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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 patients contributing isolates to this analysis.SM: streptomycin; RMP: rifampicin.
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pntd.0004158.g003: Flow chart outlining the patients contributing isolates to this analysis.SM: streptomycin; RMP: rifampicin.

Mentions: Among the 4951 clinically BU suspected patients who consulted the BU treatment centre of Gbemotin in Zagnanado in southern Benin between 1989 and 2010, we identified 100 who presented with multiple BU episodes (Fig 3). A majority of 93 patients had two disease episodes while 7 had three episodes. Twenty recurrence patients received streptomycin and/or rifampicin during their first BU episode. The distribution of patients that had received (partially) effective antibiotics is shown in the S1 Fig. Only for seven of the 100 recurrence patients were we able to successfully culture isolates from each of two or three disease episodes, owing to the limited sensitivity of culture for isolation of M. ulcerans from skin biopsies [27]. These mycobacterial isolates were stored at ≤70°C in Dubos broth enriched with growth supplement and glycerol. However, paired cultures were found to be viable for only four of these seven patients. The first two patients of these four patients each had three paired isolates while the other two patients each had two (Table 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 patients contributing isolates to this analysis.SM: streptomycin; RMP: rifampicin.
© Copyright Policy
Related In: Results  -  Collection

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

pntd.0004158.g003: Flow chart outlining the patients contributing isolates to this analysis.SM: streptomycin; RMP: rifampicin.
Mentions: Among the 4951 clinically BU suspected patients who consulted the BU treatment centre of Gbemotin in Zagnanado in southern Benin between 1989 and 2010, we identified 100 who presented with multiple BU episodes (Fig 3). A majority of 93 patients had two disease episodes while 7 had three episodes. Twenty recurrence patients received streptomycin and/or rifampicin during their first BU episode. The distribution of patients that had received (partially) effective antibiotics is shown in the S1 Fig. Only for seven of the 100 recurrence patients were we able to successfully culture isolates from each of two or three disease episodes, owing to the limited sensitivity of culture for isolation of M. ulcerans from skin biopsies [27]. These mycobacterial isolates were stored at ≤70°C in Dubos broth enriched with growth supplement and glycerol. However, paired cultures were found to be viable for only four of these seven patients. The first two patients of these four patients each had three paired isolates while the other two patients each had two (Table 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