Correa Maria, Lopes Janete, Sousa Carla A, Rocha Gustavo, Oriango Robin, Cardetas Andreia, Viegas Joao, Cornel Anthony J, Lanzaro Gregory C, Pinto João
Vector Genetics Laboratory, Department of Pathology, Microbiology, and Immunology, University of California, Davis, CA, USA.
Global Health and Tropical Medicine, LA-REAL, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal.
Malar J. 2024 Dec 18;23(1):390. doi: 10.1186/s12936-024-05212-6.
Insecticide-based malaria vector control has been implemented on the islands of São Tomé and Príncipe (STP) for more than 20 years. During this period malaria incidence was significantly reduced to pre-elimination levels. While cases remained low since 2015, these have significantly increased in the last year, challenging the commitment of the country to achieve malaria elimination by 2025. To better understand the reasons for increasing malaria cases, levels and underlying mechanisms of insecticide resistance in the local Anopheles coluzzii populations were characterized.
Mosquito larval collections were performed in the rainy and dry seasons, between 2022 and 2024, in two localities of São Tomé and one locality in Príncipe. Susceptibility to permethrin, α-cypermethrin, pirimiphos-methyl and DDT was assessed using WHO bioassays and protocols. Intensity of resistance and reversal by PBO pre-exposure were determined for pyrethroid insecticides. The kdr locus was genotyped by PCR assays in subsamples of the mosquitoes tested.
Anopheles coluzzii populations were fully susceptible to pirimiphos-methyl, but high levels of resistance to pyrethroids and DDT were detected, particularly in São Tomé rainy season collections. Increasing the pyrethroid and DDT dosages to 5 and 10 did not restore full susceptibility in all populations. Pre-exposure to PBO resulted into partial reversal of the resistance phenotype suggesting the presence of cytochrome P450 oxidases-mediated metabolic resistance. The L1014F knockdown resistance mutation was present in An. coluzzii on both islands but at much higher frequency in São Tomé where it was associated with the resistant phenotype.
Future vector control interventions should consider the use of non-pyrethroid insecticides or combination with synergists to overcome the high levels of pyrethroid resistance. Alternative control methods not dependent on the use of insecticides should be additionally implemented to achieve malaria elimination in STP.
基于杀虫剂的疟疾媒介控制措施在圣多美和普林西比(STP)诸岛已实施了20多年。在此期间,疟疾发病率显著降低至消除前水平。自2015年以来病例数一直维持在低水平,但去年显著增加,这对该国到2025年实现疟疾消除的承诺构成挑战。为更好地了解疟疾病例增加的原因,对当地科卢齐按蚊种群中杀虫剂抗性水平及潜在机制进行了特征分析。
在2022年至2024年期间的雨季和旱季,于圣多美两个地点和普林西比一个地点采集蚊虫幼虫。使用世卫组织生物测定法和方案评估对氯菊酯、α-氯氰菊酯、甲基嘧啶磷和滴滴涕的敏感性。测定拟除虫菊酯类杀虫剂的抗性强度以及经PBO预处理后的抗性逆转情况。通过PCR检测对所测试蚊虫子样本中的kdr基因座进行基因分型。
科卢齐按蚊种群对甲基嘧啶磷完全敏感,但检测到对拟除虫菊酯类和滴滴涕的高水平抗性,特别是在圣多美雨季采集的样本中。将拟除虫菊酯类和滴滴涕剂量增加到5倍和10倍并不能使所有种群恢复完全敏感性。经PBO预处理导致抗性表型部分逆转,表明存在细胞色素P450氧化酶介导的代谢抗性。L1014F击倒抗性突变在两个岛屿的科卢齐按蚊中均有存在,但在圣多美频率更高,且与抗性表型相关。
未来的媒介控制干预措施应考虑使用非拟除虫菊酯类杀虫剂或与增效剂联合使用,以克服高水平的拟除虫菊酯抗性。应额外实施不依赖杀虫剂使用的替代控制方法,以在圣多美和普林西比实现疟疾消除。