Whole genome sequencing distinguishes between relapse and reinfection in recurrent leprosy cases
Since leprosy is both treated and controlled by multidrug therapy (MDT) it is important to monitor recurrent cases for drug resistance and to distinguish between relapse and reinfection as a means of assessing therapeutic efficacy. All three objectives can be reached with single nucleotide resolutio...
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Published in | PLoS neglected tropical diseases Vol. 11; no. 6; p. e0005598 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
15.06.2017
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | Since leprosy is both treated and controlled by multidrug therapy (MDT) it is important to monitor recurrent cases for drug resistance and to distinguish between relapse and reinfection as a means of assessing therapeutic efficacy. All three objectives can be reached with single nucleotide resolution using next generation sequencing and bioinformatics analysis of Mycobacterium leprae DNA present in human skin.
DNA was isolated by means of optimized extraction and enrichment methods from samples from three recurrent cases in leprosy patients participating in an open-label, randomized, controlled clinical trial of uniform MDT in Brazil (U-MDT/CT-BR). Genome-wide sequencing of M. leprae was performed and the resultant sequence assemblies analyzed in silico.
In all three cases, no mutations responsible for resistance to rifampicin, dapsone and ofloxacin were found, thus eliminating drug resistance as a possible cause of disease recurrence. However, sequence differences were detected between the strains from the first and second disease episodes in all three patients. In one case, clear evidence was obtained for reinfection with an unrelated strain whereas in the other two cases, relapse appeared more probable.
This is the first report of using M. leprae whole genome sequencing to reveal that treated and cured leprosy patients who remain in endemic areas can be reinfected by another strain. Next generation sequencing can be applied reliably to M. leprae DNA extracted from biopsies to discriminate between cases of relapse and reinfection, thereby providing a powerful tool for evaluating different outcomes of therapeutic regimens and for following disease transmission. |
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Bibliography: | new_version ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 The authors have declared that no competing interests exist. Conceptualization: MMAS SBS GOP STC.Data curation: MMAS CA SBS AB CL PS STC MLP GOP.Formal analysis: MMAS CA SBS AB CL PS STC MLP GOP.Funding acquisition: GOP STC.Investigation: MMAS CA SBS AB CL PS EMH PB JP AS MBC MCLV SMD.Project administration: GOP STC.Resources: GOP MMAS STC MCLV.Supervision: GOP MMAS STC.Validation: GOP MMAS STC MCLV.Visualization: STC MMAS GOP SBS.Writing – original draft: MMAS CA SBS AB STC GOP.Writing – review & editing: MMAS CA SBS AB CL PS MAAP HSG EMH PB JP MISS RC AS MBC MCLV SMD IMFDB PSR MM MLFP STC GOP. |
ISSN: | 1935-2735 1935-2727 1935-2735 |
DOI: | 10.1371/journal.pntd.0005598 |