Estudo clínico e imunológico de controle de cura de paracoccidioidomicose crônica

Abstract

Paracoccidioidomycosis (PCM), caused by dimorphic fungus Paracoccidioides brasiliensis (Pb), is the most common systemic mycosis in Latin America. A major problem in managing PCM is to determine the right time to discontinue therapy. The aim of the present work was to investigate the clinical and immunological profile of patients with adult type of PCM, in order to find out parameters that better correlatewith disease activity. A cohort of 75 adult patients admitted to the Infectious Diseases Ambulatory of the General Hospital of the Federal University of Minas Gerais, Brazil, from March 2001 to December 2006, was evaluated at each six months. Clinical remission was defined as the absence of PCM symptoms and scarring of all lesions, associated to normalization or stabilization of laboratorial and radiological changes.Serum levels of inflammation markers (anti-Pb IgG antibodies, sTNF-R1, sTNF-R2, CXCL9, CCL2, CCL3, CCL11 and CCL24) were measured by ELISA assays in 26 patients from the group, at baseline and after 6, 12 and 36 months of treatment. For comparison, 37 age-matched healthy volunteers were recruited. Clinical remission was achieved by 53 (71%) patients; in 27 (51%) cases, it was noticed during the first six months of therapy. Binary logistic regression identified therapeutic regimen andpresence of mucosal lesions as the most significant predictors of bad outcome in adult type PCM; treatments with azole drugs alone or combined with sulfonamides were associated with a lower percentual of clinical remission. Determination of serum levels of anti-Pb IgG antibodies and sTNF-R2 presented higher sensitivity and specificity, in comparison to other markers, at their respective cut-off values, definedby ROC curve method, to discriminate healthy controls from adult type PCM patients. Levels of sTNF-R1, however, seem to be a better marker of disease activity in comparison to sTNF-R2. Untreated adult type PCM patients present a preferential induction of Th1 immune response; however, during the treatment, a shift to Th2 response occurs, and this may be related to immune regulation. After 36 months of follow-up, concentration of anti-Pb IgG, sTNF-R1, CCL2 and CCL24 weresignificantly higher in PCM patients in comparison to controls. Simultaneous analysis of serum levels of non-specific inflammation markers, mainly sTNF-R1 and sTNF-R2, and specific anti-Pb antibodies in addition to clinical signs may improve the accuracy to determine the right time to discontinue antifungal therapy in PCM patients. Furtherstudies are necessary to confirm if any of these inflammation markers may be used as a reliable parameter to assess disease activity in PCM patients and maybe help to reduce disease relapses.