High prevalence of drug resistance in animal trypanosomes without a history of drug exposure.

<h4>Background</h4>Trypanosomosis 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...

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Autores principales:	Simbarashe Chitanga, Tanguy Marcotty, Boniface Namangala, Peter Van den Bossche, Jan Van Den Abbeele, Vincent Delespaux
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/814400e3c0da44ba9bdfc31216df4219
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spelling	oai:doaj.org-article:814400e3c0da44ba9bdfc31216df42192021-11-18T09:14:35ZHigh prevalence of drug resistance in animal trypanosomes without a history of drug exposure.1935-27271935-273510.1371/journal.pntd.0001454https://doaj.org/article/814400e3c0da44ba9bdfc31216df42192011-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22206039/pdf/?tool=EBIhttps://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735<h4>Background</h4>Trypanosomosis 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.<h4>Methodology/principal findings</h4>Thirty-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.<h4>Conclusion/significance</h4>The 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.Simbarashe ChitangaTanguy MarcottyBoniface NamangalaPeter Van den BosscheJan Van Den AbbeeleVincent DelespauxPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 5, Iss 12, p e1454 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Simbarashe Chitanga Tanguy Marcotty Boniface Namangala Peter Van den Bossche Jan Van Den Abbeele Vincent Delespaux High prevalence of drug resistance in animal trypanosomes without a history of drug exposure.
description	<h4>Background</h4>Trypanosomosis 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.<h4>Methodology/principal findings</h4>Thirty-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.<h4>Conclusion/significance</h4>The 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.
format	article
author	Simbarashe Chitanga Tanguy Marcotty Boniface Namangala Peter Van den Bossche Jan Van Den Abbeele Vincent Delespaux
author_facet	Simbarashe Chitanga Tanguy Marcotty Boniface Namangala Peter Van den Bossche Jan Van Den Abbeele Vincent Delespaux
author_sort	Simbarashe Chitanga
title	High prevalence of drug resistance in animal trypanosomes without a history of drug exposure.
title_short	High prevalence of drug resistance in animal trypanosomes without a history of drug exposure.
title_full	High prevalence of drug resistance in animal trypanosomes without a history of drug exposure.
title_fullStr	High prevalence of drug resistance in animal trypanosomes without a history of drug exposure.
title_full_unstemmed	High prevalence of drug resistance in animal trypanosomes without a history of drug exposure.
title_sort	high prevalence of drug resistance in animal trypanosomes without a history of drug exposure.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/814400e3c0da44ba9bdfc31216df4219
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High prevalence of drug resistance in animal trypanosomes without a history of drug exposure.

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