Experimental model of progressive disseminated trichosporonosis in mice with latent trichosporonemia

Trichosporon asahii and Trichosporon mucoides are the most common strains o f fungi that cause disseminated trichosporonosis, a severe opportunistic in fection in immunocompromised hosts. We have previously established a nested PCR assay using serum samples for detection of both strains. Here we descr ibe a new experimental animal model for investigating the underlying mechan isms of disseminated trichosporonosis. T. asahii (OMU239, a clinical isolat e from a patient with acute myelogenous leukemia) and 8-week-old ICR male m ice were used in all experiments. A suspension of T. asahii (3 x 10(6) CFU/ animal) was injected into the caudal vein of each mouse after immunosuppres sion with cyclophosphamide (200 mg/kg of body weight/day for 2 days) and pr ednisolone (30 mg/kg/day for 1 day). Mice were then divided into four subgr oups (R0, R1, R2, and R3) based on the time of reimmunosuppression. The lat ter was performed using the same drugs 1 week (group R1), 2 weeks (group R2 ), and 3 weeks (group R3) after fungal infection. Reimmunosuppression was n ot performed in group R0, The 5-week-survival rates of mice after T. asahii infection were 0% for group R1, 50% for group R2, 80% for group R3, and 80 % for group R0, There was a significant difference in the survival rates be tween group R1 and either group R0 or R3 (P < 0.05), Fungal clearance in pe ripheral blood and various organs of group R1 and R2 was delayed relative t o that of group R0 but was similar to the control in group R3 in spite of r eimmunosuppression. Our results suggest that the critical period for the de velopment of disseminated trichosporonosis in our model is shorter than 3 w eeks after T. asahii infection. We concluded that mice during this critical period were in a state of latent trichosporonemia, Comparison of the survi val rates suggests that the nested PCR assay was more useful than blood cul ture and glucuronoxylomannan antigen assay in the detection of this latent trichosporonemia.