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Rotavirus carriage, asymptomatic infection, and disease in the first two years of life. I. Virus shedding.

From September 1979 to July 1980 inclusive, rotaviruses were prospectively detected by electron microscopy (EM) and ELISA in 82 (29%) of 283 children under two years of age who were admitted to a general pediatric ward in Paris. Rotavirus was found in 43 (36%) of 119 children with diarrhea and in 40 (24%) of 164 children without diarrhea; thus of 83 children shedding rotavirus, 40 (48%) were not diarrheic. Virus shedding that was not associated with diarrhea was observed in 71% of neonates, in 50% of one- to six-month-old children, and in 26% of 7-24-month-old children. Rotavirus shedding was statistically correlated (P less than .01) only with those cases of diarrhea with fever and vomiting ( DFV syndrome). Consequently, relative risk (RR) for the DFV syndrome in patients who were shedding virus was 2.07 (P less than .001) vs. 0.95 for other types of diarrhea. These observations show that asymptomatic rotaviral infection is not an infrequent occurrence; that the association between rotavirus and diarrhea is not necessarily an etiologic one; and that the DFV syndrome appears as a major clinical expression of rotaviral disease. Consequently, recovery of rotavirus from feces is of little diagnostic significance since it does not give a differentiation between rotavirus-induced and rotavirus-associated diarrhea.

Aging↗

Antigenic characterization and ELISA detection of adult diarrhea rotaviruses.

Recently, severe epidemics of diarrhea among both adults and children in China have been associated with an agent called adult diarrhea rotavirus (ADRV). We have studied ADRV from two areas of China (Jinzhou and Guangxi) and compared them with prototype group A, B, and C rotaviruses. The viral genomes were compared by electrophoresis of the RNA genome segments in polyacrylamide gels, and the antigenic relatedness of these viruses was examined by immune electron microscopic studies using virus preparations of either double- or single-capsid particles. Hyperimmune antisera (guinea pig and rabbit) to one strain of ADRV reacted with high titers with other strains of ADRV and with single-shelled capsids of a porcine group B rotavirus. The antisera to ADRV did not react with either group A or group C rotaviruses. Antisera to either bovine or porcine group B rotaviruses reacted with ADRV but not with the group A or group C viruses. Antisera to group A or group C virus reacted only with their respective homologous virus. These results and those of immunofluorescence studies place the human ADRV rotaviruses from China among the group B rotaviruses. We also report the development of an ELISA to detect ADRV; this ELISA should be useful for defining the epidemiology of these recently described rotaviruses.

Adult↗

Protection of adults rechallenged with a human rotavirus.

Previous studies of adults challenged with human rotavirus (CJN strain) showed that 74% became infected and 55% of those infected experienced illness. Protection against infection correlated with rotavirus antibody, most significantly (P = .005) serum rotavirus IgG. In this study, 20 previously challenged subjects were reinoculated with the same virus 9-12 months after their initial challenge. Only 1 of 8 subjects not infected after the initial challenge and 2 of 12 infected after the first inoculation became infected after reinoculation; none became ill. Titers of rotavirus antibodies (serum, jejunal, and stool) at the time of reinoculation were about as high as or higher than they were before the initial inoculation. This correlated with greater protection, but the extent of protection was significantly greater (P less than .0001) than predicted based on a previous model relating protection and preinoculation titers of serum rotavirus IgG. Thus, inoculation with human rotavirus provided homotypic protection for at least 9-12 months, and protection remained correlated with higher concentrations of rotavirus antibody. However, the specific relationship between protection and rotavirus antibody was altered after the initial inoculation.

Adult↗

Impact of rotavirus infection at a large pediatric hospital.

Information is limited about national patterns of rotavirus infection throughout the USA. Discharge records and laboratory rotavirus detection for 1979-1989 at the Texas Children's Hospital, Houston, were evaluated to determine the impact of rotavirus gastroenteritis at a large children's hospital. The availability since 1983 of diagnostic assays less expensive than electron microscopy was associated with increased rotavirus detection. Only 67% of rotavirus-positive samples came from children likely to have had community-acquired acute gastroenteritis. Combined laboratory results and ICD-9 discharge diagnosis codes (008.6, 008.8, and 558.9) measured rotavirus activity better than either alone. A case definition for hospitalization for rotavirus infection resulted in an estimate that an average of 473 children were hospitalized for rotavirus infection at Texas Children's Hospital each year over the 10-year period. These cases accounted for 3.0% of all hospital days and $1.5 million per year in bed costs at this hospital. Hospitalization rates and the impact of hospital costs for the USA were estimated by extrapolation.

Acute Disease↗

Molecular epidemiology of rotavirus in children attending day care centers in Houston.

Serotype distribution of group A rotavirus in children attending day care centers has not been previously reported. Fifteen centers in Houston participated in longitudinal monitoring of rotavirus infection during one to three consecutive rotavirus seasons. Monitoring included daily recording of the presence of diarrhea and weekly stool collection. Stool specimens containing rotavirus were analyzed by a monoclonal antibody (MAb)-based ELISA specific for the VP7 protein of serotypes 1, 2, 3, and 4 and by gel electrophoresis. A total of 318 children had 362 rotavirus episodes; 149 could be serotyped. Serotype distribution of this population was similar to that of children hospitalized for diarrhea in a large pediatric hospital in Houston during the same period. Symptomatic infections were predominantly due to serotype 1 rotaviruses in season 2 and serotype 3 rotaviruses in season 3. Episodes recurred in 43 children; 2 children had second symptomatic infections of the same serotype as the first. Electrophoretic differences among rotaviruses of a same serotype were common and more frequent among serotype 1 than serotype 3 viruses.

Age Factors↗

First detection of group C rotavirus in fecal specimens of children with diarrhea in the United States.

Group C rotaviruses cause sporadic cases and outbreaks of acute diarrhea in children and adults in many countries but have never been identified from patients in the United States. Fecal specimens from children with diarrhea who were hospitalized in Providence, Rhode Island, were screened for group C rotaviruses if rotavirus was detected by electron microscopy but the specimens were negative for group A rotavirus by ELISA. Of 16 specimens examined, 3 were positive for group C rotavirus by ELISA using reagents specific to the Cowden strain of porcine group C rotavirus and all 16 were positive using a more sensitive assay: reverse transcriptase-polymerase chain reaction. Group C rotavirus infections occurred primarily among infants in winter in 4 of the 5 years examined and were acquired both in community and nosocomial settings. Future clinical and epidemiologic studies with group C rotavirus will require development of assays that are more sensitive and simpler to perform.

Animals↗

Group A rotavirus veterinary vaccines.

Group A rotaviruses cause diarrhea in young livestock and poultry; consequently, vaccination strategies have focused on induction of active or passive immunity. Gnotobiotic pigs and calves serve as useful models to evaluate induction of active immunity by candidate animal or human rotavirus vaccines. However, live attenuated rotavirus vaccines lacked efficacy when administered orally to calves and pigs in the field, presumably because colostral antibodies inhibited vaccine virus replication. The widespread occurrence of rotavirus antibodies in colostrum led to strategies for maternal rotavirus vaccination to boost lactogenic immunity and transfer passive antibodies to the neonate via colostrum and milk. The variable success of maternal rotavirus vaccines in the field is influenced by vaccine dose, strain, inactivating agent, adjuvant, route of administration, and environmental rotavirus exposure levels. The use of genetically engineered rotavirus-like particle vaccines in cows to boost antibodies in mammary secretions shows promise. Such subunit vaccines possess potential advantages over existing vaccines.

Animals↗

Survival of rotavirus antibody activity derived from bovine colostrum after passage through the human gastrointestinal tract.

BACKGROUND: Rotavirus is a major cause of infectious diarrhea in infants and young children. Several studies have shown that hyperimmune bovine colostrum, derived from cows immunized with rotavirus, can prevent rotavirus diarrhea when given passively. The objective of this study was to determine whether colostral antibody activity survived transit through the gut by measuring the level of rotavirus antibody activity in the feces. METHODS: Hyperimmune colostrum containing different levels of rotavirus antibody was administered to 105 children attending nine Adelaide childcare centres. Subjects were asked to drink 100 ml of whole milk supplemented with colostrum 3 times a day, for a period of 6 days. Stool samples were collected from the subjects before, during, and after consumption of the study product. Rotavirus activity was determined using a novel virus reduction enzyme-linked immunosorbent assay (ELISA) and a virus neutralization assay. RESULTS: Rotavirus antibody activity was detected in 521 (86%) of 602 fecal specimens obtained during the study using the virus reduction ELISA. The antibody activity was detected as early as 8 hours after ingestion of hyperimmune colostrum and up to 72 hours after consumption had ceased. There was a strong relation (r = 0.81) between the titer of rotavirus antibody administered to subjects and the level of antibody activity detected in the feces. CONCLUSIONS: The results show that antirotavirus activity survived passage through the gut. Therefore, passive immunotherapy may be used to prevent or treat infectious diseases that affect the entire length of the gastrointestinal tract.

Antibodies, Viral↗

Astrovirus, adenovirus, and rotavirus in hospitalized children: prevalence and association with gastroenteritis.

BACKGROUND: Agents of viral gastroenteritis such as astrovirus, rotavirus, and adenovirus are common pediatric pathogens accounting for many physician visits, hospital admissions, and nosocomial infections. Previous hospital-based prevalence studies have examined mainly symptomatic children. PURPOSE: To evaluate the prevalence of astrovirus, rotavirus, and adenovirus infections among hospitalized children less than 6 years of age, regardless of symptoms, and determine association with gastroenteritis. METHODS: From September 1998 to June 2000, stool specimens were collected twice weekly from children less than five years of age admitted to two wards in a tertiary-care children's hospital. A total of 480 samples were obtained from 309 hospitalizations. Stools were examined using antibody-based ELISA for astrovirus, rotavirus, and adenovirus. Clinical data was abstracted from patient records. RESULTS: Twenty one percent of the children had gastroenteritis symptoms at some point during their hospitalizations (43% were hospital acquired). Astrovirus was detected in 5.2% of all children compared to 6.8% with rotavirus and 0.8% with adenovirus serotypes 40 or 41. Nosocomial acquisition was common. Seventy five percent of astrovirus infections and 90% rotavirus infections were symptomatic. Astrovirus infections were significantly more likely to occur in younger infants and in children with compromised immunity. Rotavirus infections were significantly more likely to cause dehydration. In a three-year passive surveillance of gastroenteritis at the hospital, astrovirus and rotavirus infections peaked simultaneously in winter months. CONCLUSIONS: Rotavirus and astrovirus are common symptomatic infections on pediatric wards and contribute greatly to inpatient morbidity. Adenoviruses played a limited role in gastroenteritis in hospitalized children in this study.

Adenoviridae↗

Diverse serologic response to rotavirus infection of infants in a single epidemic.

Eight infants with onset of gastroenteritis occurring within a 32-day period were examined for stool rotavirus antigen and serum antibody response to rotavirus. Each infant presented evidence of rotavirus infection but no single test for rotavirus-specific antigen or antibody was positive for every infected individual. Rotavirus was identified in the stools of five infants; in the others rotavirus etiology was determined by a specific immune response only. The neutralizing antibody response to each of four human rotavirus serotypes and to bovine rotavirus Nebraska calf diarrhea virus ranged from totally negative to a specific response to up to four serotypes. Three originally seropositive infants each showed an increase in neutralizing antibody titer to two or more serotypes. However, two of five originally seronegative infants also developed antibody to two or more serotypes. No consistent pattern of responses to different serotypes was detected.

Antibodies, Viral↗

Rotavirus in Ireland: national estimates of disease burden, 1997 to 1998.

BACKGROUND: We estimated the disease burden caused by rotavirus hospitalizations in the Republic of Ireland by using national data on the number of hospitalizations for diarrhea in children and laboratory surveillance of confirmed rotavirus detections. METHODS: We examined trends in diarrheal hospitalizations among children <5 years old as coded by ICD-9-CM for the period January, 1997, to December, 1998. We collated data on laboratory-confirmed rotavirus detections nationally for the same period among children <2 years old. We calculated the overall contribution of rotavirus to laboratory-confirmed intestinal disease in children <5 years old from INFOSCAN, a disease bulletin for one-third of the population. We compared data from all sources and estimated the proportion of diarrheal hospitalizations that are likely the result of rotavirus in children <5 years old. RESULTS: In children <5 years old, 9% of all hospitalizations are for diarrheal illness. In this age group 1 in 8 are hospitalized for a diarrheal illness, and 1 in 17 are hospitalized for rotavirus by 5 years of age. In hospitalized children <2 years old, 1 in 38 have a laboratory confirmed rotavirus infection. CONCLUSIONS: The disease burden of rotavirus hospitalizations is higher than in other industrialized countries. Access to comprehensive national databases may have contributed to the high hospitalization rates, as well as a greater tendency to hospitalize children with diarrhea in Ireland.

Child, Preschool↗

Economics of rotavirus gastroenteritis and vaccination in Europe: what makes sense?

Rotavirus is a major cause of gastroenteritis in children throughout Europe and the world. In addition to causing morbidity and mortality in children, rotavirus gastroenteritis (RVGE) creates a major economic burden on health care systems and families in Europe. The costs of hospital admissions for RVGE and nosocomial infections generate significant medical treatment costs throughout the region. Less information is available on the costs associated with less severe episodes and the costs borne by families, including lost time from work. The availability of rotavirus vaccines presents an effective opportunity to prevent RVGE and these associated economic costs, as well as providing protection to each child and hence benefiting the child's family. The adoption of rotavirus vaccine by health authorities in Europe will require a comparison of the costs and benefits. Economic evaluations that compare the costs of vaccination to the economic benefits of rotavirus vaccination will provide an estimate of its financial impact on health care systems and society. However, to provide a complete picture, economic evaluations of rotavirus vaccines will need to account for both the reduced costs and the reduced morbidity from prevented RVGE. Cost-effectiveness analyses based on quality-adjusted life years (QALYs) provide a systematic approach for assessing vaccination as a health investment, comparing the incremental costs associated with rotavirus vaccination and the reduced morbidity and mortality. QALYs provide a standardized approach for quantifying and comparing reductions in health-related quality of life and premature mortality. Although methodologic limitations exist in applying the QALY approach to childhood vaccines, their use in cost effectiveness analyses allows decision makers to consider the full health benefits of rotavirus and other vaccines.

Aged↗

A case-control study to determine risk factors for hospitalization for rotavirus gastroenteritis in U.S. children.

OBJECTIVE: The objective of this case-control study nested within a surveillance study conducted at 3 hospitals (Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Children's Hospital of New Orleans, New Orleans, LA; and Hasbro Children's Hospital, Providence, RI) was to identify risk factors for rotavirus gastroenteritis requiring hospitalization. PATIENTS: Cases were children < or =59 months of age who were admitted with acute gastroenteritis (AGE) and found to have rotavirus infection. Controls were selected from a birth certificate registry (Cincinnati and Providence) or a registry of patients from a large practice consortium in 11 locations (New Orleans). RESULTS: Three hundred forty-nine rotavirus-infected cases and 1242 control subjects were enrolled. Breast feeding was protective against hospitalization for rotavirus AGE for infants <6 months of age. (odds ratio [OR], 5.1; 95% confidence interval [CI], 1.2-13.2). Low-birth-weight (<2500 g) infants had increased risk for hospitalization even beyond the first few months of life (OR, 2.8; 95% CI, 1.6-5.0). Children in child care were more likely to be hospitalized for rotavirus AGE than those cared for at home, particularly those > or =24 months of age (OR, 3.0; 95% CI, 1.8-5.3). Other characteristics associated with rotavirus AGE hospitalization were children <24 months of age covered by Medicaid or without insurance (OR, 2.1; 95% CI, 1.4-3.2) and having another child in the house <24 months of age (OR, 1.6; 95% CI, 1.1-2.3). The data suggest that maternal age <25 years (OR, 1.4; 95% CI, 1.0-2.0) and a mother with less than a high school education (OR, 1.5; 95% CI, 1.0-2.3) may also increase risk of rotavirus hospitalization. CONCLUSION: There are socioeconomic and environmental factors and aspects of the child's medical and dietary history that identify children at risk for hospitalization with rotavirus AGE.

Age Factors↗

Distribution of G serotypes and P genotypes of bovine group A rotavirus isolated in Japan.

OBJECTIVE: To identify the distribution of G serotype and P genotype of bovine group A rotavirus in Japan. DESIGN: Detection, isolation, electropherotyping, G serotyping and P genotyping of bovine group A rotavirus in 167 diarrhoeal faecal samples. PROCEDURE: Bovine group A rotavirus was detected and isolated, and bovine group A rotavirus isolates were identified electropherotype by polyacrylamide gel electrophoresis and G serotype and P genotype by reverse transcription-poly-merase chain reaction. RESULTS: Twenty-eight bovine group A rotavirus strains were isolated from 167 samples. Electropherotypes of the bovine group A rotavirus isolates were identified as long-genome electropherotype and the most prevalent combination of G serotype and P genotype of the bovine group A rotavirus isolates was G6P5 (25/28; 89.3%), followed by G6P11 (2/28; 7.1%) and G10P11 (1/28; 3.6%). CONCLUSION: These results suggest that the bovine group A rotavirus exhibiting G6P5 is the most common in Japan.

Animals↗

[Fecal IgA antibody against rotavirus and clinical manifestations of acute viral gastroenteritis in children].

We determined the presence or absence of rotavirus antigen by the enzyme-immunoassay in 126 fecal specimens obtained from infants with acute gastroenteritis, and also measured IgA antibody titers against rotavirus in stool samples. Rotavirus-positive specimens amounted to 72. Thirty-five specimens in 126 stool samples were found to contain the IgA antibody against rotavirus. The IgA antibody against rotavirus was detected in 21% and 44% of fecal specimens obtained from age groups of less than 3 years and 3 years or more, respectively, showing a significant difference between these 2 groups. The geometric mean titer of specific IgA antibody was also higher in the latter group than in the former. This specific IgA antibody was detected in 32% and 22% of boys and girls, respectively, showing a tendency of high incidence among boys. The detection rate of specific IgA antibody was significantly higher in rotavirus-negative fecal specimens (41%) than in rotavirus-positive fecal specimens (18%). As for infants having the rotavirus antigen in their feces, their symptoms were severe in many of the infants at the age of less than 3 years, while many of the infants at the age of 3 years or more only had mild symptoms. There was a significant difference between the 2 age groups. When these infants were analyzed according to the presence or absence of specific IgA antibody in their feces, no difference in scores of severity of clinical symptoms was seen between the 2 groups. However, IgA antibody-negative infants more frequently had fever, over 39 degrees C and significantly more developed whitish and watery stool in comparison with IgA antibody-positive infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Survival and detection of rotaviruses on environmental surfaces in day care centers.

Previously, we demonstrated that children in day care centers commonly experience diarrhea due to rotavirus, giardia, and bacterial pathogens. Multiple agents frequently coexist, and the environment is heavily contaminated with enteric bacteria during outbreaks. A study of environmental surface contamination with rotavirus was performed during three non-outbreak periods. Of 25 samples collected from environmental surfaces and teachers hands at a day care center, 4 (16%) were positive for rotavirus antigen when a fluorescence assay was used. We also examined the survival of two animal viruses, rotavirus SA-11 and poliovirus type 1, and bacteriophage 12 on similar environmental surfaces in a laboratory. Poliovirus type 1 and bacteriophage f2 were more resistant to drying than rotavirus SA-11 and could be recovered after a 90-min exposure on a dry surface. Rotavirus SA-11 could be detected for 30 min. All three viruses survived longer when they were suspended in fecal material than when they were suspended in distilled water. These data suggest that several agents, including rotavirus, can remain viable on contaminated surfaces long enough to be transmitted to susceptible children. This finding helps explain why rotavirus shows a mode of spread like that of parasitic and bacterial agents within day care center settings.

Child Day Care Centers↗

Rotavirus G-type restriction, persistence, and herd type specificity in Swedish cattle herds.

G-typing of rotavirus strains enables the study of molecular epidemiology and gathering of information to promote disease prevention and control. Rotavirus strains in fecal specimens from neonatal calves in Swedish cattle herds were therefore characterized by using G1 to -4-, G6-, G8-, and G10-specific primers in reverse transcription (RT)-PCR. Fecal samples were collected from one dairy herd (herd A) for 4 consecutive years and from 41 beef and dairy herds (herd B) experiencing calf diarrhea outbreaks. Altogether, 1, 700 samples were analyzed by group A rotavirus enzyme-linked immunosorbent assay, and 98 rotavirus-positive specimens were selected for G-typing by RT-PCR. The effect of herd type, time, geographic region, and clinical symptoms on the G-type distribution was evaluated. Altogether (herds A and B), G10 was found in 59 (60. 2%) fecal specimens, G6 was found in 30 (30.6%) specimens, G3 was found in 1 (1.0%) specimen, and G8 was found in 1 (1.0%) specimen. Seven (7.1%) fecal specimens were not typeable. Herd type specificity in the G-type distribution was demonstrated in the herds in herd B. In the 6 beef suckler herds, only G6 was detected, while rotavirus strains from the 35 dairy herds were predominantly (54%) G10. The G-type distribution was restricted in herds A and B. Twenty-nine of 30 strains from herd A were characterized as G10. In the vast majority of herds in herd B, a single G-type was identified. The serotype G10 and the electropherotype persisted over time in herd A. No characteristic G-type variation in the geographic distribution of cattle herds in herd B was obvious. There was no difference in the G-type distributions between the strains from clinically and subclinically rotavirus-infected calves in dairy herd A. The results from this study strongly indicate a pronounced stability in the rotavirus G-type distribution in Swedish cattle herds, which emphasizes the importance of continuous preventive measures for control of neonatal calf diarrhea. A future bovine rotavirus vaccine in Sweden should contain G10 and G6 strains.

Animals↗

Serotypes of bovine rotaviruses distinguished by serum neutralization.

Fourteen cytopathic bovine rotaviruses isolated from naturally affected calves were characterized serologically by serum neutralization. Antisera were prepared in guinea pigs against the three isolates and the Lincoln strain of bovine rotavirus. These four rotaviruses were segregated into at least two distinct serotypes (designated types 1 and 2) by serum neutralization. The remaining 11 isolates were also placed into two groups according to neutralization specificity by using the antisera against types 1 and 2 bovine rotavirus. When colostrum-deprived calves were experimentally inoculated with type 1 or 2 bovine rotavirus, respectively, the calves produced neutralizing antibodies against the inoculated serotype but not against the other serotype. Calf sera obtained from six herds with naturally occurring rotavirus infections possessed neutralizing antibodies against type 1 or 2 or both. Thus, distinct serotypes of bovine rotavirus were demonstrated by serum neutralization. The possible role of serotypes in the epidemiology of rotavirus infection among bovine species is discussed.

Animals↗