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Markers for benzimidazole resistance in human parasitic nematodes?

Published online by Cambridge University Press:  03 July 2007

ROGER K. PRICHARD*
Affiliation:
Institute of Parasitology, McGill University, 21111 Lakeshore Road, Ste-Anne-de-Bellevue, Quebec, Canada, H9X 3V9
*
*Corresponding author: Institute of Parasitology, McGill University, 21111 Lakeshore road, Ste-Anne-de-Bellevue, Quebec, Canada, H9X 3V9. Tel: +1-514-398-7729. Fax: +1-514-398-7857. E-mail: [email protected]

Summary

Benzimidazole (BZ) resistance is widespread and appears to be readily selected in a variety of nematode parasites of animals. There have been reports of a lack of efficacy of BZ anthelmintics against soil transmitted nematode parasites of humans. However, resistance to BZs in nematodes of humans has not been confirmed. It is difficult to perform tests to confirm anthelmintic resistance in humans for a variety of technical and ethical reasons. The use of anthelmintic drugs for the control of helminth parasites in people is increasing massively as a result of numerous programmes to control gastrointestinal nematode parasites in children, the Global Program for the Elimination of Lymphatic Filariasis and other programmes. Many of these programmes are dependent on BZ anthelmintics and this will increase the pressure for resistance development to BZ anthelmintics in nematode parasites of people. We need to perform monitoring for anthelmintic resistance in these programmes and we need new tools to make that monitoring sensitive, inexpensive and practical. There is a real need for DNA-based markers for BZ resistance in nematode parasites of humans. We have a reasonable understanding of the molecular mechanisms and genetics of BZ resistance in some nematode parasites of animals and similar mechanisms are likely to prevail in nematodes of humans. Based on the likelihood that similar single nucleotide polymorphisms (SNPs) will be involved in BZ resistance in human, as in animal nematode parasites, rapid SNP assays have been developed for possible BZ resistance development in Wuchereria bancrofti.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2007

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References

Albonico, M., Bickle, Q., Ramsan, M., Montresor, A., Savioli, L. and Taylor, M. (2003). Efficacy of mebendazole and levamisole alone or in combination against intestinal nematode infections after repeated targeted mebendazole treatment in Zanzibar. Bulletin of the World Health Organization 81, 343352.Google ScholarPubMed
Albonico, M., Engels, D. and Savioli, L. (2004 a). Monitoring drug efficacy and early detection of drug resistance in human soil-transmitted nematodes: a pressing public health agenda for helminth control. International Journal for Parasitology 34, 12051210.CrossRefGoogle ScholarPubMed
Albonico, M., Wright, V. and Bickle, Q. (2004 b). Molecular analysis of the β-tubulin gene of hookworms as a basis for possible benzimidazole resistance on Pemba Island. Molecular and Biochemical Parasitology 134 281284.CrossRefGoogle ScholarPubMed
Bennett, A. B., Anderson, T. J. C., Barker, G. C., Michael, E. and Bundy, D. A. P. (2002). Sequence variation in the Trichuris trichiura beta-tubulin locus: implications for the development of benzimidazole resistance. International Journal for Parasitology 32, 15191528.CrossRefGoogle ScholarPubMed
Besier, R. B. and Love, S. C. J. (2003). Anthelmintic resistance in sheep nematodes in Australia: the need for new approaches. Australian Journal of Experimental Agriculture 43, 13831391.CrossRefGoogle Scholar
Conway, D. P. (1964). Variance in effectiveness of thiabendazole against Haemonchus contortus in sheep. American Journal of Veterinary Research 25, 844845.Google ScholarPubMed
De Clercq, D., Sacko, M., Behnke, J., Gilbert, F., Dorny, P. and Vercruysse, J. (1997). Failure of mebendazole in treatment of human hookworm infections in the southern region of Mali. American Journal of Tropical Medicine and Hygiene 57, 2530.CrossRefGoogle ScholarPubMed
Duke, B. O. L., Zea-Flores, G., Castro, J., Cupp, E. W. and Munoz, B. (1990). Effects of multiple monthly doses of ivermectin on adult Onchocerca volvulus. American Journal of Tropical Medicine and Hygiene 43, 657664.CrossRefGoogle ScholarPubMed
Eng, J. K. L., Blackhall, W. J., Osei-Atweneboana, M. Y., Bourguinat, C., Galazzo, D., Beech, R. N., Unnasch, T. R., Awadzi, K., Lubega, G. W. and Prichard, R. K. (2006). Ivermectin selection on β-tubulin: Evidence in Onchocerca volvulus and Haemonchus contortus. Molecular and Biochemical Parasitology 150, 229235.CrossRefGoogle ScholarPubMed
Eng, J. K. L. and Prichard, R. K. (2005). A comparison of genetic polymorphism in populations of Onchocerca volvulus from untreated- and ivermectin-treated patients. Molecular and Biochemical Parasitology 142, 193202.CrossRefGoogle ScholarPubMed
Farthing, M. J. G. (2006). Treatment options for the eradication of intestinal protozoa. Nature Clinical Practice Gastroenterology and Hepatology 3, 436445.CrossRefGoogle ScholarPubMed
Geerts, S. and Gryseels, B. (2001). Anthelmintic resistance in human helminths: a review. Tropical Medicine and International Health 6, 915921.CrossRefGoogle ScholarPubMed
Hampshire, V. A. (2005). Evaluation of efficacy of heartworm preventive products at the FDA. Veterinary Parasitology 133, 191195.CrossRefGoogle ScholarPubMed
Horton, J. (2000). Albendazole: a review of anthelmintic efficacy and safety in humans. Parasitology 121, S113S132.CrossRefGoogle ScholarPubMed
Kerboeuf, D., Blackhall, W., Kaminsky, R. and von Samson-Himmelstjerna, G. (2003). P-glycoprotein in helminths: function and perspectives for anthelmintic treatment and reversal of resistance. International Journal of Antimicrobial Agents 22, 332346.CrossRefGoogle ScholarPubMed
Kotze, A. C., Clifford, S., O'Grady, J., Behnke, J. M. and McCarthy, J. S. (2004). An in vitro larval motility assay to determine anthelmintic sensitivity for human hookworm and strongyloides species. American Journal of Tropical Medicine and Hygiene 71 608616.CrossRefGoogle Scholar
Michael, E., Malecela-Lazaro, M. N., Simonsen, P. E., Pedersen, E. M., Barker, G., Kumar, A. and Kazura, J. W. (2004). Mathematical modelling and the control of lymphatic filariasis. Lancet Infectious Diseases 4, 223234.CrossRefGoogle ScholarPubMed
Nare, B., Liu, Z., Prichard, R. K. and Georges, E. (1994). Benzimidazoles, potent antimitotic drugs, are substrates for the P-glycoprotein transporter in multidrug resistant cells. Biochemical Pharmacology 48, 22152222.CrossRefGoogle ScholarPubMed
Prichard, R. K. (2001). Genetic variability following selection of Haemonchus contortus with anthelmintics. Trends in Parasitology 17, 445453.CrossRefGoogle ScholarPubMed
Reynoldson, J. A., Behnke, J. M., Gracey, M., Horton, R. J., Spargo, R., Hopkins, R. M., Constantine, C. C., Gilbert, F., Stead, C., Hobbs, R. P. and Thompson, R. C. (1998). Efficacy of albendazole against Giardia and hookworm in a remote Aboriginal community in the north of Western Australia. Acta Tropica 71, 2744.CrossRefGoogle Scholar
Schwab, A. E., Boakye, D., Kyelem, D. and Prichard, R. K. (2005). Detection of benzimidazole-resistance associated mutations in the filarial nematode Wuchereria bancrofti and evidence for selection with albendazole and ivermectin treatment. American Journal of Tropical Medicine and Hygiene 73, 234238.CrossRefGoogle Scholar
Schwab, A. E., Churcher, T. S., Schwab, A. J., Basáñez, M.-G. and Prichard, R. K. (2006). Population genetics of concurrent selection with albendazole and ivermectin or diethylcarbamazine on the possible spread of albendazole resistance in Wuchereria bancrofti. Parasitology 133, 589601.CrossRefGoogle ScholarPubMed
Schwab, A. E., Churcher, T. S., Schwab, A. J., Basáñez, M.-G. and Prichard, R. K. (2007). An analysis of the population genetics of potential multi-drug resistance in lymphatic filariasis due to combination chemotherapy. Parasitology, Feb 26:116 [Epub ahead of print].Google ScholarPubMed
Upcroft, J., Mitchell, R., Chen, N. and Upcroft, P. (1996). Albendazole resistance in Giardia is correlated with cytoskeletal changes but not with a mutation at amino acid 200 in beta-tubulin. Microbial Drug Resistance 2, 303308.CrossRefGoogle Scholar
Xue, J., Hui-Qing, Q., Jun-Ming, Y., Fujiwara, R., Zhan, B., Hotez, P. and Shu-Hua, X. (2005). Necator americanus: optimization of the golden hamster model for testing anthelmintic drugs. Experimental Parasitology 111, 219223.CrossRefGoogle ScholarPubMed