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Mosquito-targeted malaria control: alternative uses for existing insecticides and antimalarial drugs

INTRODUCTION: Malaria is a deadly infectious disease that affects millions of people around the world. This vector-borne tropical disease is caused by parasites that belong to the Plasmodium genus and is transmitted through the bite of an infected female Anopheles mosquito. Tools such as long-lasting insecticide nets (LLINs) and attractive toxic sugar baits (ATSBs) have been shown to work well in delivering insecticides to mosquitoes, but due to the spread of insecticide resistance throughout sub-Saharan Africa and Southeast Asia, there has been much interest in finding alternative chemical compounds against Anopheles mosquitoes. Compounds, such as methoxyfenozide (MET), have been shown to have insecticidal effects against Anopheles gambiae females. MET alongside another insecticide, hydramethylnon (HYD), have been shown to have antimalarial properties against mosquito-stage Plasmodium falciparum parasites; HYD’s insecticidal effects on A. gambiae is unknown. Atovaquone (ATQ), a known antimalarial drug for humans, has been observed to have antimalarial properties against mosquito-stage P. falciparum. The primary focus of my study is to assess the potential of the three compounds when used in tarsal contact assays (MET) or sugar feeding assays (ATQ, HYD, and MET).
METHODS: A. gambiae females were exposed to ATQ, HYD, or MET through sugar feeding assays, and MET through tarsal contact assays to assess the effect of these compounds on mosquito survival, P. falciparum infection, or mosquito egg development. Effects on P. falciparum infection were assessed through oocyst intensity, the prevalence of infection, the oocyst size, and the number of sporozoites present in the salivary glands.
RESULTS: Through sugar feeding, ATQ induced a significant reduction in P. falciparum prevalence of infection when A. gambiae were exposed to the treated sugars before an infectious blood meal. ATQ had also significant effects on P. falciparum oocyst size and number of sporozoites when A. gambiae were continuously exposed to the treated sugars after an infectious blood meal. There was a dose-dependent survival effect caused by HYD on A. gambiae females through sugar feeding, and also a significant effect of HYD-treated sugar feeding on the prevalence of P. falciparum infections. MET had little effect through tarsal contact on infection and egg development but showed significant effects on egg development through sugar feeding.
CONCLUSION: This study identified important compounds that could be used in ATSBs and LLINs. In particular, ATQ had antimalarial effects when infected mosquitoes were exposed to ATQ-treated sugar meals, and HYD-treated sugar meals had insecticidal effects against A. gambiae mosquitoes, with promising implications for the future of vector control and malaria eradication.

Identiferoai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/41295
Date13 July 2020
CreatorsMa, Erica
ContributorsGerstenfeld, Louis, Catteruccia, Flaminia
Source SetsBoston University
Languageen_US
Detected LanguageEnglish
TypeThesis/Dissertation
RightsAttribution 4.0 International, http://creativecommons.org/licenses/by/4.0/

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