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Biomedical subjects

Roger I Glass

Publications and source records attributed to Roger I Glass.

At least 19 recordsLinked to original sources

The epidemiology and burden of rotavirus in China: a review of the literature from 1983 to 2005.

We reviewed studies of rotavirus in MEDLINE and the Chinese literature to get a preliminary estimate of the burden of rotavirus gastroenteritis in China and the epidemiology of the disease. Studies were selected if they were conducted for a period 1 year or more, had more than 100 patients enrolled, and used an accepted diagnostic test. Overall, in 27 reports of children hospitalized for diarrhea in urban areas and 3 in rural areas, 44 and 33%, respectively, had rotavirus identified as the etiologic agent. Rotavirus was less commonly detected in children with milder illness seen in clinics (26% in urban and 28% in rural areas) and those cared for in the community (9%). The four main strains of rotavirus in circulation worldwide were also found in China and while G1 was the predominant strain overall, G3 emerged to be the most common strain in 9 of the 12 most recent studies. The disease has a distinct winter seasonal pattern and affects most children in their first 2 years of life. Although further studies are required to fully assess the burden of rotavirus diarrhea before decisions can be made about vaccine use, this review suggests that development and implementation of rotavirus vaccines should be a national priority.

Age Factors↗

Prevention of rotavirus gastroenteritis among infants and children. Recommendations of the Advisory Committee on Immunization Practices (ACIP).

In February 2006, a live, oral, human-bovine reassortant rotavirus vaccine (RotaTeq) was licensed for use among U.S. infants. The Advisory Committee on Immunization Practices recommends routine vaccination of U.S. infants with 3 doses of this rotavirus vaccine administered orally at ages 2, 4, and 6 months. The first dose should be administered between ages 6-12 weeks. Subsequent doses should be administered at 4-10 week intervals, and all 3 doses should be administered by age 32 weeks. Rotavirus vaccine can be co-administered with other childhood vaccines. Rotavirus vaccine is contraindicated for infants with a serious allergic reaction to any vaccine component or to a previous dose of vaccine.

Child, Preschool↗

Quantitative evaluation of rotaviral antigenemia in children with acute rotaviral diarrhea.

BACKGROUND: Rotaviral antigen and RNA have recently been identified in the serum of patients with rotaviral gastroenteritis, but the roles they play in disease remains undetermined. METHODS: Rotaviral antigen and RNA were quantified by enzyme-linked immunosorbant assay and by quantitative reverse-transcription polymerase chain reaction in stool and serum specimens from children with rotaviral diarrhea (n=102), children with nonrotaviral diarrhea (n=40), and nondiarrheal control children (n=30). RESULTS: Rotaviral antigenemia was detected in 64%, 3%, and 0% of the children with rotaviral diarrhea, the children with nonrotaviral diarrhea, and the nondiarrheal control children, respectively. The level of rotaviral antigen in serum was approximately 2x10(2) -fold lower than that in stool, and a moderate correlation was observed between the 2 levels. Rotaviral RNA was detected in 93% of the antigen-positive serum specimens. The median number of RNA copies in serum was approximately 1 x 10(5) -fold lower than that in stool, and no correlation was observed between the 2 levels. Serum levels of both antigen and RNA were inversely associated with baseline titers of rotaviral serum immunoglobulin G (P<.01). Antigenemia was also associated with G1 serotype. CONCLUSIONS: Rotaviral antigenemia and viremia were common in children with rotaviral diarrhea, but antigen and RNA levels in serum were substantially lower than those in stool. Antigenemia was associated with infection with G1 strains and with low baseline titers of rotaviral serum antibody.

Antigens, Viral↗

Rotavirus vaccines: current prospects and future challenges.

Rotavirus is the most common cause of severe diarrhoea in children worldwide and diarrhoeal deaths in children in developing countries. Accelerated development and introduction of rotavirus vaccines into global immunisation programmes has been a high priority for many international agencies, including WHO and the Global Alliance for Vaccines and Immunizations. Vaccines have been developed that could prevent the enormous morbidity and mortality from rotavirus and their effect should be measurable within 2-3 years. Two live oral rotavirus vaccines have been licensed in many countries; one is derived from an attenuated human strain of rotavirus and the other combines five bovine-human reassortant strains. Each vaccine has proven highly effective in preventing severe rotavirus diarrhoea in children and safe from the possible complication of intussusception. In developed countries, these vaccines could substantially reduce the number and associated costs of child hospitalisations and clinical visits for acute diarrhoea. In developing countries, they could reduce deaths from diarrhoea and improve child survival through programmes for childhood immunisations and diarrhoeal disease control. Although many scientific, programmatic, and financial challenges face the global use of rotavirus vaccines, these vaccines-and new candidates in the pipeline-hold promise to make an immediate and measurable effect to improve child health and survival from this common burden affecting all children.

Child↗

Isolation and characterization of a new simian rotavirus, YK-1.

BACKGROUND: To effectively analyze the requirements for protection to rotavirus infection, a reliable animal model that reasonably mimics infection and disease in humans is needed. A requirement for an effective animal model is the availability of appropriate rotavirus stocks for challenge. RESULTS: A new simian rotavirus, designated YK-1, was isolated from a 2-year-old immunodeficient pigtailed macaque with chronic diarrhea. YK-1 was distinguishable by electropherotype from the other simian rotavirus strains, SA11 and RRV. One variant of YK-1, clone 311, which was isolated after adaptation and plaque purification in cell cultures, displayed an unusual RNA electropherotype with an abnormally migrating gene 11 segment. Sequence analysis demonstrated a genetic rearrangement that involved a partial duplication of the gene 11 ORF encoding NSP5. YK-1 was identified as a Group A rotavirus belonging to subgroup 1. To further characterize the YK-1 strain, the genes encoding VP4, VP7, and NSP4 were sequenced. Analysis of VP4 and VP7 gene fragments suggests that this strain is a G3P3 rotavirus and is closely related to the simian rotavirus strain RRV. Serotype analysis also identified YK-1 as a G3 rotavirus. The NSP4 genotype of YK-1 is C, the same genotype as RRV. CONCLUSION: This newly isolated rotavirus, YK-1, is being used to establish a nonhuman primate model for studying the infectivity, immunity, and pathogenesis of rotavirus and for evaluating candidate rotavirus vaccines.

Animals↗

Safety and immunogenicity of two live attenuated human rotavirus vaccine candidates, 116E and I321, in infants: results of a randomised controlled trial.

We evaluated safety and immunogenicity of two orally administered human rotavirus vaccine candidates 116E and I321. Ninety healthy infants aged 8 weeks received a single dose of 116E (10(5)FFu (florescence focus units)), I321 (10(5)FFu) or placebo. There were no significant differences in the number of adverse events. Fever was reported by 6/30, 1/30 and 5/30 in the 116E, I321 and placebo groups; the corresponding figures for diarrhoea were 5/30, 8/29 and 3/30. Serum IgA seroconversion rates were 73%, 39% and 20% in the 116E, I321 and placebo groups, respectively. Vaccine virus was shed on days 3, 7 or 28 in 11/30 infants of the 116E and none in the other two groups. The 116E strain is attenuated, clinically safe and highly immunogenic with a single dose.

Double-Blind Method↗

Reevaluation of epidemiological criteria for identifying outbreaks of acute gastroenteritis due to norovirus: United States, 1998-2000.

BACKGROUND: Noroviruses are believed to be the most common etiologic agent of foodborne outbreaks of gastroenteritis, yet diagnostic tests for these agents are not readily available in the United States. In the absence of assays to detect norovirus, several clinical and epidemiologic profiles--the criteria of Kaplan et al. (vomiting in >50% of patients, mean incubation period of 24-48 h, mean duration of illness of 12-60 h, and no bacterial pathogen) and the ratios of fever to vomiting and diarrhea to vomiting--have been used to distinguish foodborne outbreaks of gastroenteritis caused by noroviruses from those caused by bacteria. METHODS: To examine how well clinical and epidemiological profiles discriminate between foodborne outbreaks of gastroenteritis due to noroviruses and those due to bacteria and to estimate the proportion of reported outbreaks that might be attributable to noroviruses, we reviewed subsets of the 4050 outbreaks reported from 1998 to 2000. RESULTS: The set of criteria of Kaplan et al. is highly specific (99%) and moderately sensitive (68%) in discriminating confirmed outbreaks due to bacteria from those due to norovirus and was the most useful diagnostic aid evaluated. Each individual component of the criteria, the fever-to-vomiting ratio, and the diarrhea-to-vomiting ratio were more sensitive, yet less specific, and therefore less useful, than the criteria of Kaplan et al. We estimated that, at a minimum, 28% of all the foodborne outbreaks reported to the Centers for Disease Control and Prevention may be attributed to norovirus on the basis of these criteria. CONCLUSION: Until norovirus diagnostic tests become widely available, the criteria of Kaplan et al. remain the most useful and discriminating diagnostic aid to identify foodborne outbreaks of gastroenteritis due to noroviruses.

Acute Disease↗

Rotavirus and rotavirus vaccines.

Two new rotavirus vaccines have recently been licensed that will provide the intervention needed to diminish the huge burden of rotavirus disease among all children. In many upper and middle income countries, these vaccines will soon be available for the routine immunization of children. The impact should be a rapid and measurable reduction in hospitalizations and doctor visits for acute diarrhea in children, especially in the winter rotavirus season. While few deaths occur in these settings, the illness has consequences in terms of both medical costs and indirect costs, including parents work time lost. In the developing world, clinical trials are still needed to ensure that the vaccines being licensed will work as expected in children living in poor settings. In these settings, other enteric flora, micronutrient malnutrition, higher titers of maternal antibody and other factors still poorly defined have compromised other live oral vaccines and have required the developers to alter vaccine formulation, dose, or schedule. Until these trials are completed, we can only hope that the efficacy will be comparable and that the vaccine will prove to be life-savers. Once the efficacy and safety have been established, rotavirus vaccines could provide a major boost to programs for child survival.

Animals↗

The burden of rotavirus diarrhea in Khanh Hoa Province, Vietnam: baseline assessment for a rotavirus vaccine trial.

BACKGROUND: In Vietnam, rotavirus is seen as a priority disease because studies have demonstrated that >50% of children hospitalized for treatment of diarrhea have rotavirus as the pathogen. To anticipate the availability of new vaccines, we have examined our field area in Nha Trang, Khanh Hoa Province, Vietnam, as a potential site to conduct a field trial of a future rotavirus vaccine. METHODS: Data from a population census, incidence rates of diarrhea from a previous cholera vaccine trial and hospitalization rates from computerized records collected from the 2 main hospitals in the province were reviewed to estimate the burden of rotavirus-related diarrhea that might be expected during a field trial of a rotavirus vaccine. RESULTS: For a birth cohort of approximately 5000 children, we would expect approximately 2500 clinic visits and 650-850 hospitalizations for treatment of diarrhea, of which approximately 375-425 would be attributable to rotavirus. For the Vietnamese birth cohort of 1,639,000 children, these numbers translate into approximately 820,000 clinic visits, 122,000-140,000 hospitalizations and 2900-5400 deaths annually attributable to rotavirus-related diarrhea. CONCLUSIONS: Vietnam is an early adaptor of new vaccines, has high national coverage rates (>85%) for childhood immunization and receives international donor support for the introduction of new vaccines. We found the epidemiologic features of rotavirus in rural Vietnam to be more similar to those of rotavirus in a developed country than to those of rotavirus in India or Bangladesh.

Child, Preschool↗

Temporal and geographic trends of rotavirus activity in the United States, 1997-2004.

Rotavirus (RV) has a characteristic seasonal pattern in the 48 contiguous states of the continental United States, and climatologic factors have been implicated though not confirmed. Since 1997, three significant events occurred, including strong El Niño and La Niña climatologic phenomena, and the brief introduction of a rotavirus (RV) vaccine. We examined trends in RV activity in the continental United States between 1997 and 2004, using data from a network of over 70 laboratories that voluntarily report weekly RV detection rates within the National Respiratory and Enteric Virus Surveillance System (NREVSS). Analysis of NREVSS data indicates characteristic winter activity that begins in the Southwest in December or January, moves across the country, and ends in the Northeast in April or May. This pattern was not affected by the brief use of RV vaccine nor by periods of climate change associated with the El Niño and La Niña phenomena. The temporal and geographic pattern of RV spread in the United States has persisted since its initial description and defies easy explanation. An impact of the RV vaccine was not observed, either because of the limited uptake of the vaccine or the inherent variability of the system. NRVESS permits a gross assessment of RV geographic and temporal trends in the United States, but underscores the need for additional assessment mechanisms.

Humans↗

Hospitalizations associated with rotavirus gastroenteritis in the United States, 1993-2002.

BACKGROUND: In the United States, rotavirus gastroenteritis remains a common disease of children that results in many hospitalizations, clinic visits and medical costs. It is a common cause of morbidity and is associated with a high economic burden in developing countries. Prevention of hospitalizations is the primary target of rotavirus vaccines. METHODS: To update estimates of rotavirus hospitalization rates in the United States, we conducted a retrospective analysis of 10 years of national hospitalization data associated with gastroenteritis and used both direct and indirect methods to estimate the percentage of cases associated with rotavirus gastroenteritis. RESULTS: During 1993-2002, an average of 18% of all hospitalizations with gastroenteritis among children <5 years old were associated with rotavirus infection as determined by the rotavirus-specific International Classification of Diseases, 9th revision, Clinical Modification code. The annual proportion of rotavirus-associated hospitalizations increased from 15% in 1993-1995 to 21% in 2000-2002. Hospitalizations associated with rotavirus and those associated with nonspecific gastroenteritis had a marked winter-time seasonality and similar age distribution, which peaked among children between 3 and 24 months old. Using indirect estimation methods, 58,000 to 70,000 rotavirus-associated hospitalizations were estimated to occur each year in the United States. CONCLUSIONS: Rotavirus gastroenteritis remains an important cause of hospitalizations in the United States, and the rate has not declined from 1993 through 2002.

Age Distribution↗

Use of TaqMan real-time reverse transcription-PCR for rapid detection, quantification, and typing of norovirus.

Noroviruses (NoVs) are the most commonly identified cause of outbreaks and sporadic cases of acute gastroenteritis. We evaluated and optimized NoV-specific TaqMan real-time reverse transcription (RT)-PCR assays for the rapid detection and typing of NoV strains belonging to genogroups GI and GII and adapted them to the LightCycler platform. We expanded the detection ability of the assays by developing an assay that detects the GIV NoV strain. The assays were validated with 92 clinical samples and 33 water samples from confirmed NoV outbreaks and suspected NoV contamination cases. The assays detected NoV RNA in all of the clinical specimens previously confirmed positive by conventional RT-PCR and sequencing. Additionally, the TaqMan assays successfully detected NoV RNA in water samples containing low viral concentrations and inhibitors of RT and/or PCR, whereas the conventional method with region B primers required dilution of the inhibitors. By means of serially diluted NoV T7 RNA transcripts, a potential detection limit of <10 transcript copies per reaction mixture was observed with the GII assay and a potential detection limit of <100 transcript copies per reaction mixture was observed with the GI assay. These results and the ability to detect virus in water that was negative by RT-PCR demonstrate the higher sensitivity of the TaqMan assay compared with that of a conventional RT-PCR assay. The TaqMan methods dramatically decrease the turnaround time by eliminating post-PCR processing. These assays have proven useful in assisting scientists in public health and diagnostic laboratories report findings quickly to outbreak management teams.

Caliciviridae Infections↗

Intussusception after administration of the rhesus tetravalent rotavirus vaccine (Rotashield): the search for a pathogenic mechanism.

OBJECTIVES: The rhesus tetravalent rotavirus vaccine (RRV) was withdrawn from the routine program for childhood immunization in the United States because of the rare and unexpected occurrence of intussusception in the 2-week period after administration of the first dose. METHODS: To search for the pathogenesis of this association, we compared the pathology of surgical specimens from infants who had surgical reduction of their intussusceptions within 2 weeks of receiving the vaccine (case patients; n = 8) with the pathology of specimens from children who had surgery > 2 weeks after immunization (n = 6) or who had never been immunized (n = 26). Tissue was examined for evidence of the vaccine strain of rotavirus by reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemical staining. RESULTS: RRV was identified by RT-PCR in tissue samples from 7 of the 8 case patients and in 2 of the 6 children who received the vaccine at a more distant time (29 and 58 days before surgery), but it was not identified in samples from any of the nonvaccinated children. No evidence of rotavirus tissue involvement was detected in any of the children by in situ hybridization or immunohistochemical staining. Pathologic evidence (for example, inclusion bodies, smudge cells) of adenovirus infection was present in 35% of the 37 specimens examined by routine staining and immunohistochemistry. CONCLUSIONS: The fact that RRV was detected by RT-PCR but not by either of the other assays could be explained by RRV being present in the lumen of the gut but not in the tissues of appendix, ileum, or Peyer's patches. The Peyer's patches were not hyperplastic, and we could not establish the pathogenic mechanism for this association.

Adenoviridae↗