(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 by 12 of the 33 countries.
- Most patients are children aged under 15 years.
- 80% of cases detected early can be cured with a combination of antibiotics.
Buruli ulcer is a chronic debilitating skin disease caused by an environmental bacterium - Mycobacterium ulcerans. The organism belongs to the family of bacteria that causes tuberculosis and leprosy. Early diagnosis and treatment are the only ways to minimize morbidity and prevent long-term disability.
Early diagnosis and treatment are the only ways to minimize morbidity and prevent long-term disability.
Scope of the problem
Information gathered from scientific literature shows that 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. Out of the 33 countries 15 regularly report data to WHO.
The majority of cases are reported from West and Central Africa, including Benin, Cameroon, Côte d’Ivoire, Democratic Republic of the Congo and Ghana. In recent years Australia has been reporting a higher number of cases.
In 2014, 12 of the 15 countries regularly reporting data to WHO reported nearly 2200 new cases, more than 50% less than 2009 when 5000 cases were reported. Except for a few countries, the number of cases has declined since 2010. 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.
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. No significant difference exists between the rates of affected males and affected females.
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.
In terms of severity, the disease has been classified into three categories: Category I single small lesion (32%), Category II non-ulcerative and ulcerative plaque and oedematous forms (35%) and Category III disseminated and mixed forms such as osteitis, osteomyelitis, joint involvement (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.
Mycrobacterium ulcerans needs a temperature between 29–33 °C (Mycobacterium 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, the patient’s geographical area, the location of lesions, and the extent of pain experienced, other conditions should be excluded from the diagnosis. These other conditions include tropical phagedenic ulcers, chronic lower leg ulcers due to arterial and venous insufficiency (often in the older and elderly populations), diabetic ulcers, 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 patient2. The weakened immune system makes the clinical progression of Buruli ulcer more aggressive, and as a result the treatment outcomes are poor.
Due to international travel, cases can appear in non-endemic areas. It is therefore important that health workers are knowledgeable about Buruli ulcer and its clinical presentations.
Four standard laboratory methods can be used to confirm Buruli ulcer; IS2404 polymerase chain reaction (PCR), direct microscopy, histopathology and culture. PCR is the most commonly used method. WHO has recently published a manual on these 4 methods to guide laboratory scientists and health workers3.
A WHO network consisting of 17 laboratories in 14 endemic and non-endemic countries support national control programmes to confirm cases.
Treatment consists of a combination of antibiotics and complementary treatments (under morbidity management and disability prevention/rehabilitation). Treatment guidance for health workers can be found in the WHO publication “Treatment of mycobacterium ulcerans disease (Buruli ulcer).”
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 (15 mg/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 considered the safer option for pregnant patients. 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, disability prevention and rehabilitation
Interventions such as wound management and surgery (mainly debridement and skin grafting) are used to speed up the healing of wounds, thereby working to prevent and rehabilitate disability.
It is important to strengthen the capacity of the health system at all levels in affected areas to ensure access to quality care.
As 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.
There are 2 ongoing research activities aimed to improve the management of the disease.
1. Development of oral antibiotic treatment
A randomized clinical trial 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 by the end of 2016, with a one-year follow-up till the end of 2017.
2. Validation of fluorescent thin layer chromatography as point of care test
Preliminary results from the initial analysis of patients’ samples, using the fluorescent thin layer chromatography method to detect mycolactone, has shown great potential for a rapid diagnosis at district-level health facilities1. With the support of the Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland, and Harvard University, field evaluation of the method will start this year in Benin, Democratic Republic of the Congo, and Ghana.
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.