A field bioassay for assessing ivermectin bio-efficacy in wild malaria vectors

Abstract

Background: Ivermectin (IVM) mass drug administration is currently under evaluation as a complementary malaria vector control tool. Mosquitoes that ingest blood from treated hosts suffer reduction in survival. Estimating the bio-efficacy of IVM on wild-caught mosquitoes requires they ingest the drug in a bloodmeal either through a membrane or directly feeding on a treated host. The latter, has ethical implications, and the former results in very low feeding rates. Therefore, there is a need to develop a safe and effective method for monitoring IVM bio-efficacy in wild mosquitoes. Results: The mosquitocidal effect of IVM when administered in glucose solution is not comparable to the observed effects when same concentrations are administered in blood. Equal concentrations of IVM administered in blood resulted in more pronounced reductions in the probability of mosquito survival compared to when administered in glucose solution only. However, by adding small amounts of blood to a glucose solution, mosquito mortality rates can be increased resulting in effects closer to what is observed when blood feeding. A field bioassay was developed in the insectary to test bio-efficacy of IVM by using glucose solution containing a small amount of blood and administering it through a filter paper. Finally, the feasibility of the bioassay was tested using wild-caught mosquitoes in Kwale, Kenya. Conclusion: Bio-efficacy of ivermectin is strongly dependent on how the drug is ingested by the mosquito and is likely influenced by the associated digestive processes. The assay developed is a good candidate for field-based bio-efficacy monitoring: wild mosquitoes readily feed on the solution, the assay can be standardized using pre-selected concentrations and by not involving a treated blood host (human or animal) it avoids variation due to individual pharmacokinetic profiles as well as ethical issues. Meal volumes did not explain the difference between the lethality of IVM compared across the different meal types, further research is needed to understand the underlying mechanism.