Abstract

The widespread insecticide resistance raises concerns for vector control implementation and sustainability particularly for the control of the main vector of human malaria, Anopheles gambiae sensu stricto. However, the extent to which insecticide resistance mechanisms interfere with the development of the malignant malaria parasite in its vector and their impact on overall malaria transmission remains unknown. We explore the impact of insecticide resistance on the outcome of Plasmodium falciparum infection in its natural vector using three An. gambiae strains sharing a common genetic background, one susceptible to insecticides and two resistant, one homozygous for the ace-1R mutation and one for the kdr mutation. Experimental infections of the three strains were conducted in parallel with field isolates of P. falciparum from Burkina Faso (West Africa) by direct membrane feeding assays. Both insecticide resistant mutations influence the outcome of malaria infection by increasing the prevalence of infection. In contrast, the kdr resistant allele is associated with reduced parasite burden in infected individuals at the oocyst stage, when compared to the susceptible strain, while the ace-1 R resistant allele showing no such association. Thus insecticide resistance, which is particularly problematic for malaria control efforts, impacts vector competence towards P. falciparum and probably parasite transmission through increased sporozoite prevalence in kdr resistant mosquitoes. These results are of great concern for the epidemiology of malaria considering the widespread pyrethroid resistance currently observed in Sub-Saharan Africa and the efforts deployed to control the disease.

Highlights

  • Mosquito vectors experience a very intense selective pressure from insecticides used in malaria control programs through distribution of impregnated bed nets and use of indoor-residual spraying [1] with added pressure from the heavy use of insecticides for agricultural purposes [2,3]

  • The selection of insecticide resistance mutations has occurred in many vector species and various resistant alleles are widespread as a result of frequent applications of organochlorines (e.g. DDT), organophosphates (OP), carbamates (CX), and pyrethroids (PYR)

  • Pleiotropy underlining the fitness cost associated with resistance mechanisms is tricky to predict but resistant alleles may alter the physiology of mosquito vectors in various ways and may modify the environment of the pathogens they transmit [11]

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Summary

Introduction

Mosquito vectors experience a very intense selective pressure from insecticides used in malaria control programs through distribution of impregnated bed nets and use of indoor-residual spraying [1] with added pressure from the heavy use of insecticides for agricultural purposes [2,3]. In several mosquito species and populations, the unique G119S mutation in the ace-1 gene is responsible for OP and CX resistance [5] and the L1014F mutation in the para-type sodium channel gene (kdr-west mutation) is responsible for pyrethroid resistance in mosquitoes from West Africa [6]. The selection of these mutations leads to increased vector survival in treated environments and potentially to a greater population size, which could increase pathogen transmission. There is a gap that needs to be filled for implementing malaria control because insecticide resistance has spread to such an extent that it represents a critical issue

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