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individualized treatment for Buruli Ulcer - M. ulcerans inferction
Keywords: tropical medicine Buruli Ulcer
Researchers: Prof. dr. Y. Stienstra prof. dr. T.S. van der Werf
Nature of the research: Clinical research / field work
Fields of study: internal medicine tropical medicine

Background / introduction

Buruli Ulcer Disease (BUD) is a tropical skin disease caused by infection with M. ulcerans. Prolonged infection causes necrotic skin lesions, which can lead to disfigurement and functional limitations. BUD can be treated by antimicrobial therapy. The role of debridement surgery in larger lesions have been questioned by research by our group. Buruli ulcer has been reported in over 30 countries, but the disease is mainly found in endemic areas in rural west- and central-Africa (1).
The current WHO recommended treatment regimen consists of oral 8-week rifampicin plus clarithromycin, and is highly effective, with healing rates over 95% in early, limited cases (2, 3).
Health care facilities in endemic areas are limited, and patients must often walk and wait for hours to receive drugs and dressing changes. The 8 week duration of therapy was chosen based on a single, small sample histo-pathological study (4) in combination with expert opinion.
A chart study conducted at the Nkawie-Toase Buruli Ulcer treatment center in Ghana showed that almost half of the patients treated over five years dropped out during treatment and hence did not receive the 56 recommended drug doses. Defaulting from treatment occurs in high numbers, and it is important to know the reasons for doing so.
It is not known what the effects of shortening antimicrobial therapy are on the healing rates of BUD. Studying these healing rates in patients that defaulted from therapy will provide valuable insights that can guide future research into shortening - or perhaps rather, individualising treatment.

Research question / problem definition
1) What is the healing rate of patients who received less than 56 doses of drugs? 2) What is the level of functional limitations in patients who received less than 56 doses of drugs? 3) What were the reasons for the patient to default from treatment?

Workplan

Records at the Buruli Ulcer treatment center at Nkawie-Toase have been analysed from 2008 up to 2012, and show that through the years, over 100 patients defaulted from treatment. As the administration of a single dosage of streptomycin is marked on a form, we know exactly how many dosages each patient received. Together with the local Buruli Ulcer staff, the student will attempt to trace the patients that have defaulted. Once the patient has been located, the lesion or scar will be assessed (palpation, photography). If the skin is still ulcerated, swabs will be taken for determination of M. ulcerans through q-PCR. In addition, functional limitations will be evaluated by physical examination and a validated questionnaire: the Buruli Ulcer Functional Limitations Scale (BUFLS) (5). Finally the reasons for defaulting will be asked through a structured interview.

References

1 Portaels F, Silva MT, Meyers WM. Buruli ulcer. Clin Dermatol 2009 May-Jun;27(3):291-305.
2 Nienhuis WA, Stienstra Y, Thompson WA, Awuah PC, Abass KM, Tuah W, et al. Antimicrobial treatment for early, limited Mycobacterium ulcerans infection: a randomised controlled trial. Lancet 2010 Feb 3.
3 Phillips RO, et al. Lancet 2020
4 Etuaful S, Carbonnelle B, Grosset J, Lucas S, Horsfield C, Phillips R, 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):3182-3186.
5 Stienstra Y, Dijkstra PU, Van Wezel MJ, Van Roest MH, Beets M, Zijlstra I, et al. Reliability and validity of the Buruli ulcer functional limitation score questionnaire. Am J Trop Med Hyg 2005 Apr;72(4):449-452.

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