Background Buruli ulcer (BU) caused by Mycobacterium ulcerans is a necrotizing skin disease usually starting with a subcutaneous nodule or plaque, which may ulcerate and progress, if untreated, over months and years. During the currently recommended antibiotic treatment with rifampicin/streptomycin plaque lesions tend to ulcerate, often associated with retarded wound healing and prolonged hospital stays. Methodology/Principal Findings Included in this study were twelve laboratory reconfirmed, HIV negative BU patients presenting with plaque lesions at the CDTUB in Allada, Benin. Punch biopsies for histopathological and immunohistochemical analysis were taken before start of treatment and after four to five weeks of treatment. Where excision or wound debridement was clinically indicated, the removed tissue was also analyzed. Based on clinical judgment, nine of the twelve patients enrolled in this study received limited surgical excision seven to 39 days after completion of chemotherapy, followed by skin grafting. Lesions of three patients healed without further intervention. Before treatment, plaque lesions were characterized by a destroyed subcutis with extensive necrosis without major signs of infiltration. After completion of antibiotic treatment partial infiltration of the affected tissue was observed, but large necrotic areas remained unchanged. Conclusion/Significance Our histopathological analyses show that ulceration of plaque lesions during antibiotic treatment do not represent a failure to respond to antimycobacterial treatment. Based on our results we suggest formal testing in a controlled clinical trial setting whether limited surgical excision of necrotic tissue favours wound healing and can reduce the duration of hospital stays.
References
[1]
Asiedu K, Scherpbier R, Raviglione M (2000) Buruli ulcer: Mycobacterium ulcerans infection. Geneva: World Health Organization.
van der Werf TS, Stienstra Y, Johnson RC, Phillips R, Adjei O, et al. (2005) Mycobacterium ulcerans disease. Bull World Health Organ 83: 785–791. doi:/S0042-96862005001000016.
[4]
Thangaraj HS, Evans MR, Wansbrough-Jones MH (1999) Mycobacterium ulcerans disease; Buruli ulcer. Trans R Soc Trop Med Hyg 93: 337–340. doi: 10.1016/S0035-9203(99)90104-9
[5]
Johnson PDR, Stinear T, Small PLC, Pluschke G, Merritt RW, et al. (2005) Buruli ulcer (M. ulcerans infection): new insights, new hope for disease control. PLoS Med 2: e108. doi:10.1371/journal.pmed.0020108.
World Health organisation. (2004) Provisional guidance on the role of specific antibiotics in the managment of Mycobacterium ulcerans disease. Geneva.
[8]
Etuaful S, Carbonnelle B, Grosset J, Lucas S, Horsfield C, et al. (2005) Efficacy of the combination rifampin-streptomycin in preventing growth of Mycobacterium ulcerans in early lesions of Buruli ulcer in humans. Antimicrob Agents Chemother 49: 3182–3186. doi:10.1128/AAC.49.8.3182-3186.2005.
[9]
Kibadi K, Boelaert M, Fraga AG, Kayinua M, Longatto-Filho A, et al. (2010) Response to treatment in a prospective cohort of patients with large ulcerated lesions suspected to be Buruli Ulcer (Mycobacterium ulcerans disease). PLoS Negl Trop Dis 4: e736. doi:10.1371/journal.pntd.0000736.
[10]
Chauty A, Ardant M-F, Adeye A, Euverte H, Guedenon A, et al. (2007) Promising Clinical Efficacy of Streptomycin-Rifampin Combination for Treatment of Buruli Ulcer (Mycobacterium ulcerans Disease). Antimicrob. Agents Chemother 51: 4029–4035. doi: 10.1128/aac.00175-07
[11]
Nienhuis WA, Stienstra Y, Thompson WA, Awuah PC, Abass KM, et al. (2010) Antimicrobial treatment for early, limited Mycobacterium ulcerans infection: a randomised controlled trial. Lancet 375: 664–672. doi:10.1016/S0140-6736(09)61962-0.
[12]
Sarfo FS, Phillips R, Asiedu K, Ampadu E, Bobi N, et al. (2010) Clinical efficacy of combination of rifampin and streptomycin for treatment of Mycobacterium ulcerans disease. Antimicrob. Agents Chemother 54: 3678–3685. doi:10.1128/AAC.00299-10.
[13]
Gordon CL, Buntine JA, Hayman JA, Lavender CJ, Fyfe JAM, et al. (n.d.) All-Oral Antibiotic Treatment for Buruli Ulcer: A Report of Four Patients. PLoS Negl Trop Dis 4: doi:10.1371/journal.pntd.0000770.
[14]
Schütte D, Um-Boock A, Mensah-Quainoo E, Itin P, Schmid P, et al. (2007) Development of highly organized lymphoid structures in Buruli ulcer lesions after treatment with rifampicin and streptomycin. PLoS Negl Trop Dis 1: e2. doi:10.1371/journal.pntd.0000002.
[15]
O'Brien DP, Robson ME, Callan PP, McDonald AH (2009) “Paradoxical” immune-mediated reactions to Mycobacterium ulcerans during antibiotic treatment: a result of treatment success, not failure. Med J Aust 191: 564–566.
[16]
Rondini S, Horsfield C, Mensah-Quainoo E, Junghanss T, Lucas S, et al. (2006) Contiguous spread of Mycobacterium ulcerans in Buruli ulcer lesions analysed by histopathology and real-time PCR quantification of mycobacterial DNA. The Journal of Pathology 208: 119–128. doi: 10.1002/path.1864
[17]
Schütte D, UmBoock A, Pluschke G (2009) Phagocytosis of Mycobacterium ulcerans in the course of rifampicin and streptomycin chemotherapy in Buruli ulcer lesions. British Journal of Dermatology 160: 273–283. doi: 10.1111/j.1365-2133.2008.08879.x
[18]
WHO (2001) Buruli Ulcer. Diagnosis of Mycobacterium ulcerans disease (eds F Portaels, P Johnson, WM Meyers). WHO/CDS/CPE/GBUI/2001. 4.
[19]
Broughton G, Janis JE, Attinger CE (2006) The basic science of wound healing. Plast Reconstr Surg 117: 12S–34S. doi:10.1097/01.prs.0000225430.42531.c2.
[20]
Cornell RS, Meyr AJ, Steinberg JS, Attinger CE (2010) Débridement of the noninfected wound. J Vasc Surg 52: 31S–36S. doi:10.1016/j.jvs.2010.06.006.
[21]
Attinger CE, Janis JE, Steinberg J, Schwartz J, Al-Attar A, et al. (2006) Clinical approach to wounds: débridement and wound bed preparation including the use of dressings and wound-healing adjuvants. Plast Reconstr Surg 117: 72S–109S. doi:10.1097/01.prs.0000225470.42514.8f.
