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Melarsoprol sensitivity profile of Trypanosoma brucei gambiense isolates from cured and relapsed sleeping sickness patients from the Democratic Republic of the Congo

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dc.contributor.author Pyana Pati, P.
dc.contributor.author van Reet, N.
dc.contributor.author Mumba Ngoyi, D.
dc.contributor.author Lukusa, I. N.
dc.contributor.author Bin Shamamba, S. K.
dc.contributor.author Büscher, P.
dc.date.accessioned 2015-02-17T09:26:28Z
dc.date.available 2015-02-17T09:26:28Z
dc.date.issued 2014
dc.identifier.issn 1935-2727
dc.identifier.doi http://dx.doi.org/10.1371/journal.pntd.0003212
dc.identifier.other ITG-B2B
dc.identifier.other ITG-BLA
dc.identifier.other DBM
dc.identifier.other U-PARDIA
dc.identifier.other JIF
dc.identifier.other DOI
dc.identifier.other FTA
dc.identifier.other E-only
dc.identifier.other OAJ
dc.identifier.other Abstract
dc.identifier.other UPD57
dc.identifier.uri http://hdl.handle.net/10390/8275
dc.description.abstract BACKGROUND: Sleeping sickness caused by Trypanosoma brucei (T.b.) gambiense constitutes a serious health problem in sub-Sahara Africa. In some foci, alarmingly high relapse rates were observed in patients treated with melarsoprol, which used to be the first line treatment for patients in the neurological disease stage. Particularly problematic was the situation in Mbuji-Mayi, East Kasai Province in the Democratic Republic of the Congo with a 57% relapse rate compared to a 5% relapse rate in Masi-Manimba, Bandundu Province. The present study aimed at investigating the mechanisms underlying the high relapse rate in Mbuji-Mayi using an extended collection of recently isolated T.b. gambiense strains from Mbuji-Mayi and from Masi-Manimba. METHODOLOGY/PRINCIPAL FINDINGS: Forty five T.b. gambiense strains were used. Forty one were isolated from patients that were cured or relapsed after melarsoprol treatment in Mbuji-Mayi. In vivo drug sensitivity tests provide evidence of reduced melarsoprol sensitivity in these strains. This reduced melarsoprol sensitivity was not attributable to mutations in TbAT1. However, in all these strains, irrespective of the patient treatment outcome, the two aquaglyceroporin (AQP) 2 and 3 genes are replaced by chimeric AQP2/3 genes that may be associated with resistance to pentamidine and melarsoprol. The 4 T.b. gambiense strains isolated in Masi-Manimba contain both wild-type AQP2 and a different chimeric AQP2/3. These findings suggest that the reduced in vivo melarsoprol sensitivity of the Mbuji-Mayi strains and the high relapse rates in that sleeping sickness focus are caused by mutations in the AQP2/AQP3 locus and not by mutations in TbAT1. CONCLUSIONS/SIGNIFICANCE: We conclude that mutations in the TbAQP2/3 locus of the local T.b. gambiense strains may explain the high melarsoprol relapse rates in the Mbuji-Mayi focus but other factors must also be involved in the treatment outcome of individual patients. en_US
dc.language English en_US
dc.subject Protozoal diseases en_US
dc.subject Sleeping sickness en_US
dc.subject Trypanosomiasis, African en_US
dc.subject Trypanosoma brucei gambiense en_US
dc.subject Vectors en_US
dc.subject Tsetse flies en_US
dc.subject Glossina morsitans morsitans en_US
dc.subject Treatment outcome en_US
dc.subject Relapses en_US
dc.subject Isolation en_US
dc.subject Drug sensitivity testing en_US
dc.subject Melarsoprol en_US
dc.subject Congo-Kinshasa en_US
dc.subject Africa, Central en_US
dc.title Melarsoprol sensitivity profile of Trypanosoma brucei gambiense isolates from cured and relapsed sleeping sickness patients from the Democratic Republic of the Congo en_US
dc.type Article-E en_US
dc.citation.issue 10 en_US
dc.citation.jtitle PLoS Neglected Tropical Diseases en_US
dc.citation.volume 8 en_US
dc.citation.pages e3212 en_US
dc.identifier.pmid http://www.ncbi.nlm.nih.gov/pubmed/25275572
dc.citation.jabbreviation PLoS Negl Trop Dis en_US


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