Rhesus monkeys were experimentally infected with Lassa virus to establish their suitability as a nonhuman primate model for the human disease and to test the protective efficacy of ribavirin, an antiviral drug. Six of 10 untreated control monkeys died after subcutaneous inoculation of 10(6.1) plaque-forming units of Lassa virus (strain Josiah). Infectivity titrations of tissue homogenates from the six dead monkeys indicated significant replication in all tissues tested except the central nervous system. This distribution of virus was confirmed by direct immunofluorescence examination of cryostat-sectioned tissues. Ribavirin was beneficial in the treatment of two groups of infected monkeys. Four monkeys first treated on the day of viral inoculation experienced only mild clinical disease; four monkeys first treated five days later experienced a more severe illness. None of the eight monkeys treated with ribavirin died. Viremia titers and elevations of levels of serum transaminases in treated monkeys were significantly lower than in controls. Ribavirin may be beneficial in the treatment of humans exposed to this life-threatening virus.

No abstract

Rift Valley fever (RVF) is a major cause of human morbidity and mortality in endemic areas of sub-Saharan Africa and has the potential to cause epidemic disease in receptive areas world-wide. In this study, a RVF viral isolate from the 1977 Egyptian epidemic (ZH-501) inoculated intravenously into rhesus macaques caused a benign viremic infection in most, but resulted in the hemorrhagic fever syndrome in 20 per cent (3 of 15). Serious disease of this type has not previously been observed in nonhuman primates inoculated with RVF virus and may be a consequence of the viral strain used or the route of inoculation. Severe disease was accompanied by extensive liver necrosis, disseminated intravascular coagulation, and microangiopathic hemolytic anemia. We also attempted to prevent RVF by passive transfer of serum from vaccinated rhesus monkeys (plaque-reduction neutralization test titer 1:2,560). As little as 0.025 ml/kg prevented the development of viremia in naive rhesus monkeys after subcutaneous inoculation of virus. The monkey model should be helpful in understanding the pathogenesis and prevention of human RVF.

Lassa virus-infected cynomolgus monkeys were treated with Lassa virus-immune monkey serum containing a high concentration of neutralizing antibody, the antiviral drug ribavirin, or a combination of ribavirin plus immune serum at various times after infection. When treatment was initiated early (day 0 or 4), either ribavirin (30 mg/kg of body weight per day) or immune serum alone protected monkeys. However, when the initial treatment was delayed until day 7, only four of eight ribavirin-treated and only one of six serum-treated monkeys survived. Treatment with ribavirin combined with immune serum was more successful; all infected monkeys given combination treatment survived, including six treated initially on day 10. Increased doses of ribavirin given alone were toxic. The empirical observation that combined treatment with ribavirin plus serum results in enhanced survival in experimentally infected monkeys suggests that combined treatment might benefit human patients with Lassa fever as well.