Post-surgical assessment of excised tissue from patients with Buruli ulcer disease: progression of infection in macroscopically healthy tissue

Authors


Authors
G. Bretzel (corresponding author) and V. Siegmund, Bernhard Nocht Institute for Tropical Medicine (BNITM), Hamburg; Department of Infectious Diseases and Tropical Medicine (DITM), University of Munich, Germany. Tel.: +49 8921 803618; Fax: +49 89 336112; E-mail: bretzel@lrz.uni-muenchen.de
P. Racz, F. van Vloten and B. Fleischer, Bernhard Nocht Institute for Tropical Medicine (BNITM), Hamburg, Germany.
F. Ngos, Hôpital de District, District de Santé d'Akonolinga, Akonolinga, Cameroon.
W. Thompson, Agogo Presbyterian Hospital, Agogo, Ghana.
P. Biason, Médecins sans Frontières (MSF), Geneva, Switzerland.
O. Adjei, Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), University of Science and Technology, Kumasi, Ghana.
J. Nitschke, Bernhard Nocht Institute for Tropical Medicine (BNITM), Hamburg, Germany; Médecins Sans Frontières (MSF), Geneva, Switzerland.

Summary

Objective  The current standard of treatment of Buruli ulcer disease (BUD) is surgical excision of lesions. Excision size is determined macroscopically assuming the complete removal of all infected tissue. However, dissemination of infection beyond the excision margins into apparently healthy tissue, possibly associated with recurrences, cannot be excluded in this way. To assess the central to peripheral progression of Mycobacterium ulcerans infection and the mycobacterial infiltration of excision margins, excised tissue was examined for signs of infection.

Methods  20 BUD lesions were excised in general anaesthesia including all necrotic and subcutaneous adipose tissue down to the fascia and at an average of 40 mm into the macroscopically unaffected tissue beyond the border of the lesion. Tissue samples were subjected to PCR and histopathology.

Results  Although the bacillary load decreased from central to peripheral, M. ulcerans infection was detected throughout all examined tissue specimens including the peripheral segments as well as excision margins of all patients. During the post-operative hospitalization period (averaging 2 months) no local recurrences were observed.

Conclusion  Available data suggest a correlation of surgical techniques with local recurrences. The results of this study indicate the unnoticed early progression of mycobacterial infection into macroscopically healthy tissue. Thus, the removal of all infected tissue cannot always be verified visually by the surgeon. Provided that long-term follow up of patients with positive excision margins will establish the clinical relevance of these findings, on-site laboratory assessment of excised tissue in combination with follow up may contribute to reduce recurrence rates.

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