Liverpool School of Tropical Medicine, Liverpool, UK.
Malar J. 2013 Nov 9;12:404. doi: 10.1186/1475-2875-12-404.
With high DDT resistance present throughout much of West Africa, carbamates and organophosphates are increasingly important alternatives to pyrethroids for indoor residual spraying (IRS). Though less widespread, resistance to both of these alternative insecticide classes has also been documented within the Anopheles gambiae species pair (formerly the M and S molecular forms) in West Africa. To manage insecticide efficacy, it is important to predict how and where resistance is likely to occur and spread, which could be aided by using molecular diagnostics with high predictive value.
Anopheles coluzzii and An. gambiae s.s. were collected from 18 sites throughout southern Ghana and bioassayed with bendiocarb, the most commonly applied carbamate, and an organophosphate, fenitrothion. The Ace-1 target site substitution G119S was genotyped by qPCR.
Fenitrothion induced higher mortality than bendiocarb, though phenotypes correlated strongly across populations. Ace-1 119S was found at much higher frequency in An. gambiae s.s than An. coluzzii, exceeding 90% in a population from Greater Accra, the highest frequency reported to date. Ace-1 G119S was very strongly associated with resistance to both insecticides, providing high predictive power for diagnosis, though with some evidence for a differential effect between molecular forms for bendiocarb. Sequencing of the gene revealed a lack of variation in resistant alleles precluding determination of origin, but Ace-1 copy number variation was detected for the first time in Ghana.
The results validate G119S as a useful diagnostic of organophosphate and carbamate resistance within and among populations, whilst highlighting the potential for an aggregate nature of Ace-1 genotypes, which may comprise both single-copy and duplicated genes. Further work is now required to determine the distribution and resistance-association of Ace-1 duplication.
由于高浓度滴滴涕抗性在西非大部分地区普遍存在，氨基甲酸酯类和有机磷类杀虫剂正逐渐成为拟除虫菊酯类杀虫剂用于室内滞留喷洒（IRS）的替代品。尽管这些替代杀虫剂类别的抗性在西非的冈比亚按蚊种系（以前是 M 和 S 分子形式）中也有记录，但它们的分布范围较窄。为了管理杀虫剂的功效，预测抗性可能出现和传播的方式和地点非常重要，这可以通过使用具有高预测价值的分子诊断来辅助实现。
从加纳南部的 18 个地点收集了斑须按蚊和冈比亚按蚊 s.s.，并用最常用的氨基甲酸酯类杀虫剂丁硫克百威和有机磷杀虫剂杀螟松进行生物测定。通过 qPCR 对 Ace-1 靶位取代 G119S 进行基因分型。
杀螟松引起的死亡率高于丁硫克百威，尽管表型在不同种群之间具有很强的相关性。在冈比亚按蚊 s.s.中发现 Ace-1 119S 的频率远高于斑须按蚊，在大阿克拉地区的一个种群中超过 90%，这是迄今为止报道的最高频率。Ace-1 G119S 与两种杀虫剂的抗性非常密切相关，为诊断提供了很高的预测能力，但对于丁硫克百威，不同分子形式之间存在一定的差异效应。对基因进行测序发现，抗性等位基因缺乏变异，因此无法确定其起源，但这是加纳首次检测到 Ace-1 拷贝数的变化。
这些结果验证了 G119S 作为一种有用的诊断工具，可以在种群内和种群间检测有机磷和氨基甲酸酯类杀虫剂的抗性，同时强调了 Ace-1 基因型可能具有聚合性质，其中可能包括单拷贝和重复基因。现在需要进一步研究确定 Ace-1 重复的分布和抗性关联。
