title: A Genomic Approach to Resolving Relapse versus Reinfection among Four Cases of Buruli Ulcer.
abstract: 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Miriam
authors.initials: M
authors.lastname: Eddyani
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Vandelannoote
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Conor J
authors.initials: CJ
authors.lastname: Meehan
authors.affiliation: Helmholtz Centre for Infection Research, GMAK, Braunschweig, Germany.
authors.forename: Sabin
authors.initials: S
authors.lastname: Bhuju
authors.affiliation: Department of Microbiology and Immunology, Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Porter
authors.affiliation: Centre de Dépistage et de Traitement de l'Ulcère de Buruli Gbemotin, Zagnanado, Benin.
authors.forename: Julia
authors.initials: J
authors.lastname: Aguiar
authors.affiliation: Victorian Life Sciences Computation Initiative, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Torsten
authors.initials: T
authors.lastname: Seemann
authors.affiliation: Helmholtz Centre for Infection Research, GMAK, Braunschweig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Jarek
authors.affiliation: Helmholtz Centre for Infection Research, GMAK, Braunschweig, Germany.
authors.forename: Mahavir
authors.initials: M
authors.lastname: Singh
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Françoise
authors.initials: F
authors.lastname: Portaels
authors.affiliation: Department of Microbiology and Immunology, Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Stinear
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.|New York University, New York, New York, United States of America.
authors.forename: Bouke C
authors.initials: BC
authors.lastname: de Jong
mesh_terms: D000293:Adolescent; D001541:Benin / Q000453:epidemiology; D054312:Buruli Ulcer / Q000175:diagnosis* / Q000453:epidemiology / Q000382:microbiology; D002648:Child; D005260:Female; D016680:Genome, Bacterial; D023281:Genomics / Q000379:methods*; D006801:Humans; D008297:Male; D017720:Molecular Epidemiology / Q000379:methods; D058889:Molecular Typing / Q000379:methods*; D019911:Mycobacterium ulcerans / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D012189:Retrospective Studies