Lethal and sublethal impacts of membrane-fed ivermectin are concentration-dependant in Anopheles coluzzii
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Shepherd-Gorringe, Monique A. M., Pettit, Marie W. and Hawkes, Frances M. 
ORCID: https://orcid.org/0000-0002-0964-3702
(2024)
Lethal and sublethal impacts of membrane-fed ivermectin are concentration-dependant in Anopheles coluzzii.
Parasites and Vectors, 17:228.
ISSN 1756-3305 (Online)
(doi:10.1186/s13071-024-06287-5)
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46782 HAWKES_Lethal_And_Sublethal_Impacts_Of_Membrane-fed_Ivermectin.pdf - Published Version Available under License Creative Commons Attribution. Download (1MB) | Preview |
Abstract
Background
Ivermectin is a well-tolerated anthelminthic drug with wide clinical and veterinary applications. It also has lethal and sublethal effects on mosquitoes. Mass drug administration with ivermectin has therefore been suggested as an innovative vector control tool in efforts to curb emerging insecticide resistance and reduce residual malaria transition. To support assessments of the feasibility and efficacy of current and future formulations of ivermectin for vector control, we sought to establish the relationship between ivermectin concentration and its lethal and sublethal impacts in a primary malaria vector.
Methods
The in vitro effects of ivermectin on daily mortality and fecundity, measured by egg production, were assessed up to 14-days post-blood feed in a laboratory colony of Anopheles coluzzii. Mosquitoes were fed ivermectin in blood meals delivered by membrane feeding at one of six concentrations: 0 ng/mL (control); 10 ng/mL; 15 ng/mL; 25 ng/mL; 50 ng/mL; 75 ng/mL; and 100 ng/mL.
Results
Ivermectin had a significant effect on mosquito survival in a concentration-dependent manner. The LC50 at 7 days was 19.7 ng/mL. The time to median mortality at 50 ng/mL and above was 4days, compared to 9.6 days for control, and 6.3-7.6 days for ivermectin concentrations between 10- 25 ng/mL. Fecundity was also affected; no oviposition was observed in surviving females from the two highest concentration treatment groups. While females exposed to 10 to 50 ng/mL of ivermectin did oviposit, significantly fewer did so in the 50 ng/mL treatment group compared to the control, and they also produced significantly fewer eggs.
Conclusion
Our results showed ivermectin reduced mosquito survival in a concentration dependant manner and at ≥50 ng/mL significantly reduced fecundity in An. coluzzii. Results indicate that levels of ivermectin found in human blood following ingestion of a single 200 g/kg dose (equivalent to a 12 mg dose in a 60-kg individual) would be sufficient to achieve 50 % mortality across 7 days; however, fecundity in survivors is unlikely to be affected. At higher doses, a substantial impact on both survival and fecundity is likely. Treating human populations with ivermectin could be used as a supplementary malaria vector control method to kill mosquito populations and supress their reproduction, however strategies to safely maintain mosquitocidal blood levels of ivermectin against all Anopheles species require development.
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