Whole genome sequencing distinguishes between relapse and reinfection in recurrent leprosy cases
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2017
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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 reinfec tion 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 ofloxa cin 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 reinfec tion 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 pow erful tool for evaluating different outcomes of therapeutic regimens and for following disease
transmission.
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STEFANI, Mariane Martins de Araújo et al. Whole genome sequencing distinguishes between relapse and reinfection in recurrent leprosy cases. Plos Neglected Tropical Diseases, San Francisco, v. 11, n. 6, e0005598, 2017. DOI: 10.1371/journal.pntd.0005598. Disponível em: https://pmc.ncbi.nlm.nih.gov/articles/PMC5498066/. Acesso em: 12 fev. 2025.