A reovirus-like agent (rotavirus) in gastroenteritis of children. Virus detection and serological studies.

A reovirus-like agent (rotavirus) was detected in 26 children (44%) when fecal specimens from 59 children with acute gastroenteritis were examined by electron microscopy. No rotavirus was detected in the feces of 49 children with other diseases. Sera from the acute and the convalescent phase from 40 children with acute gastroenteritis and from 18 other patients were examined for antibodies against a bovine rotavirus by an indirect fluorescent antibody test. 26 of the patients with gastroenteritis (65%) developed antibodies during their disease, whereas none of the other patients showed a rise in antibody titre. The specimens were submitted to the laboratory from hospitalized children during the period January 1973 through March 1975. Most of the cases of rotavirus gastroenteritis occurred during late autumn and early winter among children between 0.5 and 3 years of age. It is concluded that electron microscopy is a sensitive diagnostic technique during the acute phase of the disease, and that the serological test with bovine rotavirus antigen served as a useful diagnostic tool.     

Reovirus-like agent in acute epidemic gastroenteritis in Japanese infants: fecal shedding and serologic response.

The reovirus-like agent, sometimes referred to as duovirus or rotavirus, was visualized by electron microscopy in stool extracts from Japanese infants and young children with acute epidemic gastroenteritis. The virus particles measured 70 nm in diameter and had double-shelled capsids. One hundred ten (89%) of 124 patients with the gastroenteritis had such virus particles in stools obtained during the acute phase. The virus particles were excreted in the stools usually during the first eight days of illness. Agglutination of virus particles by antibody present in convalescent-phase sera was demonstrated by immune electron microscopy. Complement-fixing antibody was detected as early as day 3 of illness, and antibody titers peaked during the second and third weeks of the disease. The antibody appearing in the acute and early convalescent phases was sensitive to 2-mercaptoethanol. Antibody resistant to 2-mercaptoethanol was produced approximately 10 days after the onset of the symptoms. The serologic evidence suggests that a primary infection with the reovirus-like agent was responsible for the clinical attack of acute gastroenteritis.     

Presence of two distinct types of rotavirus in infants and young children hospitalized with acute gastroenteritis in Mexico City, 1977.

Between December 1976 and January 1978, infection with rotavirus was detected by electron microscopy in 61 (25%) of 242 infants and young children hospitalized with acute gastroenteritis at two hospitals in Mexico City. This type of infection was more frequent in autumn than in winter. The presence of virus could also be detected by the electrophoretic pattern of its segmented, double-standed ribonucleic acid (RNA) in the stool samples taken from 52 (85%) of the 61 patients who were shown by electron microscopic examination to excrete rotavirus. Two distinct patterns, previously called 2s and 21, were observed, which were distinguishable by the relative migration of the second, 10th, and 11th viral RNA segments in gel electrophoresis; the 21 pattern was observed much more frequently than with the 2s pattern.     

Estimating hospital admissions due to rotavirus gastroenteritis from hospital episode statistics

OBJECTIVES: To determine the proportion of hospital admissions, in children < 5 years old, coded for intestinal infectious disease or non-infectious gastroenteritis, using ICD-10 codes, that were due to rotavirus infection. To assess how many children admitted with rotavirus gastroenteritis were given the specific ICD-10 code (A080) for this disease. METHODS: Sixteen-month prospective, observational study of children < 5 years old, admitted to district general hospital with: acute gastroenteritis (> or =3 loose stools/day), proven rotavirus infection and those coded as intestinal infectious disease or non-infectious gastroenteritis. RESULTS: Four hundred and twenty children < 5 years old were admitted with acute gastroenteritis. Rotavirus was detected in 170 children's stools. Acute rotavirus gastroenteritis accounted for 81/397 (20%) children coded as having non-infectious gastroenteritis and 32/81 (40%) coded for intestinal infectious disease. Only 18 children were coded for rotavirus gastroenteritis. Potentially preventable rotavirus gastroenteritis occurred in 122 children; 78 coded as non-infectious gastroenteritis (20%) and 26 coded for intestinal infectious disease (34%). CONCLUSIONS: The proportion of children coded with diarrhoeal diseases and found to have rotavirus is less than previously estimated. Using the specific code for rotavirus infection to estimate hospital admissions would be a gross underestimate. Hospital episode statistics cannot reliably estimate the burden of disease due to rotavirus.     

Human enteric coronaviruses: antigenic relatedness to human coronavirus OC43 and possible etiologic role in viral gastroenteritis

In a group of infants with acute nonbacterial gastroenteritis, examination of paired sera for antibody to human coronavirus (HCV) OC43 and neonatal calf diarrhea coronavirus showed a peculiar pattern of serological response, restricted only to HCV OC43 surface antigens, in a significantly higher proportion than among age-matched controls. In another group of infants and young children with acute nonbacterial gastroenteritis, fecal excretion of coronavirus-like particles was detected by electron microscopy in 34 (16.3%) of 208 patients as compared with three (1.6%) of 182 controls (P less than .01). Two strains of human enteric coronavirus (HECV) were purified from stools of two patients, and immune sera were raised in mice and guinea pigs. Immune electron microscopy showed a two-way cross-reactivity between HECV and HCV OC43 when tested with immune sera and convalescent-phase sera from patients with infection due to HECV or HCV OC43.     

Incidence and burden of rotavirus gastroenteritis in Japan, as estimated from a prospective sentinel hospital study

We assessed the burden of rotavirus infection-related disease, in terms of hospitalization and associated costs, at 3 sentinel hospitals in Akita prefecture, Japan. From January 2001 through December 2002, a total of 443 children <5 years of age were hospitalized for acute gastroenteritis. Of 422 stool specimens collected, 244 (58%) tested positive for rotavirus. Only 7.8% of the rotavirus disease-associated hospitalizations involved infants <6 months of age, whereas most cases of disease (39%) were reported in the second year of life, and 89% of cases had occurred by 36 months of age. The mean severity score for rotavirus gastroenteritis resulting in hospitalization was 16.5, according to the modified 20-point severity scoring system. The average associated direct medical cost was 136,000 yen (1236 US dollars) per case and was similar among the 3 hospitals. The estimated incidence of rotavirus disease-associated hospitalizations among children <5 years of age was 7.9-17.6 hospitalizations/1000 person-years, and the estimated cumulative incidence by 5 years of age was 6.6%. Thus, approximately 1 in 15 children will require hospitalization due to rotavirus diarrhea by their fifth year of life. In Japan, this would mean that 78,000 children <5 years of age would be hospitalized each year, resulting in a direct medical cost of 10 billion yen (96 US dollars million). The burden associated with rotavirus gastroenteritis in Japan is substantial and might be reduced through the introduction of vaccines.     

Common exposure outbreak of gastroenteritis due to type 2 rotavirus with high secondary attack rate within families.

A sharp outbreak of gastroenteritis associated with human rotavirus type 2 involved not only all of nine infants and young children in a playgroup but also seven of 10 parents and grandparents studied. The source of the outbreak appeared to be two non-playgroup siblings. Six of 11 individuals studied shed human rotavirus type 2, and each of seven from whom paired sera were obtained developed a type 2 sero-response. Overall, evidence of infection with rotavirus type 2 was demonstrated in 10 of 11 individuals by detection of virus in stools and/or a serologic response in an enzyme-linked immunosorbent assay.     

Diarrhea associated with rotavirus in rural Guatemala: a longitudinal study of 24 infants and young children.

A population of 24 infants and young children followed prospectively during the first 3 years of life was studied for the occurrence of rotavirus infection by using enzyme-linked immunosorbent assay to detect virus in stools. Infection with rotavirus was associated with 26 (14.2%) of 183 selected diarrheal episodes. Twenty of the 24 infants and young children had diarrhea associated with rotavirus on at least one occasion and six had two such episodes. Rotavirus infection was documented in over 50% of the dehydrating episodes studied, thus further indicating the importance of rotavirus in this population.     

A prospective case-control study of the role of astrovirus in acute diarrhea among hospitalized young children

This study examines the importance of astroviruses as a cause of acute diarrhea in hospitalized children <10 years old during a 5-year period. Stools were screened by electron microscopy and were tested for astrovirus, rotavirus, and enteric adenovirus by EIA. During the study, 14.6% of hospitalized children had diarrhea. Astroviruses were second only to rotaviruses as etiologic agents of both community-acquired and nosocomial diarrhea. Community-acquired astrovirus infection occurred in 6.8% of patients, and nosocomial disease occurred in 16.2%. Most cases occurred from March through June, and astrovirus type 1 was the most common. The symptoms of astrovirus-infected children were similar to those of children with rotavirus infection. However, astrovirus-infected children had a lower median age, less dehydration, and lower symptom severity scores and were less likely to have been admitted for gastroenteritis than were children with rotavirus. Astrovirus, for which only rehydration therapy is required, should be considered as another common diarrheal pathogen in children <2 years old.     

Rotavirus infections in families. A clinical and virological study.

Among 25 family members of 8 children with acute rotavirus gastroenteritis (8 siblings and 17 adults) gastroenteritis was recorded in 9 (5 siblings and 4 adults), and minor symptoms in 8 (2 siblings and 6 adults). A rotavirus infection was diagnosed in 7 of the family members with gastroenteritis and was probably the cause of the disease in the remaining 2 in this group. Four of the 8 family members with minor symptoms were infected with rotavirus, whereas no infection was detected among the 8 family members without symptoms. Serological findings sugggested that infants and young children underwent a primary infection with rotavirus, whereas older children and adults probably were reinfected. Adults as well as children with rotavirus infection excreted virus and may have served as sources of infection.     

Rotavirus infection in a geriatric population

An outbreak of gastroenteritis affected 19 of 34 geriatric patients and four of 23 staff assigned to the ward in a period of 3 1/2 weeks in January 1980. Fourteen of the 19 patients with gastroenteritis (17 were tested properly) and four of the ten asymptomatic patients (five asymptomatic patients were not tested) showed evidence of rotavirus infection by virus positivity and/or a significant antibody response to rotavirus. One of the four staff members with gastroenteritis showed serologic evidence (three were tested) of rotavirus infection. Nine of the 18 asymptomatic staff members (two remaining staff members were not tested) showed a fourfold rise in antibody to rotavirus but four had antibody titers of 1:32 or more. The patients had diarrhea for a mean of 2.6 days. Most of them had five or fewer diarrheal stools in one day. Six patients had a severe illness and two died. Thirteen of 15 symptomatic patients who had serum samples, collected during the acute and convalescent phases, tested manifested high titers (greater than or equal to 1:32) of complement-fixing antibody to rotavirus antigen.     

Incidence of rotavirus in the Menino Jesus Pediatric Hospital (SP): ELISA--a practical and efficient method for its detection

Seventy infants and children with age from 2 months to 4 years old were admitted to "Hospital Infantil Menino Jesus", in S?o Paulo, Brazil, in the period from March 1983 to June 1984 with acute diarrhea. Feces from these patients were analysed in the search of rotavirus and enteropathogenic bacteria (Shigella, Salmonella and E. coli), for the purpose of defining the role of rotavirus as an agent of acute diarrhea in infants and young children in this country. ELISA (Enzyme-linked Immuno Sorbent Assay) was the method of choice for the search of rotavirus, because of its simplicity of management and the high sensitivity of the results. Rotavirus alone was imputed as the cause of acute diarrhea in 12 patients (17.7%), with ages from 2 months to 3 years old and in 2 patients in association with Shigella. All but one of the patients with rotavirus were undernourished and none of the infants had been breast fed before the disease.     

Epidemiology of rotavirus in Guayaquil, Ecuador

Detection of rotavirus by electron microscopy was conducted with fecal specimens from 1,722 infants and young children with acute diarrhea, during a 41-month survey from April 1978 through December 1981 in Guayaquil, Ecuador; 376 of these specimens (21.8%) were positive. The detection rate was higher during the dry season (May to November; 25.2%) than during the rainy season (December to April; 14.7%). When rotaviruses isolated from 59 patients hospitalized with diarrhea (from April 1979 to July 1981) were subjected to genome RNA analysis by polyacrylamide gel electrophoresis, a single dominant electropherotype was found with other less common electropherotypes. An atypical rotavirus with a unique property was also found.     

Group- and type-specific serologic response in infants and children with primary rotavirus infections and gastroenteritis caused by a strain of known serotype

Antibody response to group A rotavirus (RV), investigated in paired sera from 72 infants and young children with acute gastroenteritis caused by an RV infection, was diagnosed on the basis of a fourfold or greater rise in group A common RV IgG antibody titer. Virus-specific IgM was detected in sera from 64 patients showing seroconversion; these were considered primary infection. RV was detected in stools of 56 (77.8%) patients with serologic evidence of infection and 54 were considered primary infection isolates: 39, serotype 1; 11, serotype 4; and 2, serotype 2. Two could not be typed. Neutralizing antibody studies showed that in primary infections serotype 1 induced an antibody response to serotype 4 at least fourfold lower than the homotypic response; serotype 2 elicited antibody titers to serotypes 1 and 4 at least fourfold lower than homotypic titer; and serotype 4 infections produced a response to serotype 1 as high as the homotypic response. Of 12 patients with primary infection, virus was not typed in 2 or detected in 10; however, the infecting serotype was identified on the basis of distinct patterns of homotypic and heterotypic antibody response.     

Gastroenteritis in Auckland: An aetiological and clinical study

Faecal specimens from 60 patients (under six years old), most of whom were Maoris and Pacific Islanders admitted to Auckland Hospital with gastroenteritis during the months of June and July 1977, were examined for the presence of faecal viruses, bacterial pathogens and parasites. Faecal specimens from 18 non-diarrhoeal control patients were also examined, of which three contained rotavirus. Forty-three (72 per cent) gastroenteritis patients had rotavirus detectable in stools by electron microscopy or immune electron microscopy. Of the remainder, 17 patients were regarded as having non-rotavirus diarrhoea. Enterotoxigenic Esch. coli. was isolated from seven patients of whom six yielded stable toxin producers (ST+), four labile toxin producers (LT+) and two dual toxigenic strains (ST+/LT+). All ST+ isolates appeared to be of low enterotoxigenicity as indicated by low gut weight/carcass weight ratios in the infant mouse assay. Rotavirus was the commonest aetiological agent (72 per cent), bacterial pathogens (alone) accounted for only five per cent and no enteric pathogens were found in 15 per cent of cases. Non-agglutinable rotavirus, presumably a different serotype, was seen in both gastroenteritis and control patients. Rotavirus ‘satellite’ particles previously undescribed were demonstrated in a number of stool samples.     

Epidemiological aspects of rotavirus infection in hospitalized Venezuelan children with gastroenteritis.

The prevalence of rotavirus infection in hospitalized Venezuelan children with gastroenteritis was studied during the period November 1975 to December 1976. Rotaviruses were the pathogens most frequently associated with gastroenteritis, being found in 121 of 293 (41.3%) patients and in only 3 of 66 (4.5%) controls. Other viruses (adenoviruses, enteroviruses, and small icosahedrical viruses) were detected at a lower frequency both in cases and controls. Rotaviruses were detected at a lower frequency both in cases and controls. Rotaviruses were readily detected throughout the year, which may correspond to the absence of seasonal temperature variation in a tropical country such as Venezuela. Children of all age groups examined (0-5 yr) were susceptible to rotavirus infection. The frequency of infection was slightly higher in the age group 13-24 mo, and significantly lower in children younger than 6 mo old. Rotaviruses were readily detected even after 12 days from the onset of illness. These results indicate that rotaviruses may be a major cause of infantile acute gastroenteritis in Venezuela.     

A 27-nm virus isolated during an outbreak of acute infectious nonbacterial gastroenteritis in a convalescent hospital: a possible new serotype

An outbreak of acute infectious nonbacterial gastroenteritis began among elderly patients in a convalescent hospital in Marin County in northern California in March 1978 and persisted through May 1978. The overall clinical attack rate was 51% of 187 residents and 12% of 180 employees. A 27-nm viruslike particle was observed by immune electron microscopy in stools obtained at or near the onset of illness from four of 32 patients. Seroresponses to the 27-nm particles were found by immune electron microscopy in 16 of 18 patients. In addition, serologic evidence of infection with this or a related agent was demonstrated in persons who developed illness in another large outbreak of acute infectious nonbacterial gastroenteritis which occurred in a nearby county. This agent is morphologically similar to but serologically unrelated to the Norwalk and Hawaii gastroenteritis agents and has been designated the Marin agent pending further classification.     

Rotavirus infection in children with acute gastroenteritis in Ecuador

Electron microscopic examination of stools of 702 infants and young children hospitalized in the Emergency Service of the Alejandro Mann Children's Hospital in Guayaquil, Ecuador, between August 1978 and October 1979 showed rotavirus to be present in 148 (21.1%). During the study period rotavirus was detected throughout the year, with no distinct seasonal variation. In addition to rotavirus, adenovirus was detected in stools of five (0.7%) of the patients and unidentified small round virus particles in seven (1.0%).     

A prospective study of rotavirus infection in infants and young children

Diarrhea in neonates, followed as a cohort, and their families was studied prospectively. The families were followed for an average of 16.3 months. Stool and serum specimens were obtained at least every three months. Stool specimens were examined for viruses by electron microscopy and cultured for enteropathogens, and serum specimens were tested for antibodies to rotavirus and Norwalk virus. During the study, 237 episodes of gastroenteritis were observed in 104 infants and their 62 siblings. Rotavirus, detected 82 times in 72 children, was by far the most common enteropathogen. It was associated with gastrointestinal symptoms in 72% (with diarrhea in 65%). Rotavirus diarrhea occurred mostly in winter months and was significantly more frequently associated with respiratory symptoms than were diarrheas with other etiologies. Rotavirus infection was uncommon in the first six months of life, but by two years of age, 62% of the infants had had at least one infection. Neither breast feeding nor the presence of antibody to rotavirus in cord blood appeared to be protective.     

Rotavirus

Since their discovery in the 1970s, the human rotaviruses have been recognized as the most important cause of acute infectious gastroenteritis among infants and children worldwide. Rotavirus has been found to infect almost all mammalian and avian species tested, and is primarily a disease of the young. In humans, rotavirus is the most frequent gastrointestinal pathogen in infants and children less than 2 years of age. In developing countries, the attack rate peaks at 6 months of age, whereas in developed areas of the world the virus is most commonly found among children 6-12 months of age. Rotavirus displays a marked seasonality in temperate climates, with the number of cases peaking in the colder winter months. In tropical climates, this seasonality is not as apparent, and infection may occur year round. Symptoms of rotavirus infection are non-specific and include vomiting and diarrhoea, occasionally accompanied by a low grade fever. Dehydration is more common with rotavirus infection than with most bacterial pathogens, and is the most common cause of death related to rotavirus infection. Treatment is non-specific and includes the use of oral rehydration therapy, especially in developing countries where malnutrition is common. Strategies for the prevention of rotavirus infection are dependent on advances in the understanding of the molecular biology of the rotavirus. The genetic structure of the virus has been extensively studied, and a number of the structural proteins have been identified. The neutralization antigens, located on VP4 and VP7, may be important in conferring immunity to rotavirus in vivo. Two animal-derived and several reassortant rotavirus vaccines are currently being evaluated in field studies, and a number of other candidate vaccines are being tested in vitro and in animal studies.