongside existing tools such as bed nets, insecticides and vaccines, and could be a game changer in bringing about malaria elimination.”
How An Altered Strand Of DNA Can Cause Malaria-Spreading Mosquitoes To Self-Destruct
17862R. Stein, NPR, 2021-07-28 15:19:15.
For the first time, scientists have shown that a new kind of genetic engineering can crash populations of malaria-spreading mosquitoes. In the landmark study, published Wednesday in the journal Nature Communications, researchers placed the genetically modified mosquitoes in a special laboratory that simulated the conditions in sub-Saharan Africa, where they spread the deadly disease. The male mosquitoes were engineered with a sequence of DNA known as a "gene drive" that can rapidly transmit a deleterious mutation that essentially wipes out populations of the insects. The goal is to create a powerful new tool to fight malaria, which remains one of the world's most terrible scourges. "Our study is the first [that] could show that gene-drive technology works under ecologically challenging conditions," says Ruth Muller, an entomologist who led the research at PoloGGB, a high-security lab in Terni, Italy. "This is the big breakthrough that we made with our study."
A lab experiment shows that we could engineer malaria-carrying mosquitoes to kill themselves off
17909A. Micu, ZME Science, 2021-07-28 15:17:37.
A new paper showcases how genetic engineering can be used to cause populations of malaria-spreading mosquitoes to self-destroy. An international research effort has shown, in the context of a lab experiment, that male mosquitoes engineered to carry a certain strand of DNA can rapidly destroy entire groups of these blood-sucking insects. The main importance of this experiment is that it showcases that gene-drive technology can be used even in harsh environmental conditions, such as those in sub-Saharan Africa. This “gene drive” sequence is essentially a damaging mutation that could prove to be a powerful tool against the carriers of malaria.
Malarial mosquitoes suppressed in experiments that mimic natural environments
17903H. Dunning, Phys Org, 2021-07-28 14:58:38.
Researchers have shown "gene drive" technology, which spreads a genetic modification blocking female reproduction, works in natural-like settings. The team, led by researchers from Imperial College London, Polo GGB and Liverpool School of Tropical Medicine were able to suppress populations of a malaria-carrying mosquito in a year-long experiment mimicking natural environments. This is the first time a gene drive has been shown to be as effective as expected when tested in challenging ecological conditions over a long timescale. The results are published today in Nature Communications. Despite the reduction in malaria over recent decades, there were still 229 million cases of malaria in 2019—an increase on the previous year—and 409,000 deaths. Co-lead author of the study Dr. Drew Hammond, from the Department of Life Sciences at Imperial College London and the Johns Hopkins Malaria Research Institute, said: "The challenges facing malaria elimination have intensified in recent years, due in part to the spread of insecticide resistance and large gaps in funding for parts of sub-Saharan Africa.
Horizontal Transmission of the Symbiont Microsporidia MB in Anopheles arabiensis
17856G. Nattoh, T. Maina, E. E. Makhulu, L. Mbaisi, E. Mararo, F. G. Otieno, T. Bukhari, T. O. Onchuru, E. Teal, J. Paredes, J. L. Bargul, D. M. Mburu, E. A. Onyango, G. Magoma, S. P. Sinkins and J. K. Herren, Frontiers in Microbiology, 12. 2021-07-28 13:43:29.
The recently discovered Anopheles symbiont, Microsporidia MB, has a strong malaria transmission-blocking phenotype in Anopheles arabiensis, the predominant Anopheles gambiae species complex member in many active transmission areas in eastern Africa. The ability of Microsporidia MB to block Plasmodium transmission together with vertical transmission and avirulence makes it a candidate for the development of a symbiont-based malaria transmission blocking strategy. We investigate the characteristics and efficiencies of Microsporidia MB transmission between An. arabiensis mosquitoes. We show that Microsporidia MB is not transmitted between larvae but is effectively transmitted horizontally between adult mosquitoes. Notably, Microsporidia MB was only found to be transmitted between male and female An. arabiensis, suggesting sexual horizontal transmission. In addition, Microsporidia MB cells were observed infecting the An. arabiensis ejaculatory duct. Female An. arabiensis that acquire Microsporidia MB horizontally are able to transmit the symbiont vertically to their offspring. We also investigate the possibility that Microsporidia MB can infect alternate hosts that live in the same habitats as their An. arabiensis hosts, but find no other non-anopheline hosts. Notably, Microsporidia MB infections were found in another primary malaria African vector, Anopheles funestus s.s. The finding that Microsporidia MB can be transmitted horizontally is relevant for the development of dissemination strategies to control malaria that are based on the targeted release of Microsporidia MB infected Anopheles mosquitoes.
Gene-drive suppression of mosquito populations in large cages as a bridge between lab and field
17853A. Hammond, P. Pollegioni, T. Persampieri, A. North, R. Minuz, A. Trusso, A. Bucci, K. Kyrou, I. Morianou, A. Simoni, T. Nolan, R. Müller and A. Crisanti, Nature Communications, 12:4589. 2021-07-28 12:31:16.
CRISPR-based gene-drives targeting the gene doublesex in the malaria vector Anopheles gambiae effectively suppressed the reproductive capability of mosquito populations reared in small laboratory cages. To bridge the gap between laboratory and the field, this gene-drive technology must be challenged with vector ecology.Here we report the suppressive activity of the gene-drive in age-structured An. gambiae populations in large indoor cages that permit complex feeding and reproductive behaviours.The gene-drive element spreads rapidly through the populations, fully supresses the population within one year and without selecting for resistance to the gene drive. Approximate Bayesian computation allowed retrospective inference of life-history parameters from the large cages and a more accurate prediction of gene-drive behaviour under more ecologically-relevant settings. Generating data to bridge laboratory and field studies for invasive technologies is challenging. Our study represents a paradigm for the stepwise and sound development of vector control tools based on gene-drive.
GM mosquitoes to fight malaria
17818I. Khisa, The INDEPENDENT, 2021-07-19 14:40:06.
Scientists at the Uganda Virus Research Institute (UVRI) plans to undertake a research on genetically engineered mosquitoes to tackle malaria. Dr. Jonathan Kayondo, the principal investigator Target Malaria Uganda and Senior Research Officer at UVRI had an email interview with The Independent’s Isaac Khisa about the research and here are the excerpts: n Uganda, Target Malaria’s research is still in early stages, currently at facility readiness. The Uganda Virus Research Institute became a primary Target Malaria project site in 2016. We have been laying the research groundwork by setting up the necessary infrastructure and building capacity of the teams. We constructed a new Arthropod Containment Level 2 (ACL2) insectary to facilitate future studies on development and evaluation of genetically modified mosquitoes following international containment guidelines and best practices. It was inaugurated in July 2019. Our teams are currently testing the facility for functionality by studying the local wild mosquitoes under containment and developing standard operating procedures (SOPs) as part of the capacity building efforts. We are also busy developing stakeholder engagement strategies and preparing to apply for regulatory approval for the next stage of our research.
Combating mosquito-borne diseases using genetic control technologies
17735G.-H. Wang, S. Gamez, R. R. Raban, J. M. Marshall, L. Alphey, M. Li, J. L. Rasgon and O. S. Akbari, Nature Communications, 12:4388. 2021-07-19 13:06:45.
Mosquito-borne diseases, such as dengue and malaria, pose significant global health burdens. Unfortunately, current control methods based on insecticides and environmental maintenance have fallen short of eliminating the disease burden. Scalable, deployable, genetic-based solutions are sought to reduce the transmission risk of these diseases. Pathogen-blocking Wolbachia bacteria, or genome engineering-based mosquito control strategies including gene drives have been developed to address these problems, both requiring the release of modified mosquitoes into the environment. Here, we review the latest developments, notable similarities, and critical distinctions between these promising technologies and discuss their future applications for mosquito-borne disease control.
Gene Drives – Engineering the Wild
17825L. Sharratt, Sentinel, 2021-07-13 14:52:05.
So far, genetically engineered organisms have been mostly limited to agricultural use, with partial success. Around the world, a few major crops (mostly corn, soy, and cotton) are genetically engineered, predominantly for herbicide tolerance and insect resistance. However, the newer techniques of genome editing (also called gene editing) mean that a much wider variety of organisms can now be genetically engineered, including for many purposes outside of food and farming. This increased power is most dramatically illustrated in the development of gene drive technology. Unlike genetically engineered plants and animals intended for confined use in agricultural production, gene drive organisms are expressly designed for intentional, long-lived release into the wild. Gene drives are a technology through which a few individual genetically engineered organisms would be deployed to intentionally push new genes through an entire population of a species in the wild or in a farm ecosystem. Through the gene drive mechanism, new genes would be inherited by all offspring in subsequent generations, not just the expected half in normal inheritance. When gene drive organisms reproduce, specific traits as well as the gene drive mechanism itself would be passed on. Making such spreading genetic changes to an organism, or eliminating it in the wild, could disrupt whole ecosystems in ways that are difficult or impossible to predict or reverse.
Africa Turning to Gene Drive Technology for Malaria Elimination
17669M. Hearty, Science Africa, 2021-07-09 20:02:22.
With Africa accounting for nine out of ten malaria cases globally, the continent is turning to gene drive technology to control the disease. This is according to a decision made by African leaders at the 29th Summit of Heads of States and Governments of the African Union held in Addis Ababa. There are 3500 to 4000 mosquito species worldwide and 837 of the species are in Africa, with only 3 species transmitting malaria in sub-Saharan Africa. Speaking during a virtual conference by the African Union Development Agency (AUDA-NEPAD) , Dr Abdoulaye Diabate, Head of Medical Entomology and Parasitology at the Research Institute in health Sciences in Burkina Faso who presented on Gene Drive for Malaria Control and Elimination in Africa said that two options for genetic control of mosquito-borne infectious diseases identified were population suppression and population replacement. “Population suppression involves releasing of modified mosquitoes into the population, and this can cause transient or permanent suppression. With the population replacement method, modified mosquitoes released into the population can lead to the spread of a gene that blocks malaria transmission,” the Medical Entomologist stated.
A new tool in the global fight against malaria
17666S. Laux, Brighter World, 2021-07-08 19:56:20.
McMaster researchers with the Institute on Ethics & Policy for Innovation (IEPI) have played a key role in developing updated international guidelines that will inform research and development on genetically modified mosquitoes – an initiative that could significantly affect global efforts to eradicate mosquito-borne illnesses such as dengue fever, Zika virus and malaria. Released by the World Health Organization in late May, the guidelines describe best practices to ensure that the study of genetically modified mosquitoes is scientifically rigorous and meets essential standards of safety, effectiveness, accessibility and ethics. “The previous World Health Organization guidance for testing genetically modified mosquitoes was from 2014 – and since then, there have been multiple technological developments and considerable scientific progress,” explains Claudia Emerson, the director of IEPI and a professor of philosophy who, along with IEPI researchers Travis Ramsay and Aaron Roberts, developed the guidance’s chapter on ethical considerations. “Genetically modifying organisms isn’t new, at least not from an ethical or scientific perspective – but as the technology has developed over the years, especially with respect to mosquitoes, there has been a change in its perception and the receptivity to using it. It was important to update the guidance to reflect these changes.”
Fighting disease: How are genetically engineered mosquitoes regulated?
17652A. Julie, Global News, 2021-07-08 19:26:36.
Mosquitoes have long been associated with the spread of diseases like malaria, dengue fever and the Zika virus. But scientists around the world have been exploring the possibility that mosquitoes could also be key to slowing the spread of disease. By genetically altering the DNA of mosquitoes, scientists hope to prevent them from passing on pathogens to humans and, therefore, control the spread of vector-borne diseases. To some, it is an exciting opportunity that could open up new possibilities in the fight against endemic diseases. But the practice has also raised questions from some in the scientific and environmental communities about the impact on local ecosystems, and the ripple effects such modifications could have on the mosquito populations themselves.
The (Losing) Battle Against Mosquitoes In Texas
17599J. Clayton, Texas Public Radio, 2021-06-26 14:13:20.
Jerry Clayton: Mosquitoes are a fact of life in Texas, and the battle against the pesky biting insects is never ending. But there are some new weapons on the horizon. Zach Adleman is an associate professor of entomology at Texas A&M University. He joins us today. Thanks for being here, Zach.
Stable high-density and maternally inherited Wolbachia infections in Anopheles moucheti and Anopheles demeilloni mosquitoes
17504T. Walker, S. Quek, C. L. Jeffries, J. Bandibabone, V. Dhokiya, R. Bamou, M. Kristan, L. A. Messenger, A. Gidley, E. A. Hornett, E. R. Anderson, C. Cansado-Utrilla, S. Hegde, C. Bantuzeko, J. C. Stevenson, N. F. Lobo, S. C. Wagstaff, C. A. Nkondjio, S. R., Current Biology, 31:2310. 2021-06-14 13:55:55.
Wolbachia, a widespread bacterium that can reduce pathogen transmission in mosquitoes, has recently been reported to be present in Anopheles (An.) species. In wild populations of the An. gambiae complex, the primary vectors of Plasmodium malaria in Sub-Saharan Africa, Wolbachia DNA sequences at low density and infection frequencies have been detected. As the majority of studies have used highly sensitive nested PCR as the only method of detection, more robust evidence is required to determine whether Wolbachia strains are established as endosymbionts in Anopheles species. Here, we describe high-density Wolbachia infections in geographically diverse populations of An. moucheti and An. demeilloni. Fluorescent in situ hybridization localized a heavy infection in the ovaries of An. moucheti, and maternal transmission was observed. Genome sequencing of both Wolbachia strains obtained genome depths and coverages comparable to those of other known infections. Notably, homologs of cytoplasmic incompatibility factor (cif) genes were present, indicating that these strains possess the capacity to induce the cytoplasmic incompatibility phenotype, which allows Wolbachia to spread through host populations. These strains should be further investigated as candidates for use in Wolbachia biocontrol strategies in Anopheles aiming to reduce the transmission of malaria.
European Parliament calls for ban on gene drive technology
17296Save Our Seeds, Save Our Seeds, 2021-06-09 10:56:17.
The European Parliament yesterday confirmedi it‘s precautionary stance towards the use of a new genetic engineering technology called gene drive. In its report on the EU’s Biodiversity Strategy for 2030, adopted at the European Parliament’s plenary on 08.06.2021, Parliamentarians demand that „no releases of genetically engineered gene drive organisms should be allowed, including for nature conservation purposes, in line with the precautionary principle.“ Mareike Imken, coordinator of the European Stop Gene Drive Campaign welcomes this decision and comments: „With its position today, the European Parliament recognizes that this technology raises a series of scientific, regulatory, societal and ethical questions and concerns. As its use could severely harm biodiversity, the European Parliament calls to postpone any environmental releases until these questions have been addressed and settled. This is an important message that should feed into the ongoing discussions about global regulations at the next meeting of the International Union for Conservation of Nature (IUCN) in September in Marseille and those of the Convention on Biological Diversity in October in Kunming, China.“ 27 civil society and science organisations from across the EU had sent a letter to Parliamentarians in support of the amendment ahead of the vote. It „provides reasonable suggestions on how to implement the European Parliament’s previous position in its resolution on the 15th meeting of the Conference of Parties (COP15) to the Convention on Biological Diversity (2019/2824(RSP)“. In that previous position, adopted in January 2020, the European Parliament had called “on the Commission and the Member States to call for a global moratorium at the COP15 on releases of gene drive organisms into nature, including field trials, in order to prevent these new technologies from being released prematurely and to uphold the precautionary principle, which is enshrined in the Treaty on the Functioning of the European Union as well as the CBD“.
Vector control: Discovery of Wolbachia in malaria vectors
17554P. A. Ross and A. A. Hoffmann, Current Biology, 31:R738-R740. 2021-06-07 14:28:04.
Wolbachia bacteria are being widely released for suppression of dengue transmitted by Aedes mosquitoes. Walker, Quek, Jeffries and colleagues present robust evidence for natural Wolbachia infections in malaria-vectoring Anopheles mosquitoes, paving the way for new Wolbachia-based intervention
Genetically modified mosquitoes and Africa
17194S. Bagcchi, Sci Dev Net, 2021-06-02 20:30:12.
The World Health Organization (WHO) has released new guidance for the deployment of genetically modified (GM) mosquitoes to combat vector-borne diseases like malaria and dengue. GM mosquitoes may carry a gene that kills female progeny and the technology can be used against the Aedes aegypti mosquito that carries dengue, chikungunya and Zika viruses. For malaria, genetic modification has focused on reducing the ability of the female Anopheles mosquito to carry the parasite that causes the disease. The WHO guidance, released this month, relates to research and development of GM mosquitoes as well as issues around effectiveness, safety, affordability and ethics. GDN awards advert finalised Presently, measures against mosquito vectors include the use of insecticides and elimination of the breeding spots of mosquito larva, said the guidance, developed in partnership with WHO collaborators such as the Special Programme for Research and Training in Tropical Diseases and the GeneConvene Global Collaborative.
‘Death gene’ in genetically modified male mosquitoes
17181J. Goddard, The Times, 2021-06-02 20:10:43.
Tens of thousands of bio-engineered mosquitoes have taken flight in the Florida Keys under a pilot project that aims to breed insects programmed with a “death switch”. Genetically modified males produced by Oxitec — a British-founded biotechnology company — have begun mating with local populations of invasive Aedes aegypti mosquitoes, whose female progeny are programmed to die before they mature, wiping out a generation of potential disease-carriers. “Mosquito-borne disease is a very real issue and conventional controls are losing their effectiveness,” said Dr Nathan Rose, head of regulatory affairs at Oxitec in Milton Park, Oxfordshire.
What is wrong in extinguishing a species? Charting the Ethical Challenges of using Gene-Drive Technologies to eradicate A. gambiae vector populations
17161M. Annoni and T. Pievani, Biolaw Journal-Rivista Di Biodiritto, 2021-05-31 19:04:09.
This article analyses three ethical arguments against the use of gene-drive technologies to control for, and possibly extinguish, a particular species of vector mosquitoes (Anopheles gambiae) causing the malaria infection. We conclude that none of these arguments is truly persuasive in the specific case and, therefore, that using gene-drive technologies to suppress or eradicate the population of Anopheles gambiae could be ethically justifiable provided certain cautions referring to ecological consequences, evolutionary effects and social engagement of local communities.
Improving mosquito control strategies with population genomics
18781T. L. Schmidt, N. M. Endersby-Harshman and A. A. Hoffmann, Trends in Parasitology, 37:907-921. 2021-05-29 12:41:38.
Mosquito control strategies increasingly apply knowledge from population genomics research. This review highlights recent applications to three research domains: mosquito invasions, insecticide resistance evolution, and rear and release programs. Current research trends follow developments in reference assemblies, either as improvements to existing assemblies (particularly Aedes) or assemblies for new taxa (particularly Anopheles). With improved assemblies, studies of invasive and rear and release target populations are better able to incorporate adaptive as well as demographic hypotheses. New reference assemblies are aiding comparisons of insecticide resistance across sister taxa while helping resolve taxon boundaries amidst frequent introgression. Anopheles gene drive deployments and improved Aedes genome assemblies should lead to a convergence in research aims for Anopheles and Aedes in the coming years.
Why the EU should back research into gene drive – even if Europe never uses it
17132R. Müller, The Brussels Times, 2021-05-23 12:00:13.
As the EU’s Biodiversity Strategy reaches the European Parliament, it has reopened a worrying debate about research into gene drive technology, a tool which could pave the way for biasing the inheritance of desired genetic traits through targeted species. Advances in this kind of genetic technology could allow scientists to create a blueprint for stopping diseases spread by mosquitoes and protecting endangered species, both significant reasons for supporting this emerging field. Yet even if EU decision makers see no need for gene drive technology in Europe at present, there are compelling reasons for supporting ongoing research, and rejecting irresponsible and short-sighted calls for a moratorium. Firstly, the threat of malaria and other mosquito-borne diseases may be minimal today but it existed on the continent within living memory, with Europe first becoming malaria-free in 1975, and then again only as recently as 2015.
Malaria-Resistant Mosquitoes (Diptera: Culicidae); The Principle is Proven, But Will the Effectors Be Effective?
18710Z. N. Adelman and B. B. Kojin, Journal of Medical Entomology, 58:1997-2005. 2021-05-21 13:50:24.
Over the last few decades, a substantial number of anti-malarial effector genes have been evaluated for their ability to block parasite infection in the mosquito vector. While many of these approaches have yielded significant effects on either parasite intensity or prevalence of infection, just a few have been able to completely block transmission. Additionally, many approaches, while effective against the parasite, also disrupt or alter important aspects of mosquito physiology, leading to corresponding changes in lifespan, reproduction, and immunity. As the most promising approaches move towards field-based evaluation, questions of effector gene robustness and durability move to the forefront. In this forum piece, we critically evaluate past effector gene approaches with an eye towards developing a deeper pipeline to augment the current best candidates.
Burkina Faso Testing Genetically Modified Mosquitoes to Curb Malaria
17082H. Wilkins, Voice of America, 2021-05-20 15:06:44.
The mosquito-borne disease malaria kills more than 400,000 people each year, the vast majority in Africa. Target Malaria, an international group of scientists, is working in Burkina Faso on a genetic solution. Abdoulaye Diabate, with the West African country’s Research Institute for Science and Health, said the objective of Target Malaria is to develop a genetic control tool specifically applied to mosquitoes to be able to drastically reduce or eliminate the density of mosquitoes. The scientists are genetically modifying mosquitoes so their offspring will be only male, and any females they mate with after release will also produce just males. Since only female mosquitoes spread malaria, the disease should drop off quickly along with their population. In village of Bana, where the genetically modified mosquitoes were first tested in 2019, locals were initially worried about the experiment. Kiesiara Sanou, a Bana village elder, said that at the beginning, people thought the survey would release mosquitoes in the village that could cause more diseases. But since working with Target Malaria, they’ve come to understand exactly what the purpose is and now even help them with tasks like collecting the mosquitoes. Genetically modified mosquitoes are just one malaria solution that has been tested in Burkina Faso. The country also pioneered pesticide-infused mosquito nets.
Small-Cage Laboratory Trials of Genetically-Engineered Anopheline Mosquitoes
17068R. Carballar-Lejarazú, T. B. Pham, V. Bottino-Rojas, A. Adolfi and A. A. James, J Vis Exp, 2021-05-18 14:30:01.
Control of mosquito-borne pathogens using genetically-modified vectors has been proposed as a promising tool to complement conventional control strategies. CRISPR-based homing gene drive systems have made transgenic technologies more accessible within the scientific community. Evaluation of transgenic mosquito performance and comparisons with wild-type counterparts in small laboratory cage trials provide valuable data for the design of subsequent field cage experiments and experimental assessments to refine the strategies for disease prevention. Here, we present three different protocols used in laboratory settings to evaluate transgene spread in anopheline mosquito vectors of malaria. These include inundative releases (no gene-drive system), and gene-drive overlapping and non-overlapping generation trials. The three trials vary in a number of parameters and can be adapted to desired experimental settings. Moreover, insectary studies in small cages are part of the progressive transition of engineered insects from the laboratory to open field releases. Therefore, the protocols described here represent invaluable tools to provide empirical values that will ultimately aid field implementation of new technologies for malaria elimination.
First Genetically Modified Mosquitoes Released in U.S. Are Hatching Now
17046D. Coffey, Scientific American, 2021-05-14 11:50:11.
This week, mosquito eggs placed in the Florida Keys are expected to hatch tens of thousands of genetically modified mosquitoes, a result of the first U.S. release of such insects in the wild. A biotechnology firm called Oxitec delivered the eggs in late April as part of a federally approved experiment to study the use of genetic engineering—rather than insecticides—to control disease-carrying mosquito populations. The move targets an invasive species, called Aedes aegypti, that carries Zika, dengue, chikungunya, yellow fever and other potentially deadly diseases, some of which are on the rise in Florida. The experiment relies on a genetic alteration that will be lethal to a large number of future offspring. In this case, male mosquitoes have been modified to carry a gene that makes their female progeny dependent on the antibiotic tetracycline—and thus fated to die in the wild. As the mating cycle repeats over generations, female numbers are depleted, and the population is suppressed. The modified insects eventually die off, making this approach self-limiting. Oxitec overcame significant regulatory hurdles before getting the go-ahead from the U.S. Food and Drug Administration in 2016 and then the Environmental Protection Agency in 2020. If the current pilot effort is successful, the firm is set to release as many as 20 million more males in the prime of Florida’s mosquito season later this year. The results of the experiment could ultimately help address concerns about releasing genetically modified organisms into the wild.
In a World-First, Genetically Modified Mosquitoes Are Hatching in the US
17044B. Bergan, INTERSTING ENGINEERING, 2021-05-14 11:44:58.
Mosquito eggs placed in the Florida Keys are about to hatch tens of thousands of genetically altered mosquitos, the first such release of "synthetic" insects in the world, according to an initial report from Scientific American. Pilot program for genetically modified mosquitoes could see millions more released this year. The biotechnology firm called Oxitec delivered the modified mosquito eggs late in April as part of a federally-endorsed experiment to study the use of genetic engineering, as opposed to insecticides, to control the populations of illness-spreading mosquitoes. This project targets one specific species of mosquito called Aedes aegypti, known to carry Zika, chikungunya, yellow fever, dengue, and other possibly deadly diseases. And some of these diseases have been on the rise in Florida. The new genetic contribution given to the mosquitoes will be deadly to many future offspring, with males altered to carry a gene causing female offspring to become dependent on the antibiotic called tetracycline — which is a death sentence for the female mosquitoes. After several generations, there won't be enough female mosquitoes of the species to maintain population numbers, putting a ceiling on them. But this is a temporary measure, since the genetically modified male mosquitoes will eventually all die.
A natural symbiotic bacterium drives mosquito refractoriness to Plasmodium infection via secretion of an antimalarial lipase
17027H. Gao, L. Bai, Y. M. Jiang, W. Huang, L. L. Wang, S. G. Li, G. D. Zhu, D. Q. Wang, Z. H. Huang, X. S. Li, J. Cao, L. B. Jiang, M. Jacobs-Lorena, S. Zhan and S. B. Wang, Nature Microbiology, 25. 2021-05-06 11:00:53.
The stalling global progress in the fight against malaria prompts the urgent need to develop new intervention strategies. Whilst engineered symbiotic bacteria have been shown to confer mosquito resistance to parasite infection, a major challenge for field implementation is to address regulatory concerns. Here, we report the identification of a Plasmodium-blocking symbiotic bacterium, Serratia ureilytica Su_YN1, isolated from the midgut of wild Anopheles sinensis in China that inhibits malaria parasites via secretion of an antimalarial lipase. Analysis of Plasmodium vivax epidemic data indicates that local malaria cases in Tengchong (Yunnan province, China) are significantly lower than imported cases and importantly, that the local vector A. sinensis is more resistant to infection by P. vivax than A. sinensis from other regions. Analysis of the gut symbiotic bacteria of mosquitoes from Yunnan province led to the identification of S. ureilytica Su_YN1. This bacterium renders mosquitoes resistant to infection by the human parasite Plasmodium falciparum or the rodent parasite Plasmodium berghei via secretion of a lipase that selectively kills parasites at various stages. Importantly, Su_YN1 rapidly disseminates through mosquito populations by vertical and horizontal transmission, providing a potential tool for blocking malaria transmission in the field. The symbiotic bacterium Serratia ureilytica can disseminate through mosquito populations and render mosquitoes resistant to Plasmodium infection by secreting an antimalarial lipase.
What Are GMO Mosquitoes and What Is Their Purpose?
17038A. Krosofsky, GREENMATTERS, 2021-05-01 11:29:18.
Scientists have made GMO corn, strawberries, even many types of farm animals. Now, it seems, they have managed to genetically modify mosquitoes as well. But what is the purpose of GMO mosquitoes, and why would scientists go out of their way to create something that is already a problem for a huge portion of the planet’s population? As it turns out, GMO mosquitoes are a way to fight fire with fire. By creating and releasing their own genetically modified mosquitoes into existing populations, a few clever scientists have managed to curb the spread of dangerous mosquito-borne diseases like the Zika virus. According to the CDC, GMO mosquitoes are modified from the Aedes aegypti mosquito species. Aedes aegypti mosquitoes are commonly found in many parts of the U.S., including Florida and Texas. They are well known for spreading and carrying viruses like Zika, dengue, and chikungunya, but the GMO versions of these insects are designed to stop the spread of those diseases right at the source: the carriers themselves.
Selection of Sites for Field Trials of Genetically Engineered Mosquitoes with Gene Drive
16932G. C. Lanzaro, M. Campos, M. Crepeau, A. Cornel, A. Estrada, H. Gripkey, Z. Haddad, A. Kormos, S. Palomares and W. Sharpee, bioRxiv, 2021.04.28.441877. 2021-04-28 15:53:05.
Novel malaria control strategies using genetically engineered mosquitoes (GEMs) are on the horizon. Population modification is one approach wherein mosquitoes are engineered with genes rendering them refractory to the malaria parasite coupled with a low-threshold, Cas9-based gene drive. When released into a wild vector population, GEMs preferentially transmit these beneficial genes to their offspring, ultimately modifying a vector population into a non-vector one. Deploying this technology awaits evaluation including ecologically contained field trials. Here, we consider a process for site selection, the first critical step in designing a trial. Our goal is to identify a site that maximizes prospects for success, minimizes risk, and serves as a fair, valid, and convincing test of efficacy and impacts of a GEM product intended for large-scale deployment in Africa. We base site selection on geographical, geological, and biological, rather than social or legal, criteria. We recognize the latter as critically important but not preeminent. We propose physical islands as being the best candidates for a GEM field trial and present an evaluation of 22 African islands. We consider geographic and genetic isolation, biological complexity, island size, topography, and identify two island groups that satisfy key criteria for ideal GEM field trial sites.Competing Interest StatementThe authors have declared no competing interest.
“Maskandi experience”: exploring the use of a cultural song for community engagement in preparation for a pilot Sterile Insect Technique release programme for malaria vector control in KwaZulu-Natal Province, South Africa 2019
17029P. N. Manana, S. Jewett, J. Zikhali, D. Dlamini, N. Mabaso, Z. Mlambo, R. Ngobese and G. Munhenga, Malaria Journal, 20:11. 2021-04-28 11:06:19.
Background An assessment of the Sterile Insect Technique (SIT) as a complementary malaria vector control tool, is at an advanced stage in South Africa. The technique involves the release of laboratory-reared sterilized male mosquitoes of the major malaria vector Anopheles arabiensis, raising social, ethical and regulatory concerns. Therefore, its implementation largely depends on community participation and acceptance. Against this background, it is critical that robust and effective community strategies are developed. This study describes the development of a cultural song to engage the community and increase awareness on SIT and malaria control in KwaZulu-Natal, South Africa. Methods An exploratory concurrent mixed-methods study was conducted to get opinions about the effectiveness of a cultural song developed to engage communities and increase acceptability of the SIT technology. Two self-administered surveys (expert and community) were conducted. Additionally, more in depth opinions of the song and its effectiveness in conveying the intended information were investigated through three community dialogue sessions with community members in the study area. Results A total of 40 experts and 54 community members participated in the survey. Four themes were identified in relation to the appropriateness and effectiveness of the song, with a fifth theme focused on recommendations for adaptations. Overall, the song was well received with the audience finding it entertaining and informative. Responses to unstructured questions posed after the song showed an increase in the knowledge on malaria transmission and SIT technology. In particular, the explanation that male mosquitoes do not bite allayed anxiety and fears about the SIT technology. Conclusion The song was deemed both culturally appropriate and informative in engaging community members about the SIT technology. It proved useful in promoting health messages and conveying SIT technology as a complementary malaria vector control tool. With minor adaptations, the song has potential as an area-wide community engagement tool in areas targeted for sterile male releases.
Does Gene Technology Offer Potential to Wipe Out Malaria?
16845Anonymous, AFIDEP, 2021-04-25 13:15:13.
The persisting high numbers of Malaria deaths and illnesses mean that the current tools will not get us to zero Malaria. For this reason, experts have continued to explore new tools for Malaria elimination. The gene drive technology is one of the tools being explored for Malaria elimination in Africa. The technology, developed in the past decade, enables precise editing of the genes of living organisms. For Malaria, the technology could be applied to modify the genes of Malaria-causing mosquitoes (the Anopheles) to either reduce their survival or deactivate genes that enable them to carry the Malaria parasite. If successfully applied, scientists believe that gene drive mosquitoes could significantly accelerate the path to Malaria elimination, or zero Malaria. In 2017, the African Union recognized the potential of the gene drive technology in controlling and eliminating Malaria on the continent, and committed to invest in the development and regulation of the technology. This commitment is being implemented by the African Union Development Agency (AUDA/NEPAD), which is currently spearheading efforts to build capacity and support countries to establish the necessary regulatory framework for guiding the research to test the gene drive technology for elimination of Malaria on the continent.
CRISPR may help curb malaria by altering a mosquito’s gut genes, new study suggests
16828Cornell Alliance for Science, Genetic Literacy Project, 2021-04-21 16:46:24.
Altering a mosquito’s gut genes to make them spread antimalarial genes to the next generation of their species shows promise as an approach to curb malaria, suggests a preliminary study published in eLife. The study is the latest in a series of steps toward using CRISPR-Cas9 gene-editing technology to make changes in mosquito genes that could reduce their ability to spread malaria. If further studies support this approach, it could provide a new way to reduce illnesses and deaths caused by malaria. Mosquito are becoming increasingly resistance to insecticides and malaria parasites are gaining resistance to antimalarial drugs, creating an urgent need for new ways to fight the disease. Gene drives are being tested as a new approach to controlling mosquitoes, locusts and other insects. They work by creating genetically modified mosquitoes that, when released into the environment, mate with wild insects. The offspring contain genes that either reduce mosquito populations or make the insects less likely to spread the malaria parasite. But scientists must prove that this approach is safe and effective before releasing gene drive mosquitoes into the wild.
Fighting mosquitoes with mosquitoes
16825W. Feng, The Daily Targum, 2021-04-21 16:38:39.
When you think about the animal that has killed the greatest number of humans in the world, you generally tend to think of large predators. Is it perhaps the great white shark or maybe the cute but deadly hippopotamus? While these animals are certainly deadly, the number of annual fatalities caused by them are eclipsed by the number of individuals killed by the tiny blood-sucking mosquito. According to the World Health Organization, approximately 725,000 people are killed every year by mosquito-borne diseases. The mosquito has been the center of numerous pathogenic outbreaks over the last couple decades, such as the West Nile virus, malaria and the Zika virus. While conventional control strategies have been employed, these have all failed to stop the spread of these viruses. To combat this issue, one solution that has been proposed is gene drives. While further testing and research is still required to ensure the safety and efficacy of gene drives, the benefits of this technology far outweigh any potential consequences, lending them to be extremely helpful in the battle against insect-borne diseases.
Eliminating malaria via a simple genetic modification
16822S. Gunn, Front Line Genomics, 2021-04-20 16:32:44.
Despite decades worth of research and efforts, data from 2015 onwards suggests that there has been no significant progress in reducing global malaria cases. Every year, around 400,00 people die from malaria, with over 90% of cases being within sub-Saharan Africa. The rise of mosquito resistance to pesticides as well as malaria parasite resistance to antimalarial drugs has emphasised the urgent need for the development of new tools to fight this disease. One approach that researchers are exploring is the use of gene drives. A gene drive is a genetic modification that can spread through a population at higher inheritance rates than normal. In this context, researchers can genetically modify mosquitos that, when released into the environment, would spread genes to either reduce mosquito populations or make them less likely to spread the malaria parasite. Due to concerns regarding the safety of gene drives, it is vital that researchers prove that this approach is safe and effective before releasing the modified mosquitos into the wild. There are currently no clear pathways for safely testing these tools within endemic countries.
This Malaria Preventing Mosquito Is Not A GMO But Is A Science Boost For Nature – Will Activists Want To Block It?
16816H. Campbell, science 2.0, 2021-04-20 16:13:03.
Mosquitoes like Aedes aegypti don't have any value ecologically. If Thanos snapped them out of existence tomorrow there is nothing they do that won't immediately be taken up by 3,000 other mosquito species, not to mention 25,000 bee species when it comes to pollination. The only thing they are great at is killing people; by being a leading source of vector-borne dengue disease. Not far behind is Anopheles gambiae mosquitoes, which carry malaria. Malaria kills nearly as many people each year as COVID-19 did in 2020 but there is no Warp Speed program to keep poor people in developing nations from dying. Environmental activists (overwhelmingly white and wealthy) instead spend $2 billion a year scaring people of color in other countries about science. Pesticides wiped out malaria in the U.S.(1) and remain the best way to go. DDT still works well and is in common use in afflicted countries.(2) Though banned politically in the U.S. half a century ago, our EPA literally writes the manual for how to spray it in homes elsewhere, but the Rachel Carson dream was to replace pesticides with genetically modified crops - optimizing nature to keep other parts of nature from killing everything using fewer chemicals.
Breeding Malaria Out: Scientists Engineer Mosquitos to Spread Antimalaria Genes
16800L. Papadopoulos, INTERSTING ENGINEERING, 2021-04-17 13:57:17.
According to the Centers for Disease Control and Prevention (CDC), malaria is a "serious and sometimes fatal disease caused by a parasite that commonly infects a certain type of mosquito which feeds on humans." There are four types of malaria parasites: Plasmodium falciparum, P. vivax, P. ovale, and P. malariae with P. falciparum being the one most likely to result in death. But what if these mosquitos could be genetically altered to spread antimalaria genes instead of the disease? That would be nothing short of a miracle. Researchers from Imperial College London have successfully altered a mosquito’s gut genes to make them spread antimalarial genes to the next generation of their species. This innovation may result in curbing malaria once and for all. This is especially important as the parasite that causes malaria has been becoming increasingly resistant to antimalarial drugs.
Curbing Malaria’s Spread by Genetic Engineering
16792Anonymous, Genetic Engineering & Biotechnology News, 2021-04-15 13:03:49.
There is an urgent need to find new ways to combat the growing mosquito resistance to pesticides and malaria parasite resistance to antimalarial drugs. Gene drives are being tested as a new approach. In a new study, researchers from the Imperial College London reported that their approach brings gene drives one step closer as a potential strategy for eliminating malaria. Their study was published in the journal eLife, in a paper titled, “Converting endogenous genes of the malaria mosquito into simple non-autonomous gene drives for population replacement.”
New genetic modification could cut malaria spread
16789Staff Writers, MALAYSIA NOW, 2021-04-15 12:56:54.
Altering a mosquito’s gut genes to make them spread antimalarial genes to the next generation of their species shows promise as an approach to curb malaria, suggests a preliminary study published in eLife on Tuesday. The study is the latest in a series of steps being taken toward using CRISPR-Cas9 gene-editing technology to make changes in mosquito genes that could reduce their ability to spread malaria. If further studies support this approach, it could provide a new way to reduce illnesses and deaths caused by malaria. Growing mosquito resistance to pesticides, as well as malaria parasite resistance to antimalarial drugs, has created an urgent need for new ways to fight the disease. Gene drives are being tested as a new approach. They work by creating genetically modified mosquitoes that, when released into the environment, would spread genes that either reduce mosquito populations or make the insects less likely to spread the malaria parasite.
Researchers Using Mutant Mosquitoes To End Malaria, Which Kills 4 Lakh Per Year
16797M. Mohanti, India Times, 2021-04-14 13:20:52.
Every year, more than 22 crore people get infected with malaria and more than 4 lakh die because of it. In fact, in 2019, nearly half of the world's population was at risk of malaria. According to WHO, infants or children aged under 5 years are the most vulnerable group, accounting for two-third of all malaria deaths worldwide. Malaria is caused by parasites that are transmitted to people via the bites of infected female Anopheles mozzies. In a non-immune individual, symptoms--fever, headache, and chills--usually appear 10–15 days after the infective mosquito bite. If it goes untreated for a day, these mild symptoms can progress to severe illness, often leading to death, if bitten by the P. falciparum parasite.
Why do you think a gene drive approach could help with malaria and dengue?
16682Outreach Network for Gene Drive Research, 2021-04-12 14:42:36.
Why do you think a gene drive approach could help with malaria and dengue?
CRISPR-mediated knock-in of transgenes into the malaria vector Anopheles funestus
16674C. Quinn, A. Anthousi, C. Wondji and T. Nolan, bioRxiv, 2021.03.31.437891. 2021-03-31 13:57:08.
We describe herein an optimised transformation system based on the germline delivery of CRISPR components that allows efficient cleavage of a previously validated genomic site and preferential repair of these cut sites via homology-directed repair (HDR), which allows introduction of exogenous template sequence, rather than end-joining repair. The rates of transformation achieved are sufficiently high that it should be able to introduce alleles of choice to a target locus, and recover these, without the need to include additional dominant marker genes. Moreover, the high rates of HDR observed suggest that gene drives, which employ an HDR-type mechanism to ensure their proliferation in the genome, may be well suited to work in An. funestus.Competing Interest StatementThe authors have declared no competing interest.
The ethical scientist in a time of uncertainty
16620L. Zoloth, Cell, 184:1430-1439. 2021-03-18 17:59:56.
Using the example of gene drives for malaria control to explore the problem of deep uncertainty in biomedical research, I argue that profound uncertainty is an essential feature. Applying the language and presumptions of the discipline of philosophical ethics, I describe three types of uncertainty that raise ethical challenges in scientific research. Rather than mitigate these challenges with excessive precautions and limits on progress, I suggest that researchers can cultivate classic values of veracity, courage, humility, and fidelity in their research allowing science to proceed ethically under conditions of deep uncertainty.
femaleless Controls Sex Determination and Dosage Compensation Pathways in Females of Anopheles Mosquitoes
16910E. Krzywinska, L. Ferretti, J. Li, J.-C. Li, C.-H. Chen and J. Krzywinski, Current Biology, 31:1084-1091.e4. 2021-03-08 18:07:47.
Here we show that in the African malaria mosquito Anopheles gambiae, a gene, which likely arose in the Anopheles lineage and which we call femaleless (fle), controls sex determination in females by regulating splicing of dsx and fruitless (fru; another terminal gene within a branch of the sex determination pathway). Moreover, fle represents a novel molecular link between the sex determination and dosage compensation pathways. It is necessary to suppress activation of dosage compensation in females, as demonstrated by the significant upregulation of the female X chromosome genes and a correlated female-specific lethality, but no negative effect on males, in response to fle knockdown. This unexpected property, combined with a high level of conservation in sequence and function in anopheline mosquitoes, makes fle an excellent target for genetic control of all major vectors of human malaria.
In Uganda, genetically modified mosquitoes bring hope and fear
16550Anonymous, africanews, 2021-03-05 19:32:29.
Scientists here are investigating whether populations of the malaria-carrying insects can be reduced by genetic modification. They're looking at the viability of releasing large numbers of genetically modified mosquitos into the wild to influence future generations. The study is being led by scientists here at the institute in Kampala with researchers from the Target Malaria group. Dr. Jonathan Kayondo is the principal investigator managing the project. He says the disease can be deadly for children, especially those under five-years-old. "The aim here is to develop a new vector control tool for the suppression of malaria transmission," says Dr. Jonathan Kayondo.
Renew Europe | The science & ethics of gene drive technology from a conservation & development perspective
16584Renew Europe, Renew Europe, 2021-03-05 15:18:26.
This hearing intends to examine gene-drive technology and its possible impacts, including unintended ones and reveal the complexity of an unknown technology with inherent uncertainties. Scientists from different backgrounds in the field of gene-drive research will present most recent scientific findings and allow us to exchange on a technical, but also ethical debate. Hosted by MEPs Soraya Rodríguez & Charles Goerens with a keynote speech by Commissioner for Envinronment Virginijus Sinkevičius.
Genetically modified mosquitoes for better health
16527D. Devis, COSMOS, 2021-03-04 18:24:41.
One method of preventing these mosquito-born diseases is to use insecticides to kill the mozzies and remove them, but sometimes this only works as a short term solution, or has unintended devasting effects on the ecosystem. Another method for decreasing the number of disease-carrying mozzies is to introduce disease resistant, genetically modified mozzies. These transgenic mozzies could be part of a gene drive system where they have a newly introduced disease-resistant gene, linked up with CRISPR mechanisms that help the gene dominate in the population by continuing to copy itself through the genome. All of this requires very thorough risk assessment.
Quantifying the risk of vector-borne disease transmission attributable to genetically modified vectors
16530G. R. Hosack, A. Ickowicz and K. R. Hayes, Royal Society Open Science, 8:201525. 2021-03-03 18:28:51.
The relative risk of disease transmission caused by the potential release of transgenic vectors, such as through sterile insect technique or gene drive systems, is assessed with comparison with wild-type vectors. The probabilistic risk framework is demonstrated with an assessment of the relative risk of lymphatic filariasis, malaria and o'nyong'nyong arbovirus transmission by mosquito vectors to human hosts given a released transgenic strain of Anopheles coluzzii carrying a dominant sterile male gene construct. Harm is quantified by a logarithmic loss function that depends on the causal risk ratio, which is a quotient of basic reproduction numbers derived from mathematical models of disease transmission. The basic reproduction numbers are predicted to depend on the number of generations in an insectary colony and the number of backcrosses between the transgenic and wild-type lineages. Analogous causal risk ratios for short-term exposure to a single cohort release are also derived. These causal risk ratios were parametrized by probabilistic elicitations, and updated with experimental data for adult vector mortality. For the wild-type, high numbers of insectary generations were predicted to reduce the number of infectious human cases compared with uncolonized wild-type. Transgenic strains were predicted to produce fewer infectious cases compared with the uncolonized wild-type.
How Brussels can help or hinder the fight against malaria
16511F. Okumu, EURACTIV, 2021-03-01 21:46:44.
In the wake of the pandemic, the world has much for which to thank Europe. Not only did European science lead the field in developing the first approved vaccine against COVID-19, but the EU’s long history of rigorous regulatory approval has also allowed for public confidence in its safety and efficacy. For years, the EU has provided the global gold standard for protecting human health and safety while fostering scientific innovation to improve lives and wellbeing. Heading into a crucial decade for world preservation, the EU has another chance to unleash the power of science in the search for solutions to existential challenges both at home and in neighbouring regions.
Designing gene drives to limit spillover to non-target populations
16516G. Greenbaum, M. W. Feldman, N. A. Rosenberg and J. Kim, PLOS Genetics, 17:e1009278. 2021-02-25 15:02:27.
We develop mathematical models of gene-drive dynamics that incorporate migration between a target and non-target populations to investigate the possibility of effectively applying a gene drive in the target population while limiting its spillovers to the non-target population (‘differential targeting’). We observe that the feasibility of differential targeting depends on the gene-drive design specification, as well as on the migration rates between the populations. Even when differential targeting is possible, as migration increases, the possibility for differential targeting disappears. We find that differential targeting can be effective for low migration rates, and that it is sensitive to the design of the gene drive under high migration rates. We suggest that differential targeting could be used, in combination with other mitigation measures, as an additional safeguard to limit gene drive spillovers.
Detailed genome map of malaria vector
16381The Hindu, Aspirant World, 2021-02-14 15:03:12.
In order to engineer advanced forms of defence against malaria transmission, including targeted CRISPR and gene drive–based strategies, scientists require intricate knowledge of the genomes of vector mosquitoes. CRISPR technology is a gene-editing tool which allows researchers to easily alter DNA sequences and modify gene function.They produced a new reference genome for the Asian malaria vector mosquito Anopheles stephensi.
Researchers Unveil Detailed Genome of Invasive Malaria Mosquito
16374M. Aguilera, UC San Diego News Center, 2021-02-11 20:37:12.
Mosquito-transmitted malaria remains the number one worldwide killer among vector-borne diseases, claiming more than 400,000 human lives in 2019. In order to engineer advanced forms of defense against malaria transmission, including targeted CRISPR and gene drive-based strategies, scientists require intricate knowledge of the genomes of vector mosquitoes. Mahul Chakraborty—a project scientist at the University of California, Irvine, working with colleagues at the Tata Institute for Genetics and Society (TIGS) at UC San Diego and India, and the Institute of Bioinformatics and Applied Biotechnology in Bangalore, India—has produced a groundbreaking new reference genome for the Asian malaria vector mosquito Anopheles stephensi. Full details of the genome, which the scientists say is now on par with the best animal genomes available to science (humans and fruit flies), are published in the journal BMC Biology.
Hidden genomic features of an invasive malaria vector, Anopheles stephensi, revealed by a chromosome-level genome assembly
16376M. Chakraborty, A. Ramaiah, A. Adolfi, P. Halas, B. Kaduskar, L. T. Ngo, S. Jayaprasad, K. Paul, S. Whadgar, S. Srinivasan, S. Subramani, E. Bier, A. A. James and J. J. Emerson, BMC Biology, 19:28. 2021-02-10 20:40:13.
The mosquito Anopheles stephensi is a vector of urban malaria in Asia that recently invaded Africa. Studying the genetic basis of vectorial capacity and engineering genetic interventions are both impeded by limitations of a vector’s genome assembly. The existing assemblies of An. stephensi are draft-quality and contain thousands of sequence gaps, potentially missing genetic elements important for its biology and evolution.
Experts oppose plan to breed mosquitoes
16279T. Abet, Daily Monitor, 2021-02-01 17:11:29.
Environmentalists have opposed the plan to breed and release genetically modified mosquitoes in the country to curb malaria prevalence. They say the act presents substantial human and environmental health risks. Their objection follows last week’s announcement by scientists at Uganda Virus Research Institute (UVRI) that they have embarked on a series of activities aimed at breeding and releasing genetically modified mosquitoes (GMMs) that could curb malaria transmission.
Genetically modified mosquitoes to curb malaria
16221T. Abet, Daily Monitor, 2021-01-29 16:20:15.
Scientists at Uganda Virus Research Institute (UVRI) have started breeding mosquitoes with the aim of modifying their genetic materials and releasing them to the environment to curb malaria transmission. The genetically modified mosquitoes, according to the scientists, do not transmit malaria parasites when they bite. Dr Jonathan Kayondo, the project lead coordinator at the UVRI, said when the modified male mosquito mates with common mosquitoes, the female off springs are infertile. This, he explained will significantly suppress the population or eliminate mosquitoes thereby stopping malaria transmission and deaths.
New genetically modified mosquitoes to help fight malaria
16216D. Zirimala, Capital Radio FM, 2021-01-29 16:11:15.
According to Dr. Jonathan Kayondo, the principal investigator of the Target Malaria project, the genetically modified mosquitoes do not transmit malaria parasites when they bite. These are made infertile so that when they cross breed with the female anopheles mosquito, they are not able to reproduce. He says with this new research project, they are complimenting the already existing malaria control methods such as insecticides treated mosquito nets, indoor residual spraying and drugs but there is need to get additional tools to help eradicate the disease.
Proceedings of an expert workshop on community agreement for gene drive research in Africa – Co-organised by KEMRI, PAMCA and Target Malaria [version 1; peer review: awaiting peer review]
16224D. Thizy, L. Pare Toe, C. Mbogo, D. Matoke-Muhia, V. P. Alibu, S. K. Barnhill-Dilling, T. Chantler, G. Chongwe, J. Delborne, L. Kapiriri, E. Nassonko Kavuma, S. Koloi-Keaikitse, A. Kormos, K. Littler, D. Lwetoijera, R. Vargas de Moraes, N. Mumba, L. Muten, Gates Open Research, 2021-01-28 16:25:31.
Target Malaria, the Kenya Medical Research Institute and the Pan African Mosquito Control Association co-organised a workshop with researchers and practitioners on this topic to question the model proposed by Target Malaria in its research so far that involved the release of genetically modified sterile male mosquitoes and how this could be adapted to future studies involving gene drive mosquito releases for them to offer reflections about potential best practices. This paper shares the outcomes of that workshop and highlights the remaining topics for discussion before a comprehensive model can be design
Application of the Relationship-Based Model to Engagement for Field Trials of Genetically Engineered Malaria Vectors
15898A. Kormos, G. C. Lanzaro, E. Bier, G. Dimopoulos, J. M. Marshall, J. Pinto, A. Aguiar dos Santos, A. Bacar, H. Sousa Pontes Sacramento Rompão and A. A. James, The American Journal of Tropical Medicine and Hygiene, 2020-12-21 14:17:29.
Although guidelines and recommendations for engagement for gene drives have recently been described, we argue here that communities and stakeholders should lead the planning, development, and implementation phases of engagement. The RBM provides a new approach to the development of ethical, transparent, and effective engagement strategies for malaria control programs.
A Gene Drive Could Wipe Out Mosquitoes. But What If We Want To Turn It Off?
15424A. Winkler, freethink, 2020-12-05 15:48:03.
Gene drives are powerful tools: they allow scientists to hack how animals pass down genes to their offspring. They could allow us to wipe out malaria-carrying mosquitoes, preserve endangered species, or fight off crop-eating pests. But once it's out in the wild, a gene drive can't be stopped from spreading — and that makes people nervous. If there are unintended consequences, we want to be able to pull the brakes. Now, UC San Diego researchers have developed a new genetic system that would let scientists halt or neutralize gene drives, even after they are released into the wild. The implications could be huge.
Mosquito population modification: the drive to malaria eradication
15272A. A. James, BugBitten BMC, 2020-11-27 14:37:56.
We have had considerable success in the past demonstrating that we can use modern molecular biological and insect transgenesis tools to make genes that prevent mosquitoes from passing on parasites (see 1 and 2). We have focused most recently on laboratory experiments to find ways to move these genes into wild mosquito populations.
Gene drive blocks malaria transmission in mosquitoes
15035labonline, labonline, 2020-11-09 15:46:59.
Employing a strategy known as ‘population modification’, which involves using a CRISPR-Cas9 gene drive system to introduce genes preventing parasite transmission into mosquito chromosomes, University of California (UC) researchers have made a major advance in the use of genetic technologies to control the transmission of malaria parasites. Their work has been published in the journal Nature Communications.
Gene Drives: A Controversial Tool to Fight Malaria
15008H. Albert, LABIOTECH.eu, 2020-11-09 15:41:52.
The possibility of creating gene drives was introduced into the scientific community in 2003 by Austin Burt, a professor at Imperial College London. Burt was studying ‘selfish genes’ that can copy themselves into a specific target DNA sequence. He suggested that these genes, called homing endonucleases, could be used to make the majority of an organism’s offspring inherit a specific gene, instead of only half of it. This technology has a lot of potential. For example, it could be used to decimate populations of malaria-carrying mosquitoes by making the majority of their offspring male. However, there are concerns about the permanent nature of these genetic modifications and whether it could cause irreparable damage to the ecosystem it is used in.
A gene-drive rescue system for the modification of malaria mosquito populations
14901A. Adolfi, Nature Research Bioengineering Community, 2020-11-03 18:48:29.
Mosquito populations can now be reliably modified using 1) antimalarial molecules that block parasite development and 2) a CRISPR-based gene drive system that mediates their rapid spreading across the vector population.
UC researchers pioneer more effective method of blocking malaria transmission in mosquitoes
14898UCI, UCI News, 2020-11-03 14:11:01.
University of California, Irvine postdoctoral researcher Adriana Adolfi, in collaboration with colleagues at UCI, UC Berkeley and UC San Diego, followed up on the group’s pioneering effort to develop CRISPR-based gene drive systems for making mosquito vectors resistant to transmitting malaria parasites by increasing gene drive effectiveness in female mosquito progeny.The second-generation gene drive system described in this paper can be applied to any of the several thousand genes that are essential for insects to survive or reproduce,” said UC San Diego Distinguished Professor Ethan Bier, a co-author of the study and science director at the Tata Institute for Genetics and Society. “While it was developed in fruit flies, this system is readily transportable to a broad selection of insect species that serve as vectors for devastating disorders such as Chagas disease, sleeping disease, leishmaniasis and arboviral diseases.”
Is Gene Editing the Answer to Eradicating Malaria in Africa?
14885Staff, ASH Clinical News, 2020-11-01 16:00:02.
Researchers are looking at a new technique to eradicate malaria: Engineering mosquitoes with a “gene drive” – a gene that when inserted into mosquitoes (or other organisms) will be passed on to nearly 100% of the offspring in the next generation, rather than just half the offspring – that rapidly spreads a mutation that removes the insects’ ability to spread the malaria-causing parasite.
Inauguration and first meeting of WA-IVM Technical Working Groups
14872AUDA-NEPAD, AUDA-NEPAD News, 2020-10-27 19:37:33.
African Union Development Agency – NEPAD (AUDA-NEPAD) in collaboration with the West Africa Health Organization (WAHO), the Ministry of Health and the Ministry of Environment in Cote d’Ivoire, organized the inaugural meeting of WA-IVM Technical Working Groups (TWGs) from 24 – 26 April, 2019, in Abidjan, Cote d’Ivoire. Dr. ABLE, Inspector General of the Ministry of Health and Public Hygiene, representing the Minister, co-chaired the opening ceremony with Mr LAVRY, Technical Advisor of the Ministry of Environment and Sustainable Development.
Cellular mechanisms regulating synthetic sex ratio distortion in the Anopheles gambiae germline
14790R. E. Haghighat-Khah, A. Sharma, M. R. Wunderlich, G. Morselli, L. A. Marston, C. Bamikole, A. Hall, N. Kranjc, C. Taxiarchi, I. Sharakhov and R. Galizi, Pathogens and Global Health, 114:370-378. 2020-10-20 20:24:19.
Meiotic cleavage of rDNA repeats, located in the sex chromosomes of A. gambiae SD males, affects the competitiveness of mature sperm to fertilize the female oocyte.
WHO Releases a Position Statement on Genetically Modified Mosquitoes for the Control of Vector-Borne Diseases
14793E. R. Fletcher, Health Policy Watch, 2020-10-19 14:56:43.
WHO announced their support for the continued investigation into genetically modified mosquitoes as an alternative to existing interventions to reduce or prevent vector-borne diseases.
Ethics and vector-borne diseases
14904Geneva: World Health Organization, WHO Guidance, 2020-10-14 18:57:10.
The guidance was developed by an international group of experts in vector control, infectious disease ethics, maternal and child health, ecology and climate change, research and vaccine development, and public health communication. It examines a broad range of ethical considerations related to VBD prevention and control, including the social and environmental determinants of health; vector control methods, including emerging technologies; screening, surveillance and research; vaccine campaigns; and mass drug administration.
Do Africans need genetically modified mosquitoes?
14261genetically modified, mosquito, oxitec, autocidal, SIT, perspective, malaria, gene drive synthetic, engagement,, Mail and Guardian, 2020-09-01 14:32:06.
The following is an updated version of an article I wrote for the University of Michigan Risk Science Centre a while ago:
Anthony James / Mosquito Modification
14229Big Picture Science, SETI Institute, 2020-08-24 20:26:09.
Anthony James, vector biologist at the University of California, Irvine, describeshow we might genetically modify mosquitoes to make them unable to pass malaria on to humans.
Bednets or Biotechnology: To Rescue Current Persons or Research for the Future?
14236D. E. Callies, Fudan Journal of the Humanities and Social Sciences, 14. 2020-08-13 13:44:08.
After an exploration of the duty to rescue and cost-effectiveness analysis, I suggest we look towards the literature on intergenerational justice for a justifiable answer to the question of how we ought to allocate our malaria resources.
Fighting malaria with genetically modified mosquitoes
13609E. Nakkazi, BMJ, 370:m2172. 2020-08-04 12:53:14.
Could a bold project to genetically engineer mosquitoes curb the scourge of malaria in Africa? Finding out will require careful science—and public acceptance, writes Esther Nakkazi
Exploring gene drive’s role in fight against malaria
13536J. Conrow, Genetic Literacy Project, 2020-08-02 17:02:28.
J. Conrow (2020) Genetic Literacy Project. An international initiative has formed to ensure that gene drive technology gets a chance to prove its mettle in the quest to control malaria.
Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi
13593A. Adolfi, V. M. Gantz, N. Jasinskiene, H.-F. Lee, K. Hwang, E. A. Bulger, A. Ramaiah, J. B. Bennett, G. Terradas, J. J. Emerson, J. M. Marshall, E. Bier and A. A. James, bioRxiv, 2020.08.02.233056. 2020-08-02 12:59:26.
We developed the first recoded gene-drive rescue system for population modification in the malaria vector, Anopheles stephensi, that relieves the load in females caused by integration of the drive into the kynurenine hydroxylase gene by rescuing its function. Non-functional resistant alleles are eliminated via a dominantly-acting maternal effect combined with slower-acting standard negative selection, and a functional resistant allele does not prevent drive invasion.
Après les OGM, la nouvelle technique du forçage génétique inquiète écologistes et scientifiques
13595H. Leussier, Reporterre, 2020-07-28 13:04:33.
Les organismes issus du forçage génétique peuvent transmettre, sans autre intervention humaine, des gènes modifiés à tous leurs descendants. Cette technique permettrait d’éradiquer des espèces nuisibles, comme certains moustiques vecteurs de la malaria. Mais des associations, des scientifiques et des responsables politiques, inquiets de potentiels effets dévastateurs, réclament un moratoire international.
Three innovative technologies stopping malaria
13168B. Muni, The Borgen Project, 2020-07-09 14:47:45.
Malaria has plummeted by 40% fifteen years after 2000. A report that NCBI published attributed this to mosquito preventative measures like bed netting and insecticides. These interventions and practices, like wearing light color clothing, help at-risk populations fight malaria. However, mosquitos are learning to fight back. Resistance to insecticides is evolving in mosquitos and malaria continues to afflict millions. In 2018, there were still 228 million cases of malaria and 405,000 deaths. Over 90% of these cases and deaths occurred in Sub-Saharan Africa, but there are many interventions that have the potential to stop malaria. Here are three innovative technologies stopping malaria.
Detecting the population dynamics of an autosomal sex ratio distorter transgene in malaria vector mosquitoes
13607P. Pollegioni, A. R. North, T. Persampieri, A. Bucci, R. L. Minuz, D. A. Groneberg, T. Nolan, P. A. Papathanos, A. Crisanti and R. Muller, Journal of Applied Ecology, 11. 2020-06-18 12:44:16.
A sex-distorting autosomal transgene has been developed recently in G3 mosquitoes, a laboratory strain of the malaria vectorAnopheles gambiaes.l. Following the World Health Organization guidance framework for the testing of GM mosquitoes, we assessed the dynamics of this transgene in large cages using a joint experimental modelling approach. We performed a 4-month experiment in large, indoor cages to study the population genetics of the transgene.
Fighting malaria with gene-drive technology
12417EarthWise, earthwise radio, 2020-06-08 20:03:15.
A team led by Imperial College London has created a genetic modification that distorts the sex ratio of a population of Anopheles gambiae mosquitoes using “gene drive” technology. The modification works by using a DNA-cutting enzyme to destroy the X chromosome during the production of sperm, which leads to predominantly male offspring, since females require two X chromosomes. The modification is coupled to a gene drive to allow it to spread through a population in a very effective way. A gene drive is a genetic engineering technology that propagates a particular modification by assuring that a specific form of a gene (or allele) will be transmitted with far more than the natural 50% probability.
Mosquitoes engineered to resist the malaria parasite
12440Anonymous, Lab+Life Scientist, 2020-06-07 20:22:39.
Anopheles mosquitoes that have been genetically engineered with multiple antimalaria molecules, acting at different stages of the malaria life cycle, are strongly resistant to the parasite that causes malaria and are unlikely to lose that resistance quickly.
CRISPR/Cas9 gene drive technology to control transmission of vector-borne parasitic infections
12386M. Nateghi Rostami, Parasite Immunology, preprint:e12762. 2020-06-04 18:10:02.
Gene drive is the process of copying of an endonuclease-containing cassette that leads to increased frequency of inheritance of the desired traits in a targeted population. CRISPR/Cas9 technology is advancing genetic manipulation of insects in the field of gene drive experiments. The CRISPR/Cas9 drive could be engineered for genetic manipulation of parasites and/or vectors for disease control. A number of promising CRISPR/Cas9-based gene drive strategies that interfere with parasite development or impairs the reproductive capability of the insect vector, have been proposed in the laboratory for blocking transmission of malaria and leishmaniasis. Still several technical and ethical challenges remain to be addressed, none appear insuperable in this field.
Position Paper on Integrated Vector Management: Strengthening AU Members’ Regulatory Capacities for Responsible Research Towards Elimination of Malaria in Africa
12743African Union Development Agency - NEPAD, AUDA-NEPAD, 2020-06-01 13:48:16.
Africa continues to bear a heavy brunt of the malaria which is a disease transmitted by the female Anopheles mosquito. Thousands of lives, mostly of young children, are lost every year; which undermines efforts deployed at various levels for increased life expectancy and improved wellbeing for the socio-economic transformation of the continent. Accelerated changes and complementary tools are urgently needed to ensure effective elimination of malaria on the continent. Genetic engineering has been identified as one of such promising tools when applied to mosquito populations to reduce the transmission of the malaria parasite. The African Union Development Agency – NEPAD (AUDA-NEPAD), based on recommendations from the African Union High-Level Panel on Emerging Technologies (APET), continues to provide African Union Members States with the necessary support to ensure that research on and development of new genetically-based vector control tools are conducted in a responsible manner and in full compliance with safety requirements for human health and the environment for the benefit of African communities.
New study highlights success of gene drive technology with preventing mosquito-spread diseases
12401A. Meckler-Pacheco, The California Aggie, 2020-05-25 18:47:25.
For the past 30 years, researchers have studied the usage of gene drive technology to stop the spread of malaria. The idea is to create genetically engineered mosquitoes (GEM) that are either resistant to carrying the malaria parasite or that fail to reproduce, which would result in the reduction of the mosquito population. The gene drive technology relies on the use of the Cas-9 enzyme, which ensures the passing of the new modified genes onto offspring in the introduced population.
A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae
11463A. Simoni, A. M. Hammond, A. K. Beaghton, R. Galizi, C. Taxiarchi, K. Kyrou, D. Meacci, M. Gribble, G. Morselli, A. Burt, T. Nolan and A. Crisanti, Nature Biotechnology, 2020-05-11 15:15:55.
We report a male-biased sex-distorter gene drive (SDGD) in the human malaria vector Anopheles gambiae.
Converting endogenous genes of the malaria mosquito into simple non-autonomous gene drives for population replacement
11465A. Hoermann, S. Tapanelli, P. Capriotti, E. K. G. Masters, T. Habtewold, G. K. Christophides and N. Windbichler, bioRxiv, 2020-05-10 15:19:12.
Here we explore how minimal genetic modifications of endogenous mosquito genes can convert them directly into non-autonomous gene drives without disrupting their expression.
The development of complex and controversial innovations. Genetically modified mosquitoes for malaria eradication
11431V. Cisnetto and J. Barlow, Research Policy, 49:103917. 2020-05-04 13:32:20.
e use a longitudinal process approach and qualitative system dynamics modelling to study the development of genetically modified (GM) mosquitoes for malaria eradication in an African country.
Opinions of key stakeholders on alternative interventions for malaria control and elimination in Tanzania
11461M. F. Finda, N. Christofides, J. Lezaun, B. Tarimo, P. Chaki, A. H. Kelly, N. Kapologwe, P. Kazyoba, B. Emidi and F. O. Okumu, Malaria Journal, 19:164. 2020-04-23 15:13:29.
Malaria control in Tanzania currently relies primarily on long-lasting insecticidal nets and indoor residual spraying, alongside effective case management and behaviour change communication. This study explored opinions of key stakeholders on the national progress towards malaria elimination, the potential of currently available vector control interventions in helping achieve elimination by 2030, and the need for alternative interventions that could be used to supplement malaria elimination efforts in Tanzania.
Can we kill the dreaded mosquito? Do we even want to?
11228Stacey McKenna, Sierra, 2020-04-19 15:40:08.
As a major vector for disease, the mosquito has harmed more human beings than just about any other animal, and a changing climate is only boosting those numbers. As the range of disease-carrying species of mosquitoes expands, so does their ability to transmit the parasites and viruses that result in malaria, chikungunya, Zika, yellow fever, West Nile, and dengue fever. In 2018, the continental United States saw a 25 percent increase in severe, neuroinvasive cases of West Nile virus compared with a decade earlier. And over the past three decades, the CDC reports, the worldwide incidence of dengue fever has risen 30-fold.
Gene editing and the war against malaria
11226E. Bier and E. Sobber, American Scientist, 102:162. 2020-04-16 15:34:38.
Malaria is a devastating disease transmitted from person to person by mosquitoes. It kills more than 400,000 people per year, more than half of those deaths being children 5 years old or younger. CRISPR (clustered regularly interspaced short palindromic repeats) is a new gene-editing technology that acts like a pair of molecular scissors: It is used to “cut and paste” DNA sequences to alter gene function. In “Gene Editing and the War Against Malaria” (pages 162–169), Ethan Bier and Elliott Sober describe how biologists can now alter genes in a malaria-transmitting mosquito population by engineering a CRISPR gene drive, which mimics a natural evolutionary process. With this tool, a new gene can be inserted into the genome so that the alteration is rapidly passed down to successive sexually reproducing generations. Two gene-drive strategies have been found feasible: The first drives a local malaria-transmitting population to extinction; the second renders mosquitoes unable to transmit malaria, which breaks the malaria transmission cycle.
Vector genetics, insecticide resistance and gene drives: an agent-based modeling approach to evaluate malaria transmission and elimination
7941P. Selvaraj, E. A. Wenger, D. Bridenbecker, N. Windbichler, J. R. Russell, J. Gerardin, C. A. Bever and M. Nikolov, bioRxiv, 2020.01.27.920421. 2020-02-06 20:32:18.
Vector control has been a key component in the fight against malaria for decades, and chemical insecticides are critical to the success of vector control programs worldwide. However, increasing resistance to insecticides threatens to undermine these efforts. Understanding the evolution and propagation of resistance is thus imperative to mitigating loss of intervention effectiveness. Additionally, accelerated research and development of new tools that can be deployed alongside existing vector control strategies is key to eradicating malaria in the near future. Methods such as gene drives that aim to genetically modify large mosquito populations in the wild to either render them refractory to malaria or impair their reproduction may prove invaluable tools. Mathematical models of gene flow in populations can offer invaluable insight into the behavior and potential impact of gene drives as well as the spread of insecticide resistance in the wild. Here, we present the first multi-locus, agent-based model of vector genetics that accounts for mutations and many-to-many mappings of genotypes to phenotypes to investigate gene flow and the propagation of gene drives in Anopheline populations. This model is embedded within a large scale individual-based model of malaria transmission representative of a high burden, high transmission setting characteristic of the Sahel. Results are presented for the selection of insecticide-resistant vectors and the spread of resistance through repeated deployment of insecticide treated nets (ITNs), in addition to scenarios where gene drives act in concert with existing vector control tools such as ITNs. The roles of seasonality, spatial distribution of vector habitat and feed sites, and existing vector control in propagating alleles that confer phenotypic traits via gene drives that result in reduced transmission are explored. The ability to model a spectrum of vector species with different genotypes and phenotypes in the context of malaria transmission allows us to test deployment strategies for existing interventions that reduce the deleterious effects of resistance and allows exploration of the impact of new tools being proposed or developed.Author summary Vector control interventions are essential to the success of global malaria control and elimination efforts but increasing insecticide resistance worldwide threatens to derail these efforts. Releasing genetically modified mosquitoes that use gene drives to pass on desired genes and their associated phenotypic traits to the entire population within a few generations has been proposed to address resistance and other issues such as transmission heterogeneity that can sustain malaria transmission indefinitely. While the ethics and safety of these methods are being debated, mathematical models offer an efficient way of predicting the behavior and estimating the efficacy of these interventions if deployed to specific regions facing challenges to reaching elimination. We have developed a detailed mathematical model of vector genetics where specific genomes code for physical attributes that influence transmission and are affected by the surrounding environment. This is the first model to incorporate an individual-based multi locus genetic model into a detailed individual-based model of malaria transmission. This model opens the door to investigate a number of subtle but important questions such as the effects of small numbers of mosquitoes in a region sustaining malaria transmission during the low transmission season, and the success of gene drives in regions where extant vector control interventions could kill off gene drive mosquitoes before establishment. Here, we investigate the reduced efficacy of current vector control measures in the presence of insecticide resistance and evaluate the likelihood of achieving local malaria elimination using gene drive mosquitoes released into a high transmission setting alongside other vector control measures.
Engineering Bugs, Resurrecting Species: The Wild World of Synthetic Biology for Conservation
7242P. Rejcek, Singularity Hub, 2020-02-02 15:56:24.
Imagine a world where a mosquito bite is just an itchy annoyance. No malaria. No dengue fever. Last month, scientists announced they had taken one more step toward that vision. A paper in the journal PLOS Pathogens described how they synthetically engineered mosquitoes to stop the spread of dengue fever, a viral tropical disease that sickens as many as 100 million people each year. Now imagine genetically tweaking an invasive species of mosquito to save native Hawaiian birds from extinction, or transferring genes from one species of endangered chestnut tree to another to help the latter resist blight. Employing the same sort of genetic engineering used to make a plant-based burger bleed, scientists are beginning to explore the ways synthetic biology could help protect biodiversity and conserve species.
Transcontinental dispersal of Anopheles gambiae occurred from West African origin via serial founder events
14311H. Schmidt, Y. Lee, T. C. Collier, M. J. Hanemaaijer, O. D. Kirstein, A. Ouledi, M. Muleba, D. E. Norris, M. Slatkin, A. J. Cornel and G. C. Lanzaro, Communications Biology, 2. 2019-12-19 12:47:18.
Here we present population genomic analyses of 111 specimens sampled from west to east Africa, including the first whole genome sequences from oceanic islands, the Comoros.
The potential for a released autosomal X-shredder becoming a driving-Y chromosome and invasively suppressing wild populations of malaria mosquitoes
5648Alcalay, Y., S. Fuchs, R. Galizi, F. Bernardini, R. E. Haghighat-Khah, D. B. Rusch, J. R. Adrion, M. W. Hahn, P. Tortosa and P. A. Papathanos, bioRxiv, 2019:860551. 2019-12-17 17:51:02.
Synthetic sex-ratio distorters based on X-chromosome shredding are predicted to be more efficient than sterile males for population suppression of malaria mosquitoes using genetic control. X chromosome shredding operates through the targeted elimination of X-chromosome-bearing gametes during male spermatogenesis, resulting in males that have a high fraction of male offspring. Strains harboring autosomal constructs containing a modified endonuclease I-PpoI have now been developed in the malaria mosquito Anopheles gambiae, resulting in strong sex-ratio distortion towards males. Data are being gathered for these strains for submission of regulatory dossiers for contained use and subsequent field release in West Africa. Since autosomal X shredders are transmitted in a Mendelian fashion and can be selected against their frequency in the population is expected to decline once releases are halted. However, any unintended transfer of the X-shredder to the Y-chromosome could theoretically change these dynamics: This could lead to 100% transmission of the newly Y-linked X-shredder to the predominant male-biased offspring and its insulation from negative selection in females, resulting in its potential spread in the population and ultimately to suppression. Here, we analyze plausible mechanisms whereby an autosomal X-shredder could become linked to the Y-chromosome after release and provide data regarding its potential for activity should it become linked to the Y-chromosome. Our results strongly suggest that Y-chromosome linkage through remobilization of the transposon used for the initial genetic transformation is unlikely, and that, in the unexpected event that the X-shredder becomes linked to the Y-chromosome, expression and activity of the X-shredder would likely be inhibited by meiotic sex chromosome inactivation. We conclude that a functioning X-shredding based Y-drive resulting from a naturally induced transposition or translocation of the transgene onto the Y-chromosome is unlikely.
The bold plan to end malaria with a gene drive
5462VOX, 2019-12-13 16:52:47.
How genetically engineered mosquitoes might defeat a disease that kills millions of children. This describes gene drive and features work from a group (Target Malaria) that is developing this technology for use against malaria
A Controversial Swarm Of Genetically Modified Mosquitoes In A Lab In Italy
5527NPR, 2019-10-20 19:41:57.
An international team of scientists is conducting a controversial experiment in Italy. The experiment is designed to test genetically modified mosquitoes that researchers hope could provide a powerful new weapon to fight malaria, which remains one of the world's greatest scourges.
Gene Drive Mosquitoes: Ethics, Environment and Efficacy
18233L. Wilburn, ScienceInnovationUnion, 2019-09-20 17:06:38.
The Bill and Melinda Gates foundation has recently donated over $75 million to fund gene drive mosquito research by Target Malaria , a consortium that aims to develop technology for malaria control. The first planned release of gene drive mosquitoes is set to happen over the next two years in Burkina Faso, West Africa. But what exactly is gene drive, why do we need it and what are the wider implications of the technology? Malaria is a parasitic disease spread by the bite of the female Anopheles mosquito. Malaria can present as a range of symptoms including, mild fever, muscle pains (which can progress to severe malaria where the patient can experience severe anaemia and bleeding), renal failure, neurological disorders and death. In 2017, there were an estimated 219 million cases and 435,000 deaths attributed to malaria (1). Over 91% of these cases occurred in the Africa region, and children under the age of 5 were at the highest risk of contracting severe malaria. Fortunately, due to interventions such as insecticide-treated bed nets, indoor spraying of insecticides and improved medical infrastructure, from 2010-2017 malaria deaths were reduced by an estimated 28% (1). However, these control efforts may be severely jeopardised due to the rapid emergence of resistance to all insecticide classes and the most effective anti-malarial drugs (2, 3). Currently, there are only five classes of insecticides approved for public health use. In areas such as West Africa, there are multi-resistant mosquitoes which show resistance to all insecticide classes (4). Therefore, if the World Health Organisation (WHO) is to meet its goal of reducing global malaria by 90% by 2030, novel and effective strategies for malaria control must be identified (5). One such proposed strategy is gene drive mosquitoes.
Malaria eradication within a generation: ambitious, achievable, and necessary
12533R. G. A. Feachem, I. Chen, O. Akbari, A. Bertozzi-Villa, S. Bhatt, F. Binka, M. F. Boni, C. Buckee, J. Dieleman, A. Dondorp, A. Eapen, N. Sekhri Feachem, S. Filler, P. Gething, R. Gosling, A. Haakenstad, K. Harvard, A. Hatefi, D. Jamison, K. E. Jones, C., Lancet, 394:1056-1112. 2019-09-13 15:21:30.
50 years after a noble but flawed attempt to eradicate malaria in the mid-20th century, the global malaria community is once again seriously considering eradication. Momentum towards eradication has been building for decades, and more than half of the world’s countries are now malaria free.
Gene drives as a response to infection and resistance
3919Hayirli, TCM, P.F., Infection and Drug Resistance, 12:229-234. 2019-01-17 00:00:00.
Vector-borne infectious diseases continue to be a major threat to public health. Although some prevention and treatment modalities exist for these diseases, resistance to such modalities, exacerbated by global climate change, remains a fundamental challenge. Developments in genomic engineering technologies present a new front in battling vector-borne illnesses; however, there is a lack of consensus over the scope and consequences of these approaches. In this article, we use malaria as a case study to address the developments and controversies surrounding gene drives, a novel genomic engineering technology. We draw attention to the themes of infection control, resistance, and reversibility using a science and technology studies framework. Unlike other current prevention and treatment modalities, gene drives have the capacity to alter not only single organisms but also entire species and ecologies. Therefore, broader public and scientific engagement is needed to inform a more inclusive discussion between clinicians, researchers, policy makers, and society.
The Release of Genetically Engineered Mosquitoes in Burkina Faso: Bioeconomy of Science, Public Engagement and Trust in Medicine
3890Beisel, UG, J. K., African Studies Review, 62:164-173. 2019-01-08 00:00:00.
Malaria, which is transmitted by mosquitoes, continues to be responsible for a significant number of disease episodes and childhood deaths on the African continent. A variety of mosquito control strategies are currently inplace, but since case numbers are rising again, and drug and insecticide tolerance slow down progress made, there has been a push for innovative strategies. In August 2018, the National Biosafety Agency of Burkina Faso granted approval for the release of a maximum of 10,000 male Anopheles mosquitoes in experimental trials conducted by the multi-country consortium Target Malaria. These mosquitoes are rendered infertile through genetic modification, namely through “re-programming” of endonucleases that “cut through essential genes,” in this case, genes for fertility (Target Malaria 2019). The idea is that through the sterilization of male mosquitoes, the population of malaria-transmitting mosquitoes will be reduced, thereby decreasing the overall number of malaria infections.
Why I study the most dangerous animal on earth — mosquitoes | Fredros Okumu
5448TED, 2018-12-13 16:30:22.
This is a TED talk by an African scientist who reflects on the impact of malaria on Africans and efforts to eliminate the diseases and the need for continued efforts.
Sterile insect technique field trials to eliminate malaria under way
25913Anonymous, SA Department of Science and Innovation, 2018-10-29 13:06:00.
The first South African research trial for the biological control of mosquitoes using the sterile insect technique started in Jozini in KwaZulu-Natal earlier this month, with funding from the Department of Science and Technology. South Africa is making significant progress in reducing the incidence of malaria, and is now at a level where the country in a prime position to begin with complementary vector control strategies that address the problem of insecticide resistance. However, indoor residual spraying (IRS) using DDT and pyrethroid insecticides, while effective in controlling the disease, is unlikely to eliminate malaria on its own. IRS targets mainly indoor feeding and resting mosquitoes, and is not effective against vectors that feed and rest outdoors such as Anopheles arabiensis, which is a major contributor to outdoor transmission in South Africa's malaria-affected provinces. One of the supplementary methods being explored is the use of the sterile insect technique (SIT). This works like birth control to suppress mosquito populations and reduce the spread of malaria. The technique involves the mass-rearing and sterilisation of male mosquitoes before they are released in the wild.
Global report on insecticide resistance in malaria vectors: 2010-2016.
12683WHO, World Health Organization, 2018-05-01 18:13:11.
Insecticide-based vector control is a cornerstone in the fight against malaria. Selection of vector-control interventions should take into account the resistance status of local mosquito vectors along with other factors associated with intervention deployment and use such as availability, cost and cost -effectiveness as well as population acceptance or compliance. Strategic insecticide resistance monitoring is therefore essential to inform evidence-based vector control.
Gene Drives – Wundermittel? Biowaffe?
12380Swiss Academy of Sciences, 2018-02-19 21:02:40.
Gene drives are genetic elements that skew the pattern of inheritance of a given characteristic in sexually reproduc- ing organisms. They can be used to spread a characteristic that can alter or even reduce the numbers of individuals in wild populations of a certain species.
Gene drive to reduce malaria transmission in sub-Saharan Africa
3963Burt, AC, Mamadou; Crisanti, Andrea; Diabate, Abdoulaye; Kayondo, Jonathan K., Journal of Responsible Innovation, 5:S66-S80. 2018-01-21 00:00:00.
Despite impressive progress, malaria continues to impose a substantial burden of mortality and morbidity, particularly in sub-Saharan Africa, and new tools will be needed to achieve elimination. Gene drive is a natural process by which some genes are inherited at a greater-than-Mendelian rate and can spread through a population even if they cause harm to the organisms carrying them. Many different synthetic gene drive systems have been proposed to suppress the number of mosquitoes and/or reduce vector competence. As with any control measure, due attention should be paid to the possible evolution of resistance. No gene drive construct has yet been reported that is "field-ready" for release, and when such constructs are developed, they should be assessed on a case-by-case basis. Gene drive approaches to vector control promise to have a number of key features that motivate their continued development, and scrutiny, by all concerned.
Engineered Reciprocal Chromosome Translocations Drive High Threshold, Reversible Population Replacement in Drosophila
3961Buchman, ABI, Tobin; Marshall, John M.; Akbari, Omar S.; Hay, Bruce A., ACS Synthetic Biology, 7:1359-1370. 2018-01-19 00:00:00.
Replacement of wild insect populations with transgene-bearing individuals unable to transmit disease or survive under specific environmental conditions using gene drive provides a self-perpetuating method of disease prevention. Mechanisms that require the gene drive element and linked cargo to exceed a high threshold frequency in order for spread to occur are attractive because they offer several points of control: they bring about local, but not global population replacement; and transgenes can be eliminated by reintroducing wildtypes into the population so as to drive the frequency of transgenes below the threshold frequency required for drive. Reciprocal chromosome translocations were proposed as a tool for bringing about high threshold population replacement in 1940 and 1968. However, translocations able to achieve this goal have only been reported once, in the spider mite Tetranychus urticae, a haplo-diploid species in which there is strong selection in haploid males for fit homozygotes. We report the creation of engineered translocation-bearing strains of Drosophila melanogaster, generated through targeted chromosomal breakage and homologous recombination. These strains drive high threshold population replacement in laboratory populations. While it remains to be shown that engineered translocations can bring about population replacement in wild populations, these observations suggest that further exploration of engineered translocations as a tool for controlled population replacement is warranted.
The impact of releasing sterile mosquitoes on malaria transmission
3981Hongyan, YC, Yang; Xin'an, Zhang; Jia, Li, Discrete & Continuous Dynamical Systems - B, 23:3837-3853. 2018-01-19 00:00:00.
The sterile mosquitoes technique in which sterile mosquitoes are released to reduce or eradicate the wild mosquito population has been used in preventing the malaria transmission. To study the impact of releasing sterile mosquitoes on the malaria transmission, we first formulate a simple SEIR (susceptible-exposed-infected-recovered) malaria transmission model as our baseline model, derive a formula for the reproductive number of infection, and determine the existence of endemic equilibria. We then include sterile mosquitoes in the baseline model and consider the case of constant releases of sterile mosquitoes. We examine how the releases affect the reproductive numbers and endemic equilibria for the model with interactive mosquitoes and investigate the impact of releasing sterile mosquitoes on the malaria transmission.
Identifying and detecting potentially adverse ecological outcomes associated with the release of gene-drive modified organisms
3980Hayes, KRH, G. R.; Dana, G. V.; Foster, S. D.; Ford, J. H.; Thresher, R.; Ickowicz, A.; Peel, D.; Tizard, M.; De Barro, P.; Strive, T.; Dambacher, J. M., Journal of Responsible Innovation, 5:S139-S158. 2018-01-18 00:00:00.
Synthetic gene drives could provide new solutions to a range of old problems such as controlling vector-borne diseases, agricultural pests and invasive species. In this paper, we outline methods to identify hazards and detect potentially adverse ecological outcomes at the individual (genotype, phenotype), population, community and ecosystem level, when progressing Gene Drive Modified Organisms through a phased test and release pathway. We discuss the strengths and weaknesses of checklists and structured hazard analysis techniques, identify methods to help meet some of the challenges of detecting adverse ecological outcomes in experiments and confined field trials, and discuss ways to improve the efficiency and statistical rigour of post-release monitoring strategies.
Economic issues to consider for gene drives
3997Mitchell, PDB, Z.; McRoberts, N., Journal of Responsible Innovation, 5:S180-S202. 2018-01-15 00:00:00.
We examine four economic issues regarding gene drive applications made possible by gene editing technologies. First, whether gene drives are self-sustaining or self-limiting will largely determine which types of organizations have incentives to develop and deploy gene drives and greatly influence their governance and regulation. Social factors will also play key roles, particularly public perceptions, with these perceptions co-determined with regulation and governance. Second, gene drive applications will generate unintended negative social impacts that will partially offset benefits. Third, economic surplus, the traditional measure of economic benefits, incompletely captures the welfare impacts of gene drive applications. Fourth, gene drives imply dynamic nonlinearities that make identifying economic equilibria and general policy recommendations challenging. The potentially substantial benefits, coupled with the technical, social, and economic uncertainties surrounding gene drives, suggest that a responsible course of action is to move forward while maintaining regulatory flexibility and conducting research to resolve key uncertainties.
Current vector control challenges in the fight against malaria
16269G. Benelli and J. C. Beier, Acta Tropica, 174:91-96. 2017-07-07 16:47:31.
The majority of National Malaria Control Programs in Africa still rely on indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs). These methods reduce malaria incidence but generally have little impact on malaria prevalence. In addition to outdoor transmission, growing levels of insecticide resistance in targeted vectors threaten the efficacy of LLINs and IRS.
ASSEMBLY OF THE UNION Twenty-Ninth Ordinary Session: DECISIONS, DECLARATIONS AND RESOLUTION
16078African Union, African Union, 2017-07-04 14:45:50.
Assembly/AU/Dec.649(XXIX): COMMITS to sustain the gains made in the fight against Malaria and monitor antimalarial drug resistance and insecticide resistance; COMMITS ALSO to invest in the development and regulation of the gene-drive technology as well as other new innovations including next generation insecticides for Indoor Residual Spraying and Long Lasting Insecticidal Nets, Rapid Diagnostic Tests and Artemisinin-based Combination Therapy for the elimination of malaria and REQUESTS the Commission, WHO and NEPAD Agency to support these initiatives;
Is it time for synthetic biodiversity conservation?
4062Piaggio, AJS, G.; Seddon, P. J.; Alphey, L.; Bennett, E. L.; Carlson, R. H.; Friedman, R. M.; Kanavy, D.; Phelan, R.; Redford, K. H.; Rosales, M.; Slobodian, L.; Wheeler, K., Trends in Ecology & Evolution, 32:97-107. 2017-01-20 00:00:00.
Evidence indicates that, despite some critical successes, current conservation approaches are not slowing the overall rate of biodiversity loss. The field of synthetic biology, which is capable of altering natural genomes with extremely precise editing, might offer the potential to resolve some intractable conservation problems (e.g., invasive species or pathogens). However, it is our opinion that there has been insufficient engagement by the conservation community with practitioners of synthetic biology. We contend that rapid, large-scale engagement of these two communities is urgently needed to avoid unintended and deleterious ecological consequences. To this point we describe case studies where synthetic biology is currently being applied to conservation, and we highlight the benefits to conservation biologists from engaging with this emerging technology.
Towards the genetic control of invasive species
4047Harvey-Samuel, TA, T.; Alphey, L., Biological Invasions, 19:1683-1703. 2017-01-05 00:00:00.
Invasive species remain one of the greatest threats to global biodiversity. Their control would be enhanced through the development of more effective and sustainable pest management strategies. Recently, a novel form of genetic pest management (GPM) has been developed in which the mating behaviour of insect pests is exploited to introduce genetically engineered DNA sequences into wild conspecific populations. These 'transgenes' work in one or more ways to reduce the damage caused by a particular pest, for example reducing its density, or its ability to vector disease. Although currently being developed for use against economically important insect pests, these technologies would be highly appropriate for application against invasive species that threaten biodiversity. Importantly, these technologies have begun to advance in scope beyond insects to vertebrates, which include some of the world's worst invasives. Here we review the current state of this rapidly progressing field and, using an established set of eradication criteria, discuss the characteristics which make GPM technologies suitable for application against invasive pests.
Using Gene Drive to Control Malaria
4718The Scientist, The Scientist, 2016-12-31 00:00:00.
This article provides illustrations for how gene drive works, how gene drives spread, and how gene drive could be used to control malaria using population-wide gene knockout, skewed sex ratio, and population-wide gene knock-in techniques. Visit the article to view all illustrations.
Genetic Engineering and Diseases – Gene Drive & Malaria
4714Kurzgesagt – In a Nutshell, 2016-09-21 00:00:00.
This video focuses on the basic applications of gene drive to malaria eradication and leave the viewer with the question “what do you think?”
The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015
12672S. Bhatt, D. J. Weiss, E. Cameron, D. Bisanzio, B. Mappin, U. Dalrymple, K. E. Battle, C. L. Moyes, A. Henry, P. A. Eckhoff, E. A. Wenger, O. Briët, M. A. Penny, T. A. Smith, A. Bennett, J. Yukich, T. P. Eisele, J. T. Griffin, C. A. Fergus, M. Lynch, F. L, Nature, 526:207-211. 2015-09-16 17:16:47.
Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital to inform future control planning. H
GM mosquitoes a ‘quantum leap’ towards tackling malaria
6940A. Vaughan, Guardian, 2014-06-10 15:54:00.
New technique injects mosquitoes with a gene that results in mostly male offspring, eventually leading to a population crash
The Impact of Pyrethroid Resistance on the Efficacy of Insecticide-Treated Bed Nets against African Anopheline Mosquitoes: Systematic Review and Meta-Analysis.
12678C. Strode, S. Donegan, P. Garner, A. A. Enayati and J. Hemingway, PLOS Medicine, 11:e1001619. 2014-03-18 17:48:58.
This meta-analysis found that ITNs are more effective than UTNs regardless of resistance. There appears to be a relationship between resistance and the RD for mosquito mortality in laboratory and field studies. However, the substantive heterogeneity in the studies' results and design may mask the true relationship between resistance and the RD, and the results need to be interpreted with caution. Our analysis suggests the potential for cumulative meta-analysis in entomological trials, but further field research in this area will require specialists in the field to work together to improve the quality of trials, and to standardise designs, assessment, and reporting of both resistance and entomological outcomes.
Modelling the spatial spread of a homing endonuclease gene in a mosquito population
4177North, AB, A.; Godfray, H. C. J., Journal of Applied Ecology, 50:1216-1225. 2013-01-15 00:00:00.
Homing endonuclease genes (HEGs) exist naturally in many single-celled organisms and can show extremely strong genetic drive allowing them to spread through populations into which they are introduced. They are being investigated as tools to manipulate the populations of important vectors of human disease, in particular the mosquitoes that transmit malaria. Before HEGs can be deployed, it is important to study their spatial spread in order to design efficient release strategies. A spatially explicit model is developed to study the spread of a HEG through a landscape whose structure is defined by the distribution of mosquito breeding and feeding sites. The model is motivated by the biology of the major vectors of malaria in Africa. The conditions for spread, fixation and loss of two major types of HEG are explored in different landscapes. In landscapes where mosquito resources are abundant, the conditions for spread are well approximated by a mean-field model. Where a HEG imposes a genetic load, it can cause population extinction, though spatial models more often predict population suppression. In certain types of landscapes where mosquito resources are rare, an introduced HEG may be prevented from moving between local mosquito populations and so a simple release strategy is unlikely to be effective, yet if the HEG succeeds in spreading population extinction is a feasible outcome. Increasing the number of release sites at the expense of releasing fewer mosquitoes per site reduces the probability that a HEG will fail.Synthesis and applications. The model presented asks for the first time how the spatial structure of mosquito populations will influence the effectiveness of a technology that is being rapidly developed for vector control. If homing endonuclease genes (HEGs) are to be used in this way, we have qualified the importance of accounting for landscape characteristics in both the execution and the expectation of their application. The next stage is to use the model to study the spread of HEGs through real landscapes where releases may take place, something that will be facilitated by the results of the present study. The model presented asks for the first time how the spatial structure of mosquito populations will influence the effectiveness of a technology that is being rapidly developed for vector control. If homing endonuclease genes (HEGs) are to be used in this way, we have qualified the importance of accounting for landscape characteristics in both the execution and the expectation of their application. The next stage is to use the model to study the spread of HEGs through real landscapes where releases may take place, something that will be facilitated by the results of the present study.
Ethical issues in field trials of genetically modified disease-resistant mosquitoes
13538D. B. Resnik, Developing World Bioethics, 14:37-46. 2012-07-29 19:12:07.
Mosquito-borne diseases take a tremendous toll on human populations, especially in developing nations. In the last decade, scientists have developed mosquitoes that have been genetically modified to prevent transmission of mosquito-borne diseases, and field trials have been conducted. Some mosquitoes have been rendered infertile, some have been equipped with a vaccine they transmit to humans, and some have been designed to resist diseases.
Pyrethroid resistance in African anopheline mosquitoes: what are the implications for malaria control?
12676H. Ranson, R. N’Guessan, J. Lines, N. Moiroux, Z. Nkuni and V. Corbel, Trends in Parasitology, 27:91-98. 2011-02-01 17:44:55.
The use of pyrethroid insecticides in malaria vector control has increased dramatically in the past decade through the scale up of insecticide treated net distribution programmes and indoor residual spraying campaigns. Inevitably, the major malaria vectors have developed resistance to these insecticides and the resistance alleles are spreading at an exceptionally rapid rate throughout Africa. Although substantial progress has been made on understanding the causes of pyrethroid resistance, remarkably few studies have focused on the epidemiological impact of resistance on current malaria control activities. As we move into the malaria eradication era, it is vital that the implications of insecticide resistance are understood and strategies to mitigate these effects are implemented.
Field site selection: getting it right first time around
25817C. A. Malcolm, B. El Sayed, A. Babiker, R. Girod, D. Fontenille, B. G. J. Knols, A. H. Nugud and M. Q. Benedict, Malaria Journal, 8. 2009-11-16 09:57:52.
The selection of suitable field sites for integrated control of Anopheles mosquitoes using the sterile insect technique (SIT) requires consideration of the full gamut of factors facing most proposed control strategies, but four criteria identify an ideal site: 1) a single malaria vector, 2) an unstructured, relatively low density target population, 3) isolation of the target population and 4) actual or potential malaria incidence. Such a site can exist in a diverse range of situations or can be created. Two contrasting SIT field sites are examined here: the desert-flanked Dongola Reach of the Nile River in Northern State, Sudan, where malaria is endemic, and the island of La Reunion, where autochthonous malaria is rare but risk is persistent. The single malaria-transmitting vector at both sites is Anopheles arabiensis. In Sudan, the target area is a narrow 500 km corridor stretching from the rocky terrain at the Fourth Cataract - just above the new Merowe Dam, to the northernmost edge of the species range, close to Egypt. Vector distribution and temporal changes in density depend on the Nile level, ambient temperature and human activities. On La Reunion, the An. arabiensis population is coastal, limited and divided into three areas by altitude and exposure to the trade winds on the east coast. Mosquito vectors for other diseases are an issue at both sites, but of primary importance on La Reunion due to the recent chikungunya epidemic. The similarities and differences between these two sites in terms of suitability are discussed in the context of area-wide integrated vector management incorporating the SIT.
Spatial and temporal distribution of the malaria mosquito Anopheles arabiensis in northern Sudan: influence of environmental factors and implications for vector control
25826T. B. Ageep, J. Cox, M. M. Hassan, B. G. J. Knols, M. Q. Benedict, C. A. Malcolm, A. Babiker and B. B. El Sayed, Malaria Journal, 8:14. 2009-06-09 10:20:40.
Background: Malaria is an important public health problem in northern Sudan, but little is known about the dynamics of its transmission. Given the characteristic low densities of Anopheles arabiensis and the difficult terrain in this area, future vector control strategies are likely to be based on area-wide integrated pest management (AW-IPM) that may include the sterile insect technique ( SIT). To support the planning and implementation of future AW-IPM activities, larval surveys were carried out to provide key data on spatial and seasonal dynamics of local vector populations. Methods: Monthly cross-sectional larval surveys were carried out between March 2005 and May 2007 in two localities (Dongola and Merowe) adjacent to the river Nile. A stratified random sampling strategy based on the use of Remote Sensing (RS), Geographical Information Systems (GIS) and the Global Positioning System (GPS) was used to select survey locations. Breeding sites were mapped using GPS and data on larval density and breeding site characteristics were recorded using handheld computers. Bivariate and multivariate logistic regression models were used to identify breeding site characteristics associated with increased risk of presence of larvae. Seasonal patterns in the proportion of breeding sites positive for larvae were compared visually to contemporaneous data on climate and river height. Results: Of a total of 3,349 aquatic habitats sampled, 321 (9.6%) contained An. arabiensis larvae. The frequency with which larvae were found varied markedly by habitat type. Although most positive sites were associated with temporary standing water around the margins of the main Nile channel, larvae were also found at brickworks and in areas of leaking pipes and canals-often far from the river. Close to the Nile channel, a distinct seasonal pattern in larval populations was evident and appeared to be linked to the rise and fall of the river level. These patterns were not evident in vector populations breeding in artificial water sources away from the river. Conclusion: The GIS-based survey strategy developed in this study provides key data on the population dynamics of An. arabiensis in Northern State. Quantitative estimates of the contributions of various habitat types and their proximity to settlements provide a basis for planning a strategy for reducing malaria risk by elimination of the vector population.
Towards a sterile insect technique field release of Anopheles arabiensis mosquitoes in Sudan: Irradiation, transportation, and field cage experimentation
25755M. E. H. Helinski, M. M. Hassan, W. M. El-Motasim, C. A. Malcolm, B. G. J. Knols and B. El-Sayed, Malaria Journal, 7:10. 2008-04-25 10:09:22.
Background: The work described in this article forms part of a study to suppress a population of the malaria vector Anopheles arabiensis in Northern State, Sudan, with the Sterile Insect Technique. No data have previously been collected on the irradiation and transportation of anopheline mosquitoes in Africa, and the first series of attempts to do this in Sudan are reported here. In addition, experiments in a large field cage under near-natural conditions are described. Methods: Mosquitoes were irradiated in Khartoum and transported as adults by air to the field site earmarked for future releases (400 km from the laboratory). The field cage was prepared for experiments by creating resting sites with favourable conditions. The mating and survival of (irradiated) laboratory males and field-collected males was studied in the field cage, and two small-scale competition experiments were performed. Results: Minor problems were experienced with the irradiation of insects, mostly associated with the absence of a rearing facility in close proximity to the irradiation source. The small-scale transportation of adult mosquitoes to the release site resulted in minimal mortality (< 6%). Experiments in the field cage showed that mating occurred in high frequencies (i.e. an average of 60% insemination of females after one or two nights of mating), and laboratory reared males (i.e. sixty generations) were able to inseminate wild females at rates comparable to wild males. Based on wing length data, there was no size preference of males for mates. Survival of mosquitoes from the cage, based on recapture after mating, was satisfactory and approximately 60% of the insects were recaptured after one night. Only limited information on male competitiveness was obtained due to problems associated with individual egg laying of small numbers of wild females. Conclusion: It is concluded that although conditions are challenging, there are no major obstacles associated with the small-scale irradiation and transportation of insects in the current setting. The field cage is suitable for experiments and studies to test the competitiveness of irradiated males can be pursued. The scaling up of procedures to accommodate much larger numbers of insects needed for a release is the next challenge and recommendations to further implementation of this genetic control strategy are presented.
First Anopheles arabiensis germline transformation: Toward the development of a transgenic genetic sexing strain
16649H. C. Bossin, J. Thailayil, F. Catteruccia, J. P. Benton, A. Crisanti, M. Q. Benedict, B. G. Knols and A. S. Robinson, American Journal of Tropical Medicine and Hygiene, 75:66-66. 2006-11-01 20:17:39.
The ability to genetically engineer mosquitoes is likely to have major implications for the development and implementation of genetic control systems against mosquito disease vectors such as the Sterile Insect Technique (SIT). In particular, genetically transformed mosquito strains can be created for genetic marking and sexing, two key factors known to influence the effectiveness of SIT programmes. In addition, the removal of biting females before releasing sterile males in the field will be of critical importance as they contribute to disease transmission and reduce the efficiency of the release campaign. Parallel to the creation of a conventional genetic sexing strain (Y-translocation of a resistance marker), our group is undertaking a transgenic approach to the development of an A. arabiensis genetic sexing strain (GSS). The sex separation strategy under investigation relies on the sex-specific properties of the A. gambiae B2tubulin gene regulatory regions. It is hoped this approach will achieve the high sex separation efficiency (above 99%) and strain stability required for safe and efficient male-only SIT releases. We report here the successful development of transgenic A. arabiensis lines using the pPB[DsRed]B2EGFP construct. Wild-type A. arabiensis embryos were injected with a mixture of pPB[DsRed]B2EGFP and helper plasmid phsppBac (700 and 300 ng/µI respectively) following an appropriate protocol. Injections generated several transgenic sexing lines. The effectiveness of the transgenic-based sex-separation procedure, the stability of transgenic mosquito GSS under various (mass-)rearing regimes, as well as the viability and reproductive competitiveness of transgenic sterile males are being assessed.
A cage replacement experiment involving introduction of genes for refractoriness to Plasmodium-yoelii-nigeriensis into a population of Anopheles gambiae (Diptera, Culicidae)
6230P. M. Graves and C. F. Curtis, Journal of Medical Entomology, 19:127-133. 1982-03-24 21:46:47.
A caged population of Anopheles gambiae was allowed to breed continuously and samples of the progeny were tested for susceptibility to Plasmodium yoelii nigeriensis. Males of a strain partially refractory to this parasite were released into the population for an 18-wk period. The susceptibility of the population declined from 100% to about 50% and remained at that level for several months after releases were terminated. Separate experiments showed that the fitness of the adult males and larvae of the refractory strain was much less than that of the susceptible caged strain. The observed change in the susceptibility of the caged population was compared with the expectations on various assumptions about the relative fitness of the refractory and susceptible strains. It appears that initially the efficiency of the replacement process was considerably reduced because of poor fitness of the refractory strain. Once the refractoriness genes were in the caged population, however, they were able to recombine with the genes causing poor fitness and the latter could be eliminated by natural selection, leaving a considerable degree of refractoriness in the population. The results are discussed in relation to the possibility of vector control by the release of males from a refractory strain and with particular reference to the advantages and disadvantages of the use of a negatively heterotic system to assist the replacement process and the release of both sexes.
Population replacement in Culex fatigens by means of cytoplasmic incompatibility. Laboratory experiments with non-overlapping generations
6291C. F. Curtis and T. Adak, Bulletin of the World Health Organization, 51:249-255. 1974-01-08 19:45:42.
Bidirectional cytoplasmic incompatibility in the Culex pipiens complex appears to provide a mechanism for the replacement of a wild population by a strain refractory to filaria or a strain made partly sterile by a translocation. As a preliminary test of the feasibility of the replacement process, various ratios of strains with the cytoplasm of either Delhi or Paris, which are bidirectionally incompatible, were tested in laboratory cages. Where one strain was marked with the ruby-eye gene, this strain always declined in frequency in the next generation. In experiments in which the Paris strain was marked with a male-linked translocation complex, after 2-4 generations of breeding there was complete elimination of either the Paris or the Delhi type depending, as expected, on the relative frequencies of the two types with which the population began. In one experiment a type with Paris cytoplasm devoid of the translocation was found. This type increased in frequency in succeeding generations. The possible causes of origin of this type and its relevance to the practical use of the replacement principle are discussed.
