A Genomic Approach to Resolving Relapse versus Reinfection among Four Cases of Buruli Ulcer

作者：Eddyani Miriam^*; Vandelannoote Koen; Meehan Conor J; Bhuju Sabin; Porter Jessica L; Aguiar Julia; Seemann Torsten; Jarek Michael; Singh Mahavir; Portaels Francoise; Stinear Timothy P; de Jong Bouke C

来源：PLoS Neglected Tropical Diseases, 2015, 9(11): e0004158.

DOI：10.1371/journal.pntd.0004158

Background
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.
Methodology
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.
Principal Findings
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.
Conclusions
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.

• 出版日期2015-11