Martin Jackline L, Messenger Louisa A, Rowland Mark, Mosha Franklin W, Bernard Edmund, Kisamo Monica, Limbe Shaban, Hape Patric, Thickstun Charles, Steven Crene, Moshi Oliva, Shirima Boniface, Matowo Nancy S, Mosha Jacklin F, Dee Dominic P, Churcher Thomas S, Kulkarni Manisha A, Manjurano Alphaxard, Protopopoff Natacha
Department of Parasitology, Pan-African Malaria Vector Research Consortium, Kilimanjaro Christian Medical University College, Moshi, United Republic of Tanzania.
Department of Parasitology, National Institute for Medical Research, National Institute for Medical Research- Mwanza Center, Mwanza, United Republic of Tanzania.
PLOS Glob Public Health. 2024 Oct 4;4(10):e0002586. doi: 10.1371/journal.pgph.0002586. eCollection 2024.
New classes of long-lasting insecticidal nets (LLINs), have been recommended by the World Health Organization (WHO) to control malaria vectors resistant to pyrethroid insecticides. This study was nested in a large-scale cluster-randomized controlled trial conducted (cRCT) in Tanzania. A series of experimental hut trials (EHTs) aimed to evaluate the bio-efficacy of trial LLINs on mosquito indicators most pertinent to malaria transmission over 3 years of use in the community in order to better understand the outcomes of the cRCT. The following field-collected LLINs were assessed: 1) Olyset Plus (combining piperonyl butoxide synergist and permethrin), 2) Interceptor G2 (chlorfenapyr and alpha-cypermethrin), 3) Royal Guard (pyriproxyfen and alpha-cypermethrin), 4) Interceptor (alpha-cypermethrin only) conducted in parallel with 5) a new Interceptor, and 6) an untreated net. Thirty nets of each type were withdrawn from the community at 12, 24, and 36 months after distribution and used for the EHTs. Pre-specified outcomes were 72-hour mortality for Interceptor G2, 24-hour mortality for Olyset Plus, and fertility based on egg development stage for Royal Guard. Overall, Interceptor G2 LLINs induced higher 72-hour mortality compared to standard LLINs of the same age up to12 months (44% vs 21%, OR: 3.5, 95% CI: 1.9-6.6, p-value < 0.001), and 24-hour mortality was only significantly higher in Olyset Plus when new (OR: 13.6, 95%CI: 4.4-41.3, p-value < 0.001) compared to standard LLINs but not at 12 months (17% vs 13%; OR: 2.1, 95% CI: 1.0-4.3; p-value = 0.112). A small, non-significant effect of pyriproxyfen on Anopheles fertility was observed for Royal Guard up to 12 months (75% vs 98%, OR: 1.1, 95% CI: 0.0-24.9, p-value = 0.951). There was no evidence of a difference in the main outcomes for any of the new classes of LLINs at 24 and 36 months compared to standard LLINs. Interceptor G2 LLINs showed superior bio-efficacy compared to standard LLINs only up to 12 months, and the effect of Olyset Plus was observed when new for all species and 12 months for An. gambiae s.l. only. The pyriproxyfen component of Royal Guard had a short and limited effect on fertility. The decrease in effectiveness of Olyset Plus and Royal Guard LLINs in the EHTs aligns with findings from the cRCT, whereas efficacy of Interceptor G2 lasted for a longer period in the cRCT compared to the EHT. Further investigations are needed to understand the complete scope of chlorfenapyr mode of action. Additional EHT in various contexts will help confirm the residual efficacy of the dual active ingredient LLINs and support the development of longer-lasting nets.
世界卫生组织（WHO）推荐了新型长效杀虫网（LLINs）来控制对拟除虫菊酯类杀虫剂产生抗性的疟疾传播媒介。本研究嵌套于在坦桑尼亚进行的一项大规模整群随机对照试验（cRCT）中。一系列实验小屋试验（EHTs）旨在评估试验性LLINs在社区使用3年期间对与疟疾传播最相关的蚊虫指标的生物效能，以便更好地了解cRCT的结果。对以下现场收集的LLINs进行了评估：1）Olyset Plus（含胡椒基丁醚增效剂和氯菊酯），2）Interceptor G2（溴虫腈和高效氯氰菊酯），3）Royal Guard（吡丙醚和高效氯氰菊酯），4）Interceptor（仅高效氯氰菊酯），同时与5）一种新型Interceptor，以及6）未处理蚊帐进行平行试验。每种类型的30顶蚊帐在分发后12、24和36个月从社区中收回，用于EHTs。预先设定的结果为：Interceptor G2的72小时死亡率、Olyset Plus的24小时死亡率，以及基于Royal Guard卵发育阶段的繁殖力。总体而言，与同龄标准LLINs相比，Interceptor G2 LLINs在长达12个月的时间内诱导了更高的72小时死亡率（44%对21%，OR：3.5，95%CI：1.9 - 6.6，p值<0.001），而Olyset Plus仅在新蚊帐时24小时死亡率显著高于标准LLINs（OR：13.6，95%CI：4.4 - 41.3，p值<），但在12个月时并非如此（17%对13%；OR：2.1，95%CI：1.0 - 4.3；p值 = 0.112）。在长达12个月的时间里，观察到Royal Guard的吡丙醚对按蚊繁殖力有微小的、不显著的影响（75%对98%，OR：1.）。与标准LLINs相比，在24和36个月时，没有证据表明任何新型LLINs的主要结果存在差异。Interceptor G2 LLINs仅在长达12个月的时间内显示出比标准LLINs更好的生物效能，而Olyset Plus对所有物种在新蚊帐时以及对冈比亚按蚊复合组仅在12个月时观察到其效果。Royal Guard的吡丙醚成分对繁殖力的影响短暂且有限。Olyset Plus和Royal Guard LLINs在EHTs中的有效性下降与cRCT的结果一致，而与EHT相比，Interceptor G2在cRCT中的效能持续时间更长。需要进一步研究以了解溴虫腈作用模式的完整范围。在各种情况下进行额外的EHT将有助于确认双活性成分LLINs的残留效能，并支持开发更长效的蚊帐。
