Cost-effectiveness of Precision Guided SIT for Control of Anopheles gambiae in the Upper River Region, The Gambia

Precision-guided sterile insect technique (pgSIT) is an extremely promising vector control intervention that can reduce and potentially eliminate the unacceptable malaria burden, particularly in sub-Saharan Africa. The deployment of pgSIT shows the greatest promise and does not have a near peer competitor in the fight to eradicate malaria. Here we explore the cost effectiveness of using this approach in Africa using mathematical modeling and economical analysis. Overall, we find that pgSIT represents a cost-effective and promising approach to A. gambiae control in The Gambia, with the potential to deliver significant economic and social benefits. Summary Precision-guided sterile insect technique (pgSIT) is an extremely promising vector control intervention that can reduce and potentially eliminate the unacceptable malaria burden, particularly in sub-Saharan Africa. pgSIT is a safe, innovative, and highly targeted approach to mosquito control that combines the principles of the sterile insect technique (SIT) with advanced state-of-the-art technologies of genetic engineering ([Akbari et al. 2023][1]; M. [Li et al. 2021][2]; [Kandul, Liu, and Akbari 2021][3]; [Kandul et al. 2019][4], [2022][5]). The technique involves inundative releases of genetically sterile male mosquitoes into the environment to mate with their wild counterparts, sterilizing them in the process. After multiple releases, this method can suppress, and even eradicate pest populations without the use of chemical pesticides or other less specific agents. The use of pgSIT has the potential to be a lasting, safe, cost-effective, sustainable, and environmentally friendly method to suppress a target species, acting as a chemical-free, species-specific insecticide. Before this work is considered for field application, however, we need to have a robust, data-driven modeling framework that will accurately predict the outcome of pgSIT release scenarios for malaria control, and we need an assessment of the costs and health benefits of implementing this technology in a region in Africa. This cost assessment evaluates the economic feasibility of both capacity building and establishing the infrastructure for a pgSIT facility in The Gambia to control the deadly malaria mosquito vector Anopheles gambiae . We focused on the Upper River region (URR) for three key reasons: (1) this area is known to have the highest per capita malaria rates in The Gambia (2) this region has more comprehensive historical and current data on malaria incidence and prevalence, malaria-associated healthcare and prevention costs, and human demographic data and (3) its location could feasibly demonstrate that a single pgSIT production facility can support phased suppression on a regional scale and then upon local extinction be repurposed to support vector suppression on a country or continent-wide scale. The pgSIT treatment of the URR (∼2069 km2) is predicted to prevent approximately 230 deaths and about 48,000 sick days per yea r. This estimate is based on a model for localized extinction of A. gambiae , reaching full epidemiological impact by the third year. There are multiple ways to calculate the value of this intervention monetarily, from the value of statistical life (VSL) to quality adjusted life years (QALY), which ranges from 367 million to 880 million USD saved in the first ten years of the facility being active. Other metrics such as willingness-to-pay (WTP), estimates the willingness of locals to contribute to malaria prevention financially, and estimates based on gross domestic product ( GDP) growth predict this model to save either 53 million or 551 million USD , respectively, in the first ten years of intervention. This model assumes localized extinction of A. gambiae by the second year of intervention with repeated releases to maintain extinction despite seasonal mosquito migration from beyond the treatment area. Localized extinction, however, is expected to have a year-to-year suppression effect making it easier to suppress mosquito populations with reduced sterile male releases in subsequent years. It is, therefore, likely an underestimate of the costs and benefits of pgSIT sterile male releases. In later years, the release of sterile males from this facility could be redirected to new areas to expand the suppression region. Additionally, this facility would have a significant off-season where the facility is not producing sterile male A. gambiae . This off-season could, therefore, produce sterile males to suppress A. gambiae populations in other regions with seasonal malaria during the off-season in The Gambiae. It could even be used to mass produce pgSIT sterile males for other mosquito species, such as the dengue vector, Aedes aegypti , which have eggs that can be stored for many months and consequently can be stockpiled to aid in the suppression of dengue outbreaks, which are also common in the area. Initially, however, the off-season can be used to build local capacity for genetically engineered (GE) mosquitos, which would consist of training staff, optimizing procedures, and troubleshooting any issues that arose during the higher production phases. The costs for this approach will vary as there are some unknowns and variability in the expected efficiencies of the facility, equipment, and procedures. In particular, mosquito survival rates and fecundity may vary more widely at scale and selection of the rearing equipment and protocols, and the mosquito sorting technology will dictate production levels and procedures. This variability is factored into the cost, and, therefore, a range of technologies and costs are considered. The expected start-up costs range from 6 to 11.5 million USD , which includes all necessary development, field trials, equipment, facility construction, staffing, and other establishment costs. The major upfront costs vary by facility size and capital equipment, much of which is dependent on mosquito rearing efficiencies. The annual estimated operational costs range from approximately 315,000 USD, depending on equipment selection and the size of the facility. Annually, this intervention costs less than 1 USD per person to suppress mosquitoes in the URR and prevent malaria transmission, which is about 6% of a malaria prevention WTP based on current interventions or 0.3-11% when using the VSL or QALY metrics, with most variation from the VSL calculation method. This intervention costs 15 to 124 USD (2022) to save one life-year and prevents malaria infections at 13 to 113 USD per case prevented, making this method competitive with many current interventions. WTP demonstrates that this facility could be made locally sustainable long term by local funding. Overall, the estimates of the capital and operational costs associated with the production of pgSIT sterile males, and the construction and management of the production facility indicate the cost savings associated with the annual decrease in morbidity and mortality (value of life) resulting from the use of pgSIT are significantly higher than the implementation costs. These estimates suggest that pgSIT represents a cost-effective and promising approach to A. gambiae control in The Gambia, with the potential to deliver significant economic and social benefits. ### Competing Interest Statement This work was supported by funding from an Open Philanthropy award (309937-0001). The views, opinions, and/or findings expressed are those of the authors and should not be interpreted as representing the official views or policies of the U.S. government. Figures were created using www.BioRender.com. * ABS : acrylonitrile butadiene styrene ACT : artemisinin-based combination treatment AI : artificial intelligence β 2-tubulin : beta-2 tubulin Cas9 : CRISPR associated protein 9 CHIRPS : Climate Hazards Group InfraRed Precipitation with Station COPAS Complex Object Parametric Analyzer and Sorter CRISPR : clustered regularly interspaced short palindromic repeats DNA : deoxyribonucleic acid dsx : doublesex GBP : British pound GDP : gross domestic product GE : genetically engineered GMD : Gambian dalasi HDR : homology directed repair fle femaleless : a female essential gene gRNA : guide RNA IAEA : International Atomic Energy Agency Ifegenia : inherited female elimination by genetically encoded nucleases to interrupt alleles ICL : Imperial College London IPTp : intermittent preventive treatment IRR : internal rate of return IRS : indoor residual spraying L1 : first instar larvae LLIN : long last insecticidal nets LSHTM : London School of Hygiene and Tropical Medicine MGDrivE Mosquito Gene Drive Explorer MRC : Medical Research Council NPV : net present value pgSIT : precision guided sterile insect technique pgSIT 2.0 : pgSIT incorporating SEPARATOR technology to support fluorescent sex specific sorting of the pgSIT lines PPP : purchasing power parity RIDL : Release of Insects carrying a Dominant Lethal RNA : ribonucleic acid ROI : return on investment SEPARATOR : Sexing Element Produced by Alternative RNA-splicing of A Transgenic Observable Reporter SIT : sterile insect technique SMC : seasonal malaria chemoprevention QALY : quality adjusted life years DALY : disability adjusted life years URR : Upper River region USD : United States dollar USTD : United States Transportation Department VSL : value of statistical life VTOL : vertical take-off and landing WHO : World Health Organization WTP : willingness to pay zpg : zero population growth [1]: #ref-3 [2]: #ref-60 [3]: #ref-52 [4]: #ref-54 [5]: #ref-53