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Secondary Buruli ulcer skin lesions emerging several months after completion of chemotherapy : paradoxical reaction or evidence for immune protection?

Ruf, M. T. and Chauty, A. and Adeye, A. and Ardant, M. F. and Koussemou, H. and Johnson, R. C. and Pluschke, G.. (2011) Secondary Buruli ulcer skin lesions emerging several months after completion of chemotherapy : paradoxical reaction or evidence for immune protection? PLoS neglected tropical diseases, Vol. 5, H. 8 , e1252.

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Official URL: http://edoc.unibas.ch/dok/A6002342

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Abstract

BACKGROUND: The neglected tropical disease Buruli ulcer (BU) caused by Mycobacterium ulcerans is an infection of the subcutaneous tissue leading to chronic ulcerative skin lesions. Histopathological features are progressive tissue necrosis, extracellular clusters of acid fast bacilli (AFB) and poor inflammatory responses at the site of infection. After the recommended eight weeks standard treatment with rifampicin and streptomycin, a reversal of the local immunosuppression caused by the macrolide toxin mycolactone of M. ulcerans is observed. METHODOLOGY/PRINCIPAL FINDINGS: We have conducted a detailed histopathological and immunohistochemical analysis of tissue specimens from two patients developing multiple new skin lesions 12 to 409 days after completion of antibiotic treatment. Lesions exhibited characteristic histopathological hallmarks of Buruli ulcer and AFB with degenerated appearance were found in several of them. However, other than in active disease, lesions contained massive leukocyte infiltrates including large B-cell clusters, as typically found in cured lesions. CONCLUSION/SIGNIFICANCE: Our histopathological findings demonstrate that the skin lesions emerging several months after completion of antibiotic treatment were associated with M. ulcerans infection. During antibiotic therapy of Buruli ulcer development of new skin lesions may be caused by immune response-mediated paradoxical reactions. These seem to be triggered by mycobacterial antigens and immunostimulators released from clinically unrecognized bacterial foci. However, in particular the lesions that appeared more than one year after completion of antibiotic treatment may have been associated with new infection foci resolved by immune responses primed by the successful treatment of the initial lesion
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Molecular Immunology (Pluschke)
UniBasel Contributors:Pluschke, Gerd
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Library of Science
ISSN:1935-2727
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Nov 2012 16:22
Deposited On:08 Nov 2012 16:13

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