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 beta-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 beta-tubulin allele associated with benzimidazole resistance is being selected in these populations.
Schwab
Anne E
AE
Institute of Parasitology, McGill University, Sainte-Anne-de-Bellevue, Quebec, Canada.
Boakye
Daniel A
DA
Kyelem
Dominique
D
Prichard
Roger K
RK
D015766:Albendazole / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002050:Burkina Faso / Q000453:epidemiology; D004351:Drug Resistance / Q000235:genetics*; D004359:Drug Therapy, Combination; D005368:Filariasis / Q000188:drug therapy / Q000469:parasitology; D005369:Filaricides / Q000494:pharmacology* / Q000627:therapeutic use; D005869:Ghana / Q000453:epidemiology; D006801:Humans; D007559:Ivermectin / Q000494:pharmacology / Q000627:therapeutic use; D008969:Molecular Sequence Data; D009154:Mutation; D021261:Parasitic Sensitivity Tests; D012641:Selection, Genetic; D014404:Tubulin / Q000235:genetics; D014958:Wuchereria bancrofti / Q000187:drug effects* / Q000235:genetics
D001562:Benzimidazoles; D005369:Filaricides; D014404:Tubulin; D007559:Ivermectin; C031000:benzimidazole; D015766:Albendazole