Buruli ulcer: Wikis

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Buruli ulcer
Classification and external resources

Buruli ulcer on the ankle of a person from Ghana.
ICD-10 A31.1
ICD-9 031.1
DiseasesDB 8568
MeSH D009165

The Buruli ulcer (also known as the Bairnsdale ulcer or Searl ulcer[1]:340 or Searle's ulcer[2]) is an infectious disease caused by Mycobacterium ulcerans. The genus also includes the causative agents of tuberculosis and leprosy; Mycobacterium tuberculosis and Mycobacterium 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 [3]. M. ulcerans secretes a lipid toxin, mycolactone, which functions as an immune suppressant, necrotising agent and activator of cellular apoptosis in mammalian tissues [4][5].

Buruli ulcer in a long-term traveler to Senegal.
Buruli ulcer on the hand of a patient from Peru. A) Nonulcerative edematous lesion on the right middle finger as first seen; B) ulcerated lesions on the right middle finger approximately 4 weeks later; C) extensive debridement, 5.5 weeks after first seen; D) cured lesion 5 months after first seen, 1 month after autologous skin graft.

Contents

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. In March 2008, researchers announced the isolation of Mycobacterium ulcerans, the pathogen that causes Buruli ulcer[6]. The researchers, including Anthony Ablordey from the University of Ghana, have for the first time isolated the bacteria causing Buruli's ulcer — whose incidence is rising in tropical Africa — from the environment. The researchers, writing in PLoS Neglected Tropical Diseases, say this supports the idea that the disease is transmitted via aquatic areas rather than person to person. [1]

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. Simultaneous use of multiple methods may be necessary to make the diagnosis.[7]

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 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.[8]

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).[9]

Global spread

Ear of an 18 month-old child with culture- and PCR-confirmed Buruli ulcer who briefly visited St Leonards, Victoria, Australia, in 2001.

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.

Scientists hope that now that clues to the cause of Buruli's ulcer was discovered in 2008, that progress can be made in finding new ways to reduce infections and treat them, according to a report available on the Sub-Saharan African gateway of the Science and Development Network website. The researchers, including Anthony Ablordey from the University of Ghana, for the first time isolated the bacteria causing Buruli's ulcer — whose incidence is rising in tropical Africa — from the environment. The researchers, writing in PLoS Neglected Tropical Diseases, say this supports the idea that the disease is transmitted from an aquatic areas rather than person to person. [2]

Buruli ulcer is currently endemic in the Benin, Cote d'Ivoire, Ghana, Guinea, Liberia, Nigeria, Sierra Leone and Togo.[10]

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.[11]

Additional images

See also

Notes

  1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.  
  2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. Chapter 74. ISBN 1-4160-2999-0.  
  3. ^ Portaels F, Aguiar J, Debacker M, et al. (January 2004). "Mycobacterium bovis BCG vaccination as prophylaxis against Mycobacterium ulcerans osteomyelitis in Buruli ulcer disease". Infect. Immun. 72 (1): 62–5. doi:10.1128/IAI.72.1.62-65.2004. PMID 14688081. PMC 343964. http://iai.asm.org/cgi/pmidlookup?view=long&pmid=14688081.  
  4. ^ van der Werf TS, Stinear T, Stienstra Y, van der Graaf WT, Small PL (September 2003). "Mycolactones and Mycobacterium ulcerans disease". Lancet 362 (9389): 1062–4. doi:10.1016/S0140-6736(03)14417-0. PMID 14522538. http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(03)14417-0.  
  5. ^ Adusumilli S, Mve-Obiang A, Sparer T, Meyers W, Hayman J, Small PL (September 2005). "Mycobacterium ulcerans toxic macrolide, mycolactone modulates the host immune response and cellular location of M. ulcerans in vitro and in vivo". Cell. Microbiol. 7 (9): 1295–304. doi:10.1111/j.1462-5822.2005.00557.x. PMID 16098217. http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=1462-5814&date=2005&volume=7&issue=9&spage=1295.  
  6. ^ "A first: scientists isolate, characterize the organism that causes Buruli ulcer". EurekAlert! (Public Library of Science). 2008-03-25. http://www.eurekalert.org/pub_releases/2008-03/plos-afs031908.php#. Retrieved 2008-03-27.  
  7. ^ Herbinger K-H, Adjei O, Awua‐Boateng N-Y, et al. (2009). "Comparative study of the sensitivity of different diagnostic methods for the laboratory diagnosis of Buruli ulcer disease". Clin Infect Dis 48: 1055–1064. doi:10.1086/597398.  
  8. ^ French Clay Can Kill MRSA And 'Flesh-Eating' Bacteria
  9. ^ Meyers WM, Shelly WM, Connor DH (September 1974). "Heat treatment of Mycobacterium ulcerans infections without surgical excision". Am. J. Trop. Med. Hyg. 23 (5): 924–9. PMID 4451233. http://www.ajtmh.org/cgi/pmidlookup?view=long&pmid=4451233.  
  10. ^ WHO, (2000) Buruli ulcer: Mycobacterium ulcerans infection. Geneva
  11. ^ Amofah, G.K., Bonsu, F., Tetteh, C., Okrah, J., Asamoa, K., Asiedu, K. and Addy, J. (2002) Results of a National Case Search. Emerging Infectious Diseases; Vol. 8: 167-170

References

  • MacCallum P, Tolhurst JC, Buckle G, Sissons HA (1948). "A New Mycobacterial Infection in Man". J Pathol Bacteriol 60 (1): 93–122. doi:10.1002/path.1700600111.  

External links

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