Although rotaviruses are established as the single most important cause of severe diarrhea of infants and young children world-wide, being associated with 30-50% of such illnesses, the etiologic agents of at least 30% of severe diarrhea remain to be elucidated. Two groups of viruses, the astroviruses and caliciviruses, are known to cause infection in pediatric populations but their role as etiologic agents of severe diarrheal illness of infants and young children remains controversial. The goal of this project is to place these viruses in perspective with regard to their relative contribution to various forms of acute gastroenteritis in infants and young children. The availability of stool and serum specimens from several large-scale pediatric studies should enable us to address these issues. Two major clinical studies provide the focus of this project. One is a longitudinal study (1955-1969) at Junior Village, a welfare institution for homeless but otherwise normal children, and the other a cross-sectional study (1974-1991) of children hospitalized with gastroenteritis at Children's Hospital National Medical Center, Washington, DC. Our goal in the Junior Village studies is to investigate the natural history of calicivirus and astrovirus infections in a longitudinal setting, whereas the Children's Hospital study provides materials that should allow us to determine the importance of calicivirus and astrovirus as agents of severe gastroenteritis requiring admission to the hospital. There is evidence from several studies that the caliciviruses and astroviruses both cause infection in infants but, as yet, their importance as etiologic agents of severe gastroenteritis is not established. This type of information must be obtained before priorities for vaccine development can be formulated. An essential goal of this study is the development of suitable assays for the astroviruses to enable the study of specimens obtained from the settings described above. In addition to the specific goals outlined above, a comparison of two assays used for the detection of neutralizing antibodies to rotavirus was made: one the classical plaque reduction neutralization assay and the other a recently developed ELISA-based neutralization assay (Ward).
