Factors determining the susceptibility of mice to experimental phycomycosis

Abstract

Various factors influencing the susceptibility of C3H mice to lethal infection by the phycomycete Absidia ramosa were examined. Mice 19-21 days old were exposed to graded doses of A. ramosa spores by various routes. After intravenous inoculation with doses in excess of 10(3) viable units, a variable proportion of mice developed lethal phycomycosis of the central nervous system within 2-8 days. The proportion of mice affected was related to the inoculum size, doses of 5 X 10(7) spores producing lethal infection in 90-100% of the mice. The disease was characterised by signs of involvement of the central nervous system appearing 8-12 h before death. At necropsy, fungal hyphae, frequently surrounded by infiltrations of mononuclear cells, could be demonstrated in the brain. Lesions were also often present in the kidneys; in other organs they were rare, but the presence of viable fungal spores could be detected by cultural procedures. Subcutaneous inoculation of A. ramosa spores did not produce lethal infection but intraperitoneal inoculation occasionally did so. Direct intracerebral inoculation invariably produced lethal infection even with very small doses of spores. The clinical and histopathological features of the disease were almost identical with those resulting from intravenous inoculation. Pre-inoculation treatment with azathioprine, cyclophosphamide and antithymocyte serum did not increase susceptibility. Susceptibility was increased by injections of zymosan, aggregared gamma-globulin, cortisone acetate and Fe(II) salts and by reticuloendothelial blockade. These treatments increased the proportion of mice developing lethal phycomycosis of the central nervous system, and in the case of cortisone acetate, also promoted disseminated infection. It was concluded that the natural resistance of mice to A. ramosa infection was probably dependent upon the activity of phagocytic cells, possibly acting in conjunction with complement and other non-specific serum factors.