Treatment of lethal pichinde virus infections in weanling LVG/Lak hamsters with ribavirin, ribamidine, selenazofurin, and ampligen

Smee, Donald F.; Gilbert, John; Leonhardt, J. A.; Barnett, Bill B.; Huggins, John; Sidwell, Robert W.

doi:10.1016/0166-3542(93)90059-r

Cited by 33 publications

(44 citation statements)

References 19 publications

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“…Administration of ribavirin by the i.p. route has been shown to be effective against PCV infection in hamsters (Smee et al, 1993) (McCormick et al, 1986). Despite these encouraging data, the need exists for improving current treatment regimens that require doses of ribavirin, which can lead to varying degrees of toxicity.…”

Section: Determination Of Suboptimal Doses Of Po Ribavirinmentioning

confidence: 99%

“…A key study reported remarkable efficacy with high-risk Lassa virus-infected individuals when ribavirin therapy was initiated by day 6 following the onset of fever, with more limited effectiveness seen when treatment began 7 days after signs of illness (McCormick et al, 1986). This study, as well as the treatment of experimental Lassa virus infections in non-human primates ( Jahrling et al, 1980) (Gowen et al, 2005) (Smee et al, 1993) …”

Section: The Pcv Hamster Infection Model Can Be Worked With Safely mentioning

confidence: 99%

“…route (Snell, 2001 (Smee et al, 1993) (Gowen et al, 2005 Comparison of independent and combined ribavirin and IFN alfacon-1 therapy starting on days 3 or 4 of PCV infection…”

Section: Determination Of Suboptimal Doses Of Po Ribavirinmentioning

confidence: 99%

“…Virus titres were assayed using an infectious cell culture assay as previously described (Smee et al, 1993) (Reed & Muench, 1938 …”

Section: Liver and Serum Virus Titresmentioning

confidence: 99%

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Combinatorial Ribavirin and Interferon Alfacon-1 Therapy of Acute Arenaviral Disease in Hamsters

Gowen

Smee

Wong

et al. 2006

Antivir Chem Chemother

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Several arenaviruses endemic to South America (Junin, Machupo, and Guanarito) and Africa (Lassa) are known to cause frequently fatal haemorrhagic fever. With the exception of ribavirin, which has demonstrated efficacy in cases of Lassa fever, there is no other effective therapeutic for the treatment of arenaviral haemorrhagic fever. We have recently reported that consensus interferon-α α (IFN alfacon-1) can protect hamsters from lethal Pichinde virus (PCV) infection, which serves as a model for acute arenaviral disease in humans. Here we demonstrate highly effective therapy through the combined use of ribavirin with IFN alfacon-1 for the treatment of PCV infection in hamsters. Ribavirin was given orally, twice per day for 7 days, and IFN alfacon-1 was administered intraperitoneally once per day for 10 days. Treatments were initiated 1-5 days post-virus challenge using various dose combinations, many of which were less than optimal when the drugs were given independently. Combining suboptimal doses of ribavirin (5-10 mg/kg/day) with IFN alfacon-1 (5-10 µ g/kg/day), we were able to demonstrate increased protection from mortality, reduced viral burden and liver disease, and greatly extended survival times as compared to treatments where drugs were administered alone. Our data indicate that combination therapy results in synergistic activity that may slow down the progression of the disease and decrease fatality rates associated with severe arenaviral infections in humans. Further, combination therapy reduces the effective dosage of ribavirin, which would serve to limit its toxicity.

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Section: Determination Of Suboptimal Doses Of Po Ribavirinmentioning

confidence: 99%

Section: The Pcv Hamster Infection Model Can Be Worked With Safely mentioning

confidence: 99%

“…route (Snell, 2001 (Smee et al, 1993) (Gowen et al, 2005 Comparison of independent and combined ribavirin and IFN alfacon-1 therapy starting on days 3 or 4 of PCV infection…”

Section: Determination Of Suboptimal Doses Of Po Ribavirinmentioning

confidence: 99%

“…Virus titres were assayed using an infectious cell culture assay as previously described (Smee et al, 1993) (Reed & Muench, 1938 …”

Section: Liver and Serum Virus Titresmentioning

confidence: 99%

See 2 more Smart Citations

Combinatorial Ribavirin and Interferon Alfacon-1 Therapy of Acute Arenaviral Disease in Hamsters

Gowen

Smee

Wong

et al. 2006

Antivir Chem Chemother

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show abstract

“…Treatment with ribavirin exhibited some benefit for patients suffering from Lassa fever, Argentine hemorrhagic fever, and hepatitis C (21,22,36,37,(45)(46)(47). In experimental animal model infections, ribavirin has also been demonstrated to exhibit broad antiviral activities (7,26,28,29,53,54).…”

Section: Noncytopathic Viruses Such As Human Immunodeficiency Virus (mentioning

confidence: 99%

Additive Effect of Neutralizing Antibody and Antiviral Drug Treatment in Preventing Virus Escape and Persistence

Seiler

Senn

Klenerman

et al. 2000

J Virol

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Poorly cytopathic or noncytopathic viruses can escape immune surveillance and establish a chronic infection. Here we exploited the strategy of combining antiviral drug treatment with the induction of a neutralizing antibody response to avoid the appearance of neutralization-resistant virus variants. Despite the fact that H25 immunoglobulin transgenic mice infected with lymphocytic choriomeningitis virus mounted an early neutralizing antibody response, the virus escaped from neutralization and persisted. After ribavirin treatment of H25 transgenic mice, the appearance of neutralization-resistant virus was prevented and virus was cleared. Thus, the combination of virus-neutralizing antibodies and chemotherapy efficiently controlled the infection, whereas each defense line alone did not. Similar additive effects may be unexpectedly efficient and beneficial in humans after infections with persistent viruses such as hepatitis C virus and hepatitis B virus and possibly human immunodeficiency virus.

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Molecular approaches for the treatment of hemorrhagic fever virus infections

Andrei

Clercq

1993

Antiviral Research

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Treatment of lethal pichinde virus infections in weanling LVG/Lak hamsters with ribavirin, ribamidine, selenazofurin, and ampligen

Cited by 33 publications

References 19 publications

Combinatorial Ribavirin and Interferon Alfacon-1 Therapy of Acute Arenaviral Disease in Hamsters

Combinatorial Ribavirin and Interferon Alfacon-1 Therapy of Acute Arenaviral Disease in Hamsters

Additive Effect of Neutralizing Antibody and Antiviral Drug Treatment in Preventing Virus Escape and Persistence

Molecular approaches for the treatment of hemorrhagic fever virus infections

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