Evaluation of a two-phase scid mouse model preconditioned with anti-interferon-gamma monoclonal antibody for drug testing against Cryptosporidium parvum

Abstract

One 1-mg injection of anti-interferon-gamma monoclonal antibody (anti-IFN-gamma MAb) into newly weaned scid mice 2 h before challenge with Cryptosporidium parvum oocysts markedly exacerbated the course of the infection for > or = 47 days, compared with challenged mice that received an equivalent dose of irrelevant MAb. Oocyst excretion in feces started 4-6 days after challenge and continued at high levels for > or = 47 days. Loss of body weight was also apparent. The extent and distribution of mucosal infection were profound, involving the stomach and several segments of the small and large intestines. The acute phase, which involved infection of the gut, was during the first 25 days after challenge. The following chronic phase consistently involved, in addition, infection of the hepatobiliary tract. The acute phase is a useful model in which to test luminally active drugs, while the chronic phase may be used in the future to test drugs that are active against hepatobiliary tract infections as well.