Buruli ulcer (BU) is a chronic, debilitating skin and soft tissue infection found primarily in tropical and subtropical regions. Characterized by progressive destruction of the skin and underlying tissue, it can lead to permanent disfigurement and physical disability if not treated early. The disease has been reported in at least 33 countries, mainly in West and Central Africa, though outbreaks also occur in Australia and parts of Asia. Its incidence is closely linked to specific ecological factors in the environment.
The Bacteria Responsible
Buruli ulcer is directly caused by the bacterium Mycobacterium ulcerans, a slow-growing organism related to the bacteria that cause tuberculosis and leprosy. This environmental mycobacterium produces a potent, diffusible lipid toxin called mycolactone, which is encoded on a unique megaplasmid. Mycolactone is the sole virulence factor responsible for the massive tissue destruction and unique clinical presentation of the disease.
The toxin is both cytotoxic, killing skin and fat cells, and immunosuppressive, dampening the immune response at the infection site. It achieves its destructive effects by inhibiting the Sec61 translocon, a protein channel essential for transporting newly synthesized proteins. Blocking this mechanism prevents the host cell from producing proteins needed for immune function and cell adhesion, triggering cell death and tissue necrosis. The toxin also possesses analgesic properties, which makes the resulting lesions characteristically painless, often delaying diagnosis.
How Infection Occurs
The route of transmission from the environment to humans is not fully understood, but infection is strongly associated with exposure to aquatic environments. M. ulcerans is an environmental pathogen, and human-to-human transmission is extremely rare. Endemic areas are typically found near slow-moving or stagnant water bodies, such as swamps and ponds.
One leading hypothesis involves direct inoculation of the bacteria into the skin through cuts or minor trauma while a person is in contaminated water or soil. Another theory centers on the role of insect vectors, particularly aquatic insects like water bugs and mosquitoes, which may act as mechanical carriers. For example, research suggests mosquitoes may transmit the pathogen after feeding on infected native possums, which serve as an animal reservoir in Australia. Regardless of the specific vector or reservoir, the bacteria must be introduced into the subcutaneous tissue, usually via environmental contact or an insect bite.
Stages of Disease Development
The incubation period for Buruli ulcer typically ranges from a few weeks to several months, averaging four to five months. The disease usually begins subtly, often presenting as a firm, painless lump or nodule, which is frequently mistaken for an insect bite. It may also start as a painless plaque or a diffuse, painless swelling (edema) of an entire limb.
Over weeks or months, this initial lesion progresses and ulcerates, forming the characteristic destructive open wound. These ulcers have a necrotic base and distinct, undermined edges, indicating tissue destruction extends laterally beneath the surrounding skin. Due to the toxin’s immunosuppressive effects, patients rarely experience systemic symptoms like fever unless a secondary bacterial infection occurs. If left untreated, the extensive ulceration can destroy nerves and blood vessels, potentially leading to severe complications like osteomyelitis and debilitating contractures.
Treatment and Prevention
Timely diagnosis and treatment are essential to minimize tissue damage and prevent long-term disability. The standard treatment involves multidrug antibiotic therapy, typically an eight-week course of rifampicin combined with another antibiotic, such as streptomycin or clarithromycin. This combination is highly effective and is the first-line treatment for most patients.
In advanced cases or when significant necrotic tissue is present, surgery and wound management are necessary to remove dead tissue, cover open wounds with skin grafts, and correct deformities. Prevention in endemic areas focuses on reducing exposure to environmental sources. This includes avoiding contact with stagnant water, wearing protective clothing outdoors, and promptly cleaning any cuts or abrasions with soap and antiseptic after outdoor activities.