The durability of pyrethroid LLINs with and without Piperonyl butoxide: results from a randomised control trial in Uganda.

背景与方法媒介按蚊对拟除虫菊酯类杀虫剂抗性日益增强，对长效杀虫蚊帐的使用构成威胁。为了恢复其敏感性，研究人员开发了添加增效剂胡椒酰丁醇（PBO）的LLINs。然而，关于它们的使用寿命的数据有限。在这里，两种PBO-LLINs （OlysetPlus和PermaNet3.0）的化学完整性、生物功效和织物完整性与它们的纯拟除虫菊酯等效物（Olyset和PermaNet2.0）在两年的使用中进行了比较。使用了0个月、12个月和25个月的蚊帐是由乌干达全国LLIN运动中的一项集群随机试验提供的。采用高效液相色谱法对活性成分进行定量分析，采用WHO锥型生物测定法对拟除虫菊酯抗性蝇类进行生物药效评价。冈比亚s.s.，通过测量孔洞和物理完整性。结果与讨论2年期间，所有被评估的LLINs的拟除虫菊酯类化合物含量稳定，而OlysetPlus和PermaNet3.0的PBO含量急剧下降，分别下降了55% （p<0.001）和58% （p<0.001）。在生物测定中，PermaNet3.0在基线时死亡率达到100%，但两年后下降到46.25% (CI:38.21-54.28) （p<0.001）。OlysetPlus的死亡率在所有时间点都非常低。仅使用拟除虫菊酯的LLINs在所有时间点都未能杀死人。LLIN产品之间的织物完整性没有差异。损害因房屋类型而异：茅草屋顶的平均损害为443cm2 (CI:161-1258cm2)，而铁屋顶的平均损害为32cm2 (CI:18-57cm2) （p=0.003）。这些来自乌干达的研究结果表明，这些PBO- llin中的PBO含量比拟除虫菊酯含量下降得更快，同时生物功效下降。此外，住房改善与减少物理损害有关，这可能限制蚊子的接近。

Background & MethodsThe use of long-lasting insecticidal nets (LLINs) in malaria control strategies is threatened by growing pyrethroid resistance in Anopheles vectors. To restore susceptibility, LLINs supplemented with the synergist piperonyl butoxide (PBO) have been developed. However, there is limited data on their operational lifespan. Here, the chemical integrity, bioefficacy and fabric integrity of two PBO-LLINs (OlysetPlus and PermaNet3.0) were compared with their pyrethroid-only equivalents (Olyset and PermaNet2.0) across two years of use.Nets used for 0, 12 and 25-months were provided from a cluster-randomised trial embedded into Uganda's national LLIN campaign. Active ingredients were quantified using high-performance liquid chromatography, bioefficacy assessed with WHO cone-bioassays against pyrethroid-resistant An. gambiae s.s., and physical integrity by measuring holes.Results & DiscussionThe pyrethroid content of all LLINs assessed was stable across the two-year period however the PBO content of OlysetPlus and PermaNet3.0 fell sharply, declining by 55% (p<0.001) and 58% (p<0.001) respectively. In bioassays, PermaNet3.0 achieved 100% mortality at baseline but declined to 46.25% (CI:38.21-54.28) after two years (p<0.001). Mortality with OlysetPlus was very low at all timepoints. The pyrethroid-only LLINs failed to kill at all timepoints. There was no difference in fabric integrity between LLIN products. Damage varied by housing type: mean damage was 443cm2 (CI:161-1258cm2) for thatched-roofed vs 32cm2 (CI:18-57cm2) for iron-roofed (p=0.003). These findings from Uganda indicate PBO content in these PBO-LLINs declines faster than pyrethroid content, accompanied by a reduction in bioefficacy. Additionally, housing improvement was associated with reduced physical damage which may limit accessibility to mosquitoes.