Molecular analysis of the beta-tubulin gene of human hookworms as a basis for possible benzimidazole resistance on Pemba Island.

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.