Single-Nucleotide Polymorphisms in the Beta-Tubulin Gene and Its Relationship with Treatment Response to Albendazole in Human Soil-Transmitted Helminths in Southern Mozambique.

Single-Nucleotide Polymorphisms in the Beta-Tubulin Gene and Its Relationship with Treatment Response to Albendazole in Human Soil-Transmitted Helminths in Southern Mozambique.
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DOI:
10.4269/ajtmh.21-0948
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发表时间:
2022-07-18
影响因子:
3.3
通讯作者:
Munoz, Jose
Munoz, Jose
中科院分区:
医学4区
文献类型:
--
作者:
Grau-Pujol, Berta;Gandasegui, Javier;Escola, Valdemiro;Marti-Soler, Helena;Cambra-Pelleja, Maria;Demontis, Maria;Brienen, Eric A. T.;Jamine, Jose Carlos;Muchisse, Osvaldo;Cossa, Anelsio;Sacoor, Charfudin;Cano, Jorge;Van Lieshout, Lisette;Martinez-Valladares, Maria;Munoz, Jose

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土源性蠕虫 (STH) 的基石控制策略是使用苯并咪唑进行大规模给药 (MDA)。然而,MDA 可能会导致驱虫药耐药性的选择压力,就像在家畜中发生的那样。本研究的目的是评估莫桑比克南部 STH 的 β-微管蛋白基因中对阿苯达唑的治疗反应以及与假定的苯并咪唑耐药性单核苷酸多态性 (SNP) 的关系。在对 819 名参与者进行筛查后,我们对莫桑比克南部 Manhiça 区的 184 名感染 STH 的参与者进行了队列研究。收集治疗前和治疗后的粪便样本,并通过重复 Kato-Katz 和定量聚合酶链反应 (qPCR) 鉴定 STH 感染。计算治愈率和减蛋率。通过焦磷酸测序评估了Trichuris trichiura 和美洲板口线虫中假定的苯并咪唑抗性SNP(F167Y、F200T 和E198A)。通过重复 Kato-Katz 和 qPCR,蛔虫的治愈率分别为 95.8% 和 93.6%,毛蛔虫的治愈率为 28% 和 7.8%,美洲钩虫的治愈率为 88.9% 和 56.7%。重复 Kato-Katz 的产卵率对于蚓螈为 85.4%,对于毛螽为 34.9%,对于美洲钩虫为 40.5%。在预处理时,在毛毛虫 (23%) 和美洲猪笼草 (21%) 感染参与者中检测到 β-微管蛋白基因中假定的苯并咪唑抗性 SNP。治疗前和治疗后频率之间没有观察到任何 SNP 的统计差异。尽管对阿苯达唑的治疗反应较低,特别是在毛毛虫中,但研究人群治疗后假定的苯并咪唑耐药性 SNP 并未升高。需要新的见解来更好地了解和监测人类驱虫药的耐药性。
Soil-transmitted helminth (STH) cornerstone control strategy is mass drug administration (MDA) with benzimidazoles. However, MDA might contribute to selection pressure for anthelmintic resistance, as occurred in livestock. The aim of this study is to evaluate the treatment response to albendazole and the relationship with the presence of putative benzimidazole resistance single-nucleotide polymorphisms (SNPs) in the β-tubulin gene of STH in Southern Mozambique. After screening 819 participants, we conducted a cohort study with 184 participants infected with STH in Manhiça district, Southern Mozambique. A pretreatment and a posttreatment stool samples were collected and the STH infection was identified by duplicate Kato-Katz and quantitative polymerase chain reaction (qPCR). Cure rate and egg reduction rates were calculated. Putative benzimidazole resistance SNPs (F167Y, F200T, and E198A) in Trichuris trichiura and Necator americanus were assessed by pyrosequencing. Cure rates by duplicate Kato-Katz and by qPCR were 95.8% and 93.6% for Ascaris lumbricoides, 28% and 7.8% for T. trichiura, and 88.9% and 56.7% for N. americanus. Egg reduction rate by duplicate Kato-Katz was 85.4% for A. lumbricoides, 34.9% for T. trichiura, and 40.5% for N. americanus. Putative benzimidazole resistance SNPs in the β-tubulin gene were detected in T. trichiura (23%) and N. americanus (21%) infected participants at pretreatment. No statistical difference was observed between pretreatment and posttreatment frequencies for none of the SNPs. Although treatment response to albendazole was low, particularly in T. trichiura, the putative benzimidazole resistance SNPs were not higher after treatment in the population studied. New insights are needed for a better understanding and monitoring of human anthelmintic resistance.
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