Wits Research Institute for Malaria, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2000, South Africa.
Centre for Emerging, Zoonotic & Parasitic Diseases, National Institute for Communicable Diseases, Johannesburg, 2131, South Africa.
Malar J. 2017 Nov 7;16(1):448. doi: 10.1186/s12936-017-2099-y.
The Democratic Republic of the Congo (DRC) is characterized as a holoendemic malaria area with the main vectors being Anopheles funestus and members of the Anopheles gambiae complex. Due to political instability and socio-economic challenges in the region, knowledge of insecticide resistance status and resistance mechanisms in these vectors is limited. Mosquitoes were collected from a mining site in the north-eastern part of the country and, following identification, were subjected to extensive testing for the target-site and biochemical basis of resistance. Quantitative real-time PCR was used to assess a suite of 10 genes frequently involved in pyrethroid and dichlorodiphenyltrichloroethane (DDT) resistance in An. gambiae females and males. In An. funestus, gene expression microarray analysis was carried out on female mosquitoes.
In both species, deltamethrin resistance was recorded along with high resistance and suspected resistance to DDT in An. gambiae and An. funestus, respectively. A total of 85% of An. gambiae carried the kdr mutations as either homozygous resistant (RR) (L1014S, L1014F or both) or heterozygous (RS), however only 3% carried the rdl mutant allele (RS) and no ace-1 mutations were recorded. Synergist assays indicated a strong role for P450s in deltamethrin resistance in both species. In An. gambiae, analysis of transcription levels showed that the glutathione-S-transferase, GSTS1-2, produced the highest fold change in expression (7.6-fold in females and 31-fold in males) followed by GSTE2, thioredoxin peroxidase (TPX2), and cytochrome oxidases (CYP6M2 and CYP6P1). All other genes tested produced fold change values below 2. Microarray analysis revealed significant over-transcription of cuticular proteins as well as CYP6M7, CYP6P9a and CYP6P9b in insecticide resistant An. funestus.
These data show that high levels of deltamethrin resistance in the main malaria vector species, conferred by enzymatic detoxification, are present in the DRC.
刚果民主共和国(DRC)是一个全环疟疾地区,主要病媒为冈比亚按蚊复合体中的致倦库蚊和其他成员。由于该地区政治不稳定和社会经济挑战,对这些病媒的杀虫剂耐药性现状和耐药机制知之甚少。从该国东北部的一个采矿点采集了蚊子,并在鉴定后对其进行了广泛的测试,以确定其对目标部位和生化基础的耐药性。定量实时 PCR 用于评估 10 种基因的综合表达,这些基因通常与冈比亚按蚊雌性和雄性体内的拟除虫菊酯和滴滴涕(DDT)耐药性有关。在致倦库蚊中,对雌性蚊子进行了基因表达微阵列分析。
在这两个物种中,都记录到了溴氰菊酯的耐药性,同时在冈比亚按蚊和致倦库蚊中分别观察到了对 DDT 的高耐药性和疑似耐药性。在冈比亚按蚊中,共有 85%的个体携带 kdr 突变,要么是纯合抗性(RR)(L1014S、L1014F 或两者兼有),要么是杂合抗性(RS),但只有 3%的个体携带 rdl 突变等位基因(RS),没有记录到 ace-1 突变。增效剂试验表明,在这两个物种中,P450s 在溴氰菊酯耐药性中起着重要作用。在冈比亚按蚊中,转录水平分析表明,谷胱甘肽-S-转移酶 GSTS1-2 表达的倍数变化最高(雌性为 7.6 倍,雄性为 31 倍),其次是 GSTE2、硫氧还蛋白过氧化物酶(TPX2)和细胞色素氧化酶(CYP6M2 和 CYP6P1)。其他所有测试的基因产生的倍数变化值均低于 2。微阵列分析显示,在抗杀虫剂的致倦库蚊中,表皮蛋白以及 CYP6M7、CYP6P9a 和 CYP6P9b 的转录水平显著升高。
这些数据表明,在刚果民主共和国,主要疟疾媒介物种对溴氰菊酯的高水平耐药性,是由酶解毒作用引起的。