Oxborough Richard M, N'Guessan Raphael, Jones Rebecca, Kitau Jovin, Ngufor Corine, Malone David, Mosha Franklin W, Rowland Mark W
Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK.
Department of Entomology and Parasitology, Kilimanjaro Christian Medical University College, Moshi, Kilimanjaro, Tanzania.
Malar J. 2015 Mar 24;14:124. doi: 10.1186/s12936-015-0639-x.
The rapid selection of pyrethroid resistance throughout sub-Saharan Africa is a serious threat to malaria vector control. Chlorfenapyr is a pyrrole insecticide which shows no cross resistance to insecticide classes normally used for vector control and is effective on mosquito nets under experimental hut conditions. Unlike neurotoxic insecticides, chlorfenapyr owes its toxicity to disruption of metabolic pathways in mitochondria that enable cellular respiration. A series of experiments explored whether standard World Health Organization (WHO) guidelines for evaluation of long-lasting insecticidal nets, developed through testing of pyrethroid insecticides, are suitable for evaluation of non-neurotoxic insecticides.
The efficacy of WHO recommended cone, cylinder and tunnel tests was compared for pyrethroids and chlorfenapyr. To establish bioassay exposure times predictive of insecticide-treated net (ITN) efficacy in experimental hut trials, standard three-minute bioassays of pyrethroid and chlorfenapyr ITNs were compared with longer exposures. Mosquito behaviour and response to chlorfenapyr ITN in bioassays conducted at night were compared to day and across a range of temperatures representative of highland and lowland transmission.
Standard three-minute bioassay of chlorfenapyr produced extremely low levels of mortality compared to pyrethroids. Thirty-minute day-time bioassay produced mortality closer to hut efficacy of chlorfenapyr ITN but still fell short of the WHO threshold. Overnight tunnel test with chlorfenapyr produced 100% mortality and exceeded the WHO threshold of 80%. The endogenous circadian activity rhythm of anophelines results in inactivity by day and raised metabolism and flight activity by night. A model which explains improved toxicity of chlorfenapyr ITN when tested at night, and during the day at higher ambient temperature, is that activation of chlorfenapyr and disruption of respiratory pathways is enhanced when the insect is more metabolically and behaviourally active.
Testing according to current WHO guidelines is not suitable for certain types of non-neurotoxic insecticide which, although highly effective in field trials, would be overlooked at the screening stage of evaluation through bioassay. Testing methods must be tailored to the characteristics and mode of action of each insecticide class. The WHO tunnel test on night-active anophelines is the most reliable bioassay for identifying the toxicity of novel insecticides.
在撒哈拉以南非洲地区，拟除虫菊酯抗性的快速出现对疟疾媒介控制构成严重威胁。氯虫苯甲酰胺是一种吡咯类杀虫剂，对通常用于媒介控制的杀虫剂类别无交叉抗性，且在实验小屋条件下对蚊帐有效。与神经毒性杀虫剂不同，氯虫苯甲酰胺的毒性源于其对线粒体中使细胞呼吸得以进行的代谢途径的破坏。一系列实验探讨了世界卫生组织（WHO）通过拟除虫菊酯杀虫剂测试制定的长效杀虫蚊帐评估标准指南，是否适用于非神经毒性杀虫剂的评估。
比较了拟除虫菊酯类和氯虫苯甲酰胺的WHO推荐的锥形、圆筒形和隧道试验的效果。为确定在实验小屋试验中预测杀虫剂处理蚊帐（ITN）效果的生物测定暴露时间，将拟除虫菊酯和氯虫苯甲酰胺ITN的标准三分钟生物测定与更长时间的暴露进行了比较。在夜间进行的生物测定中，将蚊子对氯虫苯甲酰胺ITN的行为和反应与白天以及代表高地和低地传播的一系列温度下的情况进行了比较。
与拟除虫菊酯类相比，氯虫苯甲酰胺的标准三分钟生物测定产生的死亡率极低。三十分钟的白天生物测定产生的死亡率更接近氯虫苯甲酰胺ITN的小屋效果，但仍未达到WHO阈值。氯虫苯甲酰胺的过夜隧道试验产生了100%的死亡率，超过了WHO的80%阈值。按蚊的内源性昼夜活动节律导致其白天不活动，夜间新陈代谢和飞行活动增强。一个解释氯虫苯甲酰胺ITN在夜间以及白天较高环境温度下测试时毒性提高的模型是，当昆虫代谢和行为更活跃时，氯虫苯甲酰胺的活化以及呼吸途径的破坏会增强。
根据当前WHO指南进行测试不适用于某些类型的非神经毒性杀虫剂，这些杀虫剂尽管在现场试验中非常有效，但在通过生物测定进行评估的筛选阶段会被忽视。测试方法必须根据每种杀虫剂类别的特性和作用方式进行调整。针对夜间活动按蚊的WHO隧道试验是鉴定新型杀虫剂毒性最可靠的生物测定方法。
