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[A study of rotavirus infections in families].

Using the PAGE method, we detected 194 stool samples collected in 72 families during the epidemic season of rotavirus infection. Rotavirus was found in 29 of the 48 stool specimens of children with diarrhea, and for comparison, it was found in only 1 of the 24 stool specimens of children without diarrhea. Rotavirus infections occurred significantly more often among adults having contacts with children infected by HRV (21.3%) than among adults having no contacts with children infected by HRV (4.5%). Rotavirus infections in most of adults were asymptomatic but some of those with abdominal cramps. The illnesses were generally mild and did not necessitate medical attention. The results suggest that asymptomatic adult contacts may be able to transmit the HRV to other people.

Adult↗

Early response to rotavirus infection involves massive B cell activation.

Rotavirus is an acute enteric pathogen which induces severe diarrhea in infants and children. To determine the immune response to rotavirus in vivo, we used a mouse model of rotavirus infection. We observed dramatic increases in the sizes of both Peyer's patches and mesenteric lymph nodes, but not spleen, between 1 and 6 days after infection with a homologous strain of murine rotavirus, EC wild type. Histological analysis showed large increases in the numbers of lymphocytes in these same tissues in rotavirus-infected mice. Flow cytometric analysis confirmed the increase in numbers of lymphocytes and revealed a large increase in the percentage of activated B, but not T, lymphocytes in both Peyer's patches and mesenteric lymph nodes of rotavirus-infected mice compared with control mice. Fragment cultures from these tissues established at 3-4 days postinfection contain rotavirus-specific IgM but not IgA Ab. A similar degree of lymphoid hyperplasia and percentage of activated B cells were observed in rotavirus-infected TCR knockout mice. Taken together, our findings show that rotavirus infection, in the context of a normal immune response, induces a large increase in the percentages of activated B cells in the absence of any detectable increase in the percentage of activated T cells, implicating a T cell-independent B cell response as the primary mechanism for initial rotavirus clearance.

Animals↗

Neonatal rotavirus infection in Bangladesh: strain characterization and risk factors for nosocomial infection.

BACKGROUND: Rotavirus (RV) diarrhea is an important cause of childhood morbidity and mortality in Bangladesh and is responsible for 24% of hospital admissions for diarrhea in children from 3 months to 2 years of age. However, the prevalence of neonatal RV infections and characteristics of RV strains infecting neonates have not been explored in Bangladesh. METHODS: We investigated neonates at six hospitals in Bangladesh to determine the prevalence of neonatal RV infection, to identify risk factors for infection and to characterize neonatal RV strains by reverse transcription-polymerase chain reaction. RESULTS: Of 381 neonates screened at 6 hospitals 61 of 146 infants (42%) at 2 hospitals in Dhaka were RV-positive. Of these 62% were detected within the first 5 days of life. We found an increased risk for neonatal RV infection among infants whose mothers reported no handwashing during care of the neonate (P = 0.03). Analysis of RV strains in enzyme-linked immunosorbent assay-positive specimens identified P[6]G4 and P[6]G1 genotypes to be most common; 7% (2 of 27) of strains were nontypable. A concurrent analysis of RV strains circulating in Bangladesh suggested that RV genotypes infecting neonates had a distinct P genotype, because most community strains were P-nontypable compared with neonatal strains, which carried the P[6] genotype. CONCLUSIONS: Hospitalized neonates in Dhaka have increased risk for infection with RV as early as the first week of life with strains having the unusual P[6] genotype. Our findings confirm studies in India showing that neonatal RV infection can be common and may occur with strains distinct from those circulating in the community. Neonatal RV infections could alter a child's response to the RV vaccine as well as the calculation of RV vaccine efficacy in these populations.

Bangladesh↗

Virus-specific immunity in neonatal and adult mouse rotavirus infection.

Mouse rotavirus (epizootic diarrhea of infant mice) was used as a model to study the role of virus-specific immunity in infection and diarrheal disease. The distribution of viral antigen in intestinal tissues was determined by immunofluorescent staining with anti-simian rotavirus (SA-11) serum. The location and proportion of antigen-positive cells appeared to vary as a function of time postinfection and age of the animal at the time of infection. In animals infected at 1 and 7 days of age, antigen-positive cells (5 to 25%) were first detected (1 day postinfection) in the proximal segment of the small intestine, and infection progressed to the middle and distal segments. At 10 days postinfection, virus-infected cells were no longer observed in the proximal segment. In animals infected at 21 days of age (disease-free), a significantly lower proportion of cells were antigen positive (2 to 5%), and they were restricted to the middle and distal segments of the small intestine. Infection, defined according to the presence of virus and viral antigens in intestinal tissues and by seroconversion in the immunoglobulin M (IgM) isotype as determined by enzyme-linked immunosorbent assay with SA-11 antigen, was observed for all age groups (neonatal to adult), even in the presence of virus-specific serum or intestinal immunoglobulins. On the other hand, diarrheal disease was not detected in neonatal mice (1 to 3 days old) positive for passively acquired virus-specific intestinal IgG. The presence of virus-specific IgA in the intestinal tract at the time of infection did not protect from subsequent diarrheal disease. Virus-specific, cell-mediated immunity, determined by a delayed-type hypersensitivity response, did not develop in neonatal mice infected at 5 and 12 days of age. Reinfection of adult mice was associated with suppression of virus-specific delayed-type hypersensitivity and a significant decrease in the titers of the virus-specific serum IgG and IgA.

Animals↗

Epidemiological studies of piglet diarrhoea in intensively managed Danish sow herds. III. Rotavirus infection.

The prevalence of rotavirus infection was studied in 1090 litters from 26 sow herds. Samples of normal, semifluid and watery stools were examined for rotavirus by an ELISA-test on faeces. Rotavirus was detected in 77% of the herds and in 30.5% of the litters (prevalence rates). The highest prevalence rate was seen in piglets between 21 and 41 days of age. Gilts' litters had a very high prevalence during the first week of life. Apart from this, no difference was found between litters from gilts and older sows. Rotavirus was detected more frequently in semiliquid, loose stools than in normal or watery stools, and an association between virus detection and diarrhoea could not be demonstrated. However, litters which shedded rotavirus during the suckling period had lower weight gains and higher incidence rates of respiratory diseases than virus-free litters. Litters weaned at 2 weeks in battery cages had slightly increased risk of shedding rotavirus compared to litters weaned in more traditional systems. The study revealed that rotavirus is widespread in Danish swine herds. The findings give evidence to suggest that the type of mild diarrhoea in 3-week-old piglets known as steatorrhoea or "white scours" may be associated with rotavirus infection, possibly in combination with E. coli and other agents. The high prevalence in piglets weaned at 2 weeks plus the higher morbidity and mortality among such piglets sustain the conclusion that piglets should not be weaned before 3 weeks of age or below a body weight of 6-7 kg.

Age Factors↗

Rotavirus infections in young Nicaraguan children.

BACKGROUND: Rotavirus is an important cause of dehydrating diarrhea in young children throughout the world. Knowledge about frequency of reinfections, development of immunity to the virus and the possible protective effect of breast milk is important, in particular in relation to possible strategies for immunization. METHODS: A prospective study of rotavirus infections in a cohort of 235 infants followed from birth until 2 years of age was performed in León, Nicaragua. Fecal and serum specimens were collected at specified times, and stools were also obtained during episodes of diarrhea. Fecal specimens were screened by rotavirus antigen detection and serum and colostral specimens were analyzed by isotype-specific rotavirus antibody enzyme-linked immunosorbent assay. RESULTS: As judged by anti-rotavirus IgA antibody seroconversion and/or demonstration of rotavirus antigen in fecal specimens, > 50% of the babies had evidence of past rotavirus infection by the age of 2 months. The total incidence of rotavirus infections, including many reinfections, was 0.7 infection/child-year, of which only 17% were associated with diarrhea. The time from birth to the first demonstration of rotavirus in stool samples correlated significantly with the concentration of anti-rotavirus IgA antibodies in colostrum. There was also a tendency toward a relationship between long duration of breast-feeding and asymptomatic infection. CONCLUSIONS: Rotavirus infections are acquired very early in infants in León, Nicaragua, and reinfections are common. Most infections are asymptomatic. Breast milk appears to confer partial protection against rotavirus infection, probably mediated by specific IgA antibodies. To be effective rotavirus vaccination would probably have to be given at a very early age to infants in developing countries.

Antibodies, Viral↗

Molecular epidemiology of rotavirus infection in Western Cameroon.

Rotavirus is the major viral cause of diarrhoea in children worldwide. In this study, the first from Cameroon, the molecular epidemiology of rotavirus infection was investigated. Eight hundred and ninety diarrhoea stools collected from children under the age of 5 years in Western Cameroon between 1999 and 2000 were analysed for rotaviruses and further characterized by antigenic and genomic methods. Rotaviruses were detected in 21.9 per cent of stools and were highest during the cool dry season. Sixteen different electrophoretic patterns, 13 of long and three of short, were detected in the study area. The predominant subgroup detected was subgroup II (66.9 per cent) and atypical strains with long electropherotype, but subgroup I specificity were also observed. Rotavirus infection was shown to be an important component of diarrhoeal disease in young children in Cameroon. The results of this study in Cameroon reinforces the need to continue with surveillance programmes in Africa.

Cameroon↗

In vitro inhibitory effect of some flavonoids on rotavirus infectivity.

The inhibitory effects of some flavonoids on the infectivity of rotavirus, which predominantly causes sporadic diarrhea in infants and young children, were investigated. Among tested flavonoids, diosmin and hesperidin had the most potent inhibitory activity on rotavirus infection. The fifty percent inhibitory concentration of both compounds was 10 microM. However, their aglycones did not have the inhibitory activity. The rutinose moiety of flavonoids should protect against the invasion of rotavirus into cells.

Animals↗

Inhibitory effect of herbal medicines on rotavirus infectivity.

The inhibitory effect of some traditional herbal medicines on the infectivity of rotavirus, which predominantly occurs in sporadic diarrhea in infants and young children, was investigated. Among the 34 kinds of herbal medicines tested, the fruit of Citrus aurantium had the most potent inhibitory activity on rotavirus infection. The active components of the fruit of Citrus aurantium were neohesperidin and hesperidin. Their 50% inhibitory concentrations were 25 and 10 microM, respectively.

Microbial Sensitivity Tests↗

Lack of association between rotavirus infection and intussusception: implications for use of attenuated rotavirus vaccines.

BACKGROUND: Withdrawal of the tetravalent rhesus-human rotavirus vaccine Rotashield because of its association with intussusception raised concerns about a potential link between natural rotavirus disease and intussusception. Our objective was to determine whether such an association exists. METHODS: In the Southern California Kaiser Permanente Health Care Plan, a large health maintenance organization, from October, 1992, to July, 1999, we retrospectively identified by computerized data and medical charts all children <3 years old with intussusception, and from 1997 to 1999 we independently identified by prospective clinical and laboratory evaluation children <3 years old with rotavirus diarrhea. We compared the epidemiologic characteristics of intussusception and rotavirus infection in our study population and evaluated for the presence of both diseases in individual patients. RESULTS: Using computerized data we identified 124 cases of intussusception, 101 (81%) of which were confirmed by medical chart and radiologic reviews. The incidences for infants <1 year old and for children <3 years old were 41 (95% confidence interval, 32 to 55) and 17 (95% confidence interval, 13 to 20) per 100,000 child years, respectively. Between November 1997 and July 1999, we identified 470 cases of rotavirus diarrhea and none had intussusception. Although rotavirus diarrhea had a distinct peak incidence between December and February, intussusception had no apparent seasonality. The age distributions overlapped, but intussusception occurred at an earlier age than rotavirus disease. CONCLUSIONS: We found no epidemiologic evidence for an association between intussusception and natural rotavirus infection, but our study was limited by an insufficient number of cases to definitively exclude a causal link. The dramatic winter peak of rotavirus disease had no discernable parallel in the incidence of intussusception. Our data suggest that the association between tetravalent rhesus-human rotavirus vaccine and intussusception may possibly result from the nonhuman rotavirus components of that vaccine.

Age Factors↗

Aerosol transmission of experimental rotavirus infection.

Several aspects of the epidemiology of rotavirus suggest the possibility that transmission may occur by nonenteral routes. We utilized the mouse model of rotavirus infection to investigate the experimental transmission of rotavirus infection by respiratory droplets. Following exposure to a defined dose of aerosolized rotavirus, the kinetics of viral replication within the lung and gastrointestinal tract was studied using a double antibody enzyme immunoassay and indirect immunofluorescence. These studies documented the efficient transmission of rotavirus infection by means of aerosol in all exposed animals. Rotavirus antigen was detected as early as 12 hours after infection in the pulmonary and gastrointestinal tracts of the infected animals and antigen remained detectable in both sites for at least 8 days following infection. Gastrointestinal illness was clearly demonstrable in the animals while pulmonary pathology was not evident. These studies document that rotavirus infection can be transmitted by aerosol droplets under experimental conditions.

Aerosols↗

Rotavirus infection in New Zealand.

Rotavirus infection is commonly found in young infants admitted to hospital with gastroenteritis. An enzyme-linked immunosorbent assay (ELISA) for virus diagnosis is described and the results of testing stool specimens from 497 children with gastroenteritis, 192 neonates and 247 asymptomatic six month old infants are presented. Rotavirus infection was found in 45 percent of all children with gastroenteritis but only in 4.7 percent of neonates and 2 percent of asymptomatic infants. These results do not support the proposal that children in our community have a high incidence of subclinical infections.

Child, Preschool↗

Risk factors associated with nosocomial rotavirus infection.

A prospective study of hospital-acquired rotavirus infection was undertaken on an infant and young toddler floor to assess the incidence of infection and risk factors associated with nosocomial transmission. During the seven-month study period, gastroenteritis accounted for 60 of 663 admissions, 23 (38%) of which were due to rotavirus. In spite of enteric isolation of 21 (91%) of 23 patients with community-acquired cases, 36 infants developed nosocomial rotavirus infections. The attack rate of hospital-acquired infection was 12.8%, ranging each month from 2% to 21%. Approximately three fourths of both community-acquired cases (17/23) and nosocomial cases (27/36) occurred during the late winter and early spring. Prolonged stays in the hospital were associated with an increased attack rate of rotavirus infection. The risk of nosocomial rotavirus infection was not significantly enhanced by room contact with a rotavirus-infected patient or by the sharing of staff. However, only 47% (17/36) of patients with nosocomial infections were appropriately isolated, despite symptoms of gastroenteritis in all cases. These findings indicate that hospital acquisition of rotavirus is common, and indicate that failure to isolate patients with nosocomial rotavirus infections could be an important factor in hospital transmission.

Child, Preschool↗

Epidemiological aspects of porcine rotavirus infection in Venezuela.

The prevalence of porcine rotavirus infection in Venezuela was studied from November 1980 to November 1981. Rotaviruses were identified in 21.3 per cent of 286 diarrhoeic samples analysed by electron microscopy and in none of the 48 controls. Rotaviruses were readily detected throughout the year, which may correspond to the absence of seasonal climatic variations in a tropical country such as Venezuela. Rotavirus infection was frequently observed in pigs that were two to six weeks old and was rare in younger animals. The age distribution of rotavirus infection correlated well with the presence of circulating antibodies, as measured by the complement fixation test. Sucking pigs less than two weeks old appeared to be protected from the infection by passive immunity; no antibodies were detected in the two- to three-week-old group, coinciding with an increased susceptibility to rotavirus infection. The antigenic specificity of the rotavirus isolates was confirmed by enzyme-linked immunosorbent assay test, using antibodies directed against the group-specific antigen of human rotavirus. Polyacrylamide gel electrophoresis of viral double-stranded RNA revealed an heterogeneity on the electropherotype of selected samples obtained at different times during the study period.

Age Factors↗

Longitudinal survey of rotavirus infection in calves.

A longitudinal survey of rotavirus infection in heifer calves was carried out on a closed Friesian dairy herd over two successive calving seasons. Rotavirus was detected by electron microscopy in the faeces of 45 of 57 (79 per cent) calves examined. On average the virus was first detected at 6.1 days of age. Clinically the disease associated with rotavirus infection was of mild to moderate severity. Only one infected calf required intravenous fluid therapy. Diarrhoea or excretion of abnormal faeces was associated with rotavirus infection in 58 per cent of infected calves, while in the remaining 42 per cent infection was subclinical. The cycle of rotavirus infection was broken by thorough cleansing and disinfection of the calf house.

Animals↗

Natural killer cell activity of chicken intraepithelial leukocytes against rotavirus-infected target cells.

Intraepithelial leukocytes (IEL) and splenocytes collected from uninfected and rotavirus-infected chickens were evaluated for cytotoxic activity against a natural killer (NK) cell-susceptible lymphoblastoid cell line (LSCC-RP9) and against rotavirus-infected chick kidney cells in 4-h chromium-release assays. Both splenocytes and IELs from uninfected and rotavirus-infected chickens were cytotoxic for LSCC-RP9, and the levels of this NK cell activity were not altered by infection of the host with rotavirus. IELs but not splenocytes from uninfected and rotavirus-infected chickens were cytotoxic for rotavirus-infected but not for uninfected chick kidney cell targets. Because this cytotoxic activity was not induced nor altered by rotavirus infection of the host, and was not major histocompatibility complex-restricted, it was considered to be due to NK cell activity. The cytotoxicity of IELs against rotavirus-infected target cells was dose-dependent; however, there was some suppression of cytotoxic activity at high effector to target cell ratios. There were no differences in the cytotoxic activities of IELs collected from the duodenum versus the jejunum. The in vitro cytotoxic activity of IELs against rotavirus-infected target cells suggested that NK cell activity may be an important immune response to rotavirus infections in vivo. The absence of cytotoxic activity by splenocytes against rotavirus-infected target cells indicated that there may be different subpopulations of NK cells in the spleen and intestinal epithelium of chickens.

Animals↗

Oral immunoglobulin for the prevention of rotavirus infection in low birth weight infants.

BACKGROUND: Rotavirus infection is the most common neonatal nosocomial viral infection. Epidemics with the newer P(6)G9 strains have been reported in neonatal units worldwide. These strains can cause severe symptoms in infected infants. Infection control measures become necessary and the utilisation of hospital resources increase. Local mucosal immunity in the intestine to rotavirus is important in the resolution of infection and protection against subsequent infections. Boosting local immunity by oral administration of anti-rotaviral immunoglobulin preparations might be a useful strategy in preventing rotaviral infections, especially in low birth weight babies. OBJECTIVES: To determine the effectiveness and safety of oral immunoglobulin preparations for the prevention of rotavirus infection in hospitalised low birthweight infants (birth weight less than 2500 gms) SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2002), MEDLINE, EMBASE and CINAHL were searched. Science Citation Index was searched for all articles which referenced Barnes 1982. The proceedings of the Pediatric Academic Societies which were published in the journal, Pediatric Research from 1991 onwards were searched as well as abstracts of doctoral dissertations and theses from 1960 onwards. The above mentioned search strategy was completed in June 2002. Authors prominent in the field were contacted for any unpublished articles and more information on published articles was sought. Reference lists of identified clinical trials and personal files were reviewed. SELECTION CRITERIA: The criteria used to select studies for inclusion were: 1) DESIGN: randomised or quasi-randomised controlled trials. 2) PARTICIPANTS: Hospitalised low birthweight infants. 3) INTERVENTION: Oral immunoglobulin preparations for prevention of rotavirus infection compared to placebo OR no intervention. 4) At least one of the following outcomes were reported: All cause mortality during hospital stay, mortality due to rotavirus infection during hospital stay, rotavirus infection, duration of diarrhoea, need for rehydration, duration of viral excretion, duration of infection control measures, length of hospital stay in days, recurrent diarrhoea or chronic diarrhoea. DATA COLLECTION AND ANALYSIS: The two reviewers independently abstracted data from the included trials MAIN RESULTS: One published study (Barnes 1982) was eligible for inclusion in this review. Two additional studies are awaiting assessment re eligibility for inclusion. Barnes 1982 found no significant difference in the rates of rotavirus infection after oral gammaglobulin versus placebo in hospitalised low birthweight babies [RR 1.27 (95% CI 0.65-2.37)]. In the subset of infants who became infected with rotavirus after receiving gammaglobulin or placebo for prevention of rotavirus infection, there was no significant difference in the duration of rotavirus excretion between the group who had gammaglobulin (mean 2 days, range 1-4 days) and the group who had placebo (mean 3 days, range 1-6 days). No adverse effects were reported by Barnes 1982 after administration of oral immunoglobulin preparations. REVIEWER'S CONCLUSIONS: Current evidence from one randomised controlled trial does not support the routine use of oral immunoglobulin preparations for the prevention of rotavirus infection in low birth-weight infants. However, newer immunoglobulin preparations which have been found to be effective in older children have not been tested in neonatal trials. Therefore, researchers should be encouraged to conduct well designed trials in neonates at risk for rotavirus infections using the newer preparations of anti-rotaviral immunoglobulins (colostrum, egg yolk immunoglobulins). Such trials should also include cost effectiveness evaluations.

Administration, Oral↗

Disease burden and related medical costs of rotavirus infections in Taiwan.

BACKGROUND: The disease burden and associated medical costs of rotavirus infections in inpatient and outpatient sectors in Taiwan were examined in anticipation of the availability of new rotavirus vaccines. METHODS: The yearly national case number and medical costs for all for inpatients and outpatients with acute gastroenteritis (AGE) were extracted from the Bureau of National Health Insurance database in Taiwan according to ICD-9-CM codes. A retrospective study was also performed using records of children with AGE seen at three hospitals in Taiwan in 2001 to identify laboratory confirmed rotavirus infection cases. The annual incidence and related medical costs of AGE due to rotavirus infection were then estimated. RESULTS: Children <5 years old comprised 83.6% of inpatient and 62.0% of outpatient pediatric AGE cases in Taiwan in 2001. Rotavirus was the most common agent detected among AGE patients in this age group in the three hospitals, and was detected in 32.9% (221/672) of inpatient and 24% (23/96) of outpatient stool specimens tested for microbial etiologies. An estimated 277,400 to 624,892 cases of rotavirus infections sought medical care in Taiwan in 2001, equaling one in 2 to 5 children <5 years old required medical care due to rotavirus infection. The incidence of hospitalization due to rotavirus infections was 1,528-1,997/100,000 for children <5 years old. The total associated medical costs due to rotavirus infection were estimated at US $10-16 millions in Taiwan in 2001. Although the per-capita medical cost of rotavirus infection was lower in Taiwan than in the United States or Hong Kong, the personal economic burden was similar among the three places when normalized for gross national incomes per capita. CONCLUSION: Infections caused by rotavirus constitute an important human and economic burden among young children in Taiwan. A safe and effective vaccine is urgently needed.

Adolescent↗