Keywords: Field trials

Mark–release–recapture study of irradiated male Aedes albopictus under stressful field conditions

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Qingdeng Feng, Ming Li, Jeremy Bouyer, et al.,  Pest Management Science,  2026-03-09 10:33:54.
The sterile insect technique (SIT) suppresses mosquito populations by releasing sterile males. Its success mainly depends on the performance of sterile males. Mark–Release–Recapture (MRR) experiments are used to evaluate male performance in the field, yet most previous experiments were conducted under mild conditions (e.g. 25–28 °C) in which mosquitoes could easily adapt. Male mosquito performance under stressful field conditions remains poorly understood. This study evaluated the field performance of irradiated Aedes albopictus males under high-temperature conditions (>30 °C in average) in southern China, Foshan City, located in a sub-tropical area. Two MRR experiments were conducted in a 5-ha village during July–August of 2023 and 2024. Lifespan and dispersal of postreleased males were examined using BG-Sentinel mosquito traps, human landing catches, and ovitraps. A total of 54 546 and 58 440 sterile males were released in 2023 and 2024, respectively, with recapture rates of 8.53% and 5.64%. The mean dispersal distances ranged from 58.88–77.19 m (2023) to 81.82–90.86 m (2024). Daily survival probabilities were 0.15–0.28 in 2023 and 0.45–0.62 in 2024, corresponding to average expected lifespans of 0.53–0.78 days and 1.26–2.13 days, respectively. Estimated wild male densities ranged from 302–986 males ha−1 in 2023 to 416–3785 males ha−1 in 2024. Stressful field conditions severely reduced sterile male survival and dispersal, highlighting the need to optimize release protocols in challenging climates. These findings provide critical baseline data for advancing Ae. albopictus SIT programmes in southern China. 

Spatial Dynamics and Sterilization Range of Incompatible Aedes albopictus Males: Advancing Toward an Optimized IIT Approach

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Lampazzi, E., Virgillito, C., Caputo, B., et al.,  Tropical Medicine and Infectious Disease,  11. 2026-02-06 18:17:05.
The Incompatible Insect Technique (IIT) is a species-specific, eco-friendly mosquito control method that relies on releasing Wolbachia-infected males, which induce cytoplasmic incompatibility (CI), rendering eggs inviable when mating with wild females. Aiming at optimizing IIT protocols in terms of cost-effectiveness, data on incompatible male dispersal and survival and the distance- and time-related impact of induced sterility are fundamental. This study plans to fill this gap and reports findings from a two-year field trial (2022–2023) at the ENEA-Casaccia Research Center, based on single-spot releases of incompatible Aedes albopictus males (ARwP strain). Male releases were carried out in late September 2022 (~15,000 released males) and the early Ae. albopictus season (at the end of June 2023; ~24,000 released males). Fifty-eight ovitraps were located at a 20–900 m distance from the ARwP release spot and were monitored weekly from May to November to assess egg hatching rates and measure CI effects in relation to both distance and time. Following the 2023 release, samples of adults were collected at increasing distances from the release site and at multiple post-release time points to assess, individually, wild female fertility and ARwP male dispersal and survival using Wolbachia as a genetic marker. Statistical analyses revealed that: (a) the highest reduction in the egg hatching was found within 100 m from the release spot (46.5% and 19.9%, respectively, in 2022 and 2023) but remained significant even at greater distances (29.9% and 7.7% at 300 m, respectively, in 2022 and 2023); (b) accordingly, the highest reduction in the wild female fertility occurred within 100 m from the release spot (47.3%), but similar effects were recognizable up to 600 m; (c) the overflooding ratio of the ARwP males did not significantly differ between 3 and 11 days after the release, with ARwP males remaining active up to 18 days and dispersing as far as 400 m. These results demonstrate the potential of localized, non-inundative IIT trials to furnish clues for the setup of spatially optimized release strategies, especially in scaled-up applications. The study also emphasizes the need for standardized assessment tools and further research regarding environmental and behavioral factors influencing long-term suppression outcomes.

Field implementation of the sterile insect technique against Aedes aegypti in Recife, Brazil: operational challenges and impact of release frequency on vector dynamics

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Macedo, 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.

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

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Mwima, 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.

Monitoring the Capacity of Microsporidia MB Transgenerational Spread in Anopheles arabiensis Populations

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Boanyah, G. Y., Koekemoer, L. L., Herren, J. K., & Bukhari, T.,  Insects,  16. 2026-01-05 11:06:39.
Microsporidia MB is a natural symbiont of Anopheles arabiensis Patton, 1905 that blocks Plasmodium transmission without compromising mosquito fitness. Developing this symbiont for malaria control requires a thorough understanding of its transmission dynamics across generations under environmentally relevant conditions. This study aimed to evaluate the transgenerational spread of Microsporidia MB in semi-field settings. From field-collected infected females (G0), several independent replicates of Microsporidia MB-infected An. arabiensis were established and maintained under semi-field conditions for six generations (F1–F6). All the mosquitoes were screened for Microsporidia MB prevalence and infection intensity using qPCR after death. Temperature and humidity and wing size were recorded. Two replicates sustained through F6. Microsporidia MB prevalence and intensity increased from F1 to F3–F4 before declining. A weak positive correlation was observed between prevalence and temperature, but not humidity. Female mosquitoes exhibited higher infection intensities. Female wing size varied across generations, while male size remained consistent. This first study on Microsporidia MB transgenerational transmission under semi-field conditions revealed a pattern of initial increase followed by decline in prevalence and intensity. The stability of male size supports the potential use of infected males in release programs. These findings underscore additional investigations into environmental drivers for mosquito symbiont prevalence.

A target product profile for a rapid diagnostic test to monitor mosquito gene drive presence and frequency

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Prateek Verma, Sebald Verkuijl, Calvin K. Yee, et al.,  bioRxiv,  2025-12-18 10:23:36.
Malaria remains a major global health challenge, with over 263 million cases and nearly 600,000 deaths reported in 2023, the majority in sub-Saharan Africa. While conventional interventions such as insecticide-treated nets, indoor residual spraying and antimalarial drugs have reduced transmission, progress has stalled due to the limitations of these interventions and the emergence of resistance. Gene drive-modified mosquitoes represent a promising, potentially transformative vector control strategy, capable of spreading malaria-refractory traits or suppressing mosquito populations. Successful field deployment will depend upon monitoring systems to track the presence and frequency of gene drive constructs as they spread and persist. Current molecular surveillance techniques, though effective, are resource-intensive and reliant on laboratory infrastructure and technical competencies. Here, we make the case for a near-universal and low-cost rapid diagnostic test (RDT) designed to detect gene drive mosquitoes in the field, to complement existing surveillance infrastructure. Two use cases are outlined: i) to detect the presence of the drive construct in a new population, and ii) to provide an estimate of drive frequency prior to more accurate laboratory-based measurements. We provide a target product profile for the RDT outlining minimally essential and ideal characteristics, including test procedures, sensitivity, specificity, usability by a range of stakeholders in field settings, and compatibility with pooled testing of mosquito samples. An RDT for gene drive construct detection would support community access and participation in monitoring, enhance regulatory oversight, and promote transparency in field trials, thereby facilitating responsible deployment of gene drive-based malaria interventions.

Integrating mosquito genomics into simulation modeling: Opportunities for better-informed biocontrol

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Gordana Rašić, John M. Marshall,  Current Opinion in Insect Science,  2025-11-03 11:25:51.
Mosquito-borne diseases remain a major global health burden, and novel biocontrol tools are quickly advancing from the laboratory to the field. Mathematical models play a central role in evaluating these interventions, yet their predictive accuracy depends on robust parameterization. Population genomics presents a powerful opportunity to address this challenge. Here, we review progress at the interface between mosquito genomics and biocontrol modeling, highlighting how genomic data have informed our understanding of mosquito population structure, standing genetic variation at gene drive target sites, and sources of resurgence for suppressed populations. We also discuss frontiers, including new approaches to quantifying gene flow, mating behaviors, and inbreeding depression, all of which shape intervention outcomes. By tapping this potential to better quantify our understanding of mosquito ecology, modelers can develop context-specific models with better predictive accuracy, supporting efficacy and risk assessment, design of field trials and interventions, and promotion of regulation and public trust.

Requirements for designing cluster randomised control trials to detect suppression of malaria vector population densities

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Hancock, 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.

Impact of sterile Aedes aegypti males releases on vector dynamics: insights from Malaysian field trials

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Nazni, W.A., Teoh, GN., Nuradila, M.A. et al.,  Infectious Diseases of Poverty,  14. 2025-05-04 16:00:48.
The Sterile insect technique (SIT) has been successfully used in agricultural pest control, leading to interest in its application for public health, particularly in controlling Aedes mosquitoes in the USA, Italy, Cuba, and Greece. Malaysia has conducted a small-scale SIT pilot trial since 2019 for dengue control. This study evaluates mosquito populations in treated and untreated sites through three objectives: (1) comparing mean larvae per trap (MLT) and dengue cases for Ae. aegypti and Aedes albopictus; (2) estimating survival rates and wild populations using mark-release-recapture (MRR); and (3) analysing spatial distribution in treated and untreated sites. Ae. aegypti males, irradiated at 55 Gray, were released in three locations: Pangsapuri Kota Laksamana (KT), Malacca (19 months), Pangsapuri Taman Tasik Utama (TTU), Malacca (8 months), and the Customs, Immigration, and Quarantine Complex (CIQ), Johor (7 months). Statistical analyses assessed SIT effectiveness, including T-tests for larval density and ovitrap indices, Mulla’s formula and relative variance (RV) for population reduction, and the Lincoln Index for estimating wild male populations and probability of daily survival. Weekly releases of sterile Ae. aegypti males at doses of 1278–7942 males/ha achieved a sterile-to-wild male ratio of 5.85 and a mean daily survival rate of 0.61, leading to significant reductions in larval densities: 76.25% in Kota Laksamana (KT), 96.74% in Taman Tasik Utama (TTU), and 89.00% in CIQ Gelang Patah, thereby supporting dengue control efforts. In KT, the MLT was initially low but increased, although with suppression < 90%, there was a reduce of dengue cases throughout the release period. The MRR’s mean survival rate (± standard deviation) in KT was 0.61 (± 0.08). The spatial clustering of Ae. aegypti was observed in central blocks during the high MLT period. However, larval densities rebounded after releases ceased. Spatial clustering revealed no initial clustering, though clustering patterns emerged over time in KT. SIT effectively suppressed Ae. aegypti populations and supported dengue control. Optimizing sterile-to-wild male ratios, spatial distribution, and monitoring strategies is essential for sustainable vector control. These findings provide insights for scaling up SIT field trials, with future efforts focusing on refining release and monitoring strategies to enhance SIT as an effective dengue control tool. Trial registration NMRR-17–2652-39,099 “Field evaluation of Sterile Insect for Aedes aegypti Suppression.”

GeneConvene Global Collaborative | Considerations for the First Field Trials of Gene Drive for Malaria

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GeneConvene Global Collaborative,  YouTube,  2024-11-04 17:19:36.
A webinar organized by the GeneConvene Global Collaborative discussed the potential first field trials of gene drive technology for malaria control. This genetic modification approach aims to alter mosquito populations to reduce their ability to transmit malaria. While laboratory results are promising, no field trials have been conducted yet. Experts convened to explore key considerations for trial design, including efficacy, safety, and stakeholder perceptions. The challenges of indefinite spread associated with low-threshold gene drives complicate trial logistics, necessitating a phased testing approach recommended by the WHO. Key factors for site selection include regulatory structures, existing health data, and the need for isolated mosquito populations. The session aimed to share insights and foster discussion on the future of gene drive applications in malaria control.

Effectiveness evaluation of mosquito suppression strategies on dengue transmission under changing temperature and precipitation

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Kaihui Liu, Shuanghui Fang, Qiong Li, et al.,  Acta Tropica,  2024-03-05 20:16:41.

Efficacy of Wolbachia-mediated sterility to reduce the incidence of dengue: a synthetic control study in Singapore

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Jue Tao Lim, Somya Bansal*, Chee Seng Chong*, Borame Dickens, Youming Ng, Lu Deng, Caleb Lee, Li Yun Tan, Grace Chain, Pei Ma, Shuzhen Sim, Cheong Huat Tan, Alex R Cook, Lee Ching Ng,  The Lancet Microbe,  2024-02-27 18:18:52.
Our study comprised an at-risk population of 607 872 individuals living in intervention sites and 3 894 544 individuals living in control sites. Interventions demonstrated up to 77·28% (121/156, 95% CI 75·81–78·58) intervention efficacy despite incomplete coverage across all towns until EW 26, 2022. Intervention efficacies increased as release coverage increased across all intervention sites. Releases led to 2242 (95% CI 2092–2391) fewer cases per 100 000 people in intervention sites during the study period. Secondary analysis showed that these intervention effects were replicated across all age groups and both sexes for intervention sites.

The mosquito knows no borders: Regional challenges for global confrontation in the dengue battle

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Barçante JMdP, Cherem J,  PLoS Neglected Tropical Diseases,  18. 2024-01-04 14:05:29.
Dengue fever is a neglected disease with a global impact, and its incidence and geographical reach are rapidly expanding. Global warming marked by higher average temperatures, precipitation, and longer periods of drought could prompt a record number of dengue fever infections worldwide, due to the thermal biology of mosquitoes. Additionally, increased movement of people, urbanization, and pressure on water and sanitation have driven the spread of dengue fever. The absence of access to tap water leads to an increased reliance on water-storing containers, which can facilitate the breeding of mosquitoes. Similarly, the lack of sanitation can contribute to the formation of small pools of stagnant water, serving as ideal breeding grounds for Aedes. While more prevalent in the tropical and subtropical regions, this viral infection, transmitted by Aedes aegypti and Ae. albopictus mosquitoes, poses a serious public health problem, with outbreaks increasing in number and severity worldwide. In Europe, Aedes mosquito vector species are established in about 22 countries, and dengue fever has been reported for over a decade. In addition to the factors mentioned earlier, the increase in mosquito breeding sites has been identified as a determining factor for the rise in the number of cases.

Utility of surveillance data for planning for dengue elimination in Yogyakarta, Indonesia: a scenario-tree modelling approach

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Melanie 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.

MGDrivE 3: A decoupled vector-human framework for epidemiological simulation of mosquito genetic control tools and their surveillance

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A. Mondal, C. H. M. Sanchez and J. M. Marshall,  bioRxiv,  2023.09.09.556958. 2023-09-12 08:11:56.
We present MGDrivE 3 (Mosquito Gene Drive Explorer 3), a new version of a previously-developed framework, MGDrivE 2, that investigates the spatial population dynamics of mosquito genetic control systems and their epidemiological implications. The new framework incorporates three major developments: i) a decoupled sampling algorithm allowing the vector portion of the MGDrivE framework to be paired with a more detailed epidemiological framework, ii) a version of the Imperial College London malaria transmission model, which incorporates age structure, various forms of immunity, and human and vector interventions, and iii) a surveillance module that tracks mosquitoes captured by traps throughout the simulation. Example MGDrivE 3 simulations are presented demonstrating the application of the framework to a CRISPR-based homing gene drive linked to dual disease-refractory genes and their potential to interrupt local malaria transmission. Simulations are also presented demonstrating surveillance of such a system by a network of mosquito traps. MGDrivE 3 is freely available as an open-source R package on CRAN (https://cran.r-project.org/package=MGDrivE2) (version 2.1.0), and extensive examples and vignettes are provided.

MGSurvE: A framework to optimize trap placement for genetic surveillance of mosquito population

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C. H. Sánchez, D. L. Smith and J. M. Marshall,  bioRxiv,  2023-06-23 13:35:51.
Genetic surveillance of mosquito populations is becoming increasingly relevant as genetics-based mosquito control strategies advance from laboratory to field testing. Especially applicable are mosquito gene drive projects, the potential scale of which leads monitoring to be a significant cost driver. For these projects, monitoring will be required to detect unintended spread of gene drive mosquitoes beyond field sites, and the emergence of alternative alleles, such as drive-resistant alleles or non-functional effector genes, within intervention sites. This entails the need to distribute mosquito traps efficiently such that an allele of interest is detected as quickly as possible - ideally when remediation is still viable. Additionally, insecticide-based tools such as bednets are compromised by insecticide-resistance alleles for which there is also a need to detect as quickly as possible. To this end, we present MGSurvE (Mosquito Gene SurveillancE): a computational framework that optimizes trap placement for genetic surveillance of mosquito populations such that the time to detection of an allele of interest is minimized. A key strength of MGSurvE is that it allows important biological features of mosquitoes and the landscapes they inhabit to be accounted for, namely: i) resources required by mosquitoes (e.g., food sources and aquatic breeding sites) can be explicitly distributed through a landscape, ii) movement of mosquitoes may depend on their sex, the current state of their gonotrophic cycle (if female) and resource attractiveness, and iii) traps may differ in their attractiveness profile. Example MGSurvE analyses are presented to demonstrate optimal trap placement for: i) an Aedes aegypti population in a suburban landscape in Queensland, Australia, and ii)an Anopheles gambiae population on the island of São Tomé, São Tomé and Príncipe. Further documentation and use examples are provided in project's documentation. MGSurvE is freely available as an open-source Python package on pypi ( https://pypi.org/project/MGSurvE/ ). It is intended as a resource for both field and computational researchers interested in mosquito gene surveillance. AUTHOR SUMMARY: Mosquito-borne diseases such as malaria and dengue fever continue to pose a major health burden throughout much of the world. The impact of currently-available tools, such as insecticides and antimalarial drugs, is stagnating, and gene drive-modified mosquitoes are considered a novel tool that could contribute to continuing reductions in disease transmission. Gene drive approaches are unique in the field of vector control in that they involve transgenes that could potentially spread on a wide scale, and consequently, surveillance is expected to be a major cost driver for the technology. This is needed to monitor for unintended spread of intact drive alleles, and the emergence of alternative alleles such as homing-resistance alleles and non-functional effector genes. Additionally, surveillance of insecticide-resistance alleles is of interest to support the impact of insecticide-based tools such as bednets. Here, we present MGSurvE, a computational framework that optimizes trap placement for genetic surveillance of mosquito populations in order to minimize the time to detection for an allele of interest. MGSurvE has been tailored to various features of mosquito ecology, and is intended as a resource for researchers to optimize the efficiency of limited surveillance resources.

Impact of randomised wmel Wolbachia deployments on notified dengue cases and insecticide fogging for dengue control in Yogyakarta City

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C. Indriani, S. K. Tanamas, U. Khasanah, M. R. Ansari, Rubangi, W. Tantowijoyo, R. A. Ahmad, S. M. Dufault, N. P. Jewell, A. Utarini, C. P. Simmons and K. L. Anders,  Glob Health Action,  16:2166650. 2023-01-26 09:27:00.
BACKGROUND: Releases of Wolbachia (wMel)-infected Aedes aegypti mosquitoes significantly reduced the incidence of virologically confirmed dengue in a previous cluster randomised trial in Yogyakarta City, Indonesia. Following the trial, wMel releases were extended to the untreated control areas, to achieve city-wide coverage of Wolbachia. OBJECTIVE: In this predefined analysis, we evaluated the impact of the wMel deployments in Yogyakarta on dengue hemorrhagic fever (DHF) case notifications and on the frequency of perifocal insecticide spraying by public health teams. METHODS: Monthly counts of DHF cases notified to the Yogyakarta District Health Office between January 2006 and May 2022 were modelled as a function of time-varying local wMel treatment status (fully- and partially-treated vs untreated, and by quintile of wMel prevalence). The frequency of insecticide fogging in wMel-treated and untreated areas was analysed using negative binomial regression. RESULTS: Notified DHF incidence was 83% lower in fully treated vs untreated periods (IRR 0.17 [95% CI 0.14, 0.20]), and 78% lower in areas with 80-100% wMel prevalence compared to areas with 0-20% wMel (IRR 0.23 [0.17, 0.30]). A similar intervention effect was observed at 60-80% wMel prevalence as at 80-100% prevalence (76% vs 78% efficacy, respectively). Pre-intervention, insecticide fogging occurred at similar frequencies in areas later randomised to wMel-treated and untreated arms of the trial. After wMel deployment, fogging occurred significantly less frequently in treated areas (IRR 0.17 [0.10, 0.30]). CONCLUSIONS: Deployments of wMel-infected Aedes aegypti mosquitoes resulted in an 83% reduction in the application of perifocal insecticide spraying, consistent with lower dengue case notifications in wMel-treated areas. These results show that the Wolbachia intervention effect demonstrated previously in a cluster randomised trial was also measurable from routine surveillance data.

Simple, sensitive, and cost-effective detection of wAlbB Wolbachia in Aedes mosquitoes, using loop mediated isothermal amplification combined with the electrochemical biosensing method

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P. Thayanukul, B. Lertanantawong, W. Sirawaraporn, S. Charasmongkolcharoen, T. Chaibun, R. Jittungdee and P. Kittayapong,  PLOS Neglected Tropical Diseases,  16:e0009600. 2022-05-13 07:05:35.
Author summary Mosquito-borne diseases such as dengue, chikungunya, zika, and yellow fever are transmitted to humans mainly by the bites of Aedes aegypti mosquitoes. Controlling the vectors of these diseases relies mostly on the use of insecticides. However, the efficiency has been reduced through the development of insecticide resistance in mosquitoes. Wolbachia is an endosymbiotic bacterium that is naturally found in 40% of insects, including mosquitoes. The bacterium can protect its insect hosts from viral infections and can also cause sterility in insect host populations, therefore, providing an opportunity to use it for human disease control. Application of a Wolbachia trans-infected mosquitoes needs simple, rapid and sensitive methods for detecting the bacteria in released mosquitoes. In this paper, we develop the methods of LAMP and BIOSENSORS for detecting wAlbB Wolbachia in mosquitoes. Our positive LAMP reaction can be visualized by color change from violet to blue at a sensitivity of ≥ 10 pg of genomic DNA. When used in combination with the BIOSENSOR method, the sensitivity increases a millionfold without losing specificity. Our study suggests that both developed methods, either used in combination or stand-alone, are efficient and cost-effective, hence, they could be applied for routine surveys of Wolbachia in mosquito control programs that use Wolbachia-based approaches.

First U.S. Open-Air Test of Genetically Modified Mosquitoes Deemed a Success

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S. Kuta,  Smithosonian Magazine,  2022-04-21 06:47:16.
A private company that released genetically modified mosquitoes into the open air of the Florida Keys last spring says the experiment was a success, reports Emily Waltz for Nature. Oxitec, a United Kingdom-based biotech firm initially founded at Oxford University, released the bugs in an effort to curb wild mosquito populations. The company has not yet published data from the experiment, but representatives said during a webinar earlier this month that the results were promising. Oxitec had already tested the genetically modified mosquitoes in the field in Brazil, Panama, the Cayman Islands and Malaysia, according to Nature, but this was the first open-air trial of genetically modified mosquitoes in the United States.

EVITA Dengue: a cluster-randomized controlled trial to EValuate the efficacy of Wolbachia-InfecTed Aedes aegypti mosquitoes in reducing the incidence of Arboviral infection in Brazil

20526
M. H. Collins, G. E. Potter, M. D. T. Hitchings, E. Butler, M. Wiles, J. K. Kennedy, S. B. Pinto, A. B. M. Teixeira, A. Casanovas-Massana, N. G. Rouphael, G. A. Deye, C. P. Simmons, L. A. Moreira, M. L. Nogueira, D. A. T. Cummings, A. I. Ko, M. M. Teixeir,  Trials,  23:185. 2022-03-02 08:20:38.
BACKGROUND: Arboviruses transmitted by Aedes aegypti including dengue, Zika, and chikungunya are a major global health problem, with over 2.5 billion at risk for dengue alone. There are no licensed antivirals for these infections, and safe and effective vaccines are not yet widely available. Thus, prevention of arbovirus transmission by vector modification is a novel approach being pursued by multiple researchers. However, the field needs high-quality evidence derived from randomized, controlled trials upon which to base the implementation and maintenance of vector control programs. Here, we report the EVITA Dengue trial design (DMID 17-0111), which assesses the efficacy in decreasing arbovirus transmission of an innovative approach developed by the World Mosquito Program for vector modification of Aedes mosquitoes by Wolbachia pipientis. METHODS: DMID 17-0111 is a cluster-randomized trial in Belo Horizonte, Brazil, with clusters defined by primary school catchment areas. Clusters (n = 58) will be randomized 1:1 to intervention (release of Wolbachia-infected Aedes aegypti mosquitoes) vs. control (no release). Standard vector control activities (i.e., insecticides and education campaigns for reduction of mosquito breeding sites) will continue as per current practice in the municipality. Participants (n = 3480, 60 per cluster) are children aged 6-11 years enrolled in the cluster-defining school and living within the cluster boundaries who will undergo annual serologic surveillance for arboviral infection. The primary objective is to compare sero-incidence of arboviral infection between arms. DISCUSSION: DMID 17-0111 aims to determine the efficacy of Wolbachia-infected mosquito releases in reducing human infections by arboviruses transmitted by Aedes aegypti and will complement the mounting evidence for this method from large-scale field releases and ongoing trials. The trial also represents a critical step towards robustness and rigor for how vector control methods are assessed, including the simultaneous measurement and correlation of entomologic and epidemiologic outcomes. Data from this trial will inform further the development of novel vector control methods. TRIAL REGISTRATION: ClinicalTrials.gov NCT04514107 . Registered on 17 August 2020 Primary sponsor: National Institute of Health, National Institute of Allergy and Infectious Diseases.

Monitoring Needs for Gene Drive Mosquito Projects: Lessons From Vector Control Field Trials and Invasive Species

20177
G. Rašić, N. F. Lobo, E. H. Jeffrey Gutiérrez, C. H. Sánchez and J. M. Marshall,  Frontiers in Genetics,  12:780327. 2022-01-25 09:18:49.
As gene drive mosquito projects advance from contained laboratory testing to semi-field testing and small-scale field trials, there is a need to assess monitoring requirements to: i) assist with the effective introduction of the gene drive system at field sites, and ii) detect unintended spread of gene drive mosquitoes beyond trial sites, or resistance mechanisms and non-functional effector genes that spread within trial and intervention sites. This is of particular importance for non-localized gene drive projects, as the potential scale of intervention means that monitoring is expected to be more costly than research, development and deployment. Regarding monitoring needs for population replacement systems, lessons may be learned from experiences with Wolbachia-infected mosquitoes, and for population suppression systems, from experiences with releases of genetically sterile male mosquitoes. For population suppression systems, assessing monitoring requirements for tracking population size and detecting rare resistant alleles are priorities, while for population replacement systems, allele frequencies must be tracked, and pressing concerns include detection of gene drive alleles with non-functional effector genes, and resistance of pathogens to functional effector genes. For spread to unintended areas, open questions relate to the optimal density and placement of traps and frequency of sampling in order to detect gene drive alleles, drive-resistant alleles or non-functional effector genes while they can still be effectively managed. Invasive species management programs face similar questions, and lessons may be learned from these experiences. We explore these monitoring needs for gene drive mosquito projects progressing through the phases of pre-release, release and post-release.

Field Trials of Gene Drive Mosquitoes: Lessons from Releases of Genetically Sterile Males and Wolbachia-infected Mosquitoes

19925
J. M. Marshall and V. N. Vásquez,  Genetically Modified and other Innovative Vector Control Technologies,  2021-12-21 09:27:08.
The discovery of CRISPR-based gene editing and its application to homing-based gene drive has been greeted with excitement, for its potential to control mosquito-borne diseases on a wide scale, and concern, for the invasiveness and potential irreversibility of a release. At the same time, CRISPR-based gene editing has enabled a range of self-limiting gene drive systems to be engineered with much greater ease, including (1) threshold-dependent systems, which tend to spread only when introduced above a certain threshold population frequency, and (2) temporally self-limiting systems, which display transient drive activity before being eliminated by virtue of a fitness cost. As these CRISPR-based gene drive systems are yet to be field-tested, plenty of open questions remain to be addressed, and insights can be gained from precedents set by field trials of other novel genetics-based and biological control systems, such as trials of Wolbachia-transfected mosquitoes, intended for either population replacement or suppression, and trials of genetically sterile male mosquitoes, either using the RIDL system (release of insects carrying a dominant lethal gene) or irradiation. We discuss lessons learned from these field trials and implications for a phased exploration of gene drive technology, including homing-based gene drive, chromosomal translocations, and split gene drive as a system potentially suitable for an intermediate release.

Population replacement gene drive characteristics for malaria elimination in a range of seasonal transmission settings: a modeling study

19134
S. Leung, N. Windbichler, E. Wenger, C. Bever and P. Selvaraj,  bioRxiv,  2021.11.01.466856. 2021-11-03 14:42:23.
Genetically engineering mosquitoes is a promising new vector control strategy to reinvigorate the fight against malaria in Sub-Saharan Africa. Using an agent-based model of malaria transmission with vector genetics, we examine the impacts of releasing population-replacement gene drive mosquitoes on malaria transmission and quantify the gene drive system parameters required to achieve local elimination within a spatially-resolved, seasonal Sahelian setting. We evaluate the performance of two different gene drive systems: "classic" and "integral". Various transmission regimes (low, moderate, and high - corresponding to annual entomological inoculation rates of 10, 30, and 80 infectious bites per person) and other simultaneous interventions, including deployment of insecticide-treated nets (ITNs) and passive healthcare seeking, are also simulated. Local elimination probabilities decreased with pre-existing population target site resistance frequency, increased with transmission-blocking effectiveness of the introduced antiparasitic gene and drive efficiency, and were context dependent with respect to fitness costs associated with the introduced gene. Of the four parameters, transmission-blocking effectiveness may be the most important to focus on for improvements to future gene drive strains because a single release of classic gene drive mosquitoes is likely to locally eliminate malaria in low to moderate transmission settings only when transmission-blocking effectiveness is very high (above approximately 80-90‰). However, simultaneously deploying ITNs and releasing integral rather than classic gene drive mosquitoes significantly boosts elimination probabilities, such that elimination remains highly likely in low to moderate transmission regimes down to transmission-blocking effectiveness values as low as approximately 50‰ and in high transmission regimes with transmission-blocking effectiveness values above approximately 80-90‰. Thus, a single release of currently achievable population replacement gene drive mosquitoes, in combination with traditional forms of vector control, can likely locally eliminate malaria in low to moderate transmission regimes within the Sahel. In a high transmission regime, higher levels of transmission-blocking effectiveness than are currently available may be required.Competing Interest StatementThe authors have declared no competing interest.

GeneConvene Global Collaborative Webinar Series | Decision and Analysis Tools for Complex Problems

18961
Hector Quemada and David O'Brochta,  GeneConvene Global Collaborative,  2021-10-13 20:07:26.
The challenges associated with the multiple phases of testing and possible deployment of gene drive-containing organisms appear to have similarities to those associated with various aspects of invasive species management. Preventing unwanted spread of the target species as well as monitoring and surveillance over large spatial scales are just two. Managing invasive species depends on making decisions based on an incomplete and sometimes very limited understanding of the relevant community ecology and the ever-present risk of unintended consequences. Can the deep experiences of those involved in invasive species management be leveraged against challenges in the gene drive domain? This webinar series will begin to explore that question.

Identifying Sites for Testing Modified Mosquitoes as a Strategy to Eradicate Malaria

18222
A. Fell,  UC Davis News,  2021-08-18 15:34:12.
In a newly published article in the journal Evolutionary Applications Professor Greg Lanzaro and his team at the Vector Genetics Laboratory, UC Davis School of Veterinary Medicine, set forth a framework for the selection of field sites in Africa best suited for testing genetically engineered mosquitoes (GEMs).“We followed earlier recommendations from the National Academy of Sciences and the World Health Organization that argued that a physical island would be a logical place to initiate early field trials of a GEM that uses gene drive technology,” Lanzaro said.n this paper, they establish a set of criteria including geographic and genetic isolation, biological complexity, island size, and topography and apply these criteria to a set of 22 potential island sites located off the coast of Africa. Their goal is to identify sites that maximize prospects for success, minimize risk, and serve as a fair, valid and convincing test of the efficacy and impacts of a GEM product intended for large-scale deployment in Africa.

GeneConvene Global Collaborative Webinar Series | Invasive Species Management: Informing Gene Drive Considerations

19307
David O'Brochta and Hector Quemada,  GeneConvene Global Collaborative,  2021-08-07 13:38:24.
The management, control and elimination of invasive species involves solving problems that have analogs to those anticipating the use of gene drive technologies to control and eliminate malaria in Africa.  Avoiding unintended consequences from interventions designed to reduce or remove a species from an ecosystem has parallels in some applications of gene drive technologies.  Monitoring and surveilling for the movement of invasive species is critical for making management decisions and methods and approaches that have been devised to deal with challenges such as large geographic areas, low species densities, limited resources to name just a few could inform thinking about monitoring and surveillance of gene drive-containing organisms.  This series of webinars by invasive species specialists will feature research into how these challenges are being successfully addressed.

Risk management recommendations for environmental releases of gene drive modified insects

17829
Y. Devos, J. D. Mumford, M. B. Bonsall, D. C. M. Glandorf and H. D. Quemada,  Biotechnology Advances,  2021-07-25 13:02:06.
The ability to engineer gene drives (genetic elements that bias their own inheritance) has sparked enthusiasm and concerns. Engineered gene drives could potentially be used to address long-standing challenges in the control of insect disease vectors, agricultural pests and invasive species, or help to rescue endangered species. However, risk concerns and uncertainty associated with potential environmental release of gene drive modified insects (GDMIs) have led some stakeholders to call for a global moratorium on such releases or the application of other strict precautionary measures to mitigate perceived risk assessment and risk management challenges. Instead, we provide recommendations that may help to improve the relevance of risk assessment and risk management frameworks for environmental releases of GDMIs. These recommendations include: (1) developing additional and more practical risk assessment guidance to ensure appropriate levels of safety; (2) making policy goals and regulatory decision-making criteria operational for use in risk assessment so that what constitutes harm is clearly defined; (3) ensuring a more dynamic interplay between risk assessment and risk management to manage uncertainty through closely interlinked pre-release modelling and post-release monitoring; (4) considering potential risks against potential benefits, and comparing them with those of alternative actions to account for a wider (management) context; and (5) implementing a modular, phased approach to authorisations for incremental acceptance and management of risks and uncertainty. Along with providing stakeholder engagement opportunities in the risk analysis process, the recommendations proposed may enable risk managers to make choices that are more proportionate and adaptive to potential risks, uncertainty and benefits of GDMI applications, and socially robust.

INSIDER: alignment-free detection of foreign DNA sequences

17657
A. P. Tay, B. Hosking, C. Hosking, D. C. Bauer and L. O. W. Wilson,  Computational and Structural Biotechnology Journal,  19:3810-3816. 2021-06-29 19:39:26.
External DNA sequences can be inserted into an organism’s genome either through natural processes such as gene transfer, or through targeted genome engineering strategies. Being able to robustly identify such foreign DNA is a crucial capability for health and biosecurity applications, such as anti-microbial resistance (AMR) detection or monitoring gene drives. This capability does not exist for poorly characterised host genomes or with limited information about the integrated sequence. To address this, we developed the INserted Sequence Information DEtectoR (INSIDER). INSIDER analyses whole genome sequencing data and identifies segments of potentially foreign origin by their significant shift in k-mer signatures. We demonstrate the power of INSIDER to separate integrated DNA sequences from normal genomic sequences on a synthetic dataset simulating the insertion of a CRISPR-Cas gene drive into wild-type yeast. As a proof-of-concept, we use INSIDER to detect the exact AMR plasmid in whole genome sequencing data from a Citrobacter freundii patient isolate. INSIDER streamlines the process of identifying integrated DNA in poorly characterised wild species or when the insert is of unknown origin, thus enhancing the monitoring of emerging biosecurity threats.

Burkina Faso Testing Genetically Modified Mosquitoes to Curb Malaria

17082
H. Wilkins,  Voice of America,  2021-05-20 15:06:44.
The mosquito-borne disease malaria kills more than 400,000 people each year, the vast majority in Africa. Target Malaria, an international group of scientists, is working in Burkina Faso on a genetic solution. Abdoulaye Diabate, with the West African country’s Research Institute for Science and Health, said the objective of Target Malaria is to develop a genetic control tool specifically applied to mosquitoes to be able to drastically reduce or eliminate the density of mosquitoes.  The scientists are genetically modifying mosquitoes so their offspring will be only male, and any females they mate with after release will also produce just males. Since only female mosquitoes spread malaria, the disease should drop off quickly along with their population. In village of Bana, where the genetically modified mosquitoes were first tested in 2019, locals were initially worried about the experiment. Kiesiara Sanou, a Bana village elder, said that at the beginning, people thought the survey would release mosquitoes in the village that could cause more diseases. But since working with Target Malaria, they’ve come to understand exactly what the purpose is and now even help them with tasks like collecting the mosquitoes. Genetically modified mosquitoes are just one malaria solution that has been tested in Burkina Faso. The country also pioneered pesticide-infused mosquito nets.

Small-Cage Laboratory Trials of Genetically-Engineered Anopheline Mosquitoes

17068
R. Carballar-Lejarazú, T. B. Pham, V. Bottino-Rojas, A. Adolfi and A. A. James,  J Vis Exp,  2021-05-18 14:30:01.
Control of mosquito-borne pathogens using genetically-modified vectors has been proposed as a promising tool to complement conventional control strategies. CRISPR-based homing gene drive systems have made transgenic technologies more accessible within the scientific community. Evaluation of transgenic mosquito performance and comparisons with wild-type counterparts in small laboratory cage trials provide valuable data for the design of subsequent field cage experiments and experimental assessments to refine the strategies for disease prevention. Here, we present three different protocols used in laboratory settings to evaluate transgene spread in anopheline mosquito vectors of malaria. These include inundative releases (no gene-drive system), and gene-drive overlapping and non-overlapping generation trials. The three trials vary in a number of parameters and can be adapted to desired experimental settings. Moreover, insectary studies in small cages are part of the progressive transition of engineered insects from the laboratory to open field releases. Therefore, the protocols described here represent invaluable tools to provide empirical values that will ultimately aid field implementation of new technologies for malaria elimination.

Selection of Sites for Field Trials of Genetically Engineered Mosquitoes with Gene Drive

16932
G. C. Lanzaro, M. Campos, M. Crepeau, A. Cornel, A. Estrada, H. Gripkey, Z. Haddad, A. Kormos, S. Palomares and W. Sharpee,  bioRxiv,  2021.04.28.441877. 2021-04-28 15:53:05.
Novel malaria control strategies using genetically engineered mosquitoes (GEMs) are on the horizon. Population modification is one approach wherein mosquitoes are engineered with genes rendering them refractory to the malaria parasite coupled with a low-threshold, Cas9-based gene drive. When released into a wild vector population, GEMs preferentially transmit these beneficial genes to their offspring, ultimately modifying a vector population into a non-vector one. Deploying this technology awaits evaluation including ecologically contained field trials. Here, we consider a process for site selection, the first critical step in designing a trial. Our goal is to identify a site that maximizes prospects for success, minimizes risk, and serves as a fair, valid, and convincing test of efficacy and impacts of a GEM product intended for large-scale deployment in Africa. We base site selection on geographical, geological, and biological, rather than social or legal, criteria. We recognize the latter as critically important but not preeminent. We propose physical islands as being the best candidates for a GEM field trial and present an evaluation of 22 African islands. We consider geographic and genetic isolation, biological complexity, island size, topography, and identify two island groups that satisfy key criteria for ideal GEM field trial sites.Competing Interest StatementThe authors have declared no competing interest.

Sterile Insect Technique (SIT) against Aedes Species Mosquitoes: A Roadmap and Good Practice Framework for Designing, Implementing and Evaluating Pilot Field Trials

16659
C. 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.

Application of the Relationship-Based Model to Engagement for Field Trials of Genetically Engineered Malaria Vectors

15898
A. Kormos, G. C. Lanzaro, E. Bier, G. Dimopoulos, J. M. Marshall, J. Pinto, A. Aguiar dos Santos, A. Bacar, H. Sousa Pontes Sacramento Rompão and A. A. James,  The American Journal of Tropical Medicine and Hygiene,  2020-12-21 14:17:29.
Although guidelines and recommendations for engagement for gene drives have recently been described, we argue here that communities and stakeholders should lead the planning, development, and implementation phases of engagement. The RBM provides a new approach to the development of ethical, transparent, and effective engagement strategies for malaria control programs.

Core commitments for field trials of gene drive organisms

15161
K. C. Long, L. Alphey, G. J. Annas, C. S. Bloss, K. J. Campbell, J. Champer, C.-H. Chen, A. Choudhary, G. M. Church, J. P. Collins, K. L. Cooper, J. A. Delborne, O. R. Edwards, C. I. Emerson, K. Esvelt, S. W. Evans, R. M. Friedman, V. M. Gantz, F. Gould,,  Science,  370:1417-1419. 2020-12-17 20:01:12.
While field trials of gene drive organisms (GDOs) ultimately will depend on public policy decisions, those engaged in GDO work can play critical roles in support of these decisions by generating evidence and developing evaluation strategies in fair and effective partnerships with relevant authorities and other stakeholders. The authorship of this statement reflects the current reality that GDO development is occurring primarily in high-income countries. However, fair partnership with counterparts and communities in low- and middle-income countries where many GDOs have the highest potential for positive impact, as well as recognition of the need for capacity-building and global cooperation, underlies each of our commitments.

Scientists paved the way for field trials of gene-driven organisms

15559
K. Winslet,  FLORIDA News Times,  2020-12-17 15:01:59.
The recent rise of gene drive research, accelerated by CRISPR-Cas9 gene editing technology, has brought about a wave of transformation throughout science.Developed with selected traits that have been genetically engineered to spread throughout the population, Gene Drive Organisms (GDOs) provide solutions to a variety of difficult health and environmental challenges, from control to protection of dengue and malaria. A crop against plant pests that has the power to dramatically change the way it develops.But before these gene-drive organisms move from laboratory to field testing, scientists are proposing courses for responsible testing of this powerful technology. These issues are addressed in the new Policy Forum article on Biotechnology Governance, “Core Commitment for Field Trials of Gene Drive Organisms,” published December 18, 2020. Science By more than 40 researchers, including several scientists at the University of California, San Diego.“Gene drives have led to rapid research, so we need to take a step back and think about its application and its impact on humankind,” said Akbari, the lead author of the article. Associate Professor, Faculty of Biological Sciences, University of California, San Diego. “A new initiative to tackle field testing is to ensure that testing is conducted safely, transparent, publicly accountable, and scientifically, politically and socially robust.”

Scientists Set a Path for Field Trials of Gene Drive Organisms

15551
M. Aguilera,  UC San Diego News Center,  2020-12-17 14:41:55.
The modern rise of gene drive research, accelerated by CRISPR-Cas9 gene editing technology, has led to transformational waves rippling across science. Gene drive organisms (GDOs), developed with select traits that are genetically engineered to spread through a population, have the power to dramatically alter the way society develops solutions to a range of daunting health and environmental challenges, from controlling dengue fever and malaria to protecting crops against plant pests. But before these gene drive organisms move from the laboratory to testing in the field, scientists are proposing a course for responsible testing of this powerful technology. These issues are addressed in a new Policy Forum article on biotechnology governance, “Core commitments for field trials of gene drive organisms,” published Dec. 18, 2020 in Science by more than 40 researchers, including several University of California San Diego scientists.

Interdisciplinary development of a standardized introduction to gene drives for lay audiences

15381
C. 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.

Further guidance required for assessment of gene drive technology, says EFSA

15137
Euractiv,  The World News Monitor,  2020-11-16 16:25:26.
Existing guidelines are adequate for evaluating risks associated with gene-drive modified insects, but further guidance is needed for some areas, most notably for environmental risk assessments. The evaluation was requested to explore the issue ahead of the consideration of any possible applications of the technology and is also designed to support the EU in discussions on the biosafety of GMOs in international fora such as the United Nations. It found that while existing guidelines are sufficient for evaluating risks associated with technology, further guidance is needed for some areas, such as molecular characterisation, environmental risk assessment and post-market environmental monitoring.

Adequacy and sufficiency evaluation of existing EFSA guidelines for the molecular characterisation, environmental risk assessment and post-market environmental monitoring of genetically modified insects containing engineered gene drives

15043
E. Panel o. G. M. Organisms, H. Naegeli, J.-L. Bresson, T. Dalmay, I. C. Dewhurst, M. M. Epstein, P. Guerche, J. Hejatko, F. J. Moreno, E. Mullins, F. Nogué, N. Rostoks, J. J. Sánchez Serrano, G. Savoini, E. Veromann, F. Veronesi, M. B. Bonsall, J. Mumfor,  EFSA Journal,  18:e06297. 2020-11-12 19:24:46.
As a proactive measure, the European Food Safety Authority (EFSA) has been requested by the European Commission to review whether its previously published guidelines for the risk assessment of genetically modified animals (EFSA, 2012 and 2013), including insects (GMIs), are adequate and sufficient for GDMIs, primarily disease vectors, agricultural pests and invasive species, for deliberate release into the environment. Under this mandate, EFSA was not requested to develop risk assessment guidelines for GDMIs. In this Scientific Opinion, the Panel on Genetically Modified Organisms (GMO) concludes that EFSA's guidelines are adequate, but insufficient for the molecular characterisation (MC), environmental risk assessment (ERA) and post-market environmental monitoring (PMEM) of GDMIs. While the MC,ERA and PMEM of GDMIs can build on the existing risk assessment framework for GMIs that do not contain engineered gene drives, there are specific areas where further guidance is needed for GDMIs.

EFSA advises on risk assessment of engineered gene drives

15069
EFSA,  European Food and Safety Authority,  2020-11-12 18:15:34.
EFSA’s existing guidelines for the risk assessment of genetically modified animals are adequate for evaluating risks associated with gene drive modified insects. However, further guidance is needed for some areas, such as molecular characterisation, environmental risk assessment and post-market environmental monitoring, say EFSA’s experts on Genetically Modified Organisms.

MGDrivE 2: A simulation framework for gene drive systems incorporating seasonality and epidemiological dynamics

14733
S. L. Wu, J. B. Bennett, H. M. Sanchez C, A. J. Dolgert, T. M. Leon and J. M. Marshall,  bioRxiv,  2020.10.16.343376. 2020-10-17 15:42:27.
We present MGDrivE 2 (Mosquito Gene Drive Explorer 2): an extension of and development from the MGDrivE 1 simulation framework that investigates the population dynamics of a variety of gene drive architectures and their spread through spatially-explicit mosquito populations.

Swarms of genetically modified mosquitoes could soon be descending on Florida

11594
A. J. Dellinger,  Mic,  2020-05-06 15:42:53.
Mosquitoes are a pain in the ass, so much so that the Environmental Protection Agency has approved a new and controversial field test aimed at curbing their population.

Two unresolved issues in community engagement for field trials of genetically modified mosquitoes

13541
D. B. Resnik,  Pathogens and Global Health,  113:238-245. 2019-09-25 19:32:29.
There is an emerging consensus among scientists, ethicists, and public health officials that substantive and effective engagement with communities and the wider public is required prior to releasing genetically modified mosquitoes into the environment.

Scientists release sterile mosquitoes in Burkina to fight malaria

17024
T. Ndiaga,  Reuters,  2019-09-18 13:18:20.
Scientists in Burkina Faso have deployed a new weapon in the fight against malaria, and waded into a thorny bioethics debate, by letting loose thousands of genetically sterilized mosquitoes.Their experiment is the first outside the lab to release genetically altered mosquitoes in the hope of reducing their ability to spread the often deadly disease. It works using a technique called a gene drive, which edits and then propagates a gene in a population - in this case to prevent males from producing offspring. Investments in anti-malarial drugs, mosquito nets and insecticides have slowed malaria over the past two decades in Africa, which accounts for more than 90% of global cases. But malaria still killed more than 400,000 people across the continent in 2017, and the World Health Organization says progress against the disease is stalling, leading researchers to push for fresh approaches.

Ecological effects on underdominance threshold drives for vector control

16267
D. Khamis, C. El Mouden, K. Kura and M. B. Bonsall,  Journal of Theoretical Biology,  456:1-15. 2018-11-07 16:39:27.
Here, ecological and epidemiological dynamics are coupled to a model of mosquito genetics to investigate theoretically the impact of different types of underdominance gene drive on disease prevalence. We model systems with two engineered alleles carried either on the same pair of chromosomes at the same locus or homozygously on different pairs at different loci, genetic lethality that affects both sexes or only females, and bi-sex or male-only releases.

Identifying and detecting potentially adverse ecological outcomes associated with the release of gene-drive modified organisms

3980
Hayes, KRH, G. R.; Dana, G. V.; Foster, S. D.; Ford, J. H.; Thresher, R.; Ickowicz, A.; Peel, D.; Tizard, M.; De Barro, P.; Strive, T.; Dambacher, J. M.,  Journal of Responsible Innovation,  5:S139-S158. 2018-01-18 00:00:00.
Synthetic gene drives could provide new solutions to a range of old problems such as controlling vector-borne diseases, agricultural pests and invasive species. In this paper, we outline methods to identify hazards and detect potentially adverse ecological outcomes at the individual (genotype, phenotype), population, community and ecosystem level, when progressing Gene Drive Modified Organisms through a phased test and release pathway. We discuss the strengths and weaknesses of checklists and structured hazard analysis techniques, identify methods to help meet some of the challenges of detecting adverse ecological outcomes in experiments and confined field trials, and discuss ways to improve the efficiency and statistical rigour of post-release monitoring strategies.

Informed consent in field trials of gene-drive mosquitoes

15682
P. A. Kolopack and J. V. Lavery,  Gates Open Research,  2017-12-11 14:46:00.
We argue that informed consent from individual research participants in gene drive trials may be required: (1) when blood and other forms of clinical data are collected from them, as will likely be the case in some studies involving epidemiological endpoints, such as the incidence of new infections with dengue and malaria; (2) when they participate in social science and/or behavioral research involving the completion of surveys and questionnaires; or (3) when their home or property is accessed and the location recorded as a spatial variable for the release or collection of mosquitoes because the precise location of the household is important for entomological reasons and these data constitute identifiable private information at the household level. Importantly, most regulations and guidelines allow these requirements to be waived or modified, to various degrees, according to the judgment of Institutional Review Boards.

A Revolutionary Genetic Experiment is Planned for a West African Village – If Residents Agree

11446
Ike Swetitz,  STAT,  2017-03-14 18:05:29.
This small village of mud-brick homes in West Africa might seem the least likely place for an experiment at the frontier of biology. Yet scientists here are engaged in what could be the most promising, and perhaps one of the most frightening, biological experiments of our time. They are preparing for the possible release of swarms of mosquitoes that, until now, have been locked away in a research lab behind double metal doors and guarded 24/7. The goal: to nearly eradicate the population of one species of mosquito, and with it, the heavy burden of malaria across Africa.

Modelling the spatial spread of a homing endonuclease gene in a mosquito population

4177
North, AB, A.; Godfray, H. C. J.,  Journal of Applied Ecology,  50:1216-1225. 2013-01-15 00:00:00.
Homing endonuclease genes (HEGs) exist naturally in many single-celled organisms and can show extremely strong genetic drive allowing them to spread through populations into which they are introduced. They are being investigated as tools to manipulate the populations of important vectors of human disease, in particular the mosquitoes that transmit malaria. Before HEGs can be deployed, it is important to study their spatial spread in order to design efficient release strategies. A spatially explicit model is developed to study the spread of a HEG through a landscape whose structure is defined by the distribution of mosquito breeding and feeding sites. The model is motivated by the biology of the major vectors of malaria in Africa. The conditions for spread, fixation and loss of two major types of HEG are explored in different landscapes. In landscapes where mosquito resources are abundant, the conditions for spread are well approximated by a mean-field model. Where a HEG imposes a genetic load, it can cause population extinction, though spatial models more often predict population suppression. In certain types of landscapes where mosquito resources are rare, an introduced HEG may be prevented from moving between local mosquito populations and so a simple release strategy is unlikely to be effective, yet if the HEG succeeds in spreading population extinction is a feasible outcome. Increasing the number of release sites at the expense of releasing fewer mosquitoes per site reduces the probability that a HEG will fail.Synthesis and applications. The model presented asks for the first time how the spatial structure of mosquito populations will influence the effectiveness of a technology that is being rapidly developed for vector control. If homing endonuclease genes (HEGs) are to be used in this way, we have qualified the importance of accounting for landscape characteristics in both the execution and the expectation of their application. The next stage is to use the model to study the spread of HEGs through real landscapes where releases may take place, something that will be facilitated by the results of the present study. The model presented asks for the first time how the spatial structure of mosquito populations will influence the effectiveness of a technology that is being rapidly developed for vector control. If homing endonuclease genes (HEGs) are to be used in this way, we have qualified the importance of accounting for landscape characteristics in both the execution and the expectation of their application. The next stage is to use the model to study the spread of HEGs through real landscapes where releases may take place, something that will be facilitated by the results of the present study.

Ethical issues in field trials of genetically modified disease-resistant mosquitoes

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D. B. Resnik,  Developing World Bioethics,  14:37-46. 2012-07-29 19:12:07.
Mosquito-borne diseases take a tremendous toll on human populations, especially in developing nations. In the last decade, scientists have developed mosquitoes that have been genetically modified to prevent transmission of mosquito-borne diseases, and field trials have been conducted. Some mosquitoes have been rendered infertile, some have been equipped with a vaccine they transmit to humans, and some have been designed to resist diseases.

RSPM No. 27 Guidelines for Importation and Confined Field Release of Transgenic Arthropods in NAPPO Member Countries

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NAPPPO,  NAPPO Regional Standards for Phytosanitary Measures,  2007-10-22 20:04:03.
This Standard is designed to provide guidance to NAPPO member countries on the importation and confined field release of transgenic arthropods that are known plant pests or have the potential to affect plant health. This includes transgenic arthropods used for biological control and transgenic beneficial arthropods with the potential to affect plant health. Transgenic arthropod species that are not plant pests, but that may pose a phytosanitary risk because of the genetic modification may also be considered under this Standard. Transgenic arthropods that have undergone a previous pest risk analysis by the regulatory authority of the importing country and been determined not to pose a phytosanitary risk may be exempted from importation requirements under this standard.