Buruli ulcer

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Buruli ulcer
ICD-10 A31.1
ICD-9 031.1
DiseasesDB 8568
MeSH D009165

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The Buruli ulcer (also known as the Bairnsdale ulcer) is an infectious disease caused by Mycobacterium ulcerans, from the same family of bacteria which causes tuberculosis and leprosy. The infection causes painless swelling, with lesions developing in the skin later on. Further progression of this bacteria produces toxins that suppress the immune system and destroy skin, underlying tissue and bone, causing severe deformities. It predominantly affects the limbs.

Identification and naming

It was first described in 1948 from the Bairnsdale district in south-east Australia. The disease was well known in Africa before this time but the mycobacterium had never been identified. James Augustus Grant, in his book A Walk across Africa, describes how his leg became grossly swollen and stiff with later a copious discharge. This was almost certainly the severe oedematous form of the disease, and is the first known description of the infection. The name "Buruli ulcer" comes from an area in Uganda where the disease was once most prevalent, especially during the 1960s.

Just recently, an international team of researchers led by Monash University scientist Dr Tim Stinear has unlocked the entire genomic makeup of this mysterious disease hoping it could provide researchers with the knowledge of creating a treatment or even a vaccine.

Infection

Being one of the less known diseases caused by mycobacteria, means of infection are not completely clear. However, the mycobacterium has been identified in stagnant or slowly moving water sources in endemic areas and in aquatic insects (Naucoridiae). Transmission to man may be by means of insects or by a contaminated aerosol generated from decaying vegetation in the water source. Infection in Australia has occurred in an alpaca, in koalas, possums and other marsupials.

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.

Pathology

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 hideous deformity.

Th1-mediated immune responses are protective against M. ulcerans infection, whereas Th2-mediated responses are not.

Diagnosis

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.

Treatment

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 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

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).[1]

Global spread

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.

References

MacCallum P, Tolhurst JC, Buckle G, Sissons HA (1948). A New Mycobacterial Infection in Man. J Pathol Bacteriol 60 (1): 93–122.

  1. Meyers WM, Shelly WM, Connor DH (1974). "Heat treatment of Mycobacterium ulcerans infections without surgical excision". Am J Trop Med Hyg 23: 924–29.

de:Buruli-Ulkus

Cost Effectiveness of Buruli ulcer

| group5 = Clinical Trials Involving Buruli ulcer | list5 = Ongoing Trials on Buruli ulcer at Clinical Trials.govTrial results on Buruli ulcerClinical Trials on Buruli ulcer at Google


| group6 = Guidelines / Policies / Government Resources (FDA/CDC) Regarding Buruli ulcer | list6 = US National Guidelines Clearinghouse on Buruli ulcerNICE Guidance on Buruli ulcerNHS PRODIGY GuidanceFDA on Buruli ulcerCDC on Buruli ulcer


| group7 = Textbook Information on Buruli ulcer | list7 = Books and Textbook Information on Buruli ulcer


| group8 = Pharmacology Resources on Buruli ulcer | list8 = AND (Dose)}} Dosing of Buruli ulcerAND (drug interactions)}} Drug interactions with Buruli ulcerAND (side effects)}} Side effects of Buruli ulcerAND (Allergy)}} Allergic reactions to Buruli ulcerAND (overdose)}} Overdose information on Buruli ulcerAND (carcinogenicity)}} Carcinogenicity information on Buruli ulcerAND (pregnancy)}} Buruli ulcer in pregnancyAND (pharmacokinetics)}} Pharmacokinetics of Buruli ulcer


| group9 = Genetics, Pharmacogenomics, and Proteinomics of Buruli ulcer | list9 = AND (pharmacogenomics)}} Genetics of Buruli ulcerAND (pharmacogenomics)}} Pharmacogenomics of Buruli ulcerAND (proteomics)}} Proteomics of Buruli ulcer


| group10 = Newstories on Buruli ulcer | list10 = Buruli ulcer in the newsBe alerted to news on Buruli ulcerNews trends on Buruli ulcer</small>


| group11 = Commentary on Buruli ulcer | list11 = Blogs on Buruli ulcer

| group12 = Patient Resources on Buruli ulcer | list12 = Patient resources on Buruli ulcerDiscussion groups on Buruli ulcerPatient Handouts on Buruli ulcerDirections to Hospitals Treating Buruli ulcerRisk calculators and risk factors for Buruli ulcer


| group13 = Healthcare Provider Resources on Buruli ulcer | list13 = Symptoms of Buruli ulcerCauses & Risk Factors for Buruli ulcerDiagnostic studies for Buruli ulcerTreatment of Buruli ulcer

| group14 = Continuing Medical Education (CME) Programs on Buruli ulcer | list14 = CME Programs on Buruli ulcer

| group15 = International Resources on Buruli ulcer | list15 = Buruli ulcer en EspanolBuruli ulcer en Francais

| group16 = Business Resources on Buruli ulcer | list16 = Buruli ulcer in the MarketplacePatents on Buruli ulcer

| group17 = Informatics Resources on Buruli ulcer | list17 = List of terms related to Buruli ulcer


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