Abstract
BackgroundThere is growing concern that malaria vector resistance to pyrethroid insecticides may reduce the effectiveness of long-lasting insecticidal nets (LLINs). Combination LLINs are designed to control susceptible and pyrethroid-resistant mosquito populations through a mixture of pyrethroid with piperonyl butoxide (PBO) synergist. A cluster randomized trial with entomology outcome measures was conducted in Mali to determine the added benefit over mono-treated pyrethroid predecessors. Four LLIN treatments; permethrin + PBO, permethrin, deltamethrin + PBO, and deltamethrin, were randomly allocated to four villages each (16 villages total) and distributed to cover every sleeping place. Entomological monitoring of indoor Anopheles resting densities, host preference, vector longevity, and sporozoite rates were monitored every 2 months over 2 years in 2014 and 2015.ResultsBottle bioassays confirmed permethrin and deltamethrin resistance in Anopheles gambiae sensu lato (s.l.), (the predominant species throughout the study) with pre-exposure to PBO indicating partial involvement of oxidases. Between 2014 and 2015 the mean indoor resting density was greater in the deltamethrin + PBO LLIN arm than the deltamethrin LLIN arm at 3.05 (95% CI 3.00–3.10) An. gambiae s.l. per room per day compared with 1.9 (95% CI 1.87–1.97). There was no significant difference in sporozoite rate at 3.97% (95% CI 2.91–5.02) for the deltamethrin LLIN arm and 3.04% (95% CI 2.21–3.87) for deltamethrin + PBO LLIN arm (P = 0.17). However, when analysed by season there was some evidence that the sporozoite rate was lower in the deltamethrin + PBO LLIN arm than deltamethrin LLIN arm during the rainy/high malaria transmission seasons at 1.95% (95% CI 1.18–2.72) and 3.70% (95% CI 2.56–4.84) respectively (P = 0.01).ConclusionsWhile there was some evidence that An. gambiae s.l. sporozoite rates were lower in villages with deltamethrin + PBO LLINs during the high malaria transmission seasons of 2014–2015, there was no reduction in parity rates or indoor resting densities. There was also no evidence that permethrin + PBO LLINs provided any improved control when compared with permethrin LLINs. Combination nets may have a greater impact in areas where mixed function oxidases play a more important role in pyrethroid resistance.
Highlights
There is growing concern that malaria vector resistance to pyrethroid insecticides may reduce the effectiveness of long-lasting insecticidal nets (LLINs)
Between 2000 and 2015 it is estimated that Plasmodium falciparum infection prevalence in Africa was reduced by 50%, with LLINs and indoor residual spraying (IRS) contributing to 81% of this decline [5]
Testing was conducted between August and September 2013 to determine pyrethroid resistance status of An. gambiae s.l. and whether resistance was associated with elevated expression of mixed function oxidases (MFOs)
Summary
There is growing concern that malaria vector resistance to pyrethroid insecticides may reduce the effectiveness of long-lasting insecticidal nets (LLINs). Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are frontline tools for malaria vector control. There is clear evidence that high coverage and utilization of LLINs reduces malaria mortality and morbidity rates and improves pregnancy outcomes in a range of transmission settings [2]. In sub-Saharan Africa, households owning at least one LLIN have increased from < 2% in 2000 to 55% (95% CI 50–58%) in 2015 [4]. The investment in malaria vector control including LLIN distribution and IRS appears to be justified. Mass nationwide distribution of LLINs and IRS in select districts have been primary elements of the national malaria control strategy in Mali since 2007. By 2015 this had increased to 92% of households in Mali having at least one LLIN, with an average of 3 LLINs per house [8]
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