Grau-Pujol Berta, Gandasegui Javier, Escola Valdemiro, Marti-Soler Helena, Cambra-Pellejà Maria, Demontis Maria, Brienen Eric A T, Jamine Jose Carlos, Muchisse Osvaldo, Cossa Anelsio, Sacoor Charfudin, Cano Jorge, Van Lieshout Lisette, Martinez-Valladares Maria, Muñoz Jose
Barcelona Institute for Global Health (ISGlobal), Hospital Clínic - University of Barcelona, Barcelona, Spain.
Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique.
Am J Trop Med Hyg. 2022 Jul 18;107(3):649-57. doi: 10.4269/ajtmh.21-0948.
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.
土壤传播蠕虫(STH)的基础控制策略是使用苯并咪唑进行群体药物给药(MDA)。然而,MDA可能会像在牲畜中那样,导致对抗蠕虫药产生选择压力。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抗性单核苷酸多态性(SNP)存在之间的关系。在对819名参与者进行筛查后,我们在莫桑比克南部的曼希卡区对184名感染STH的参与者进行了一项队列研究。收集治疗前和治疗后的粪便样本,并通过重复的加藤-厚涂片法和定量聚合酶链反应(qPCR)鉴定STH感染情况。计算治愈率和虫卵减少率。通过焦磷酸测序评估毛首鞭形线虫和美洲板口线虫中假定的苯并咪唑抗性SNP(F167Y、F200T和E198A)。对于蛔虫,重复加藤-厚涂片法和qPCR的治愈率分别为95.8%和93.6%;对于毛首鞭形线虫,分别为28%和7.8%;对于美洲板口线虫,分别为88.9%和56.7%。重复加藤-厚涂片法的虫卵减少率,蛔虫为85.4%,毛首鞭形线虫为34.9%,美洲板口线虫为40.5%。在治疗前,在感染毛首鞭形线虫(23%)和美洲板口线虫(21%)的参与者中检测到β-微管蛋白基因中假定的苯并咪唑抗性SNP。对于任何SNP,治疗前和治疗后的频率均未观察到统计学差异。尽管对阿苯达唑的治疗反应较低,尤其是在毛首鞭形线虫中,但在所研究的人群中治疗后假定的苯并咪唑抗性SNP并未更高。需要新的见解来更好地理解和监测人类抗蠕虫药抗性。