title: A diminazene-resistant strain of Trypanosoma brucei brucei isolated from a dog is cross-resistant to pentamidine in experimentally infected albino rats.
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.
authors.affiliation: Faculty of Veterinary Medicine, University of Nigeria, Nsukka, Enugu State, Nigeria.
authors.forename: B M
authors.initials: BM
authors.lastname: Anene
authors.forename: R C
authors.initials: RC
authors.lastname: Ezeokonkwo
authors.forename: T I
authors.initials: TI
authors.lastname: Mmesirionye
authors.forename: J N A
authors.initials: JN
authors.lastname: Tettey
authors.forename: J M
authors.initials: JM
authors.lastname: Brock
authors.forename: M P
authors.initials: MP
authors.lastname: Barrett
authors.forename: H P
authors.initials: HP
authors.lastname: De Koning
mesh_terms: D000818:Animals; D004133:Diminazene / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D021261:Parasitic Sensitivity Tests; D010419:Pentamidine / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome; D014344:Trypanocidal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000472:pathogenicity; D014353:Trypanosomiasis, African / Q000188:drug therapy*
chemical_list: D014344:Trypanocidal Agents; D010419:Pentamidine; C003915:diminazene aceturate; D004133:Diminazene