(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 in Africa, South America and Western Pacific regions.
- In 2014, 2200 new cases were reported annually from 12 of the 33 countries.
- Most patients are children under 15.
- 80% of cases detected early can be cured with a combination of antibiotics.
Buruli ulcer 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 problem
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, China and Japan. 15 of these countries regularly report data to WHO.
Some countries in West and Central Africa – Benin, Cameroon, Côte d’Ivoire, Democratic Republic of the Congo and Ghana – report the majority of cases.
In 2014, 12 of the 15 countries reported nearly 2200 new cases to WHO, more than 50% reduction from 2009 when 5000 cases were reported. Except for a few countries, the number of cases has declined since 2010 although the exact cause of decline is unknown.
Clinical and epidemiological characteristics of cases
The clinical and epidemiological aspects of cases vary considerably within and across different countries and settings. Environmental and climatic changes appear to influence the number of new cases from year to year.
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. There is no important differences between males and females.
Lesions frequently occur in the limbs: 35% on the upper limbs and 55% on the lower limbs; 10% on the other parts of the body.
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 terms of disease severity, Category I (32%), Category II (35%) and Category III (33%). In Australia and Japan, most lesions (>90%) are diagnosed in Category I.
In all countries, at least 70% of all cases are diagnosed in the ulceration stage.
M. 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 unique toxin – mycolactone – which causes tissue damage and inhibits the immune response.
The exact mode of transmission of M. ulcerans is still unknown.
Signs and symptoms
Buruli ulcer often starts as a painless swelling (nodule). It can also initially 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 4 weeks with the classical, undermined borders. Occasionally, bone is affected causing gross deformities.
In general, with trained health professionals in endemic areas, clinical diagnosis is reliable.
Depending on the patient’s age, location of lesions, pain and geographical 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 ulcerative yaws and ulcers caused by Haemophilus ducreyi1.
Due to international travel, a few cases which appeared in non-endemic were misdiagnosed and mismanaged.
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.
HIV infection is not a risk factor but in co-endemic countries, HIV infection complicates the management of the patient.2 The weakened immune system makes the clinical progression of Buruli ulcer more aggressive and treatment outcomes are poor.
Four standard laboratory methods can be used to confirm Buruli ulcer; IS2404 polymerase chain reaction (PCR), direct microscopy, histopathology and culture. However, is the common method for confirmation because it has the highest sensitivity and results can be available within 48 hours. WHO has recently published a manual on these 4 methods to guide laboratory scientists and health workers.3
A WHO network consisting 17 laboratories in 14 endemic and non-endemic institutions support national control programmes to confirm cases.
The treatment of Buruli ulcer can be straightforward if the patient is detected early or complicated and costly if found in the advanced stage. This consists of combination of antibiotics and complementary treatments (under morbidity management and disability prevention). Treatment guidance for health workers can be found at the Buruli ulcer website. 4
Different combination of antibiotics given for 8 weeks are used to treat the Buruli ulcer irrespective of the stage. One of the following combinations may be used depending on the patient:
- 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 its effectiveness has not been proven by a randomized trial.
Since streptomycin is contraindicated in pregnancy, the combination of rifampicin and clarithromycin is also considered the safer option for pregnant patients; or a combination of rifampicin (10 mg/kg once daily) and moxifloxacin (400 mg once daily) has also been used though its effectiveness has not been proven by randomized trial.
Morbidity management and disability prevention
These include treatments that speed up the healing of the wounds and prevent disability.
The treatments are wound management, surgery (mainly debridement and skin grafting) and interventions to minimize or prevent disabilities.
It is important to strengthen the health system in affected areas to ensure access to quality care. Patients, family members and health workers work together to obtain the best results.
Since there is no knowledge of how Buruli ulcer is transmitted, preventive measures cannot be applied.
The objective of Buruli ulcer control is to minimize the suffering, disabilities and socioeconomic burden. Early detection and antibiotic treatment is the cornerstone of the WHO Buruli ulcer control strategy. WHO has developed technical and information materials to support the implementation of these activities.
National control programmes are expected to report their key performance based on the four programmatic targets set during the meeting on Buruli ulcer control and research held in Geneva, Switzerland, 25–27 March 2013.
- At least 70% of cases reported from any district or country to be confirmed by positive PCR (measure of better clinical diagnosis).
- The proportion of category III lesions reported from any district or country to be below 25% (measure of early detection).
- The proportion of patients presenting with limitation of movement at diagnosis from any district or country to be below 15% (measure of early detection).
- The proportion of ulcerative lesions at diagnosis reported from any district or country to be reduced from the 2012 average of 84% to 60% (measure of early detection).
There are 3 main priorities for BU research which can lead to improved control measures in the field:
1. Development of oral antibiotic treatment
A randomized clinical trial being coordinated by WHO started in Benin and Ghana in 2013 with the objective of developing an oral-based treatment for Buruli ulcer. The recruitment is expected to be completed in 2016.
2. Development of rapid point-of-care diagnostic tests
The development of a rapid point-of care diagnostic test is a top priority. During the meeting on Buruli ulcer control and research held in Geneva, Switzerland, on 23–25 March 2015, progress in 4 key areas were presented. These are:
- Antigen capture, converted to a lateral flow assay.
- Loop-mediated isothermal amplification assay (LAMP).
- Mycolactone detection by thin layer chromatography
- Mycolactone antibody discovery.
Studies are planned in 2015 to validate these tests in the field and the Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland, is supporting the development of these tests.
3. Mode of transmission
The mode of transmission remains unknown despite more than a decade of efforts to decipher it. However, research is still in progress to address this problem.
WHO and global response
WHO provides technical guidance, develops policies, and coordinates control and research efforts. WHO brings together all major actors involved in Buruli ulcer on a regular basis 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 nongovernmental organizations, research institutions and governments of affected countries, steady and impressive progress has been made.
1Mitjà, O et al. Haemophilus ducreyi as a cause of skin ulcers in children from a yaws-endemic area of Papua New Guinea. Lancet Global Health: 2014; Vol 2, Issue 4: e235 - e241.
2Management of Buruli ulcer and HIV co-infection: http://apps.who.int/iris/bitstream/10665/154241/1/WHO_HTM_NTD_IDM_2015.01_eng.pdf?ua=1
3Laboratory diagnosis of Buruli ulcer: http://www.who.int/iris/bitstream/10665/111738/http://apps.who.int//iris/bitstream/10665/111738/1/9789241505703_eng.pdf
4Treatment of Mycobacterium ulcerans disease (Buruli Ulcer)http://www.who.int/iris/bitstream/10665/77771/http://apps.who.int//iris/bitstream/10665/77771/1/9789241503402_eng.pdf