|Classification and external resources|
Buruli ulcer on the ankle of a person from Ghana.
|ICD-10||A31.1 (ILDS A31.120)|
Buruli ulcer (also known as the Bairnsdale ulcer, Searls ulcer, or Daintree ulcer:340) is an infectious disease caused by Mycobacterium ulcerans. The genus also includes the causative agents of tuberculosis and leprosy (M. tuberculosis and M. leprae, respectively). The early stage of infection is characterised by a painless nodule, with non-pyogenic, necrotising lesions developing in the skin, and occasionally in adjacent bone, as the disease progresses. M. ulcerans secretes a lipid toxin, mycolactone, which functions as an immune suppressant, necrotising agent and activator of cellular apoptosis in mammalian tissues.
Signs and symptoms
The infection in most instances presents as a subcutaneous nodule, which is characteristically painless. In southern Australia the presentation is more often as a papule (or pimple), which is in the skin (dermis) rather than subcutaneous. The infection is mostly on the limbs, most often on exposed areas but not on the hands or feet. In children all areas may be involved, including the face or abdomen. A more severe form of infection produces diffuse swelling of a limb, which, unlike the papule or nodule, can be painful and accompanied by fever. Infection may frequently follow physical trauma, often minor trauma such as a small scratch.
A typical Buruli ulcer on the left hand of a 17-year-old boy in Nigeria.
Healed Buruli ulcer lesions in a Ghanaian woman.
The disease is primarily an infection of subcutaneous fat, resulting in a focus of necrotic (dead) fat containing myriads of the mycobacteria in characteristic spherules formed within the dead fat cells. Skin ulceration is a secondary event. The mycobacterium produces a toxin, named mycolactone, which causes this fat necrosis and inhibits an immune response. Healing may occur spontaneously but more often the disease is slowly progressive with further ulceration, granulation, scarring, and contractures. Secondary infection may occur with other nodules developing and infection may occur into bone. Although seldom fatal, the disease results in considerable morbidity and deformity.
Th1-mediated immune responses are protective against M. ulcerans infection, whereas Th2-mediated responses are not.
The diagnosis of Buruli ulcer is usually based on the characteristic appearance of the ulcer in an endemic area. If there is any doubt about the diagnosis, then PCR using the IS2404 target is helpful, but this is not specific for M. ulcerans. The Ziehl-Neelsen stain is only 40–80% sensitive, and culture is 20–60% sensitive. Simultaneous use of multiple methods may be necessary to make the diagnosis.
Treatment is by surgical excision (removal) of the lesion, which may be only a minor operation and very successful if undertaken early. Advanced disease may require prolonged treatment with extensive skin grafting. Surgical practice can be dangerous and scarcely available in affected third world countries.
Antibiotics currently play little part in the treatment of Buruli ulcer. The WHO currently recommend rifampicin and streptomycin for eight weeks in the hope of reducing the need for surgery. The combination of rifampicin and clarithromycin has been used for many years in Australia. Rifampicin must never be used alone because the bacterium quickly becomes resistant.
There are a number of experimental treatments currently being investigated:
- Sitafloxacin and rifampicin is a synergistic combination that has only been trialled in mice.
- Rifalazil is a rifamycin antibiotic that appears to be more potent than rifampicin that has only been trialled in mice.
- Epiroprim and dapsone are synergistic when used in combination (in vitro studies only at present)
- Diarylquinoline shows high potency in vitro
- Application of French clay.
In a small series of eight patients, local heat at 40°C led to complete healing without surgery (except the initial removal of dead tissue).
The infection occurs in well defined areas throughout the world, mostly tropical areas - in several areas in Australia, in Uganda, in several countries in West Africa, in Central and South America, in southeast Asia and New Guinea. It is steadily rising as a serious disease, especially in West Africa and underdeveloped countries, where it is the third leading cause of mycobacterial infection in healthy people, after tuberculosis and leprosy. In East Africa, thousands of cases occur annually and in these areas the disease has displaced leprosy to become the second most important mycobacterial disease of man (after tuberculosis).
The disease is more likely to occur where there have been environmental changes such as the development of water storages, sand mining and irrigation.
Buruli ulcer is currently endemic in the Benin, Côte d'Ivoire, Ghana, Guinea, Liberia, Nigeria, Sierra Leone and Togo. In Ghana, 1999 data indicated that the prevalence rate of the disease in the Ga West District was 87.7 per 100,000, higher than the estimated national prevalence rate at 20.7 per 100,000 generally, and 150.8 per 100,000 in the most disease-endemic districts.
James Augustus Grant, in his book A Walk across Africa (1864), describes how his leg became grossly swollen and stiff with later a copious discharge. This was almost certainly the severeoedematous form of the disease, and is the first known description of the infection. Buruli ulcer disease was identified in 1897 by Sir Albert Cook, a British physician, at Mengo Hospital in Kampala, Uganda. A detailed description of the disease was written in 1948 by Professor Peter MacCallum and his colleagues, who were treating patients from the Bairnsdale district, near Melbourne,Australia. They were the first to identify Mycobacterium ulcerans as the pathogencausing it. The disease was so named after Buruli County in Uganda (now called Nakasongola District), because of the many cases that occurred there in the 1960s. The incidence of the disease has recently been rising in tropical Africa.
In March 2008, researchers announced the first isolation of M. ulcerans from the environment. This suggests that the disease might be transmitted via contact with the environment rather than person to person. An international team of researchers led by University of Melbourne scientist Dr Tim Stinear has sequenced the entire genome of M. ulcerans.
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- French Clay Can Kill MRSA And 'Flesh-Eating' Bacteria
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