Abstract

BackgroundThe effectiveness of long-lasting insecticidal nets (LLIN), the primary method for preventing malaria in Africa, is compromised by evolution and spread of pyrethroid resistance. Further gains require new insecticides with novel modes of action. Chlorfenapyr is a pyrrole insecticide that disrupts mitochrondrial function and confers no cross-resistance to neurotoxic insecticides. Interceptor® G2 LN (IG2) is an insecticide-mixture LLIN, which combines wash-resistant formulations of chlorfenapyr and the pyrethroid alpha-cypermethrin. The objective was to determine IG2 efficacy under controlled household-like conditions for personal protection and control of wild, pyrethroid-resistant Anopheles funestus mosquitoes.MethodsExperimental hut trials tested IG2 efficacy against two positive controls—a chlorfenapyr-treated net and a standard alpha-cypermethrin LLIN, Interceptor LN (IG1)—consistent with World Health Organization (WHO) evaluation guidelines. Mosquito mortality, blood-feeding inhibition, personal protection, repellency and insecticide-induced exiting were recorded after zero and 20 washing cycles. The trial was repeated and analysed using multivariate and meta-analysis.ResultsIn the two trials held in NE Tanzania, An. funestus mortality was 2.27 (risk ratio 95% CI 1.13–4.56) times greater with unwashed Interceptor G2 than with unwashed Interceptor LN (p = 0.012). There was no significant loss in mortality with IG2 between 0 and 20 washes (1.04, 95% CI 0.83–1.30, p = 0.73). Comparison with chlorfenapyr treated net indicated that most mortality was induced by the chlorfenapyr component of IG2 (0.96, CI 0.74–1.23), while comparison with Interceptor LN indicated blood-feeding was inhibited by the pyrethroid component of IG2 (IG2: 0.70, CI 0.44–1.11 vs IG1: 0.61, CI 0.39–0.97). Both insecticide components contributed to exiting from the huts but the contributions were heterogeneous between trials (heterogeneity Q = 36, P = 0.02). WHO susceptibility tests with pyrethroid papers recorded 44% survival in An. funestus.ConclusionsThe high mortality recorded by IG2 against pyrethroid-resistant An. funestus provides first field evidence of high efficacy against this primary, anthropophilic, malaria vector.

Highlights

  • The effectiveness of long-lasting insecticidal nets (LLIN), the primary method for preventing malaria in Africa, is compromised by evolution and spread of pyrethroid resistance

  • What is needed is an array of alternative insecticides that can complement the pyrethroids on Dual-active ingredient (AI) LLIN

  • Epidemiological evidence of effectiveness against malaria in cluster randomized trials (CRT) is a prerequisite before the World Health Organization (WHO) will grant recommendation of any new class of LLIN for malaria control

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Summary

Introduction

The effectiveness of long-lasting insecticidal nets (LLIN), the primary method for preventing malaria in Africa, is compromised by evolution and spread of pyrethroid resistance. The halving of the malaria burden over the last 15 years is largely attributed to increasing coverage of pyrethroid LLIN, which culminated in universal free distribution across all age groups in Africa [2] Concurrent with this public health achievement and cultural shift in sleeping behaviour has been the evolution and spread of pyrethroid resistance across Africa in the two primary vector mosquito species complexes. This is no trivial task as alternative insecticides for nets need to be safe to humans, toxic to mosquitoes, wash-tolerant on nets and exhibit no cross resistance to pyrethroids.

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