ABSTRACT
BACKGROUND: In recent years, first-line therapy for Mycobacterium ulcerans infection in French Guiana has consisted of antibiotics active against this organism. Two regimens are used comprising rifampicin associated with clarithromycin or amikacin. PATIENTS AND METHODS: We describe four patients presenting apparent worsening of their lesions during treatment: ulceration of a nodular lesion in a 32-year-old woman and worsening of an ulcerated lesion in three patients aged 16, 27 and 79 years. DISCUSSION: In these 4 patients, we concluded that the symptoms were caused by a paradoxical response or a reaction, a phenomenon already described in tuberculosis and leprosy. Such worsening is transient and must not be misinterpreted as failure to respond to treatment. The most plausible pathophysiological hypothesis involves the re-emergence of potentially necrotizing cellular immunity secondary to the loss of mycolactone, a necrotizing and immunosuppressive toxin produced by M. ulcerans, resulting from the action of the antibiotics.
Subject(s)
Amikacin/adverse effects , Anti-Bacterial Agents/adverse effects , Buruli Ulcer/drug therapy , Clarithromycin/adverse effects , Rifampin/adverse effects , Adolescent , Adult , Aged , Amikacin/administration & dosage , Amikacin/pharmacology , Amikacin/therapeutic use , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Asia/ethnology , Brazil/ethnology , Buruli Ulcer/pathology , Buruli Ulcer/surgery , Clarithromycin/administration & dosage , Clarithromycin/pharmacology , Clarithromycin/therapeutic use , Combined Modality Therapy , Debridement , Drug Therapy, Combination , Europe/ethnology , Female , Foot Ulcer/drug therapy , Foot Ulcer/etiology , Foot Ulcer/surgery , French Guiana , Humans , Immunity, Cellular/drug effects , Macrolides/metabolism , Male , Mycobacterium ulcerans/drug effects , Mycobacterium ulcerans/metabolism , Rifampin/administration & dosage , Rifampin/pharmacology , Rifampin/therapeutic use , Wound HealingABSTRACT
The nucleotide sequence of a gene coding for a 37 kDa subunit of a cytosolic malate dehydrogenase of Trichomonas vaginalis was established. The sequence of a gDNA clone and a cDNA clone, which lacked seven amino-terminal codons, were identical, indicating an absence of introns from the gene. Cell fractionation combined with sequencing of peptide fragments of the purified enzyme showed that the gene codes for an expressed cytosolic enzyme. The derived amino acid sequence was closely related to cytosolic malate dehydrogenases from animals and plants and from the eubacteria Thermus aquaticus and Mycobacterium leprae and was more distant from the enzyme of mitochondria and from Escherichia coli and certain other eubacteria. In phylogenetic reconstructions this enzyme shared a most recent common ancestor with other cytosolic enzymes.