The “Buruli Score”: Development of a Multivariable Prediction Model for Diagnosis of Mycobacterium ulcerans Infection in Individuals with Ulcerative Skin Lesions, Akonolinga, Cameroon

Müeller, Yolanda; Bastard, Mathieu; Nkemenang, Patrick; Comte, Éric; Ehounou, Geneviève; Eyangoh, Sara; Rusch, Barbara; Tabah, Earnest Njih; Trellu, Laurence Marie Toutous; Étard, Jean-François

doi:10.1371/journal.pntd.0004593

Cited by 15 publications

(16 citation statements)

References 17 publications

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“…We found the characteristic smell of ulcerated BU lesions to be strongly associated with a PCR confirmation, suggesting that it is specific for BU. This was also reported by Mueller et al in a BU treatment centre in Cameroon [ 22 ]. In our clinical experience, this characteristic smell, distinct from the smell of “putrid” wounds, draws our attention to a BU diagnosis even in atypical presentations.…”

Section: Discussionsupporting

confidence: 81%

“…Most of the epidemiological and clinical criteria for a BU diagnosis defined by WHO [ 4 ] were associated with a positive PCR result with varying OR’s aligning with the clinical and epidemiological description of BU patients in literature [ 2 , 3 , 12 , 22 , 23 ]. The localization of lesions on the limbs was not associated with a positive PCR result and was therefore not predictive of BU.…”

Section: Discussionmentioning

confidence: 99%

“…Smelling may be among the oldest diagnostic methods, as different pathologies, such as infectious and endogenous metabolic disorders, can affect human body odors [ 21 ]. A study in Cameroon found the characteristic smell of BU to be strongly associated with a confirmed BU diagnosis and described it as the smell of rotten fish, cassava or cheese, mixed with that of pyocyanic bacteria [ 22 ]. In our clinical experience, this characteristic smell draws our attention to a BU diagnostic, even in atypical presentations.…”

Section: Introductionmentioning

confidence: 99%

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Improving clinical and epidemiological predictors of Buruli ulcer

Ayelo¹,

Sopoh

Houezo³

et al. 2018

PLoS Negl Trop Dis

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BackgroundBuruli ulcer (BU) is a chronic necrotizing infectious skin disease caused by Mycobacterium ulcerans. The treatment with BU-specific antibiotics is initiated after clinical suspicion based on the WHO clinical and epidemiological criteria. This study aimed to estimate the predictive values of these criteria and how they could be improved.Methodology/Principal findingsA total of 224 consecutive patients presenting with skin and soft tissue lesions that could be compatible with BU, including those recognized as unlikely BU by experienced clinicians, were recruited in two BU treatment centers in southern Benin between March 2012 and March 2015. For each participant, the WHO and four additional epidemiological and clinical diagnostic criteria were recorded. For microbiological confirmation, direct smear examination and IS2404 PCR were performed. We fitted a logistic regression model with PCR positivity for BU confirmation as outcome variable. On univariate analysis, most of the clinical and epidemiological WHO criteria were associated with a positive PCR result. However, lesions on the lower limbs and WHO category 3 lesions were rather associated with a negative PCR result (respectively OR: 0.4, 95%CI: 0.3–0.8; OR: 0.5, 95%IC: 0.3–0.9). Among the additional characteristics studied, the characteristic smell of BU was strongest associated with a positive PCR result (OR = 16.4; 95%CI = 7.5–35.6).Conclusion/SignificanceThe WHO diagnostic criteria could be improved upon by differentiating between lesions on the upper and lower limbs and by including lesion size and the characteristic smell recognized by experienced clinicians.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Improving clinical and epidemiological predictors of Buruli ulcer

Ayelo¹,

Sopoh

Houezo³

et al. 2018

PLoS Negl Trop Dis

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“…The forearm was chosen because lesions on the upper limbs are more likely to be BU compared to lesions on the lower limbs. [ 17 ] The sample was stored and processed in the same way as our other clinical samples. For comparisons, we also included the data from three healthy individuals from three other publically available studies.…”

Section: Methodsmentioning

confidence: 99%

Bacterial diversity in Buruli ulcer skin lesions: Challenges in the clinical microbiome analysis of a skin disease

et al. 2017

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BackgroundBuruli ulcer (BU) is an infectious disease caused by Mycobacterium ulcerans and considered the third most prevalent mycobacterial disease in humans. Secondary bacterial infections in open BU lesions are the main cause of pain, delayed healing and systemic illness, resulting in prolonged hospital stay. Thus, understanding the diversity of bacteria, termed the microbiome, in these open lesions is important for proper treatment. However, adequately studying the human microbiome in a clinical setting can prove difficult when investigating a neglected tropical skin disease due to its rarity and the setting.Methodology/Principal findingsUsing 16S rRNA sequencing, we determined the microbial composition of 5 BU lesions, 3 non-BU lesions and 3 healthy skin samples. Although no significant differences in diversity were found between BU and non-BU lesions, the former were characterized by an increase of Bacteroidetes compared to the non-BU wounds and the BU lesions also contained significantly more obligate anaerobes. With this molecular-based study, we were also able to detect bacteria that were missed by culture-based methods in previous BU studies.Conclusions/SignificanceOur study suggests that BU may lead to changes in the skin bacterial community within the lesions. However, in order to determine if such changes hold true across all BU cases and are either a cause or consequence of a specific wound environment, further microbiome studies are necessary. Such skin microbiome analysis requires large sample sizes and lesions from the same body site in many patients, both of which can be difficult for a rare disease. Our study proposes a pipeline for such studies and highlights several drawbacks that must be considered if microbiome analysis is to be utilized for neglected tropical diseases.

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“…Studies on the accuracy of diagnostic tests of BU have used varying reference standards including histopathology [10], PCR [11, 12], at least 1 positive test result [13], a composite reference standard of several tests [12, 14], and latent class analysis (LCA) [15]. This diversity in reference standards makes it difficult to summarize findings on diagnostic test accuracy [8].…”

mentioning

confidence: 99%

Diagnostic Accuracy of Clinical and Microbiological Signs in Patients With Skin Lesions Resembling Buruli Ulcer in an Endemic Region

Eddyani

Sopoh²,

Ayelo³

et al. 2018

Clinical Infectious Diseases

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BackgroundThe diagnosis of the neglected tropical skin and soft tissue disease Buruli ulcer (BU) is made on clinical and epidemiological grounds, after which treatment with BU-specific antibiotics is initiated empirically. Given the current decline in BU incidence, clinical expertise in the recognition of BU is likely to wane and laboratory confirmation of BU becomes increasingly important. We therefore aimed to determine the diagnostic accuracy of clinical signs and microbiological tests in patients presenting with lesions clinically compatible with BU.MethodsA total of 227 consecutive patients were recruited in southern Benin and evaluated by clinical diagnosis, direct smear examination (DSE), polymerase chain reaction (PCR), culture, and histopathology. In the absence of a gold standard, the final diagnosis in each patient was made using an expert panel approach. We estimated the accuracy of each test in comparison to the final diagnosis and evaluated the performance of 3 diagnostic algorithms.ResultsAmong the 205 patients with complete data, the attending clinicians recognized BU with a sensitivity of 92% (95% confidence interval [CI], 85%–96%), which was higher than the sensitivity of any of the laboratory tests. However, 14% (95% CI, 7%–24%) of patients not suspected to have BU at diagnosis were classified as BU by the expert panel. The specificities of all diagnostics were high (≥91%). All diagnostic algorithms had similar performances.ConclusionsA broader clinical suspicion should be recommended to reduce missed BU diagnoses. Taking into consideration diagnostic accuracy, time to results, cost-effectiveness, and clinical generalizability, a stepwise diagnostic approach reserving PCR to DSE-negative patients performed best.

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The “Buruli Score”: Development of a Multivariable Prediction Model for Diagnosis of Mycobacterium ulcerans Infection in Individuals with Ulcerative Skin Lesions, Akonolinga, Cameroon

Cited by 15 publications

References 17 publications

Improving clinical and epidemiological predictors of Buruli ulcer

Improving clinical and epidemiological predictors of Buruli ulcer

Bacterial diversity in Buruli ulcer skin lesions: Challenges in the clinical microbiome analysis of a skin disease

Diagnostic Accuracy of Clinical and Microbiological Signs in Patients With Skin Lesions Resembling Buruli Ulcer in an Endemic Region

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