Preclinical evaluation in monkeys of a ribavirin regimen proposed for use in Lassa fever patients

Wannarka, Gerald L.; Stephen, Edward L.; Canonico, Peter G.

doi:10.1016/0041-008x(82)90334-9

Cited by 9 publications

(5 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3), but it resolved promptly and consistently on withdrawal of drug therapy. Rhesus macaques have been shown to be particularly sensitive to the erythrotoxic effects of ribavirin, to an extent greater than that seen in humans (2,21). While the short-term impact on bone marrow in these animals can only be inferred from peripheral hematological studies, histopathological findings conducted up to 5 months following therapy revealed no long-term adverse effects.…”

Section: Discussionmentioning

confidence: 93%

“…These findings persisted for 2 to 3 weeks and then gradually disappeared. Moderate weight loss occurred, averaging 10% of preinfection values; however, weight change did not differ significantly (P < 0.05) between prophylactic and placebo groups until 21 days postinfection. All animals in group 2 survived (P = 0.03 versus group 1).…”

Section: Resultsmentioning

confidence: 99%

“…2). Beginning 1 week after the initiation of drug therapy, platelet counts increased progressively, reaching a significant deviation from that in the placebo group (P = 0.007) by day 21 (Fig. 3).…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Ribavirin prophylaxis and therapy for experimental argentine hemorrhagic fever

McKee

Huggins

Trahan

et al. 1988

Antimicrob Agents Chemother

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Ribavirin prophylaxis and therapy for experimental argentine hemorrhagic fever

McKee

Huggins

Trahan

et al. 1988

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…After much experimentation, ,it was found that 30 mg/kg ribavirin daily for nine to 19 days arid three doses of 1 ml/kg of immune serum at three-day intervals approximated a successful therapeutic regimen (102). Time after infection seemed to be the critical factor.…”

Section: Lassa Fevermentioning

confidence: 99%

Ribavirin: A clinical overview

Fernandez¹,

Banks²,

Smith³

1986

Eur J Epidemiol

View full text Add to dashboard Cite

Ribavirin, a broad spectrum, non-interferon-inducing virustatic chemotherapeutic agent, demonstrates activity against a wide range of RNA and DNA viruses, including the retrovirus known to cause the acquired immune deficiency syndrome. The drug's proposed mechanism of action, as well as pharmacokinetics are discussed, and preclinical toxicity, safety and clinical efficacy studies are presented. To date, the best success has occurred in the use of ribavirin to treat respiratory syncytial virus infection in infants and young children and to treat influenza A and B virus infections in young adults. Viral infections, particularly viral pneumonia, are often life-threatening in infants with severe combined immunodeficiency disease (SCID), and ribavirin aerosol has been used successfully to treat respiratory syncytial virus and parainfluenza virus infection of immunodeficient children. Special note is taken of ribavirin's clinical benefit in treating severe and life-threatening infections caused by the Lassa fever virus and the significant improvement over either the use of immune plasma or supportive therapy alone. Indeed, ribavirin thus emerges as the first antiviral drug that is able to reduce mortality in a highly lethal systemic disease by more than 90%. Additional studies demonstrate the drug's efficacy in acute viral hepatitis, herpesvirus infections, and measles. Controlled clinical trials are underway to test the drug in patients infected with the AIDS virus.

show abstract

“…The views of the authors do not purport to reflect the positions of the Department of the Army or the Department of Defense. Preclinical toxicology studies of riba virin have shown that high doses produce anemia in rhesus monkeys [15]. More de tailed studies of the effect of ribavirin on the blood and bone marrow of rhesus monkeys [3,4] have established that the drug causes a normochromic normocytic anemia which is a consequence of in creased red cell destruction, as well as de creased red cell production.…”

Section: Introductionmentioning

confidence: 99%

Morphological Alterations in Blood and Bone Marrow of Ribavirin-Treated Monkeys

Cosgriff¹,

Hodgson²,

Canonico³

et al. 1984

Acta Haematol

View full text Add to dashboard Cite

The antiviral drug ribavirin (1, β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) produced significant hematologic effects when administered to rhesus monkeys by intramuscular injection over 10 days in doses of 30 or 100 mg/kg/day. The monkeys developed dose-related progressive anemia and thrombocytosis associated with marrow erythroid hypoplasia and megakaryocyte hyperplasia. In addition, bone marrow examination revealed phagocytosis of erythroid elements by histiocytes; vacuolization of erythroid precursors, and to a lesser extent precursors of other cell types; and occasional erythroid precursors with megaloblastoid appearance. The alterations were transient and disappeared on discontinuation of the drug.

show abstract

Preclinical evaluation in monkeys of a ribavirin regimen proposed for use in Lassa fever patients

Cited by 9 publications

References 5 publications

Ribavirin prophylaxis and therapy for experimental argentine hemorrhagic fever

Ribavirin prophylaxis and therapy for experimental argentine hemorrhagic fever

Ribavirin: A clinical overview

Morphological Alterations in Blood and Bone Marrow of Ribavirin-Treated Monkeys

Contact Info

Product

Resources

About