Animal Models of Cryptosporidium Gastrointestinal Infection

This chapter presents three animal models of Cryptosporidium gastrointestinal infection, which include models of neonatal mouse, immunocompromised rat, and severe combined immunodeficiency (SCID) mouse. The neonatal mouse model uses outbred nursing mice, aged between five and nine days old. Mice that are 7–8 days old appear to produce the most consistent results. In this model, mouse pups are cross-fostered when they are two days old, based on weight prior to allocation of litters into treatment groups. The pups are weighed daily and treated orally with a microdoser and syringe pump equipped with a tuberculin syringe fitted with a 27G needle with microbore tubing. The primary advantage of this model is that large numbers of animals can be used and the infection dynamics are well-characterized. The immunosuppressed rat model uses Sprague-Dawley rats of 200–250 g, which are immunosuppressed by giving 0.25 mg/kg dexamethasone daily in the drinking water for 10 days prior to oral inoculation C. parvum oocysts. Anticryptosporidial agents are given in the water, in medicated feed or by gavage. Cryptosporidial infections peak at seven days post-infection and most parasites are present in the terminal 2 cm of the ileum. Histological scoring of ileal tissue sections taken at 11 days is used to judge the efficacy of prophylactic treatments and 21 days post-infection to judge therapeutic treatments which are initiated on day 10 post-infection. SCID mice are used as models of cryptosporidiosis in AIDS patients. The mice are maintained under pathogen-free conditions and housed in microisolator cages in high-efficiency laminar flow units. All animal manipulations are done on a high-efficiency particulate air-filtered bench. The primary advantage of the SCID mouse model is that it is both an infection and a disease model.