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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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Related in: MedlinePlus

A: Geographical origin of the 58 isolates included in the study.Patients of special interest are colored accordingly. The size of the dots is proportional to the number of patients originating from a specific village varying from 1 to 3. The Ouémé river and its tributaries, and the BU treatment center of Zagnanado are shown as well. B: Median-Joining network showing patterns of descent among the 58 studied M. ulcerans isolates. Each circle represents a unique genotype, and the size of the circle is proportional to the number of individuals sharing that type. Every edge represents a single mutational step (or SNP) separating the sampled and hypothetical genotypes. Genotypes obtained from patients of special interest are colored accordingly.
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pntd.0004158.g002: A: Geographical origin of the 58 isolates included in the study.Patients of special interest are colored accordingly. The size of the dots is proportional to the number of patients originating from a specific village varying from 1 to 3. The Ouémé river and its tributaries, and the BU treatment center of Zagnanado are shown as well. B: Median-Joining network showing patterns of descent among the 58 studied M. ulcerans isolates. Each circle represents a unique genotype, and the size of the circle is proportional to the number of individuals sharing that type. Every edge represents a single mutational step (or SNP) separating the sampled and hypothetical genotypes. Genotypes obtained from patients of special interest are colored accordingly.

Mentions: The open source geographic information system Quantum GIS (QGIS v1.8.0) [25] was used to generate the illustration of the geographical distribution of all included M. ulcerans genomes in Fig 2. The geographical locations of the residences of BU patients at the time of their first consultation are shown. The river layer (Ouémé river and its tributaries) was digitized from declassified Soviet military topographic maps b31-03, b31-09, and b31-15 (scale 1:200k). The administrative borders of African countries were rendered from the Global Administrative Unit Layers data set of FAO [26].


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)

A: Geographical origin of the 58 isolates included in the study.Patients of special interest are colored accordingly. The size of the dots is proportional to the number of patients originating from a specific village varying from 1 to 3. The Ouémé river and its tributaries, and the BU treatment center of Zagnanado are shown as well. B: Median-Joining network showing patterns of descent among the 58 studied M. ulcerans isolates. Each circle represents a unique genotype, and the size of the circle is proportional to the number of individuals sharing that type. Every edge represents a single mutational step (or SNP) separating the sampled and hypothetical genotypes. Genotypes obtained from patients of special interest are colored accordingly.
© Copyright Policy
Related In: Results  -  Collection

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

pntd.0004158.g002: A: Geographical origin of the 58 isolates included in the study.Patients of special interest are colored accordingly. The size of the dots is proportional to the number of patients originating from a specific village varying from 1 to 3. The Ouémé river and its tributaries, and the BU treatment center of Zagnanado are shown as well. B: Median-Joining network showing patterns of descent among the 58 studied M. ulcerans isolates. Each circle represents a unique genotype, and the size of the circle is proportional to the number of individuals sharing that type. Every edge represents a single mutational step (or SNP) separating the sampled and hypothetical genotypes. Genotypes obtained from patients of special interest are colored accordingly.
Mentions: The open source geographic information system Quantum GIS (QGIS v1.8.0) [25] was used to generate the illustration of the geographical distribution of all included M. ulcerans genomes in Fig 2. The geographical locations of the residences of BU patients at the time of their first consultation are shown. The river layer (Ouémé river and its tributaries) was digitized from declassified Soviet military topographic maps b31-03, b31-09, and b31-15 (scale 1:200k). The administrative borders of African countries were rendered from the Global Administrative Unit Layers data set of FAO [26].

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