London School of Hygiene & Tropical Medicine, London, UK.
Centre de Recherche Entomologique de Cotonou, Cotonou, Benin.
Malar J. 2023 Jul 21;22(1):214. doi: 10.1186/s12936-023-04648-6.
Pyrethroid-chlorfenapyr (CFP) and pyrethroid-piperonyl butoxide (PBO) nets are being scaled across endemic countries to improve control of malaria transmitted by pyrethroid-resistant mosquitoes. CFP is a pro-insecticide requiring activation by mosquito cytochrome P450 monooxygenase enzymes (P450s) while PBO improves pyrethroid potency by inhibiting the action of these enzymes in pyrethroid-resistant mosquitoes. The inhibitory action of PBO against P450s may thus reduce the efficacy of pyrethroid-CFP nets when applied inside the same household as pyrethroid-PBO nets.
Two experimental hut trials were performed to evaluate the entomological impact of two different types of pyrethroid-CFP ITN (Interceptor G2, PermaNet Dual) when applied alone and in combination with pyrethroid-PBO ITNs (DuraNet Plus, PermaNet 3.0) against a pyrethroid-resistant vector population in southern Benin. In both trials, all net types were tested as single and double net treatments. Bioassays were also performed to assess the resistance profile of the vector population at the hut site and investigate interactions between CFP and PBO.
The vector population was susceptible to CFP but exhibited a high intensity of pyrethroid resistance that was overcame by PBO pre-exposure. Vector mortality was significantly lower in huts with combinations of pyrethroid-CFP nets plus pyrethroid-PBO nets compared to huts with two pyrethroid-CFP nets (74% vs. 85% for Interceptor G2 and 57% vs. 83% for PermaNet Dual, p < 0.001). PBO pre-exposure reduced the toxicity of CFP in bottle bioassays suggesting this effect may be partly attributable to antagonism between CFP and PBO. Higher levels of vector mortality were observed in huts with net combinations that included pyrethroid-CFP nets compared to those that did not and highest mortality was achieved when pyrethroid-CFP nets were applied alone as two nets together (83-85%).
This study shows evidence of a reduced performance of pyrethroid-CFP nets when combined with pyrethroid-PBO ITNs compared to when applied alone and higher efficacy with net combinations that included pyrethroid-CFP nets. These findings suggest that in similar contexts, prioritizing distribution of pyrethroid-CFP nets over other net types would maximize vector control impact.
拟除虫菊酯-氯氰菊酯(CFP)和拟除虫菊酯-增效醚(PBO)蚊帐正在流行国家推广,以改善对拟除虫菊酯抗性蚊子传播的疟疾的控制。CFP 是一种前体杀虫剂,需要被蚊子细胞色素 P450 单加氧酶(P450s)激活,而 PBO 通过抑制 P450s 在拟除虫菊酯抗性蚊子中的作用来提高拟除虫菊酯的效力。因此,当拟除虫菊酯-CFP 蚊帐与拟除虫菊酯-PBO 蚊帐一起在同一家庭中使用时,PBO 对 P450s 的抑制作用可能会降低拟除虫菊酯-CFP 蚊帐的效果。
在贝宁南部进行了两项实验性小屋试验,以评估两种不同类型的拟除虫菊酯-CFP ITN(Interceptor G2,PermaNet Dual)在单独使用和与拟除虫菊酯-PBO ITN(DuraNet Plus,PermaNet 3.0)联合使用时对耐拟除虫菊酯的蚊子种群的昆虫学影响。在这两项试验中,所有的蚊帐类型都作为单和双网处理进行了测试。还进行了生物测定,以评估蚊子种群在小屋现场的抗药性概况,并研究 CFP 和 PBO 之间的相互作用。
该蚊子种群对 CFP 敏感,但表现出高度的拟除虫菊酯抗性,这种抗性可通过 PBO 预暴露克服。与两个拟除虫菊酯-CFP 蚊帐的小屋相比,拟除虫菊酯-CFP 蚊帐加拟除虫菊酯-PBO 蚊帐组合的蚊子死亡率明显较低(Interceptor G2 为 74%,PermaNet Dual 为 85%,p<0.001)。PBO 预暴露降低了 CFP 在瓶生物测定中的毒性,这表明这种效应可能部分归因于 CFP 和 PBO 之间的拮抗作用。与不包括拟除虫菊酯-CFP 蚊帐的组合相比,包括拟除虫菊酯-CFP 蚊帐的组合的蚊子死亡率更高,单独使用拟除虫菊酯-CFP 蚊帐(83-85%)时死亡率最高。
本研究表明,与单独使用相比,拟除虫菊酯-CFP 蚊帐与拟除虫菊酯-PBO ITN 联合使用时,其性能降低,而包括拟除虫菊酯-CFP 蚊帐的网组合具有更高的效果。这些发现表明,在类似情况下,优先分发拟除虫菊酯-CFP 蚊帐而不是其他类型的蚊帐,将最大限度地提高蚊虫控制的效果。