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Biomedical subjects

R I Glass

Publications and source records attributed to R I Glass.

At least 37 records · Page 2Linked to original sources

Rotavirus and central nervous system symptoms: cause or contaminant? Case reports and review.

Rotavirus is a common cause of severe gastroenteritis in children. In 2 patients with rotavirus gastroenteritis who developed encephalopathy, rotavirus RNA was detected in the cerebrospinal fluid (CSF) by reverse transcription-polymerase chain reaction; in 1 patient, rotavirus RNA was detected on 2 occasions 3 weeks apart. There are increasing reports of cases in which patients who have seizures after an episode of rotavirus diarrhea have evidence of rotavirus in their CSF. A search of 2 large hospital discharge databases suggested that seizures are noted as part of the discharge diagnosis in the records of, at most, <4% of patients with rotavirus diarrhea versus 7% of patients with bacterial diarrhea. Although evidence suggesting that rotavirus is a cause of central nervous system sequelae remains inconclusive, the 2 case reports presented in this study further illustrate a possible association. Further study is required to determine whether detection of rotavirus in CSF represents a true pathogen, CSF contamination that occurs at the time of lumbar puncture or in the laboratory, or carriage of rotavirus RNA in trafficking lymphocytes.

Central Nervous System Diseases↗

"Norwalk-like viruses". Public health consequences and outbreak management.

"Norwalk-like viruses" (NLVs) cause outbreaks of gastroenteritis and are spread frequently through contaminated food or water. Molecular diagnostics now enables detecting viruses in clinical and environmental specimens, linking of NLV strains causing outbreaks in multiple geographic locations, and tracing them to their sources in contaminated food or water. This report reviews recent advances in NLV detection and provides guidelines and recommendations for investigating NLV-related outbreaks, including specimen collection and disease prevention and control. This report also updates information provided in CDC's previously published, Viral Agents of Gastroenteritis: Public Health Importance and Outbreak Management (MMWR 1990;39 [No. RR-5]: 1-24). These CDC recommendations are intended for public health professionals who investigate outbreaks of acute gastroenteritis but could be useful in academic and research settings as well.

Caliciviridae Infections↗

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

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

Astroviridae Infections↗

The epidemiology and disease burden of rotavirus in Vietnam: sentinel surveillance at 6 hospitals.

The disease burden of rotavirus diarrhea in Vietnam was assessed by surveillance of children <5 years old who were hospitalized for diarrhea at 3 centers in the north and 3 centers in the south. Rotavirus was identified in 56% (range, 47%-60%) of the 5768 patients surveyed between July 1998 and June 2000. G-typing of the first 224 strains indicated that only 2% were non-typeable, 9% were in mixed infections, and the remainder were of the common serotypes G1, G2, G3, G4, and G9. In Vietnam, diarrhea accounts for 9880 deaths per year, which is approximately 15% of all deaths among children <5 years old, or 6.5 deaths per 1000 children. If even 50% of these diarrhea-related deaths in Vietnam were due to rotavirus, the number would represent 4%-8% of all deaths among children <5 years old, 2700-5400 rotavirus-related deaths per year, and 1 death per 280-560 children during the first 5 years of life. Thus, the disease burden of rotavirus in Vietnam is substantial, and programs to encourage the use of oral rehydration should be encouraged while efforts to develop vaccines continue.

Age Distribution↗

Gastroenteritis viruses: an overview.

Acute gastroenteritis is among the most common illnesses of humankind, and its associated morbidity and mortality are greatest among those at the extremes of age, children and the elderly. In developing countries, gastroenteritis is a common cause of death in children < 5 years that can be linked to a wide variety of pathogens. In developed countries, while deaths from diarrhoea are less common, much illness leads to hospitalization or doctor visits. Much of the gastroenteritis in children is caused by viruses belonging to four distinct families--rotaviruses, caliciviruses, astroviruses and adenoviruses. Other viruses, such as the toroviruses, picobirnaviruses, picornavirus (the Aichi virus), and enterovirus 22, may play a role as well. Viral gastroenteritis occurs with two epidemiologic patterns, diarrhoea that is endemic in children and outbreaks that affect people of all ages. Viral diarrhoea in children is caused by group A rotaviruses, enteric adenoviruses, astroviruses and the caliciviruses; the illness affects all children worldwide in the first few years of life regardless of their level of hygiene, quality of water, food or sanitation, or type of behaviour. For all but perhaps the caliciviruses, these infections provide immunity from severe disease upon reinfection. Epidemic viral diarrhoea is caused primarily by the Norwalk-like virus genus of the caliciviruses. These viruses affect people of all ages, are often transmitted by faecally contaminated food or water, and are therefore subject to control by public health measures. The tremendous antigenic diversity of caliciviruses and short-lived immunity to infection permit repeated episodes throughout life. In the past decade, the molecular characterization of many of these gastroenteritis viruses has led to advances both in our understanding of the pathogens themselves and in development of a new generation of diagnostics. Application of these more sensitive methods to detect and characterize individual agents is just beginning, but has already opened up new avenues to reassess their disease burden, examine their molecular epidemiology, and consider new directions for their prevention and control through vaccination, improvements in food and water quality and sanitary practices.

Adenoviruses, Human↗

Epidemiology of rotavirus in India.

Rotavirus is the leading cause of childhood diarrhea worldwide, causing an estimated 600,000 deaths each year. To assess the potential benefits of a national rotavirus immunization program in India, we analyzed 40 published studies of rotavirus that were conducted between 1976 and 1997 and included a total of approximately 13,000 Indian pediatric inpatients. Pediatric studies featuring 100 or more patients and lasting at least 12 months in duration and all neonatal studies were analyzed. Rotavirus was detected in a median of 18% of pediatric patients and 28% of neonates surveyed. Fifty percent of all children hospitalized with rotavirus by age 5 were hospitalized by the age of 6 months, 75% by the age of 9 months, and almost 100% by the age of 2 years. Rotavirus was most prevalent (31%) in children between 7 and 12 months of age, followed by children between 1 and 2 years of age (20%), and children < 7 months of age (13%). VP7 genotypes G1 and G2 were most commonly isolated although significant heterogeneity of serotypes was observed. P[11], G9 strains were most frequently isolated among neonates. In 1998; approximately 98,000 childhood deaths were caused by rotavirus. These data underscore the urgent need for safe and effective interventions against rotavirus such as vaccines. The significant diversity of rotavirus strains and young age of hospitalization pose unique challenges to the formulation of a rotavirus immunization program in India, but raise the possibility of utilizing a neonatal vaccine to provide effective coverage.

Child, Preschool↗

Cost of diarrhea-associated hospitalizations and outpatient visits in an insured population of young children in the United States.

OBJECTIVE: To assess the financial and clinical burden of diarrhea- and rotavirus-associated disease among a population of privately insured US children. METHODS: For the period 1993 through 1996, we analyzed medical claims data from a large, administrative database containing information on approximately 300,000 children <5 years of age to examine trends in, and costs associated, with hospitalizations and outpatient visits for diarrhea. RESULTS: An annual average of 1,186 diarrhea-associated hospitalizations (35 per 10,000 children <5 years) and 33 386 outpatient visits (943 per 10,000 children <5 years) were reported, accounting for 4% of all hospitalizations and 2% of all outpatient visits among children <5 years of age. Diarrhea-associated hospitalizations and outpatient visits showed a distinct winter-spring peak consistent with that of rotavirus infection. The excess of diarrhea-associated events occurring during the winter-spring peak accounted for an average of 50% of all diarrhea-associated hospitalizations and 18% of all diarrhea-associated outpatient visits. The median cost (in 1998 constant dollars) of a diarrhea-associated hospitalization was $2,307, and that for a rotavirus-associated hospitalization was $2,303. Median costs of diarrhea- and rotavirus-associated outpatient visits were $47 and $57, respectively. CONCLUSIONS: Diarrhea is an important cause of morbidity in this insured population of young children. The epidemiologic features of diarrhea-associated events suggest that rotavirus is an important contributor to the overall morbidity from diarrhea. These disease burden and cost estimates should provide useful information with which to assess the costs and benefits of future interventions for rotavirus-associated illness.

Child, Preschool↗

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↗

Safety and immunogenicity of tetravalent rhesus-based rotavirus vaccine in Bangladesh.

BACKGROUND: Rotavirus is the most common cause of severe gastroenteritis among children worldwide. OBJECTIVES: To compare the safety, immunogenicity and shedding patterns of rhesus rotavirus (RRV)-tetravalent vaccine vs. placebo among infants in rural Bangladesh. METHODS: A double blinded, placebo-controlled trial was conducted in which infants (n = 120) were randomly assigned to receive three doses of either vaccine or placebo administered at approximately 6, 10 and 14 weeks of age together with routine immunizations. Data on possible adverse effects of vaccinations were collected daily for 7 days after each dose. Stool samples were collected after each dose, and serum samples were obtained before the first and after the third vaccination. RESULTS: Fever (> or = 38 degrees C), as measured by study assistants, was noted more frequently among vaccinees (15%) than among placebo recipients (2%) during the 7 days after vaccination but was not reported more frequently by parents of vaccinees vs. placebo recipients. Overall 87% of vaccinees had an antibody response (measured by IgA or anti-RRV-neutralizing antibodies) after vaccination compared with 32% of placebo recipients. Rates of seroconversion were higher among subjects with lower levels of prevaccination antibodies and those who shed rotavirus after vaccination. Vaccine strain viruses were detected in stools from placebo vaccine recipients who had evidence of IgA seroconversion. CONCLUSIONS: In this population RRV-tetravalent vaccine was comparably immunogenic and safe as in trials conducted in developed countries, where this vaccine has been proved effective in preventing severe rotavirus diarrhea. These data support continued evaluation of rotavirus vaccines in developing countries.

Antibodies, Viral↗

Great diversity of group A rotavirus strains and high prevalence of mixed rotavirus infections in India.

We previously observed a marked diversity of rotavirus strains and a high prevalence of the uncommon serotype G9 in a small survey of rotavirus strains collected from six centers in India. In the present study, we characterized a larger collection of strains from children hospitalized with severe diarrhea in seven Indian cities between 1996 and 1998. A total of 287 strains were G and P genotyped by reverse transcription-PCR, and some were further characterized by electropherotyping and subgrouping. Of the four strains common globally, three were found in only 43% of samples (P[8], G1, 15%; P[4], G2, 22%; P[8], G4, 6%), whereas G9 strains made up 17% of the total. Three different G9 strains were present: a P[8], G9 strain, which displayed the long electropherotype and subgroup II VP6 specificity, and two P[6], G9 strains, one with the long electropherotype and subgroup II specificity and the other with the short electropherotype and subgroup I specificity. Marked diversity was observed among strains collected from different cities and collected over time. Of the 253 strains that were fully typed, 54 (21%) had a mixed G or P genotype. Serotype G2 strains were detected more often in infections caused by single strains than in mixed infections (P < 0.05), whereas serotype G1 strains were found more often in mixed infections than in infections caused by single strains (P < 0.05). The diversity of rotavirus strains and the high prevalence of mixed infections confirm trends reported earlier and help to better characterize the strains of rotavirus circulating in India. Vaccines under development should clearly target G9 strains, and G9 should be included as one of the common global serotypes.

Child↗

Characterization of capsid genes, expressed in the baculovirus system, of three new genetically distinct strains of "Norwalk-like viruses".

"Norwalk-like viruses" (NLVs), members of a newly defined genus of the family Caliciviridae, are the most common agents of outbreaks of gastroenteritis in the United States. Two features of NLVs have hindered the development of simple methods for detection and determination of serotype: their genetic diversity and their inability to grow in cell culture. To assess the immune responses of patients involved in outbreaks of gastroenteritis resulting from infection with NLVs, we previously used recombinant-expressed capsid antigens representing four different genetic clusters, but this panel proved insufficient for detection of an immune response in many patients. To extend and further refine this panel, we expressed in baculovirus the capsid genes of three additional genetically distinct viruses, Burwash Landing virus (BLV), White River virus (WRV), and Florida virus. All three expressed proteins assembled into virus-like particles (VLPs) that contained a full-length 64-kDa protein, but both the BLV and WRV VLPs also contained a 58-kDa protein that resulted from deletion of 39 amino acids at the amino terminus. The purified VLPs were used to measure the immune responses in 403 patients involved in 37 outbreaks of acute gastroenteritis. A majority of patients demonstrated a fourfold rise in the titer of immunoglobulin G to the antigen homologous to the outbreak strain, but most seroconverted in response to other genetically distinct antigens as well, suggesting no clear pattern of type-specific immune response. Further study of the antigenicity of the NLVs by use of VLPs should allow us to design new detection systems with either broader reactivity or better specificity and to define the optimum panel of antigens required for routine screening of patient sera.

Amino Acid Sequence↗

Intussusception, rotavirus diarrhea, and rotavirus vaccine use among children in New York state.

OBJECTIVE: To describe epidemiologic features of intussusception and rotavirus diarrhea in New York, to examine the baseline incidence and trends over time, and to ascertain whether an excess of cases occurred in the 9 months of vaccination with the newly licensed rotavirus vaccine. METHODS: Hospital discharge data from 1989 through 1998 were reviewed for children (<1 year old) whose primary or secondary diagnosis was coded as intussusception or rotavirus diarrhea. Characteristics of patients admitted for intussusception and rotavirus diarrhea were compared, and trends over time were examined. For a subset of patients, medical records and vaccine histories for intussusception hospitalizations from October 1998 through June 1999 were analyzed. The number of intussusception cases attributable to rotavirus vaccine was calculated based on the penetration of the vaccine (21%) and a range of excess risks of intussusception among vaccinated children as estimated by the National Immunization Program (NIP). RESULTS: From 1989 through 1998, 1450 intussusception-associated hospitalizations were reported in children <1 year old (average annual incidence 5.4/10 000). Among these children, 47% were treated medically and 53% had surgery, with 9% needing surgical resection. The incidence of intussusception declined over time from 6.1 per 10 000 in 1989 to 3.9 per 10 000 in 1998. Intussusception hospitalizations occurred throughout the year, whereas rotavirus-associated hospitalizations peaked from February to April. Of 20 patients with intussusception whose hospitalization charts were reviewed, 5 had received rotavirus vaccine. All 5 were hospitalized after their first dose of vaccine, were admitted before 7 months of age, were white, and had private insurance. A total of 81 cases of intussusception occurred during the 9-month period of rotavirus vaccination, compared with 78 during the same period in the prevaccination year. The number of excess intussusception cases observed (n = 3) was lower than expected using the NIP estimate of excess risk (1.8) among rotavirus vaccinated children (n = 12) but not significantly different from the risks identified in the NIP cohort studies (1 in 12 000). CONCLUSION: Our data suggest that in New York the rate of intussusception has declined, and approximately 1 child in 2600 develops intussusception before 1 year of age. The different seasonality between intussusception and rotavirus-related hospitalizations suggests that if any causal association exists, it must be small. Unlike other studies, analysis of New York hospitalized discharge data failed to show an appreciable increase in the incidence of intussusception after introduction of the rotavirus vaccine.

Diarrhea↗

Rotavirus diarrhea disease burden in Peru: the need for a rotavirus vaccine and its potential cost savings.

OBJECTIVE: To assess the disease burden of rotavirus diarrhea in Peru as well the need for and the potential cost savings with a rotavirus vaccine in that country. METHODS: To assess the burden of rotavirus diarrhea in Peru, we reviewed published and unpublished reports where rotavirus was sought as the etiologic agent of diarrhea in children. Rotavirus detection rates obtained from these studies were combined with diarrhea incidence rates from a number of national surveys in order to estimate both the burden of rotavirus diarrhea in the country and its associated medical costs. RESULTS: Rotavirus is a significant cause of morbidity and mortality in Peruvian children. In their first 5 years of life, an estimated 1 in 1.6 children will experience an episode of rotavirus diarrhea, 1 in 9.4 will seek medical care, 1 in 19.7 will require hospitalization, and 1 in 375 will die of the disease. Per year, this represents approximately 384,000 cases, 64,000 clinic visits, 30,000 hospitalizations, and 1,600 deaths. The annual cost of medical care alone for these children is approximately US$ 2.6 million--and that does not take into account the indirect or societal costs of the illness and the deaths. CONCLUSIONS: Rotavirus immunization provides the prospect of decreasing the morbidity and mortality from diarrhea in Peru, but a vaccine regimen would have to be relatively inexpensive, a few dollars or less per child. Future cost-effectiveness analyses should explore the total costs (medical as well as indirect or societal) associated with rotavirus diarrhea. Newly licensed vaccines should be tested according to both their ability to avert deaths and their efficacy with fewer than three doses. All three of these factors could increase the cost savings associated with a rotavirus vaccine.

Cost Savings↗

Molecular characterization of serotype G9 rotavirus strains from a global collection.

Between 1992 and 1998, serotype G9 human rotavirus (RV) strains have been detected in 10 countries, including Thailand, India, Brazil, Bangladesh, Malawi, Italy, France, the United States, the United Kingdom, and Australia, suggesting the possible emergence of the fifth common serotype worldwide. Unlike the previously characterized reference G9 strains (i.e., WI61 and F45), the recent G9 isolates had a variety of gene combinations, raising questions concerning their origin and evolution. To identify the progenitor strain and examine the on-going evolution of the recent G9 strains, we characterized by genetic and antigenic analyses 16 isolates obtained from children with diarrhea in India, Bangladesh, the United States, and Malawi. Specifically, we sequenced their VP7 and NSP4 genes and compared the nucleotide (nt) and deduced amino acid sequences with the reference G9 strains. To identify reassortment, we examined the products of five gene segments; VP4, VP7, and NSP4 genotypes (genes 4, 9, and 10); subgroups (gene 6); electropherotypes (gene 11); and the genogroup profiles of all of the recent G9 isolates. Sequence analysis of the VP7 gene indicated that the recent U.S. P[6],G9 strains were closely related to the Malawian G9 strains (>99% nt identity) but distinct from G9 strains of India ( approximately 97% nt identity), Bangladesh ( approximately 98% nt identity), and the reference strains ( approximately 97% nt identity). Phylogenetic analysis identified a single cluster for the U.S. P[6],G9 strains that may have common progenitors with Malawian P[6],G9 strains whereas separate lineages were defined for the Indian, Bangladeshi, and reference G9 strains. Northern hybridization results indicated that all 11 gene segments of the Malawian P[6],G9 strains hybridized with a probe derived from a U.S. strain of the same genotype and may have the same progenitor, different from the Indian G9 strains, whereas the Bangladesh strains may have evolved from the U.S. G9 progenitors. Overall, our findings suggest that much greater diversity among the newly identified G9 strains has been generated by reassortment between gene segments than through the accumulation of mutations in a single gene.

Antigens, Viral↗

Cloning of human picobirnavirus genomic segments and development of an RT-PCR detection assay.

Nearly full-length genomic segments 2 and a partial-length genomic segment 1 of human picobirnavirus were cloned and sequenced. The clones were derived from viruses obtained from human immunodeficiency virus (HIV)-infected patients in Atlanta, Georgia (strains 3-GA-91 and 4-GA-91) and a nonHIV-infected person from China (strain 1-CHN-97). The picobirnavirus genomic segments lacked sequence similarities with other viral sequences in GenBank and EMBL. Comparison of genomic segment 1 from a human and a rabbit picobirnavirus identified a region of 127 nucleotides with 54.7% identity. The genomic segments 2 of the 4-GA-91 and 1-CHN-97 strains had 41.4% nucleic acid identity and 30.0% amino acid similarity and contained amino acid motifs typical of RNA-dependent RNA polymerase genes. Reverse transcription-PCR detection assays were developed with primers targeted to the genomic segments 2 of strains 4-GA-91 or 1-CHN-97. Picobirnaviruses related to the China strain were the predominant viruses detected in stool samples from people in four countries on three continents. Picobirnaviruses were detected in samples from two outbreaks of gastroenteritis in long-term elder care facilities but were not determined to be the primary pathogen. Our findings support the view that picobirnaviruses constitute a distinct family of viruses.

Amino Acid Sequence↗

Serum antibody as a marker of protection against natural rotavirus infection and disease.

To determine whether naturally acquired serum IgA and IgG antibodies were associated with protection against rotavirus infection and illness, a cohort of 200 Mexican infants was monitored weekly for rotavirus excretion and diarrhea from birth to age 2 years. Serum samples collected during the first week after birth and every 4 months were tested for anti-rotavirus IgA and IgG. Children with an IgA titer >1:800 had a lower risk of rotavirus infection (adjusted relative risk [aRR], 0.21; P<.001) and diarrhea (aRR, 0. 16; P=.01) and were protected completely against moderate-to-severe diarrhea. However, children with an IgG titer >1:6400 were protected against rotavirus infection (aRR, 0.51; P<.001) but not against rotavirus diarrhea. Protective antibody titers were achieved after 2 consecutive symptomatic or asymptomatic rotavirus infections. These findings indicate that serum anti-rotavirus antibody, especially IgA, was a marker of protection against rotavirus infection and moderate-to-severe diarrhea.

Antibodies, Viral↗

Molecular and serologic characterization of novel serotype G8 human rotavirus strains detected in Blantyre, Malawi.

During a 2-year study of diarrhea among children in Blantyre, Malawi, greater than 50% of rotavirus strains genotyped by using reverse transcription-polymerase chain reaction possessed previously unrecognized combinations of the neutralization proteins VP7 and VP4. Serotype G8 rotaviruses, which have been identified recently in several African countries, were found to possess P[4] or P[6] VP4 genotype specificity. Two of these short electropherotype rotaviruses were further investigated: these comprised a P[6], G8 representative strain (MW23) and a P[4], G8 representative strain (MW333). The VP7 gene sequences of both strains exhibited greatest homology to human and animal serotype G8 rotaviruses. Sequence analysis of the VP4 gene of MW23 indicated closest identity to the P2A[6], G9 strain US1205 from the United States. The VP4 gene of MW333 was most closely related to the P[4], G12 strain L26 isolated in the Philippines and the Australian P[4], G2 strain RV-5. The NSP4 gene sequences of both strains were classified in NSP4 genetic group I. RNA-RNA hybridization demonstrated that each of these two strains is related to the DS-1 genogroup of human rotaviruses. Subgroup analysis and virus neutralization confirmed complete antigenic characterization of MW23 as subgroup I, P2A[6], G8 and MW333 as subgroup I, P1B[4], G8. The similarity of the VP7 gene sequences of the prototype strains described in this report to bovine serotype G8 rotaviruses suggests that they may represent human/bovine reassortant viruses.

Animals↗