Efficacy of Post-Exposure Treatment of Yellow Fever With Ribavirin in a Hamster Model of the Disease

Sbrana, Elena; Xiao, Shu Yuan; Guzmán, Hilda; Ye, Mengyi; Rosa, A.P.A. Travassos da; Tesh, Robert B.

doi:10.4269/ajtmh.2004.71.306

Cited by 50 publications

(29 citation statements)

References 23 publications

(36 reference statements)

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“…Ribavirin has been shown to be effective in the treatment of viral diseases, decreasing viral load. 64 Humans with acute NiV encephalitis who were treated with ribavirin had partial recovery from the disease. 11 Ribavirin and 6-aza-uridine have been shown to delay but not prevent NiV-induced mortality in hamsters.…”

Section: Antiviral Therapeutics and Vaccinesmentioning

confidence: 99%

Henipavirus: A Review of Laboratory Animal Pathology

Williamson¹,

Torres-Vélez

2010

Vet Pathol

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The genus Henipavirus contains two members-Hendra virus (HeV) and Nipah virus (NiV)-and each can cause fatal disease in humans and animals. HeV and Niv are currently classified as biosafety level 4, and NiV is classified as a category C priority pathogen. The aim of this article is to discuss the pathology of laboratory animal models of henipavirus infection and to assess their suitability as animal models for the development and testing of human therapeutics and vaccines. There has been considerable progress in the development of animal models for henipavirus disease. Suitable animal models include the golden hamster, ferrets, cats, and pigs, which develop disease resembling that observed in humans. Guinea pigs are a less reliable model for henipavirus disease, but they do develop henipavirus-induced encephalitis. Because human efficacy studies with henipaviruses are not permitted, animal studies are critical for the development of antiviral therapeutics and vaccines. Current research indicates that passive immunotherapy using monoclonal antibodies is protective of ferrets against NiV infection and that passive immunotherapy using NiV antibodies protects hamsters from HeV. Recombinant vaccines have been used to protect cats and pigs against NiV infection. Ribavirin and 6-aza-uridine were able to delay but not prevent NiV-induced mortality in hamsters. Further research is needed to develop a model and therapy for late-onset henipavirus encephalitis.

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Section: Antiviral Therapeutics and Vaccinesmentioning

confidence: 99%

Henipavirus: A Review of Laboratory Animal Pathology

Williamson¹,

Torres-Vélez

2010

Vet Pathol

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“…A hamster model of YFV disease has recently been characterized, and the infection in hamsters is similar in many regards to that in humans (20,23,26). This hamster model has served as a useful tool for the evaluation of antiviral agents for the treatment of YFV disease (11,19). The hamster-adapted Jimenez strain of YFV used in this model causes disease and death after intraperitoneal (i.p.)…”

mentioning

confidence: 99%

“…injection of hamsters (23). Useful parameters for the evaluation of antiviral compounds include the rate of survival; the YFV titer in the liver; serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels; weight change; and several serum parameters, including elevated bilirubin and blood urea nitrogen levels (10,11,19).…”

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confidence: 99%

Activity of T-705 in a Hamster Model of Yellow Fever Virus Infection in Comparison with That of a Chemically Related Compound, T-1106

Julander

Shafer

Smee

et al. 2009

Antimicrob Agents Chemother

124

107

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Treatment with the nucleoside analog T-1106 was previously shown to be effective in a hamster model of yellow fever virus (YFV) disease, even though it had only slight activity in cell culture. In the study described in this report, the activity of T-705, a chemically related compound currently undergoing clinical trials for the treatment of influenza (FDANews 4:1, 2007), was tested against YFV in cell culture and in the hamster model. The antiviral efficacy of T-705 in cell culture occurred at a concentration of 330 M, which was more than threefold lower than the concentration at which T-1106 had antiviral efficacy, as determined by a virus yield reduction assay and confirmed by a luciferase-based ATP detection assay. Time-of-addition studies revealed that addition of T-705, T-1106, or ribavirin at 0, 4, 8, or 12 h after virus challenge was effective in inhibiting virus in Vero cells, suggesting that these three agents have similar mechanisms of action in cell culture. Because of its more potent activity in cell culture, it was anticipated that T-705 treatment of hamsters infected with YFV would result in protection from disease. Significant improvements in survival and disease parameters were seen in infected animals when T-705 was administered orally at a dose of 200 or 400 mg/kg of body weight per day when it was given twice a day for 8 days. Significant improvements were also observed with a dose of 400 mg/kg/day when treatment initiation was delayed as late as 3 days after virus inoculation. Although the dose of T-705 required for efficacy in hamsters is higher than that of T-1106 required for efficacy, T-705 treatment is effective in significantly improving disease parameters in YFV-infected hamsters, which may indicate its potential utility in the treatment of YFV disease in humans.

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“…A hamster model of YFV disease has been characterized and is similar to infection of humans in many ways, and YFV disease in this model tends to be less virulent than infection in nonhuman primates (13,16,18). This hamster model has shown utility in antiviral studies and has been used for the evaluation of ribavirin and interferon alfacon-1 (6,12).…”

mentioning

confidence: 99%

Activity of T-1106 in a Hamster Model of Yellow Fever Virus Infection

Julander

Furuta²,

Shafer

et al. 2007

Antimicrob Agents Chemother

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Yellow fever virus (YFV) causes 30,000 deaths worldwide, despite the availability of a vaccine. There are no approved antiviral therapies for the treatment of YFV disease in humans, and, therefore, these studies were designed to investigate the anti-YFV properties of T-1106, a substituted pyrazine, in a hamster model of YFV disease. Intraperitoneal (i.p.) treatment with 100 mg/kg of body weight/day of T-1106 starting 4 h prior to virus inoculation and continuing twice daily through 7 days post-virus inoculation (dpi) resulted in significantly improved survival, alanine aminotransferase levels in the serum, weight gain, and mean day to death. Virus titer in the liver at 4 dpi was significantly reduced in treated animals, as determined by both quantitative real-time PCR and infectious cell culture assay. No toxicity (weight loss or mortality) was observed at a dose of 100 mg/kg/day in sham-infected control animals. The observed minimal effective dose of T-1106 was 32 mg/kg/day administered either by oral or i.p. treatment. Therapeutic treatment was effective in significantly improving survival when T-1106 was administered beginning as late as 4 days after virus challenge with twice-daily treatment for 8 days at a dose of 100 mg/kg/day. With favorable safety, bioavailability, and postviral challenge treatment efficacy, T-1106 was effective in the treatment of disease in hamsters infected with YFV and should be further studied for potential use as a therapy for human YFV disease.

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Efficacy of Post-Exposure Treatment of Yellow Fever With Ribavirin in a Hamster Model of the Disease

Cited by 50 publications

References 23 publications

Henipavirus: A Review of Laboratory Animal Pathology

Henipavirus: A Review of Laboratory Animal Pathology

Activity of T-705 in a Hamster Model of Yellow Fever Virus Infection in Comparison with That of a Chemically Related Compound, T-1106

Activity of T-1106 in a Hamster Model of Yellow Fever Virus Infection

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