Keywords: Vector control
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.
Modelling Aedes albopictus management, incorporating immigration and bi-directional Wolbachia interactions
35520Ryan, M., Mendiolar, M., Pagendam, D. et al., J Pest Sci, 99. 2026-03-10 09:16:51.
Aedes albopictus mosquitoes are competent vectors for the spread of at least 24 different arboviruses, including dengue, Ross River, and Japanese encephalitis viruses. However, they remain less studied than their more urban cousins, Aedes aegypti. We model an incompatible insect technique (IIT) strategy for mosquito control, with bi-directional incompatibility between two strains of Wolbachia (wAlbA/wAlbB ARwP) and age-based cytoplasmic incompatibility decay in a well-mixed population. We include mosquito immigration to explore potential reversibility, an important consideration in bi-directional IIT control programs. We also explore the establishment probability after female contamination of an artificially-infected Wolbachia mosquito strain, consider the suppression dynamics and probability of mosquito management success for different release strategies, and determine a corresponding cost proxy for release (numbers of mosquitoes released). We found an establishment probability threshold of 40% in the absence of mating preferences, though this threshold needs validation in future field and laboratory experiments. We found differences in suppression success between release cessation and 6 months later for different immigration rates. There are similar short-term costs with differences in medium- and longer-term costs between release strategies. Our model suggests bi-directional IIT control programs are reversible with low amounts of wild-type immigration. This work demonstrates opportunities to optimise the suppression of these medically important mosquitoes.
Advances in male sex separation for the support of mosquito control programs
35526Duman-Scheel M, Frontiers in Insect Science, 6. 2026-03-09 09:05:10.
Several mosquito control technologies, including the sterile insect technique (SIT), the incompatible insect technique (IIT), and a variety of genetic technologies are emerging as promising solutions for combatting insecticide resistance and the spread of vector-borne diseases. These approaches involve mass releases of male mosquitoes in an effort to suppress mosquito populations in an eco-friendly manner. At small scale, male mosquito selection can be achieved through the use of mechanical separation techniques, but such methods are not sufficient for scaled implementation of emerging mosquito population control technologies. This review discusses mechanical, genetic, and automated mosquito sex sorting techniques that have emerged to address the need for scaled male mosquito production, as well as the potential contributions of RNA interference (RNAi) to facilitate this process. One RNAi method utilizes the oral delivery of yeast expressing interfering RNA targeting genes required for female larval survival. The yeast, which can be incorporated into normal insect larval diets, enables male sex selection during larval rearing in mosquitoes and could easily be extended to other insects. RNAi-mediated sex-sorting technologies, in combination with mechanical, genetic, and automated sorting technologies, could facilitate the scaled production of adult males in support of global insect population suppression efforts.
Present and Future of Mosquito-Borne Disease Control in Europe with a Specific Focus on the Mediterranean
35535Cholvi, M., Moretti, R., Osório, H. C., et al., Insects, 17. 2026-02-27 19:18:24.
Mosquito-borne diseases are an emerging public health challenge in Europe, driven by the spread of invasive mosquito species capable of sustaining outbreaks of tropical arboviral diseases. Rising temperatures, shifting precipitation patterns, human-driven habitat changes, and prolonged transmission seasons have increased the risk of dengue, chikungunya, and West Nile virus outbreaks, among other vector-borne diseases. Effective control requires a multifaceted approach, combining traditional and novel methods with advanced surveillance technologies and community involvement. However, growing insecticide resistance and concerns about insecticide use highlight the need for more prudent management of current tools and the development of innovative alternatives. Genetic control strategies, including the Sterile Insect Technique (SIT), Wolbachia-based approaches, and genetically modified (GM) mosquitoes, offer promising solutions but still face scientific, regulatory, and societal challenges. This review explores the current landscape of mosquito-borne disease control in Mediterranean Europe, emphasizing key challenges and emerging solutions. An integrated approach that strengthens surveillance, promotes sustainable control methods, and incorporates novel biotechnological tools supported by smart technologies will be essential to reduce the future burden of mosquito-borne diseases in the region.
Locally Acquired Dengue in Townsville, Australia, 2024–2025: An Outbreak Report in a Non-Endemic Region with wMel Wolbachia-Infected Aedes aegypti
35533Thompson, K., Lyons, S., Malone, K., Fryk, J., Pyke, A., & Murton, K., Tropical Medicine and Infectious Disease, 11. 2026-02-26 19:11:49.
During the 2024/2025 wet season, Townsville had its first sustained autochthonous outbreak of dengue disease caused by dengue virus type 2 (DENV-2), the second locally transmitted outbreak of dengue since 2014 following the introduction of wMel strain Wolbachia-infected mosquitoes, a control strategy for dengue virus (DENV) and other Aedes-transmitted arboviruses. In comparison to two recorded locally acquired cases of dengue in 2020, the 2024/2025 outbreak resulted in sixteen cases in two inner-city suburbs of Townsville during the wet season associated with higher-than-average rainfall. This second dengue outbreak since 2014 highlights that Townsville and other north Queensland communities where Wolbachia mosquito programs have been deployed remain vulnerable to DENV incursions and local disease outbreaks despite the apparent high coverage of Wolbachia-infected mosquitoes. Whilst these control strategies have likely contributed to a reduction in the number and frequency of autochthonous DENV outbreaks in north Queensland, ongoing maintenance and monitoring of Wolbachia-infected mosquito coverage is necessary, together with timely review and improvement in dengue awareness and prevention health promotion activities in the community.
Field implementation of the sterile insect technique against Aedes aegypti in Recife, Brazil: operational challenges and impact of release frequency on vector dynamics
35418Macedo, A.T., Carvalho, D.O., Gomez, M. et al., Infectious Diseases of Poverty, 15. 2026-02-02 16:59:43.
The sterile insect technique (SIT) is an environmentally friendly tool for suppressing Aedes aegypti populations. While promising in controlled settings, its application in large urban environments presents logistical and biological challenges. This trial focused on releasing sterile males, sent from a long-distance production facility to suppress the local mosquito population. Sterile males of Ae. aegypti were mass-reared, irradiated, and transported 712.2 km from a central facility to Recife, Brazil. Releases were performed once (SIT 1 ×) or twice per week (SIT 2 ×). Entomological indices—including eggs/trap per day (ETD), hatch rate, induced sterility, and adult female abundance—were monitored through ovitraps and BG-Sentinel traps. Data were analyzed using generalized linear mixed models (GLMMs) and Bayesian time-series modeling (CausalImpact). Dose–response experiments established that pupae required 35 Gy and adults 65 Gy to achieve > 99% sterility, with no difference between gamma and X-ray sources. Adult sterilization was effective across 24–96 h post-emergence, facilitating operational flexibility. Handling and transport reduced flight ability by up to 35 percentage points, highlighting cumulative stress effects. In field trials, SIT 1 × yielded limited suppression, with ETD values remaining similar to or higher than those of the control. In contrast, SIT 2 × produced consistent suppression, reducing ETD by 39%, hatch rate by 33%, and female abundance by 51%. In this study, increasing the release frequency was essential to achieve significant model outcomes, representing varying degrees of mild suppression of Ae. aegypti in a complex urban setting. In Addition, male handling, chilling, and transport emphasize the need to reduce the exposure to these parameters by improving the protocols. These results highlight key areas for scaling SIT within integrated vector management strategies in tropical urban settings.
Serratia species as paratransgenic vehicles: potential applications in vector-borne disease control
35422Mahor S, Gupta H. 0., Clinical Microbiology Reviews, 2026-02-02 15:13:09.
Paratransgenesis employs insect-associated bacteria to deliver antipathogen effectors and is an emergent complementary strategy for vector control. This review synthesizes current evidence for Serratia species as paratransgenic vehicles, combining mechanistic insights into effector molecules (e.g., scorpine, MP2, multi-fusion constructs, and the naturally secreted antimalarial lipase AmLip), with comparative evidence on colonization, transmission, and efficacy. Serratia strains (e.g., AS1, Su_YN1) demonstrate rapid dissemination in laboratory populations and potent reductions in Plasmodium development (reported oocyst inhibition in laboratory studies ranging from ~60% to >90% for specific effectors). We critically examine biosafety, genetic stability, and ecological factors and propose a minimum evidence package and translational roadmap comprising multigeneration stability assays, horizontal gene transfer monitoring, non-target impact assessments, and community and regulatory engagement to responsibly advance Serratia-based paratransgenesis toward field evaluation. This comparative framing integrates Serratia-focused detail with the broader paratransgenesis literature to clarify both its promise and remaining knowledge gaps.
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.
The Genomic Arms Race in Mosquito-Borne Diseases: Integrating Entomopathogenic Fungi, Gene Drive, and Symbiont Technologies for Sustainable Vector Control
35503Rajendran Yamini, Pagalahalli Sankaran Shanmugam, Marimuthu Murugan, et al., J Pure Appl Microbiol., 20:53-65. 2026-01-20 09:32:56.
Mosquito-borne diseases such as malaria, dengue, Zika, chikungunya, and lymphatic filariasis continue to impose enormous health and economic burdens worldwide. The traditional reliance on chemical insecticides has been undermined by the rapid evolution of resistance, ecological concerns, and declining efficacy. Next-generation biocontrol strategies are framed within the concept of a “genomic arms race” between mosquitoes, pathogens, and microbial agents. Entomopathogenic fungi are eco-friendly bioinsecticides with demonstrated efficacy in laboratory, semi-field, and transgenic applications. Symbiont-based approaches, particularly those involving Wolbachia, have been evaluated for their ability to reduce vector competence and spread through populations. Parallel advances in CRISPR-based gene drive technologies have provided transformative tools for population suppression and modification, although their deployment is limited by ethical, ecological, and regulatory concerns. An integrated vector management (IVM) framework combining fungi, gene drives, and symbiont-based tools is proposed as the most promising approach for sustainable mosquito management. This multipronged strategy has the potential to reduce disease transmission, delay resistance development, and minimize ecological disruption, paving the way for resilient, eco-friendly solutions against vector-borne diseases.
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.
Genetic Biocontrol Strategy Considerations for Mosquito Control in the Pacific Island Countries and Territories
35315Adam E. Vorsino, Tim Harvey-Samuel, Limb K. Hapairai, et al., Current Opinion in Insect Science, 2026-01-05 10:49:54.
Mosquito-borne diseases pose an existential threat to the health, economies, and unique ecosystems of Pacific Island Countries and Territories (PICTs). The remoteness of these islands, combined with the presence of highly competent mosquito vectors, complicates disease surveillance and vector control efforts. In response, the PICTs have become a focal point for the development and application of Genetic BioControl (GBC) technologies designed to break vector-borne disease transmission cycles. However, the application of GBC tools in this region warrants careful consideration of its unique history, including a legacy of colonialism, and challenges associated with logistic hurdles. Through meaningful community engagement and authentic collaborations, drawing from local knowledge, and building local capacity, the sustainable, efficient and effective deployment of GBC tools may be achieved.
Wolbachia as a transformative tool for mosquito-borne disease control: a comprehensive review of mechanisms, efficacy, and future directions
35325Minaei, M. E., Yousefi Nojookambari, N., Ghodraty, M., & Yazdansetad, S., Pathogens and Global Health, 2025-12-23 12:15:44.
Mosquito-borne infectious diseases such as dengue, Zika, chikungunya, and malaria continue to pose significant public health challenges worldwide. Traditional control methods, including the use of insecticides and environmental management, have shown limited effectiveness due to insecticide resistance and logistical challenges. Wolbachia-based strategies, which leverage the bacterium’s unique ability to manipulate mosquito reproduction and block pathogens, present a promising, albeit not universally applicable, method for reducing the transmission of mosquito-borne diseases. Field trials have demonstrated significant but variable efficacy. This systematic review synthesizes the latest findings on Wolbachia-based interventions, focusing on their mechanisms, efficacy, and potential for large-scale implementation. We conducted a comprehensive literature search across multiple databases, including PubMed, Scopus, and Web of Science, to identify relevant studies published between 1990 and 2025. Our review highlights the promising results of Wolbachia-based strategies in reducing mosquito populations and disease transmission, while also addressing the challenges and limitations of this approach. We conclude that Wolbachia-based strategies hold great potential for revolutionizing mosquito-borne disease control, but further research and careful consideration of ecological and ethical implications are necessary for their successful implementation.
Rethinking the future of mosquito control
35341Kabirul Bashar, Dr Zonaed Siddiki. Dr Zonaed Siddiki, et al., Dhaka Tribune, 2025-12-17 11:37:26.
Bangladesh is once again in the grip of a severe dengue and chikungunya crisis in 2025. Hospitals are overwhelmed, fever wards are full, and doctors are working tirelessly. Families live in fear of mosquito bites, while daily news reports chronicle rising infections and deaths. As of December 16, 2025, the Directorate General of Health Services (DGHS) has reported more than 100,000 confirmed dengue cases and 409 deaths. However, this figure represents only the tip of the iceberg, as it reflects data solely from hospitalized patients, specifically from 77 hospitals in Dhaka and reports from 64 civil surgeon offices. A substantial number of dengue patients are receiving treatment at home or in various small and large hospitals and clinics that are not included in the official count. This underscores the overwhelming pressure on the country’s health system. At the same time, the Institute of Epidemiology, Disease Control and Research (IEDCR) has recorded a resurgence of chikungunya, reporting 337 suspected cases, 153 of which were laboratory-confirmed in Dhaka between January and May 2025. Researchers estimate that the true number of chikungunya infections this year may be close to one hundred thousand. As chikungunya testing is available only in a limited number of major hospitals in Dhaka, many cases remain undiagnosed and unreported.
Improving Wolbachia-based control programs in urban settings: Insights from spatial modeling
35335Florez D, Cortez R, Hyman JM, Qu Z, PLoS Neglected Tropical Diseases, 19. 2025-12-12 11:08:20.
Arboviral diseases remain a major public health concern, particularly in tropical and subtropical regions where mosquito populations thrive. One promising strategy to curb transmission is the release of Aedes aegypti mosquitoes infected with Wolbachia, a bacterium that reduces their ability to spread viruses. However, past large-scale releases have not always been successful, especially in complex urban settings, where restricted access to certain areas often leads to infection establishment failures and wasted resources. To address this, we developed a spatial model that simulates how Wolbachia-infected mosquitoes are established in different urban environments. We also explored strategies to improve their success under constraints on release size and the efficacy level of insecticide used for pre-release interventions. Our findings suggest that targeted releases are most effective in areas with limited mosquito movement without additional insecticide use. In higher-dispersal areas, reducing at least 35% of wild mosquitoes before release significantly improves establishment within nine months. Additionally, distributing releases over 2-5 weekly batches enhances success more than a single large release, even without other interventions. These findings offer practical insights for designing cost-effective and efficient Wolbachia-based mosquito control programs, reducing the burden of mosquito-borne diseases on vulnerable communities.
A male-drive female-sterile system for the self-limited control of the malaria mosquito Anopheles gambiae
35261Strampelli, A., Willis, K., Gulliford, H.R. et al., Nature Communications, 16. 2025-10-28 08:43:17.
Despite great leaps forward in preventing and treating malaria, several challenges, including insecticide resistance, have hindered progress in fighting the disease. Thus, there is a pressing need for new tools to control malaria, including the use of genetically modified mosquitoes (GMMs) in the field. Various genetic strategies for vector control are currently explored, ranging from self-sustaining GMMs with unrestricted geographic and temporal spread to self-limiting alternatives. Here, we describe a self-limiting gene drive strategy called Male Drive Female Sterile (MDFS) targeting Anopheles gambiae, a major malaria vector. The MDFS genetic construct causes dominant sterility in females, while transgenic males remain fertile, allowing them to transmit the female sterility trait at super-Mendelian rates. Laboratory studies show that repeated releases of MDFS can lead to elimination of caged mosquito populations. Based on these findings, modelling suggests MDFS could be a highly effective and self-limiting strategy for suppressing wild malaria mosquito populations.
Requirements for designing cluster randomised control trials to detect suppression of malaria vector population densities
35239Hancock, P.A., Hui, TY.J., Epopa, P.S. et al., BMC Biology, 23. 2025-10-15 08:17:09.
Novel interventions for mosquito-borne disease control which release modified mosquitoes that are sterilised or genetically modified to cause offspring inviability are progressing towards field applications. Cluster randomised control trials (CRCTs) could provide robust assessment of intervention efficacy in suppressing mosquito populations in field environments, but guidance on designing CRCTs to detect mosquito suppression impacts is limited. We developed statistical models to simulate CRCTs, informed by a 5-year time series measuring densities of malaria vector species from the Anopheles gambiae complex in four villages in western Burkina Faso. We estimated requirements for parallel and step wedge designs, varying the targeted vector species, the suppression effect and the monitoring regime. For a suppression effect of 50%, 21–22 clusters were required to detect suppression with 90% power when all An. gambiae complex species were targeted, while 24–26 clusters were required when only An. coluzzii was targeted and 60–66 clusters were required when only An. gambiae was targeted. For stronger suppression effects, required trial sizes depended less on target species, with 9–10 clusters being sufficient to detect a 90% suppression effect. We investigated how reducing sampling effort, by sampling fewer houses and restricting sampling to rainy season months, affected statistical power. Our results provide empirically based guidance for designing CRCTs to evaluate interventions aiming to suppress malaria vector populations.
CRISPR/Cas9-germline editing of Biomphalaria glabrata: A breakthrough in genetic modification of snails that transmit schistosomiasis
35226Kouhei Oonuma et al., Science Advances, 11. 2025-10-09 10:03:53.
Human schistosomiasis remains one of the most devastating parasitic diseases worldwide, and the development of genetically modified vector snails has long been a goal in the field. Here, we report the successful creation of genetically modified Biomphalaria glabrata, an important intermediate host, using CRISPR/Cas9 gene editing. We targeted the fibrinogen-related protein 3.1 (FREP3.1) gene, confirmed stable germline transmission of the mutated gene, and established two different homozygous FREP3.1-edited lines. Disruption of the FREP 3.1 gene did not alter snail susceptibility to Schistosoma mansoni infection, possibly due to a limited role of FREP3.1 in resistance or to functional redundancy and/or compensatory expression within the highly diverse FREP gene family. Our study demonstrates successful germline editing, effective ex ovo culture of decapsulated embryos, and the generation of viable, genetically modified B. glabrata snails, thereby establishing a foundation for future genetic strategies to control schistosomiasis.
Bacteria-mediated dsRNA delivery for mosquito-borne virus control
35219Mine Altinli, Sean P. Leonard, Alain Kohl, et al., Trends in Parasitology, 41:880-893. 2025-10-05 14:37:07.
Mosquito-borne viruses represent an increasing global public health threat, exacerbated by urbanisation and climate change, thus making effective mosquito control essential. RNA interference (RNAi), a sequence-specific gene regulation mechanism, can be a flexible vector control tool. RNAi effectors, such as double-stranded RNA (dsRNA), can target mosquito genes or the viruses they carry, disrupting development or suppressing infection. However, current RNAi delivery methods are ineffective. Engineered bacterial symbionts offer a promising alternative for delivery, as they can produce dsRNA directly within mosquitoes. However, bacterial RNAi delivery in mosquitoes remains underexplored. We review emerging genetic tools, insights from RNAi and bacteria–mosquito interactions to outline priorities for realising bacterial RNAi as an efficient and sustainable vector control strategy.
Dispersal and survival of gamma-irradiated Culex quinquefasciatus: Implications for sterile insect technique applications
35207Nungki Hapsari Suryaningtyas, Raden Wisnu Nurcahyo, Beni Ernawan, et al., Open Veterinary Journal, 15:3054-3062. 2025-10-02 14:51:05.
Culex quinquefasciatus is a major vector of filariasis and other mosquito-borne diseases. The sterile insect technique (SIT) has been widely used to suppress mosquito populations, but its effectiveness depends on the dispersal, survival, and competitiveness of sterile males. This study evaluated the dispersal range, survival rate, and recapture success of gamma-irradiated Cx. quinquefasciatus under field conditions. A mark-release-recapture (MRR) experiment was conducted using sterile male and female Cx. quinquefasciatus. Two release events were conducted, and recapture data were collected over seven days using BG-Sentinel-2 traps baited with octanol placed within a 250-m radius. The irradiated males traveled an average of 143.18 m (FR50: 92.78 m; FR90: 220.02 m), and the females dispersed 146.26 m (FR50: 95.26 m; FR90: 227.25 m). Dispersal distance was significantly influenced by release site in males (p = 0.0089) and females (p = 0.0042) but not by recapture day (p > 0.89). Recapture location significantly affected dispersal in both sexes (p < 0.0001). The daily survival probabilities of males and females were 0.88 and 0.69, respectively, with corresponding life expectancies of 7.57 and 2.71 days. The dispersal and survival of sterile Cx. quinquefasciatus are affected by release strategies. To optimize SIT, further studies should refine the marking techniques, explore a combination of trapping methods, and evaluate the dispersal patterns across varied landscapes. These findings offer valuable insights into improving the implementation of SIT for Cx. quinquefasciatus population control.
Suppression of Aedes albopictus in Sri Lanka using the Sterile Insect Technique (SIT) with a sustained effect
35157Menaka Hapugoda, Nilmini Silva Gunawardene, Tharaka Ranathunge, Sudath Samaraweera, K. Karunathilake, Bazoumana B.D. Sow, Gayan Parakrama Withanage, Indika Weerasinghe, Hamidou Maiga and Jeremy Bouyer, Parasite, 32. 2025-09-22 10:50:08.
Dengue fever remains a significant public health concern in Sri Lanka, leading to recurrent epidemics and imposing substantial socio-economic burdens. This study aimed to assess the efficacy of the Sterile Insect Technique (SIT) against Aedes albopictus (Skuse), the predominant dengue vector in the country, through a pilot field trial of an Integrated Vector Management (IVM) strategy including the SIT. The pilot trial was conducted in the Gampaha district, which reports the second-highest number of dengue cases in the country. A total of 3,300,000 sterile males, exposed to a 50 Gy radiation dose, were released over 33 weeks (100,000/week) within a 30-hectare release area. Entomological assessments were conducted at 115 trapping stations over a period of 71 weeks (October 2020–August 2022). Induced sterility of 98.16% in mosquito eggs was reached within the release area as compared to the control area (binomial generalized linear mixed model, deviance 2.408, df = 2, p = 0.016), indicating a notable impact of the SIT. The trial achieved nearly 98% suppression of adult vector mosquitoes, with a sustained suppression effect for 13 weeks post cessation of releases. These findings suggest that SIT can be effectively integrated as a potential additional tool into the future IVM strategy in Sri Lanka.
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.
Reprogramming Sex for Vector Control: Maleness-Associated Transgenes in Aedes albopictus
35151Doron Shalom Yishai Zaada, Philippos Aris Papathanos, Eric Marois, Current Opinion in Insect Science, 2025-09-22 10:21:15.
Among other challenges, the world currently faces the expansion of pest insects such as the tiger mosquito Aedes albopictus, a growing threat to public health due to the pathogens it can transmit. Current control approaches based on insecticides or elimination of mosquito larval breeding sites are insufficient to suppress this highly invasive species. The discovery of Nix, a gene necessary and sufficient to determine the male sex in this mosquito, opens new prospects for genetic control strategies, in particular those based on transgenes that convert females into males, or that reduce female fitness. Such forms of genetic control could be effective on larger spatial and time scales compared to classical control approaches. This overview of current and emerging genetic control strategies targeting Aedes mosquitoes emphasizes the unique characteristics of Ae. albopictus, that make it particularly amenable to masculinization-based genetic control.
Genetically engineered mice could take the bite out of Lyme disease on Nantucket, scientists say
35149Jon LaPook, Denise Schrier Cetta, Aliza Chasan, Katie Brennan, CBS News, 2025-09-21 10:07:27.
Over the past 40 years, Dr. Timothy Lepore has been the emergency room head, sole surgeon and medical examiner on Nantucket, a small island off Cape Cod, Massachusetts. Today he runs the only private practice, where he treats dozens of patients with Lyme disease each year. About 15% of residents on the island have been afflicted with the disease, which can cause a wide range of symptoms like a fever, rash, facial paralysis, an irregular heartbeat and arthritis. Lepore, 80, may finally be able to retire if a team of scientists' dream to curb the transmission of Lyme disease on the island becomes a reality. The scientists' target is not the deer or ticks often associated with the disease: it's wild mice, the main host of Lyme bacteria. The hope is that by genetically engineering mice to be immune to Lyme and releasing them in Nantucket, the population of mice able to spread Lyme disease on the island will shrink. The problem on Nantucket can be traced back to 1926, when the community voted to import two female deer to the island to give a lone buck company. On top of that, by the 1950s, half the land on the island was put into conservation. The untamed brush and wild grasslands create an ideal ecosystem for Lyme's hosts to thrive. As the deer population grew, so did the population of ticks. Deer don't get Lyme, but female ticks feed on them, and then lay as many as 2,000 eggs in a single batch. Deer also spread the disease as thousands of them carry ticks across Nantucket. Not all ticks carry Lyme disease, and a tick bite doesn't guarantee the transmission. Even if the tick is carrying Lyme, the tick has to be attached for more than 24 hours to infect someone.
Wolbachia Infection in Iranian Malaria Vectors: Prevalence and Biocontrol Implications
35124Shahin Saeedi, Fateh Karimian, Seyed Hassan Moosa-Kazemi, et al., Tropical Medicine & International health, 2025-09-08 08:50:24.
Wolbachia-based vector control is an emerging tool in malaria prevention research. This study evaluates Wolbachia infection in Iranian mosquitoes, focusing on seven known malaria vectors. Mosquitoes were collected from nine provinces of Iran (2016–2019), and Wolbachia infection status was analysed via PCR targeting eight genes: wsp, gatB, ftsZ, dnaA, groEL, gltA, CoxA and fbpA. We examined 1094 specimens from seven malaria vectors (Anopheles stephensi Liston, 1901; Anopheles culicifacies s.l. James, 1901; Anopheles fluviatilis s.l. James, 1902; Anopheles maculipennis s.l. Meigen, 1818; Anopheles sacharovi Favr, 1903; Anopheles dthali Patton, 1905; Anopheles superpictus s.l. Grassi, 1899), four non-malaria vectors (Anopheles mongolensis Linton, Lee and Curtis, 2005; Anopheles hyrcanus Pallas, 1771; Anopheles claviger Meigen, 1804; Anopheles turkhudi Liston, 1901) and three Culex species (Culex pipiens Linnaeus, 1758; Culex perexiguus Theobald, 1903; Culex theileri Theobald, 1903). PCR revealed Wolbachia DNA exclusively in An. dthali and Culex species, with infection rates of 73.4% for An. dthali and 77.78%–96.77% for Culex, notably higher in males. Wolbachia was detected in all regions except one in the north. Phylogenetic analysis revealed Wolbachia strains in An. dthali and Culex belong to supergroup B, closely related to strains in An. moucheti and An. demeilloni. This suggests broader applications for biocontrol strategies. The high Wolbachia prevalence in An. dthali is promising for malaria prevention. Future research should confirm cytoplasmic incompatibility and explore wAdth's potential to block malaria transmission.
Application of Sterile Insect Technique (SIT) for Aedes albopictus (Skuse, 1895) in Sri Lanka: Dose optimization, mating competitiveness and release ratios
35114Harishchandra J, Abeyewickreme W, Premaratne R, Hapugoda M, PLoS One, 20. 2025-09-05 08:04:10.
Sri Lanka has experienced severe dengue epidemics in recent years, despite the extensive vector control measures taken. Therefore, it is necessary to find sustainable vector control strategies against dengue. Novel vector control tools need to be tested for the feasibility of applying them against local vectors. Sterile Insect Technique (SIT) is an increasingly popular vector control technique which has been adopted by many countries to suppress insect pest populations and is being tested for dengue vectors. In this study, SIT was developed for Aedes albopictus (Skuse, 1895), one of the 2 dengue vectors present in Sri Lanka. The optimum radiation dose for sterilizing male pupae (age 24–48 hours) using a Co 60 source was determined based on the post-irradiation pupal and adult survival in males and induced sterility in females at different doses. Further, the effect of irradiation on mating competitiveness of the selected mosquito strain was assessed under laboratory and semi-field conditions. The optimum release ratio of irradiated males to wild males was assessed in laboratory and semi-field settings. The optimum radiation dose was 50 Gy among the series of doses (25, 30, 40, 50, 60, and 70 Gy) tested. When pupae were exposed to the optimal radiation dose, 100% pupal survival, 19-day median adult survival time and 99% induced sterility resulted. A 5:1 ratio of irradiated males to non-irradiated laboratory-reared or wild males in laboratory cages resulted in induced sterility of 75% and 62%, respectively. The respective values were 74% and 61% in large semi-field cages. Fried Competitiveness Index (FCI) of irradiated males against wild males of laboratory and wild origin were 0.63 and 0.43 in laboratory cages and 0.57 and 0.55 in large semi-field cages. The males of Ae. albopictus irradiated at 50 Gy are adequately sterile and are competitive against the wild males. The release ratio of 5:1 irradiated males to wild males is a suitable ratio for the field application of SIT. The findings of the study will be important for the development of a protocol for future application of SIT for Ae. albopictus in Sri Lanka.
Long-Term Durability and Public Health Impact of City-Wide wMel Wolbachia Mosquito Releases in Niterói, Brazil, During a Dengue Epidemic Surge
35107Anders, Katherine L., Gabriel Sylvestre Ribeiro, Renato da Silva Lopes, Pilar Amadeu, Thiago Rodrigues da Costa, Thais Irene Souza Riback, Karlos Diogo de Melo Chalegre, Wesley Pimentel de Oliveira, Cátia Cabral da Silva, Marcos Vinicius Ferreira Mendes B, Tropical Medicine and Infectious Disease, 10. 2025-09-02 18:57:03.
In 2024, the Americas experienced the largest dengue outbreak on record and Brazil was among the worst affected countries, reporting 6.6 million cases and 6200 deaths. We report the long-term entomological and epidemiological effectiveness of city-wide deployment of wMel-strain Wolbachia-infected Aedes aegypti in Niterói, a city of half a million people in Rio de Janeiro state, where Wolbachia releases across three-quarters of the urban population in 2017–2019 were expanded to remaining populated areas in 2023. wMel was durably established at ≥95% prevalence in Ae. aegypti populations throughout Niterói four years post-release, and up to seven years in the earliest release sites. Notified dengue case incidence in Niterói was 89% lower following Wolbachia releases, compared to the 10-year pre-intervention period of 2007–2016. Dengue incidence in Niterói in 2024, during a period of record high incidence in Brazil and the region, was 374 per 100,000 population, substantially lower than overall in Rio de Janeiro state (1884 per 100,000) and nationwide in Brazil (3157 per 100,000). Our findings show that city-wide Wolbachia coverage in Niterói provided sustained population-level reduction in dengue incidence throughout the five years post-intervention, including during the 2024 epidemic surge, averting an estimated three-quarters of the dengue case burden that may otherwise have been expected in Niterói in 2024.
Comparison of the standard and boosted sterile insect techniques for the suppression of Aedes albopictus populations under semi-field conditions
35085Marlène Dupraz, Renaud Lancelot, Gorgui Diouf, et al., Parasite, 32. 2025-08-28 18:38:54.
Innovative control tools are needed against Aedes mosquitoes. The boosted sterile insect technique (bSIT) consists of treating sterile males with a biocide prior to their release to contaminate larval habitats. We compared the efficacy of SIT and boosted SIT to prevent the emergence of adult Aedes albopictus in large cages. We tested two sterile-to-fertile male ratios: 5:1 (SIT5) and 1:1 (SIT1), with and without pyriproxyfen enhancement (bSIT or SIT). The eggs were collected in ovitraps and the immature stages were monitored until adult emergence or up to 15 days after hatching to estimate the relative risk (RR) of adult emergence compared to the control category. The concentration of pyriproxyfen in the ovitrap water did not change when sterile males were released with females or alone (χ2 = 0.99, df = 1, p = 0.547). This concentration was higher when the sterile-to-fertile male ratio was increased from 1:1 to 5:1: χ2 = 18.8, df = 1, p = 0.006. All four treatment categories were effective in suppressing mosquito populations. With a relative risk RR = 0.194 95% CI [0.128; 0.275], SIT5 was the most effective. Boosted SIT was not as effective as SIT. However, bSIT1 (RR = 0.418 [0.351; 0.492]) and bSIT5 (RR = 0.512 [0.431; 0.596]) were equally effective. Boosted males directly vectored pyriproxyfen to breeding sites. Boosted SIT was more effective than SIT alone with a low sterile-to-fertile male ratio. Under operational conditions, it could be initially deployed to suppress the target population and then switched to standard SIT.
Emerging challenges for mosquito-borne disease control and the promise of symbiont-based transmission-blocking strategies
35064Gao H, Hu W, Cui C, Wang Y, Zheng Y, Jacobs-Lorena M, et al., PLoS Pathog, 21. 2025-08-26 17:16:49.
Mosquitoes serve as vectors for a variety of pathogens that cause life-threatening diseases, such as malaria, dengue, Zika, and yellow fever. With the rise of antimalarial drug resistance and a lack of therapeutics or prophylactics for dengue and Zika, current disease control strategies rely heavily on mosquito population management. However, the effectiveness of conventional approaches is increasingly compromised, highlighting an urgent need for innovative tools to combat mosquito-borne diseases. One promising strategy for blocking the transmission of these diseases is to populate mosquitoes with anti-pathogen gut symbionts. Here, we discuss the major challenges facing current mosquito-borne disease control efforts and explore how mosquito gut microbiota-based control strategies may address them. We highlight recent advances that may accelerate field applications and offer perspectives on future directions and the translational potential of symbiont-based strategies for mitigating mosquito-borne disease transmission.
Effectiveness of the sterile insect technique in controlling Aedes albopictus as part of an integrated control measure: evidence from a first small-scale field trial in Switzerland
35042Parrondo Monton, D., Ravasi, D., Campana, V. et al., Infect Dis Poverty, 14. 2025-08-24 16:54:24.
The invasive Asian tiger mosquito (Aedes albopictus) poses growing health risks across Europe. In Switzerland, a preliminary field trial was conducted to assess the feasibility of integrating the sterile insect technique (SIT) into existing integrated vector management (IVM), which includes breeding site removal and application of biological larvicides. SIT involves repeated releases of irradiated sterile males, which mate with wild females, producing non-viable eggs and leading to population decline. Following a preliminary release test in 2022, a small-scale SIT trial took place in 2023 in Morcote, Switzerland. Approximately 150,000 sterile males were released weekly over a 45-hectare area throughout the entire mosquito activity season, from May to September. This SIT area also received routine IVM. Population dynamics were compared with a control area where only IVM was applied. Monitoring included egg counts, hatch rates, and adult female densities. Generalized additive mixed-effects models (GAMM) and generalized additive models (GAM) accounted for spatial, temporal, and random effects. Model selection used AIC, BIC, and Chi-square tests (significance at 5%). The SIT-treated area showed a significant mosquito population reduction. Egg counts dropped by 57% (GAMM regression coefficient: − 0.8513, P < 0.001), with temporal patterns differing between SIT-treated and control areas (P < 0.001). Egg hatch rates were also lower in the SIT area, with odds of hatching reduced by 1.24 log-odds units (P < 0.001). Adult female densities declined by 66% (regression coefficient: − 1.0818, P < 0.001). Spatial GAMs revealed heterogeneous effects: up to 90% egg reduction in the western release area, while the eastern edge, bordering untreated zones, showed up to 300% higher egg counts. Similar spatial trends were observed for hatch rates and adult females (P < 0.01). These findings highlight both the overall effectiveness of SIT and the influence of mosquito immigration on spatial patterns. This trial demonstrated the potential of SIT as a complementary tool in Swiss vector control. Public interest and acceptance were high. To improve cost-effectiveness, further optimization of male production, sterilization, transport, and release processes is needed. Continued implementation over multiple seasons is recommended to enhance long-term effectiveness.
Knowledge, attitude, and practice (KAP), and acceptance and willingness to pay (WTP) for mosquito-borne diseases control through sterile mosquito release in Bangkok, Thailand
34991Kittayapong P, Ninphanomchai S, Jalichandra N, Sringernyuang L, Sherer P, Meemon N, PLoS Negl Trop Dis, 19. 2025-07-30 11:03:04.
A questionnaire survey was conducted in seven communities in Bangkok, Thailand to obtain baseline information on knowledge, attitudes and practices (KAP) related to mosquito-borne diseases, i.e., dengue, chikungunya and Zika, including mosquito vectors and how to control them. The questionnaire also asked about the acceptance and willingness to pay (WTP) for sterile mosquitoes used in controlling mosquito populations. Our results showed that, from a total of 400 sampling households, about 85% of participants were familiar with dengue and its mosquito vectors, as well as their prevention and control. Furthermore, participants with lower ages and higher incomes had more knowledge on mosquito vectors (p < 0.05). Even though the majority of participants did not have any knowledge on sterile mosquito release, they showed a positive perception about it. However, more than half of them were not willing to pay for sterile mosquitoes, since they would like to receive them as public support from the government. If they were to pay, the cost that they could afford was 1–2 THB (~US$ 0.03- 0.06) per sterile mosquito. These findings should be useful for public health authorities when planning to apply the sterile mosquito release as an alternative mosquito control approach in Bangkok, Thailand.
Vector Control District Plans Experimental Mosquito Control Program
34982Contributing Editor, MyNewsLA.com, 2025-07-24 09:51:29.
Batches of irradiated male mosquitoes are slated for release Wednesday in Lake Elsinore with the goal of pairing the modified insects with as many females as possible to kill off the overall mosquito population, under an experimental program that apparently hasn’t generated concerns among public officials. The “Sterile Insect Technique Pilot Program” is being managed by the Northwest Mosquito & Vector Control District, which serves segments of western Riverside County. The district is believed to be the first countywide to inaugurate an SIT mosquito control program. Questions regarding when it was authorized, the estimated number of modified mosquitoes that will be released and any potential public health risks were not answered by the agency as of Tuesday afternoon. Lake Elsinore officials also did not respond to requests for comment. The West Valley Mosquito & Vector Control District, which encompasses Ontario, Montclair and neighboring municipalities in San Bernardino County, was the first district in California to receive authorization from state regulators to initiate mosquito SIT releases last year, under a pilot program similar to that of the Northwest Mosquito & Vector Control District. It’s still unknown whether West Valley’s experimental program has netted any benefits. “Sterile male mosquitoes are released to mate with local females, and the resulting eggs are unable to hatch,” NMVCD said in a statement regarding the Lake Elsinore program. “The release of adult male mosquitoes will not increase local bite pressure, as only female mosquitoes bite.”
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.
Integrated vector management with the sterile insect technique component for the suppression of Aedes aegypti in an urban setting in Indonesia
34954Sasmita HI, Neoh K-B, Ernawan B, Indarwatmi M, Nasution IA, Fitrianto N, et al., PLoS Neglected Tropical Diseases, 2025-07-08 13:14:26.
The sterile insect technique (SIT) involves subjecting laboratory-bred male mosquitoes to radiation, typically gamma rays, X-rays, or electrons, that render them sterile. These sterile male mosquitoes are then released into the field to mate with wild female mosquitoes. From that mating, no viable eggs are produced. The SIT is a mosquito population control strategy that prevents the spread of the dengue virus through Aedes aegypti female mosquitoes. Considerable progress has been made regarding the SIT, and its effectiveness has been tested in numerous regions for managing local mosquito populations. In the present study, the field performance of sterile male mosquitoes was evaluated through a mark–release–recapture study, which was followed by an SIT trial. In an SIT pilot trial, pre-release control measures, including insecticide application and mosquito breeding site removal, were applied within the framework of integrated vector management. Community engagement activities were designed to ensure community acceptance and support for the SIT. The trial led to substantial reductions in the egg hatching, numbers of eggs and female mosquitoes despite challenges related to sterile male production and population isolation. This study revealed the key factors contributing to the success of an SIT trial to be the field performance of sterile male mosquitoes, complementary vector control methods, population isolation, and support from local residents.
Extended time to maturity in Anopheles coluzzii: Implications of late egg hatch for vector control and transgene fitness
34947Emmanuel C. Ottih, Joe M. Roberts, Toby J. A. Bruce, Frédéric Tripet, Medical and Veterinary Entomology, 2025-06-24 10:11:30.
Maintaining fitness is an important consideration when mosquitoes are mass-reared for the deployment of genetic interventions that are designed to suppress populations because released mosquitoes need to compete with wild-type mosquitoes. Late-hatching mosquitoes are more suitable for transportation to remote field sites. Here, we investigated the fitness of late-hatching phenotypes in Anopheles coluzzii. Selected lines of the VK strain (from Burkina Faso) were created through bidirectional selection for early and late hatching, over 20 generations. These were compared with each other and the established Mopti reference strain from Mali, reared in the lab for >16 years. Significant differences in life-history traits were found between Mopti and VK strains but few differences were found between the selected VK lines. Considering that late-hatching VK lines showed no evidence of fitness costs, our results suggest that the late selected VK lines, which start hatching after 4 days, are an alternative option for egg shipment for mass mosquito releases over the well-established Mopti that hatches within 2 days and has lower adult survival.
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.
Suppression of Aedes mosquito populations with the boosted sterile insect technique in tropical and Mediterranean urban areas
34854Bouyer, J., Gil, D.A., Mora, I.P. et al., Scientific Reports, 15. 2025-05-26 20:31:16.
Aedes mosquitoes are the vectors of dengue viruses and other arboviruses, which threaten billions of people all over the world. The boosted sterile insect technique (boosted SIT) is a version of SIT in which irradiated sterile males also transmit a biocide to immature stages. We describe three field trials that were run in 2021: one against Aedes aegypti in La Reunion and two against Aedes albopictus in Spain, each using pyriproxyfen as a biocide. The relative density of adults (compared to their density in control sites: without sterile male release) decreased from 1.00 to 0.09, 95% credible interval [0.06, 0.15] (La Reunion, July) and to 0.02 [0.01, 0.03] and 0.11 [0.08, 0.16] (Spain, July and October). The success rate, corresponding to the proportion of traps with suppression greater than 80%, ranged from 0.43 to 0.71 in La Reunion, from 0.26 to 1.00, and from 0.50 to 0.70 in Spain. In Spain, suppression with boosted SIT was higher than with non-boosted SIT, in 2020 and 2022. This work is in line with the predictions of the model of a better efficacy of boosted SIT compared to SIT, together with partial protection from invasion of treated areas by fertile females, paving the way for larger-scale field trials.
Spiroplasma infection in colonized Glossina fuscipes fuscipes: impact on mass rearing and the sterile insect technique
34846Kiswend-sida M. Dera, Daouda Tande Barro, Bénéwendé Aristide Kaboré, et al, Insect Science, 2025-05-26 20:02:52.
Tsetse flies (Glossina spp.) can vector the parasites (Trypanosoma spp.) that cause the socioeconomically devastating neglected tropical diseases human and animal African trypanosomoses. In addition to this parasite, tsetse can harbor four genera of endosymbiotic bacteria, including Wigglesworthia, Sodalis, Wolbachia, and Spiroplasma, which are functionally crucial for the fly's physiological homeostasis and/or are potentially useful for the development of disease control strategies. Recent discoveries indicate that Spiroplasma infection negatively impacts tsetse fecundity. Conversely, housing the bacterium can benefit its fly host by making it unusually refractory to infection with parasitic African trypanosomes. In this study, we assessed the physiological impact of Spiroplasma infection on a laboratory colony of Glossina fuscipes fuscipes (Gff). For this purpose, two distinct Gff colonies were established: a Spi– colony that harbors a low Spiroplasma infection prevalence and a Spi+ colony that harbors a high Spiroplasma infection prevalence. Fitness parameters for both colonies revealed no significant differences in the length of larval development, adult eclosion rate, and flight propensity. However, flies from the Spi+ colony presented with lower fecundity and higher overall mortality than did individuals from the Spi– colony. Furthermore, males from the Spi– colony exhibited a competitive mating advantage over their Spi+ counterparts in a field cage setting. These findings have potential implications for the improvement of mass-rearing of Gff for sterile insect technique (SIT) applications.
Overview of the sterile insect technique for Aedes aegypti in Lee County, Florida, USA
34841Morreale, R., Stenhouse, S., Bajonero, J. et al., Infectious Diseases of Poverty, 14. 2025-05-12 20:10:08.
Lee County Mosquito Control District (LCMCD) is an independent taxing district that works to protect human health and improve quality of life in Lee County, Florida, USA. With local dengue transmission in southern Florida, LCMCD prioritized the control of Aedes aegypti. Due to the cryptic larval habitats of Ae. aegypti and insecticide resistance, effective control using conventional methods is difficult. Thus, the sterile insect technique (SIT) program, using X-ray irradiated male mosquitoes, was created to target Ae. aegypti. The goal of this program was to suppress Ae. aegypti through establishing a robust SIT program and performing a pilot study in the field to assess the impacts of SIT releases. The SIT program at LCMCD released sterile male Ae. aegypti from 2020 to 2022 in Captiva Island, Florida. The SIT program works within a larger Integrated Mosquito Management (IMM) framework and is not a standalone tool. The SIT program consists of nine employees, one of which is dedicated to quality assurance. Quality assurance assessments are performed routinely and periodically. Due to widespread destruction throughout Captiva and Sanibel Islands from Hurricane Ian in September 2022, the SIT pilot in Captiva Island was concluded and moved to Fort Myers, Florida. During the pilot study on Captiva Island, various lessons were learned and this knowledge has been applied to efforts in Fort Myers. LCMCD has established a successful SIT program to suppress populations of Ae. aegypti. Through connections with the International Atomic Energy Agency (IAEA) and the University of Florida, LCMCD received guidance from experts in the field to help ensure the program’s success. Stable funding through taxes levied specifically for mosquito control provided essential consistency, allowing the program to grow and evolve. Consistent trapping routines provided immense amounts of entomological data. Thoughtful and intentional community engagement was essential in ensuring acceptance of the SIT program in Lee County. Following the phased conditional approach suggested by IAEA, LCMCD has built an effective and resilient SIT program. The integration of the SIT as a tool of an area-wide mosquito control program is a feature that distinguishes LCMCD’s SIT program from others.
Optimizing Cost-Effective Larval Diets for Mass Rearing of Aedes Mosquitoes in Vector Control Programs
34810Li, Q., Wei, T., Sun, Y., Khan, J., & Zhang, D., Insects, 16. 2025-05-04 15:43:50.
Larval diet composition significantly influences the developmental, physiological, and reproductive traits of Ae. albopictus and Ae. aegypti, major arbovirus vectors. Optimizing larval nutrition is essential for mass-rearing programs supporting the sterile insect technique and incompatible insect technique. This study evaluated the effects of three larval diets on key fitness traits, including pupation rate, male flight ability, adult longevity, female fecundity, pupal size, and wing length, which are critical for the success of SIT and IIT programs. (2) Methods: Ae. albopictus (GT strain) and Ae. aegypti (AEG strain) were reared on three diets with varying protein sources: diet 1 (≈1.23 dollars/kg; porcine liver/shrimp/yeast = 6:3:1), the IAEA-recommended diet; diet 2 (≈1.78 dollars/kg; bovine liver/shrimp/yeast = 6:3:1), a modified IAEA diet; and diet 3 (≈0.55 dollars/kg; tortoise food), a low-cost laboratory formulation. Life history traits were assessed using standardized protocols, and data were analyzed with ANOVA and Tukey’s post hoc test. (3) Results: Diet 3 consistently improved pupation rates, adult longevity, and male flight ability compared with diet 2. Mosquitoes reared on diets 1 and 3 exhibited significantly larger pupae and longer wings, while diet 2 performed sub-optimally. Adult eclosion rates (~100%) remained high across all diets. Male flight ability varied by species, with Ae. albopictus performing best on diet 1 and Ae. aegypti on diet 3. Female fecundity was diet-dependent, with diet 1 favoring Ae. albopictus and diet 3 benefitting Ae. aegypti. Longevity was highest in mosquitoes reared on diet 3, with a median survival of 19.5 days for GT males and 37.5 days for GT females. (4) Conclusions: Diet 3 emerged as the most cost-effective option, enhancing key fitness traits essential for SIT and IIT. Future studies should refine nutrient formulations and validate findings under field conditions to optimize mass-rearing efficiency in vector control.
Synthetic Homing Endonuclease Gene Drives to Revolutionise Aedes aegypti Biocontrol – Game Changer or Pipe Dream?
34756Joshua X.D. Ang, Sebald A.N. Verkuijl, Michelle A.E. Anderson, Luke Alphey, Current Opinion in Insect Science, 2025-04-10 09:10:46.
The increasing burden of Aedes aegypti-borne diseases, particularly dengue, is a growing global concern, further exacerbated by climate change. Current control strategies have proven insufficient, necessitating novel approaches. Synthetic homing endonuclease gene (sHEG) drives represent one of the few emerging technologies with the potential to offer a cost-effective and equitable solution to this escalating public health challenge. However, despite multiple attempts, the homing efficiencies of Ae. aegypti sHEG systems lag behind those achieved in Anopheles mosquitoes. We discuss key insights from efforts to develop sHEGs in Ae. aegypti and highlight critical factors that may unlock further advances in this species.
Comparison of oviposition and adult trapping to monitor wMel introgression for Wolbachia-based vector control
34738Nelson, E., Pereira, T.N., Ribeiro E., et al., bioRxiv, 2025-04-03 17:36:42.
Wolbachia introgression into Aedes aegypti mosquito populations has been shown to be effective in preventing dengue and is being evaluated for WHO prequalification. Monitoring the long-term introgression of Wolbachia (wMel)-positive Aedes aegypti mosquitoes, however, requires labor-intensive and costly BG-Sentinel traps (BG-traps). More affordable alternatives, such as using oviposition traps (ovitraps), have not been fully evaluated. Ae. aegypti eggs and adults were collected from 124 ovitraps and 237 BG-traps, respectively, across 12 clusters in Belo Horizonte, Brazil from March to May 2023 as part of the EVITA Dengue trial. We used a qPCR assay to detect wMel in a sample of L3-L4 stage larvae (up to 29) that were reared from eggs in ovitraps and adults from BG-traps (up to 10 per BG-trap). We used mixed effects models to compare estimates of cluster-level wMel introgression from ovitrap and BG-trap data over time. Among 3,675 larvae reared from ovitraps, wMel prevalence was 0.50 (95% CI: 0.48-0.51). Among 1,244 adult Ae. aegypti tested from BG-traps, wMel prevalence was 0.45 (95% CI: 0.42-0.48). Cluster-level wMel introgression in larvae and adults was highly correlated (Spearman’s r = 0.70, p = 6.71e-06). Multivariate analysis found that ovitrap estimates of introgression were associated with BG-trap estimates in the same month when models incorporated the previous month’s ovitrap wMel-positive count, the proportion of wMel in ovitraps in the current and previous month, and Ae. aegypti abundance. Leveraging this model, predicted wMel introgression from ovitrap data were highly correlated with observed introgression from BG-trap data (rs,counts=0.98, p=1.53e-14; rs,prevalences=0.82, p=0.11e-05) and provided greater precision than crude ovitrap-based estimates.
Exploiting Wolbachia as a Tool for Mosquito-Borne Disease Control: Pursuing Efficacy, Safety, and Sustainability
34677Moretti, R., Lim, J. T., Ferreira, A. G. A., et al, Pathogens, 14:285. 2025-03-28 09:41:16.
Despite the application of control measures, mosquito-borne diseases continue to pose a serious threat to human health. In this context, exploiting Wolbachia, a common symbiotic bacterium in insects, may offer effective solutions to suppress vectors or reduce their competence in transmitting several arboviruses. Many Wolbachia strains can induce conditional egg sterility, known as cytoplasmic incompatibility (CI), when infected males mate with females that do not harbor the same Wolbachia infection. Infected males can be mass-reared and then released to compete with wild males, reducing the likelihood of wild females encountering a fertile mate. Furthermore, certain Wolbachia strains can reduce the competence of mosquitoes to transmit several RNA viruses. Through CI, Wolbachia-infected individuals can spread within the population, leading to an increased frequency of mosquitoes with a reduced ability to transmit pathogens. Using artificial methods, Wolbachia can be horizontally transferred between species, allowing the establishment of various laboratory lines of mosquito vector species that, without any additional treatment, can produce sterilizing males or females with reduced vector competence, which can be used subsequently to replace wild populations. This manuscript reviews the current knowledge in this field, describing the different approaches and evaluating their efficacy, safety, and sustainability. Successes, challenges, and future perspectives are discussed in the context of the current spread of several arboviral diseases, the rise of insecticide resistance in mosquito populations, and the impact of climate change. In this context, we explore the necessity of coordinating efforts among all stakeholders to maximize disease control. We discuss how the involvement of diverse expertise—ranging from new biotechnologies to mechanistic modeling of eco-epidemiological interactions between hosts, vectors, Wolbachia, and pathogens—becomes increasingly crucial. This coordination is especially important in light of the added complexity introduced by Wolbachia and the ongoing challenges posed by global change.
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.
Assessing Radiation-Induced Enzyme Activation in Aedes aegypti: Potential Challenges for SIT-Based Vector Management
34370Edvane Borges da Silva, Sloana Giesta Lemos Florêncio, Ademir Amaral, et al., Acta Tropica, 261. 2025-01-28 14:35:08.
This study characterizes the Aedes aegypti population from Fernando de Noronha Island, Pernambuco, Brazil, prior to implementing the Sterile Insect Technique (SIT). The main objective was to assess changes in glutathione S-transferase (GST) enzyme activity, previously linked to cypermethrin resistance in this population, in 2010. GST activity was measured in both male and female mosquitoes, mass-produced in the lab, after exposure to ionizing radiation. The population evaluation after six years showed complete susceptibility to cypermethrin, deltamethrin, and lambda-cyhalothrin, although GST activity remained altered, increasing further following irradiation (50% higher in irradiated males and 31% higher in irradiated females compared to non-irradiated controls). This stress response to gamma radiation suggests implications for the effectiveness and viability of sterile males, particularly when SIT is combined with chemical insecticides. These findings enhance our understanding of radiation's impact on metabolic responses of the sterile males and provide valuable insights for refining integrated control strategies in vector management programs.
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.
A comprehensive review of biological and genetic control approaches for leishmaniasis vector sand flies; emphasis towards promoting tools for integrated vector management
34611Kumari, Y., Gunathilaka, N., Amarasinghe, D., PLOS Neglected Tropical Diseases, 19. 2025-01-27 11:07:43.
Leishmaniasis is a health problem in many regions with poor health and poor life resources. According to the World Health Organization (WHO), an estimated 700,000–1 million new cases arise annually. Effective control of sand fly vector populations is crucial for reducing the transmission of this disease. Therefore, this review aims to comprehensively examine and evaluate the current methods for controlling sand fly populations, focusing on biological and gene drive techniques. A detailed, comprehensive literature search was carried out using databases including Google Scholar, PubMed, ScienceDirect, and the National Library of Medicine (NIH). These searches were done using specific keywords related to the field of study. This current review identified several promising methods, including genetically modified sand flies, using transgenic approaches by taking advanced gene editing tools like Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9) and genetic modification of symbiotic microorganisms for controlling sand fly populations, which appeared to be proven under laboratory and field settings. Genetic control approaches have many benefits over chemical control, including long-lasting effects on targets, high specificity, and less environmental impact. Advances in genetic engineering technologies, particularly CRISPR/Cas9, sterile insect techniques, and gene drive insect modification, offer new avenues for precise and efficient sand fly management. Future research should prioritize optimizing rearing and sterilization techniques, conducting controlled field trials, and fostering collaboration across disciplines to realize the potential of genetic control strategies in combating leishmaniasis.
Female mosquito targeted with venom to curb disease
34263Dann Okoth, Scidev.net, 2025-01-14 10:10:57.
A genetic biocontrol method which reduces the lifespan of female insects could work as fast as pesticides to reduce populations of disease-spreading mosquitoes and destructive crop pests, according to researchers. Insect pests pose a huge threat to global health and agriculture, causing hundreds of thousands of deaths, millions of infections, and costing billions in healthcare and crop damage each year. Biocontrol is increasingly seen as a viable alternative to pesticides, which can harm non-target species and ecosystems and are losing efficacy as resistance to them grows. A new approach called Toxic Male Technique (TMT), developed by researchers at the ARC Centre of Excellence in Synthetic Biology at Macquarie University, Australia, involves genetically engineering male insects to reduce the lifespan of the females they mate with. Researchers say it can be used to respond rapidly to outbreaks of agricultural pests as well as to fight mosquito-borne diseases such as malaria, dengue and Zika. “We hold that our technology has the potential of working as fast as pesticides without the attendant risks of harming other species and the environment,” says Samuel Beach a researcher in applied biosciences at Macquarie University and lead author of the study, published today in Nature Communications. According to Beach, the approach is more efficient than existing methods such as the Sterile Insect Technique or the release of insects carrying lethal genes, which work by releasing masses of sterilized or genetically modified males to mate with wild females.
Assessment of drive efficiency and resistance allele formation of a homing gene drive in the mosquito Aedes aegypti
34261Yang, X., Xu, X., Chen, Y. et al., Journal of Pest Science, 2025-01-14 09:57:33.
Aedes aegypti, known for transmitting viruses such as dengue, Zika and yellow fever, poses a significant public health threat. Conventional insecticides give rise to a range of issues, including ecological contamination and insect resistance. Hence, there is a pressing demand for environmentally-friendly, safer and more efficacious strategies for mosquito control. With the rapid advancement of the CRISPR/Cas9 system in gene function exploration and pest population control, substantial progress has been achieved in utilizing CRISPR/Cas9-based gene drive systems across various mosquito species. Only a few studies on gene drive technology have been conducted in Ae. aegypti. In this study, we constructed two complete drives for Ae. aegypti with different Cas9 promoters, each targeting kmo. Our drive based on PubCas9 had limited activity, but one with ExuCas9 exhibited super-Mendelian inheritance rates of approximately 60%. We observed low but detectable somatic activity of the drive and no evidence of maternally deposited Cas9. Germline resistance allele formation rates were similar to drive conversion rates, but most wild-type alleles in the germline remained uncut. Injections into the ExuCas9 drive line had 100% knockout efficiency among surviving offspring at three separate target genes. These results support the development and application of novel genetic pest control technologies aimed at combating Ae. aegypti.
Genetically Engineered Male Insects Shorten Their Mates’ Lifespans
34253Sneha Khedkar, The Scientist, 2025-01-13 15:13:56.
On a still night, as the air is thick with silence, the sharp, whining buzz of a mosquito shatters the calm. These blood-sucking insects that disturb people’s deep slumber are also responsible for spreading diseases such as dengue, chikungunya, malaria and Zika fever, which affect millions of people each year worldwide. Given the harmful effects of pesticides on the environment, combined with the emergence of mosquitoes resistant to pesticides, scientists are looking for alternative environment-friendly approaches for pest management. Now, researchers have developed a new population control method where male insects carrying toxic proteins can poison disease-spreading females during mating. The results, published in Nature Communications, describe a genetic biocontrol method that offers a fast and effective solution to managing pests. Such approaches are not entirely new. In the 1950s, when researchers mated female insects with radiologically sterilized males, they did not produce offsprings, reducing the next generation’s population. More recently, scientists propagated transgenes in insects that lower the fitness of future generations, resulting in decreased insect population. Although such methods are promising, they require at least one generation to take effect: Female insects may not produce offsprings, but they can continue transmitting infections. “As we’ve learned from COVID-19, reducing the spread of these diseases as quickly as possible is important to prevent epidemics,” said study author Samuel Beach, a graduate student in biologist Maciej Maselko’s lab at Macquarie University, in a press release.
Wolbachia-Based Approaches to Controlling Mosquito-Borne Viral Threats: Innovations, AI Integration, and Future Directions in the Context of Climate Change
34249Branda, F., Cella, E., Scarpa, F., et al., Viruses, 16:1868. 2025-01-13 14:55:50.
Wolbachia-based mosquito control strategies have gained significant attention as a sustainable approach to reduce the transmission of vector-borne diseases such as dengue, Zika, and chikungunya. These endosymbiotic bacteria can limit the ability of mosquitoes to transmit pathogens, offering a promising alternative to traditional chemical-based interventions. With the growing impact of climate change on mosquito population dynamics and disease transmission, Wolbachia interventions represent an adaptable and resilient strategy for mitigating the public health burden of vector-borne diseases. Changes in temperature, humidity, and rainfall patterns can alter mosquito breeding habitats and extend the geographical range of disease vectors, increasing the urgency for effective control measures. This review highlights innovations in Wolbachia-based mosquito control and explores future directions in the context of climate change. It emphasizes the integration of Wolbachia with other biological approaches and the need for multidisciplinary efforts to address climate-amplified disease risks. As ecosystems shift, Wolbachia interventions could be crucial in reducing mosquito-borne diseases, especially in vulnerable regions. AI integration in Wolbachia research presents opportunities to enhance mosquito control strategies by modeling ecological data, predicting mosquito dynamics, and optimizing intervention outcomes. Key areas include refining release strategies, real-time monitoring, and scaling interventions. Future opportunities lie in advancing AI-driven approaches for integrating Wolbachia with other vector control measures, promoting adaptive, data-driven responses to climate-amplified disease transmission.
Mitigating dengue transmission in Africa: the need for Wolbachia-infected mosquitoes’ rollout
34211Samson Ogunlade, Adeshina Adekunle, Emma McBryde, Frontiers, 12. 2025-01-07 08:57:15.
Dengue fever is a mosquito-borne viral disease that poses a significant public health concern globally. The disease is primarily transmitted by Aedes aegypti mosquitoes and the range of clinical manifestations vary from flu-like symptoms to more serious conditions such as dengue haemorrhagic fever and dengue shock syndrome. The dengue virus (DENV) infects about 400 million people yearly, of which 50–100 million of those become symptomatic, with over 20,000 deaths. Dengue notifications are increasing in Africa. The continent's tropical and subtropical climatic conditions create a conducive breeding environment for mosquitoes and hence, contribute to the spread of the virus. While recent statistics show that there were 15.7 million reported dengue infections in 2010, recent studies show that dengue cases are on the rise in Africa. This situation presents an increasing threat to public health systems already under pressure from other infectious illnesses. Traditionally established vector control methods such as the use of insecticide, emptying or covering water-filled containers and eliminating mosquito breeding sites have had limited success in curbing the spread of dengue. This calls for experimental and innovative strategies to combat the disease effectively. One promising approach—the Wolbachia-based approach, involves the deployment of Wolbachia-infected mosquitoes into the wild mosquito population. This technique has shown great potential in reducing dengue transmission. While the Wolbachia-based technique has demonstrated highly positive results in mitigating DENV, it is not always successful—Wolbachia strategies may struggle in high temperature settings, because some mosquitoes infected with Wolbachia (such as wMel strain) are unable to transmit Wolbachia maternally to their offspring and establish themselves under high temperatures. Therefore, using thermally tolerant strains may be beneficial in establishing Wolbachia infections in mosquitoes especially in regions with high heat conditions. Although Wolbachia-infected mosquitoes have been rolled out in different countries such as Brazil, Colombia in South America; Indonesia, Taiwan, Viet Nam, Thailand, Malaysia, India in South Asia; Northern Queensland in Australia; and the United States of America, there is arguably no deployment yet made in 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.
Variable effects of transient Wolbachia infections on alphaviruses in Aedes aegypti
33429Brittany L. Dodson, Sujit Pujhari, et al., PLoS Neglected Tropical Diseases, 2024-11-05 11:32:58.
Wolbachia pipientis (= Wolbachia) has promise as a tool to suppress virus transmission by Aedes aegypti mosquitoes. However, Wolbachia can have variable effects on mosquito-borne viruses. This variation remains poorly characterized, yet the multimodal effects of Wolbachia on diverse pathogens could have important implications for public health. Here, we examine the effects of transient somatic infection with two strains of Wolbachia (wAlbB and wMel) on the alphaviruses Sindbis virus (SINV), O’nyong-nyong virus (ONNV), and Mayaro virus (MAYV) in Ae. aegypti. We found variable effects of Wolbachia including enhancement and suppression of viral infections, with some effects depending on Wolbachia strain. Both wAlbB- and wMel-infected mosquitoes showed enhancement of SINV infection rates one week post-infection, with wAlbB-infected mosquitoes also having higher viral titers than controls. Infection rates with ONNV were low across all treatments and no significant effects of Wolbachia were observed. The effects of Wolbachia on MAYV infections were strikingly strain-specific; wMel strongly blocked MAYV infections and suppressed viral titers, while wAlbB had more modest effects. The variable effects of Wolbachia on vector competence underscore the importance of further research into how this bacterium impacts the virome of wild mosquitoes including the emergent human pathogens they transmit.
TWiV 1161: Baby you can drive my gene
33394MicrobeTV, YouTube, 2024-11-04 17:40:40.
TWiV reviews continuing expansion of poliovirus type 2, removal of influenza B/Yamagata from the vaccine, Nobel Prize for miRNAs, protective immune response with a adenovirus-associated virus vector expressing a computationally designed hemagglutinin, and viral gene drive during herpes simplex 1 infection in mice.
Wolbachia-based emerging strategies for control of vector-transmitted disease
32708Diego Montenegro, Gerardo Cortés-Cortés, María Guadalupe Balbuena-Alonso, et al., Acta Tropica, 260. 2024-10-22 17:28:54.
Dengue fever is a mosquito-transmitted disease of great public health importance. Dengue lacks adequate vaccine protection and insecticide-based methods of mosquito control are proving increasingly ineffective. Here we review the emerging use of mosquitoes transinfected with the obligate intracellular bacterium Wolbachia pipientis for vector control. Wolbachia often induces cytoplasmic incompatibility in its mosquito hosts, resulting in infertile progeny between an infected male and an uninfected female. Wolbachia infection also suppresses the replication of pathogens in the mosquito, a process known as “pathogen blocking”. Two strategies have emerged. The first one releases Wolbachia carriers (both male and female) to replace the wild mosquito population, a process driven by cytoplasmic incompatibility and that becomes irreversible once a threshold is reached. This suppresses disease transmission mainly by pathogen blocking and frequently requires a single intervention. The second strategy floods the field population with an exclusively male population of Wolbachia-carrying mosquitoes to generate infertile hybrid progeny. In this case, transmission suppression depends largely on decreasing the population density of mosquitoes driven by infertility and requires continued mosquito release. The efficacy of both Wolbachia-based approaches has been conclusively demonstrated by randomized and non-randomized studies of deployments across the world. However, results conducted in one setting cannot be directly or easily extrapolated to other settings because dengue incidence is highly affected by the conditions into which the mosquitoes are released. Compared to traditional vector control methods, Wolbachia-based approaches are much more environmentally friendly and can be effective in the medium/long term. On the flip side, they are much more complex and cost-intensive operations, requiring a substantial investment, infrastructure, trained personnel, coordination between agencies, and community engagement. Finally, we discuss recent evidence suggesting that the release of Wolbachia-transinfected mosquitoes has a moderate potential risk of spreading potentially dangerous genes in the environment.
Practical Application of a Relationship-Based Model to Engagement for Gene-Drive Vector Control Programs
32533Ana Kormos, Lodney Nazaré, Adionilde Aguiar dos Santos, and Gregory C. Lanzaro, The American Journal of Tropical Medicine and Hygiene, 111:341-360. 2024-10-15 12:04:35.
Engagement is an important component in the advancement of gene-drive vector control research programs as developers look to transition the technology from the laboratory to the field. As research advances and engagement surrounding this novel technology is put into practice, knowledge can be gained from practical experiences and applications in the field. A relationship-based model (RBM) provides a framework for end-user development of engagement programs and strategies. The model places end users at the center of the engagement decision-making processes rather than as recipients of predetermined strategies, methods, and definitions. Successful RBM application for healthcare delivery has previously been demonstrated, and the University of California Malaria Initiative (UCMI) has applied this model to its gene-drive program in the Democratic Republic of São Tomé and Príncipe. The model emphasizes the importance of local leadership in the planning, development, and implementation of all phases of project engagement. The primary aim of this paper is to translate the model from paper to practice and provide a transparent description, using practical examples, of the UCMI program implementation of RBM at its field site. End-user development of the UCMI engagement program provides a unique approach to the development of ethical, transparent, and effective engagement strategies for malaria control programs. This paper may also serve as a reference and example for projects looking to establish an engagement program model that integrates end-user groups in the decision-making processes surrounding engagement.
Exploring new tools to fight vector-borne diseases: research and governance implications
32541Alekos Simoni, Outreach Network for Gene Drive Research, 2024-10-08 12:24:29.
I recently had the honor and pleasure of attending an event co-organized by the Outreach Network for Gene Drive Research at the European Parliament in Brussels, and delivering a presentation on our work at Target Malaria to develop new genetic tools to reduce malaria transmission in Africa. The event was an opportunity to discuss advancements in the development of gene drive technologies and governance implications related to these new tools. With climate change creating favorable conditions for the spread of disease-carrying mosquitoes, and challenges such as drug and insecticide resistance threatening the efficacy of current interventions, a global, coordinated response is needed to tackle vector-borne diseases. In this context, gene drive technologies could offer a promising addition to existing approaches. MEP Charles Goerens opened the session by highlighting the global burden of vector-borne diseases, such as malaria and dengue, which cause over 700,000 deaths every year. He stressed the importance of innovation to address global health challenges and the critical role of the European Parliament in ensuring responsible oversight of new tools, such as gene drive technologies.
Evaluation of Wolbachia infection in Aedes aegypti suggests low prevalence and highly heterogeneous distribution in Medellín, Colombia
32509rley Calle-Tobón, Raúl Rojo-Ospina, et al., Acta Tropica, 260. 2024-10-08 09:19:14.
Dengue virus, transmitted mainly by Aedes aegypti mosquitoes, is a significant public health challenge in tropical and subtropical countries, with an incidence that is growing at an alarming rate. The release of Wolbachia-carrying mosquitoes has been suggested as a strategy to reduce the incidence of multiple arboviruses. In Medellín, Colombia, large-scale releases of Wolbachia-infected Ae. aegypti mosquitoes were performed between 2017 and 2022 by the World Mosquito Program to facilitate population replacement. In this study, we evaluated the prevalence and distribution of Wolbachia-infected Ae. aegypti two years after completion of these releases. We conducted the sampling across 19 communes in Medellín, using 416 ovitraps to collect Ae. aegypti eggs from epidemiological weeks 26 to 41 in 2023. Upon hatching the collected eggs, we identified and pooled adult female Ae. aegypti for DNA extraction. Subsequently, we conducted PCR assays for the detection of Wolbachia infection in these mosquitoes. We used maximum likelihood estimation (MLE) and Bayesian methods to estimate the prevalence of Wolbachia infection, while using QGIS to analyze spatial distribution of infection in the region. A total of 774 female Ae. aegypti mosquitoes from 182 pools were evaluated. We detected Wolbachia in 33.5 % of pools, with an estimated individual minimum infection rate of 9.5 % and a maximum of 33.2 %. The prevalence varied significantly across communes, with the highest rates observed in the northeastern and southwestern areas. Spatial analysis revealed a highly heterogeneous island-like distribution of Wolbachia across Medellín with a few hotspots. The observed Wolbachia prevalence in this work was lower than previously reported. We suspect a decline in the prevalence of Wolbachia-infected Ae. aegypti mosquitoes in Medellín following the completion of their release.
Wolbachia infection in Aedes aegypti does not affect its vectorial capacity for Dirofilaria immitis
32124Shirozu, T., Regilme, M.A.F., Ote, M. et al., Scientific Reports, 14. 2024-10-03 09:25:30.
Mosquito-borne diseases such as dengue and filariasis are a growing public health concern in endemic countries. Biological approaches, such as the trans-infection of Wolbachia pipientis in mosquitoes, are an alternative vector control strategy, especially for arthropod-borne viruses such as dengue. In the present study, the effect of Wolbachia (wMel strain) on the vectorial capacity of Aedes aegypti for Dirofilaria immitis was studied. Our results showed that Wolbachia does not affect the phenotype of mosquito survival or the prevalence, number, and molting rate of third-stage larvae in both susceptible and resistant strains of Ae. aegypti. RNA-seq analysis of Malpighian tubules at 2 days post-infection with D. immitis showed the differentially expressed genes (DEGs) with and without wMel infection. No characteristic immune-related gene expression patterns were observed among the DEGs. No significant change in the amount of Wolbachia was observed in the Ae. aegypti after D. immitis infection. Our results suggest that infection of D. immitis in Ae. aegypti populations will not interfere with Wolbachia-based vector control strategies in dengue-endemic areas where cases of D. immitis are present. This study demonstrated the veterinary medical validity of a dengue control program using Wolbachia.
Current status of the sterile insect technique for the suppression of mosquito populations on a global scale
32019Bouyer, J., Infectious Diseases of Poverty, 13. 2024-10-01 16:03:32.
The World Health Organization (WHO) has emphasized the urgent need for alternative strategies to chemical insecticides for controlling mosquito populations, particularly the invasive Aedes species, which are known vectors of arboviruses. Among these alternative approaches, the sterile insect technique (SIT) is experiencing rapid development, with numerous pilot trials being conducted worldwide. This review aims to elucidate the principles of SIT and highlight the significant recent advancements that have facilitated its scalability. I also employ a phased conditional approach to categorize the progression of 39 projects, drawing on peer reviewed studies, press releases and direct communication with project managers. This review indicates that a substantial number of projects illustrate the efficacy of SIT in suppressing Aedes populations, with one project even demonstrating a reduction in dengue incidence. I offer several recommendations to mitigate potential failures and address the challenges of compensation and overcompensation when implementing SIT field trials. Furthermore, I examine the potential implications of male mating harassment on the effectiveness of SIT in reducing disease transmission. This comprehensive assessment underscores the promise of SIT as a viable strategy for mosquito control. The insights gained from these trials not only contribute to the understanding of SIT’s effectiveness but also highlight the importance of careful project management and ecological considerations in the pursuit of public health objectives.
Applications of Mathematical Programming to Genetic Biocontrol
31592Váleri N. Vásquez, John M. Marshall, SIAM Journal on Applied Mathematics, 84. 2024-09-17 12:36:59.
We review existing approaches to optimizing the deployment of genetic biocontrol technologies—tools used to prevent vector-borne diseases such as malaria and dengue—and formulate a mathematical program that enables the incorporation of crucial ecological and logistical details. The model is comprised of equality constraints grounded in discretized dynamic population equations, inequality constraints representative of operational limitations including resource restrictions, and an objective function that jointly minimizes the count of competent mosquito vectors and the number of transgenic organisms released to mitigate them over a specified time period. We explore how nonlinear programming (NLP) and mixed integer nonlinear programming (MINLP) can advance the state of the art in designing the operational implementation of three distinct transgenic public health interventions, two of which are presently in active use around the world.
Mark–Release–Recapture Trial with Aedes albopictus (Diptera, Culicidae) Irradiated Males: Population Parameters and Climatic Factors
31590Amaro FIF, Soares P, Velo E, et al, Insects, 15. 2024-09-17 12:23:28.
Aedes albopictus mosquitoes spread arboviruses like dengue, Zika, or chikungunya. The Sterile Insect Technique (SIT) can be used as a prevention and control tool against Ae. albopictus populations. Mark–release–recapture (MRR) trials are fundamental to estimate the size of the wild population in target areas and to determine the dispersal capacity and survival of sterile males in open field conditions. Environmental conditions can affect the MRR trial’s results; thus, the influence of climatic factors on the first MRR trial with Ae. albopictus marked sterile males conducted in Portugal was analyzed. In October 2022, for three consecutive weeks at two different release points, 84,000 sterile males were released over 50 ha of the study area, in the municipality of Faro, Southern Portugal, and mosquitoes were recaptured by human landing collection (HLC) one, two, four, and six days after release. Distance travelled, daily survival, and life expectancy in the field were estimated for the released sterile males and the influence of climatic factors was analyzed. Despite no statistically significant association being found with humidity, temperature, and precipitation, it is crucial to plan MRRs, considering weather conditions for a more efficient application of the SIT in an integrated vector management program.
Genetically Modified Wolbachia mosquitoes help reduce virus transmission
31461Precision Vaccinations, 2024-08-20 10:33:21.
Every year on World Mosquito Day, diseases spread by mosquitoes, which account for over 17% of all infectious diseases and lead to more than 700,000 deaths annually, are highlighted. Parasites, bacteria, or viruses can cause these diseases, including chikungunya, malaria, dengue, Zika, and yellow fever. While some diseases can be prevented with innovative travel vaccines, some can not. This is why the World Mosquito Program exists today. According to the World Mosquito Program, the Wolbachia method is vital in fighting mosquito-borne diseases and protecting communities worldwide. This program can reduce the number of Aedes aegypti mosquitoes. When male Ae. aegypti mosquitoes with Wolbachia mate with wild female mosquitoes that do not have Wolbachia. The eggs will not hatch. Because the eggs don't hatch, the number of Ae. aegypti mosquitoes decreases. They do this by breeding with wild mosquitoes until, over several generations, they replace the local mosquito population. This means Wolbachia mosquitoes help decrease the risk of dengue, Zika, chikungunya, and yellow fever outbreaks. The World Mosquito Program is currently operating in 13 countries—Australia, Brazil, Colombia, Indonesia, Sri Lanka, Honduras, Laos, Vietnam, Kiribati, Fiji, Vanuatu, New Caledonia, and Mexico—and protects more than 11.4 million people. In the United States, communities in Texas, Florida, and California have released mosquitoes with Wolbachia over the past seven years and a significant decrease in Ae. aegypti mosquitoes have been reported. In 2023, the state of Hawaiʻi also launched a Wolbachia program. Most importantly, the U.S. CDC says no data suggests that Wolbachia bacteria harm people, animals, or the environment. Let's hope locally-acquired chikungunya, dengue, and malaria cases soon become distant memories as disease-carrying mosquitos disappear.
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.
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.
To fend off aggressive female mosquitoes, L.A. is releasing thousands of sterile males
29882Evan Bush, NBC News, 2024-05-07 15:46:02.
In Los Angeles, those who wage war on mosquitoes are adding a weapon to their arsenal: more mosquitoes. The Greater Los Angeles County Vector Control District on Thursday launched a pilot program to release tens of thousands of irradiated, lab-raised mosquitoes into the local environment. These mosquitoes are all male and have been sterilized by the radiation, so the hope is that they will find wild female mates and impregnate them with dead-end sperm, rendering the resulting eggs worthless. The target is a particular species, Aedes aegypti. The insects, which began to populate Los Angeles County in 2014, have evolved to hone in on one thing — you. “Thousands of years ago, a strain of Aedes aegypti moved in close to people and started to specialize to live near houses and bite people,” said Daniel Hahn, a professor in the University of Florida’s Department of Entomology and Nematology. “They’re characterized as aggressive nuisance biters because they’ll bite you all day long.” Aedes Aegypti thrive in backyards and make their homes in small containers like bottle caps and dog bowls. They can carry worrisome diseases like yellow fever, Chikungunya, Zika and dengue. “We know our residents are suffering,” said Susanne Kluh, the general manager of the Greater Los Angeles County Vector Control District, which serves 6 million people and has more than 90 full-time staffers. The district on Thursday released about 20,000 sterile male mosquitoes, dyed to appear fluorescent under a black light, as part of its final pilot program test. Male Aedes Aegypti mosquitoes don’t bite, so experts say the program poses near-zero risk to humans.
Monitoring Aedes populations for arboviruses, Wolbachia, insecticide resistance and its mechanisms in various agroecosystems in Benin
29064S. Ateutchia-Ngouanet, F. Nanfack-Minkeu, K. Mavridis, S. Wanji, M. Demanou, J. Vontas, R. Djouaka, Acta Tropica, 253. 2024-04-02 11:34:55.
The susceptibility of arbovirus vectors to insecticides and the microbiome of Aedes species are understudied in Benin.
Acceptability of emergent Aedes aegypti vector control methods in Ponce, Puerto Rico: A qualitative assessment
29010Pérez-Guerra CL, Rosado-Santiago C, Ramos SA, Marrero-Santos KM, González-Zeno G, Partridge SK, et al., PLoS Global Public Health, 2024-03-11 13:41:04.
Aedes aegypti control has been fraught with challenges in Puerto Rico. The government has implemented commonly used vector control methods, but arboviral epidemics still occur. It is necessary to explore new Ae. aegypti control methods. This study aimed to understand the perceptions of community members in Ponce, Puerto Rico about emergent and traditional Ae. aegypti vector control methods and determine their acceptability and support for these methods. We identified the type of information needed to increase support for emergent vector control methods, and the preferred strategies to disseminate this information. Four group discussions were conducted with a total of 32 participants representing eight of the 14 clusters participating in the Communities Organized for the Prevention of Arboviruses (COPA), a project designed to mobilize communities in Ponce, Puerto Rico to prevent diseases transmitted by mosquitoes. Group discussions began with an overview of different methods used for controlling Ae. aegypti mosquitoes. These overviews facilitated participant understanding of the mosquito control methods presented. Use of source reduction, autocidal gravid ovitraps (AGO), and manual application of larvicide for arboviral mosquito control received support from almost all participants. Vector control methods that use more familiar techniques in Puerto Rico such as truck-mounted larvicide spraying (TMLS) and insecticide residual spraying received support from most participants. More than half of participants supported the use of emergent mosquito control methods including Wolbachia suppression, Wolbachia replacement, or genetically modified mosquitoes (GMM). Participants preferred to receive vector control information through house-to-house visits with the distribution of written materials, followed by dissemination of information through traditional (i.e., radio, television) and social media. The detailed information resulting from this study was used to develop messages for a communications campaign to garner future community support. Community acceptance and support are critical for the success of vector control programs using emergent mosquito control methods.
Aedes aegypti Controls Ae. aegypti: SIT and IIT—An Overview
29003Robert L. Aldridge; Seth Gibson; Kenneth J. Linthicum, Journal of the American Mosquito Control Association, 20:32-49. 2024-03-11 12:34:19.
The sterile insect technique (SIT) and the incompatible insect technique (IIT) are emerging and potentially revolutionary tools for controlling Aedes aegypti (L.), a prominent worldwide mosquito vector threat to humans that is notoriously difficult to reduce or eliminate in intervention areas using traditional integrated vector management (IVM) approaches. Here we provide an overview of the discovery, development, and application of SIT and IIT to Ae. aegypti control, and innovations and advances in technology, including transgenics, that could elevate these techniques to a worldwide sustainable solution to Ae. aegypti when combined with other IVM practices.
Stakeholder engagement in the development of genetically modified mosquitoes for malaria control in West Africa: lessons learned from 10 years of Target Malaria’s work in Mali
28850Bakara Dicko, Souleymane Kodio, Hatouma Samoura, Fatoumata Traoré, Naima Sykes, Mouhamed Drabo, Delphine Thizy, Isabelle Coche, Benjamin Robinson, Kadiatou Sanogo, Bilkissou Yagouré, Samba Diop, Mamadou B. Coulibaly, Frontiers in Bioengineering and Biotechnology, 11. 2024-01-28 13:28:47.
From 2012 to 2023, the Malaria Research and Training Center (MRTC), based out of the University of Sciences, Techniques and Technologies of Bamako (USTTB), was part of the Target Malaria research consortium working towards developing novel gene drive-based tools for controlling populations of malaria vector mosquitoes. As part of this work, Target Malaria Mali has undertaken a range of in-depth engagement activities with the communities where their research is conducted and with other stakeholders nationally. These activities were meant to ensure that the project’s activities took place with the agreement of those communities, and that those communities were able to play a role in shaping the project’s approach to ensure that its eventual outcomes were in line with their needs and concerns. This paper aims to conduct a critical assessment of those 10 years of stakeholder engagement in order to identify good practices which can inform future engagement work on gene drive research in West Africa. It sets out a range of approaches and practices that enabled the Target Malaria Mali team to engage a variety of stakeholders, to share information, collect feedback, and determine community agreement, in a manner that was inclusive, effective, and culturally appropriate. These can be useful tools for those working on gene drive research and other area-wide vector control methods in West African contexts to ensure that their research is aligned with the interests of the communities who are intended to be its ultimate beneficiaries, and to allow those communities to play a meaningful role in the research process.
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.
Advances and challenges in synthetic biology for mosquito control
28545Shih-Che Weng, Reem A. Masri, Omar S. Akbari, Trends in Parasitology, 2023-11-28 11:40:23.
Mosquito-borne illnesses represent a significant global health peril, resulting in approximately one million fatalities annually. West Nile, dengue, Zika, and malaria are continuously expanding their global reach, driven by factors that escalate mosquito populations and pathogen transmission. Innovative control measures are imperative to combat these catastrophic ailments. Conventional approaches, such as eliminating breeding sites and using insecticides, have been helpful, but they face challenges such as insecticide resistance and environmental harm. Given the mounting severity of mosquito-borne diseases, there is promise in exploring innovative approaches using synthetic biology to bolster mosquitoes' resistance to pathogens, or even eliminate the mosquito vectors, as a means of control. This review outlines current strategies, future goals, and the importance of gene editing for global health defenses against mosquito-borne diseases.
Utility of surveillance data for planning for dengue elimination in Yogyakarta, Indonesia: a scenario-tree modelling approach
28536Melanie Bannister-Tyrrell, Alison Hillman, Citra Indrian, Riris Andono Ahmad, Adi Utarini, Cameron P Simmons, Katherine L Anders, Evan Sergeant, BMJ Global Health, 8. 2023-11-28 10:54:45.
Field trials and modelling studies suggest that elimination of dengue transmission may be possible through widespread release of Aedes aegypti mosquitoes infected with the insect bacterium Wolbachia pipientis (wMel strain), in conjunction with routine dengue control activities. This study aimed to develop a modelling framework to guide planning for the potential elimination of locally acquired dengue in Yogyakarta, a city of almost 400 000 people in Java, Indonesia. A scenario-tree modelling approach was used to estimate the sensitivity of the dengue surveillance system (including routine hospital-based reporting and primary-care-based enhanced surveillance), and time required to demonstrate elimination of locally acquired dengue in Yogyakarta city, assuming the detected incidence of dengue decreases to zero in the future. Age and gender were included as risk factors for dengue, and detection nodes included the probability of seeking care, probability of sample collection and testing, diagnostic test sensitivity and probability of case notification. Parameter distributions were derived from health system data or estimated by expert opinion. Alternative simulations were defined based on changes to key parameter values, separately and in combination. For the default simulation, median surveillance system sensitivity was 0.131 (95% PI 0.111 to 0.152) per month. Median confidence in dengue elimination reached 80% after a minimum of 13 months of zero detected dengue cases and 90% confidence after 25 months, across different scenarios. The alternative simulations investigated produced relatively small changes in median system sensitivity and time to elimination. This study suggests that with a combination of hospital-based surveillance and enhanced clinic-based surveillance for dengue, an acceptable level of confidence (80% probability) in the elimination of locally acquired dengue can be reached within 2 years. Increasing the surveillance system sensitivity could shorten the time to first ascertainment of elimination of dengue and increase the level of confidence in elimination.
Targeting Sex Determination to Suppress Mosquito Populations
24988L. Ming, P. K. Nikolay, S. Ruichen, Y. Ting, D. B. Elena, J. B. Daniel, A. Igor, M. S. C. Hector, Z. Yinpeng, A. D. Nicolas, M. L. YuMin, P. S. Matthew, M. Craig, M. M. John and S. A. Omar, bioRxiv, 2023.04.18.537404. 2023-04-20 14:45:03.
Each year, hundreds of millions of people are infected with arboviruses such as dengue, yellow fever, chikungunya, and Zika, which are all primarily spread by the notorious mosquito Aedes aegypti. Traditional control measures have proven insufficient, necessitating innovations. In response, here we generate a next generation CRISPR-based precision-guided sterile insect technique (pgSIT) for Aedes aegypti that disrupts genes essential for sex determination and fertility, producing predominantly sterile males that can be deployed at any life stage. Using mathematical models and empirical testing, we demonstrate that released pgSIT males can effectively compete with, suppress, and eliminate caged mosquito populations. This versatile species-specific platform has the potential for field deployment to control wild populations, safely curtailing disease transmission.Competing Interest StatementO.S.A. is a founder of Agragene, Inc. with equity interest. O.S.A., M.L., and N.P.K are founders of Synvect with equity interest. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. All remaining authors declare no competing interests.
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.
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.
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.
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.
Genetic Stability and Fitness of Aedes aegypti Red-Eye Genetic Sexing Strains With Pakistani Genomic Background for Sterile Insect Technique Applications
22452M. Misbah-ul-Haq, D. O. Carvalho, L. D. de la Fuente, A. A. Augustinos and K. Bourtzis, Frontiers in Bioengineering and Biotechnology, 10. 2022-03-31 09:37:56.
The mosquito species Aedes aegypti is the primary transmitter of viruses that cause endemic diseases like dengue in Pakistan. It is also a cause of other vector-borne diseases like yellow fever, Zika fever, and chikungunya, which significantly impact human health worldwide. In the absence of efficient vaccines (except for yellow fever) or drugs, vector control methods, such as the sterile insect technique (SIT), have been proposed as additional tools for the management of these diseases. Mosquito SIT programs are based on the release of sterile males and it is important female releases to be ideally zero or to be kept at a minimum, since females are the ones that bite, blood-feed and transmit pathogens. Recently, an Ae. aegypti genetic sexing strain (GSS), with and without a recombination-suppressing inversion (Inv35), was developed using the eye color as a selectable marker, with males having black eyes and females red eyes. In the present study, we introgressed the sexing features and the Inv35 of the Ae. aegypti red-eye GSS into the Pakistani genomic background aiming to their future use for SIT applications in the country. Both introgressed strains, the Red-eye GSS-PAK and the Red-eye GSS/Inv35-PAK, were evaluated in respect to their genetic stability and biological quality by assessing parameters like recombination rate, fecundity, fertility, pupal and adult recovery, time of development, pupal weight, survival, and flight ability in comparison with a wild Pakistani population (PAK). The results suggest that the sexing features and the recombination suppression properties of Inv35 were not affected after their introgression into the local genomic background; however, some biological traits of the two newly constructed strains were affected, positively or negatively, suggesting that a thorough quality control analysis should be performed after the introgression of a GSS into a new genomic background prior to its use in SIT field trials or applications. The importance of using GSS with local genomic background for SIT applications against Aedes aegypti is also discussed.
Sterile Insect Technique in an Integrated Vector Management Program against Tiger Mosquito Aedes albopictus in the Valencia Region (Spain): Operating Procedures and Quality Control Parameters
16663C. Tur, D. Almenar, S. Benlloch-Navarro, R. Argilés-Herrero, M. Zacarés, V. Dalmau and I. Pla, Insects, 12. 2021-03-23 14:20:04.
The Agriculture Department of the Valencian Region is promoting an ongoing pilot project to evaluate the efficacy of an integrated vector management program (IVM) based on the use of the SIT as the main method of control. The laboratory studies for evaluating the entomological efficacy of SIT through the phased conditional testing process recommended by World Health Organization and the International Atomic Energy Agency (WHO-IAEA) are addressed. This study describes the routine operating procedures and quality control parameters for the medium-scale rearing of sterile male A. albopictus. More than 15 million sterile males have been produced and released in an area of 80 ha between 2018 and 2020. Of the initial L1 larvae, we recovered 17.2% of male pupae after sex sorting to be sterilized and released on the field, while the rest of the pupae remained available to maintain the rearing colony. The residual percentage of females after sex sorting was on average 0.17%. The obtained values in terms of production and quality control as well as the proposed rearing methodology can be useful for designing a medium-scale mosquito-rearing pipeline.
Thirteenth meeting of the WHO Vector Control Advisory Group
17109Vector Control Advisory Group, WHO, 2021-03-08 18:23:57.
VCAG experts met virtually with product developers, innovators and researchers from 7 to 10 December 2020 for the 13th VCAG meeting. This report details the proceedings and outcomes of the meeting, including advice provided to the following applicants: bait stations; lethal house lures; reduced pathogen transmission induced by Wolbachia; spatial repellents; and treatment of humans and/or livestock with an endectocide
Sterile Insect Technique (SIT) against Aedes Species Mosquitoes: A Roadmap and Good Practice Framework for Designing, Implementing and Evaluating Pilot Field Trials
16659C. F. Oliva, M. Q. Benedict, C. M. Collins, T. Baldet, R. Bellini, H. Bossin, J. Bouyer, V. Corbel, L. Facchinelli, F. Fouque, M. Geier, A. Michaelakis, D. Roiz, F. Simard, C. Tur and L.-C. Gouagna, Insects, 12. 2021-02-24 13:44:35.
We offer here a pragmatic and accessible ‘roadmap’ for the pre-pilot and pilot phases to guide any interested party. This will support stakeholders, non-specialist scientists, implementers, and decision-makers. Applying these concepts will ensure, given adequate resources, a sound basis for local field trialing and for developing experience with the technique in readiness for potential operational deployment. This synthesis is based on the available literature, in addition to the experience and current knowledge of the expert contributing authors in this field. We describe a typical path to successful pilot testing, with the four concurrent development streams of Laboratory, Field, Stakeholder Relations, and the Business and Compliance Case. We provide a graphic framework with criteria that must be met in order to proceed.
The Antiviral Small-Interfering RNA Pathway Induces Zika Virus Resistance in Transgenic Aedes aegypti
15482A. E. Williams, I. Sanchez-Vargas, W. R. Reid, J. Y. Lin, A. W. E. Franz and K. E. Olson, Viruses, 12:18. 2020-12-15 14:45:29.
We used CRISPR/Cas9 to re-target a previously characterized locus (Chr2:321382225) and engineered mosquitoes expressing an inverted repeat (IR) dsRNA against the NS3/4A region of the ZIKV genome. Small RNA analysis revealed that the IR effector triggered the mosquito's siRNA antiviral pathway in bloodfed females. Nearly complete (90%) inhibition of ZIKV replication was found in vivo in both midguts and carcasses at 7 or 14 days post-infection (dpi). Furthermore, significantly fewer transgenic mosquitoes contained ZIKV in their salivary glands (p = 0.001), which led to a reduction in the number of ZIKV-containing saliva samples as measured by transmission assay. Our work shows that Ae. aegypti innate immunity can be co-opted to engineer mosquitoes resistant to ZIKV.
Interdisciplinary development of a standardized introduction to gene drives for lay audiences
15381C. E. Schairer, C. Triplett, A. Buchman, O. S. Akbari and C. S. Bloss, BMC Medical Research Methodology, 20:15. 2020-12-10 15:09:37.
While there is wide consensus that the public should be consulted about emerging technology early in development, it is difficult to elicit public opinion about innovations unfamiliar to lay audiences. We sought public input on a program of research on genetic engineering to control mosquito vectors of disease that is led by scientists at the University of California and funded by the U.S. Defense Advanced Research Projects Agency (DARPA). In preparation for this effort, we developed a series of narrated slideshows to prompt responses to the development of gene drive mosquito control strategies among lay people. We describe the development and content of these slideshows and evaluate their ability to elicit discussions among focus group participants.
Burkina Faso Stakeholders consultations on Gene Drive Technology for integrated vector management towards malaria elimination
15384AUDA-NEPAD, AUDA-NEPAD, 2020-12-08 15:09:47.
Under its flagship Integrated Vector Management (IVM) Programme, African Union Development Agency (AUDA-NEPAD) in partnership with the National biosafety agency (ANB) of Burkina Faso organized an information sharing workshop on the applications of "Gene Drive" technology and facilitated discussions for the establishment of a consultative group on integrated vector management in Burkina Faso. The meeting was held from November 30th to December 1st, in Ouagadougou and brought together healthcare, environmental and biosafety regulators and other decision makers from different relevant institutions in the country.
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.
On Nonlinear Pest/Vector Control via the Sterile Insect Technique: Impact of Residual Fertility
14291M. S. Aronna and Y. Dumont, Bulletin of Mathematical Biology, 82:29. 2020-07-09 14:09:49.
We consider a minimalist model for the Sterile Insect Technique (SIT), assuming that residual fertility can occur in the sterile male population.
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.
Mosquito-Borne Diseases Emergence/Resurgence and How to Effectively Control It Biologically
12383H. Dahmana and O. Mediannikov, Pathogens, 9:26. 2020-04-23 17:49:22.
Deadly pathogens and parasites are transmitted by vectors and the mosquito is considered the most threatening vector in public health, transmitting these pathogens to humans and animals. We are currently witnessing the emergence/resurgence in new regions/populations of the most important mosquito-borne diseases, such as arboviruses and malaria. This resurgence may be the consequence of numerous complex parameters, but the major cause remains the mismanagement of insecticide use and the emergence of resistance. Biological control programmes have rendered promising results but several highly effective techniques, such as genetic manipulation, remain insufficiently considered as a control mechanism. Currently, new strategies based on attractive toxic sugar baits and new agents, such as Wolbachia and Asaia, are being intensively studied for potential use as alternatives to chemicals. Research into new insecticides, Insect Growth Regulators, and repellent compounds is pressing, and the improvement of biological strategies may provide key solutions to prevent outbreaks, decrease the danger to at-risk populations, and mitigate resistance.
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.
Winning the tug-of-war between effector gene design and pathogen evolution in vector population replacement strategies
5609Marshall, J. M., R. R. Raban, N. P. Kandul, J. R. Edula, T. M. León and O. S. Akbari, Frontiers in Genetics, 10:1072. 2019-12-17 16:13:33.
While efforts to control malaria with available tools have stagnated, and arbovirus outbreaks persist around the globe, the advent of clustered regularly interspaced short palindromic repeat (CRISPR)-based gene editing has provided exciting new opportunities for genetics-based strategies to control these diseases. In one such strategy, called “population replacement”, mosquitoes, and other disease vectors are engineered with effector genes that render them unable to transmit pathogens. These effector genes can be linked to “gene drive” systems that can bias inheritance in their favor, providing novel opportunities to replace disease-susceptible vector populations with disease-refractory ones over the course of several generations. While promising for the control of vector-borne diseases on a wide scale, this sets up an evolutionary tug-of-war between the introduced effector genes and the pathogen. Here, we review the disease-refractory genes designed to date to target Plasmodium falciparum malaria transmitted by Anopheles gambiae, and arboviruses transmitted by Aedes aegypti, including dengue serotypes 2 and 3, chikungunya, and Zika viruses. We discuss resistance concerns for these effector genes, and genetic approaches to prevent parasite and viral escape variants. One general approach is to increase the evolutionary hurdle required for the pathogen to evolve resistance by attacking it at multiple sites in its genome and/or multiple stages of development. Another is to reduce the size of the pathogen population by other means, such as with vector control and antimalarial drugs. We discuss lessons learned from the evolution of resistance to antimalarial and antiviral drugs and implications for the management of resistance after its emergence. Finally, we discuss the target product profile for population replacement strategies for vector-borne disease control. This differs between early phase field trials and wide-scale disease control. In the latter case, the demands on effector gene efficacy are great; however, with new possibilities ushered in by CRISPR-based gene editing, and when combined with surveillance, monitoring, and rapid management of pathogen resistance, the odds are increasingly favoring effector genes in the upcoming evolutionary tug-of-war.
A Y-chromosome shredding gene drive for controlling pest vertebrate populations
3938Prowse, TAAA, F.; Cassey, P.; Thomas, P.; Ross, J. V., eLife, 8:19. 2019-01-16 00:00:00.
Self-replicating gene drives that modify sex ratios or infer a fitness cost could be used to control populations of invasive alien species. The targeted deletion of Y sex chromosomes using CRISPR technology offers a new approach for sex bias that could be incorporated within gene-drive designs. We introduce a novel gene-drive strategy termed Y-CHromosome deletion using Orthogonal Programmable Endonucleases (Y-CHOPE), incorporating a programmable endonuclease that 'shreds' the Y chromosome, thereby converting XY males into fertile XO females. Firstly, we demonstrate that the CRISPR/Cas12a system can eliminate the Y chromosome in embryonic stem cells with high efficiency (c. 90%). Next, using stochastic, individual-based models of a pest mouse population, we show that a Y-shredding drive that progressively depletes the pool of XY males could effect population eradication through mate limitation. Our molecular and modeling data suggest that a Y-CHOPE gene drive could be a viable tool for vertebrate pest control.
Engineered resistance to Zika virus in transgenic Aedes aegypti expressing a polycistronic cluster of synthetic small RNAs
3895Buchman, AG, S.; Li, M.; Antoshechkin, I.; Li, H. H.; Wang, H. W.; Chen, C. H.; Klein, M. J.; Duchemin, J. B.; Paradkar, P. N.; Akbari, O. S., Proceedings of the National Academy of Sciences of the United States of America, 116:3656-3661. 2019-01-13 00:00:00.
Recent Zika virus (ZIKV) outbreaks have highlighted the necessity for development of novel vector control strategies to combat arboviral transmission, including genetic versions of the sterile insect technique, artificial infection with Wolbachia to reduce population size and/or vectoring competency, and gene drive-based methods. Here, we describe the development of mosquitoes synthetically engineered to impede vector competence to ZIKV. We demonstrate that a polycistronic cluster of engineered synthetic small RNAs targeting ZIKV is expressed and fully processed in Aedes aegypti, ensuring the formation of mature synthetic small RNAs in the midgut where ZIKV resides in the early stages of infection. Critically, we demonstrate that engineered Ae. aegypti mosquitoes harboring the anti-ZIKV transgene have significantly reduced viral infection, dissemination, and transmission rates of ZIKV. Taken together, these compelling results provide a promising path forward for development of effective genetic-based ZIKV control strategies, which could potentially be extended to curtail other arboviruses.
Transgenic Mosquitoes – Fact or Fiction?
5907Wilke, A. B. B., J. C. Beier and G. Benelli, Trends in Parasitology, 34:456-465. 2018-03-08 16:14:34.
echnologies for controlling mosquito vectors based on genetic manipulation and the release of genetically modified mosquitoes (GMMs) are gaining ground. However, concrete epidemiological evidence of their effectiveness, sustainability, and impact on the environment and nontarget species is lacking; no reliable ecological evidence on the potential interactions among GMMs, target populations, and other mosquito species populations exists; and no GMM technology has yet been approved by the WHO Vector Control Advisory Group. Our opinion is that, although GMMs may be considered a promising control tool, more studies are needed to assess their true effectiveness, risks, and benefits. Overall, several lines of evidence must be provided before GMM-based control strategies can be used under the integrated vector management framework.
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.
Area-wide Integrated Pest Management
13603Food and Agriculture Organization of the United Nations (FAO), International Atomic Energy Agency, 2017-05-22 13:34:46.
Throughout history, people have had to fight insect pests to reduce diseases, minimize food losses, protect agricultural trade or simply to avoid the nuisance of stinging, biting and buzzing bugs. Insect pest control is usually implemented locally in individual fields or properties. These uncoordinated efforts often prove inefficient since they only suppress a proportion of the targeted pest population. Pests from nearby untreated areas remain unscathed and can re-enter the treated areas, the damage continues, and people have little choice but to apply the control measures again and again to protect their livelihoods. Area-wide pest management provides a more cost-effective and sustainable approach by proactively targeting entire pest populations. In this way, pest populations can be contained at low levels for longer periods and pest management methods can be integrated that are less reliant on pesticides and that better address ecological and environmental concerns.
Ethical issues associated with vector-borne diseases. Report of a WHO scoping meeting, Geneva, 23–24 February 2017
34043Geneva: World Health Organization, Licence: CC BY-NC-SA 3.0 IGO, WHO Reference Number: WHO/HTM/NTD/VEM/2017. 2017-02-24 00:00:00.
Gene drives do not always increase in frequency: from genetic models to risk assessment
4036de Jong, TJ, Journal Fur Verbraucherschutz Und Lebensmittelsicherheit-Journal of Consumer Protection and Food Safety, 12:299-307. 2017-01-14 00:00:00.
Homing genes encode endonucleases that make a double stranded break in the DNA, destroying a target site on the homologous chromosome. When the cell repairs the break the homing allele is copied, converting a heterozygote into a homozygote. This results in gene drive (GD), an overrepresentation of the homing allele in the next generation. GD may propel CRISPR-Cas9 genes and new genes physically coupled to the GD through natural populations. I revisit the population genetic models of GD with the aim of making these models more understandable to non-specialists. What can we learn about risk evaluation from the models? A GD with no or a small effect on fitness (viability) always spreads in the population and goes to fixation. That is provided that no resistance mechanism evolves, for instance due to a mutation in the target site. However, when GDs have a large negative effect on fitness, their spread depends on a threshold or they may not spread at all. The chance of GDs increasing until fixation is much higher in systems with meiotic drive than in systems with embryo conversion. The presence or absence of a meiotic promoter is therefore relevant to take into account in the environmental risk assessment.
Requirements for effective malaria control with homing endonuclease genes
4203Deredec, AG, H. C. J.; Burt, A., Proceedings of the National Academy of Sciences of the United States of America, 108:e874-e880. 2011-01-21 00:00:00.
Malaria continues to impose a substantial burden on human health. We have previously proposed that biological approaches to control the mosquito vector of disease could be developed using homing endonuclease genes (HEGs), a class of selfish or parasitic gene that exists naturally in many microbes. Recent lab studies have demonstrated that HEGs can function in mosquitoes. We constructed and analyzed a model of mosquito population genetics and malaria epidemiology to determine how well HEGs need to function in order to have a significant effect on the burden of disease. Our model, combined with currently available data, indicates that populations of Anopheles gambiae could be eliminated by releasing 2-3 HEGs targeting female fertility genes, or a driving-Y chromosome that is transmitted to 75-96% of progeny. Combinations of fertility-targeting HEGs and Y drive may also be effective. It is possible to eliminate the disease without eliminating the vector, but the parameter space producing this outcome appears to be small. HEGs causing a quantitative reduction in adult survival can be more effective than those targeting female fertility, but the selection coefficients that need to be imposed are still large, unless many HEGs are to be released. Simulations show that HEG-based strategies can be effective over socially relevant time frames. Important limiting assumptions of the models are that there is only a single vector species, and we model a homogeneous population, not a landscape. Nevertheless, we conclude that HEG-based approaches could have a transformational effect on malaria control efforts.
Site-specific selfish genes as tools for the control and genetic engineering of natural populations
4306Burt, A, Proceedings of the Royal Society B-Biological Sciences, 270:921-928. 2003-01-04 00:00:00.
Site-specific selfish genes exploit host functions to copy themselves into a defined target DNA sequence, and include homing endonuclease genes, group II introns and some LINE-like transposable elements. If such genes can be engineered to target new host sequences, then they can be used to manipulate natural populations, even if the number of individuals released is a small fraction of the entire population. For example, a genetic load sufficient to eradicate a population can be imposed in fewer than 20 generations, if the target is an essential host gene, the knockout is recessive and the selfish gene has an appropriate promoter. There will be selection for resistance, but several strategies are available for reducing the likelihood of it evolving. These genes may also be used to genetically engineer natural populations, by means of population-wide gene knockouts, gene replacements and genetic transformations. By targeting sex-linked loci just prior to meiosis one may skew the population sex ratio, and by changing the promoter one may limit the spread of the gene to neighbouring populations. The proposed constructs are evolutionarily stable in the face of the mutations most likely to arise during their spread, and strategies are also available for reversing the manipulations.
Stable transformation of the yellow fever mosquito, Aedes aegypti, with the Hermes element from the housefly
6254N. Jasinskiene, C. J. Coates, M. Q. Benedict, A. J. Cornel, C. S. Rafferty, A. A. James and F. H. Collins, Proceedings of the National Academy of Sciences of the United States of America, 95:3743-3747. 1998-03-07 19:28:29.
The mosquito Aedes aegypti is the world's most important vector of yellow fever and dengue viruses, Work is currently in progress to control the transmission of these viruses by genetically altering the capacity of wild Ae, aegypti populations to support virus replication. The germ-line transformation system reported here constitutes a major advance toward the implementation of this control strategy, A modified Hermes transposon carrying a 4.7-kb fragment of genomic DNA that includes a wild-type allele of the Drosophila melanogaster cinnabar (cn) gene was used to transform a white-eyed recipient strain of Ae, aegypti. Microinfection of preblastoderm mosquito embryos with this construct resulted in 50% of the emergent G(0) adults showing some color in their eyes, Three transformed families were recovered, each resulting from an independent insertion event of the cn(+)-carrying transposon, The cn(+) gene functioned as a semidominant transgene and segregated in Mendelian ratios, Hermes shows great promise as a vector for efficient, heritable, and stable transformation of this important mosquito vector species.
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