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A diminazene-resistant strain of Trypanosoma brucei brucei isolated from a dog is cross-resistant to pentamidine in experimentally infected albino rats

Published online by Cambridge University Press:  12 September 2005

B. M. ANENE ,
R. C. EZEOKONKWO ,
T. I. MMESIRIONYE ,
J. N. A. TETTEY ,
J. M. BROCK ,
M. P. BARRETT  and
H. P. DE KONING
B. M. ANENE
Affiliation:
Faculty of Veterinary Medicine, University of Nigeria, Nsukka, Enugu State, Nigeria
R. C. EZEOKONKWO
Affiliation:
Faculty of Veterinary Medicine, University of Nigeria, Nsukka, Enugu State, Nigeria
T. I. MMESIRIONYE
Affiliation:
Faculty of Veterinary Medicine, University of Nigeria, Nsukka, Enugu State, Nigeria
J. N. A. TETTEY
Affiliation:
Department of Pharmaceutical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, UK
J. M. BROCK
Affiliation:
Institute of Biomedical and Life Sciences, Division of Infection and Immunity, University of Glasgow, Joseph Black Building, Glasgow G12 8QQ, UK
M. P. BARRETT
Affiliation:
Institute of Biomedical and Life Sciences, Division of Infection and Immunity, University of Glasgow, Joseph Black Building, Glasgow G12 8QQ, UK
H. P. DE KONING
Affiliation:
Institute of Biomedical and Life Sciences, Division of Infection and Immunity, University of Glasgow, Joseph Black Building, Glasgow G12 8QQ, UK
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Abstract

Trypanosomosis is a major cause of mortality for dogs in Nigeria and treatment with diminazene aceturate has steadily become less effective, either as a result of low quality of the locally available diminazene preparations or of drug resistance. To investigate these alternatives, samples of locally obtained drugs were analysed for diminazene aceturate content and a strain of Trypanosoma brucei brucei was isolated from a diminazene-refractory dog in Nsukka, south-eastern Nigeria, and used to infect albino rats. The quality of diminazene aceturate-based preparations was variable, with two preparations containing less than 95% of the stated active compound. Rats infected with T. brucei isolated from the dog were treated 7 and 10 days after infection either with 7 mg/kg diminazene aceturate (intraperitoneally, once) or with 4 mg/kg pentamidine isethionate (intramuscularly, 7 consecutive days). Relapse rates were 100% for both trypanocides in the groups of rat treated 10 days post-infection, and 83% and 50% of rats treated 7 days after infection relapsed to diminazene aceturate and pentamidine isethionate, respectively. Careful consideration of physiological parameters showed that pentamidine was only marginally superior to diminazene aceturate as applied in this study. It was concluded that dogs in Nigeria are infected with genuinely diminazene aceturate-resistant trypanosomes that appear to be cross-resistant to pentamidine isethionate.

Keywords

Trypanosoma brucei bruceidrug resistancecanine trypanosomosisdiminazene aceturatepentamidine isethionatecross-resistance
Type
Research Article
Information
Parasitology , Volume 132 , Issue 1 , January 2006 , pp. 127 - 133
Copyright
© 2005 Cambridge University Press

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References

REFERENCES

Anene, B. M. and Omamegbe, J. O. ( 1987). Common diseases of dogs in Nigeria. Zariya Veterinarian 2, 46–55.Google Scholar
Anene, B. M., Chukwu, C. C., Chime, A. B. and Anika, S. M. ( 1989). Comparative clinical and haematological observations in dogs infected with Trypanosoma brucei brucei and Trypanosoma congolense treated with diminazene aceturate. Zariya Veterinarian 4, 11–18.Google Scholar
Anene, B. M., Chukwu, C. C. and Anika, S. M. ( 1999). Sensitivity to diminazene aceturate and isometamidium chloride of trypanosomes isolated from dogs in Nsukka area, Nigeria. Revue d'Elevage et de Medecine Veterinaire des Pays Tropicaux 52, 129–131.Google Scholar
Anene, B. M., Onah, D. N. and Nawa, Y. ( 2001). Drug resistance in pathogenic African trypanosomes: what hopes for the future? Veterinary Parasitology 96, 83–100.Google Scholar
Anika, S. M., Shetty, S. N., Asuzu, I. U. and Chime, A. B. ( 1987). Effects of some trypanocides and anti-inflammatory agents in experimental Trypanosoma brucei infection in mice. Zariya Veterinarian 2, 9–15.Google Scholar
Atsriku, C., Watson, D. G., Tettey, J. N. A., Grant, M. H. and Skellern, G. G. ( 2002). Determination of diminazene aceturate in pharmaceutical formulations by HPLC and identification of related substances by LC/MS. Journal of Pharmaceutical and Biomedical Analysis 30, 979–986.CrossRefGoogle Scholar
Bacchi, C. J. ( 1993). Resistance to clinical drugs in African trypanosomes. Parasitology Today 9, 190–193.CrossRefGoogle Scholar
Barrett, M. P. and Fairlamb, A. H. ( 1999). The biochemical basis for arsenical-diamidine cross-resistance in African trypanosomes. Parasitology Today 15, 136–140.CrossRefGoogle Scholar
Berger, B. J., Carter, N. S. and Fairlamb, A. H. ( 1995). Characterisation of pentamidine-resistant Trypanosoma brucei brucei. Molecular and Biochemical Parasitology 69, 289–298.CrossRefGoogle Scholar
Bray, P. G., Barrett, M. P., Ward, S. A. and De Koning, H. P. ( 2003). Pentamidine uptake and resistance in pathogenic protozoa. Trends in Parasitology 19, 232–239.CrossRefGoogle Scholar
Chukwu, C. C., Anene, B. M. and Anika, S. M. ( 1990). Relapse infection after chemotherapy in dogs experimentally infected with Trypanosoma brucei brucei. Journal of Small Animal Practice 31, 141–144.CrossRefGoogle Scholar
De Koning, H. P. ( 2001 a). Uptake of Pentamidine in Trypanosoma brucei brucei is mediated by three distinct transporters: Implications for cross-resistance with arsenicals. Molecular Pharmacology 59, 586–592.Google Scholar
De Koning, H. P. ( 2001 b). Transporters in African trypanosomes: role in drug action and resistance. International Journal for Parasitology 31, 512–522.Google Scholar
De Koning, H. P., Anderson, L. F., Stewart, M., Burchmore, R. J. S., Wallace, L. J. M. and Barrett, M. P. ( 2004). The trypanocide diminazene aceturate is accumulated predominantly through the TbAT1 purine transporter: Additional insights on diamidine resistance in African trypanosomes. Antimicrobial Agents and Chemotherapy 48, 1515–1519.CrossRefGoogle Scholar
De Koning, H. P., MacLeod, A., Barrett, M. P., Cover, B. and Jarvis, S. M. ( 2000). Further evidence for a link between melarsoprol resistance and P2 transporter function in African trypanosomes. Molecular and Biochemical Parasitology 106, 181–185.CrossRefGoogle Scholar
Fairlamb, A. H., Carter, N. S., Cuningham, M. and Smith, K. ( 1992). Characterisation of Melarsen-resistant Trypanosoma brucei brucei with respect to other drugs and trypanothione metabolism. Molecular and Biochemical Parasitology 53, 213–222.CrossRefGoogle Scholar
Geerts, S., Holmes, P. H., Diall, O. and Eisler, M. C. ( 2001). African bovine trypanosomiasis: the problem of drug resistance. Trends in Parasitology 17, 25–29.CrossRefGoogle Scholar
Herbert, W. J. and Lumsden, W. H. R. ( 1976). Trypanosoma brucei: a rapid “matching” method for estimating the host's parasitaemia. Experimental Parasitology 40, 427–431.CrossRefGoogle Scholar
Jennings, F. W., Whitelaw, D. D. and Urquhart, G. M. ( 1977). The relationship between duration of infection with Trypanosoma brucei in mice and the efficacy of chemotherapy. Parasitology 75, 143–153.CrossRefGoogle Scholar
Jennings, F. W., Whitelaw, D. D., Holmes, P. H., Chizyuka, H. G. B. and Urquhart, G. M. ( 1979). The brain as a source of relapsing T. brucei infection in mice after chemotherapy. International Journal for Parasitology 9, 381–384.Google Scholar
Kaggwa, E., Munyua, W. K. and Mugera, G. M. ( 1984). The pathogenicity of Trypanosoma brucei brucei in dogs. Bulletin of Animal Health and Production in Africa 82, 360–368.Google Scholar
Kaggwa, E., Munyua, W. K. and Mugera, G. M. ( 1988). Relapses in dogs experimentally infected with Trypanosoma brucei and treated with diminazene aceturate or isometamidium chloride. Veterinary Parasitology 27, 199–208.CrossRefGoogle Scholar
Kalu, A. U. ( 1995 a). Studies on the chemotherapeutic control of animal trypanosomiasis in Nigeria. Studies and Researches in Veterinary Medicine 3, 82–89.Google Scholar
Kalu, A. U. ( 1995 b). Sensitivity of animal-derived Trypanozoon stocks from sleeping sickness endemic foci of Nigeria to trypanocides and human plasma. Revue d'Elevage et de Medecine Veterinaire des Pays Tropicaux 48, 139–144.Google Scholar
Kaminsky, R. and Mäser, P. ( 2000). Drug resistance in African trypanosomes. Current Opinion in Anti-infective Investigational Drugs 2, 76–82.Google Scholar
Masiga, D. K., Smyth, A. J., Hayes, P., Bromridge, T. J. and Gibson, W. C. ( 1992). Sensitive detection of trypanosomes in tsetse flies by DNA amplification. International Journal for Parasitology 22, 909–918.CrossRefGoogle Scholar
Matovu, E., Seebeck, T., Enyaru, J. C. K. and Kaminsky, R. ( 2001). Drug resistance in Trypanosoma brucei spp., the causative agents of sleeping sickness in man and nagana in cattle. Microbes and Infection 3, 763–770.Google Scholar
Matovu, E., Stewart, M., Geiser, F., Brun, R., Mäser, P., Wallace, L. J. M., Burchmore, R. J. S., Enyaru, J. C. K., Barrett, M. P., Kaminsky, R., Seebeck, T. and De Koning, H. P. ( 2003). Mechanisms of arsenical and diamidine uptake and resistance in Trypanosoma brucei. Eukaryotic Cell 2, 1003–1008.CrossRefGoogle Scholar
Mbwanbo, H. A., Mella, P. N. P. and Lekaki, K. A. ( 1988). Berenil (diminazene aceturate) resistant Trypanosoma congolense in cattle under natural tse tse challenge at Kilaha Tanzania. Acta Tropica 45, 239–244.Google Scholar
Omamegbe, J. O., Orajaka, L. J. E. and Emehelu, C. O. ( 1984). The incidence and clinical forms of naturally occurring canine trypanosomiasis in two Veterinary clinics in Anambra State of Nigeria. Bulletin of Animal Health and Production in Africa 32, 23–29.Google Scholar
Pepin, T. and Milord, F. ( 1994). The treatment of human African trypanosomiasis. Advances in Parasitology 33, 1–47.CrossRefGoogle Scholar
Peregrine, A. S. ( 1991). Chemotherapy and delivery systems; haemoparasites. Veterinary Parasitology 54, 223–248.Google Scholar
Radwanska, M., Claws, F., Magez, S., Magnus, E., Perez-Morga, D., Pays, E. and Büscher, P. ( 2002). Novel primer sequences for polymerase chain reaction-based detection of Trypanosoma brucei gambiense. American Journal of Tropical Medicine and Hygiene 67, 289–295.CrossRefGoogle Scholar
Sayer, P. G., Morrison, W. I., Preston, T. M., Hird, S. F., Price, J. E. and Murray, M. ( 1979). African trypanosomiasis in the dog. In 15th International Scientific Council for Trypanosomiasis Research and Control (OAU/STRC), Banjul, The Gambia. pp. 489–496.
Soulsby, E. J. L. ( 1982). Helminths, Arthropods and Protozoa of Domesticated Animals, 7th Edn. Bailliere Tindall, London, UK.
Tait, A., Babiker, E. A. and Le Ray, D. ( 1984). Enzyme variation in Trypanosoma brucei spp. I Evidence for the sub-speciation of Trypanosoma brucei gambiense. Parasitology 89, 311–326.Google Scholar