{"doi":"10.1371/journal.pgph.0003558","title":"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":"Long-lasting insecticidal nets (LLINs) are the cornerstone of malaria control, but their effectiveness is threatened by pyrethroid resistance. We embedded a pragmatic, cluster-randomised trial into Uganda's national LLIN distribution campaign in 2020-2021, comparing pyrethroid-piperonyl butoxide (PBO) LLINs to pyrethroid-pyriproxyfen LLINs. Target communities surrounding public health facilities (clusters, n=64), covering 32 districts 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. Malaria surveillance data were collected from health facilities from 1 November 2019 until 31 March 2023. Cluster-level estimates of malaria incidence in residents of all ages (primary outcome) were generated from enhanced health facility surveillance data. Cross-sectional community surveys were conducted in randomly selected households (at least 50 per cluster) at 12-months (24 November 2021 to 1 April 2022) and 24-months (23 November 2022 to 21 March 2023) post-LLIN distribution. Overall, 186,364 clinical malaria episodes were diagnosed in cluster residents during 398,931 person-years of follow-up. At 24-months, malaria incidence was lower than 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 there was no evidence of a difference between the arms (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 (24-months: 26.1% pyrethroid-PBO; 29.5% pyrethroid-pyriproxyfen; odds ratio 1.29 [95% CI: 0.81-2.05], p=0.29). The effectiveness of pyrethroid-PBO LLINs and pyrethroid-pyriproxyfen LLINs was no different in Uganda, but two years after mass distribution, LLIN coverage was inadequate. Trial registration: NCT04566510. Registered 28 September 2020, https://clinicaltrials.gov/ct2/show/NCT04566510.","journal":"PLOS Global Public Health","year":2025,"id":516496,"datarank":0.36030358935356144,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.014915825404454517,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.014915825404454517,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":5,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9428,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT04566510"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":587091,"name":"Jane Frances Namuganga","orcid":"0000-0001-8452-4247","position":1,"is_corresponding":false},{"id":810877,"name":"Martha Nassali","orcid":null,"position":2,"is_corresponding":false},{"id":260124,"name":"Catherine Maiteki‐Sebuguzi","orcid":"0000-0003-1471-7996","position":3,"is_corresponding":false},{"id":810876,"name":"Isaiah Nabende","orcid":null,"position":4,"is_corresponding":false},{"id":273698,"name":"Adrienne Epstein","orcid":"0000-0002-8253-6102","position":5,"is_corresponding":false},{"id":326864,"name":"Katherine Snyman","orcid":"0000-0002-0074-2720","position":6,"is_corresponding":false},{"id":260122,"name":"Joaniter I. Nankabirwa","orcid":"0000-0001-7818-3845","position":7,"is_corresponding":false},{"id":287604,"name":"Jimmy Opigo","orcid":"0009-0003-1521-4159","position":8,"is_corresponding":false},{"id":326557,"name":"Martin J. Donnelly","orcid":"0000-0001-5218-1497","position":9,"is_corresponding":false},{"id":242454,"name":"Grant Dorsey","orcid":"0000-0003-0740-0317","position":10,"is_corresponding":false},{"id":242453,"name":"Moses R. Kamya","orcid":"0000-0001-9106-4234","position":11,"is_corresponding":false},{"id":260131,"name":"Sarah G. Staedke","orcid":"0000-0003-2505-821X","position":12,"is_corresponding":false},{"id":325069,"name":"Samuel Gonahasa","orcid":"0000-0003-4865-0718","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-19T02:48:49.486328Z","pmid":"40009611","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}