Buruli ulcer

Buruli ulcer is caused by a bacterium called Mycobacterium ulcerans. It often affects the skin and sometimes bone and can lead to permanent disfigurement. The bacterium produces a toxin that causes skin damage. Without early treatment, Buruli ulcer (BU) can lead to long-term disability, stigma associated with socioeconomic burden. The exact mode of transmission remains unknown. Buruli ulcer has been reported in 33 countries in Africa, the Americas, Asia and the Western Pacific. Most cases occur in tropical and subtropical regions except in Australia and Japan. Out of the 33 countries, 14 regularly report data to WHO. More than 90% of global cases are reported in Africa where nearly 50% of the people affected are children under the age of 15 years.

The annual number of suspected Buruli ulcer cases reported globally was around 5000 cases up until 2010 when it started to decrease. In the WHO African region, the trend of annual cases of BU is like the global one, since more than 90% of global cases are reported in Africa. In 2022, 1775 cases were reported in Africa Region compared to 4850 in 2010 (70% reduction in reported cases).

Transmission

The exact mode of transmission of Mycobacterium ulcerans (M. ulcerans) is still unclear. Buruli ulcer usually occurs near slow moving or stagnant bodies of water, where M. ulcerans is found in aquatic insects, molluscs, fish and the water itself. It is not clear how M. ulcerans is transmitted to humans.

Signs and symptoms

Buruli ulcer often starts as a painless swelling (nodule), a large painless area of induration (plaque) or a diffuse painless swelling of the legs, arms or face (oedema). The disease may progress with no pain or fever. Without treatment or sometimes during antibiotics treatment, the nodule, plaque or oedema will ulcerate within 4 weeks. Bone is occasionally affected, causing deformities.

The disease has been classified into three categories of severity: Category I, single small lesion (32%) less than 5 cm on diameter; Category II, non-ulcerative and ulcerative plaque and edematous forms between 5-15 cm (35%); and Category III lesions more than 15 cm in diameter including, disseminated and mixed forms such as, osteomyelitis and joint involvement, lesions at critical sites (head, breast, genitalia), (33%).

Lesions frequently occur in the limbs: 35% on the upper limbs, 55% on the lower limbs, and 10% on the other parts of the body. Health workers should be careful in the diagnosis of Buruli ulcer in patients with lower leg lesions to avoid confusion with other causes of ulceration such as diabetes, arterial and venous insufficiency lesion.

Diagnosis

Differential diagnoses of Buruli ulcer include tropical phagedenic ulcers, chronic lower leg ulcers due to arterial and venous insufficiency (often in elderly populations), diabetic ulcers, cutaneous leishmaniasis, extensive ulcerative yaws and ulcers caused by Haemophilus ducreyi.

Early nodular and papular lesions may be confused with insect bite, boils, lipomas, ganglions, lymph node tuberculosis, onchocerciasis nodules or deep fungal subcutaneous infections. Cellulitis may look like oedema caused by Mycobacterium ulceransinfection but in the case of cellulitis, there is pain and fever. Four standard laboratory methods can be used to confirm Buruli ulcer: IS2404 polymerase chain reaction (PCR), direct microscopy, histopathology and culture. The bacterium grows best at temperatures between 29–33 °C (Mycobacterium tuberculosis grows at 37 °C) and needs a low (2.5%) oxygen concentration.

In 2019, WHO established the Buruli ulcer Laboratory Network for Africa  to help strengthen PCR confirmation in 9 endemic countries in Africa. Thirteen laboratories participate in this network, supported by the American Leprosy Missions, Anesvad, Raoul Follereau Foundation and coordinated by the Pasteur Center of Cameroon.

In 2021, WHO completed an online consultation for a draft document on Target Product Profiles to develop rapid test for the diagnosis of Buruli ulcer. With the availability of simple oral treatment for Buruli ulcer, a rapid test to allow early confirmation of diagnosis can facilitate the timely treatment of the disease. The current turnaround time of a PCR test is too long to guide early treatment decisions.

Treatment

Treatment consists of a combination of antibiotics and complementary treatments. A combination of rifampicin (10 mg/kg once daily) and clarithromycin (7.5 mg/kg twice daily) is now the recommended treatment. Interventions such as wound and lymphoedema management and surgery (mainly debridement and skin grafting) are used to speed up healing, thereby shortening the duration of hospitalization. Physiotherapy is needed in severe cases to prevent disability. Those left with disability require long-term rehabilitation. These same interventions are applicable to other neglected tropical diseases, such as leprosy and lymphatic filariasis.

The WHO has developed a treatment guidance for health workers.

HIV infection complicates the management of the patient, making clinical progression more aggressive and resulting in poor treatment outcomes. WHO has published a technical guide to help clinicians in the management of co-infection.