Abstract
ABSTRACT.Malaria vectors have acquired an enzyme that metabolizes pyrethroids. To tackle this problem, we evaluated long-lasting insecticidal nets incorporating piperonyl butoxide (PBO-LLINs) with a community-based cluster randomized control trial in western Kenya. The primary endpoints were anopheline density and Plasmodium falciparum polymerase chain reaction (PCR)-positive prevalence (PCRpfPR) of children aged 7 months to 10 years. Four clusters were randomly selected for each of the treatment and control arms (eight clusters in total) from 12 clusters, and PBO-LLINs and standard LLINs were distributed in February 2011 to 982 and 1,028 houses for treatment and control arms, respectively. Entomological surveys targeted 20 houses in each cluster, and epidemiological surveys targeted 150 children. Cluster-level permutation tests evaluated the effectiveness using the fitted values from individual level regression models adjusted for baseline. Bootstrapping estimated 95% confidence intervals (CIs). The medians of anophelines per house were 1.4 (interquartile range [IQR]: 2.3) and 3.4 (IQR: 3.7) in the intervention and control arms after 3 months, and 0.4 (IQR: 0.2) and 1.6 (IQR: 0.5) after 10 months, respectively. The differences were –2.5 (95% CI: –6.4 to –0.6) and –1.3 (95% CI: –2.0 to –0.7), respectively. The datasets of 861 and 775 children were analyzed in two epidemiological surveys. The median PCRpfPRs were 25% (IQR: 11%) in the intervention arm and 52% (IQR: 11%) in the control arm after 5 months and 33% (IQR: 11%) and 45% (IQR: 5%) after 12 months. The PCRpfPR ratios were 0.67 (95% CI: 0.38, 0.91) and 0.74 (95% CI: 0.53, 0.90), respectively. We confirmed the superiority of PBO-LLINs.
Highlights
Because an effective vaccine is not available for malaria, targeting vectors is an efficient way to reduce parasite infection
Modeling based on the results of meta-analyses indicates that even low levels of resistance are able to increase the incidence of malaria.[8]
The present study shows that piperonyl butoxide (PBO)-long-lasting insecticidal nets (LLINs) are more effective than standard LLINs in reducing P. falciparum infection in children
Summary
Because an effective vaccine is not available for malaria, targeting vectors is an efficient way to reduce parasite infection. The infection prevalence in endemic Africa halved between 2000 and 2015.4,5 the pace of reduction has stalled in recent years,[6,7] and the current situation is far from realizing elimination. A significant change in the current control strategy is needed to push forward the efforts for malaria elimination. Modeling based on the results of meta-analyses indicates that even low levels of resistance are able to increase the incidence of malaria.[8] Malaria vectors have developed two main resistance mechanisms, target site resistance and metabolic resistance.[9] The former resistance is related to the knockdown resistance (kdr) within the voltage-gated sodium channel gene; a point mutation at 1014L (L1014F or L1014S) causes insensitivity to pyrethroid insecticides.[10] Metabolic resistance is mediated by the enhanced activity of one or more enzymes (cytochrome P450s) that metabolize pyrethroid insecticides.[11,12]
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