The prophylactic effectiveness of oral administration of ribavirin (1-(3-n-ribofuranosyl-1,2,4-triazole-3-carboxamide) against experimentally induced influenza A infection was evaluated in a double-blind clinical trial in normal volunteers. Fourteen men received ribavirin capsules (1,000 mg/day in four divided doses) and 15 other men received identical-appearing placebo capsules beginning 6 h after the intranasal inoculation of 3.4 log10 50%o tissue culture infectious doses of influenza virus A/Victoria/3/75 H3N2 and continuing for 5 days after challenge. The total number of moderate-to-severe symptom scores and the total number of temperatures :100'F (37.8°C) were significantly lower in the ribavirin group compared with the placebo group. The mean quantity of virus shed in nasal wash specimens and the total number of days that there were viral titers greater than 1.0 log1o 50% tissue culture infectious doses per ml were significantly greater in the placebo group. There was no difference between the frequencies of virus isolated or the antibody responses in the two groups. Therefore, prophylactic ribavirin ameliorated symptoms and fever indicative of moderate-to-severe illness, but had no effect on the manifestations of mild illness in response to influenza A challenge. A transient rise in total serum bilirubin occurred in 29o of the ribavirin-treated volunteers and in none of the placebo-treated volunteers.Ribavirin (1-,&D-ribofuranosyl-1,2,4-triazole-

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The prophylactic and/or therapeutic effect of a low-molecular-weight interferon inducer, CP-20,961, was tested in a double-blind placebo controlled study of experimental influenza A/England/42/72 (H3N2) infection in normal volunteers. Ten volunteers received 961 and 10 received placebo. Interferon was detected in nasal secretions of nine of the former and three of the latter group (P < 0.05). Seven in each group became ill, and severity of illness was not different. Also, quantitative virus shedding patterns and antibody response were not different between the two groups. The negative result may have been due to the relatively low quantities of interferon induced.

Live attenuated cold-adapted influenza vaccine is undergoing evaluation in man. Several strains have proven to be safe, immunogenic, nontransmissible, and protective against experimental challenge. In this study of A/Peking/2/79(H3N2), with six internal genes from the cold-adapted (Ca) parent A/Ann Arbor/6/60(H2N2), we encountered at the highest input multiplicity, 28% illness rate among individuals infected with vaccine. Reversion to wild type and excessive viral replication did not occur. Physical characteristics of the vaccine were similar to nonreactogenic vaccine A/Washington/897/80(H3N2). At ten- and 100-fold lower input multiplicities, infection frequency was maintained, but reactions did not occur. We compared the observations in this study with those made in a similar study of A/Scotland/840/74(H3N2), a cold-adapted vaccine with five genes from the Ca parent in which reactogenicity also was noted. The dose of vaccine virus in relation to tissue culture infectious doses required to infect 50% of susceptibles (HID50) was proportionally lower for both A/Peking/2/79(H3N2) and A/Scotland/80(H3N2). Hence, when the vaccine was undiluted the recipients were inoculated with more than 100 HID50. We concluded that the very high input could be avoided if vaccines were screened beginning at 1/1,000 of maximum titers. Ca vaccines must be safe before they undergo field trials.

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