Trypanocidal drugs and the problem of drug resistance in West Africa

For more than half a century, livestock trypanosomosis in West Africa has been the subject of various research papers published in the scientific literature. Since the discovery of the first Trypanosoma congolense (T. congolense) resistant strain in 1984, several studies have alerted on the increasing phenomenon of trypanocidal drug resistance (TDR) in the cotton belt of West Africa against the two commonly molecules used in this area i.e. diminazene aceturate and isometamidium chloride. The recently developed molecular tools for the diagnosis of TDR allowed gaining better information on the spread of TDR. The work that is presented in this thesis aimed at (i) improving the performance of the PCR-RFLP tool used for the diagnosis of diminazene aceturate resistance in T. congolense under field conditions, (ii) prospect the development of a similar molecular tool for the diagnosis of T. vivax resistance to diminazene aceturate, and using these molecular tools to monitor TDR in West Africa through the epidemiosurveillance network of hemoresistance to trypanocidal and acaricides drugs in West Africa called RESCAO, (iii) determining the impact of TDR on livestock health and production in endemic areas of West Africa and (iv) proposing an alternative to contain or reduce the TDR phenomenon. The first chapter of this thesis gives general information on the disease and its components (parasite and vector). Moreover, it reviews our current knowledge on the pharmacology of diminazene aceturate, isometamidium chloride and homidium salts and on the phenomenon of trypanocidal drug resistance. Chapter 2 describes the work for the improvement of the performance of a PCR-RFLP for the detection of diminazene resistance in T. congolense under field conditions. We used blood spots on filters papers collected from parasitologically positive cattle in South-east Mali. This study permitted to increase the specificity of the PCR-RFLP test and to enhance its sensitivity in determining a low parasitaemia observed in the field. This molecular tool was used to update the current situation of T. congolense resistance to diminazene aceturate in the countries that are members of RESCAO - the West African’s epidemiosurveillance network of chemoresistance to trypanocidal and acaricides drugs. From this study we can learn that TDR in widely distributed West Africa. In chapter 3, an exhaustive exploration of the genes predicted to code for nucleoside transporters in T. vivax was performed. For this analysis, T. vivax samples used were already characterized in goats for their sensitivity and/or resistance against diminazene aceturate. SSCP analysis and sequencing shows that the P2-type putative adenosine transporters genes seem not to been involved in diminazene resistance in this trypanosome species. More studies are therefore needed to understand this mechanism of resistance or alternatively to find a trustable genetic marker. Chapter 4 aimed at studying the impact of TDR in livestock health and production in endemic areas of West Africa. We used 60 female goats infected with T. vivax strains collected in the vicinity of Bobo-Dioulasso (Burkina Faso). This study showed that drug resistant T. vivax strains inoculated to goats might probably had no significant impact on the PCV and body weight losses except for a few highly virulent strains. This still needs to be confirmed in cattle under natural tsetse and Trypanosoma challenge. Chapter 5 aimed at finding an alternative to contain and/or reduce TDR by potentiating the efficacy of isometamidium chloride by associating it to two veterinary affordable antibiotics i.e. tetracyclines and enrofloxacin. The obtained results are encouraging even if more studies are still needed to determine the best galenic solution, the optimal ombination of the chemosensitizer with isometamidium and to test this combination in livestock under controlled and field conditions in areas with high tsetse challenge and high trypanocidal drug resistance. In the last chapter (Chapter 6), the major findings of the thesis are discussed in the wide context of the management of animal trypanosomosis in West Africa