Buruli Ulcer
No Results
No Results
processing….
Buruli ulcer, caused by Mycobacterium ulcerans, is a chronic, debilitating, necrotizing disease of the skin and soft tissue. Buruli ulcer is an emerging infectious disease and is the third most common mycobacterial disease of the immunocompetent host, after tuberculosis and leprosy. [1] Although it has been reported in over 33 countries around the world, the greatest burden of disease is in the tropical regions of West and Central Africa, Australia, and Japan. [2] It primarily affects children aged 5-15 years. [2] Buruli ulcers generally begin as a painless dermal papule or subcutaneous edematous nodule, which, over a period of weeks to months, breaks down to form an extensive necrotic ulcer with undermined edges. Treatment includes a prolonged course of antibiotics and surgical debridement. Early identification and treatment are key, as lesions heal with scarring that can be a significant source of morbidity. Other names for this entity include Bairnsdale ulcer, Daintree ulcer, Mossman ulcer, and Searl ulcer. Note the image below.
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. A reemergence of cases led the 1998 World Health Organization (WHO) to reclassify Buruli ulcer as a “neglected emerging infectious disease,” which has stimulated ongoing research into diagnosis, pathogenesis, and effective treatment. [3, 4, 5]
M ulcerans are slow-growing mycobacteria that produce a soluble polyketide exotoxin called mycolactone, which can diffuse extensively in the subcutaneous tissue. Because mycolactone has both immunosuppressive properties and cytotoxic properties, dramatic tissue destruction occurs without inducing inflammation or systemic symptoms, such as fever, malaise, or adenopathy. [6, 7, 8, 9, 10] Mycolactone was first identified in 1999. Research has revealed the mechanisms of action of mycolactone, as described below.
Mycolactone targets scaffolding proteins, such as the Wiskott-Aldrich syndrome protein (WASP), [11] which controls actin dynamics and leads to a loss of cellular detachments and cell death. [12]
Mycolactone also inhibits the function of the Sec61 translocation, which is responsible for protein translocation into the endoplasmic reticulum. This affects 30-50% of mammalian proteins, including circulating inflammatory mediators and proteins involved in lipid metabolism, coagulation, and tissue remodeling. [13] Therefore, patients with M ulcerans infections have global and chronic defects in protein metabolism. This is evident by reduced levels of total serum proteins and blood urea nitrogen, without the presence of malnutrition, kidney impairment, or liver impairment. [13]
Buruli ulcers are traditionally thought to be painless ulcers. Research has shown that the hypoalgesic effect occurs via activation of the angiotensin II type 2 receptor (AT2R), leading to neurite degeneration and cell death. [14] Another prominent feature of Buruli ulcers is extensive coagulative necrosis caused by mycolactone.
Ogbechi et al showed that mycolactone decreased thrombomodulin expression on the surface of human dermal microvascular endothelial cells, thereby impairing the activation of protein C. This study also showed that fibrin deposition is a prominent feature of these ulcers and the tissue necrosis could be caused by fibrin-driven ischemia. [15]
Genetic susceptibility may be associated with the SCLC11A1 (NRAMP1) D543 polymorphism. [16]
According to the World Health Organization (WHO), as of 2015, there have been no cases of confirmed Buruli ulcers originating in the United States. [3]
Approximately 6000 cases are reported annually around the world, especially from rural Africa. [3]
Buruli ulcers have been reported in 33 countries. The largest number of endemic cases occur in countries in central and western Africa, such as Côte d’Ivoire, Benin, Ghana, Democratic Republic of the Congo, Cameroon, Nigeria, Togo, and Liberia. Other involved geographic areas include Australia, Papa New Guinea, Japan, and sporadic cases in Central and South America. Subtropical and swampy terrain are major endemic foci for M ulcerans.
No specific racial predilection is known.
No differences exist in the rates of infection among males and females.
Buruli ulcer may affect any age group, but most cases occur in children ages 5-15 years, except in Australia, where Buruli ulcer is more prevalent in adults older than 50 years. [17]
Most patients have complete healing, with or without significant scarring or impairment. Even with medical and surgical care, patients often require hospitalizations averaging 3 months. The best prognosis occurs when treatment is instituted as early as possible before significant tissue destruction can occur. Without medical care, more than half the affected individuals are left with a functional limitation. The scarring can be disfiguring and can have a significant emotional and socioeconomic impact on patients. Treatment involves long hospital stays (average of 3 months), antibiotic regimens, and surgical procedures, which are resources often limited in endemic areas. [18]
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 and may extend deep, exposing fascia, muscle, and bone.
When Buruli ulcers are identified early and treated appropriately, the prognosis is good. Klis et al found that 85% of patients who presented with small lesions and who received 8 weeks of antibiotics indicated no effect, or only a small effect, of the disease on their current life at long-term follow up visits. [19] The median score on the Dermatology Life Quality Index was 0 (range, 0-4), indicating a good quality of life. [19] These results highlight the importance of early identification and treatment, in stark contrast with the debilitating contracted scars that result if these ulcers are not treated in a timely manner.
The majority of the systemic complications from Buruli ulcers are from the toxicities of long-term antibiotic use. See Treatment/Complications section.
Elderly patients have a tendency towards more severe disease and increased complications from treatment. [17]
Sizaire V, Nackers F, Comte E, Portaels F. Mycobacterium ulcerans infection: control, diagnosis, and treatment. Lancet Infect Dis. 2006 May. 6(5):288-96. [Medline].
Yotsu RR, Murase C, Sugawara M, Suzuki K, Nakanaga K, Ishii N, et al. Revisiting Buruli ulcer. J Dermatol. 2015 Nov. 42 (11):1033-41. [Medline].
World Health Organization. Buruli ulcer disease (Mycobacterium ulcerans infection). World Health Organization. Available at http://www.who.int/mediacentre/factsheets/fs199/en/. Accessed: 8/13/2016.
Walsh DS, Portaels F, Meyers WM. Buruli ulcer (Mycobacterium ulcerans infection). Trans R Soc Trop Med Hyg. 2008 Oct. 102(10):969-78. [Medline].
Wansbrough-Jones M, Phillips R. Buruli ulcer: emerging from obscurity. Lancet. 2006 Jun 3. 367(9525):1849-58. [Medline].
George KM, Chatterjee D, Gunawardana G, et al. Mycolactone: a polyketide toxin from Mycobacterium ulcerans required for virulence. Science. 1999 Feb 5. 283(5403):854-7. [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. 2005 Aug. 73(2):410-5. [Medline].
Pimsler M, Sponsler TA, Meyers WM. Immunosuppressive properties of the soluble toxin from Mycobacterium ulcerans. J Infect Dis. 1988 Mar. 157(3):577-80. [Medline].
Phillips R, Sarfo FS, Guenin-Macé L, Decalf J, Wansbrough-Jones M, Albert ML, et al. Immunosuppressive signature of cutaneous Mycobacterium ulcerans infection in the peripheral blood of patients with buruli ulcer disease. J Infect Dis. 2009 Dec 1. 200(11):1675-84. [Medline].
Boleira M, Lupi O, Lehman L, Asiedu KB, Kiszewski AE. Buruli ulcer. An Bras Dermatol. 2010 Jun. 85(3):281-298; quiz 299-301. [Medline]. [Full Text].
Guenin-Macé L, Veyron-Churlet R, Thoulouze MI, Romet-Lemonne G, Hong H, Leadlay PF, et al. Mycolactone activation of Wiskott-Aldrich syndrome proteins underpins Buruli ulcer formation. J Clin Invest. 2013 Apr 1. 123(4):1501-12. [Medline]. [Full Text].
Sarfo FS, Phillips R, Wansbrough-Jones M, Simmonds RE. Recent advances: role of mycolactone in the pathogenesis and monitoring of Mycobacterium ulcerans infection/Buruli ulcer disease. Cell Microbiol. 2016 Jan. 18 (1):17-29. [Medline].
Phillips RO, Sarfo FS, Landier J, Oldenburg R, Frimpong M, Wansbrough-Jones M, et al. Combined inflammatory and metabolic defects reflected by reduced serum protein levels in patients with Buruli ulcer disease. PLoS Negl Trop Dis. 2014 Apr. 8 (4):e2786. [Medline].
Anand U, Sinisi M, Fox M, MacQuillan A, Quick T, Korchev Y, et al. Mycolactone-mediated neurite degeneration and functional effects in cultured human and rat DRG neurons: Mechanisms underlying hypoalgesia in Buruli ulcer. Mol Pain. 2016. 12:[Medline].
Ogbechi J, Ruf MT, Hall BS, Bodman-Smith K, Vogel M, Wu HL, et al. Mycolactone-Dependent Depletion of Endothelial Cell Thrombomodulin Is Strongly Associated with Fibrin Deposition in Buruli Ulcer Lesions. PLoS Pathog. 2015 Jul. 11 (7):e1005011. [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. 2006 Apr. 7(3):185-9. [Medline].
O’Brien DP, Friedman ND, Cowan R, Pollard J, McDonald A, Callan P, et al. Mycobacterium ulcerans in the Elderly: More Severe Disease and Suboptimal Outcomes. PLoS Negl Trop Dis. 2015 Dec. 9 (12):e0004253. [Medline].
Chany AC, Tresse C, Casarotto V, Blanchard N. History, biology and chemistry of Mycobacterium ulcerans infections (Buruli ulcer disease). Nat Prod Rep. 2013 Dec. 30(12):1527-67. [Medline].
Klis S, Ranchor A, Phillips RO, Abass KM, Tuah W, Loth S, et al. Good quality of life in former Buruli ulcer patients with small lesions: long-term follow-up of the BURULICO trial. PLoS Negl Trop Dis. 2014 Jul. 8 (7):e2964. [Medline].
Trubiano JA, Lavender CJ, Fyfe JA, Bittmann S, Johnson PD. The incubation period of Buruli ulcer (Mycobacterium ulcerans infection). PLoS Negl Trop Dis. 2013. 7(10):e2463. [Medline]. [Full Text].
Landier J, Constantin de Magny G, Garchitorena A, Guégan JF, Gaudart J, Marsollier L, et al. Seasonal Patterns of Buruli Ulcer Incidence, Central Africa, 2002-2012. Emerg Infect Dis. 2015 Aug. 21 (8):1414-7. [Medline].
Vogel M, Bayi PF, Ruf MT, Bratschi MW, Bolz M, Um Boock A, et al. Local Heat Application for the Treatment of Buruli Ulcer: Results of a Phase II Open Label Single Center Non Comparative Clinical Trial. Clin Infect Dis. 2016 Feb 1. 62 (3):342-50. [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. 2004 Sep. 70(9):5679-81. [Medline].
Marsollier L, Severin T, Aubry J, et al. Aquatic snails, passive hosts of Mycobacterium ulcerans. Appl Environ Microbiol. 2004 Oct. 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. 2004 Feb. 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. 2005 May 15. 40(10):1445-53. [Medline].
N’krumah RT, Koné B, Tiembre I, Cissé G, Pluschke G, Tanner M, et al. Socio-Environmental Factors Associated with the Risk of Contracting Buruli Ulcer in Tiassalé, South Côte d’Ivoire: A Case-Control Study. PLoS Negl Trop Dis. 2016 Jan. 10 (1):e0004327. [Medline].
Jacobsen KH, Padgett JJ. Risk factors for Mycobacterium ulcerans infection. Int J Infect Dis. 2010 Aug. 14(8):e677-81. [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. 1974 Sep. 23(5):919-23. [Medline].
Landier J, Boisier P, Fotso Piam F, Noumen-Djeunga B, Simé J, Wantong FG, et al. Adequate wound care and use of bed nets as protective factors against Buruli Ulcer: results from a case control study in Cameroon. PLoS Negl Trop Dis. 2011 Nov. 5(11):e1392. [Medline]. [Full Text].
Johnson PD, Azuolas J, Lavender CJ, et al. Mycobacterium ulcerans in mosquitoes captured during outbreak of Buruli ulcer, southeastern Australia. Emerg Infect Dis. 2007 Nov. 13(11):1653-60. [Medline].
Fyfe JA, Lavender CJ, Handasyde KA, Legione AR, O’Brien CR, Stinear TP, et al. A major role for mammals in the ecology of Mycobacterium ulcerans. PLoS Negl Trop Dis. 2010 Aug 10. 4(8):e791. [Medline]. [Full Text].
Merritt RW, Walker ED, Small PL, Wallace JR, Johnson PD, Benbow ME, et al. Ecology and transmission of Buruli ulcer disease: a systematic review. PLoS Negl Trop Dis. 2010 Dec 14. 4(12):e911. [Medline]. [Full Text].
Wilson MD, Boakye DA, Mosi L, Asiedu K. In the case of transmission of mycobacterium ulcerans in buruli ulcer disease acanthamoeba species stand accused. Ghana Med J. 2011 Mar. 45(1):31-4. [Medline].
Ohtsuka M, Kikuchi N, Yamamoto T, Suzutani T, Nakanaga K, Suzuki K, et al. Buruli ulcer caused by Mycobacterium ulcerans subsp shinshuense: a rare case of familial concurrent occurrence and detection of insertion sequence 2404 in Japan. JAMA Dermatol. 2014 Jan. 150 (1):64-7. [Medline].
Silva MT, Portaels F, Pedrosa J. Pathogenetic mechanisms of the intracellular parasite Mycobacterium ulcerans leading to Buruli ulcer. Lancet Infect Dis. 2009 Nov. 9(11):699-710. [Medline].
[Guideline] Guidance on sampling techniques for laboratory-confirmation of Mycobacterium ulcerans infection (Buruli ulcer disease). Available at http://www.who.int/buruli/Guidance_sampling_techniques_MU_infection.pdf?ua=1.
O’Brien DP, Walton A, Hughes AJ, Friedman ND, McDonald A, Callan P, et al. Risk factors for recurrent Mycobacterium ulcerans disease after exclusive surgical treatment in an Australian cohort. Med J Aust. 2013 May 6. 198(8):436-9. [Medline].
Mueller YK, Bastard M, Nkemenang P, Comte E, Ehounou G, Eyangoh S, et al. The “Buruli Score”: Development of a Multivariable Prediction Model for Diagnosis of Mycobacterium ulcerans Infection in Individuals with Ulcerative Skin Lesions, Akonolinga, Cameroon. PLoS Negl Trop Dis. 2016 Apr. 10 (4):e0004593. [Medline].
Pommelet V, Vincent QB, Ardant MF, Adeye A, Tanase A, Tondeur L, et al. Findings in patients from Benin with osteomyelitis and polymerase chain reaction-confirmed Mycobacterium ulcerans infection. Clin Infect Dis. 2014 Nov 1. 59 (9):1256-64. [Medline].
Ruf MT, Bolz M, Vogel M, Bayi PF, Bratschi MW, Sopho GE, et al. Spatial Distribution of Mycobacterium ulcerans in Buruli Ulcer Lesions: Implications for Laboratory Diagnosis. PLoS Negl Trop Dis. 2016 Jun. 10 (6):e0004767. [Medline].
Walsh DS, Portaels F, Meyers WM. Buruli ulcer: Advances in understanding Mycobacterium ulcerans infection. Dermatol Clin. 2011 Jan. 29(1):1-8. [Medline].
Herbinger KH, Adjei O, Awua-Boateng NY, Nienhuis WA, Kunaa L, Siegmund V, et al. Comparative study of the sensitivity of different diagnostic methods for the laboratory diagnosis of Buruli ulcer disease. Clin Infect Dis. 2009 Apr 15. 48(8):1055-64. [Medline].
Herbinger KH, Beissner M, Huber K, Awua-Boateng NY, Nitschke J, Thompson W, et al. Efficiency of fine-needle aspiration compared with other sampling techniques for laboratory diagnosis of Buruli ulcer disease. J Clin Microbiol. 2010 Oct. 48(10):3732-4. [Medline]. [Full Text].
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. 2005 Aug. 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. 2006 Nov. 44(11):4273-5. [Medline].
Yeboah-Manu D, Asante-Poku A, Asan-Ampah K, Ampadu ED, Pluschke G. Combining PCR with microscopy to reduce costs of laboratory diagnosis of Buruli ulcer. Am J Trop Med Hyg. 2011 Nov. 85(5):900-4. [Medline]. [Full Text].
de Souza DK, Quaye C, Mosi L, Addo P, Boakye DA. A quick and cost effective method for the diagnosis of Mycobacterium ulcerans infection. BMC Infect Dis. Jan 2012. 12:Jan 18. [Medline]. [Full Text].
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. 2007 Jul 1. 45(1):68-75. [Medline].
Gordon CL, Buntine JA, Hayman JA, Lavender CJ, Fyfe JA, Hosking P, et al. All-oral antibiotic treatment for buruli ulcer: a report of four patients. PLoS Negl Trop Dis. 2010 Nov 30. 4(11):e770. [Medline]. [Full Text].
Eddyani M, Vandelannoote K, Meehan CJ, Bhuju S, Porter JL, Aguiar J, et al. A Genomic Approach to Resolving Relapse versus Reinfection among Four Cases of Buruli Ulcer. PLoS Negl Trop Dis. 2015 Nov. 9 (11):e0004158. [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. 2008 Oct. 34(10):1554-63. [Medline].
Guarner J, Bartlett J, Whitney EA, Raghunathan PL, Stienstra Y, Asamoa K, et al. Histopathologic features of Mycobacterium ulcerans infection. Emerg Infect Dis. 2003 Jun. 9 (6):651-656. [Medline].
Converse PJ, Nuermberger EL, Almeida DV, Grosset JH. Treating Mycobacterium ulcerans disease (Buruli ulcer): from surgery to antibiotics, is the pill mightier than the knife?. Future Microbiol. 2011 Oct. 6(10):1185-98. [Medline]. [Full Text].
[Guideline] World Health Organization. Treatment of mycobaterium ulcerans disease (Buruli ulcer): guidance for health workers:. World Health Organization. Available at http://ttp://www.who.int/iris/bitstream/10665/77771/1/9789241503402_eng.pdf. Accessed: March 2013.
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. 2007 Nov. 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. 2005 Aug. 49(8):3182-6. [Medline].
Sarfo FS, Phillips R, Asiedu K, Ampadu E, Bobi N, Adentwe E, et al. Clinical efficacy of combination of rifampin and streptomycin for treatment of Mycobacterium ulcerans disease. Antimicrob Agents Chemother. 2010 Sep. 54(9):3678-85. [Medline]. [Full Text].
Streptomycin: Drug information Lexicomp. UpToDate. Available at https://www.uptodate.com/contents/streptomycin-drug-information?source=search_result&search=streptomycin&selectedTitle=1~101. 2016; Accessed: 08/14/2016.
Nienhuis WA, Stienstra Y, Thompson WA, et al. Antimicrobial treatment for early, limited Mycobacterium ulcerans infection: a randomised controlled trial. Lancet. 2010 Feb 20. 375(9715):664-72. [Medline].
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. 2007 Jan 15. 186(2):64-8. [Medline].
Friedman ND, Athan E, Hughes AJ, Khajehnoori M, McDonald A, Callan P, et al. Mycobacterium ulcerans disease: experience with primary oral medical therapy in an Australian cohort. PLoS Negl Trop Dis. 2013. 7(7):e2315. [Medline]. [Full Text].
Converse PJ, Tyagi S, Xing Y, Li SY, Kishi Y, Adamson J, et al. Efficacy of Rifampin Plus Clofazimine in a Murine Model of Mycobacterium ulcerans Disease. PLoS Negl Trop Dis. 2015. 9 (6):e0003823. [Medline].
Velding K, Klis SA, Abass KM, van der Werf TS, Stienstra Y. The Application of Modern Dressings to Buruli Ulcers: Results from a Pilot Implementation Project in Ghana. Am J Trop Med Hyg. 2016 Jul 6. 95 (1):60-2. [Medline].
Meyers WM, Shelly WM, Connor DH. Heat treatment of Mycobacterium ulcerans infections without surgical excision. Am J Trop Med Hyg. 1974 Sep. 23(5):924-9. [Medline].
Junghanss T, Um Boock A, Vogel M, Schuette D, Weinlaeder H, Pluschke G. Phase change material for thermotherapy of Buruli ulcer: a prospective observational single centre proof-of-principle trial. PLoS Negl Trop Dis. 2009. 3(2):e380. [Medline]. [Full Text].
Krieg RE, Wolcott JH, Confer A. Treatment of Mycobacterium ulcerans infection by hyperbaric oxygenation. Aviat Space Environ Med. 1975 Oct. 46(10):1241-5. [Medline].
Bertolotti A, Izzo A, Grigolato PG, Iabichella ML. The use of ozone therapy in Buruli ulcer had an excellent outcome. BMJ Case Rep. 2013 Jan 31. 2013:[Medline].
Murase C, Kono M, Nakanaga K, Ishii N, Akiyama M. Buruli Ulcer Successfully Treated With Negative-Pressure Wound Therapy. JAMA Dermatol. 2015 Oct. 151 (10):1137-9. [Medline].
Adu E, Ampadu E, Acheampong D. Surgical management of buruli ulcer disease: a four-year experience from four endemic districts in ghana. Ghana Med J. 2011 Mar. 45(1):4-9. [Medline]. [Full Text].
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. 2005 Nov. 10(11):1199-206. [Medline].
Minutilli E, Orefici G, Pardini M, et al. Squamous cell carcinoma secondary to buruli ulcer. Dermatol Surg. 2007 Jul. 33(7):872-5. [Medline].
Beissner M, Arens N, Wiedemann F, Piten E, Kobara B, Bauer M, et al. Treatment Outcome of Patients with Buruli Ulcer Disease in Togo. PLoS Negl Trop Dis. 2015. 9 (10):e0004170. [Medline].
Pommelet V, Vincent QB, Ardant MF, Adeye A, Tanase A, Tondeur L, et al. Findings in patients from Benin with osteomyelitis and polymerase chain reaction-confirmed Mycobacterium ulcerans infection. Clin Infect Dis. 2014 Nov 1. 59 (9):1256-64. [Medline].
O’Brien DP, Robson ME, Callan PP, McDonald AH. “Paradoxical” immune-mediated reactions to Mycobacterium ulcerans during antibiotic treatment: a result of treatment success, not failure. Med J Aust. 2009 Nov 16. 191(10):564-6. [Medline].
O’Brien DP, Robson M, Friedman ND, Walton A, McDonald A, Callan P, et al. Incidence, clinical spectrum, diagnostic features, treatment and predictors of paradoxical reactions during antibiotic treatment of Mycobacterium ulcerans infections. BMC Infect Dis. 2013 Sep 5. 13:416. [Medline]. [Full Text].
Friedman ND, McDonald AH, Robson ME, O’Brien DP. Corticosteroid use for paradoxical reactions during antibiotic treatment for Mycobacterium ulcerans. PLoS Negl Trop Dis. 2012. 6(9):e1767. [Medline]. [Full Text].
Barogui YT, Klis SA, Johnson RC, Phillips RO, van der Veer E, van Diemen C, et al. Genetic Susceptibility and Predictors of Paradoxical Reactions in Buruli Ulcer. PLoS Negl Trop Dis. 2016 Apr. 10 (4):e0004594. [Medline].
Phillips RO, Frimpong M, Sarfo FS, Kretschmer B, Beissner M, Debrah A, et al. Infection with Mansonella perstans Nematodes in Buruli Ulcer Patients, Ghana. Emerg Infect Dis. 2014 Jun. 20 (6):1000-3. [Medline].
Wanda F, Nkemenang P, Ehounou G, Tchaton M, Comte E, Toutous Trellu L, et al. Clinical features and management of a severe paradoxical reaction associated with combined treatment of Buruli ulcer and HIV co-infection. BMC Infect Dis. 2014 Jul 30. 14:423. [Medline].
Klis S, Stienstra Y, Phillips RO, Abass KM, Tuah W, van der Werf TS. Long term streptomycin toxicity in the treatment of Buruli Ulcer: follow-up of participants in the BURULICO drug trial. PLoS Negl Trop Dis. 2014 Mar. 8 (3):e2739. [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. 2006 Oct. 75(4):768-74. [Medline].
van der Werf TS, Stienstra Y, Johnson RC, et al. Mycobacterium ulcerans disease. Bull World Health Organ. 2005 Oct. 83(10):785-91. [Medline].
Abass KM, van der Werf TS, Phillips RO, Sarfo FS, Abotsi J, Mireku SO, et al. Buruli ulcer control in a highly endemic district in Ghana: role of community-based surveillance volunteers. Am J Trop Med Hyg. 2015 Jan. 92 (1):115-7. [Medline].
Phanzu DM, Suykerbuyk P, Imposo DB, Lukanu PN, Minuku JB, Lehman LF, et al. Effect of a control project on clinical profiles and outcomes in buruli ulcer: a before/after study in Bas-Congo, Democratic Republic of Congo. PLoS Negl Trop Dis. 2011 Dec. 5(12):e1402. [Medline]. [Full Text].
Buruli ulcer: first programme review meeting for west Africa–summary report. Wkly Epidemiol Rec. 2009 Feb 6. 84(6):43-8. [Medline].
Ackumey MM, Kwakye-Maclean C, Ampadu EO, de Savigny D, Weiss MG. Health services for Buruli ulcer control: lessons from a field study in Ghana. PLoS Negl Trop Dis. 2011 Jun. 5(6):e1187. [Medline]. [Full Text].
[Guideline] Valérie Simonet. Prevention of disability in Buruli ulcer:basic rehabilitationPractical field guide. Available at http://whqlibdoc.who.int/hq/2008/WHO_HTM_NTD_IDM_GBUI_2008.1_eng.pdf. Accessed: May 28 2012.
Barclay L. IDSA: skin and soft tissue infections guidelines updated. Medscape Medical News. Available at http://www.medscape.com/viewarticle/827399. Accessed: June 26, 2014.
[Guideline] Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of america. Clin Infect Dis. 2014 Jul 15. 59(2):e10-52. [Medline]. [Full Text].
Method
Pros
Cons
Direct smear examination
• Easy to perform at local level
• Does not require expensive materials and equipment
• Rapid results
• Uses swabs, fine-needle aspiration, and biopsy samples
• Low sensitivity (<60%)
• Needs trained personnel
• Needs external quality assurance
PCR
• Results fairly rapid
• Uses swabs, fine-needle aspiration, and biopsy samples
• High sensitivity (>95%)
• Requires a sophisticated laboratory
• Expensive to perform
• Needs trained personnel
• Requires strict quality control
Culture of M ulcerans
• Uses swabs, fine-needle aspiration, and biopsy samples
• Requires a sophisticated laboratory
• Needs trained personnel
• Results take >8 weeks
• Low sensitivity (20-60%)
• Not useful for immediate patient management
Histopathology
• Sensitivity is about 90%
• Results fairly rapid (if services are available)
• Useful in establishing differential diagnosis and monitoring unexpected response to treatment
• Requires a sophisticated laboratory
• Expensive to perform
• Needs trained personnel
• Requires invasive procedure (ie, biopsy)
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)
Complete antibiotics
If at or near a joint, maintain same movement as on unaffected side
If surgery is needed in noncritical areas, consider this after 8 weeks of antibiotic treatment
Cure without surgery
Cure without movement limitations
Reduce or prevent recurrence
Community health centers and district hospitals
Strong clinical diagnosis (with or without laboratory confirmation)
II
Nonulcerative and ulcerative plaque and edematous forms
Single, large ulcerative lesion 5-15 cm in diameter
Complete antibiotics, before surgery (if possible)
If at or near a joint, maintain same movement as on unaffected side
Cure without surgery
Reduce extent of the surgical debridement when needed
Cure without movement limitations
Reduce or prevent recurrence
Health centers, district and tertiary hospitals
Strong clinical diagnosis (with or without laboratory confirmation)
III
Lesions in the head and neck region, particularly the face
Disseminated/mixed forms (eg, osteitis, osteomyelitis, joint involvement)
Multiple lesions and osteomyelitis
Extensive lesion >15 cm
Complete antibiotics, before surgery (if possible)
If at or near a joint, maintain same movement as on unaffected side
Cure without surgery
Cure without movement limitations
Reduce or prevent recurrence
District and tertiary hospitals
Strong clinical diagnosis (with or without laboratory confirmation)
Shannon C Brown, MD Resident Physician, Department of Dermatology, Texas A&M Health Science Center, Baylor Scott and White Health
Shannon C Brown, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Gold Humanism Honor Society, Society for Pediatric Dermatology, Texas Dermatological Society, Texas Medical Association, Women’s Dermatologic Society
Disclosure: Nothing to disclose.
Kirstin Altman, MD Assistant Professor of Dermatology, Texas A&M Health Science Center College of Medicine
Kirstin Altman, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Texas Dermatological Society
Disclosure: Nothing to disclose.
Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society
Disclosure: Nothing to disclose.
Paul Krusinski, MD Director of Dermatology, Fletcher Allen Health Care; Professor, Department of Internal Medicine, University of Vermont College of Medicine
Paul Krusinski, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, Society for Investigative Dermatology
Disclosure: Nothing to disclose.
William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine
William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology
Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD.
Franklin Flowers, MD Department of Dermatology, Professor Emeritus Affiliate Associate Professor of Pathology, University of Florida College of Medicine
Franklin Flowers, MD is a member of the following medical societies: American College of Mohs Surgery
Disclosure: Nothing to disclose.
Aaron Z Hoover, MD, FAAD Staff Dermatologist/Dermatopathologist, Front Range Dermatology Associates
Aaron Z Hoover, MD, FAAD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Christian Medical and Dental Associations, International Society of Dermatopathology
Disclosure: Nothing to disclose.
Special thanks to Ms Carmen Urich for helping me obtain articles needed to update this publication.
The authors and editors of Medscape Reference gratefully acknowledge the contributions of the following previous authors, Brian P. Green, DO, MS, PA-C; Sean T. Gunning, MD; and Mary K. Mather, MD, to the development and writing of this article.
The authors and editors of Medscape Reference would also like to thank Wayne M. Meyers, MD, for his clinical images from his article with Douglas S. Walsh, MD, in Transactions of the Royal Society of Tropical Medicine and Hygiene. [4]
Buruli Ulcer
Research & References of Buruli Ulcer|A&C Accounting And Tax Services
Source
0 Comments