Excision of Pre-Ulcerative Forms of Buruli Ulcer Disease: A Curative Treatment (original) (raw)
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PLOS Neglected Tropical Diseases, 2016
Background Current laboratory diagnosis of Buruli ulcer (BU) is based on microscopic detection of acid fast bacilli, quantitative real-time PCR (qPCR), histopathology or cultivation. Insertion sequence (IS) 2404 qPCR, the most sensitive method, is usually only available at reference laboratories. The only currently available point-of-care test, microscopic detection of acid fast bacilli (AFB), has limited sensitivity and specificity. Methodology/ Principal Findings Here we analyzed AFB positive tissue samples (n = 83) for the presence, distribution and amount of AFB. AFB were nearly exclusively present in the subcutis with large extracellular clusters being most frequently (67%) found in plaque lesions. In ulcerative lesions small clusters and dispersed AFB were more common. Beside this, 151 swab samples from 37 BU patients were analyzed by IS2404 qPCR and ZN staining in parallel. The amount of M. ulcerans DNA in extracts from swabs correlated well with the probability of finding AFB in direct smear microscopy, with 56.1% of the samples being positive in both methods and 43.9% being positive only in qPCR. By analyzing three swabs per patient instead of one, the probability to have at least one positive swab increased from 80.2% to 97.1% for qPCR and from 45% to 66.1% for AFB smear examination. Conclusion / Significance Our data show that M. ulcerans bacteria are primarily located in the subcutis of BU lesions, making the retrieval of the deep subcutis mandatory for examination of tissue samples for AFB. When laboratory diagnosis is based on the recommended less invasive collection of
Journal of clinical …, 2006
We determined by real-time PCR the distribution of Mycobacterium ulcerans DNA in the excised lesion of a Buruli ulcer patient. A new lesion developed adjacent to the site of excision in the patient. The excised margin around the primary lesion contained a small amount of mycobacterial DNA in the area where the secondary lesion developed. These results suggest that a relatively small number of infiltrating mycobacteria can lead to the development of a recurrence.
Journal of Clinical Microbiology, 2009
In a previous study, we reported that the sensitivity of PCR targeting the IS2404 insertion sequence of Mycobacterium ulcerans was 98% when it was applied to 4-mm punch biopsy samples of Buruli lesions. Fine-needle aspiration (FNA) is a less traumatic sampling technique for nonulcerated lesions, and we have studied the sensitivity of PCR using FNA samples. Fine-needle aspirates were taken with a 21-gauge needle from 43 patients diagnosed clinically with M. ulcerans disease. Four-millimeter punch biopsies were obtained for microscopy, culture, and PCR targeting the IS2404 insertion sequence. The sensitivity of PCR using samples obtained by FNA was 86% (95% confidence interval [95% CI], 72 to 94%) compared with that for PCR using punch biopsy samples. In this study, the sensitivities of culture and microscopy for punch biopsy samples were 44% (95% CI, 29 to 60%) and 26% (95% CI, 14 to 41%), respectively. This demonstrates that PCR on an FNA sample is a viable minimally invasive technique to diagnose M. ulcerans lesions.
Journal of Clinical Microbiology, 2012
We compared two DNA extraction methods (a semiautomated method using a Maxwell kit and a modified Boom method) and three amplification procedures (a single-step PCR, a nested PCR, and a real-time quantitative PCR) on 74 surgical tissue specimens from patients with clinically suspected Buruli ulcer. All of these procedures were compared before and after decontamination. We observed that, among the procedures tested, real-time PCR after the modified Boom extraction method or a single-run PCR assay after the Maxwell 16 extraction method, performed on nondecontaminated suspensions, are the best for the molecular diagnosis of Mycobacterium ulcerans disease.
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.
Buruli Ulcer (Mycobacterium ulcerans Infection): a Re-emerging Disease
Clinical Microbiology Newsletter, 2009
Mycobacterium ulcerans infection is an emerging disease that causes indolent, necrotizing skin lesions known as Buruli ulcer (BU). Approximately 10% of patients develop reactive osteitis or osteomyelitis beneath skin lesions or metastatic osteomyelitis from lymphohematogenous spread of M. ulcerans. The most plausible mode of transmission is by skin trauma at sites contaminated by M. ulcerans. Pathogenesis is mediated by a necrotizing, immunosuppressive toxin produced by M. ulcerans called mycolactone. The incidence of BU is highest in children up to 15 years old and is a public health problem in countries of endemicity due to disabling scarring and bone destruction. Today, most BU occurs in West Africa, but the disease has been reported in over 30 countries. Treatment options for BU are antibiotics and surgery. BCG vaccination provides short-term protection against BU and prevents osteomyelitis. HIV seropositivity may increase the risk for BU and render BU osteomyeletis highly aggressive.
2006
Buruli ulcer caused by Mycobacterium ulcerans is of important public health problem especially in West-Africa. It is the third most common mycobacterial disease, after tuberculosis and leprosy. The World Health Organisation currently recommends the use of a combination of streptomycin and rifampicin for eight weeks before surgical excision. Stepwise implementation of this recommendation has started in some of the worst affected West African countries, including Ghana. Therefore this study was initiated to assess the susceptibility of M. ulcerans isolates from Ghana to isoniazid, rifampicin, ethambutol and streptomycin, using a microplate Alamar blue assay. Out of the 28 isolates tested, one was resistant to all four drugs analysed. All isolates with the exception of two (7.1%) and three (10.7%) were resistant to isoniazid and ethambutol respectively. On the contrary all isolates, except two (7.1%) and three (10.7%), were susceptible to rifampicin and streptomycin, respectively. This first report of rifampicin resistance in clinical M. ulcerans isolates raises major concern about antibiotic treatment modalities for Buruli ulcer.