2. Introduction Reoviruses are medium-sized viruses with a double-stranded, segmented RNA genome. The family includes human rotaviruses, the most important cause of infantile gastroenteritis around the world (Figure ). Acute gastroenteritis is a very common disease with significant public health impact. In developing countries it is estimated to cause as many as 1.5 million deaths of preschool children annually, of which rotavirus is responsible for about 600,000 deaths.

4. Virion: Icosahedral, 60–80 nm in diameter, double capsid shell. Composition: RNA (15%), protein (85%). Genome: Double-stranded RNA, linear, segmented (10–12 segments); total genome size 16–27 kbp. Proteins: Nine structural proteins; core contains several enzymes. Envelope: None (transient pseudoenvelope is present during rotavirus particle morphogenesis). Replication: Cytoplasm; virions not completely uncoated. Outstanding characteristics: Genetic reassortment occurs readily Rotaviruses are the major cause of infantile diarrhea Reoviruses are good models for molecular studies of viral pathogenesis

5. Classification & Antigenic Properties Rotaviruses have been classified into five species (A–E), plus two tentative species (F and G), based on antigenic epitopes on the internal structural protein VP6. These can be detected by immunofluorescence, ELISA, and immune electron microscopy (IEM). Group A rotaviruses are the most frequent human pathogens. Outer capsid proteins VP4 and VP7 carry epitopes important in neutralizing activity, with VP7 glycoprotein being the predominant antigen. Five serotypes are responsible for the majority of human disease.

7. Pathogenesis Rotaviruses infect cells in the villi of the small intestine (gastric and colonic mucosa are spared). They multiply in the cytoplasm of enterocytes and damage their transport mechanisms. One of the rotavirus-encoded proteins, NSP4, is a viral enterotoxin and induces secretion by triggering a signal transduction pathway. Damaged cells may slough into the lumen of the intestine and release large quantities of virus, which appear in the stool (up to 10 12 particles per gram of feces). Viral excretion usually lasts 2–12 days in otherwise healthy patients but may be prolonged in those with poor nutrition. Diarrhea caused by rotaviruses may be due to impaired sodium and glucose absorption as damaged cells on villi are replaced by nonabsorbing immature crypt cells. It may take 3–8 weeks for normal function to be restored.

8. Clinical Findings & Laboratory Diagnosis Rotaviruses cause the major portion of diarrheal illness in infants and children worldwide but not in adults. There is an incubation period of 1–3 days. Typical symptoms include watery diarrhea, fever, abdominal pain, and vomiting, leading to dehydration. In infants and children, severe loss of electrolytes and fluids may be fatal unless treated. Patients with milder cases have symptoms for 3–8 days and then recover completely. However, viral excretion in the stool may persist up to 50 days after onset of diarrhea. Asymptomatic infections, with seroconversion, occur. In children with immunodeficiencies, rotavirus can cause severe and prolonged disease. Adult contacts may be infected, as evidenced by seroconversion, but they rarely exhibit symptoms, and virus is infrequently detected in their stools. A common source of infection is contact with pediatric cases. However, epidemics of severe disease have occurred in adults, especially in closed populations, as in a geriatric ward. Group B rotaviruses have been implicated in large outbreaks of severe gastroenteritis in adults in China.

10. Laboratory diagnosis rests on demonstration of virus in stool collected early in the illness and on a rise in antibody titer. Virus in stool is demonstrated by enzyme immunoassays (EIAs). Genotyping of rotavirus nucleic acid from stool specimens by the polymerase chain reaction is the most sensitive detection method. Serologic tests can be used to detect an antibody titer rise, particularly ELISA. Epidemiology & Immunity Rotaviruses are the single most important worldwide cause of gastroenteritis in young children. Estimates range from 3 billion to 5 billion for annual diarrheal episodes in children under 5 years of age in Africa, Asia, and Latin America, resulting in as many as 1 million deaths. Developed countries have a high morbidity rate but a low mortality rate. Typically, up to 50% of cases of acute gastroenteritis of hospitalized children throughout the world are caused by rotaviruses. Rotavirus infections usually predominate during the winter season. Symptomatic infections are most common in children between ages 6 months and 2 years, and transmission appears to be by the fecal–oral route. Nosocomial infections are frequent.

11. By age 3 years, 90% of children have serum antibodies to one or more types. This high prevalence of rotavirus antibodies is maintained in adults, suggesting subclinical reinfections by the virus. Rotavirus reinfections are common; it has been shown that young children can suffer up to five reinfections by 2 years of age. Asymptomatic infections are more common with successive reinfections. Local immune factors, such as secretory IgA or interferon, may be important in protection against rotavirus infection. Asymptomatic infections are common in infants before age 6 months, the time during which protective maternal antibody acquired passively by newborns should be present. Such neonatal infection does not prevent reinfection, but it does protect against the development of severe disease during reinfection.

12. Treatment & Control Treatment of gastroenteritis is supportive, to correct the loss of water and electrolytes that may lead to dehydration, acidosis, shock, and death. Management consists of replacement of fluids and restoration of electrolyte balance either intravenously or orally, as feasible. The infrequent mortality from infantile diarrhea in developed countries is due to routine use of effective replacement therapy. In view of the fecal–oral route of transmission, wastewater treatment and sanitation are significant control measures. An oral live attenuated rhesus-based rotavirus vaccine was licensed in the United States in 1998 for vaccination of infants. It was withdrawn a year later because of reports of intussusception (bowel blockages) as an uncommon but serious side effect associated with the vaccine. In 2006, an oral pentavalent bovine-based rotavirus vaccine was licensed in the United States, followed by licensing of an oral monovalent human- based rotavirus vaccine in 2008. Neither vaccine appears to be associated with intussusception. A safe and effective vaccine remains the best hope for reducing the worldwide burden of rotavirus disease.