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High prevalence of drug resistance in animal Trypanosomes without a history of drug exposure

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dc.contributor.author Chitanga, S.
dc.contributor.author Marcotty, T.
dc.contributor.author Namangala, B.
dc.contributor.author Van den Bossche, P.
dc.contributor.author Van Den Abbeele, J.
dc.contributor.author Delespaux, V.
dc.date.accessioned 2012-01-17T11:02:30Z
dc.date.available 2012-01-17T11:02:30Z
dc.date.issued 2011
dc.identifier.issn 1935-2727
dc.identifier.doi http://dx.doi.org/10.1371/journal.pntd.0001454
dc.identifier.other ITG-A1B
dc.identifier.other ITG-A2A
dc.identifier.other ITG-A4A
dc.identifier.other ITG-A5A
dc.identifier.other ITG-ALA
dc.identifier.other ANIMAL
dc.identifier.other U-VCONT
dc.identifier.other U-VPROT
dc.identifier.other JIF
dc.identifier.other DOI
dc.identifier.other FTA
dc.identifier.other Abstract
dc.identifier.other UPD42
dc.identifier.uri http://hdl.handle.net/10390/6776
dc.description.abstract BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION/SIGNIFICANCE: 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. en
dc.language English en
dc.subject Protozoal diseases en
dc.subject Animal diseases en
dc.subject Nagana en
dc.subject Trypanosoma congolense en
dc.subject Cattle en
dc.subject Vectors en
dc.subject Tsetse flies en
dc.subject Glossina en
dc.subject Drug resistance en
dc.subject Diminazene aceturate en
dc.subject Mutations en
dc.subject Drug effects en
dc.subject Exposure en
dc.subject Treatment en
dc.subject Isolation en
dc.subject Mice en
dc.subject In vivo en
dc.subject PCR-RFLP en
dc.subject Parasitemia en
dc.subject Zambia en
dc.subject Zimbabwe en
dc.subject South Africa en
dc.subject Africa, Southern en
dc.title High prevalence of drug resistance in animal Trypanosomes without a history of drug exposure en
dc.type Article-E en
dc.citation.issue 12 en
dc.citation.jtitle PLoS Neglected Tropical Diseases en
dc.citation.volume 5 en
dc.citation.pages e1454 en
dc.identifier.pmid http://www.ncbi.nlm.nih.gov/pubmed/22206039
dc.citation.jabbreviation PLoS Negl Trop Dis en


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