Trypanocidal drugs and the problem of drug resistance in West Africa

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Résumé

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 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
chemoresistance 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


Summary 139
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
combination 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.

Mots-clés

trypanosomosis, drug, drug resistance