Parsons. Bynoe, Pereira, and Tyrrell (8) conducted a volunteer study using Coxsackie A-2 1 virus and showed that this agent could produce a mild upper respiratory illness in young adults after an incubation period of 2 to 4 days. Virus was detected in pharyngeal specimens over a 6-day period of observation, but was less often found in fecal specimens. In two recent reports (5, 6), Coxsackie A-21 virus was associated with mild upper respiratory illness in military personnel at Camp Lejeune, North Carolina. Virus was readily recovered from pharyngeal specimens of ill recruits, and significant rises in neutralizing and hemagglutination-inhibiting antibodies were demonstrated.The evidence that this agent was a cause of human disease suggested the need for additional knowledge of its effects in man. Accordingly, studies were made in normal volunteers in which virus was administered by the nasopharyngeal route, or directly into the intestinal tract in subjects with no, intermediate, or high titers of homologous antibody. The study revealed that nasopharyngeal inoculation of subjects without measurable prechallenge antibody was followed by a systemic illness with fever and myalgia that was more severe when the inoculum was large. The presence of intermediate amounts of antibody before inoculation was associated with a syndrome of common cold, whereas men with high titers exhibited no illness. It was also found that the agent, although designated an enterovirus, was isolated most frequently from throat swabs. This finding was confirmed when it was found that direct intestinal inoculation produced only transient infection and no illness or antibody response. These findings are described in the following report.
METHODS1 %olhteers. The men who participated in these experiments were volunteers from several federal correctional institutions. Selection was based on willingness to participate, good health, and on the presence of a suitable level of antibody to Coxsackie A-21 for a particular experiment.Clinical studies. Men were confined 3 per room for 3 to 4 days before and 3 weeks after viral inoculation. Examinations of the volunteers were made twice daily by two physicians who were unaware of the virus to be given, or of the antibody status of individual volunteers. Diagnosis of illness was made in a volunteer only by mutual agreement of both examiners. Oral temperatures were taken four times a day, and significant fever was considered to be any temperature greater than 37.50 C (99.50 F). Initial preinoculation leukocyte counts, sedimentation rate, and hemoglobin determination were obtained and then repeated on days 1, 2, 3, 5 to 9, and 12 to 15 after inoculation. A urine analysis was performed before and once after inoculation. Studies of liver function including bilirubin, alkaline phosphatase, transaminase, Bromsulphalein retention, thymol turbidity, and cephalin flocculation were made before and 3 days after inoculation. Electrocardiograms and chest roentgeno-840