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[Antigenic types of circulating rotavirus in children with acute diarrhea in Santiago de Chile].

Protective immunity against rotavirus infection is directed against antigenic epitopes on the outer capsid proteins VP7 and VP4. The aim of this study was to characterize the VP7 and VP4 antigenic types circulating in different hospital areas of Santiago, Chile, over different time periods. Between April 1993 and April 1994 a total of 1206 stool samples were obtained from children consulting for acute no bloody diarrhea in 5 hospitals representative of the 5 major health areas of Santiago. In addition, 256 rotavirus positive samples, obtained from children with acute diarrhea consulting in the north health area of Santiago between 1985-1987 were studied. All samples were processed for rotavirus by an ELISA and all rotavirus positive samples were VP7 typed (types G1-G4) by a monoclonal antibody based ELISA. 50 rotavirus positive samples were selected for VP4 typing by PCR (types P1-P4). A total of 782 rotavirus positive samples were obtained of which 618 (79%) were typable for one specific VP7 type. VP7 type G1 represented 63% of the rotavirus positive samples and predominated in all areas evaluated throughout the entire period of observation. VP7 type G2 represented 13% of rotavirus samples, following G1 in predominance. G2 types decreased progressively in all areas in both study periods. G4 types were detected mainly during 1985-1987, and G3 types have so far not been detected. Preliminary analysis of VP4 types suggests that P1 types are predominant and closely associated with VP7 G1 type. These results are relevant for the adoption of appropriate preventive strategies for rotavirus infection, specifically aimed to the development of effective vaccines.

Acute Disease↗

[The role of rotaviruses in digestive tract infections of hospitalized children with diarrhoea at the Health Care Consortium in Sokoł Podlaski].

The aim of the study was a trial of establishing of the frequency of rotavirus infection and mixed bacterial-viral infections in children treated for diarrhoea in a hospital in the period from July 1 1996 to June 30 1997. Moreover, an attempt was made at establishing of the frequency of rotavirus colonization of the digestive tract in healthy newborns born in that hospital during the period of that study. The studies were done on feces samples from 169 children with diarrhoea from 4 days to 13 years, and from 30 healthy peers. In all samples rotaviruses were sought along with pathogenic Enterobacteriaceae Tests for rotaviruses were done with Slidex-Rota Kit 2 (Bio-Merieux) and for EPEC with the EPEC latex test (Biomex). In all, rotaviruses were found in 88 ill children (52.1%) including mixed bacterial-viral infections in 10 (5.1%) children. In 9 children beside rotaviruses enteropathogenic E. coli (EPEC) were disclosed, and in 1 child S. enteritidis. Moreover, in 1 child (0.6%) culture yielded simultaneously S. sonnei and E. coli 0127. No rotaviruses were found in any 30 healthy newborns, but from one of them E. coli 018 was cultured. The second most frequent aetiological factor in diarrhoea were EPEC organisms found in 17 (10.0%) children, the third factor were S. enteritidis strains in 6 children (3.6%). In one case S. sonnei and E. coli 0127 were obtained from faces. Rotavirus infection was most frequent in children aged from 2 months to 3 years, and EPEC infection in children up to 2 years. The incidence was highest in winter/spring, with peak in April when 27 cases of rotavirus diarrhoea were noted.

Adolescent↗

Rotavirus typing methods and algorithms.

Vaccination is the current strategy for control and prevention of severe rotavirus infections, a major cause of acute, dehydrating diarrhoea in young children worldwide. Public health interventions aimed at improving water, food and sanitation are unlikely adequately to control the disease. The development of vaccines against severe rotavirus diarrhoea is based upon homotypic or heterotypic protection provided against either a single common G serotype (monovalent vaccines) or against multiple serotypes (multivalent vaccines). Rotavirus strain surveillance has a high priority in disease control programmes worldwide. The continued identification of the most common G and P serotypes for inclusion in vaccines is an important priority. And subsequent to the introduction of a vaccine candidate, not only monitoring of circulating strains is recommended, but also surveillance of potential reassortment of animal rotavirus genes from the vaccine into human rotavirus strains is critical. Conventional methods used in the characterisation of rotavirus strains, such as enzyme immunoassay serotyping and reverse-transcription PCR-based genotyping often fail to identify uncommon and newly appearing strains. The application of newer molecular approaches, including sequencing and oligonucleotide microarray hybridisation, may be required to characterise such strains. The present paper presents a brief overview of the variety of standard methods available, followed by suggestions for a systematic approach for routine rotavirus strain surveillance as well as for characterisation of incompletely typed rotavirus strains. Improved detection and characterisation of incompletely typed strains will help to develop a comprehensive strain surveillance that may be required for tailoring effective rotavirus vaccines.

Algorithms↗

Immunity to rotavirus in T cell deficient mice.

Rotavirus infection was studied in adult nude mice (BALB/c background), alpha beta or gamma delta and alpha beta/gamma delta T cell receptor (TCR) knockout (-/-) mice (C57BL/6 and C57BL/6 x 129 backgrounds), and SCID mice (C57BL/6 background). The gamma delta TCR -/- mice cleared infection just like control mice. All of the nude mice, alpha beta, and alpha beta/gamma delta TCR -/- mice cleared primary rotavirus infection, with a short delay, compared to immunocompetent control mice and developed a rotavirus-specific intestinal IgA measured by ELISA. Elispot analysis with spleen and lamina propia cells showed that the virus-specific intestinal IgA response in immunocompetent C57BL/6 mice was similar to the gamma delta TCR -/- mice and 7- to 60-fold higher than in the alpha beta TCR -/- and alpha beta/gamma delta TCR -/- mice. Likewise, the response of nude +/- mice was 20 times greater than that of nude -/- littermates. While the intestinal IgA antibodies of C57BL/6 mice, gamma delta TCR -/- mice, and nude +/- mice recognized insect cells infected with recombinant baculovirus expressing rotavirus VP6 and VP4 proteins, those of the alpha beta TCR -/-, alpha beta/gamma delta TCR -/-, and nude -/- mice recognized only VP6. Immunocompetent C57BL/6 mice depleted of CD4+ T cell developed similar levels of rotavirus-specific intestinal IgA as the alpha beta TCR -/- mice, suggesting that this T cell-independent IgA response is present in normal mice. In contrast to previously published results with BALB/c SCID and RAG 2 -/- (C57BL/6 x 129 background) mice, all of which become chronically infected with murine rotavirus, 40% of the C57BL/6 SCID mice cleared primary rotavirus infection. These results suggest that both a T cell-independent antibody response and innate mechanisms can contribute to immunity to murine rotavirus and show that gamma delta T cells are not necessary for efficient clearance of primary rotavirus infection in mice.

Animals↗

Determinants of rotavirus host range restriction--a heterologous bovine NSP1 gene does not affect replication kinetics in the pig.

The genetic basis of rotavirus host range restriction (host species specificity) is unknown but the NSP1 (fifth) gene has been implicated in some studies. We studied the replication kinetics in vivo of a NSP1 gene monoreassortant, E11, to assess the influence of a heterologous NSP1 gene on the ability to replicate in pigs. The monoreassortant possessed 10 genes from the porcine parent rotavirus SW20/21, which replicated productively in pigs, and the NSP1 gene from the bovine rotavirus UK which produced an abortive infection in pigs. Groups of up to four pigs were inoculated orally with 10(5) to 10(6) TCID50 of the monoreassortant, the porcine parent rotavirus, or the bovine parent rotavirus or were sham inoculated. The monoreassortant replicated productively in pigs with replication kinetics almost identical to the porcine parent rotavirus. During a 9-day observation period after inoculation, the number of days with virus in the faeces, the onset and duration of virus excretion, and peak titres in faeces were similar for the monoreassortant and the parent porcine rotavirus. The genetic composition of the viruses excreted in the faeces was confirmed as that of the inocula by PAGE. Thus possession of a heterologous NSP1 gene from a bovine rotavirus which failed to replicate in pigs did not produce an abortive infection or affect the replication kinetics in vivo. The genetic basis of host range restriction between porcine and bovine rotaviruses remains to be established.

Animals↗

Interleukin-8 gene regulation in intestinal epithelial cells infected with rotavirus: role of viral-induced IkappaB kinase activation.

Rotavirus is the major etiologic agent of diarrhea in children and the most common cause of severe pediatric gastroenteritis. Rotavirus infection is limited to mature enterocytes that line the villi of the small intestine. Gut epithelial cells, upon infection and cytokine stimulation, are able to produce chemokines, a family of small chemotactic cytokines that regulate the migration and activation of leukocytes. We have previously shown that rotavirus infection of the intestinal epithelial cell line HT-29 induces increased expression of the CXC chemokine interleukin- (IL) 8. Mechanisms responsible for the transcriptional regulation of the IL-8 gene in intestinal epithelial cells during viral infections have not been fully elucidated. Therefore, the purpose of this study was to define the molecular mechanisms of IL-8 gene expression in HT-29 cells infected with rotavirus. Transient transfection analysis of 5' deletions and mutations of the IL-8 promoter driving expression of luciferase reporter gene indicates that the activating protein- (AP) 1 and nuclear factor- (NF) kappaB elements are necessary for IL-8 promoter activation during rotavirus infection. The importance of NF-kappaB activation for IL-8 gene expression was further demonstrated by the inhibition of rotavirus-induced IL-8 gene transcription and protein synthesis following blockade of degradation of the NF-kappaB cytoplasmic inhibitor IkappaB-alpha. Rotavirus infection of HT-29-induced IkappaB kinase (IKK) activation and overexpression of a dominant negative mutant of IKK-beta greatly reduced rotavirus-induced IL-8 promoter activation and NF-kappaB-driven transcription, indicating that IKK is involved in rotavirus-induced IL-8 gene expression and NF-kappaB activation.

Epithelial Cells↗

Non-neutralizing monoclonal antibodies to a trypsin-sensitive site on the major glycoprotein of rotavirus which discriminate between virus serotypes.

Monoclonal antibodies were derived to a human rotavirus purified from stools. Three of the antibodies immunoprecipitated the rotavirus outer capsid glycoprotein gp 34 and were non-neutralizing. These antibodies reacted by enzyme immunoassay with cultivable rotaviruses showing the "long" RNA electropherotype but were inefficient as detectors of "long" RNA pattern rotaviruses in stools. Treatment of SA 11 rotavirus with 7.5 micrograms/ml porcine trypsin for 30 minutes at 37 degrees C irreversibly reduced binding of the antibodies to SA 11 rotavirus in enzyme immunoassays by 50 per cent. Binding was abolished in the presence of rotavirus-negative faecal extracts. These results indicate that non-neutralizing sites on gp 34 of rotaviruses can vary with RNA electropherotype and serotype, and that levels of trypsin currently in use to assist growth of rotaviruses in cell culture may alter the serological profile of the viruses.

Animals↗

Active hospital-based surveillance of rotavirus diarrhea in Austrian children, period 1997 to 2003.

BACKGROUND: Rotavirus is the most common pathogen causing severe dehydrating diarrhea in infants and young children worldwide. Any decision on implementation of rotavirus vaccination will be strongly influenced by the expected reduction in severe and therefore costly outcomes associated with rotavirus infection. The aim of this study was to provide data on hospitalization of young children with rotavirus infection in Austria. METHODS: The data were derived from active hospital-based sentinel surveillance for rotavirus during the period 1997 to 2003. RESULTS: During this period 25,600 children<15 years of age were hospitalized with acute laboratory-confirmed rotavirus gastroenteritis, the infection showing seasonal peaks between February and March. In 5 % of the cases first symptoms of diarrhea occurred at a minimum of 48 hours after hospital admission, indicating healthcare-associated origin of infection. The mean annual incidence of hospitalization per 100,000 population for the age group<5 years was 766 and for those<2 years 1742, the latter meaning that 1 in 60 Austrian children up to 2 years of age required hospitalization. An average peak incidence was observed between 8 and 14 months of age, with an average of 68% of the reported cases occurring in children aged<or=24 months. The mean length of hospital stay was 4.7 days, resulting in 17,200 rotavirus-associated hospital days per year. CONCLUSIONS: The observed incidence of hospitalization due to rotavirus in Austria is slightly higher than that reported in other industrialized countries. Our results reflect the considerable number of rotavirus-associated pediatric hospital in-patient days per year and the substantial annual direct costs of hospital care.

Adolescent↗

Analysis of the gene encoding the outer capsid glycoprotein (VP7) of group C rotaviruses by northern and dot blot hybridization.

The genetic diversity of gene 8 (encoding the outer capsid glycoprotein VP7) among group (Gp) C rotaviruses was examined by Northern and dot blot hybridization. A cDNA clone of the porcine Gp C Cowden strain gene 8 was labeled with 32P by nick translation and used as a probe. The gene 8 probe hybridized with the corresponding gene of one human (88-196) and four porcine (Cowden, NB, WH, and Wi) strains of Gp C rotaviruses under both moderate (50% formamide, 5X SSC, and 42 degrees) and high (50% formamide, 5X SSC, and 52 degrees) stringency conditions. However, under high stringency conditions little or no hybridization was detected with the corresponding gene of one bovine (Shintoku) and three other porcine (Ah, HF, and KH) strains of Gp C rotaviruses. In control experiments, the Cowden gene 8 probe did not hybridize with Gp A (Gottfried strain) or Gp B (Ohio strain) rotaviruses. These data demonstrate that the Cowden gene 8 probe is Gp C rotavirus-specific and that genetic diversity exists among Gp C rotaviruses in the gene encoding the outer capsid glycoprotein VP7. Our gene 8 probe may be useful in hybridization assays for serotyping Gp C rotaviruses, analogous to the use of VP7 probes for serotyping Gp A rotaviruses. However, final confirmation of our genetic approach to serotype Gp C rotaviruses awaits the serologic analysis of these viruses.

Animals↗

Priming and induction of anti-rotavirus antibody response by synthetic peptides derived from VP7 and VP4.

Synthetic peptides derived from bovine rotavirus C-486 (BRV) outer capsid (VP7 and VP4) and inner capsid (VP6) proteins were tested to evaluate their ability to prime and induce an anti-rotavirus antibody response. Peptides corresponding to the amino acid residues 232-255 of VP4 (VP4-peptide), 275-295 of VP7 (VP7-peptide) and 40-60 of VP6 (VP6-peptide) of BRV were chemically synthesized. These peptides were coupled to carrier proteins (either keyhole limpet haemocyanin (KLH) or recombinant rotavirus inner capsid protein-VP6 assembled into virus-like particles (VP6-carrier) were used as carrier to link the synthetic peptides under study), and the resulting conjugates were used to immunize rotavirus seronegative mice. An enzyme-linked immunosorbent assay (ELISA) was used to determine anti-peptide and anti-rotavirus antibody titres in serum samples collected after immunization. All peptides were immunogenic in mice and induced the production of anti-peptide antibodies, but with the exception of VP6-peptide they were not able to induce anti-rotavirus antibodies as measured by ELISA. Western blot analysis indicated that antibodies against each peptide were able to react with the respective authentic viral proteins of various rotavirus serotypes. To determine if a peptide-primed animal would respond to native viral proteins, animals were subsequently injected with purified BRV. A rapid and high anti-rotavirus antibody titre, in addition to a rise in anti-peptide antibody titre, was observed in peptide-primed mice. Furthermore, the sera obtained from these mice neutralized the virus under in vitro conditions. The significance of these results in relation to a potential rotavirus synthetic peptide-based vaccine is discussed.

Amino Acid Sequence↗

Homeostasis and function of goblet cells during rotavirus infection in mice.

Rotaviruses are the leading cause of severe viral gastroenteritis in young children. To gain insight in goblet cell homeostasis and intestinal mucin expression during rotavirus infection, 6-day-old mice were inoculated with murine rotavirus. To determine epithelial cell migration, mice were injected with BrdU just before inoculation. Small intestines were isolated at different days postinfection (dpi) and evaluated for rotavirus and goblet cell-specific gene expression. Small intestinal mucins of control and infected animals at 1, 2, and 4 dpi were isolated and tested for their capability to neutralize rotavirus infection in vitro. After inoculation, two peaks of viral replication were observed at 1 and 4 dpi. During infection, the number of goblet cells in infected mice was decreased in duodenum and jejunum, but was unaffected in the ileum. Goblet cells in infected animals accumulated at the tips of the villi. Muc2 mRNA levels were increased during the peak of viral replication at 1 dpi, whereas at other time points Muc2 and Tff3 mRNA levels were maintained at control levels. Muc2 protein levels in the tissue were also maintained, however Tff3 protein levels were strongly decreased. The number of goblet cells containing sulfated mucins was reduced during the two peaks of infection. Mucins isolated at 1 and 2 dpi from control and infected mice efficiently neutralized rotavirus infection in vitro. Moreover, mucins isolated from infected mice at 4 dpi were more potent in inhibiting rotavirus infection than mucins from control mice at 4 dpi. In conclusion, these data show that during rotavirus infection, goblet cells, in contrast to enterocytes, are relatively spared from apoptosis especially in the ileum. Goblet cell-specific Muc2 expression is increased and mucin structure is modified in the course of infection. This suggests that goblet cells and mucins play a role in the active defense against rotavirus infection and that age-dependent differences in mucin quantities, composition, and/or structure alter the anti-viral capabilities of small intestinal mucins.

Animals↗

Induction of mucosal immune responses and protection against enteric viruses: rotavirus infection of gnotobiotic pigs as a model.

Enteric viruses are a major cause of diarrhea in animals and humans. Among them, rotaviruses are one of the most important causes of diarrhea in young animals and human infants. A lack of understanding of mechanisms to induce intestinal immunity and the correlates of protective immunity in neonates has impaired development of safe and effective vaccines against enteric viruses. Studies of candidate vaccines using an adult mouse model of subclinical enteric viral infections often do not predict vaccine efficacy against disease evaluated in neonatal large animals. A series of studies have been conducted using a neonatal gnotobiotic pig model of rotavirus infection and diarrhea to identify correlates of protective immunity and to evaluate traditional and novel vaccine approaches for the induction of mucosal immune responses and protection to enteric viruses. Gnotobiotic pigs recovered from infection with virulent Wa human rotavirus (HRV) (mimic natural infection) had high numbers of intestinal IgA rotavirus-specific primary antibody-secreting cells (ASCs) and memory B-cells (to recall antigen) measured by ELISPOT assay, which correlated with complete protection against rotavirus challenge. Most short-term IgA memory B-cells were resident in the ileum, the major site of rotavirus replication. Spleen, not the bone marrow, was the major resident site for longer-term IgG memory B-cells. Candidate rotavirus vaccines evaluated in pigs for their ability to induce intestinal or systemic ASC and protection against rotavirus infection and diarrhea included attenuated live virus, inactivated virus, and baculovirus-expressed double-layered rotavirus-like particles (2/6-VLPs). In combination with those candidate vaccines, various adjuvants, delivery systems, and immunization routes were tested, including incomplete Freund's adjuvant for i.m. immunization, and a mutant Escherichia coli heat labile enterotoxin R192G (mLT) for i.n. immunization. It was shown that orally administered replicating vaccines were most effective for priming for intestinal IgA ASC and memory B-cell responses, but i.n. administered non-replicating 2/6-VLPs plus mLT were effective as booster vaccines. We conclude that protective immunity depends on the magnitude, location, viral protein-specificity, and isotype of the antibody responses induced by vaccination. Therefore highly effective enteric viral vaccines should: (i) induce sufficient levels of intestinal IgA antibodies; (ii) include viral antigens that induce neutralizing antibodies; and (iii) require the use of effective mucosal adjuvants or antigen delivery systems for non-replicating oral or i.n. vaccines.

Animals↗

Sequence analysis of the VP6 gene in group A turkey and chicken rotaviruses.

cDNAs corresponding to the VP6 gene of the turkey rotavirus strains Ty-1 and Ty-3, and the chicken rotavirus strain Ch-1, were cloned and sequenced. The nucleotide and deduced amino acid sequence homology in the coding region of the VP6 gene in avian rotaviruses ranged from 78.1 to 93.9% and 86.1 to 98.7%, respectively. Both sequences of VP6 from avian rotaviruses exhibited a low degree of sequence homology (67.8-70.7% and 69.8-74.6%, respectively) compared with mammalian rotaviruses. Phylogenetic tree analysis showed that all avian rotaviruses were included in a single cluster and have separated early or from mammalian rotaviruses during evolution. The chicken rotavirus strain Ch-1 was a distant relative of other avian rotaviruses.

Amino Acid Sequence↗

Prospective longitudinal study of rotavirus infections in children from birth to two years of age in Central Africa.

A cohort of 111 children born in Bangui (Central African Republic) was followed from birth to two years of age for rotavirus infections by biweekly stool investigations until six months of age, as well as at each diarrhoeic episode. Thirty-eight children (34.2%) exhibited at least one rotavirus infection by the age of 6 months. Thirty children (27%) presented with rotavirus-associated diarrhoea before 2 years of age. Until the children reached the age of 12 months, rotavirus was identified significantly more frequently in diarrhoeic stools than in non-diarrhoeic stools (p less than 0.001). A low diversity of characterized rotavirus strains was found; only two electrophoretypes were identified, and 91% of the strains belonged to subgroup II, serotype 1, with no special strain identified in newborns. A total of 38 children had a rotavirus infection before the age of six months, while 73 did not: only 2.6% of the first group had diarrhoea associated with rotavirus between 6 and 24 months, versus 20.5% in the second group (p less than 0.05). In two-thirds of the cases of infection, the presence of rotavirus in stools was detected only once; repetitive isolations were more frequent in diarrhoeic than in asymptomatic infections. The isolation rate of rotavirus in the general populations was found to be very low (0.2%).

Age Factors↗

Effect of Lactobacillus GG and breast-feeding in the prevention of rotavirus nosocomial infection.

BACKGROUND: Rotavirus is one of the leading etiologic agents of nosocomial infections among children. The development of preventive measures is therefore important. The efficacy of GG in the treatment of rotavirus infection has been reported in literature, but there is only one recent study about its effectiveness in prevention of infection. The role of breast-feeding in the prevention of rotavirus infection is still debated. The aim of our study was to assess the efficacy of GG and breast-feeding in the prevention of nosocomial rotavirus infections. METHODS: In a randomized, placebo-controlled, double-blind study, 220 children aged 1 to 18 months hospitalized from December 1999 to May 2000, received GG (n = 114) at a dose of 10 colony-forming units or a comparable placebo (n = 106) every day of their hospital stay. Rotavirus testing on stool samples was performed for every patient on admission, during hospitalization, and after discharge. RESULTS: The total incidence of nosocomial rotavirus infections was 27.7% (61 of 220 patients). The attack rate of rotavirus infections among the patients who received probiotic was 25.4% (29 of 114 patients), while for the placebo group it was 30.2% (32 of 106 patients). The difference is not significant (P = 0.432). Forty-seven of 220 infants (21.4%) were breast-fed, and 173 of 220 (78.6%) were non-breast-fed. The attack rate of rotavirus infections among breast-fed infants was 10.6% (5 of 47 infants), while for non-breast-fed infants it was 32.4% (56 of 173 infants). The difference is significant (P = 0.003). CONCLUSION: In our study, GG was ineffective in preventing nosocomial rotavirus infections, whereas breast-feeding was effective.

Breast Feeding↗

Epidemiologic patterns of diarrheal disease in Argentina: estimation of rotavirus disease burden.

BACKGROUND: Information on the burden of diarrheal diseases and rotavirus diarrheal diseases would help define strategies for management and prevention and clarify the potential benefits of candidate vaccines. This report of our study of the epidemiology of rotavirus diseases in Argentina analyzes the burden of rotavirus diarrhea, based on those studies and national statistics of diarrhea-associated medical visits, hospital discharges and deaths. METHODS: Information of diarrhea-associated medical visits, hospital discharges and deaths were provided by the Argentine Health Ministry. Estimation of rotavirus disease burden was performed using the percentage of rotavirus identification from previous reports. RESULTS: The incidence of diarrhea-associated medical visits (1999) was 14 times greater for ages 0 to 4 years than for ages of > or =5 years. Diarrhea-associated hospital discharges (0 to 4 years of age) decreased between 1981 and 1995 from 1.3 per 100 to 0.9 per 100 person-years) and diarrheal deaths (<2 years of age) decreased by a factor of 4 between 1985 and 1999 (64.7 per 100 000 to 16.1 per 100 000 person-years). Frequency of diarrheal deaths, hospital discharges and medical visits were highest in some of the northern Argentine provinces (26.2, 14.7 and 5.9 times greater, respectively, than in the lower risk areas of the country). We estimated that 1 in 2 children born in 1995 visited a public hospital, 1 in 12 required hospitalization, 1 in 1599 died of diarrheal diseases before their fifth year of life; 1 in 6, 1 in 35 and 1 in 4169 of those, respectively, died as a result of rotavirus diarrhea before their third year of life. CONCLUSIONS: The number of preventable diarrhea-associated and rotavirus-associated hospitalizations and deaths in Argentina is significant. The lack of rotavirus diagnostic capability in Argentine hospitals has resulted in underestimation of the disease burden of this virus. A rotavirus vaccine would have the potential to avoid thousands of hospitalizations and dozens of deaths, especially in the poor high risk Argentine provinces.

Age Factors↗

Rotavirus in El Salvador: an outbreak, surveillance and estimates of disease burden, 2000-2002.

BACKGROUND: In December 2000, a large outbreak of gastroenteritis occurred in El Salvador that was associated with hospitalizations and deaths among children nationwide. Public concern was raised because the etiology was initially unknown and enteric control measures seemed ineffective. The outbreak was eventually linked to rotavirus, control measures were redirected to improving treatment with oral rehydration and surveillance was initiated to characterize the etiologic agents of gastroenteritis. METHODS: Demographic and clinical data and fecal specimens were collected from a systematic sample of children younger than 5 years old with acute gastroenteritis. Stools were tested for rotavirus, bacteria and parasites. Surveillance results were extrapolated to national data to estimate the national burden of rotavirus disease. RESULTS: Surveillance between May 2001 and April 2002 demonstrated that rotavirus has winter seasonality, was associated with vomiting and dehydration and accounted for an estimated 27% of 12,083 consultations for diarrhea. Children with rotavirus gastroenteritis were younger (median, 9 months) than those with gastroenteritis caused by other agents (median, 13 months for bacteria, 16 months for parasites). Extrapolating to national data, we estimated the risk of a child experiencing a rotavirus-related medical visit, hospitalization and death by the age of 5 years as 1:7, 1:56 and 1:531, respectively. CONCLUSIONS: The outbreak of gastroenteritis among children younger than 5 years of age between December 2000 and February 2001 represented an exaggerated rotavirus season. The surveillance activity after the outbreak suggests that rotavirus is the most common cause of diarrheal disease in El Salvador. Further surveillance could provide a sound basis for improving the response to epidemics of gastroenteritis and could provide data needed to decide whether rotavirus vaccination should be included in the national program for childhood immunizations.

Child, Preschool↗

Impact of acute rotavirus gastroenteritis on pediatric outpatient practices in the United States.

OBJECTIVES: The objectives of this study were to determine the presenting symptoms, healthcare utilization, and lost time from work and day care associated with acute rotavirus gastroenteritis. METHODS: During the winter to spring seasons of 2002-2003 or 2003-2004, children <36 months of age presenting with acute gastroenteritis to urban and suburban pediatric outpatient practices affiliated with 5 academic centers across the United States were enrolled in similarly designed studies. The case definition required >or=3 watery or looser-than-normal stools and/or forceful vomiting within a 24-hour period beginning <or=72 hours before presentation. Stool samples were tested for rotavirus antigen by standard commercial assays. Symptom frequencies for laboratory-confirmed rotavirus and nonrotavirus gastroenteritis were compared by Fisher's exact test; the number of healthcare contacts and lost days from work or day care were compared with the median 2-sample test. RESULTS: Stool specimens were obtained from 284 of 303 (94%) participants; 115 (40%) of tested specimens were positive for rotavirus (range, 31-50% across the 5 centers). Compared with participants with nonrotavirus gastroenteritis, children with rotavirus gastroenteritis were more likely to have 1) vomiting (83% versus 66%; P = 0.003), 2) combined diarrhea and vomiting (75% versus 50%; P < 0.001), and 3) fever (60% versus 43%; P = 0.010). More time from work was lost by parents/guardians of children with rotavirus than nonrotavirus gastroenteritis (median 2 versus 0 day; P = 0.007). More day care was missed by children with rotavirus than nonrotavirus gastroenteritis (median 3 versus 1 day; P = 0.002). CONCLUSIONS: In this multicenter study, rotavirus consistently caused a sizable proportion of cases of acute gastroenteritis seen in pediatric outpatient practices in the United States during the winter and spring. Rotavirus gastroenteritis was more frequently associated with vomiting, combined diarrhea and vomiting, fever and lost time from work and day care than nonrotavirus gastroenteritis.

Acute Disease↗