Wanjiku, C. (Caroline)

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    A field bioassay for assessing ivermectin bio-efficacy in wild malaria vectors
    (2023) Yaah, F. (Festus ); Kamau, Y. (Yvonne); Karisa, J. (Jonathan); Ondieki, Z. (Zedekiah); Babu, L. (Lawrence); Musani, H. (Haron); Muriu, S. (Simon); Ominde, K. (Kelly); Kiuru, C. (Caroline); Chaccour, C.J. (Carlos J.); Tuwei, M. (Mercy); Maia, M. (Marta); Muturi, M. (Martha); Wanjiku, C. (Caroline); Mwangangi, J. (Joseph)
    Background Ivermectin (IVM) mass drug administration is a candidate complementary malaria vector control tool. Ingestion of blood from IVM treated hosts results in reduced survival in mosquitoes. Estimating bio-efficacy of IVM on wild-caught mosquitoes requires they ingest the drug in a blood meal either through a membrane or direct feeding on a treated host. The latter, has ethical implications, and the former results in low feeding rates. Therefore, there is a need to develop a safe and effective method for IVM bio-efficacy monitoring in wild mosquitoes. Methods Insectary-reared Anopheles gambiae s.s. were exposed to four IVM doses: 85, 64, 43, 21 ng/ml, and control group (0 ng/ml) in three different solutions: (i) blood, (ii) 10% glucose, (iii) four ratios (1:1, 1:2, 1:4, 1:8) of blood in 10% glucose, and fed through filter paper. Wild-caught An. gambiae s.l. were exposed to 85, 43 and 21 ng/ml IVM in blood and 1:4 ratio of blood-10% glucose mixture. Survival was monitored for 28 days and a pool of mosquitoes from each cohort sacrificed immediately after feeding and weighed to determine mean weight of each meal type. Results When administered in glucose solution, mosquitocidal effect of IVM was not comparable to the observed effects when similar concentrations were administered in blood. Equal concentrations of IVM administered in blood resulted in pronounced reductions in mosquito survival compared to glucose solution only. However, by adding small amounts of blood to glucose solution, mosquito mortality rates increased resulting in similar effects to what was observed during blood feeding. Conclusion Bio-efficacy of ivermectin is strongly dependent on mode of drug delivery to the mosquito and likely influenced by digestive processes. The assay developed in this study 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 treated blood hosts (human or animal) variation in individual pharmacokinetic profiles as well as ethical issues are bypassed. Meal volumes did not explain the difference in the lethality of IVM across the different meal types necessitating further research on the underlying mechanisms.
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    Effects of larval exposure to sublethal doses of ivermectin on adult fitness and susceptibility to ivermectin in Anopheles gambiae s.s
    (2023) Babu, L. (Lawrence); Ominde, K. (Kelly); Kiuru, C. (Caroline); Chaccour, C.J. (Carlos J.); Maia, M. (Marta); Muturi, M. (Martha); Wanjiku, C. (Caroline)
    Background The effects of ivermectin (endectocide) on mosquito survival make it a potential new malaria vector control tool. The drug can be administered to mosquito disease vectors through blood hosts that include humans and livestock. Its increased use may cause contamination of larval habitats, either directly through livestock excreta or indirectly through leaching or run-off from contaminated soil, albeit in sublethal doses. However, the effects of such exposure on immature stages and the subsequent adults that emerge are poorly understood. This study was undertaken to evaluate the impact of ivermectin exposure on Anopheles gambiae s.s. larvae and its effects on fitness and susceptibility to ivermectin in the emerging adults. Methods Laboratory-reared An. gambiae s.s. (Kilifi strain) larvae were exposed to five different ivermectin concentrations; 0, 0.00001, 0.0001, 0.001, and 0.01 ppm, and larval survival was monitored to determine the appropriate sublethal dose. Concentrations with survival > 50% (0.00001 and 0.0001 ppm) were selected and used as the sub-lethal doses. The fecundity, fertility, and susceptibility to ivermectin of adults emerging after larval exposure to the sub-lethal doses were examined. Results Overall, exposure of An. gambiae s.s. aquatic stages to ivermectin caused a dose-dependent reduction in larval survival irrespective of the stage at which the larvae were exposed. Exposure to ivermectin in the larval stage did not have an effect on either the number of eggs laid or the hatch rate. However, exposure of first/second-instar larvae to 0.0001 ppm and third/fourth-instar larvae to 0.001 ppm of ivermectin reduced the time taken to oviposition. Additionally, exposure to ivermectin in the larval stage did not affect susceptibility of the emerging adults to the drug. Conclusions This study shows that contamination of larval habitats with ivermectin affects An. gambiae s.s. larval survival and could potentially have an impact on public health. However, there are no carry-over effects on the fecundity, fertility, and susceptibility of the emerging adults to ivermectin. In addition, this study shows that environmental exposure to ivermectin in the larval habitats is unlikely to compromise the efficacy of ivermectin in the emerging adults.