02129nas a2200265   4500000000100000008004100001100001400042700002000056700001400076700001200090700001400102700001300116700001400129700001200143700001200155700001500167700001500182700001200197245009700209856007900306300001300385490000600398520144500404022001401849       2015                            d1 aEddyani M1 aVandelannoote K1 aMeehan CJ1 aBhuju S1 aPorter JL1 aAguiar J1 aSeemann T1 aJarek M1 aSingh M1 aPortaels F1 aStinear TP1 aJong BC00aA genomic approach to resolving relapse versus reinfection among four cases of Buruli ulcer.  uhttp://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0004158   ae00041580 v93 a<p><strong>EDITOR's BACKGROUND: </strong>Increased availability of Next Generation Sequencing (NGS) techniques allows, for the first time, to distinguish relapses from reinfections in patients with multiple Buruli ulcer (BU) episodes.</p>

<p><strong>METHODOLOGY: </strong>We compared the number and location of single nucleotide polymorphisms (SNPs) identified by genomic screening between four pairs of Mycobacterium ulcerans isolates collected at the time of first diagnosis and at recurrence, derived from a collection of almost 5000 well characterized clinical samples from one BU treatment center in Benin.</p>

<p><strong>PRINCIPAL FINDINGS: </strong>The findings suggest that after surgical treatment-without antibiotics-the second episodes were due to relapse rather than reinfection. Since specific antibiotics were introduced for the treatment of BU, the one patient with a culture available from both disease episodes had M. ulcerans isolates with a genomic distance of 20 SNPs, suggesting the patient was most likely reinfected rather than having a relapse.</p>

<p><strong>CONCLUSIONS: </strong>To our knowledge, this study is the first to study recurrences in M. ulcerans using NGS, and to identify exogenous reinfection as causing a recurrence of BU. The occurrence of reinfection highlights the contribution of ongoing exposure to M. ulcerans to disease recurrence, and has implications for vaccine development.</p>
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