Background
Buruli ulcer, also known as Bairnsdale ulcer, Daintree ulcer, Mossman ulcer, and Searl ulcer, is a chronic, indolent, necrotizing disease of the skin and soft tissue. Buruli ulcer is the third most common mycobacterial disease of immunocompetent hosts, after tuberculosis and leprosy, and is caused by toxin-producing mycobacteria named Mycobacterium ulcerans.[1] Buruli ulcer generally begins as a painless dermal papule or subcutaneous nodule, which, over a period of weeks to months, breaks down to form a necrotic ulcer with extensively undermined edges. Lesions heal with scarring, which is a significant source of morbidity.
Buruli ulcer was first described by Sir Albert Cook in patients from Buruli County in Uganda, and the causative organism was isolated in 1948 by MacCallum in the Bairnsdale region of Victoria, Australia. Over the last 2 decades, a reemergence of cases has occurred, leading to the 1998 World Health Organization (WHO)[2] Buruli Ulcer Initiative and the Fifty-Seventh World Health Assembly Resolution on Buruli Ulcer, which have stimulated ongoing research into diagnosis, pathogenesis, and effective treatment.[3, 4]
Pathophysiology
M ulcerans are slow-growing mycobacteria that affect the skin and the mucous membranes. The organism produces a soluble polyketide toxin called mycolactone. Mycolactone has both immunosuppressive properties and cytotoxic properties, which explains the lack of host symptoms, such as fever, malaise, or adenopathy.[5, 6] Mycolactone is responsible for the extensive tissue necrosis seen in Buruli ulcers.
Mycolactone has been shown to induce apoptosis without inducing inflammation.[7] Thus, M ulcerans does not cause the same degree of inflammation associated with other mycobacterial infections, such as Mycobacterium leprae and Mycobacterium tuberculosis.
Genetic susceptibility is a possibility, associated with the SCLC11A1 (NRAMP1) D543 polymorphism.[8]
Epidemiology
Frequency
United States
Three cases have been diagnosed in the United States, all of which originated from outside the United States.
International
Buruli ulcers have been reported in more than 30 countries. The largest number of endemic cases occur in countries in central and western Africa, such as Zaire, Congo, Cameroon, Nigeria, Benin,[9] Ghana,[10] Togo,[11] Liberia, and the Ivory Coast. Other involved geographic areas include Australia, Southeast Asia, and sporadic cases in Central America and South America. Subtropical and swampy terrain are major endemic foci for M ulcerans.
Mortality/Morbidity
Buruli ulcer has a low mortality rate; however, it is a significant source of morbidity and socioeconomic burden. Skin and soft tissue necrosis can be extensive, involving as much as 15% of the patient's skin surface. Note the image below.
Buruli ulcer can extend to 15% of a person's skin surface and may destroy nerves and blood vessels. Metastatic bone lesions may develop. The infection may extend deep, exposing fascia, muscle, and bone. More than half the affected individuals are left with a functional limitation. The scarring can be disfiguring and can have a significant emotional impact on patients. Treatment involves long hospital stays, antibiotic regimens, and surgical procedures, which are resources often limited in endemic areas.
Race
No specific racial predilection is known.
Sex
No differences exist in the rates of infection among males and females.
Age
Cases most commonly occur in children ages 5-15 years, except in Australia, where Buruli ulcer is more prevalent in adults older than 50 years; however, Buruli ulcer may affect any age group.
Sizaire V, Nackers F, Comte E, Portaels F. Mycobacterium ulcerans infection: control, diagnosis, and treatment. Lancet Infect Dis. May 2006;6(5):288-96. [Medline].
World Health Organization. Buruli ulcer disease (Mycobacterium ulcerans infection). World Health Organization. Available at http://www.who.int/mediacentre/factsheets/fs199/en/. Accessed December 3, 2008.
Walsh DS, Portaels F, Meyers WM. Buruli ulcer (Mycobacterium ulcerans infection). Trans R Soc Trop Med Hyg. Oct 2008;102(10):969-78. [Medline].
Wansbrough-Jones M, Phillips R. Buruli ulcer: emerging from obscurity. Lancet. Jun 3 2006;367(9525):1849-58. [Medline].
George KM, Chatterjee D, Gunawardana G, et al. Mycolactone: a polyketide toxin from Mycobacterium ulcerans required for virulence. Science. Feb 5 1999;283(5403):854-7. [Medline].
Pimsler M, Sponsler TA, Meyers WM. Immunosuppressive properties of the soluble toxin from Mycobacterium ulcerans. J Infect Dis. Mar 1988;157(3):577-80. [Medline].
Walsh DS, Meyers WM, Portaels F, et al. High rates of apoptosis in human Mycobacterium ulcerans culture-positive buruli ulcer skin lesions. Am J Trop Med Hyg. Aug 2005;73(2):410-5. [Medline].
Stienstra Y, van der Werf TS, Oosterom E, et al. Susceptibility to Buruli ulcer is associated with the SLC11A1 (NRAMP1) D543N polymorphism. Genes Immun. Apr 2006;7(3):185-9. [Medline].
Guedenom A, Zinsou C, Josse R, et al. Traditional treatment of Buruli ulcer in Benin. Arch Dermatol. Jun 1995;131(6):741-2. [Medline].
Aiga H, Amano T, Cairncross S, Adomako J, Nanas OK, Coleman S. Assessing water-related risk factors for Buruli ulcer: a case-control study in Ghana. Am J Trop Med Hyg. Oct 2004;71(4):387-92. [Medline].
Meyers WM, Tignokpa N, Priuli GB, Portaels F. Mycobacterium ulcerans infection (Buruli ulcer): first reported patients in Togo. Br J Dermatol. Jun 1996;134(6):1116-21. [Medline].
Eddyani M, Ofori-Adjei D, Teugels G, et al. Potential role for fish in transmission of Mycobacterium ulcerans disease (Buruli ulcer): an environmental study. Appl Environ Microbiol. Sep 2004;70(9):5679-81. [Medline].
Marsollier L, Severin T, Aubry J, et al. Aquatic snails, passive hosts of Mycobacterium ulcerans. Appl Environ Microbiol. Oct 2004;70(10):6296-8. [Medline].
Marsollier L, Stinear T, Aubry J, et al. Aquatic plants stimulate the growth of and biofilm formation by Mycobacterium ulcerans in axenic culture and harbor these bacteria in the environment. Appl Environ Microbiol. Feb 2004;70(2):1097-103. [Medline].
Raghunathan PL, Whitney EA, et al. Risk factors for Buruli ulcer disease (Mycobacterium ulcerans Infection): results from a case-control study in Ghana. Clin Infect Dis. May 15 2005;40(10):1445-53. [Medline].
Meyers WM, Shelly WM, Connor DH, Meyers EK. Human Mycobacterium ulcerans infections developing at sites of trauma to skin. Am J Trop Med Hyg. Sep 1974;23(5):919-23. [Medline].
Johnson PD, Azuolas J, Lavender CJ, et al. Mycobacterium ulcerans in mosquitoes captured during outbreak of Buruli ulcer, southeastern Australia. Emerg Infect Dis. Nov 2007;13(11):1653-60. [Medline].
Phillips R, Horsfield C, Kuijper S, et al. Sensitivity of PCR targeting the IS2404 insertion sequence of Mycobacterium ulcerans in an Assay using punch biopsy specimens for diagnosis of Buruli ulcer. J Clin Microbiol. Aug 2005;43(8):3650-6. [Medline].
Rondini S, Mensah-Quainoo E, Junghanss T, Pluschke G. What does detection of Mycobacterium ulcerans DNA in the margin of an excised Buruli ulcer lesion tell us?. J Clin Microbiol. Nov 2006;44(11):4273-5. [Medline].
Siegmund V, Adjei O, Nitschke J, et al. Dry reagent-based polymerase chain reaction compared with other laboratory methods available for the diagnosis of Buruli ulcer disease. Clin Infect Dis. Jul 1 2007;45(1):68-75. [Medline].
Leigheb G, Cammarota T, Zavattaro E, et al. Ultrasonography for the monitoring of subcutaneous damage in Mycobacterium ulcerans infection (Buruli ulcer). Ultrasound Med Biol. Oct 2008;34(10):1554-63. [Medline].
Chauty A, Ardant MF, Adeye A, et al. Promising clinical efficacy of streptomycin-rifampin combination for treatment of buruli ulcer (Mycobacterium ulcerans disease). Antimicrob Agents Chemother. Nov 2007;51(11):4029-35. [Medline].
Etuaful S, Carbonnelle B, Grosset J, et al. Efficacy of the combination rifampin-streptomycin in preventing growth of Mycobacterium ulcerans in early lesions of Buruli ulcer in humans. Antimicrob Agents Chemother. Aug 2005;49(8):3182-6. [Medline].
World Health Organization. Provisional guidance on the role of specific antibiotics in the management of Mycobacterium ulcerans disease (Buruli ulcer). World Health Organization. Available at http://www.who.int/buruli/information/antibiotics/en/. Accessed December 3, 2008.
Johnson PD, Hayman JA, Quek TY, et al. Consensus recommendations for the diagnosis, treatment and control of Mycobacterium ulcerans infection (Bairnsdale or Buruli ulcer) in Victoria, Australia. Med J Aust. Jan 15 2007;186(2):64-8. [Medline].
[Best Evidence] Nienhuis WA, Stienstra Y, Thompson WA, et al. Antimicrobial treatment for early, limited Mycobacterium ulcerans infection: a randomised controlled trial. Lancet. Feb 20 2010;375(9715):664-72. [Medline].
Meyers WM, Shelly WM, Connor DH. Heat treatment of Mycobacterium ulcerans infections without surgical excision. Am J Trop Med Hyg. Sep 1974;23(5):924-9. [Medline].
Krieg RE, Wolcott JH, Confer A. Treatment of Mycobacterium ulcerans infection by hyperbaric oxygenation. Aviat Space Environ Med. Oct 1975;46(10):1241-5. [Medline].
Phillips R, Adjei O, Lucas S, Benjamin N, Wansbrough-Jones M. Pilot randomized double-blind trial of treatment of Mycobacterium ulcerans disease (Buruli ulcer) with topical nitrogen oxides. Antimicrob Agents Chemother. Aug 2004;48(8):2866-70. [Medline].
Nackers F, Dramaix M, Johnson RC, et al. BCG vaccine effectiveness against Buruli ulcer: a case-control study in Benin. Am J Trop Med Hyg. Oct 2006;75(4):768-74. [Medline].
van der Werf TS, Stienstra Y, Johnson RC, et al. Mycobacterium ulcerans disease. Bull World Health Organ. Oct 2005;83(10):785-91. [Medline].
Bretzel G, Siegmund V, Racz P, et al. Post-surgical assessment of excised tissue from patients with Buruli ulcer disease: progression of infection in macroscopically healthy tissue. Trop Med Int Health. Nov 2005;10(11):1199-206. [Medline].
Minutilli E, Orefici G, Pardini M, et al. Squamous cell carcinoma secondary to buruli ulcer. Dermatol Surg. Jul 2007;33(7):872-5. [Medline].
Connor DH, Meyers WM, Kreig RE. Infection by Mycobacterium ulcerans. In: Binford CH, Connor DH, eds. Pathology of Tropical and Extraordinary Diseases. Washington, DC: Armed Forces Institute of Pathology; 1976:226-35.
Health Section of the Secretariat of the League of Nations. Buruli ulcer disease. Wkly Epidemiol Rec. May 14 2004;79(20):194-9. [Medline].
Meyers WM. Atypical mycobacteria skin infections. In: Strickland GT, ed. Hunter's Tropical Medicine. Philadelphia, Pa: WB Saunders; 1991:495-6.
Prevot G, Bourreau E, Pascalis H, et al. Differential production of systemic and intralesional gamma interferon and interleukin-10 in nodular and ulcerative forms of Buruli disease. Infect Immun. Feb 2004;72(2):958-65. [Medline].
Stienstra Y, van der Werf TS, van der Graaf WT, et al. Buruli ulcer and schistosomiasis: no association found. Am J Trop Med Hyg. Sep 2004;71(3):318-21. [Medline].
Wagner D, Young LS. Nontuberculous mycobacterial infections: a clinical review. Infection. Oct 2004;32(5):257-70. [Medline].
| Category | Form of Disease | Treatment | Primary Aim | Secondary Aim | level of Health Care System | Diagnosis |
| I | Small early lesion (eg, nodules, papules, plaques, ulcers < 5 cm in diameter) | For papules and nodules, if immediate excision and suturing is possible, start antibiotics at least 24 hours before surgery and continue for 4 weeks. Otherwise, treat all lesions in this category with antibiotics for 8 weeks. | Cure without surgery except for simple removal of dead tissue | Reduce or prevent recurrence | Community health centers and district hospitals | Clinical and laboratory |
| II | Nonulcerative and ulcerative plaque and edematous forms Large ulcerative lesions (>5 cm in diameter) Lesions in the head and neck region, particularly the face | Treat with antibiotics for at least 4 weeks, then surgery (if necessary), followed by another 4 weeks of antibiotics. | Reduce extent of the surgical excision | Reduce or prevent recurrence | District and tertiary hospitals | Clinical and laboratory |
| III | Disseminated/mixed forms (eg, osteitis, osteomyelitis, joint involvement) | Treat with antibiotics for at least 1 week before surgery and continue for a total of 8 weeks. | Reduce M ulcers infection and dissemination before and after surgery | Reduce or prevent recurrence; reduce extent of surgical excision | District and tertiary hospitals | Clinical and laboratory |
| From " Provisional guidance on the role of specific antibiotics in the management of Mycobacterium ulcerans disease (Buruli ulcer). "[24] | ||||||

