The Guinea Pig Model for Argentine Hemorrhagic Fever *

Oubiña, José R.; Carballal, Guadalupe; Videla, Cristina; Cossio, Patricio M.

doi:10.4269/ajtmh.1984.33.1251

Cited by 22 publications

(8 citation statements)

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“…These findings strongly suggest that cell-mediated immunity is markedly impaired in the guinea pig infected with the XJ strain (11). These animals died without detectable CF, neutralizing or IF antibodies (69). High levels of interferon were also detected in infected guinea pigs (30).…”

Section: Studies With the Xj Prototype Strain In Guinea Figs And Primmentioning

confidence: 80%

“…No virus can be recovered from brain unless a viral strain highly passaged in guinea pig is used (69). In this case, an enhanced neurotropism, with neurologic signs, viral isolation and antigen detection in brain has been reported after peripheral inoculation, thus suggesting selection of viral subpopulations with high neurotropism (70).…”

Section: Studies With the Xj Prototype Strain In Guinea Figs And Primmentioning

confidence: 84%

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Epidemiology of argentine hemorrhagic fever

1988

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Present knowledge points to horizontal transmission as the most significant mechanism for Junín virus maintenance in the main natural reservoirs, namely Calomys musculinus and Calomys laucha. The existence of naturally infected Akodon azarae, both within and outside the endemic area, as well as the finding that other species, ecologically and phylogenetically related to the main reservoirs, such as Akodon molinae and Calomys callidus, can experimentally develop persistent infections with virus shedding through fauces, suggest a potential role for these cricetids as alternative reservoirs. Furthermore, since those rodents inhabit the borders of the area in which Argentine Hemorrhagic fever is endemic, the risk of spread of this area is to be expected. Whether the establishment of Junín virus persistence in Calomys musculinus and other reservoirs depends on viral or host factors, such as a selective defect in L3T4+ lymphocytes as recently shown for mice, remains to be explored.

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Section: Studies With the Xj Prototype Strain In Guinea Figs And Primmentioning

confidence: 80%

Section: Studies With the Xj Prototype Strain In Guinea Figs And Primmentioning

confidence: 84%

Epidemiology of argentine hemorrhagic fever

1988

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“…3). Within (15,16), with peak geometric mean titers reaching 3.49 and 3.46 log1o PFU/ml on day 17 postinoculation in serum and throat swabs, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Guinea pigs (7,17,25), marmosets (5,22), and rhesus macaques (6,15,16) have been shown to be useful models for studying issues related to the pathogenesis of AHF. Recently, ribavirin (1--D-ribofuranosyl-1,2,4-triazole-3-carboxyamide), a broad-spectrum antiviral compound with significant activity in vitro and in vivo against a variety of viruses that cause hemorrhagic fever syndromes in humans, was evaluated for its therapeutic efficacy in guinea pigs infected with Junin virus (12).…”

mentioning

confidence: 99%

Ribavirin prophylaxis and therapy for experimental argentine hemorrhagic fever

McKee

Huggins

Trahan

et al. 1988

Antimicrob Agents Chemother

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Junin virus-infected rhesus macaques received prophylactic and therapeutic ribavirin to assess the potential of this drug for treating humans with Argentine hemorrhagic fever. When ribavirin was administered intramuscularly at the time of experimental infection with the lethal P3790 strain of Junin virus, all animals were protected from clinical disease. A delay in the initiation of therapy until after the onset of illness resulted in improvement and resolution of systemic signs of disease; however, survivors subsequently developed a late-onset central nervous system infection which was fatal in two of three animals. Side effects of ribavirin included thrombocytosis and severe anemia, both of which resolved promptly on withdrawal of drug therapy. Results of this study suggest that ribavirin may prove useful in treating humans with Argentine hemorrhagic fever.

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“…Guinea pig infection models have been described for LASV, JUNV and Guanarito virus (GTOV) [28], [29], [30], [31], and are the best-suited small animal models to further investigate the activity of favipiravir. Due to the maximum containment requirement and high costs associated with conducting studies with highly pathogenic arenaviruses, the aim of the present work was to evaluate favipiravir in the guinea pig PICV infection model [32], [33], as a means to optimize treatment conditions to assist in the planning of future studies in biosafety level 4 (BSL-4) containment.…”

Section: Introductionmentioning

confidence: 99%

Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of Clinical Disease in a Model of Arenavirus Hemorrhagic Fever

et al. 2011

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BackgroundLassa and Junín viruses are the most prominent members of the Arenaviridae family of viruses that cause viral hemorrhagic fever syndromes Lassa fever and Argentine hemorrhagic fever, respectively. At present, ribavirin is the only antiviral drug indicated for use in treatment of these diseases, but because of its limited efficacy in advanced cases of disease and its toxicity, safer and more effective antivirals are needed.Methodology/Principal FindingsHere, we used a model of acute arenaviral infection in outbred guinea pigs based on challenge with an adapted strain of Pichindé virus (PICV) to further preclinical development of T-705 (Favipiravir), a promising broad-spectrum inhibitor of RNA virus infections. The guinea pig-adapted passage 19 PICV was uniformly lethal with an LD50 of ∼5 plaque-forming units and disease was associated with fever, weight loss, thrombocytopenia, coagulation defects, increases in serum aspartate aminotransferase (AST) concentrations, and pantropic viral infection. Favipiravir (300 mg/kg/day, twice daily orally for 14 days) was highly effective, as all animals recovered fully from PICV-induced disease even when therapy was initiated one week after virus challenge when animals were already significantly ill with marked fevers and thrombocytopenia. Antiviral activity and reduced disease severity was evidenced by dramatic reductions in peak serum virus titers and AST concentrations in favipiravir-treated animals. Moreover, a sharp decrease in body temperature was observed shortly after the start of treatment. Oral ribavirin was also evaluated, and although effective, the slower rate of recovery may be a sign of the drug's known toxicity.Conclusions/SignificanceOur findings support further development of favipiravir for the treatment of severe arenaviral infections. The optimization of the experimental favipiravir treatment regimen in the PICV guinea pig model will inform critical future studies in the same species based on challenge with highly pathogenic arenaviruses such as Lassa and Junín.

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The Guinea Pig Model for Argentine Hemorrhagic Fever *

Cited by 22 publications

References 0 publications

Epidemiology of argentine hemorrhagic fever

Epidemiology of argentine hemorrhagic fever

Ribavirin prophylaxis and therapy for experimental argentine hemorrhagic fever

Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of Clinical Disease in a Model of Arenavirus Hemorrhagic Fever

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