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

疟疾控制策略中长效驱虫蚊帐（LLINs）的使用受到按蚊媒介对拟除虫菊酯耐药性不断增长的威胁。为了恢复敏感性，已经开发了补充有三丁基胡椒基丁醚（PBO）的长效驱虫蚊帐。然而，有关其使用寿命的数据有限。在此，两种PBO-LLIN（OlysetPlus和PermaNet3.0）的化学完整性、生物功效和织物完整性与其仅含拟除虫菊酯的等同物（Olyset和PermaNet2.0）在两年的使用中进行了比较。使用0、12和25个月的蚊帐来自嵌入乌干达国家LLIN运动的一项群集随机试验。采用高效液相色谱法对活性成分进行定量分析，采用WHO锥虫法对拟除虫菊酯耐药株进行生物活性评价。gambiae s.s.，结果与讨论所有评估的长效驱虫蚊帐的拟除虫菊酯含量在两年期间是稳定的，但是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在基线时达到100%的死亡率，但在两年后下降至46.25%（CI：38.21-54.28）（p<0.001）。OlysetPlus组在所有时间点的死亡率均非常低。仅含拟除虫菊酯的长效驱虫蚊帐在所有时间点均未杀灭。LLIN产品之间的织物完整性没有差异。损伤因房屋类型而异：茅草屋顶的平均损伤为443 cm 2（CI：161- 1258 cm 2），铁皮屋顶的平均损伤为32 cm 2（CI：18- 57 cm 2）（p=0.003）。乌干达的这些研究结果表明，这些PBO长效驱虫蚊帐中的PBO含量下降速度快于拟除虫菊酯含量，同时生物效力也会降低。此外，住房改善与减少可能限制蚊子进入的物理损害有关。

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.