Molecular and Biological Diagnostic Tests for Monitoring Benzimidazole Resistance in Human Soil-Transmitted Helminths

Molecular and Biological Diagnostic Tests for Monitoring Benzimidazole Resistance in Human Soil-Transmitted Helminths
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DOI:
10.4269/ajtmh.12-0484
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发表时间:
2013-06-01
影响因子:
3.3
通讯作者:
Prichard, Roger K.
Prichard, Roger K.
中科院分区:
医学4区
文献类型:
--
作者:
Diawara, Aissatou;Schwenkenbecher, Jan M.;Prichard, Roger K.

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在有土壤传播蠕虫的流行国家,正在将阿苯达唑或甲苯达唑作为一项控制战略进行大规模用药。然而,众所周知,在兽医蠕虫中,使用相同的苯并咪唑药物可以对β -微管蛋白基因进行选择,从而导致耐药性。鉴于对人类土壤传播的蠕虫可能产生耐药性的担忧,迫切需要开发准确的诊断工具来监测耐药性。在这项研究中,我们建立了分子检测方法来检测蛔虫、毛滴虫和钩虫可能的抗性遗传变化,并优化了犬钩虫Ancylostoma caninum的卵孵化试验,并将其应用于美洲Necator americanus。两种分析方法均在现场样品上进行了测试。分子分析证明了它们的可重复性和检测携带假定的抗性相关遗传变化的蠕虫的能力。然而,需要进一步的调查来验证我们对其他野外分离株的分子和生物学测试。
In endemic countries with soil-transmitted helminths mass drug administration with albendazole or mebendazole are being implemented as a control strategy. However, it is well known in veterinary helminths that the use of the same benzimidazole drugs can place selection on the beta-tubulin gene, leading to resistance. Given the concern that resistance could arise in human soil-transmitted helminths, there is an urgent need to develop accurate diagnostic tools for monitoring resistance. In this study, we developed molecular assays to detect putative resistance genetic changes in Ascaris lumbricoides, Trichuris trichiura, and hookworms, and we optimized an egg hatch assay for the canine hookworm Ancylostoma caninum and applied it to Necator americanus. Both assays were tested on field samples. The molecular assays demonstrated their reproducibility and capacity to detect the presence of worms carrying putative resistance-associated genetic changes. However, further investigations are needed to validate our molecular and biological tests on additional field isolates.