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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A nonhuman primate model for Argentine hemorrhagic fever has been developed that closely mimics the human clinical syndrome. Parenteral infection of adult Macaca mulatta with low-passage isolates of two Junin viral strains resulted in distinctive hemorrhagic or neurological disease in rhesus macaques that correlated with clinical illness patterns present in the humans from whom the viral strains were obtained. Transient leukopenia, together with thrombocytopenia and secondary bacterial septicemia, were documented among animals infected with both viral strains. In contrast, differing patterns of viremia, oropharyngeal viral shedding, and antibody response occurred in the two virus-infected groups. These results, together with postmortem virologic and histopathologic findings, suggest that viral-strain-specific factors are important determinants of clinical disease patterns in this model system.
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