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DETECTION OF BENZIMIDAZOLE RESISTANCE–ASSOCIATED MUTATIONS IN THE FILARIAL NEMATODE WUCHERERIA BANCROFTI AND EVIDENCE FOR SELECTION BY ALBENDAZOLE AND IVERMECTIN COMBINATION TREATMENT

The Global Program to Eliminate Lymphatic Filariasis has been implemented to reduce human microfilaremia to levels low enough to break the transmission of the disease by using single annual doses of albendazole in combination with diethylcarbamazine or ivermectin. Many veterinary helminth parasites have developed resistance against both albendazole and ivermectin. Resistance to albendazole in veterinary nematodes is known to be caused by either of two single amino acid substitutions from phenylalanine to tyrosine in parasite ß-tubulin at position 167 or 200. We have developed assays capable of detecting these single nucleotide polymorphisms (SNPs) in Wuchereria bancrofti, and have applied them to microfilaria obtained from patients in Ghana and Burkina Faso. One of the SNPs was found in worms from untreated populations in both locations. Worms from treated patients had significantly higher frequencies of these mutations. These findings indicate that a ß-tubulin allele associated with benzimidazole resistance is being selected in these populations.

Received September 2, 2004. Accepted for publication January 11, 2005.

Acknowledgments: We thank Drs. Brian Bagnall and Mark Bradley (GlaxoSmithKline) for their interest and encouragement.

Financial support: This study was supported by the Formation de Chercheurs et l’Aide à la Recherche (Quebec, Canada), the Natural Sciences and Engineering Research Council of Canada (Ottawa, Ontario, Canada), the Centre for Host Parasite Interactions (Sainte-Anne-de-Bellevue, Quebec, Canada), and GlaxoSmithKline (Brentford, Middlesex, United Kingdom).

^* Address correspondence to Roger K. Prichard, Institute of Parasitology, McGill University, 21111 Lakeshore Road, Sainte-Anne-Bellevue, Quebec H9X 3V9, Canada. E-mail: roger.prichard{at}mcgill.ca

Authors’ addresses: Anne E. Schwab, Institute of Parasitology, McGill University, 21111 Lakeshore Road, Sainte-Anne-de-Bellevue, Quebec H9X 3V9, Canada, Telephone: 514-398-8767, Fax: 514-398-7857, E-mail: aschwa4{at}po-box.mcgill.ca. Daniel A. Boakye, Noguchi Memorial Institute for Medical Research, PO Box LG581, Legon, Ghana, Telephone: 233-21-501-178, Fax: 233-21-502-182, E-mail: dboakye{at}noguchi.mimcom. Dominique Kyelem, Ministry of Health, 01 BP 2935, Ouagadougou 01, Burkina Faso, Telephone: 226-30-87-90, Fax: 226-326-335, E-mail: dominiquekyelem{at}yahoo.fr. Roger K. Prichard, Institute of Parasitology, McGill University, 21111 Lakeshore Road, Sainte-Anne-de-Bellevue, Quebec H9X 3V9, Canada, Telephone: 514-398-7961, Fax: 514-398-7857, E-mail: roger.prichard{at}mcgill.ca.

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