LLIN Evaluation in Uganda Project (LLINEUP2) – Effect of long-lasting insecticidal nets (LLINs) treated with pyrethroid plus pyriproxyfen vs LLINs treated with pyrethroid plus piperonyl butoxide in Uganda: a cluster-randomised trial

Abstract

AbstractBackgroundWe embedded a pragmatic, cluster-randomised trial into Uganda’s national campaign to distribute long-lasting insecticidal nets (LLINs) in 2020–2021, comparing LLINs treated with pyrethroids plus the synergist piperonyl butoxide (PBO), to LLINs treated with pyrethroids plus pyriproxyfen, an insect growth regulator.MethodsTarget communities surrounding public health facilities (clusters, n=64), covering 32 high-burden districts not receiving indoor residual spraying, were included. Clusters were randomised 1:1 in blocks of two by district to receive: (1) pyrethroid-PBO LLINs (PermaNet 3.0, n=32) or (2) pyrethroid-pyriproxyfen LLINs (Royal Guard, n=32). LLINs were delivered from 7 November 2020 to 26 March 2021 and malaria outcome data were collected until 31 March 2023. Estimates of malaria incidence in residents of all ages (the primary outcome) were generated for each cluster from enhanced health facility surveillance data. At 12- (24 November 2021 to 1 April 2022) and 24-months (23 November 2022 to 21 March 2023) post-LLIN distribution, cross-sectional community surveys were conducted in randomly selected households (at least 50 per cluster, 3,200 per survey).FindingsIn the two years following LLIN distribution, 186,364 episodes of malaria were diagnosed in cluster residents during 398,931 person-years of follow-up. Malaria incidence after 24-months was lower than at baseline in both arms (pyrethroid-PBO: 465 vs 676 episodes per 1000 person-years; pyrethroid-pyriproxyfen: 469 vs 674 episodes per 1000 person-years); but the difference between the arms was not statistically significant (incidence rate ratio 1.06, 95% confidence interval [CI] 0.91– 1.22, p=0.47). Two years post-distribution, ownership of at least one LLIN for every two household residents was low in both arms (41.1% pyrethroid-PBO vs 38.6% pyrethroid-pyriproxyfen). Parasite prevalence in children aged 2-10 years was no different between the arms in either survey and similar results were observed for prevalence of anaemia in children aged 2-4 years.InterpretationThe effectiveness of pyrethroid-PBO LLINs and pyrethroid-pyriproxyfen LLINs was no different in Uganda, but two years after mass distribution, LLIN coverage was inadequate.FundingUS National Institutes for Health, Bill and Melinda Gates FoundationTrial registrationNCT04566510. Registered 28 September 2020,https://clinicaltrials.gov/ct2/show/NCT04566510