(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.
- The disease occurs in Africa, South America and Western Pacific regions.
- Most patients 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 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.
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 2013, 14 of the 33 countries reported data to WHO.
Clinical and epidemiological characteristics of cases
The clinical and epidemiological aspects of cases vary considerably within and across 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;
- Australia – 55% males and 45% females;
- 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 Australia and Japan, most lesions (>90%) are diagnosed in Category I.
In some countries in Africa, about 70% of cases are diagnosed with ulceration while in Australia and Japan, more than 90% are diagnosed at the ulceration stage but most of the lesions are small (Category I).
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.
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 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 ulcerative yaws and ulcers caused by Haemophilus ducreyi1.
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. 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) is the common method for confirmation because it has the highest sensitivity and results can be available within 48 hours. Other methods are direct microscopy, histopathology and culture.
WHO has recently published a manual on these 4 methods to guide laboratory scientists and health workers.
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 antibiotics and complementary treatments.
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 preventing 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. There is no vaccine for primary prevention of Buruli ulcer, though Bacille Calmette–Guérin (BCG) vaccination appears to offer some short-term protection from the disease. Secondary prevention is based on early detection and treatment of cases.
Objectives and strategy
The objective 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;
- health workers and village volunteer training;
- laboratory confirmation of cases;
- standardized recording and reporting system and mapping;
- health facilities strengthening;
- monitoring and evaluation of control activities.
WHO has developed technical and information materials to support the implementation of these 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 any district or country to be confirmed by positive PCR.
- By the end of 2014, the proportion of category III lesions reported from any district or country to be reduced from 2012 average of 33% to below 25%.
- By the end of 2014, the proportion of patients presenting with limitation of movement at diagnosis from any district or country to be reduced from the 2012 average of 25% to 15%.
- By the end of 2014, the proportion of ulcerative lesions at diagnosis reported from any district or country to be reduced from the 2012 average of 84% to 60%.
Based on the need to improve control measures in the field, there are 3 main priorities for BU research:
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 study is expected to be completed in 2016.
2. Development of rapid point-of-care diagnostic tests
The development a rapid point-of care diagnostic test would simplify the control and management of the disease in the field. In November 2013, WHO and Foundation for Innovative New Diagnostics (FIND), convened a meeting in Geneva on priority areas and gaps for accelerating the development of a rapid test. An innovative method to detect the toxin, mycolactone, in human tissues is in progress and may provide a simpler, faster and cheaper alternative to confirm suspected Buruli ulcer cases2 .
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 non-governmental organizations, research institutions and governments of affected countries, steady and impressive progress has been made.
This has changed Buruli ulcer from a devastating, debilitating and difficult disease to one that can now be cured with antibiotics.
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.
2Converse PJ et al. Accelerated detection of mycolactone production and response to antibiotic treatment in a mouse model of Mycobacterium ulcerans disease . PLOS Neglected Tropical Diseases, January 02, 2014