Abstract

BackgroundEstablishing the extent, geographical distribution and mechanisms of insecticide resistance in malaria vectors is a prerequisite for resistance management. Here, we report a widespread distribution of insecticide resistance in the major malaria vector An. funestus across Uganda and western Kenya under the control of metabolic resistance mechanisms.Methodology/Principal FindingsFemale An. funestus collected throughout Uganda and western Kenya exhibited a Plasmodium infection rate between 4.2 to 10.4%. Widespread resistance against both type I (permethrin) and II (deltamethrin) pyrethroids and DDT was observed across Uganda and western Kenya. All populations remain highly susceptible to carbamate, organophosphate and dieldrin insecticides. Knockdown resistance plays no role in the pyrethroid and DDT resistance as no kdr mutation associated with resistance was detected despite the presence of a F1021C replacement. Additionally, no signature of selection was observed on the sodium channel gene. Synergist assays and qRT-PCR indicated that metabolic resistance plays a major role notably through elevated expression of cytochrome P450s. DDT resistance mechanisms differ from West Africa as the L119F-GSTe2 mutation only explains a small proportion of the genetic variance to DDT resistance.ConclusionThe extensive distribution of pyrethroid and DDT resistance in East African An. funestus populations represents a challenge to the control of this vector. However, the observed carbamate and organophosphate susceptibility offers alternative solutions for resistance management.

Highlights

  • Establishing the extent, geographical distribution and mechanisms of insecticide resistance in malaria vectors is a prerequisite for resistance management

  • The extensive distribution of pyrethroid and DDT resistance in East African An. funestus populations represents a challenge to the control of this vector

  • Sporozoite infection rates A total of 18 out of 286 field-caught An. funestus were positive for Plasmodium falciparum sporozoites (Table S2)

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Summary

Introduction

Establishing the extent, geographical distribution and mechanisms of insecticide resistance in malaria vectors is a prerequisite for resistance management. We report a widespread distribution of insecticide resistance in the major malaria vector An. funestus across Uganda and western Kenya under the control of metabolic resistance mechanisms. Malaria burden remains high in sub-Saharan Africa where 90% of the 630,000 malaria deaths occurs [1]. Malaria is hyperendemic in Uganda and is the main cause of morbidity and mortality with about 100,000 deaths recorded annually (Ugandan Ministry of Health). About 50% of the reported fatalities occur in under-five children and nearly a third of the deaths are reported in pregnant women. Resistance to the main insecticides in the major malaria vectors such as An. gambiae and An. funestus is threatening the success of these control interventions

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