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Whole genome sequencing distinguishes between relapse and reinfection in recurrent leprosy cases.

Abstract：

BACKGROUND: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. METHODOLOGY: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. PRINCIPAL FINDINGS: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. CONCLUSIONS/SIGNIFICANCE: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.

journal_name

PLoS Negl Trop Dis

journal_title

PLoS neglected tropical diseases

authors

Stefani MMA,Avanzi C,Bührer-Sékula S,Benjak A,Loiseau C,Singh P,Pontes MAA,Gonçalves HS,Hungria EM,Busso P,Piton J,Silveira MIS,Cruz R,Schetinni A,Costa MB,Virmond MCL,Diorio SM,Dias-Baptista IMF,Rosa PS,Matsuoka M

doi

10.1371/journal.pntd.0005598

subject

Has Abstract

pub_date

2017-06-15 00:00:00

pages

e0005598

issue

eissn

1935-2727

issn

1935-2735

pii

PNTD-D-17-00193

journal_volume

pub_type

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Whole genome sequencing distinguishes between relapse and reinfection in recurrent leprosy cases.