Infection dynamics and clinical features of cryptosporidiosis in SCID mice

Abstract

Cryptosporidial infections in severe combined immune deficient (SCID) mice produce a chronic disease state which in the later stages leads to extraintestinal involvement and hepatic dysfunction. To further characterize the infection dynamics in this model and monitor the changes in the hepatic system, a dose titration of the oocyst inoculum was performed and alkaline phosphatase levels in the sera were assayed. Ten SCID mice per dose were inoculated with 103, 104, 105, 106, or 107 oocysts. Oocyst shedding in the feces was quantified by microscopic enumeration. Mice inoculated with 106 oocysts and those inoculated with 107 oocysts demonstrated similar oocyst shedding patterns, but the 107-oocyst group exhibited signs of distress (e.g., weight loss and icterus) earlier. The intensity of the infection increased markedly approximately 14 days postinoculation (p.i.) and continued to increase steadily over the next 6 weeks. Inoculation with lower oocyst doses produced a delay in patency (e.g., it occurred 7 days later with the 105-oocyst inoculum and 14 days later with the 104-oocyst inoculum). Mean serum alkaline phosphatase levels in the 107-oocyst group were more than twice control values at 5 weeks p.i. and continued to increase over the next 8 weeks. Oocyst doses and alkaline phosphatase levels were positively correlated with hepatobiliary colonization (r = 0.71) and liver necrosis (r = 0.65) at 13 weeks p.i. A strong positive correlation between hepatobiliary colonization and liver necrosis at 13 weeks p.i. (r = 0.87) was observed.