Molecular analysis of the β-tubulin gene of human hookworms as a basis for possible benzimidazole resistance on Pemba Island
Molecular analysis of the β-tubulin gene of human hookworms as a basis for possible benzimidazole resistance on Pemba Island
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DOI：
10.1016/j.molbiopara.2003.12.008
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发表时间：
2004-04-01
影响因子：
1.5
通讯作者：
Bickle, Q
中科院分区：
文献类型：
--
作者：
Albonico, M;Wright, V;Bickle, Q
由肠道线虫引起的感染是人类和家畜群体中显著发病率的原因[1，2]。这些感染的治疗主要依赖于有限数量的化疗药物，但在家畜中，大规模使用、对封闭种群的频繁治疗以及剂量不当导致对苯并咪唑（BZ）、左旋咪唑和伊维菌素产生耐药性[3，4]。特别是苯并咪唑类药物广泛用于以学校为基础的人类肠道线虫驱虫计划[5]。这种一年两次或一年三次的大规模单次剂量治疗可以降低感染强度，但对鞭虫和钩虫的治愈率很低[6]。这些方案的日益广泛使用，包括在消除淋巴丝虫病群众治疗方案中将阿苯达唑添加到抗丝虫药物伊维菌素或乙胺嗪中[7]，增加了选择人类肠道线虫耐药菌株的可能性。在桑给巴尔的奔巴岛，自1994年以来一直在实施以学校为基础的常规靶向BZ化疗，我们最近观察到钩虫对甲苯咪唑的敏感性与治疗前活动值或邻近Mafia岛的疗效数据相比有所降低[8，9]。本研究旨在寻找该人群中BZ耐药的分子证据。
Infections caused by intestinal nematodes are responsible for significant morbidity both in human and in domestic animal populations [1, 2]. Treatment of these infections relies mainly on a limited number of chemotherapeutic agents but in domestic animals, large-scale use, frequent treatment of confined populations, and improper dosing have led to the development of resistance against benzimidazoles (BZ), levamisole and ivermectin [3, 4]. The benzimidazoles in particular are widely used in school-based deworming programmes for human gut nematodes [5]. Such biannual or triannual mass, single-dose treatments administered by schoolteachers reduce intensity of infection but have low cure rates for Trichuris trichiura and hookworms [6]. The increasingly widespread use of such programmes, including the addition of albendazole to the anti-filarial drugs ivermectin or diethylcarbamazin in the mass treatment Programme for the Elimination of Lymphatic Filariasis [7], raises the possibility of the selection of drug resistant strains of human gut nematodes. In Pemba Island, Zanzibar, a region in which regular school-based targeted BZ chemotherapy has been practised since 1994, we have recently observed reduced sensitivity of hookworms to mebendazole compared with pre-treatment campaign values or with efficacy data from the neighbouring island of Mafia [8, 9]. The present study was to develop methods to look for molecular evidence of BZ drug resistance in this population.