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Chemotherapy-associated changes of histopathological features of Mycobacterium ulcerans lesions in a Buruli ulcer mouse model

Ruf, M. T. and Schütte, D. and Chauffour, A. and Jarlier, V. and Ji, B. and Pluschke, G.. (2012) Chemotherapy-associated changes of histopathological features of Mycobacterium ulcerans lesions in a Buruli ulcer mouse model. Antimicrobial agents and chemotherapy : AAC, Vol. 56, H. 2. pp. 687-696.

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Official URL: http://edoc.unibas.ch/dok/A6002436

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Abstract

Combination chemotherapy with rifampicin and streptomycin (RIF-STR) for eight weeks is currently recommended by WHO as first line treatment in Mycobacterium ulcerans infection (Buruli ulcer). To gain better insight into the mode of action of these antibiotics against established M. ulcerans infection foci and to characterize recovery of local immune responses during chemotherapy, we conducted a detailed histopathological study in M. ulcerans infected and RIF-STR treated mice. Mice were inoculated with M. ulcerans in the footpad and eleven weeks later treated with RIF-STR. Development of lesions during the first eleven weeks after infection and subsequent differences in disease progression between RIF-STR treated and untreated mice were studied. Changes in histopathological features, footpad swelling and number of colony forming units were analyzed. After inoculation with M. ulcerans massive infiltrates dominated by polymorphonuclear leukocytes developed at the inoculation site, but did not prevent bacterial multiplication. Huge clusters of extracellular bacteria located in large necrotic areas and surrounded by dead leukocytes developed in the untreated mice. Chemotherapy with RIF-STR led to a rapid drop in colony forming units associated with loss of solid Ziehl-Neelsen staining of acid-fast bacilli. Development of B-lymphocyte clusters and of macrophage accumulations surrounding the mycobacteria demonstrated the resolution of local immune suppression.. Results demonstrate that the experimental M. ulcerans mouse infection model will be a valuable tool to investigate efficacy of new treatment regimens and of candidate vaccines.
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 and Ruf, Marie-Thérèse
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society for Microbiology
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:24 May 2013 08:59
Deposited On:08 Nov 2012 16:21

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