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Roger I Glass

Publications and source records attributed to Roger I Glass.

At least 37 records · Page 2Linked to original sources

Diarrhea- and rotavirus-associated hospitalizations among children less than 5 years of age: United States, 1997 and 2000.

OBJECTIVE: A new rotavirus vaccine may be licensed in the United States in early 2006. Estimates of the burden of severe rotavirus disease, particularly hospitalizations, will help evaluate the potential benefits of a national rotavirus immunization program. DESIGN: The Kids' Inpatient Database, a robust sample of 10% of the uncomplicated births and 80% of other pediatric discharges was used to estimate the number and rate of diarrhea- and rotavirus-associated hospitalizations among US children <5 years of age in 1997 and 2000. RESULTS: In 1997 and 2000, diarrhea was coded in 13% of all childhood hospitalizations, for an estimated cumulative incidence of 1 diarrhea hospitalization per 23 to 27 children by age 5. Most diarrhea-associated hospitalizations (62%) were coded as unspecified etiology, and 35% as viral. Rotavirus was the most common pathogen recorded for 18% and 19% of diarrhea-associated hospitalizations in 1997 and 2000, respectively. Diarrhea-associated hospitalizations coded as unspecified or viral exhibited a marked winter peak similar to that of hospitalizations coded as rotavirus, suggesting that the rotavirus-specific code captures a fraction of all rotavirus hospitalizations. Using indirect methods, we estimated that rotavirus was associated with 51142-60155 and 46839-56820 hospitalizations in 1997 and 2000, respectively. By these estimates, rotavirus is associated with 4% to 5% of all childhood hospitalizations, and 1 in 67 to 1 in 85 children will be hospitalized with rotavirus by 5 years of age. CONCLUSIONS: Diarrhea is an important cause of hospitalization in US children, and rotavirus is the most important etiology. Disease burden estimates have remained stable during the past decade. An effective rotavirus vaccine will likely reduce substantially the burden of severe rotavirus disease, estimated to account for 4% to 5% of all hospitalizations and approximately 30% of hospitalizations for watery diarrhea among children <5 years of age.

Child, Preschool↗

Rotavirus vaccination and intussusception: can we decrease temporally associated background cases of intussusception by restricting the vaccination schedule?

OBJECTIVE: The first rotavirus vaccine that was licensed in the United States, RotaShield, could have prevented the enormous burden of rotavirus diarrhea in American children but left instead the unfortunate legacy that live oral rotavirus vaccines may be associated with a serious but rare adverse event: intussusception. Although large trials indicate that the next generation of rotavirus vaccines is not associated with this complication, many children likely will develop intussusception by chance alone in the 2-week window after immunization, raising concerns about whether these cases might be "caused" by the vaccine. Our objective for this study was to model and compare the number of temporally associated intussusception events that are expected by chance alone under 2 rotavirus vaccination strategies. METHODS: We used national vaccine coverage rates and age-specific incidence of intussusception by months to model the number of temporally associated cases of intussusception that are expected by chance alone for 2 potential vaccination strategies: a strict schedule, limiting immunization to children within 1 month of the designated age for each dose (ie, 60-89, 120-149, and 180-209 days for doses 1, 2, and 3, respectively) versus a free schedule whereby infants are immunized whenever they appear for their routine vaccines up to 1 year of age. RESULTS: The number of intussusception events during the 2-week postvaccination window was 24% lower for the strict versus the free schedule (138 vs 182, respectively). This reduction was attributable largely to the smaller number of infants who were immunized fully under the strict schedule (vaccine coverage for 3 doses, 67% vs 89%). The cumulative risk for intussusception's occurring by chance in the 2-week postvaccination window essentially was the same between schedules (4.59 vs 4.76 per 100000 doses). Most cases occurred after the second or third dose. CONCLUSIONS: Although an age-restricted vaccination schedule substantially reduced the number of intussusception events that were observed in the 2-week postvaccination window when compared with a schedule with fewer restrictions, this decrease was attributable to a lower rate of vaccine coverage rather than a safer schedule of vaccination. The risk for intussusception did not differ significantly between vaccination strategies. Public health policy and education messages for physicians and parents should be developed to anticipate intussusception events that will occur by chance alone but are temporally related to rotavirus vaccination.

Age Factors↗

Rotavirus and severe childhood diarrhea.

Studies published between 1986 and 1999 indicated that rotavirus causes approximately 22% (range 17%-28%) of childhood diarrhea hospitalizations. From 2000 to 2004, this proportion increased to 39% (range 29%-45%). Application of this proportion to the recent World Health Organization estimates of diarrhea-related childhood deaths gave an estimated 611,000 (range 454,000-705,000) rotavirus-related deaths.

Child↗

Molecular and epidemiologic trends of caliciviruses associated with outbreaks of acute gastroenteritis in the United States, 2000-2004.

Between July 2000 and June 2004, fecal specimens from 270 outbreaks of acute gastroenteritis were sent to the Centers for Disease Control and Prevention by local or state health departments for calicivirus testing. Of the 226 outbreaks that met the criteria for inclusion in the present study, caliciviruses were detected in 184 (81%) by reverse-transcription polymerase chain reaction and nucleotide sequencing. Nursing homes, retirement centers, and hospitals were the most frequently reported settings, and person-to-person contact was the most common mode of transmission, followed by foodborne spread. Overall, genogroup II norovirus (NoV) strains were the most abundant (79%), followed by genogroup I NoV strains (19%) and sapovirus (2%). Nucleotide-sequence analysis indicated a great diversity of NoV strains and implicated the emergence of one particular sequence variant in outbreaks occurring between July 2002 and June 2003. The public health impact of caliciviruses will not be fully appreciated, nor will interventions be completely evaluated, until methods to detect these viruses are more routinely used.

Acute Disease↗

Norovirus classification and proposed strain nomenclature.

Without a virus culture system, genetic analysis becomes the principal method to classify norovirus (NoV) strains. Currently, classification of NoV strains beneath the species level has been based on sequences from different regions of the viral genome. As a result, the phylogenetic insights of some virus were not appropriately interpreted, and no consensus has been reached to establish a uniform classification scheme. To provide a consistent and reliable scientific basis for classifying NoVs, we analyzed the amino acid sequences for the major capsid protein of 164 NoV strains by first using an alignment based on the predicted 3D structures. A Bayesian tree was generated, and the maximum likelihood pairwise distances of the aligned sequences were used to evaluate the results from the uncorrected pairwise distance method. Analyses of the pairwise distances demonstrated three clearly resolved peaks, suggesting that NoV strains beneath the species level can be classified at three levels: strain (S), cluster (C), and genogroup (G). The uncorrected pairwise distance ranges for S, C, and G were 0-14.1%, 14.3-43.8%, and 44.9-61.4%, respectively. A scheme with 29 genetic clusters [8 in genogroup 1 (G1), 17 in G2, 2 in G3, and 1 each in G4 and G5] was defined on the basis of the tree topology with the standards provided and was supported by the distance analysis. Of these, five clusters in G2 and one in G1 are newly described. This analysis can serve as the basis for a standardized nomenclature to genetically describe NoV strains.

Animals↗

Health care costs of diarrheal disease and estimates of the cost-effectiveness of rotavirus vaccination in Vietnam.

BACKGROUND: Rotavirus disease causes a significant health and economic burden worldwide. Several rotavirus vaccines may soon be available for use. A country's decision to introduce these vaccines will depend on its rotavirus disease burden, on the cost of the vaccine, and on the results of an economic assessment of the cost and effectiveness of a rotavirus vaccination program. METHODS: Data on medical and nonmedical direct costs and indirect costs were established in Khanh Hoa Province, Vietnam, and extrapolated to national estimates on the basis of the birth cohort in 2004. The main outcome measures were economic burden and cost-effectiveness ratio (United States dollars per disability-adjusted life-year averted and dollars per life saved) of vaccination. RESULTS: The disease burden is equivalent to an economic burden of an estimated 3.1 million US dollars in medical direct costs, 685,000 US dollars in nonmedical direct costs, and 1.5 million US dollars in indirect costs. From a societal perspective, treatment of rotavirus disease costs an estimated 5.3 million US dollars per year. From the health care system perspective, universal vaccination of infants at a cost of < or = 7.26 US dollars/vaccine dose would be a cost-effective public health intervention, according to the World Bank cost-effectiveness standard for low-income countries (140 US dollars/disability-adjusted life-year). CONCLUSIONS: Vaccination can effectively reduce the disease burden and health care costs of rotavirus-specific diarrhea in Vietnam.

Child, Preschool↗

Estimates of rotavirus disease burden in Hong Kong: hospital-based surveillance.

BACKGROUND: We conducted prospective, hospital-based surveillance for rotavirus disease for a 2-year period at 4 of 12 public government (Hospital Authority [HA]) hospitals in Hong Kong. It has been estimated that HA hospitals provide 90% of inpatient care in Hong Kong. METHODS: Information was collected for children <5 years old who had a primary or secondary diagnosis of diarrhea or for whom a stool sample was tested for the presence of rotavirus (by enzyme immunoassay) or bacteria (by culture). Surveillance data were compared with routine discharge information from the HA's computerized Clinical Management System (CMS). RESULTS: During a 2-year period (1 April 2001 through 31 March 2003), 7391 children were admitted to the hospital with diarrhea or developed diarrhea during their hospital stay. Of these children, 5881 (80%) had a stool sample tested for the presence of rotavirus, and 30% were positive for rotavirus (representing 24% of all diarrhea-associated admissions). CMS data underreported the total percentage of diarrhea-associated admissions (15% vs. 20%) and the percentage of diarrhea-associated admissions that were the result of rotavirus infection (13% vs. 24%). Estimated rates of hospitalization for rotavirus infection (8.8 admissions/1000 children <5 years old and 18.4 admissions/1000 children <1 year old) were 4-fold higher than our previous estimates, which were determined on the basis of CMS data alone. We estimate that the cumulative risk of hospitalization with rotavirus diarrhea by age 5 years is 1 in 24. Combined active and passive (CMS) surveillance data indicate that 4.6% of all general pediatric admissions to HA hospitals in Hong Kong were associated with rotavirus infection. CONCLUSION: Our study combined passive surveillance data from all Hong Kong HA hospitals with active surveillance data from 4 sentinel hospitals. The estimates of rotavirus disease burden obtained will help emphasize the effect of this important disease and create awareness of the potential for rotavirus vaccines. The surveillance model developed could also be a powerful tool for monitoring the effect of a vaccine.

Child, Preschool↗

Hospital-based study of the economic burden associated with rotavirus diarrhea in Hong Kong.

BACKGROUND: Rotavirus infection is the most common cause of severe diarrhea in both developed and developing countries. METHODS: To estimate the economic burden associated with rotavirus infection in Hong Kong, we combined data on the disease burden of rotavirus-associated hospital admissions with detailed cost data for a subsample of 471 children with diarrhea admitted to hospitals. RESULTS: The annual total social cost and total direct medical cost for rotavirus-associated admissions were calculated as 4.3 US dollars and 4 million US dollars, respectively, by use of data collected during March 2001 to March 2003. The estimate of the direct medical costs was approximately 4-fold higher than a previous estimate; this difference largely reflects the greater disease burden identified through active disease surveillance conducted under the auspices of the Asian Rotavirus Surveillance Network. On average, families spent 120 US dollars when their child's admission was associated with rotavirus infection; this cost represents approximately 10% of the monthly salary of an unskilled or service worker. CONCLUSIONS: These data emphasize the potential for a safe and effective rotavirus vaccine to reduce the economic burden associated with rotavirus disease.

Child, Preschool↗

Estimates of the burden of rotavirus disease in Malaysia.

BACKGROUND: Accurate national estimates of the disease burden associated with rotavirus diarrhea are essential when considering implementation of a rotavirus vaccination program. We sought to estimate rotavirus disease-associated morbidity and mortality in Malaysia, using available sources of information. METHODS: We analyzed national data from the Ministry of Health (Kuala Lumpur, Malaysia) to derive rates of hospitalization, clinic visits, and deaths related to acute gastroenteritis (AG) among children <5 years of age. The number of events attributable to rotavirus infection was estimated by multiplying age-stratified rates of detection of rotavirus from 2 hospital surveillance sites by national data. RESULTS: In 1999 and 2000, an average of 13,936 children (1 in 187 children) were hospitalized annually for AG. Surveillance of visits to outpatient clinics for AG identified an average of 60,342 such visits/year between 1998 and 2000. The AG-associated mortality rate was 2.5 deaths/100,000 children. On the basis of the finding that 50% of children were hospitalized for rotavirus diarrhea, we estimated that 1 in 61 children will be hospitalized for rotavirus disease and that 1 in 37 children will seek treatment as an outpatient. CONCLUSIONS: Among Malaysian children, there is a significant burden associated with AG- and rotavirus disease-related hospitalizations and outpatient visits, and this burden potentially could be prevented by the use of rotavirus vaccines.

Child, Preschool↗

Development of candidate rotavirus vaccines derived from neonatal strains in India.

The need for a rotavirus vaccine in India is based on the enormous burden associated with the >100,000 deaths due to rotavirus diarrhea that occur annually among Indian children. Two rotavirus strains identified during nosocomial outbreaks of rotavirus infection in New Delhi and Bangalore, India, more than a decade ago are being developed as live oral vaccines. Infected newborns had no symptoms, shed virus for up to 2 weeks after infection, mounted a robust immune response, and demonstrated protection against severe rotavirus diarrhea after reinfection. The 2 strains are naturally occurring bovine-human reassortants. The New Delhi strain, 116E, is characterized as having a P[11],G9 genotype, and the Bangalore strain, I321, is characterized as having a P[11],G10 genotype. The strains have been prepared as pilot lots for clinical trials to be conducted in New Delhi. This unique project, which is developing a new rotavirus vaccine in India with the use of Indian strains, an Indian manufacturer, and an Indian clinical development program, aims to expedite introduction of rotavirus vaccines in India.

Administration, Oral↗

Serotype diversity and reassortment between human and animal rotavirus strains: implications for rotavirus vaccine programs.

The development of rotavirus vaccines that are based on heterotypic or serotype-specific immunity has prompted many countries to establish programs to assess the disease burden associated with rotavirus infection and the distribution of rotavirus strains. Strain surveillance helps to determine whether the most prevalent local strains are likely to be covered by the serotype antigens found in current vaccines. After introduction of a vaccine, this surveillance could detect which strains might not be covered by the vaccine. Almost 2 decades ago, studies demonstrated that 4 globally common rotavirus serotypes (G1-G4) represent >90% of the rotavirus strains in circulation. Subsequently, these 4 serotypes were used in the development of reassortant vaccines predicated on serotype-specific immunity. More recently, the application of reverse-transcription polymerase chain reaction genotyping, nucleotide sequencing, and antigenic characterization methods has confirmed the importance of the 4 globally common types, but a much greater strain diversity has also been identified (we now recognize strains with at least 42 P-G combinations). These studies also identified globally (G9) or regionally (G5, G8, and P2A[6]) common serotype antigens not covered by the reassortant vaccines that have undergone efficacy trials. The enormous diversity and capacity of human rotaviruses for change suggest that rotavirus vaccines must provide good heterotypic protection to be optimally effective.

Animals↗

Epidemiological profile and burden of rotavirus diarrhea in Vietnam: 5 years of sentinel hospital surveillance, 1998-2003.

For 5 years, we have conducted sentinel surveillance for rotavirus at 6 hospitals in 4 cities in Vietnam. Stool samples obtained from >10,000 children <5 years old who were admitted to the hospital with diarrhea have been screened for rotavirus. Overall, 55% of samples were positive, and there was little variability in rates of detection of rotavirus between sites (44%-62%). In Vietnam, the characteristics of rotavirus infection more closely resemble those seen in developed countries, rather than those seen in developing countries: children become infected at an older age, the percentage of stool samples in which rotavirus is detected is extremely high, and the rotavirus strains appear to be the common types, with fewer mixed infections occurring. It is estimated that 5300-6800 children <5 years old die of rotavirus infection each year in Vietnam, representing 8%-11% of all deaths in this age group (cumulative risk per child by age 5 years, 1 in 200 to 1 in 285). Additional studies are ongoing to document the economic cost of the disease and to assess the burden of both fatal cases and milder cases of disease. Study outcomes will provide information for future testing and potential use of a rotavirus vaccine.

Child, Preschool↗

Rotavirus vaccines: targeting the developing world.

For the past 2 decades, rotavirus infection, the most common cause of severe diarrhea in children, has been a priority target for vaccine development. This decision to develop rotavirus vaccines is predicated on the great burden associated with fatal rotavirus disease (i.e., 440,000 deaths/year), the firm scientific basis for developing live oral vaccines, the belief that increased investment in development at this time could speed the introduction of vaccines in developing countries, and the appreciation that implementation of a vaccine program should result in a measurable decrease in the number of hospitalizations and deaths associated with rotavirus disease within 2-3 years. RotaShield (Wyeth-Ayerst), the first rotavirus vaccine licensed in the United States, was withdrawn after 9 months because of a rare association of the vaccine with the development of intussusception. In the developing world, this vaccine could still have had a measurable effect, because the benefits of preventing deaths due to rotavirus disease would have been substantially greater than the rare risk of intussusception. Two live oral vaccines being prepared by GlaxoSmithKline and Merck have completed large-scale clinical trials. The GlaxoSmithKline vaccine has been licensed in Mexico and the Dominican Republic, and the Merck vaccine could be licensed in the United States within 1 year; several other candidate vaccines are in earlier stages of testing. However, many challenges remain before any of these vaccines can be incorporated into childhood immunization programs in the developing world. First, vaccine efficacy, which has already been demonstrated in children in industrialized and middle-income countries, needs to be proven in poor developing countries in Africa and Asia. The safety of vaccines with regard to the associated risk of intussusception must be demonstrated as well. Novel financing strategies will be needed to ensure that new vaccines are affordable and available in the developing world. Decision makers and parents in developing countries need to know about this disease that has little name recognition and is rarely diagnosed. Finally, for the global effort toward the prevention of rotavirus disease to be successful, special efforts will be required in India, China, and Indonesia, because one-third of all deaths due to rotavirus disease occur in these countries, and because these countries depend almost entirely on vaccines manufactured domestically.

Administration, Oral↗

Sentinel hospital surveillance for rotavirus diarrhea in the People's Republic of China, August 2001-July 2003.

China has the second largest birth cohort in the world and the second highest number of deaths due to rotavirus infection. It is also the only country with a licensed rotavirus vaccine. Chinese policy makers now need credible estimates of the burden of rotavirus disease, to decide about vaccine use. From August 2001 through July 2003, prospective hospital-based surveillance for rotavirus diarrhea among children <5 years of age was conducted in 6 sentinel hospitals. Rotavirus isolates were characterized to determine the G and P genotypes circulating during the study. Of 3149 children who were admitted to the hospitals for diarrhea and for whom screening for rotavirus was performed, 1590 (50%) had positive results of an antigen detection assay. Of all episodes of rotavirus diarrhea, 95% occurred during the first 2 years of life. The most common rotavirus strain was P[8]G3 (49% of episodes), and all the common strains were detected, including G9 strains (4% of episodes). Ongoing efforts are under way to more precisely define the burden of rotavirus diarrhea in urban and rural populations, to assess the proportion of episodes that may be due to unusual or emerging strains, and to estimate the economic burden of rotavirus disease.

Child, Preschool↗

Rotavirus antigenemia in patients with acute gastroenteritis.

Although rotavirus infections are generally considered to be confined to the intestine, recent reports suggest that extraintestinal disease occurs. We studied whether rotavirus infection was associated with antigenemia during a major outbreak of gastroenteritis in the Kingston metropolitan area, during July-August 2003. Rotavirus antigen was identified in 30 of 70 acute-phase serum samples (including from 2 deceased individuals) but in only 1 of 53 control samples. Serum antigen levels were inversely associated with time since symptom onset and were directly associated with antigen levels in stool (P = .02). Serum antigen levels were significantly elevated during primary infections (acute-phase serum immunoglobulin G [IgG] titers, <25), compared with those in subsequent infections (acute-phase serum IgG titers, > or = 25) (P = .02). Antigenemia was common in this outbreak and might provide a mechanism to help explain rare but well-documented reports of findings of extraintestinal rotavirus. In situations in which stool samples are not readily available (i.e., patients with severe dehydration or those recently recovered or deceased), serum testing by enzyme immunoassay offers a new and practical diagnostic tool.

Antibodies, Viral↗

Serum IgG mediates mucosal immunity against rotavirus infection.

We evaluated the protective role of passively transferred circulating antibodies in protecting non-human primates against experimental rotavirus infection. Pooled sera with rotavirus-specific IgG titers that were either high (1:10,000), intermediate (1:300), or negative (< 1:25) were infused i.v. into naive pigtailed macaques (ages 3-6 months). Rotavirus-specific IgG could be detected in the sera at 18 h in all animals infused with antibody-containing serum, and fecal IgG titers could be detected only in animals given high-titer pooled sera. When orally challenged with 10(6) fluorescent-forming units of a simian rotavirus strain, YK-1, at 18 h after serum transfer, control animals shed virus starting 1-3 days after challenge and continued to shed virus at high titers for 6-8 days, whereas passively immunized macaques did not shed virus or had delayed shedding at low titers for only a limited time. The observation that passively transferred antibodies can suppress or delay viral infection in rotavirus-challenged pigtailed macaques has important implications for the design and testing of parenteral candidate rotavirus vaccines.

Animals↗

Experimental infection of pigtailed macaques with a simian rotavirus, YK-1.

Experimental rotavirus infection was investigated in pigtailed macaques to study the infectivity, immunity, and pathogenesis of rotavirus. A challenge virus, YK-1, was administered intragastrically to four seronegative macaques (age: 11-16 months). Although none of the monkeys developed diarrhea, an active infection occurred with high titers of rotavirus antigen detected in stools 2-10 days after challenge. These animals developed rotavirus-specific antibody responses similar to those seen following primary exposure to rotavirus. YK-1 was then inoculated in four seropositive macaques (age: 14-16 months). All animals shed viral antigen in their stool, but the titers and duration were significantly less when compared to seronegative macaques. When rechallenged 28 days after initial YK-1 challenge, the macaques demonstrated significant protection against reinfection. All seropositive animals developed a rise in rotavirus-specific serum and fecal antibodies during YK-1 challenge and rechallenge. To independently assess the role of age and preexisting IgG titers to rotavirus, a 4-month-old seronegative and 6-month-old seropositive macaque were inoculated with YK-1. The seronegative macaque shed high titers of virus for 9 days, while the seropositive macaque shed only 3 days and in low titer. These data suggest that a primate model of rotavirus infection using the YK-1 strain may be useful in examining the immune response and protection from infection in pigtailed macaques and indicate that levels and duration of shedding may provide a good measure of protection from natural infection and from that induced by oral or parenteral vaccines.

Animals↗