Long-Lasting Insecticidal Nets Incorporating Piperonyl Butoxide Reduce the Risk of Malaria in Children in Western Kenya: A Cluster Randomized Controlled Trial

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.

Effect of long-lasting insecticidal nets with and without piperonyl butoxide on malaria indicators in Uganda (LLINEUP): final results of a cluster-randomised trial embedded in a national distribution campaign

“…The findings of a subsequently published cluster-randomised trial conducted in western Kenya in 2009-11 were consistent with these conclusions; parasite prevalence measured by PCR in children aged 7 months to 10 years was significantly lower at 5 and 12 months post-LLIN distribution in clusters that received PBO LLINs (Olyset Plus) compared with conventional LLINs (Olyset Net). 30 Considering the available data, in April 2021, WHO's Vector Control Advisory Group concluded that PBO LLINs are more effective than conventional non-PBO LLINs in areas with high-level pyrethroid resistance in malaria mosquito vectors, confirming the public health value of PBO LLINs. 31 In conclusion, we found that PBO LLINs provide superior protection against malaria prevalence and vector abundance 25 months post-distribution.…”

Clinical malaria incidence and health seeking pattern in geographically heterogeneous landscape of western Kenya

“…Clinical malaria incidences were high among school-aged children aged 5-14 years in all study zones, according to the findings. Lower bednet usage among school-aged children exposes them to high mosquito bites at night, which may explain why clinical malaria incidences are higher in this age group [34,39,40]. The low infection rate among children under the age of five compared to school-age children could be attributed to the children being cared for by their parents and sleeping under mosquito nets at night [12,[41][42][43].…”

Evaluation of the protective efficacy of Olyset®Plus ceiling net on reducing malaria prevalence in children in Lake Victoria basin, Kenya: study protocol for a cluster-randomized controlled trial

“…PBO inhibits the enzymes that break down pyrethroids. Previous studies have demonstrated the increased insecticidal effect of Olyset®Plus when compared with the standard LLINs, even in areas where pyrethroid-resistant mosquitoes were widely reported (20)(21)(22).…”