Development of Highly Organized Lymphoid Structures in Buruli Ulcer Lesions after Treatment with Rifampicin and Streptomycin

Abstract

Buruli ulcer (BU) is a debilitating disease of the skin presenting with extensive tissue destruction and suppression of local host defence mechanisms. Surgical removal of the affected area has been the standard therapy until in 2004 WHO recommended eight weeks' treatment with the anti-mycobacterial drugs rifampicin and streptomycin. We performed a detailed histological analysis of the local immune response in biopsies from five children medicated according to WHO provisional guidelines. One patient still revealed all histopathological signatures of an active BU lesion with huge bacterial clusters in areas of fatty tissue necrosis. Different factors can contribute to treatment failure, such as poor patient compliance and resistant bacterial strains. In four patients, different compartments of the skin presented active immune processes with only limited residues of bacterial material persisting. We demonstrated that antibiotic treatment not only directly controls the infectious agent but is also associated with fulminant host immune responses. Characterization of the healing process in BU due to therapy is highly relevant to increase our knowledge of the impact of treatment strategies to fight the disease