(Mycobacterium ulcerans infection)
- Buruli ulcer is a chronic debilitating skin and soft tissue infection that can lead to permanent disfigurement and disability.
- It is caused by the Mycobacterium ulcerans bacterium.
- At least 33 countries with tropical, subtropical and temperate climates have reported Buruli ulcer.
- Between 5000–6000 cases are reported annually from 15 of the 33 countries.
- Most cases occur in rural communities in sub-Saharan Africa.
- Nearly half of people affected in Africa are children under 15.
- 80% of cases detected early can be cured with a combination of antibiotics.
Buruli ulcer is one of the 17 neglected tropical diseases. It is caused by infection with Mycobacterium ulcerans, an organism which belongs to the family of bacteria that causes tuberculosis and leprosy.
Infection leads to destruction of skin and soft tissue with large ulcers usually on the legs or arms. Patients who are not treated early suffer long-term functional disability. Early diagnosis and treatment are the only ways to minimize morbidity and prevent disability.
Scope of the problemBuruli 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, China and Japan.
West Africa, Benin, Côte d’Ivoire and Ghana report most cases with Côte d’Ivoire reporting almost half of the global cases. Only 15 of the 33 countries reported data in 2012.
Clinical and epidemiological characteristics of casesThe clinical and epidemiological aspects of cases vary (according to geographic area) in different countries and settings.
In Africa, about 48% of those affected are children under 15 years, whereas in Australia (10% are children under 15 years) and in Japan (19% are children under 15 years).
Gender distribution of the disease also varies: Africa - 52% males and 48% females; and Japan - 34% males and 66% females.
In general, about 35% of lesions occur on the upper limbs, 55% on the lower limbs and 10% on the other parts of the body.
In Africa, most cases are still diagnosed late: Category I (32%), Category II (35%) and Category III (33%). In North Africa about 26% of cases are diagnosed before ulceration while in Australia and Japan, less than 10% are diagnosed before ulceration.
Difference in data is largely due to demographical characteristics of the population, level of endemicity, awareness about the disease, extent of active surveillance efforts and accessibility to treatment.
Causative organismM. ulcerans needs a temperature between 29–33 °C (M. tuberculosis grows at
37°C) and a low (2.5%) oxygen concentration to grow. The organism produces a destructive toxin – mycolactone – which causes tissue damage and inhibits the immune response.
TransmissionThe exact mode of transmission of M. ulcerans is still unknown. However, it appears that different modes of transmission occur in different geographic areas and epidemiological settings. There may be some role for living agents as reservoirs and as vectors of M. ulcerans, in particular aquatic insects, adult mosquitoes or other biting arthropods.
In Victoria, Australia, Buruli ulcer also occurs in native wildlife and domestic animals. Laboratory-confirmed cases have been diagnosed in koalas, common ringtail possums, a common brushtail possum, a mountain brushtail possum, a long-footed potoroo, horses, dogs, alpacas and a cat.
Signs and symptomsBuruli ulcer often starts as a painless swelling (nodule). It can initially also present as a large painless area of induration (plaque) or a diffuse painless swelling of the legs, arms or face (oedema). Local immunosuppressive properties of the mycolactone toxin enable the disease to progress with no pain and fever. Without treatment or sometimes during antibiotics treatment, the nodule, plaque or oedema will ulcerate within four weeks with the classical, undermined borders. Occasionally, bone is affected causing gross deformities.
DiagnosisThere is no diagnostic test that can be used in the field. Research is progressing to develop one.
Four standard laboratory methods can be used to confirm Buruli ulcer. IS2404 polymerase chain reaction (PCR) is the common method for confirmation because it has the highest sensitivity and results can be available within 48 hours.
During a meeting on Buruli ulcer control and research held in Geneva from 25–27 March 2013, experts recommended that at least 70% of cases reported need to be confirmed by PCR. A WHO network consisting of 16 laboratories in 13 endemic and non-endemic institutions support national control programmes to implement this recommendation.
Depending on the patient’s age, location of lesions, pain, and geographic area, other conditions should be excluded from the diagnosis. These include tropical phagedenic ulcers, chronic lower leg ulcers due to arterial and venous insufficiency (often in the older and elderly populations), diabetic ulcer, cutaneous leishmaniasis, extensive yaws.
Early nodular lesions are occasionally confused with boils, lipomas, ganglions, lymph node tuberculosis, onchocerciasis nodules or other subcutaneous infections such as fungal infection. In Australia, papular lesions may initially be confused with an insect bite. Cellulitis may look like oedema caused by M. ulcerans infection but in the case of cellulitis, the lesions are painful and the patient is ill and febrile.
TreatmentFor treatment WHO recommends the following:
1. Different combination of antibiotics given for eight weeks are used to treat the Buruli ulcer:
- a combination of rifampicin (10 mg/kg once daily) and streptomycin (15mg/kg once daily); or
- a combination of rifampicin (10 mg/kg once daily) and clarithromycin (7.5 mg/kg twice daily) has been used though effectiveness not proven by a randomized trial. Since streptomycin is contraindicated in pregnancy, the combination of rifampicin and clarithromycin is also considered the safer option for this group of patients; or
- a combination of rifampicin (10 mg/kg once daily) and moxifloxacin (400 mg once daily) has also been used though effectiveness not proven by randomized trial.
HIV infection is not a risk factor but it weakens the immune system, making the progress of Buruli ulcer more aggressive. Coinfected patients often present multifocal lesions and osteomyelitis. Although further studies are required, management of BU/HIV coinfection may follow guidelines for managing TB/HIV coinfection.
- HIV counselling and testing should be offered to all patients presenting with BU.
- BU/HIV co-infected patients should be screened for tuberculosis.
- As for TB, BU/HIV co-infected patients may receive early antiretroviral treatment to ensure a better response to treatment.
PreventionThere is no vaccine for primary prevention of Buruli ulcer. Bacille Calmette–Guérin (BCG) vaccination appears to offer some short-term protection from the disease. Secondary prevention is based on early detection of cases.
ControlThe aim of Buruli ulcer control is to minimize the suffering, disabilities and socioeconomic burden.
The strategy is based on early detection and antibiotic treatment. The following activities are essential for implementing this strategy:
- health education at the community level to enhance early reporting;
- training of health workers and village volunteers;
- laboratory confirmation of cases;
- standardized recording and reporting system and mapping;
- strengthening of health facilities;
- monitoring and evaluation of control activities.
The following programmatic targets were agreed upon during the Meeting on Buruli ulcer control and research held in Geneva, Switzerland, 25–27 March 2013.
- By the end of 2014, at least 70% of cases reported from from any district or country to be confirmed by positive PCR.
- By the end of 2014, proportion of category III lesions reported from from any district or country to reduce from 2012 average of 33% to below 25%.
- By the end of 2014, proportion of patients presenting with limitation of movement at diagnosis from from any district or country to reduce from the 2012 average of 25% to 15%.
- By the end of 2014, proportion of ulcerative lesions at diagnosis reported from any district or country to reduce from the 2012 average of 84% to 60%.
Targets 2–4 reflect the impact of early detection efforts (village education and active surveillance).
Research prioritiesBased on the need to improve control measures in the field, there are three main priorities for BU research:
- simplify antibiotic treatment
- develop point-of-care diagnostic tests
- decipher mode of transmission.
WHO and global responseWHO provides technical guidance, develops policies and coordinates control and research efforts.
WHO convenes all major actors involved in Buruli ulcer on a regular basis which provides an opportunity to share information, coordinate disease control and research efforts, and monitor progress. These efforts have also helped to raise the visibility of Buruli ulcer, and mobilized resources to fight it.
Under WHO’s leadership and with support of non-governmental organizations, research institutions and governments of affected countries, steady and impressive progress has been made. This has changed the face of Buruli ulcer from a devastating, debilitating and difficult disease to one that can be treated and cured.