Secondary Buruli Ulcer Skin Lesions Emerging Several Months after Completion of Chemotherapy Paradoxical Reaction or Evidence for Immune Protection 英文参考文献.docVIP

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Secondary Buruli Ulcer Skin Lesions Emerging Several Months after Completion of Chemotherapy Paradoxical Reaction or Evidence for Immune Protection 英文参考文献.doc

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Secondary Buruli Ulcer Skin Lesions Emerging Several Months after Completion of Chemotherapy Paradoxical Reaction or Evidence for Immune Protection 英文参考文献

SecondaryBuruliUlcerSkinLesionsEmergingSeveral MonthsafterCompletionofChemotherapy:Paradoxical ReactionorEvidenceforImmuneProtection? Marie-The′re`seRuf1,2,AnnickChauty3,4,AmbroiseAdeye3,4,Marie-Franc?oise Ardant3,4 ,Hugues Koussemou3,4,RochChristianJohnson4,GerdPluschke1,2* 1SwissTropicalandPublicHealthInstitute,Basel,Switzerland,2UniversityofBasel,Basel,Switzerland,3CentredeDiagnosticetdeTraitementdel’Ulce`redeBuruli,Pobe`, Benin,4FondationRaoulFollereau,Cotonou,Benin 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 recommendedeightweeksstandardtreatmentwithrifampicinandstreptomycin,areversalofthelocalimmunosuppres- sioncausedbythemacrolidetoxinmycolactoneofM.ulceransisobserved. Methodology/PrincipalFindings:Wehaveconductedadetailedhistopathologicalandimmunohistochemicalanalysisof 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 infiltratesincludinglargeB-cellclusters,astypicallyfoundincuredlesions. Conclusion/Significance:Ourhistopathologicalfindingsdemonstratethattheskinlesionsemergingseveralmonthsafter completion of antibiotic treatment were associated with M. ulcerans infection. During antibiotic therapy of Buruli ulcer developmentofnewskinlesionsmaybecausedbyimmuneresponse-mediatedparadoxicalreactions.Theseseemtobe triggeredbymycobacterialantigensandimmunostimulatorsreleasedfromclinicallyunrecognizedbacterialfoci.However, in particular the lesion