Buruli ulcer (BU) is a skin neglected tropical disease (NTD) targeted for control.
It is a chronic debilitating disease that affects mainly the skin and also the soft tissue and bone and leads to the formation of large ulcers found usually on legs and arms.
Although most ulcers eventually heal, poorly managed patients may develop severe scars and deformities which lead to long term disability. The scarring and disability often lead to stigmatization, movement limitations, participation restrictions, and social exclusion.
The name Buruli comes from a county in Uganda (currently Nakasongola district) where a lot of cases were reported in the 1960s.
BU is caused by an environmental bacterium known as Mycobacterium ulcerans which belongs to the family of bacteria that causes tuberculosis and leprosy.
M. ulcerans grows at temperatures between 29–33 °C (M. tuberculosis grows at 37°C) and a low 2.5% oxygen concentration to grow.
This organism produces a unique toxin – mycolactone – that causes tissue damage and inhibits the local immune response. The toxin´s local immunosuppressive properties enable the disease to progress rapidly with no pain and fever.
Although it is known that the disease is associated with exposure to the environment, particularly to slow-moving or stagnant bodies of water, the mode of transmission has not been yet established and remains unknown.
The incubation period is believed to be between 4-5 months as an average but remains unclear.
Signs and symptoms
BU often starts as a painless swelling (nodule) without fever, which makes early detection difficult. 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).
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 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%)
- Category III: disseminated and mixed forms such as osteitis, osteomyelitis and joint involvement (33%)
In most cases, experienced health professionals in endemic areas can make a reliable clinical diagnosis but training is essential.
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 ducreyi.
Early nodular lesions are occasionally confused with boils, lipomas, ganglions, lymph node tuberculosis, onchocerciasis nodules or other subcutaneous infections such as fungal infection. 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.
In Australia, papular lesions may initially be confused with an insect bite.
Four standard laboratory methods can be used to confirm Buruli ulcer:
- IS2404 polymerase chain reaction (PCR)
- direct microscopy
PCR is the most commonly used method. A simple method developed by researchers at Harvard University in USA using fluorescent thin-layer chromatography to selectively detect mycolactone (2) in infected tissue is being used as a rapid diagnostic test.
Treatment consists of a combination of antibiotics during 8 weeks irrespective of the stage and complementary treatments.
Current WHO recommendations are:
- rifampicin 10 mg/kg per body weight daily
- clarithromycin 7.5 mg/kg per body weight twice daily.
This combination is safe for pregnant women.
In addition to the antibiotics and depending on the stage of the disease, other interventions under morbidity management and disability prevention/rehabilitation such as wound and lymphoedema management, surgery (mainly debridement and skin grafting to speed up healing) and physiotherapy are needed in severe cases.
Psychological support may also be needed for those with severe disease.
As there is no knowledge of how BU is transmitted, preventive measures cannot be applied. Bacillus Calmette–Guérin (BCG) vaccination appears to provide a limited protection.
Early diagnosis and treatment are crucial to minimizing morbidity, costs and prevent long-term disability. It is the cornerstone of the BU control strategy.
Disease awareness, community health education, screening, training of health workers and active involvement of village volunteers are crucial to ensure early diagnosis and treatment of the disease.
Buruli ulcer has been reported in 33 countries in Africa, the Americas, Asia and the Western Pacific with tropical, subtropical and temperate climates. Out of the 33 countries 14 regularly report data to WHO.
In Africa, the majority of cases are reported from West and Central Africa, including Benin, Cameroon, Côte d’Ivoire, Democratic Republic of the Congo, Nigeria and Ghana. Liberia has recently started to report large number of suspected cases. Outside Africa, the Australia remains a major endemic country where cases have been reported since 1930s and has in increasing number of severe cases since 2013.
Ghana, Australia and Nigeria report most cases globally. But, overall, the disease is considerably under reported.
In Africa, about half of the patients are children under 15 years. In Australia, the average age is around 60 years.
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 all countries, at least 70% of all cases are diagnosed in the ulceration stage.
No significant difference exists between the rates of affected males and affected females. In Africa slightly more males are affected before the age of 20 and more females after the age of 20.
Which of the crosscutting issues are relevant
Water, sanitation and hygiene (WASH) are critical in the prevention and care for BU and NTDs in general. Provision of safe water, sanitation and hygiene is one of the five key interventions within the global NTD roadmap.
Wound management, which requires clean water and good hygiene at home and in health care facilities, is needed to speed up wound healing, in order to reduce disability.
Limited access to water and sanitation can lead to poor cleanliness and care, which can contribute to the isolation and exclusion of affected persons. Exposure to dirty water can lead to wound infection and further complications.
Interventions related to reduce stigma and improve mental wellbeing are essential components to be considered in the holistic care of patients suffering from BU and/or long term related disability.
Global Buruli Ulcer Initiative (GBUI)
In February 1998 with the financial support from the Nippon Foundation WHO established the Global Buruli Ulcer Initiative to coordinate BU control and research efforts in response to the growing spread of the disease particularly in West Africa.
In July 1998, WHO organized the first international conference on Buruli ulcer control and research. This conference marked a significant first step in drawing the attention of the world to the suffering caused by this neglected disease and led to the Yamoussoukro Declaration.
Supported by an Advisory group, this Initiative has drawn together global expertise and led mobilization of needed resources.
NTD NGO Network (NNN) Skin NTDs Cross-Cutting Group
Skin NTDs are a group of diseases for which the primary presentations are changes in the skin (lumps or swelling, ulcers, swollen limbs and patches on the face or body). These diseases, if not diagnosed and treated early, can lead to long-term disfigurement, disability, stigmatization and socioeconomic problems.
The integration of management of these diseases that have skin problems as commonality creates an opportunity to tackle many conditions at once in a cost-effective way, and may open up more financial opportunities to finally address them and aim at their elimination in those countries where they are endemic.
The awareness of the current challenges on treating skin related diseases, and the poor knowledge about how to detect and manage them, has prompted several organizations to start focusing on this topic, for instance, by developing new tools to map skin related NTDs and guidelines to support health staff in the differential diagnosis of skin diseases.
Several organizations have agreed to create a new Cross-Cutting Group called “Skin NTDs” to ensure that these neglected diseases receive adequate attention and financial support within the NTD Roadmap.
Visit the website of the NNN to read more about the functions of the Skin NTDs group and on how to become a member.