A diminazene-resistant strain ofTrypanosoma brucei bruceiisolated 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.

Comparative mild, moderate and severe effects of Trypanosomiasis and Ancylostomiasis on the Haemogram of Local dog breeds

“…Trypanosomiasis is a widespread disease of animals in Nigeria and a continual major cause of mortality in companion animals especially dogs [30][31][32]. Trypanosomiasis causes great haematological alterations in the infected animals [33].…”

Presence of Trypanosome Species and Anemic Status of Dogs in Zuru, Nigeria

“…Though dogs are known to pose minimal risk for human infection (HAT), they are important as a sentinel for infection (13). Canine trypanosomiasis has been reported as constituting a major health threat to canine population in the south-eastern part of Nigeria (10,11,16).…”

Aspectos epidemiológicos, clínicos e anatomopatológicos da intoxicação por aceturato de diminazeno em cães

“…Isso ocorre principalmente porque são reconhecidamente eficazes no tratamento de doenças causadas por hematozoários em cães (Jacobson et al 1996, Akpa et al 2008. Nos Estados Unidos, aceturato de diminazeno tem uso proibido pelo FDA (Food and Drug Administration) (Taboada & Lobetti 2006), mas, em outros países, principalmente naqueles da África, o fármaco é ainda hoje bastante utilizado no tratamento da babesiose (Collett 2000) e da tripanossomíase (Obi et al 2013) caninas, duas dentre as causas mais comuns de morte de cães na África do Sul (Collett 2000) e Nigéria (Anene et al 2006), respectivamente. Nesses dois países, aceturato de diminazeno ainda permanece sendo o agente antiprotozoário mais comumente utilizado (Naidoo et al 2009), apesar de haver relatos de resistência por determinadas cepas de Babesia gibsoni (Hwang et al 2010) e Trypanosoma brucei brucei (Anene et al 2006).…”

“…Nos Estados Unidos, aceturato de diminazeno tem uso proibido pelo FDA (Food and Drug Administration) (Taboada & Lobetti 2006), mas, em outros países, principalmente naqueles da África, o fármaco é ainda hoje bastante utilizado no tratamento da babesiose (Collett 2000) e da tripanossomíase (Obi et al 2013) caninas, duas dentre as causas mais comuns de morte de cães na África do Sul (Collett 2000) e Nigéria (Anene et al 2006), respectivamente. Nesses dois países, aceturato de diminazeno ainda permanece sendo o agente antiprotozoário mais comumente utilizado (Naidoo et al 2009), apesar de haver relatos de resistência por determinadas cepas de Babesia gibsoni (Hwang et al 2010) e Trypanosoma brucei brucei (Anene et al 2006). Embora a intoxicação por aceturato de diminazeno tenha sido descrita em cães desde a década de 1970, existem apenas cinco citações sobre essa toxicose na literatura internacional, a saber: 1) um resumo em anais de congresso (Boyt et al 1968), 2) um relato curto de alguns casos (Losos & Crockett 1969), 3) um trabalho científi-co experimental (Naudé et al 1970), 4) um relato de um caso (van Heerden 1981) e 5) uma descrição acerca de um caso submetido ao seminário semanal (Wednesday Slide Conference) da AFIP (Armed Forces Institute of Pathology) em 2000 (AFIP 2000).…”