Pathogenesis of Trichosporon asahii and strategies for infectious control of disseminated trichosporonosis

Abstract

Deep-seated trichosporonosis is a lethal opportunistic infection in immunocompromised patients. Trichosporon asahii and T. mucoides are the most common strains of fungi that cause disseminated trichosporonosis. Thirteen patients were diagnosed with disseminated trichosporonosis over a 20 year period in Oita Medical University Hospital. The majority of them had underlying hematologic malignancies, for which they received cytotoxic chemotherapy resulting in neutropenia. For the rapid diagnosis of this condition, we developed a novel nested-PCR assay that detected DNA specific for Trichosporon asahii and Trichosporon mucoides in the serum of patients with the condition. In a retrospective study using these serum samples, the specific DNA fragment was detected a few days to a few weeks earlier than blood culture. To treat this infection, we studied the efficacy of granulocyte colony-stimulating factor (GCS-F) alone and in combination with antifungal agents against disseminated trichosporonosis in neutropenic mice. The results suggested that GCS-F might be a useful immunomodulator against Trichosporon infections in neutropenic mice and the therapeutic outcome improved when used in combination with fluconazole. Furthermore our experimental animal model demonstrated that disseminated trichosporonosis is induced by immunosuppresion in hosts with latent trichosporonemia which was detectable by the nested PCR but not by blood culture. We found that there is a critical period for the progression of disseminated trichosporonosis after entry of fungi into the bloodstream.