Susceptibility to Buruli ulcer is associated with the SLC11A1 (NRAMP1) D543N polymorphism.

Similar to other mycobacterial diseases, susceptibility to Buruli ulcer (Mycobacterium ulcerans infection) may be determined by host genetic factors. We investigated the role of SLC11A1 (NRAMP1) in Buruli ulcer because of its associations with both tuberculosis and leprosy. We enrolled 182 Buruli ulcer patients (102 with positive laboratory confirmation) and 191 healthy neighbourhood-matched controls in Ghana, and studied three polymorphisms in the SLC11A1 gene: 3' UTR TGTG ins/del, D543N G/A, and INT4 G/C. Finger prick blood samples from study subjects were dried on filter papers (FTA) and processed. D543N was significantly associated with Buruli ulcer: the odds ratio (adjusted for gender, age, and region of the participant) of the GA genotype versus the GG genotype was 2.89 (95% confidence intervals (CI): 1.41-5.91). We conclude that a genetic polymorphism in the SLC11A1 gene plays a role in susceptibility to develop Buruli ulcer, with an estimated 13% population attributable risk.

Mycobacterium ulcerans infection.

After tuberculosis and leprosy, Buruli-ulcer disease (caused by infection with Mycobacterium ulcerans) is the third most common mycobacterial disease in immunocompetent people. Countries in which the disease is endemic have been identified, predominantly in areas of tropical rain forest; the emergence of Buruli-ulcer disease in West African countries over the past decade has been dramatic. Current evidence suggests that the infection is transmitted through abraded skin or mild traumatic injuries after contact with contaminated water, soil, or vegetation; there is one unconfirmed preliminary report on possible transmission by insects. The clinical picture ranges from a painless nodule to large, undermined ulcerative lesions that heal spontaneously but slowly. Most patients are children. The disease is accompanied by remarkably few systemic symptoms, but occasionally secondary infections resulting in sepsis or tetanus cause severe systemic disease and death. Extensive scarring can lead to contractures of the limbs, blindness, and other adverse sequelae, which impose a substantial health and economic burden. Treatment is still primarily surgical, and includes excision, skin grafting, or both. Although BCG has a mild but significant protective effect, new vaccine developments directed at the toxins produced by M. ulcerans are warranted. In West Africa, affected populations are underprivileged, and the economic burden imposed by Buruli-ulcer disease is daunting. Combined efforts to improve treatment, prevention, control, and research strategies (overseen by the WHO and funded by international relief agencies) are urgently needed.

PIP: This paper focuses on Buruli-ulcer disease, the third most common mycobacterial disease among immunocompetent people. Buruli-ulcer disease is caused by an infection with Mycobacterium ulcerans, which belongs to the large group of environmental mycobacteria. It is endemic in many countries, usually in areas of tropical rain forest. Transmission of infection is through abraded skin or mild traumatic injuries after contact with contaminated water, soil, or vegetation. This disease mostly affects children which manifest from painless nodules to large, undermined ulcerative lesions that heals spontaneously but slowly. Buruli-ulcer disease is accompanied by few systemic symptoms, but occasionally secondary infections resulting in sepsis or tetanus cause severe systemic disease and death. However, extensive scarring can lead to contractures of the limbs, blindness, and other adverse complications. Management of the disease is still primarily surgical, and includes excision, skin grafting, or both. Although Bacillus Calmette-Guerin vaccine has mild but a significant protective effect, vaccine developments directed at the toxin produced by M. ulcerans are needed.

[Buruli ulcer (Mycobacterium ulcerans infection); report from the International Congress in Yamoussoukro, Ivory Coast]. / Buruli-ulcus (infectie met Mycobacterium ulcerans); verslag van een internationaal congres in Yamoussoukro, Ivoorkust.

Mycobacterium ulcerans infection (Buruli ulcer) is the third important mycobacterial disease world-wide in immunocompetent humans, after tuberculosis and leprosy. M. ulcerans is an environmental mycobacterium which has now been recovered from water and soil in swampy areas, and transmission to man occurs presumably through minor skin traumas. Endemic foci are known throughout the world, predominantly in tropical rain forest areas. The clinical presentation varies between a papule, a nodule or an ulceration with typically undermined edges. Surgery is the only effective treatment. BCG vaccination has a moderate protective effect. An association with HIV infection has not been demonstrated so far. Poor communities, with limited access to health care, and especially children are affected. The medical and socioeconomic burden imposed by the disease is tremendous. During the last decade the incidence of the disease has increased dramatically, particularly in West Africa. Possibly this is connected with changes in the natural ecosystem. The Yamoussoukro declaration on Buruli ulcer, adopted July 6, 1998, is the basis of improvement of awareness, health education, treatment, and research on M. ulcerans infection. Support by the international community is urgently needed.