Differences in susceptibility to cryptosporidial infections were investigated between 2 strains of gamma interferon knockout (GKO) mice. Male C57BL/6J-Ifg and BALB/c-Ifg (GKO) mice, ages 8-10 wk, were inoculated with infectious oocysts at various doses. C57BL/6J-Ifg mice developed overwhelming infections and died 9-12 days after infection. Low inoculum doses (1 x 10(3)) did not increase the survival time significantly. The infection intensity in C57BL/6J-Ifg mice inoculated with 1 x 10(5) oocysts/mouse increased markedly on day 4 postinfection (PI) and continued to increase significantly over the next 6-7 days. Most of the C57BL/6J-Ifg mice exceeded 15% weight loss and died by day 10 PI. In contrast, BALB/c-Ifg mice developed moderate infections from which they recovered. The average parasite load in the BALB/c-Ifg mice was 100 times lower than in C57BL/6J-Ifg mice. Mice survived until termination of the experiment (39 days) even when 1 x 10(6) oocysts per mouse were used for inoculation. BALB/c-Ifg mice did not exhibit significant weight loss (or difference in stool consistency). These 2 mouse strains make excellent models for studying differences in recovering and nonrecovering immune mechanisms.
Severe cryptosporidial infections were produced in gamma interferon (IFN-gamma) knockout mice. Mean oocyst shedding increased from 332 to 30,717 oocysts/100 microliters of faecal suspension between day 4 and 9 after administration of 1 x 10(5) oocysts/mouse. No significant differences in oocyst shedding were observed in mice after being inoculated with 1 x 10(5), 1 x 10(4) or 1 x 10(3) oocysts/mouse (P > 0.05). Infected mouse weights decreased an average 3-4 g before death or euthanization. Histological studies revealed heavy parasite colonization in small intestinal epithelium (approximately 250 organisms/high-power field at x 400). Mesenteric lymph nodes in infected mice were markedly enlarged compared to controls (P < 0.05). Both CD4+ and CD8+ T cell populations increased in spleens of infected mice while the B cell population increased in mesenteric lymph nodes from infected mice. No significant proliferation was observed when pooled lymphocytes from infected mice were exposed to C. parvum antigens in vitro. Addition of recombinant mouse IFN-gamma did not restore antigen responsiveness. While lymphoproliferative responses to specific antigen were not significant in the short period following infection, this mouse model provides unique features to study the characteristics of acute infection and the immune response against C. parvum.
Despite the evaluation of over 100 antimicrobial drugs, the diarrheal disease cryptosporidiosis has remained refractory to treatment. We report the evaluation of five dinitroaniline herbicides including trifluralin, profluralin, nitralin, pendimethalin, and fluchloralin for anticryptosporidial activity in an in vitro cultivation model of Cryptosporidium parvum. All five compounds exhibited significant anticryptosporidial activities with no corresponding evidence of toxicity. The most active compound was pendimethalin with an IC50 of 0.19 microM while nitralin was the least active with an IC50 of 4.5 microM. These compounds should be evaluated further in an animal model of cryptosporidiosis.
Despite the evaluation of over 100 antimicrobial drugs, the diarrheal disease cryptosporidiosis has remained refractory to treatment. We report the evaluation of five dinitroaniline herbicides including trifluralin, profluralin, nitralin, pendimethalin, and fluchloralin for anticryptosporidial activity in an in vitro cultivation model of Cryptosporidium parvum. All five compounds exhibited significant anticryptosporidial activities with no corresponding evidence of toxicity. The most active compound was pendimethalin with an IC50 of 0.19 microM while nitralin was the least active with an IC50 of 4.5 microM. These compounds should be evaluated further in an animal model of cryptosporidiosis.
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