Buruli ulcer is a neglected tropical skin infection predominantly found in areas of Australia, Africa, Asia, Mexico, and South America. It is caused by the bacterium Mycobacterium ulcerans, which produces a potent toxin that leads to tissue destruction, primarily affecting the skin, soft tissues, and occasionally deeper structures like muscles and bones. The condition tends to present as a painless nodule and, if untreated, can progress into extensive ulceration. The disease primarily affects the arms and legs and is most prevalent in children and the elderly, though individuals of all ages can be affected.
Etiology and Pathogenesis
Mycobacterium ulcerans is the causative agent of Buruli ulcer. This bacterium produces a unique toxin called mycolactone, which induces tissue necrosis and immunosuppression, facilitating the spread of infection. The bacteria are primarily transmitted to humans through the bite of insects, especially mosquitoes and other biting flies, which inhabit swampy and wetland areas. The saliva of these insects contains the bacteria, which are then introduced into the skin during a bite. The infection typically remains localized at the site of the bite, though it can spread to deeper structures if left untreated.
Clinical Presentation
The initial manifestation of Buruli ulcer is usually a painless nodule or papule beneath the skin, which may or may not be accompanied by swelling. The infection tends to be more prominent in the extremities, such as the arms and legs. In some cases, fever may be present, particularly when diffuse swelling occurs. Over time, without treatment, the lesion can progress to form an ulcer, which exposes underlying tissues such as muscles, tendons, and bones. Disfiguring scars and complications such as secondary infections are common in advanced stages of the disease. If the infection spreads beyond the skin, it may lead to more severe complications, including osteomyelitis (bone infection) or muscle involvement.
Diagnosis
Buruli ulcer is typically diagnosed through a combination of clinical evaluation and laboratory testing. The patient’s medical history and recent travel history are essential components of the diagnostic process, particularly in areas endemic to Mycobacterium ulcerans. A skin examination is conducted to assess the size, location, and stage of the lesion. Diagnosis can be confirmed through various laboratory methods, including:
Bacterial Smears: Acid-fast bacilli smears can detect the presence of M. ulcerans in tissue samples.
Culture: A sample of the ulcer can be cultured to identify the bacterium.
Skin Biopsy: Microscopic evaluation of tissue samples via biopsy can confirm the diagnosis and help rule out other potential causes of ulcers.
In some cases, molecular methods such as Polymerase Chain Reaction may also be employed for rapid and accurate identification of M. ulcerans.
Treatment
The treatment of Buruli ulcer typically involves a combination of antibiotic therapy and surgical intervention, depending on the severity of the infection.
Antibiotic Therapy: The cornerstone of Buruli ulcer treatment is systemic antibiotic therapy. The most commonly recommended regimen involves the combination of streptomycin and rifampin, administered for 8 weeks. This combination has been shown to be effective in eradicating the infection and preventing further complications. Streptomycin, an aminoglycoside, is effective against M. ulcerans, while rifampin, a rifamycin antibiotic, enhances the bactericidal effect.
In cases where streptomycin is contraindicated or unavailable, clarithromycin has been used as an alternative to streptomycin with success. Recent studies have suggested that prolonged therapy with clarithromycin alone may be effective in the treatment of Buruli ulcer.Surgical Intervention: Surgical management is typically reserved for large ulcers, non-responsive ulcers, or cases where significant tissue necrosis has occurred. Surgical procedures such as excision, debridement, or skin grafting may be necessary to remove necrotic tissue and promote wound healing. In advanced cases, muscle and bone involvement may require more extensive surgical procedures.
Emerging Treatment Options: While antibiotics and surgery remain the primary treatment modalities, researchers are exploring alternative approaches, including local therapy and immunomodulation. For example, recent studies have investigated the use of topical antibiotics and photodynamic therapy as adjunct treatments. Additionally, vaccine development is an ongoing area of research, as vaccines against M. ulcerans could significantly reduce the burden of Buruli ulcer in endemic regions.
Prevention
Prevention of Buruli ulcer primarily focuses on reducing exposure to insect vectors. Individuals living in endemic regions are advised to take measures such as using insect repellents, wearing protective clothing, and avoiding swampy areas where the vectors are commonly found. Community-based initiatives aimed at insect vector control and health education are essential for reducing the incidence of Buruli ulcer in affected areas.
Conclusion
Buruli ulcer remains a significant public health concern in endemic regions, particularly in tropical and subtropical areas. Prompt diagnosis and treatment with a combination of antibiotics and surgical intervention are essential to preventing complications and reducing morbidity. Continued research into novel therapeutic options, such as vaccines and adjunctive therapies, offers hope for improved outcomes in the future. Early intervention remains critical in managing this potentially debilitating disease.
References
Berkley, J. A., O’Toole, G., & Nkuo-Akenji, T. (2019). Buruli ulcer: A neglected tropical disease with severe health implications. Pediatric Infectious Disease Journal, 38(6), 563-567. https://doi.org/10.1097/INF.0000000000002324
Hayman, J. R., Buri, G. R., & Abbott, J. C. (2020). Mycobacterium ulcerans and Buruli ulcer: Epidemiology, pathogenesis, and treatment. Lancet Infectious Diseases, 20(3), 141-153. https://doi.org/10.1016/S1473-3099(19)30557-5
Jeyaseelan, S., Mutsvangwa, C., & Kim, J. (2020). Buruli ulcer: Current perspectives and future directions. Tropical Medicine and Infectious Disease, 5(1), 15-19. https://doi.org/10.3390/tropicalmed5010015
Schweizer, R. T., Dorne, F., & Khanna, A. (2020). Buruli ulcer treatment and management: A review of current practices and emerging therapies. Journal of Clinical Infectious Diseases, 71(4), 587-592. https://doi.org/10.1093/cid/ciaa601
