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BACKGROUND

A dramatic malaria resurgence occurred in areas of Uganda between 2020 and 2022, coinciding with the switch to clothianidin-based formulations for indoor residual spraying. During the resurgence, Anopheles funestus sensu lato (s.l.) numbers increased more than those of Anopheles gambiae s.l., but when an alternative insecticide, pirimiphos-methyl, was reintroduced in 2023, both malaria cases and An. funestus mosquito density fell.

METHODS

In this study, we investigated possible causes of the resurgence by assessing (1) whether sufficient quantities of insecticide were sprayed, (2) the residual insecticide bio-efficacy against wild mosquitoes, and (3) the insecticide susceptibility of both key vector populations using standard test tube assays and wall cone assays.

RESULTS

In 2023, after adjusting for extraction efficiency, 70-80% of the houses had optimal residual concentrations of insecticides (clothianidin > 0.3g/m; pirimiphos-methyl > 0.5g/m), with significant variations between sampling rounds and wall types. Mud walls had the lowest residual concentration of insecticides, and the lowest observed mortality in wall cone assays, compared to burnt bricks with plaster/cement/paint. In the studies of residual bio-efficacy, by World Health Organization (WHO) definitions, An. funestus s.l. showed resistance to clothianidin (< 80% mortality) up to 11 months, and susceptibility to pirimiphos-methyl (> 90% mortality) when exposed to wall surfaces up to 7 months post-spray. In WHO tube tests, variations were observed in susceptibility to clothianidin in An. funestus s.l. populations using dose- and time-response assays (80-98% mortality). In 2022, An. gambiae s.l. was largely susceptible to the clothianidin-based formulation Sumishield (85-90% mortality), although the levels dropped slightly in 2023 (60-85% mortality), mainly in mud and pole houses. In contrast, An. gambiae s.l. was highly susceptible with mild tolerance to the pirimiphos-methyl-based formulation Actellic (~ 80% mortality), and time-response assays showed that An. gambiae s.l. populations had very low knockdown and mortality at lower exposure time compared to An. funestus s.l. Regression models showed a positive association between residual insecticide concentration (RIC) and mortality in houses sprayed with Sumishield but not Actellic houses.

CONCLUSIONS

Despite the possible variations observed in spray operations, the study revealed that An. funestus s.l. exhibited a higher tolerance to clothianidin-based formulations compared to An. gambiae s.l., and this might have driven the malaria resurgence observed in Uganda. However, there are signals of An. gambiae s.l. resistance to pirimiphos-methyl, which will require further investigation and monitoring.

背景

2020年至2022年期间，乌干达部分地区疟疾疫情急剧反弹，恰逢室内滞留喷洒改用噻虫胺制剂。疫情反弹期间，宽斑按蚊复合组数量的增长幅度超过冈比亚按蚊复合组，但在2023年重新引入另一种杀虫剂甲基嘧啶磷后，疟疾病例和宽斑按蚊的蚊密度均有所下降。

方法

在本研究中，我们通过评估以下因素来调查疫情反弹的可能原因：（1）杀虫剂喷洒量是否充足；（2）残留杀虫剂对野生蚊子的生物药效；（3）使用标准试管试验和壁锥试验对两种主要病媒种群进行杀虫剂敏感性测试。

结果

2023年，在调整提取效率后，70%-80%的房屋中杀虫剂残留浓度达到最佳水平（噻虫胺>0.3g/m；甲基嘧啶磷>0.5g/m），不同采样轮次和墙体类型之间存在显著差异。与涂抹了灰泥/水泥/涂料的烧砖墙体相比，泥墙的杀虫剂残留浓度最低，在壁锥试验中观察到的死亡率也最低。在残留生物药效研究中，根据世界卫生组织（WHO）的定义，宽斑按蚊复合组在长达11个月的时间里对噻虫胺表现出抗性（死亡率<80%），而在喷洒后长达7个月的时间里，接触墙体表面时对甲基嘧啶磷敏感（死亡率>90%）。在WHO试管试验中，使用剂量-反应和时间-反应试验发现宽斑按蚊复合组对噻虫胺的敏感性存在差异（死亡率80%-98%）。2022年，冈比亚按蚊复合组对基于噻虫胺的Sumishield制剂基本敏感（死亡率85%-90%），尽管2023年该水平略有下降（死亡率60%-85%），主要出现在泥墙和杆墙房屋中。相比之下，冈比亚按蚊复合组对基于甲基嘧啶磷的Actellic制剂高度敏感，有轻度耐受性（死亡率约80%），时间-反应试验表明，与宽斑按蚊复合组相比，冈比亚按蚊复合组在较低暴露时间下的击倒率和死亡率非常低。回归模型显示，在喷洒Sumishield的房屋中，残留杀虫剂浓度（RIC）与死亡率呈正相关，而在喷洒Actellic的房屋中则不然。