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Whole genome sequencing distinguishes between relapse and reinfection in recurrent leprosy cases
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نویسنده
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stefani m.m.a. ,avanzi c. ,bührer-sékula s. ,benjak a. ,loiseau c. ,singh p. ,pontes m.a.a. ,gonçalves h.s. ,hungria e.m. ,busso p. ,piton j. ,silveira m.i.s. ,cruz r. ,schetinni a. ,costa m.b. ,virmond m.c.l. ,diorio s.m. ,dias-baptista i.m.f. ,rosa p.s. ,matsuoka m. ,penna m.l.f. ,cole s.t. ,penna g.o.
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منبع
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plos neglected tropical diseases - 2017 - دوره : 11 - شماره : 6
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چکیده
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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 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. © 2017 stefani et al.
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آدرس
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tropical pathology and public health institute,federal university of goiás,goiania,goiás, Brazil, global health institute,école polytechnique fédérale de lausanne, Switzerland, tropical pathology and public health institute,federal university of goiás,goiania,goiás,brazil,university of amazonas state,manaus,amazonas,brazil,tropical medicine foundation dr. heitor vieira dourado,manaus,amazonas, Brazil, global health institute,école polytechnique fédérale de lausanne, Switzerland, global health institute,école polytechnique fédérale de lausanne,switzerland,department of medical parasitology and infection biology,swiss tropical and public health institute, Switzerland, global health institute,école polytechnique fédérale de lausanne,switzerland,department of microbiology and biotechnology centre,maharaja sayajirao university of baroda,vadodara, India, dona libânia dermatology centre,fortaleza,ceará, Brazil, dona libânia dermatology centre,fortaleza,ceará, Brazil, tropical pathology and public health institute,federal university of goiás,goiania,goiás, Brazil, global health institute,école polytechnique fédérale de lausanne, Switzerland, global health institute,école polytechnique fédérale de lausanne, Switzerland, dona libânia dermatology centre,fortaleza,ceará, Brazil, university of amazonas state,manaus,amazonas,brazil,tropical dermatology and venerology,alfredo da matta foundation,manaus,amazonas, Brazil, tropical dermatology and venerology,alfredo da matta foundation,manaus,amazonas, Brazil, faculty of medicine,federal university of goiás,goiania,goiás, Brazil, lauro souza lima institute,bauru,são paulo, Brazil, lauro souza lima institute,bauru,são paulo, Brazil, lauro souza lima institute,bauru,são paulo, Brazil, lauro souza lima institute,bauru,são paulo, Brazil, department of mycobacteriology,leprosy research center,national institute of infectious diseases,higashimurayama,tokyo,japan,jyu-kanbo national museum,kusatsu,gunma, Japan, epidemiology and biostatistics department,universidade federal fluminense,rio de janeiro, Brazil, global health institute,école polytechnique fédérale de lausanne, Switzerland, tropical medicine centre,university of brasília,brasília df,brazil,fiocruz,brasilia, Brazil
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Authors
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