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Biomedical subjects

R I Glass

Publications and source records attributed to R I Glass.

At least 127 records · Page 7Linked to original sources

Trends in hospitalizations for diarrhea in United States children from 1979 through 1992: estimates of the morbidity associated with rotavirus.

OBJECTIVES: To examine trends in the hospitalizations of children for diarrheal disease in the U.S. and to provide estimates for the burden of disease associated with rotavirus diarrhea. METHODS: Data for diarrheal hospitalizations among U.S. children ages 1 month through 4 years were compiled from the National Hospital Discharge Survey for the years 1979 through 1992. Between 1979 and 1992, 12% of all hospitalizations of U.S. children 1 month through 4 years of age had an International Classification of Diseases code for diarrhea listed in one of the top three positions on the discharge diagnosis. RESULTS: The annual rate of diarrheal hospitalizations, 97 per 10 000 persons (average, 185 742 per year), did not change substantially during the 14-year study period and accounted annually for 724 394 inpatient days (3.9 days per hospitalization). For most diarrheal hospitalizations (75.9%) no causative agent was specified in the National Hospital Discharge Survey records; of the remaining 24.8%, viruses were most commonly reported (19.3%), followed by bacteria (5.1%) and parasites (0.7%). The proportion of hospitalizations associated with viral diarrheas rose from 13% to 27% during the 14-year study period, whereas the proportion of hospitalizations for noninfectious diarrhea declined from 79% to 60%. Every year the number of hospitalizations peaked from November through April, the "winter" months, among children ages 4 through 35 months; this peak began in the West during November and December and reached the Northeast by March. CONCLUSIONS: Diarrhea continues to be a common cause of hospitalization among children in the United States and the winter seasonality estimated to be caused in large part by rotavirus would be expected to decrease if rotavirus vaccines currently being developed were introduced. Our analysis of temporal trends in diarrheal hospitalizations provides a unique surrogate with which to estimate the disease burden associated with rotavirus diarrhea.

Bacterial Infections↗

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↗

Unusual diversity of human rotavirus G and P genotypes in India.

Between April and December 1993, we determined P and G genotypes of group A rotavirus strains obtained from children admitted to diarrhea treatment centers in five Indian cities. From a total of 63 rotavirus-positive specimens, we identified 10 different strains with five different G genotypes and four distinct P types by using reverse transcription-PCR. The common worldwide strains G1P8, G2P4, G3P8, and G4P8 were underrepresented among Indian children (33%), whereas strains of P type 6 (G1P6, G2P6, G3P6, G4P6, and G9P6), which primarily infect asymptomatic newborns but are rare in children with diarrhea were common in India (43%). Of these, G9P6, a strain not previously reported to be found in children with diarrhea, was the most prevalent (22%). Eleven percent of the strains were nontypeable, and another 11% of the specimens had mixed infections. Using digoxigenin-labeled, genotype-specific hybridization probes, we confirmed all G9 strains and mixed infections tested and identified three nontypeable strains (one G9 and two P8). The epidemiological significance of G9 rotavirus strains, if confirmed in other settings, may have important implications for vaccine development.

Base Sequence↗

Safety and efficacy of high-dose rhesus-human reassortant rotavirus vaccines--report of the National Multicenter Trial. United States Rotavirus Vaccine Efficacy Group.

OBJECTIVE: Rotavirus is a leading cause of morbidity and mortality from dehydrating gastroenteritis in infants and young children worldwide. Virtually every child is infected by age 4 years, justifying universal childhood immunization when a safe and effective vaccine is available. We report the results of a multicenter, placebo-controlled field trial in the United States of monovalent serotype 1 and tetravalent (TV) rhesus-human reassortant rotavirus vaccines (RRVs). DESIGN: In this randomized, double-blind trial, 1278 healthy infants ages 5 to 25 weeks received three oral doses of RRV serotype 1, RRV-TV, or a placebo at approximately 2, 4, and 6 months of age. Vaccines contained 4 x 10(5) plaque-forming units of virus. Gastroenteritis episodes were monitored, and severity was graded throughout one rotavirus season. Two stool specimens per episode were tested for rotavirus. RESULTS: The incidence of reactions did not differ among treatment groups during the 5-day, postvaccination safety surveillance period for any of the three doses. Both vaccines significantly reduced the incidence of rotavirus gastroenteritis. Vaccination was most protective against serious rotavirus illness; RRV-TV prevented 49% of rotavirus episodes, 80% of very severe episodes, and 100% of dehydrating rotavirus illness. Reduction of rotavirus disease by RRV-TV resulted in significantly fewer total episodes of gastroenteritis of all causes and an 82% reduction in all cases of dehydrating diarrhea. CONCLUSION: RRV-TV is highly protective against very severe, dehydrating rotavirus gastroenteritis.

Administration, Oral↗

Trends of diarrheal disease--associated mortality in US children, 1968 through 1991.

OBJECTIVES: To describe temporal patterns in mortality related to diarrheal disease in US children and to assess progress toward its prevention and control. DESIGN: Retrospective analyses of death certificate data on diarrhea of all causes compiled by the National Center for Health Statistics, Centers for Disease Control and Prevention, Atlanta, Ga. PATIENTS: Children aged 1 month through 4 years who died with diarrhea. SETTING: United States, 1968 through 1991. RESULTS: A total of 14 137 deaths associated with diarrhea among children were reported in the United States between 1968 and 1991. Of these, 78% occurred in infants (ie, aged 1 to 11 months); the median age at the time of death has declined from 5 to 1.5 months. Diarrheal disease mortality dropped by approximately 75% during the first 18 years of the study, but no decline has occurred since 1985. Infant mortality due to diarrhea (per 100 000 live births) averaged 12.8 and was found to be high for blacks (33.1) and for residents of the southern United States (18.5). The infant mortality due to diarrhea from 1986 through 1991 is 5.9. Peaks in winter deaths previously associated with rotavirus were prominent in the early years among infants aged 4 through 11 months. Such peaks have virtually disappeared since 1985. Diarrhea was the principal cause of death, as the leading associated diagnoses (electrolyte disorders [30%], cardiac arrest [16%], shock [8%], and nausea/vomiting [4%]) were commonly recognized complications of diarrhea. Since 1979, prematurity has emerged as a common associated diagnosis. CONCLUSIONS: Diarrheal deaths nationwide have declined 75% from 1968 to 1985 but stabilized since then at about 300 deaths per year. Because many of these deaths may still be preventable by early rehydration, future prevention efforts should be directed at educating health care providers about the continuing problem and recognition of the high-risk infant and at teaching mothers of such infants to begin rehydration early and to seek medical attention when their infant develops diarrhea.

Cause of Death↗

Evaluation of rhesus rotavirus monovalent and tetravalent reassortant vaccines in US children. US Rotavirus Vaccine Efficacy Group.

OBJECTIVE: To determine the safety and relative efficacy of two reassortant rhesus rotavirus vaccines over two rotavirus seasons. DESIGN: A prospective, double-masked, placebo-controlled trial. SETTING: Twenty-three centers in the United States. PARTICIPANTS: A total of 1006 healthy infants between 4 and 26 weeks of age were enrolled, and 898 received three doses of vaccine or placebo. MAIN OUTCOME MEASURES: Reactogenicity was determined by comparing the incidence of fever, diarrhea, and/or vomiting for 5 days after each dose of vaccine. Rotavirus IgA and neutralizing antibody to rhesus rotavirus and four rotavirus serotypes were measured in a subset of subjects. Relative efficacy was determined by comparing the incidence of rotavirus gastroenteritis after three doses of vaccine or placebo over two rotavirus seasons. RESULTS: Adverse reactions were mild and limited to a small but significant increase in the incidence of fever after the first dose of tetravalent but not monovalent vaccine. The relative efficacy against rotavirus disease over the 2 years of observation was 40% (98.3% confidence interval, 7% to 62%) for the monovalent and 57% (98.3% confidence interval, 29% to 74%) for the tetravalent vaccine. In post hoc analyses, the relative efficacy against very severe rotavirus gastroenteritis was 73% and 82% for monovalent and tetravalent vaccine recipients, respectively. Also, a 67% and 78% reduction in medical visits for rotavirus gastroenteritis was observed. Both vaccines protected against disease caused by serotype 1 rotavirus, but only the tetravalent vaccine reduced the incidence of disease caused by non-serotype 1 rotavirus infection detected in the second season. It is unclear, however, whether this result represents serotype-specific protection or a difference in the duration of protection. CONCLUSIONS: Vaccination with both vaccines was safe and significantly reduced the incidence of rotavirus gastroenteritis, but only the tetravalent vaccine provided protection against disease caused by non-serotype 1 rotaviruses during the second year of follow-up.

Antibodies, Viral↗

An outbreak of Norwalk virus gastroenteritis associated with eating raw oysters. Implications for maintaining safe oyster beds.

OBJECTIVE: To determine the characteristics and the cause of an outbreak of gastroenteritis associated with eating raw oysters. DESIGN: Survey of groups of persons reporting illness to the health department after eating oysters; survey of convenience sample of oyster harvesters; and tracing of implicated oysters. SETTING: General community. MAIN OUTCOME MEASURES: Relative risk for illness after oyster consumption, source bed of contaminated oysters, presence of antibodies to Norwalk virus in serum, presence of a Norwalk virus in stool by direct electron microscopy and reverse transcription-polymerase chain reaction (RT-PCR), and DNA sequences of RT-PCR products. RESULTS: Seventy (83%) of 84 persons who ate raw oysters became ill vs three (7%) of 43 people who did not eat raw oysters (relative risk, 11.9; 95% confidence interval, 4.0 to 34.2). Eleven (79%) of 14 serum pairs had at least a fourfold increase in antibody to Norwalk virus. All 12 stool samples tested were positive by electron microscopy and/or RT-PCR for Norwalk virus. The RT-PCR products from all seven stool samples tested had identical DNA sequences. Implicated oysters were harvested November 9 through 13, 1993, from a remote oyster bed. Crews from 22 (85%) of 26 oyster harvesting boats working in this area reported routine overboard disposal of sewage. One harvester with a high level of antibodies to Norwalk virus reported having gastroenteritis November 7 through 10 and overboard disposal of feces into the oyster bed. CONCLUSIONS: This outbreak was caused by contamination of oysters in the oyster bed, probably by stool from one or more ill harvesters. Education of oyster harvesters and enforcement of regulations governing waste disposal by oyster harvesting boats might prevent similar outbreaks.

Adolescent↗

Epidemiologic applications of novel molecular methods to detect and differentiate small round structured viruses (Norwalk-like viruses).

The molecular epidemiology of a large, multistate outbreak of oyster-associated gastroenteritis [Kohn et al. (1995): Journal of the American Medical Association 273:466-471. Dowell et al. (1995): Journal of Infectious Diseases 171:1497-1503.] was examined using new methods to detect small round structured viruses (SRSVs) by reverse transcription-polymerase chain reaction (RT-PCR) and to characterize strains by Southern hybridization and nucleotide sequencing of 81-bp of a PCR product amplified from the RNA polymerase gene. Of 37 stool specimens examined from patients in eight clusters of the multistate outbreak, 32 (86%) gave RT-PCR products specific for SRSVs of P1-A phylogenetic group. Nineteen PCR products from the eight clusters were confirmed to have the identical sequence, indicating that this large outbreak was attributed to a single strain of SRSV. In one of the eight clusters, five (63%) of eight patients had a mixed infection with a second SRSV strain that belonged to P2-B phylogenetic group. Of 12 specimens from patients in five other outbreaks and one sporadic case which occurred at the same time as the multistate outbreak, 10 (83%) gave products specific for SRSVs representing four phylogenetic groups (P1-A, P1-B, P2-A, and P2-B). The sequences of the P1-A products from two outbreaks and that of the P2-B product from another outbreak were identical to the P1-A sequence from the eight clusters and the P2-B sequence from the one cluster of the multistate outbreak, respectively. These results demonstrate the first application of these methods to enhance our understanding of the molecular epidemiology of SRSVs and provide answers of public health interest that could not have been obtained using classical epidemiologic methods alone.

Animals↗

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↗

Virologic features of an astrovirus diarrhea outbreak in a day care center revealed by reverse transcriptase-polymerase chain reaction.

Astroviruses cause outbreaks of diarrhea in children attending day care centers (DCCs). Reverse transcriptase-polymerase chain reaction (RT-PCR) was compared with EIA detection of astrovirus in stool specimens to characterize further the molecular epidemiology of an outbreak of astrovirus-associated gastroenteritis. Three hundred sixty-eight stool specimens collected prospectively from 36 children enrolled in a DCC during an 11-week outbreak of diarrhea were evaluated by EIA and RT-PCR. Astrovirus was detected in 32% of specimens by RT-PCR versus 10% by EIA (P < .001) and in 89% of children by RT-PCR versus 50% by EIA. The median duration of astrovirus excretion episodes detected by EIA was 1.5 days versus 4 days by RT-PCR (P = .06). Astrovirus was excreted for prolonged periods by immunocompetent children during this outbreak. RT-PCR was more sensitive than EIA for detection of astrovirus in stool specimens and redefined the epidemiology of astrovirus infection in this setting.

Age Factors↗

Detection and differentiation of antigenically distinct small round-structured viruses (Norwalk-like viruses) by reverse transcription-PCR and southern hybridization.

Application of reverse transcription (RT)-PCR to detect small round-structured viruses (SRSVs) from fecal specimens of patients with gastroenteritis has been insensitive because of the tremendous sequence heterogeneity between strains. We have designed two RT-PCR primer sets (G-1 and G-2) based on the nucleotide sequence diversity in the RNA polymerase gene of SRSVs belonging to two distinct genogroups represented by Norwalk virus (primers G-1) and Snow Mountain agent (primers G-2). All 22 SRSV strains examined that had been classified previously by solid-phase immune electron microscopy into four antigenic types (UK1, UK2, UK3, and UK4) could be detected by RT-PCR with these two primer sets. The G-1 primer set detected 6 UK2 strains, and the G-2 primers detected 16 strains, including 7 UK1, 5 UK3, and 4 UK4 strains. On the basis of nucleotide sequences of 81-bp fragments of the RT-PCR products from 13 strains determined in this study, together with those previously reported for 17 SRSV strains, we designed four sets of internal oligonucleotide probes (P1-A, P1-B, P2-A, and P2-B) for Southern hybridization, using chemiluminescent detection. The P1-A probe hybridized with PCR products from the UK2 strains; the P1-B probe, with products from two of the seven UK1 strains; the P2-A probe, with four of the remaining five UK1 strains; and the P2-B probe, with products from both UK3 and UK4 strains, as well as with one strain originally typed as UK1 which showed cross-reactivity with UK4 upon retesting by solid-phase immune electron microscopy. RT-PCR with both the G-1 and the G-2 primer sets can increase the detection rate of the many antigenically distinct SRSVs and, when combined with Southern hybridization, may predict the antigenic type of the SRSV associated with infection.

Adult↗

Use of solid-phase immune electron microscopy for classification of Norwalk-like viruses into six antigenic groups from 10 outbreaks of gastroenteritis in the United States.

Norwalk-like viruses observed in fecal specimens from 10 outbreaks of gastroenteritis investigated in the United States between 1987 and 1992 were analyzed by solid-phase immune electron microscopy. Outbreak virus strains were classified into six antigenic groups: the four types (UK1 to UK4) previously defined in the United Kingdom, Norwalk virus, and the Oklahoma agent that was newly defined in this study. The diversity of antigenic types demonstrated in these outbreaks was greater than previously recognized and will serve as a basis for characterization of these strains at the molecular level.

Antibodies, Viral↗

Typing of human astroviruses from clinical isolates by enzyme immunoassay and nucleotide sequencing.

A typing enzyme immunoassay (TYPE-EIA) was used to determine the antigenic types of 64 astrovirus-positive specimens from nine collections from seven countries. Six of the seven known astrovirus types were detected in the collections, with HAstV-1 predominating in all collections for one from the United Kingdom. Selected specimens were analyzed further by reverse transcriptase PCR and nucleotide sequencing of 348 bp within the capsid protein precursor region of the genome. The phylogenetic groupings (genotypes) determined from the sequences were entirely consistent with the antigenic groupings (serotypes) of isolates obtained by using the TYPE-EIA. The genetic variation within genotypes was small compared with the variation between genotypes, allowing unambiguous categorization of all specimens. Although some strains from widely separated geographic areas had identical sequences, in general, within a region most strains of the same type were identical. The TYPE-EIA may help further our understanding of the epidemiology of astrovirus and the possible role of serotype-specific immunity, while further knowledge of sequences could facilitate the development of simpler molecular methods of typing astrovirus strains.

Antigens, Viral↗

Comparison of immunogenicity and efficacy of rhesus rotavirus reassortant vaccines in breastfed and nonbreastfed children. US Rotavirus Vaccine Efficacy Group.

OBJECTIVE: To evaluate whether breastfeeding affected the immunogenicity and/or efficacy of candidate rhesus-human rotavirus reassortant vaccines. METHODS: A total of 989 healthy infants between 4 and 26 weeks of age were enrolled into a 23-center, prospective, randomized, double-masked, controlled study of the safety, immunogenicity, and efficacy of three doses (4 x 10(4) plaque-forming units) of monovalent rhesus-human viral protein 7, or G, serotype 1 reassortant vaccine, (RRV-S1) or tetravalent vaccine (RRV-TV) consisting of rhesus-human reassortant G serotypes 1, 2, and 4, and the parent RRV G serotype 3. Vaccine efficacy was compared in the breastfed and nonbreastfed children as well as seroconversion rates and postvaccination geometric mean titers (GMTs) of neutralizing antibodies to human serotypes 1, 2, 3, and 4, RRV, and immunoglobulin A to RRV. GMTs in the two feeding groups were compared with and without adjustment for age at initiation of vaccination, prevaccination antibody titers, and the age and prevaccination titer interaction. RESULTS: The seroconversion rates to both vaccines by one or more assays were similar for the breastfed and the nonbreastfed groups (RRV-S1, 84% and 85%, respectively; RRV-TV, 94% and 93%, respectively). There were no significant differences in postvaccination GMTs to either vaccine, measured by any serologic assay, in the two feeding groups. The efficacy of the RRV-S1 vaccine was not significantly lower among the breastfed children than the nonbreastfed children (28% and 39%, respectively). RRV-TV, which is the vaccine being further evaluated for licensure, was equally protective in breastfed and nonbreastfed infants (50% and 51%, respectively). Logistic regression analysis, taking into account differences in age at vaccination and day 1 titer, revealed no evidence of differential vaccine efficacy in the two feeding groups for either vaccine. CONCLUSIONS: These results indicate that the RRV-TV vaccine, given as three doses of 4 x 10(4) plaque-forming units, induces similar seroresponses and protection in breastfed and nonbreastfed US children.

Animals↗

Cost-effectiveness analysis of a rotavirus immunization program for the United States.

OBJECTIVE: To estimate the economic consequences in the United States of routine childhood immunization of children younger than 1 year of age with a rotavirus (RV) vaccine. DESIGN: Cost-effectiveness analysis of a national RV immunization program from the perspective of the health care system and the perspective of society. Estimates of disease incidence, medical expenditures, productivity costs, vaccine efficacy, and vaccine coverage rates were derived from published literature and unpublished vaccine trial reports. The impact of changes in estimates of vaccine efficacy and medical costs was determined by sensitivity analysis. MAIN OUTCOME MEASURES: Incremental cost effectiveness, expressed as savings per case of RV diarrhea prevented. RESULTS: Given a vaccine efficacy rate of 50% and a vaccine cost of $30 per dose, an RV immunization program would prevent more than 1 million cases of RV diarrhea, 58,000 hospitalizations, and 82 deaths per year. A vaccine program would cost $243 million per year but would yield net savings of $79 million from the perspective of the health care system and $466 million from the perspective of society. The incremental cost effectiveness was a savings of $459 per case prevented from the societal perspective and $78 per case prevented from the health care system perspective. Sensitivity analyses substantiated net savings over a wide range of variables, and cost effectiveness increased with greater vaccine efficacy or decreased vaccine cost. CONCLUSIONS: Economic and disease reduction benefits would be realized from the use of an RV vaccine that is partially protective against severe RV diarrhea. These findings suggest that immunization with an RV vaccine would be cost effective and cost saving.

Child, Preschool↗

Prevalence of antibodies to Norwalk virus among Amerindians in isolated Amazonian communities.

The seroepidemiology of Norwalk virus infections was examined among Amerindians belonging to eight relatively isolated communities in the Amazon region by means of a new enzyme immunoassay using recombinant Norwalk virus antigen. The seroprevalence of antibodies to Norwalk virus ranged from 39% in the Maiogong to 100% in the Kubenkrankrein. The distribution of antibody levels varied greatly among groups; five of the eight communities had an antibody prevalence greater than 90% with many high values (> 100 units), while three had both a low seroprevalence and a preponderance of low values (< 100 units). While few children less than 5 years of age were sampled, no significant differences in antibody prevalence were noted among age groups, and the prevalence of antibody among children 5-10 years of age approached that of the older age groups. The low prevalence of titers of antibodies to Norwalk virus in several tribes living in these isolated Indian communities suggests that Norwalk virus may have been only recently introduced.

Adolescent↗