BACKGROUND Long-lasting insecticidal nets (LLINs) are the primary malaria prevention tool, but their effectiveness is threatened by pyrethroid resistance. We embedded a pragmatic cluster-randomised trial into Uganda's national LLIN campaign to compare conventional LLINs with those containing piperonyl butoxide (PBO), a synergist that can partially restore pyrethroid susceptibility in mosquito vectors. METHODS 104 health sub-districts, from 48 districts in Uganda, were randomly assigned to LLINs with PBO (PermaNet 3.0 and Olyset Plus) and conventional LLINs (PermaNet 2.0 and Olyset Net) by proportionate randomisation using an iterative process. At baseline 6, 12, and 18 months after LLIN distribution, cross-sectional surveys were done in 50 randomly selected households per cluster (5200 per survey); a subset of ten households per cluster (1040 per survey) were randomly selected for entomological surveys. The primary outcome was parasite prevalence by microscopy in children aged 2-10 years, assessed in the as-treated population at 6, 12, and 18 months. This trial is registered with ISRCTN, ISRCTN17516395. FINDINGS LLINs were delivered to households from March 25, 2017, to March 18, 2018, 32 clusters were randomly assigned to PermaNet 3.0, 20 to Olyset Plus, 37 to PermaNet 2.0, and 15 to Olyset Net. In the as-treated analysis, three clusters were excluded because no dominant LLIN was received, and four clusters were reassigned, resulting in 49 PBO LLIN clusters (31 received PermaNet 3.0 and 18 received Olyset Plus) and 52 non-PBO LLIN clusters (39 received PermaNet 2.0 and 13 received Olyset Net). At 6 months, parasite prevalence was 11% (386/3614) in the PBO group compared with 15% (556/3844) in the non-PBO group (prevalence ratio [PR] adjusted for baseline values 0·74, 95% CI 0·62-0·87; p=0·0003). Parasite prevalence was similar at month 12 (11% vs 13%; PR 0·73, 95% CI 0·63-0·85; p=0·0001) and month 18 (12% vs 14%; PR 0·84, 95% CI 0·72-0·98; p=0·029). INTERPRETATION In Uganda, where pyrethroid resistance is high, PBO LLINs reduced parasite prevalence more effectively than did conventional LLINs for up to 18 months. This study provides evidence needed to support WHO's final recommendation on use of PBO LLINs. FUNDING The Against Malaria Foundation, UK Department for International Development, Innovative Vector Control Consortium, and Bill and Melinda Gates Foundation.

中文翻译：

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乌干达使用或不使用胡椒基丁醚的长效杀虫网对疟疾指标的影响（LLINEUP）：一项纳入全国LLIN分销活动的实用，整群随机试验。

背景技术长效杀虫网（LLIN）是主要的疟疾预防工具，但其有效性受到拟除虫菊酯抗性的威胁。我们在乌干达的全国性LLIN运动中进行了一项实用的集群随机试验，以比较常规LLIN与含有胡椒基丁醚（PBO）的增效剂，该协同剂可以部分恢复蚊媒对拟除虫菊酯的敏感性。方法将来自乌干达48个地区的104个健康分区随机分配到具有PBO（PermaNet 3.0和Olyset Plus）的LLIN和传统LLIN（PermaNet 2.0和Olyset Net），并采用迭代过程按比例随机分配。在LLIN分发后的第6、12和18个月的基线，每个集群中随机选择了50个家庭（每个调查5200个）进行了横断面调查。每个集群十个家庭的子集（每个调查1040个）被随机选择进行昆虫学调查。主要结果是2-10岁儿童的显微镜下寄生虫患病率，在接受治疗的6、12和18个月的人群中进行了评估。该试用版已在ISRCTN，ISRCTN17516395中注册。结果从2017年3月25日到2018年3月18日，向家庭分发了LLIN，将32个集群随机分配给PermaNet 3.0、20个分配给Olyset Plus，37个分配给PermaNet 2.0、15个分配给Olyset Net。在处理后的分析中，由于未接收到主导LLIN而排除了三个群集，并且重新分配了四个群集，从而导致49个PBO LLIN群集（31个接收PermaNet 3.0，18个接收Olyset Plus）和52个非PBO LLIN群集（39个）收到了PermaNet 2.0，而13则收到了Olyset Net）。在六个月后 PBO组的寄生虫患病率为11％（386/3614），而非PBO组的寄生虫患病率为15％（556/3844）（针对基线值0·74、95％CI 0·62- 0·87； p = 0·0003）。第12个月的寄生虫流行率相似（11％vs 13％; PR 0·73，95％CI 0·63-0·85; p = 0·0001）和18个月（12％vs 14％; PR 0·84） ，95％CI 0·72-0·98； p = 0·029）。解释在拟除虫菊酯抗性较高的乌干达，长达18个月的PBO LLIN比常规LLIN更有效地降低了寄生虫患病率。这项研究提供了支持WHO关于使用PBO LLIN的最终建议所需的证据。资金筹集对抗疟疾基金会，英国国际发展部，创新媒介控制协会以及比尔和梅琳达·盖茨基金会。