PDF(Pubmed)
Abstract：
BACKGROUND: Anopheles funestus is a leading vector of malaria in most parts of East and Southern Africa, yet its ecology and responses to vector control remain poorly understood compared with other vectors such as Anopheles gambiae and Anopheles arabiensis. This study presents the first large-scale survey of the genetic and phenotypic expression of insecticide resistance in An. funestus populations in Tanzania.
METHODS: We performed insecticide susceptibility bioassays on An. funestus mosquitoes in nine regions with moderate-to-high malaria prevalence in Tanzania, followed by genotyping for resistance-associated mutations (CYP6P9a, CYP6P9b, L119F-GSTe2) and structural variants (SV4.3 kb, SV6.5 kb). Generalized linear models were used to assess relationships between genetic markers and phenotypic resistance. An interactive R Shiny tool was created to visualize the data and support evidence-based interventions.
RESULTS: Pyrethroid resistance was universal but reversible by piperonyl-butoxide (PBO). However, carbamate resistance was observed in only five of the nine districts, and dichloro-diphenyl-trichloroethane (DDT) resistance was found only in the Kilombero valley, south-eastern Tanzania. Conversely, there was universal susceptibility to the organophosphate pirimiphos-methyl in all sites. Genetic markers of resistance had distinct geographical patterns, with CYP6P9a-R and CYP6P9b-R alleles, and the SV6.5 kb structural variant absent or undetectable in the north-west but prevalent in all other sites, while SV4.3 kb was prevalent in the north-western and western regions but absent elsewhere. Emergent L119F-GSTe2, associated with deltamethrin resistance, was detected in heterozygous form in districts bordering Mozambique, Malawi and the Democratic Republic of Congo. The resistance landscape was most complex in western Tanzania, in Tanganyika district, where all five genetic markers were detected. There was a notable south-to-north spread of resistance genes, especially CYP6P9a-R, though this appears to be interrupted, possibly by the Rift Valley.
CONCLUSIONS: This study underscores the need to expand resistance monitoring to include An. funestus alongside other vector species, and to screen for both the genetic and phenotypic signatures of resistance. The findings can be visualized online via an interactive user interface and could inform data-driven decision-making for resistance management and vector control. Since this was the first large-scale survey of resistance in Tanzania\'s An. funestus, we recommend regular updates with greater geographical and temporal coverage.
METHODS: We performed insecticide susceptibility bioassays on An. funestus mosquitoes in nine regions with moderate-to-high malaria prevalence in Tanzania, followed by genotyping for resistance-associated mutations (CYP6P9a, CYP6P9b, L119F-GSTe2) and structural variants (SV4.3 kb, SV6.5 kb). Generalized linear models were used to assess relationships between genetic markers and phenotypic resistance. An interactive R Shiny tool was created to visualize the data and support evidence-based interventions.
RESULTS: Pyrethroid resistance was universal but reversible by piperonyl-butoxide (PBO). However, carbamate resistance was observed in only five of the nine districts, and dichloro-diphenyl-trichloroethane (DDT) resistance was found only in the Kilombero valley, south-eastern Tanzania. Conversely, there was universal susceptibility to the organophosphate pirimiphos-methyl in all sites. Genetic markers of resistance had distinct geographical patterns, with CYP6P9a-R and CYP6P9b-R alleles, and the SV6.5 kb structural variant absent or undetectable in the north-west but prevalent in all other sites, while SV4.3 kb was prevalent in the north-western and western regions but absent elsewhere. Emergent L119F-GSTe2, associated with deltamethrin resistance, was detected in heterozygous form in districts bordering Mozambique, Malawi and the Democratic Republic of Congo. The resistance landscape was most complex in western Tanzania, in Tanganyika district, where all five genetic markers were detected. There was a notable south-to-north spread of resistance genes, especially CYP6P9a-R, though this appears to be interrupted, possibly by the Rift Valley.
CONCLUSIONS: This study underscores the need to expand resistance monitoring to include An. funestus alongside other vector species, and to screen for both the genetic and phenotypic signatures of resistance. The findings can be visualized online via an interactive user interface and could inform data-driven decision-making for resistance management and vector control. Since this was the first large-scale survey of resistance in Tanzania\'s An. funestus, we recommend regular updates with greater geographical and temporal coverage.
摘要：
背景：在东非和南部非洲的大部分地区，按蚊是疟疾的主要媒介，然而，与冈比亚按蚊和阿拉伯按蚊等其他载体相比，其生态学和对载体控制的反应仍然知之甚少。这项研究首次对An中杀虫剂抗性的遗传和表型表达进行了大规模调查。坦桑尼亚的funestus人口。
方法：我们对An进行了杀虫剂敏感性生物测定。坦桑尼亚9个疟疾流行中到高的地区的funestus蚊子，其次是抗性相关突变的基因分型(CYP6P9a，CYP6P9b,L119F-GSTe2）和结构变体（SV4.3kb，SV6.5kb)。使用广义线性模型来评估遗传标记与表型抗性之间的关系。创建了一个交互式RShiny工具来可视化数据并支持基于证据的干预措施。
结果：拟除虫菊酯抗性是普遍的，但通过胡椒基丁醚（PBO）是可逆的。然而,在九个地区中只有五个地区观察到氨基甲酸酯抗性，和二氯-二苯基-三氯乙烷（DDT）抗性仅在基隆贝罗山谷中发现，坦桑尼亚东南部。相反，在所有地点都对有机磷吡米磷-甲基存在普遍敏感性。抗性的遗传标记具有不同的地理模式，具有CYP6P9a-R和CYP6P9b-R等位基因，和SV6.5kb结构变体在西北部不存在或检测不到，但在所有其他地点普遍存在，而SV4.3kb在西北和西部地区很普遍，但在其他地方却没有。与溴氰菊酯抗性相关的新兴L119F-GSTe2，在与莫桑比克接壤的地区以杂合子形式检测到，马拉维和刚果民主共和国。坦桑尼亚西部的抵抗景观最为复杂，在坦any尼喀区，在那里检测到所有五个遗传标记。有一个明显的从南向北传播的抗性基因,尤其是CYP6P9a-R,虽然这似乎被打断了,可能是裂谷。
结论：本研究强调了扩大耐药性监测范围的必要性。funestus和其他媒介物种一起，并筛选抗性的遗传和表型特征。研究结果可以通过交互式用户界面在线可视化，并可以为数据驱动的阻力管理和媒介控制决策提供信息。因为这是坦桑尼亚安省第一次大规模的抵抗调查。funestus,我们建议定期更新，具有更大的地理和时间覆盖范围。
方法：我们对An进行了杀虫剂敏感性生物测定。坦桑尼亚9个疟疾流行中到高的地区的funestus蚊子，其次是抗性相关突变的基因分型(CYP6P9a，CYP6P9b,L119F-GSTe2）和结构变体（SV4.3kb，SV6.5kb)。使用广义线性模型来评估遗传标记与表型抗性之间的关系。创建了一个交互式RShiny工具来可视化数据并支持基于证据的干预措施。
结果：拟除虫菊酯抗性是普遍的，但通过胡椒基丁醚（PBO）是可逆的。然而,在九个地区中只有五个地区观察到氨基甲酸酯抗性，和二氯-二苯基-三氯乙烷（DDT）抗性仅在基隆贝罗山谷中发现，坦桑尼亚东南部。相反，在所有地点都对有机磷吡米磷-甲基存在普遍敏感性。抗性的遗传标记具有不同的地理模式，具有CYP6P9a-R和CYP6P9b-R等位基因，和SV6.5kb结构变体在西北部不存在或检测不到，但在所有其他地点普遍存在，而SV4.3kb在西北和西部地区很普遍，但在其他地方却没有。与溴氰菊酯抗性相关的新兴L119F-GSTe2，在与莫桑比克接壤的地区以杂合子形式检测到，马拉维和刚果民主共和国。坦桑尼亚西部的抵抗景观最为复杂，在坦any尼喀区，在那里检测到所有五个遗传标记。有一个明显的从南向北传播的抗性基因,尤其是CYP6P9a-R,虽然这似乎被打断了,可能是裂谷。
结论：本研究强调了扩大耐药性监测范围的必要性。funestus和其他媒介物种一起，并筛选抗性的遗传和表型特征。研究结果可以通过交互式用户界面在线可视化，并可以为数据驱动的阻力管理和媒介控制决策提供信息。因为这是坦桑尼亚安省第一次大规模的抵抗调查。funestus,我们建议定期更新，具有更大的地理和时间覆盖范围。
