高疟原虫感染和尼日尔共和国萨赫勒地区主要疟疾病媒按蚊 Anopheles coluzzii 的多种杀虫剂耐药性。
High Plasmodium infection and multiple insecticide resistance in a major malaria vector Anopheles coluzzii from Sahel of Niger Republic.
机构信息
Vector Biology Department, Liverpool School of Tropical Medicine (LSTM), Pembroke Place, L3 5QA, UK.
Department of Biochemistry, Bayero University, PMB 3011, Kano, Nigeria.
出版信息
Malar J. 2019 May 24;18(1):181. doi: 10.1186/s12936-019-2812-0.
BACKGROUND
Information on insecticide resistance and the mechanisms driving it in the major malaria vectors is grossly lacking in Niger Republic, thus hindering control efforts. To facilitate evidence-based malaria control, the role of Anopheles coluzzii population from southern Niger, in malaria transmission, its insecticides resistance profile and the molecular mechanisms driving the resistance were characterized.
METHODS
Blood fed female Anopheles gambiae sensu lato resting indoor were collected at Tessaoua, Niger. Source of blood was established using PCR and infection with Plasmodium determined using TaqMan assay. Resistance profile was established with the major public health insecticides, and resistance intensity determined with deltamethrin. Synergist assays were conducted with piperonyl butoxide and diethyl maleate. Presence of L1014F and L1014S knockdown resistance (kdr) mutations in the voltage-gated sodium channel (VGSC) was investigated using TaqMan genotyping, and strength of selection pressure acting on the Anopheles populations determined by assessing the genetic diversity of a fragment spanning exon-20 of the VGSC from alive and dead females.
RESULTS
High human blood index (96%) and high Plasmodium falciparum infection (~ 13%) was observed in the An. coluzzii population. Also, a single mosquito was found infected with Plasmodium vivax. High pyrethroid and organochloride resistance was observed with mortalities of less than 20% for deltamethrin, permethrin, α-cypermethrin, and DDT. A high LD (156.65 min) was obtained for deltamethrin, with a resistance ratio of ~ 47.18 compared to the susceptible Ngoussou colony. Moderate carbamate resistance was observed, and a full susceptibility to organophosphates recorded. Synergist bioassays with piperonyl butoxide and diethyl maleate significantly recovered deltamethrin and DDT susceptibility, respectively implicating CYP450 s (mortality = 82%, χ = 84.51, p < 0.0001) and glutathione S-transferases (mortality = 58%, χ = 33.96, p < 0.001) in resistance. A high frequency of 1014F kdr mutation (82%) was established, with significant difference in genotype distribution associated with permethrin resistance [odds ratio = 7.71 (95% CI 2.43-14.53, χ = 13.67, p = 0.001]. Sequencing of intron-1 of the voltage-gated sodium channel (VGSC) revealed a low genetic diversity.
CONCLUSION
High pyrethroid resistance highlight the challenges to the effectiveness of the pyrethroids-based ITNs and indoor residual spraying (IRS) against An. coluzzii in Niger. The pyrethroids-synergists LLINs and organophosphate-based IRS maybe the alternatives for malaria control in southern Niger.
背景
尼日尔共和国在主要疟疾传播媒介伊蚊的杀虫剂耐药性及其驱动机制方面的信息严重匮乏，这阻碍了控制工作的开展。为了促进基于证据的疟疾控制，本研究对来自尼日尔南部的致倦库蚊种群在疟疾传播中的作用、其杀虫剂耐药谱以及驱动耐药性的分子机制进行了研究。
方法
在尼日尔的泰萨乌阿收集了吸食人血后在室内休息的雌性冈比亚按蚊属按蚊。通过 PCR 确定血液来源，并使用 TaqMan 检测法确定疟原虫感染情况。使用主要的公共卫生杀虫剂建立了耐药谱，并使用溴氰菊酯测定了耐药强度。使用增效醚和马来酸二乙酯进行增效剂试验。使用 TaqMan 基因分型法研究了电压门控钠离子通道（VGSC）中的 L1014F 和 L1014S 击倒抗性（kdr）突变的存在，并通过评估来自活和死雌性的跨越 VGSC 外显子-20 的片段的遗传多样性来确定对蚊群的选择压力强度。
结果
在致倦库蚊种群中观察到高人体血液指数（96%）和高恶性疟原虫感染率（13%）。此外，一只蚊子同时感染了间日疟原虫。对拟除虫菊酯和有机氯杀虫剂的高度耐药性，溴氰菊酯、氯菊酯、α-氯氰菊酯和滴滴涕的死亡率均低于 20%。溴氰菊酯获得了较高的 LD（156.65 分钟），与敏感的 Ngoussou 品系相比，抗性比为47.18。观察到中度氨基甲酸酯类耐药性，有机磷类完全敏感。增效醚和马来酸二乙酯的增效生物测定显著恢复了溴氰菊酯和滴滴涕的敏感性，这表明细胞色素 P450（死亡率=82%，χ=84.51，p<0.0001）和谷胱甘肽 S-转移酶（死亡率=58%，χ=33.96，p<0.001）在耐药性中起作用。高频率的 1014F kdr 突变（82%）被确定，与拟除虫菊酯耐药性相关的基因型分布存在显著差异[优势比=7.71（95%CI 2.43-14.53，χ=13.67，p=0.001]。对电压门控钠离子通道（VGSC）的内含子 1 进行测序显示，遗传多样性较低。
结论
对拟除虫菊酯类的高度耐药性突显了在尼日尔，基于拟除虫菊酯的 ITNs 和室内滞留喷洒（IRS）对致倦库蚊的有效性面临的挑战。拟除虫菊酯增效剂长效蚊帐和有机磷类基于 IRS 可能是尼日尔南部疟疾控制的替代方法。
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