Characterization of a Dexamethasone-Treated Rat Model of Cryptosporidial Infection

Rehg, Jerold E.; Hancock, Michael L.; Woodmansee, Douglas B.

doi:10.1093/infdis/158.6.1406

Cited by 67 publications

(36 citation statements)

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“…The minimal dosage of paromomycin exhibiting an anticryptosporidial effect against ileal infection was 200 mg/kg/day, and paromomycin at up to 400 mg/kg/day was found to enhance cecal infection. Although the model that we have used is inspired by the experimental infection previously described and used by Regh et al (17,18), data from the control groups show that ileal infection was less important and cecal infection was more severe in our study. These differences may explain our findings of the efficiency of a lower paromomycin dosage against the ileal infection.…”

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confidence: 65%

Evaluation of high-dose regimen of paromomycin against cryptosporidiosis in the dexamethasone-treated rat model

Verdon

Polianski

Gaudebout

et al. 1995

Antimicrob Agents Chemother

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In the dexamethasone-treated rat model of cryptosporidiosis, paromomycin was effective at a dosage of 50 mg/kg/day or more for ileal infection and 200 mg/kg/day or more for cecal infection. At 1 and 3 weeks after treatment, a persistent infection was demonstrated in all rats. These results confirm the anticryptosporidial activity of paromomycin and underscore the limitations of this compound because of its potential toxicity at such high dosages and its inability to eradicate the infection. Infection byCryptosporidium parvum causes self-limited gastroenteritis in immunocompetent hosts and chronic diarrhea in immunosuppressed hosts, such as patients with AIDS (6). Only paromomycin and, to a lesser extent, azithromycin have shown some benefit for patients. Paromomycin has been shown to have an anticryptosporidal effect in in vitro assays (7, 13), animal models (8,9,17,19,21), and uncontrolled clinical evaluations (1, 2, 5, 10, 11). In AIDS patients, the beneficial but limited effect of paromomycin at 25 to 35 mg/kg/day upon oocyst shedding and stool frequency has been demonstrated (22). Azithromycin was active in the dexamethasonetreated rat model (16), but few data for human patients are available (20). Other chemical compounds have been shown to reduce the intensity of the infection by C. parvum in animal models, but such agents are not available for use in humans (4,14).In a previous study, we found that paromomycin at 100 mg/kg/day, but not 50 mg/kg/day, was associated with a significant decrease in oocyst shedding and in the intensity of ileal infection (21). Similarly, in the hydrocortisone protein-deprived rat model, paromomycin treatment at the dosage of 50 mg/kg/day was found to be ineffective (3). Activity of paromomycin against C. parvum has also been observed in prophylactic trials in calves and BALB/c mice at dosages of 100 and 200 mg/kg/day, respectively (8, 9). Such studies suggest that dosages higher than the currently used 25 to 50 mg/kg/day could be of interest for use in human patients. The aim of this study was to determine the curative effect of high dosages of paromomycin in the dexamethasone-treated rat model.One hundred twenty female Sprague-Dawley rats weighing 200 to 215 g were given dexamethasone in the drinking water at a concentration of 0.25 mg/kg/day throughout the experiment. Ten days after the beginning of immunosuppressive therapy, the animals were inoculated by gavage with 4 ϫ 10 5 oocysts of C. parvum of human origin, propagated in calves (obtained from M. Naciri, Tours, France). Seven days after oocyst challenge, the animals were randomly divided into the following groups: (i) five groups, of 20 animals each, were given paromomycin sulfate (Parkes-Davis, Courbevoie, France) at 50, 100, 200 or 400 mg/kg/day by gavage twice daily, or given distilled water (control group), respectively, for 10 days (days 7 to 17 postchallenge) and then sacrificed; and (ii) two groups, of 10 rats each, were given paromomycin at 200 or 400 mg/kg/day, respectively, for 10 days (from days 7 to 17 post...

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confidence: 65%

Evaluation of high-dose regimen of paromomycin against cryptosporidiosis in the dexamethasone-treated rat model

Verdon

Polianski

Gaudebout

et al. 1995

Antimicrob Agents Chemother

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“…In the present study, a corticosteroid immunosuppression procedure was adapted from rat cryptosporidiosis models since no infection was obtained in immunocompetent gerbils (data not shown) (6,30). This differs from other intestinal protozoal pathogen infections, to which immunocompetent adult gerbils were found experimentally to be at least partially permissive, including Cryptosporidium muris with protracted chronic infections in methylprednisolone immunosuppressed animals (18).…”

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Infectivity of Cryptosporidium hominis and Cryptosporidium parvum Genotype 2 Isolates in Immunosuppressed Mongolian Gerbils

et al. 2005

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One-month-old dexamethasone-immunosuppressed Mongolian gerbils were challenged with 1 oocyst to 2 ؋ 10 5 oocysts from two isolates genotyped as Cryptosporidium hominis and C. parvum (genotype 2), respectively. A similar dose-dependent gut infection was obtained, and the initial genotype maintained for 21 to 22 days. The data suggest that immunosuppressed gerbils provide a reliable rodent model of persistent C. hominis infection.

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“…Dexamethasone (DEX) (Sigma Chemical Co., St. Louis, Mo.) was administered in the drinking water at a concentration equivalent to 0.25 ,ug/g/day (12). The immunosuppressant was administered for 10 days before intragastric inoculation with oocysts, except for an initial experiment in which the drug was administered for 7 days.…”

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confidence: 99%

Effectiveness of dehydroepiandrosterone in reduction of cryptosporidial activity in immunosuppressed rats

Rasmussen

Arrowood

Healey

1992

Antimicrob Agents Chemother

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Characterization of a Dexamethasone-Treated Rat Model of Cryptosporidial Infection

Cited by 67 publications

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Evaluation of high-dose regimen of paromomycin against cryptosporidiosis in the dexamethasone-treated rat model

Evaluation of high-dose regimen of paromomycin against cryptosporidiosis in the dexamethasone-treated rat model

Infectivity of Cryptosporidium hominis and Cryptosporidium parvum Genotype 2 Isolates in Immunosuppressed Mongolian Gerbils

Effectiveness of dehydroepiandrosterone in reduction of cryptosporidial activity in immunosuppressed rats

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