Risk factors for Buruli ulcer disease (Mycobacterium ulcerans Infection): results from a case-control study in Ghana.

BACKGROUND: Morbidity due to Buruli ulcer disease (BUD), a cutaneous infection caused by Mycobacterium ulcerans, has been increasingly recognized in rural West Africa. The source and mode of transmission remain unknown. METHODS: To identify BUD risk factors, we conducted a case-control study in 3 BUD-endemic districts in Ghana. We enrolled case patients with clinically diagnosed BUD and obtained skin biopsy specimens. M. ulcerans infection was confirmed by at least 1 of the following diagnostic methods: histopathologic analysis, culture, polymerase chain reaction, and Ziehl-Neelsen staining of a lesion smear. We compared characteristics of case patients with confirmed BUD with those of age- and community-matched control subjects using conditional logistic regression analysis. RESULTS: Among 121 case patients with confirmed BUD, leg lesions (49%) or arm lesions (36%) were common. Male case patients were significantly more likely than female case patients to have lesions on the trunk (25% vs. 6%; P = .009). Multivariable modeling among 116 matched case-control pairs identified wading in a river as a risk factor for BUD (odds ratio [OR], 2.69; 95% confidence interval [CI], 1.27-5.68; P = .0096). Wearing a shirt while farming (OR, 0.27; 95% CI, 0.11-0.70; P = .0071), sharing indoor living space with livestock (OR, 0.36; 95% CI, 0.15-0.86; P = .022), and bathing with toilet soap (OR, 0.41; 95% CI, 0.19-0.90; P = .026) appeared to be protective. BUD was not significantly associated with penetrating injuries (P = .14), insect bites near water bodies (P = .84), bacille Calmette-Guerin vaccination (P = .33), or human immunodeficiency virus infection (P = .99). CONCLUSIONS: BUD is an environmentally acquired infection strongly associated with exposure to river areas. Exposed skin may facilitate transmission. Until transmission is better defined, control strategies in BUD-endemic areas could include covering exposed skin.

Reliability and validity of the Buruli ulcer functional limitation score questionnaire.

The reliability and validity of the earlier developed Buruli ulcer functional limitation score (BUFLS) questionnaire was assessed. Of 638 former Buruli ulcer patients (of 678 individuals examined), sufficient items on daily activities (>or= 13 of the 19) were applicable to calculate a score. To determine the validity, the functional limitation scores of the 638 individuals were compared with the global impression of the limitations, range of motion (ROM), and the social impact (change of occupation or education) of Buruli ulcer. To determine inter-observer reliability, the functional limitation score was reassessed in 107 participants within one and three weeks after the first interview by another interviewer and interpreter. Both global impression and ROM correlated well with the functional limitation scores (rho = 0.66 and rho = 0.61). The inter-observer reliability of 107 participants as measured by an intra-class correlation coefficient of 0.86 was very good. The functional limitation scores measured in the second assessment were significantly higher than in the first assessment. This should be taken into account when the functional limitation score is used for the individual patient. The BUFLS can be used as for between group comparisons of endpoints in clinical trials and in the planning of resources.

Distribution of Buruli ulcer lesions over body surface area in a large case series in Ghana: uncovering clues for mode of transmission.

We studied hospital records of 750 consecutive Buruli ulcer patients in a highly endemic area in Amansie West, Ghana. Although more Buruli ulcer lesions were found on the right side of the body, comparison of lesions on arms and legs showed a bilaterally symmetrical distribution. Upper and lower extremities were affected equally by Buruli ulcers, if correction was made for differences in body surface area. Patients from outside the Amansie West district presented significantly more often with ulcerated lesions, which were more often located on a joint, than patients who lived in Amansie West, suggesting that longer travel distance might have caused delay. Our observations of a bilaterally symmetrical distribution of lesions on extremities and equal upper and lower extremity involvement are compatible with a mode of transmission that involves passive exposure of exposed body parts. An asymmetrical distribution of lesions was found in an earlier study, suggesting transmission by vegetation near the ground, through activities like farming or play. Perhaps, transmission in or near water, e.g. by bites of infected aquatic insects, might favour the pattern of distribution of lesions that we found.

Malignant melanoma of the buttock presenting as a Buruli ulcer.

We report an unusual case of malignant melanoma clinically diagnosed as Buruli ulcer, that arose in a 13-year-old boy and presented as an ulcerated, fungating 2 cm mass on the right buttock. The tumor showed the histology and immunohistology of a malignant melanoma. We present this interesting case of malignant melanoma of soft tissue, arising in an unusual location of the body. The tumor presented with clinical features of Buruli ulcer in an area endemic for this disease as well as other tropical ulcerations. Neoplasms, including melanoma, should be considered in the differential diagnosis of Buruli ulcer in endemic areas.

Factors associated with functional limitations and subsequent employment or schooling in Buruli ulcer patients.

OBJECTIVES: To evaluate former Buruli ulcer disease (BUD) patients to assess the factors associated with functional limitations and subsequent employment or schooling. METHODS: The previously validated Buruli ulcer functional limitation score (BUFLS) questionnaire and interviews about educational and professional consequences incurred by BUD. RESULTS: Of 638 participants, 362 (57%) had a functional limitation after a median period of almost 4 years after treatment for BUD. A lesion on a joint, older age, female gender, a lesion on a distal part of an extremity and a persistent wound were found to be independent risk factors for stopping work or education. The same risk factors applied to the development of a functional limitation. Both functional limitations and financial difficulties due to BUD disease often led to job loss and school dropout. CONCLUSIONS: Rehabilitation programmes are urgently needed to diminish the suffering from the functional limitations and employment or schooling problems caused by BUD.

Phenolic glycolipid-1 (PGL-1) in Buruli ulcer lesions. First demonstration by immuno-histochemistry.

Buruli ulcer, caused by Mycobacterium ulcerans, is emerging as the third most common mycobacterial disease after leprosy and tuberculosis in some tropical regions. Although a toxin of the polyketide family is central to the pathogenesis of the disease, there are still several parameters that need clarification. Among them and of crucial interest are the curative drug treatment and the test for early detection of the disease. In this study, we used mouse monoclonal antibodies, raised against synthetic sugars of the terminal trisaccharide of M. leprae PGL-1, to detect the immunoreactivity of this antigen in tissue infected with M. ulcerans. Thirty specimens of skin tissue from Buruli ulcer patients (3 plaques, 10 nodules, 1 ulcerated nodule, 7 deep ulcer beds and 9 ulcers in healing) were obtained from Ghana. Eighty-three percent of the submitted cases were compatible with the lesions of Buruli ulcer. AFB were positive in 33% of plaques, 40% of nodules, 44% of actives ulcers and 22% of the ulcer in healing stage. Immunohistochemically, phenolic glycolipid-1 (PGL-1) was detected in all AFB-positive cases. This observation implies that Mycobacterium ulcerans may express an M. leprae PGL-1-like substance and should tentatively emulate research to further characterize such a substance. The search for an early diagnostic tool for the Buruli disease may benefit from such investigations.

Histopathologic features of Mycobacterium ulcerans infection.

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.