Mongolian gerbils were susceptible to infection with Giardia lamblia cysts from patients. Inoculation of gerbils with 5 x 10(3) cysts each resulted in an infection characterized by the intermittent release of cysts for up to 39 days. The mean number of cysts released per gerbil in a 2-hr period was 8.8 x 10(2) (range, 0-5 x 10(3)). The highest number of trophozoites found in the intestine was on day 15 after infection, when the mean number of trophozoites per gerbil was 6.36 x 10(6). Administration of cysts from different patients to gerbils resulted in a similar pattern of cyst release during the first 30 days of infection. Mongolian gerbils were also susceptible to infection with cultured trophozoites (Portland 1 strain). The pattern of cyst release and the number of trophozoites in the intestines of orally and duodenally inoculated gerbils were similar. Gerbils were protected against reinfection with G. lamblia for up to eight months after primary infection.

SUMMARY The sequence of changes in the activity of six disaccharidases in the small intestine of gerbils during primary and secondary G lamblia infections was examined. The primary G lamblia infection induced a transient reduction in disaccharidase activity which was related to the highest trophozoite burden in the small intestine. During the primary exposure, a 30% to 85% decrease in the activity of enzymes was observed on days 10 and 20 after infection. Secondary exposure of gerbils to G lamblia caused a sharp decrease in disaccharidase activity as early as 24 h after challenge. The reduction in the enzyme activity was not influenced by the size of the challenge inoculum and occurred even when there were no live trophozoites in the small intestine. Disaccharidase deficiency could also be induced by challenge with the soluble extract of the trophozoites. Multiple challenge administrations of G lamblia trophozoites to gerbils induced a persistent disaccharidase deficiency. The results indicate that disaccharidase deficiency associated with the primary G lamblia infection probably represents a direct effect of the parasite on the brush border of the small intestine. On the other hand, the observed disaccharidase deficiency in the secondary G lamblia infection appears to be induced by the local immune responses of the host.Various abnormalities of small bowel pathology have been identified consistently in human giardiasis and these include disaccharidase deficiencies,' 2 increased intraepithelial lymphocyte counts'4 and, in patients with malabsorption crypt hyperplasia with short villi and increased lamina propria cellularity.) Low serum calcium and folate concentrations were consistent features in elderly people having giardiasis and aroused suspicion of underlying malabsorption." A decrease in the disaccharidase activity has been observed in vitro. Mouse mucosal cells incubated with G lamblia trophozoites showed a reduction in the activities of lactase, sucrase, and maltase.7We have recently described an animal model for giardiasis using gerbils and G lamblia isolated from humans.' In this study, we examined the progression

The susceptibility and resistance of inbred mice to Giardia muris was studied during the acute and elimination phases of infection. The infection in susceptible A/J and C3H/He mice was characterized by a short latent period, high cyst output during the acute phase of infection, and prolonged periods of cyst release. In contrast, resistant B1O.A and DBA/2 mice had a longer latent period, a lower cyst output during the acute phase, and relatively rapid resolution of infection. The trait of susceptibility and resistance during both acute and elimination phases of the infection was found to be under complex multigenic control as determined by examination of the response of F1 hybrid mice and backcross analyses. The genes controlling this trait did not appear to be linked to the H-2 locus. In addition, the control of the response of mice to G. muris during the acute phase of infection was probably mediated by mechanisms independent from those controlling the response during the elimination phase of infection.

Mongolian gerbils (Meriones unguiculatus) were inoculated with known numbers of Giardia cysts isolated from humans, beavers and mice. The pattern of cyst release in the feces was studied for a period of 35 days. After a latent period of 5 days, animals infected with G. muris release cysts in their feces every day until day 14. Gerbils infected with human or beaver isolates released cysts in their feces intermittently for 30 days. These results indicated that the mode of cyst release in these animals was characteristic of the parasite, and was independent of the host. Mongolian gerbils acquire complete resistance upon homologous species challenge but demonstrate only partial protection when challenged with a different species of Giardia. We concluded that the Mongolian gerbil model could be useful in epidemiological studies for two reasons: it can be used for determination of cyst viability, and for the identification of the etiological agent.

The kinetics of anti-sheep erythrocyte (SRBC) response were studied in susceptible (A/J) and resistant (B10.A) mice during infection with Giardia muris. Mice infected with G. muris were found to be less responsive to either intraperitoneally or intraduodenally administered SRBC. Immunodepression was of relatively short duration, occurring during the period of highest trophozoite density in the small intestine, and was present in both spleen and, in particular, mesenteric lymph node cell populations. The main difference in the kinetics of anti-SRBC responses between A/J and B10.A mice was that susceptible mice were significantly less responsive to SRBCs than were the resistant B10.A animals. The difference in the kinetics of the anti-SRBC response between A/J and B10.A mice was not due to T-suppressor cell activity. Mesenteric lymph node cell transfers but not spleen cell transfers from infected mice to syngeneic recipients caused depressed normal anti-SRBC response. Furthermore, administration of the soluble extract of the trophozoites to uninfected mice resulted in a depressed response against SRBCs. Pronounced immunodepression in gut-associated lymphoid tissues may be more relevant than systemic immunodepression to survival and reproduction of trophozoites in murine giardiasis.