[Rotaviruses in human and veterinary medicine]

Abstract

Rotaviruses are the commonest cause of diarrhea and are responsible for more than 25% of all deaths from diarrhea worldwide. Children become infected early in life and most infections in infants older than 3 months are symptomatic. These viruses account for 18 million cases of moderate or severe disease and 900,000 deaths each year. The incidence of rotaviral disease is similar in developed and developing countries but the number of deaths is higher in developing countries. Infections occur throughout the year in developing countries but are seasonal in developed countries, occurring mainly between October and March. The mean age at first infection is 6 to 9 months in developing countries and 9 to 15 months in developed countries. The greater severity of infections in developing countries is associated with malnutrition, lower hygiene standards and the lactose malabsorption and deficiencies of zinc and vitamin A that accompany diarrhea. Many mixed infections also increase the severity of the rotavirus infection. The clinical symptoms of the disease in hospitalized patients are diarrhea, vomiting and dehydration. There is more vomiting than with bacterial infections. The severity of the clinical symptoms depends on the virulence of different strains. The disease is more severe and persistent in patients with reduced immunity. Age also has an effect. All children may have rotavirus in their feces but the percentage of children developing diarrhea is highest at an age of 3 to 6 months and decreases steadily thereafter. Rotaviruses can survive in air and may remain on surfaces for several hours. They are thus often responsible for nosocomial infections. Rotavirus was first identified in cattle in 1969. The virulence of the strain and the age of the calf at infection are important in the pathogenesis of rotaviral infection in cattle. Replacement of villous enterocytes is slow in newborn calves. This means that newborn calves are susceptible to disease caused by strains that are only moderately virulent. They are, however, protected during the first days of life by antibodies transmitted via the colostrum. There is competition between the rate of replication of rotavirus and replacement of enterocytes in older animals so only more virulent strains cause diarrhea in six-week-old calves. Adult animals become resistant to disease, but not to infection. The rotavirus genome consists of 11 segments of double-stranded RNA. Genetic recombination between these segments occurs naturally and can be reproduced in vitro. Recombinants between human and bovine strains have been identified but the epidemiological importance of this is unknown. The genomic segments encode 6 structural proteins (VP) and 5 non-structural proteins (NSP). VP6, the major capsid antigen, present can be used to identify groups of rotaviruses. The presence of VP7 indicates that the virus belongs to the G (glycoprotein) group of serotypes. There are 14 G serotypes, 10 of which can infect humans. The four main G serotypes are G1 to G4, with G1 accounting for 60% of human serotypes. The presence of VP4 identifies the P (protease-sensitive) serotype. The serotypes have different geographic distributions with G1P8 responsible for more than 50% of epidemics worldwide. The WHO project for the control of rotaviral infections focuses on avoiding fecal contamination. This is achieved by ensuring high standards of food hygiene, sewage treatment and chlorinated running water and by introducing vaccination when vaccines become available. Recombinant animal (bovine or simian) and human rotaviruses are currently being tested in phase III studies. Attenuated live human viruses, including cold-adapted strains are being tested in phase I trials. The quadrivalent recombinant rhesuslhuman vaccine had only mild side-effects in children and was effective, giving 82-92% protection against severe diarrhea over two years and 50% protection on average. (ABSTRACT TRUNCATED)