Abstract

BackgroundTrypanosomosis caused by Trypanosoma congolense is a major constraint to animal health in sub-Saharan Africa. Unfortunately, the treatment of the disease is impaired by the spread of drug resistance. Resistance to diminazene aceturate (DA) in T. congolense is linked to a mutation modifying the functioning of a P2-type purine-transporter responsible for the uptake of the drug. Our objective was to verify if the mutation was linked or not to drug pressure.Methodology/Principal FindingsThirty-four T. congolense isolates sampled from tsetse or wildlife were screened for the DA-resistance linked mutation using DpnII-PCR-RFLP. The results showed 1 sensitive, 12 resistant and 21 mixed DpnII-PCR-RFLP profiles. This suggests that the mutation is present on at least one allele of each of the 33 isolates. For twelve of the isolates, a standard screening method in mice was used by (i) microscopic examination, (ii) trypanosome-specific 18S-PCR after 2 months of observation and (iii) weekly trypanosome-specific 18S-PCR for 8 weeks. The results showed that all mice remained microscopically trypanosome-positive after treatment with 5 mg/kg DA. With 10 and 20 mg/kg, 8.3% (n = 72) and 0% (n = 72) of the mice became parasitologically positive after treatment. However, in these latter groups the trypanosome-specific 18S-PCR indicated a higher degree of trypanosome-positivity, i.e., with a unique test, 51.4% (n = 72) and 38.9% (n = 72) and with the weekly tests 79.2% (n = 24) and 66.7% (n = 24) for 10 and 20 mg/kg respectively.Conclusion/SignificanceThe widespread presence of the DA-resistance linked mutation in T. congolense isolated from wildlife suggests that this mutation is favourable to parasite survival and/or its dissemination in the host population independent from the presence of drug. After treatment with DA, those T. congolense isolates cause persisting low parasitaemias even after complete elimination of the drug and with little impact on the host's health.

Highlights

  • Animal trypanosomosis is one of the major constraints to animal health and production in sub-Saharan Africa and has a major impact on people’s livelihoods

  • Due to the privatization of veterinary services in most parts of Africa, farmers have easy access to these trypanocides and this has resulted in rampant misuse and under-dosage of the medications, actions which have been blamed for the emergence of trypanocidal drug resistance [4,5]

  • Trypanosomosis is responsible for the death of 3 million heads of cattle yearly, with 50 million animals at risk in subSaharan Africa

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Summary

Introduction

Animal trypanosomosis is one of the major constraints to animal health and production in sub-Saharan Africa and has a major impact on people’s livelihoods. The main drugs used by livestock keepers are isometamidium chloride (ISM) which has both curative and prophylactic effects and DA which has only curative properties. There are 18 countries in which trypanocidal drug resistance has been reported [2] and more recently in Benin, Ghana and Togo (Reseau d’epidemiosurveillance de la resistance aux trypanocides et aux acaricides en Afrique de l’Ouest – RESCAO, unpublished data). Most of these reports seem to be confined to areas where the disease is endemic [6]. Our objective was to verify if the mutation was linked or not to drug pressure

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