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

Eddyani M, Vandelannoote K, Meehan CJ, Bhuju S, Porter JL, Aguiar J, Seemann T, Jarek M, Singh M, Portaels F, Stinear TP, de Jong BC - PLoS Negl Trop Dis (2015)

Bottom Line: 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.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.The occurrence of reinfection highlights the contribution of ongoing exposure to M. ulcerans to disease recurrence, and has implications for vaccine development.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

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.

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.

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Flow chart outlining the M. ulcerans isolates included in this analysis.
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pntd.0004158.g001: Flow chart outlining the M. ulcerans isolates included in this analysis.

Mentions: We compared the number of SNP differences separating the paired isolates and a random selection of 36 isolates from 36 patients living in the same geographical area and diagnosed with BU in the same time frame (1998–2008) as the patients with multiple episodes. We also compared genomic relatedness between six patients with two M. ulcerans cultures isolated from the same disease episode. This genetic background helped to avoid misclassifying any second episodes with similar M. ulcerans strains prevalent in the patient’s environment as relapses rather than reinfections. As such a total of 58 M. ulcerans isolates obtained from 46 patients was included in this study (Fig 1).


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

Eddyani M, Vandelannoote K, Meehan CJ, Bhuju S, Porter JL, Aguiar J, Seemann T, Jarek M, Singh M, Portaels F, Stinear TP, de Jong BC - PLoS Negl Trop Dis (2015)

Flow chart outlining the M. ulcerans isolates included in this analysis.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664471&req=5

pntd.0004158.g001: Flow chart outlining the M. ulcerans isolates included in this analysis.
Mentions: We compared the number of SNP differences separating the paired isolates and a random selection of 36 isolates from 36 patients living in the same geographical area and diagnosed with BU in the same time frame (1998–2008) as the patients with multiple episodes. We also compared genomic relatedness between six patients with two M. ulcerans cultures isolated from the same disease episode. This genetic background helped to avoid misclassifying any second episodes with similar M. ulcerans strains prevalent in the patient’s environment as relapses rather than reinfections. As such a total of 58 M. ulcerans isolates obtained from 46 patients was included in this study (Fig 1).

Bottom Line: 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.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.The occurrence of reinfection highlights the contribution of ongoing exposure to M. ulcerans to disease recurrence, and has implications for vaccine development.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

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.

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.

Show MeSH
Related in: MedlinePlus