Diagnostic Value of Histological Analysis of Punch Biopsies in Suspected Cutaneous Buruli Ulcer: A Study on 32 Cases of Confirmed Buruli Ulcer in Cameroon (original) (raw)
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Histopathologic Features of Mycobacterium ulcerans Infection
Emerging Infectious Diseases, 2003
Because of the emergence of Buruli ulcer disease, the World Health Organization launched a Global Buruli Ulcer Initiative in 1998. This indolent skin infection is caused by Mycobacterium ulcerans. During a study of risk factors for the disease in Ghana, adequate excisional skin-biopsy specimens were obtained from 124 clinically suspicious lesions. Buruli ulcer disease was diagnosed in 78 lesions since acid-fast bacilli (AFB) were found by histopathologic examination. Lesions with other diagnoses included filariasis (3 cases), zygomycosis (2 cases), ulcerative squamous cell carcinomas (2 cases), keratin cyst (1 case), and lymph node (1 case). Thirty-seven specimens that did not show AFB were considered suspected Buruli ulcer disease cases. Necrosis of subcutaneous tissues and dermal collagen were found more frequently in AFB-positive specimens compared with specimens from suspected case-patients (p<0.001). Defining histologic criteria for a diagnosis of Buruli ulcer disease is of clinical and public health importance since it would allow earlier treatment, leading to less deforming sequelae.
Clinical and Laboratory Diagnosis of Buruli Ulcer Disease: A Systematic Review
Canadian Journal of Infectious Diseases and Medical Microbiology, 2016
Background.Buruli ulcer (BU) is a necrotizing cutaneous infection caused byMycobacterium ulcerans.Early diagnosis is crucial to prevent morbid effects and misuse of drugs. We review developments in laboratory diagnosis of BU, discuss limitations of available diagnostic methods, and give a perspective on the potential of using aptamers as point-of-care.Methods.Information for this review was searched through PubMed, web of knowledge, and identified data up to December 2015. References from relevant articles and reports from WHO Annual Meeting of the Global Buruli Ulcer initiative were also used. Finally, 59 articles were used.Results.The main laboratory methods for BU diagnosis are microscopy, culture, PCR, and histopathology. Microscopy and PCR are used routinely for diagnosis. PCR targetingIS2404is the gold standard for laboratory confirmation. Culture remains the only method that detects viable bacilli, used for diagnosing relapse and accrued isolates for epidemiological investiga...
Tropical Medicine & International Health, 2008
Clinical diagnosis of Mycobacterium ulcerans infection is currently accepted as sufficient basis for treating the disease. Inadequate laboratory resources in the highly endemic areas of Africa often limit possibilities for in-country confirmation of clinical judgement. We analysed records of 99 Buruli ulcer (BU) patients diagnosed clinically and treated surgically at Amasaman Health Centre in Ghana, for whom post-treatment diagnostic laboratory tests were performed. Comparison of clinical diagnoses with test results obtained by an in-country laboratory on samples of excised tissue showed a high specificity of clinical judgement. Among lesions with three laboratory tests (microscopy for acid fast bacilli, culture and IS2404 polymerase chain reaction) done, 94% tested positive at least once and 83% twice. Thus correct clinical diagnosis of BU by well trained health workers is achievable, although the quality of clinical diagnosis should be monitored by intermittent testing in national reference laboratories. However, being retrospective, this study did not permit sensitivity and negative predictive value analysis.
Background: Buruli ulcer is the third most common mycobacterial infection worldwide. It is endemic in tropical, subtropical, and temperate climates. It causes devastating disease with morbidity and mortality. The treatment duration is long and the regimens considered are limited. Chronic cutaneous ulcers of mycobacterial etiology have been reported previously in Amman, but these were not associated with Mycobacterium ulcerans infection. Methods: The case patient's initial diagnosis was based on chronological and morphological features, combined with appropriate diagnostic tests. The skin features were assessed histopathologically. Skin testing was positive for acid-fast bacilli (AFB), and M. ulcerans was identified by DNA strip test (GenoType Mycobacterium CM/AS, Hain Lifescience), which is based on a PCR technique targeting a 23S rRNA gene region, followed by reverse hybridization and a line probe technology. Results: The skin mycobacterial infection was evaluated and verified as having a Mycobacterium marinum–M. ulcerans pattern in the GenoType CM assay. It was then counted as a pattern representing individual species and was resolved with the GenoType AS assay as having an M. ulcerans pattern. M. ulcerans DNA was isolated and amplified by PCR, and then detected against reverse hybridization probes in the strip assay. Conclusions: An indigenous case of M. ulcerans (Buruli ulcer) is reported for the first time from Jordan and the surrounding region.
Clinical Infectious Diseases, 2009
Background. Several diagnostic laboratory methods are available for case confirmation of Buruli ulcer disease. This study assessed the sensitivity of various diagnostic tests in relation to clinical presentation of the disease, type of diagnostic specimen, and treatment history. Methods. Swab samples, 3-mm punch biopsy tissue specimens, and surgically excised tissue specimens from 384 individuals with suspected Buruli ulcer disease were obtained at 9 different study sites in Ghana and were evaluated with dry reagent-based polymerase chain reaction (PCR), microscopic examination, culture, and histopathological analysis. The study subjects presented with nonulcerative and ulcerative lesions and were divided into 3 treatment groups: (1) previously untreated patients scheduled for antimycobacterial treatment, (2) patients treated with surgery alone, and (3) patients treated with surgery in combination with previous antimycobacterial treatment. Results. Of 384 suspected cases of Buruli ulcer disease, 268 were confirmed by at least 1 positive test result. The overall sensitivity of PCR (85%) was significantly higher than that of microscopic examination (57%) and culture (51%). After data were stratified by treatment group, type of lesion, and diagnostic specimen type, analysis revealed that PCR of 3-mm punch biopsy tissue specimens (obtained from previously untreated nonulcerative lesions) and of swab samples (obtained from previously untreated ulcers) had the highest diagnostic sensitivity (94% and 90%, respectively). Although duration of the disease did not significantly influence the sensitivity of any test, previous antimycobacterial treatment was significantly associated with decreased sensitivity of PCR and culture. Conclusions. Across all subgroups, PCR had the highest sensitivity. PCR assessment of 3-mm punch biopsy tissue specimens proved to be the best diagnostic tool for nonulcerative lesions, and PCR assessment of swab samples was the best diagnostic tool for ulcerative lesions. For monitoring of antimycobacterial treatment success within controlled trials, however, only culture is appropriate. Buruli ulcer disease (BUD), which is caused by Mycobacterium ulcerans, affects the skin and subcutaneous adipose tissue. BUD occurs in 130 countries worldwide,
Laboratory confirmation of Buruli ulcer cases in Ghana, 2008-2016
PLOS Neglected Tropical Diseases
Background Buruli ulcer (BU), a necrotizing skin infection caused by Mycobacterium ulcerans is the third most important mycobacterial disease globally after tuberculosis and leprosy in immune competent individuals. This study reports on the retrospective analyses of microbiologically confirmed Buruli ulcer (BU) cases in seventy-five health facilities in Ghana. Method/Principal findings Pathological samples were collected from BU lesions and transported either through courier services or by car directly to the laboratory. Samples were processed and analysed by IS2404 PCR, culture and Ziehl-Neelsen staining for detection of acid-fast bacilli. From 2008 to 2016, we analysed by PCR, 2,287 samples of 2,203 cases from seventy-five health facilities in seven regions
Buruli Ulcer: a Review of the Current Knowledge
Current Tropical Medicine Reports
Purpose of the Review Buruli ulcer (BU) is a necrotizing and disabling cutaneous disease caused by Mycobacterium ulcerans, one of the skin-related neglected tropical diseases (skin NTDs). This article aims to review the current knowledge of this disease and challenges ahead. Recent Findings Around 60,000 cases of BU have been reported from over 33 countries between 2002 and 2017. Encouraging findings for development of point-of-care tests for BU are being made, and its treatment is currently in the transition period from rifampicin plus streptomycin (injection) to all-oral regimen. A major recent advance in our understanding of its pathogenesis has been agreement on the mechanism of action of the major virulence toxin mycolactone in host cells, targeting the Sec61 translocon during a major step in protein biogenesis. Summary BU is distributed mainly in West Africa, but cases are also found in other parts of the world. We may be underestimating its true disease burden, due to the limited awareness of this disease. More awareness and more understanding of BU will surely contribute in enhancing our fight against this skin NTD. Keywords Buruli ulcer. Mycobacterium ulcerans. Mycolactone. Non-tuberculous mycobacterial disease. Skin neglected tropical diseases. Skin NTDs This article is part of the Topical Collection on Cutaneous Mycobacterial Diseases of the Skin and Soft Tissues
Journal of Clinical Microbiology, 2005
Punch biopsy specimens from Mycobacterium ulcerans disease lesions were used to compare the sensitivities and specificities of direct smear, culture, PCR, and histopathology in making a diagnosis of M. ulcerans disease in a field setting. PCR for the insertion element IS2404 was modified to include uracil-N-glycosylase and deoxyuridine triphosphate instead of deoxythymidine triphosphate to reduce the risk of cross contamination. The "gold standard" for confirmation of clinically diagnosed Buruli ulcer was a definite histological diagnosis, a positive culture for M. ulcerans, or a smear positive for acid-fast bacilli (AFB), together with a possible histological diagnosis. For 70 clinically diagnosed cases of M. ulcerans disease, the modified PCR was 98% sensitive and gave a rapid result. The sensitivities of microscopy, culture, and histology were 42%, 49%, and 82%, respectively. The use of a 4-mm punch biopsy specimen was preferred to a 6-mm punch biopsy specimen since the wound was less likely to bleed and to need stitching. Given adequate technical expertise and the use of controls, the PCR was viable in a teaching hospital setting in Ghana; and in routine practice, we would recommend the use of Ziehl-Neelsen staining of biopsy specimens to detect AFB, followed by PCR, in AFBnegative cases only, in order to minimize costs. Histology and culture remain important as quality control tests, particularly in studies of treatment efficacy.