Volume 73, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


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 β-tubulin at position 167 or 200. We have developed assays capable of detecting these single nucleotide polymorphisms (SNPs) in , 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 β-tubulin allele associated with benzimidazole resistance is being selected in these populations.


Article metrics loading...

Loading full text...

Full text loading...



  1. WHO, 1999. Building Partnerships for Lymphatic Filariasis: Strategic Plan. Geneva: World Health Organization. WHO/FIL/ 99.198WHO/l.
  2. Prichard RK, 1990. Anthelmintic resistance in nematodes: extent, recent understanding and future directions for control and research. Int J Parasitol 20 : 515–523.
  3. Coles GC, 1999. Anthelmintic resistance and the control of worms. J Med Microbiol 48 : 323–325.
  4. Krogstad DL, Gluzman IY, Kyle DE, Oduola AM, Martin SK, Milhous WK, Schlesinger PH, 1987. Efflux of chloroquine from Plasmodium falciparum: mechanism of chloroquine resistance. Science 238 : 1283–1285.
  5. Friedman PA, Platzer EG, 1978. Interaction of anthelmintic benzimidazoles and benzimidazole derivatives with bovine brain tubulin. Biochim Biophys Acta 544 : 605–614.
  6. Köhler P, Bachmann R, 1981. Intestinal tubulin as possible target for the chemotherapeutic action of mebendazole in parasitic nematodes. Mol Biochem Parasitol 4 : 325–336.
  7. Lubega GW, Prichard RK, 1990. Specific interaction of benzimidazole anthelmintics with tubulin: high-affinity binding and benzimidazole resistance in Haemonchus contortus. Mol Biochem Parasitol 38 : 221–232.
  8. Kwa MSG, Veenstra JG, Roos MH, 1993. Molecular characterisation of β-tubulin genes present in benzimidazole-resistant populations of Haemonchus contortus. Mol Biochem Parasitol 60 : 133–144.
  9. Kwa MSG, Veenstra JG, Roos MH, 1993. Benzimidazole resistance in Haemonchus contortus is correlated with a conserved mutation at amino acid 200 in beta-tubulin isotype 1. Mol Biochem Parasitol 63 : 299–303.
  10. Elard L, Comes AM, Humbert JF, 1996. Sequences of β-tubulin cDNA from benzimidazole-susceptible and -resistant strains of Teladorsagia circumcincta, a nematode parasite of small ruminants. Mol Biochem Parasitol 79 : 249–253.
  11. Silvestre A, Cabaret J, 2002. Mutation in position 247 of isotype 1 β-tubulin gene of Trichostrongylid nematodes: role in benzimidazole resistance? Mol Biochem Parasitol 120 : 297–300.
  12. Prichard R, 2001. Genetic selection following selection of Haemonchus contortus with anthelmintics. Trends Parasitol 17 : 445–453.
  13. Driscoll M, Dean E, Reilly E, Bergholz E, Chalfie M, 1989. Genetic and molecular analysis of a Caenorhabditis elegans beta-tubulin that conveys benzimidazole sensitivity. J Cell Biol 109 : 2993–3003.
  14. Pape M, Samson-Himmelstjerna G, Schnieder T, 1999. Characterization of a beta-tubulin gene of Cyclicyclus nassatus. Int J Parasitol 29 : 1941–1947.
  15. von Samson-Himmelstjerna G, Harder A, Pape M, Schnieder T, 2001. Novel small strongyle (Cyathostominae) beta-tubulin sequences. Parasitol Res 87 : 122–125.
  16. Elard L, Humbert JF, 1999. Importance of the mutation of amino acid 200 of the isotype 1 β-tubulin gene in the benzimidazole resistance of the small-ruminant parasite Teladorsagia circumcincta. Parasitol Res 85 : 452–456.
  17. Jung MK, Wilder IB, Oakley BR, 1992. Amino acid alterations in the benA (tubulin) gene of Aspergillus nidulans that confer benomyl resistance. Cell Motil Cytoskeleton 22 : 170–174.
  18. Koenraadt H, Sommerville SC, Jones AL, 1992. Characterisation of mutations on the beta-tubulin gene of benomyl-resistant field strains of Venturia inaequalis and other pathogenic fungi. Mol Plant Pathol 82 : 1348–1354.
  19. Orbach MJ, Porro EB, Yanofsky C, 1986. Cloning and characterization of the gene for beta-tubulin from a benomyl-resistant mutant of Neurospora crassa and its use as a dominant selectable marker. Mol Cell Biol 6 : 2452–2461.
  20. Yarden O, Katan T, 1993. Mutations leading to substitutions at amino-acid 198 and 200 of beta-tubulin that correlate with benomyl-resistant phenotypes of field strains of Botrytis cinerea. Mol Plant Pathol 83 : 1478–1483.
  21. Edlind T, Visvesvara G, Li J, Katiya S, 1994. Cryptosporidium and microsporidial β-tubulin sequences: predictions of benzimidazole sensitivity and phylogeny. J Eukaryot Microbiol 41 : 38S.
  22. Albonico M, Wright V, Bickle O, 2004. Molecular analysis of the beta-tubulin gene of human hookworms as a basis for possible benzimidazole resistance on Pemba Island. Mol Biochem Parasitol 134 : 281–284.
  23. Hoti SL, Subramaniyan K, Das PK, 2003. Detection of codon for amino acid 200 in isotype 1 beta-tubulin gene of Wuchereria bancrofti isolates, implicated in resistance to benzimidazoles in other nematodes. Acta Trop 88 : 77–81.
  24. Beech RN, Prichard RK, Scott ME, 1994. Genetic variability of the β-tubulin genes in benzimidazole-susceptible and -resistant strains of Haemonchus contortus. Genetics 38 : 103–110.
  25. Hall A, Adjei S, Kihamia C, 1996. School health programmes. Afr Health Sci 18 : 22–23.
  26. Geary TG, Nulf SC, Favreau MA, Tang L, Prichard RK, Hatzenbuhler NT, Shea MH, Alexander SJ, Klein RD, 1992. Three β-tubulin cDNAs from the parasitic nematode Haemonchus contortus. Mol Biochem Parasitol 50 : 295–306.
  27. Guenette S, Prichard RK, Matlashewski G, 1992. Identification of a novel Brugia pahangi β-tubulin gene (β2) and a 22-nucleotide spliced leader sequence on β1-tubulin mRNA. Mol Biochem Parasitol 50 : 275–284.

Data & Media loading...

  • Received : 02 Sep 2004
  • Accepted : 11 Jan 2005

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error