Abstract
Prompted by the discovery of new gastrointestinal viruses, the NIH, NIAID and WHO investigated the etiology of acute diarrhea that occurred from 1976–1979 in a global cohort of infants and young children. Rotaviruses were found to be major pathogens worldwide, whereas the Norwalk virus could not be detected using a radioimmunoassay. The aim of this study is to re-evaluate the role and diversity of rotaviruses and noroviruses in the original cohort using more sensitive current technologies. Stools collected from Asia, Africa, and South America (n = 485) were evaluated for viral genotypes by RT-PCR and sequencing. Rotaviruses were detected in 28.9% and noroviruses in 9.7% of the specimens, with G1 rotaviruses and GII noroviruses accounting for the majority of each respective virus. Various strains in this study predated the currently assigned dates of discovery for their particular genotype, and in addition, two noroviruses (KL45 and T091) could not be assigned to current genotypes. Phylogenetic analyses demonstrated a relative constancy in circulating rotavirus genotypes over time, with several genotypes from this study becoming established in the current repertoire of viral species. Similarly, GII noroviruses have maintained dominance, with GII.4 noroviruses continuing as a predominant genotype over time. Taken together, the complex molecular epidemiology of rotaviruses and noroviruses circulating in the 1970’s is consistent with current patterns, an important consideration in the design of multivalent vaccines to control these viruses.
Highlights
Diarrhea has consistently been described as the second leading cause of mortality among children under five years old worldwide [1]
Relative Detection of Rotaviruses and Noroviruses A total of 485 diarrheic stools obtained in a multi-center epidemiologic study in 1976–1979 were examined for rotaviruses and noroviruses using quantitative RT-PCR [23] and diagnostic sequencing [24,25]
Following the discovery of rotaviruses in 1973 [18] and noroviruses in 1972 [17], the Laboratory of Infectious Diseases (LID) collaborated with the World Health Organization (WHO) to assess the role of viruses in childhood diarrhea [19]
Summary
Diarrhea has consistently been described as the second leading cause of mortality among children under five years old worldwide [1]. Rotaviruses are the single most important agents of acute diarrhea associated with mortality in this age group, as these viruses were estimated to cause approximately 453,000 deaths a year, mostly in countries of Africa and Asia [2]. Noroviruses are the second leading cause of viral gastroenteritis in children under five years old, and are estimated to cause as many as 200,000 deaths annually among children in this age group in developing countries [3]. The most prevalent G-types that infect humans globally are characteristically G1 through G4, with G9 and G12 emerging in prevalence and G8 and G10 more geographically restricted [4,6,7,8,9]. Rotavirus vaccines are less efficacious in developing countries [11], which demonstrates the need for improved preventive and therapeutic strategies in areas where the disease burden is greatest
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