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Biomedical subjects

Umesh D Parashar

Publications and source records attributed to Umesh D Parashar.

At least 19 recordsLinked to original sources

Rotavirus vaccine effectiveness against rotavirus and acute gastroenteritis mortality: an analysis of pooled case-control studies from the MNSSTER-V dataset.

BACKGROUND: Rotavirus accounts for an estimated 25% of diarrhoea deaths in children under 5 years globally, and more than 140 countries have included rotavirus vaccines in their routine national infant vaccination programmes. We aimed to calculate rotavirus vaccine effectiveness against rotavirus-positive and all-cause acute gastroenteritis deaths. METHODS: The Multi-National Subpopulations Study to Evaluate Rotavirus Vaccines (MNSSTER-V) dataset combines child-level data from test-negative case-control studies of rotavirus vaccine effectiveness that enrolled children under 5 years of age seeking care for acute gastroenteritis at hospitals or emergency departments in 24 countries between July 1, 2007, and Aug 24, 2023. Children were included in this study if they were: younger than 5 years, met the acute gastroenteritis case definition (had at least three episodes of diarrhoea in a 24-h period, had non-bloody and non-chronic diarrhoea, and were enrolled within 7 days of diarrhoea onset), met vaccine card quality metrics, had vaccine delivery dates if the child was reported to have received a rotavirus vaccine, and had a reported outcome of death or discharge. In-hospital acute gastroenteritis deaths were characterised, and rotavirus vaccine effectiveness against all-cause and rotavirus-positive acute gastroenteritis mortality was calculated using an unconditional logistic regression model with adjustment for national under-5 mortality strata and child's age. Vaccine effectiveness analyses against all-cause and rotavirus-positive acute gastroenteritis mortality were restricted to children aged at least 3 months who received any routine vaccines from countries reporting at least one acute gastroenteritis death. FINDINGS: From the MNSSTER-V dataset, we included 27 252 children younger than 5 years enrolled from 22 countries; outcomes of patients were not available for two countries. At least one in-hospital acute gastroenteritis death was reported from 16 countries including 21 522 children; in total, 183 all-cause acute gastroenteritis deaths and 25 rotavirus-positive deaths were reported. Among children aged at least 3 months who had received any routine vaccines, receiving at least one dose of a rotavirus vaccine had an adjusted vaccine effectiveness of 75·8% (95% CI 28·4 to 91·8; n=13 630) against rotavirus-positive acute gastroenteritis mortality and 20·8% (-47·0 to 57·3; n=20 005) against all-cause acute gastroenteritis mortality. INTERPRETATION: Rotavirus vaccines are effective in preventing rotavirus-positive acute gastroenteritis mortality. Continued efforts to improve vaccine delivery could help to reduce acute gastroenteritis mortality due to rotavirus worldwide. FUNDING: None.

Humans↗

Severe acute respiratory syndrome in children.

BACKGROUND: Severe acute respiratory syndrome (SARS) is a febrile, respiratory tract illness caused by infection with the newly identified SARS-associated coronavirus. A notable feature of the 2003 global SARS outbreak was the relative paucity of cases reported among children. We reviewed the epidemiologic and clinical features of SARS in children and discuss implications of these findings for diagnosis, treatment and prevention of SARS. METHODS: We performed a literature search to identify reports of pediatric (younger than 18 years of age) patients meeting the World Health Organization case definitions for SARS and abstracted relevant clinical and epidemiologic information. RESULTS: We identified 6 case series reporting 135 pediatric SARS patients (80 laboratory-confirmed, 27 probable and 28 suspect) from Canada, Hong Kong, Taiwan and Singapore. Among laboratory-confirmed and probable SARS cases, the most common symptoms included fever (98%), cough (60%) and nausea or vomiting (41%); 97% had radiographic abnormalities. The clinical presentation of SARS in patients older than 12 years of age was similar to that in adults. However, patients 12 years of age or younger had milder disease and were less likely than older children to be admitted to an intensive care unit, receive supplemental oxygen or be treated with methylprednisolone. No deaths were reported among children or adolescents with SARS, and at 6 months after illness only mild residual changes were reported in exercise tolerance and pulmonary function. There is only 1 published report of transmission of SARS virus from a pediatric patient. CONCLUSIONS: Children and adolescents are susceptible to SARS-associated coronavirus infection, although the clinical course and outcome are more favorable in children younger than 12 years of age compared with adolescents and adults. Transmission of SARS from pediatric patients appears to be uncommon but is possible.

Adolescent↗

Will pediatricians adopt the new rotavirus vaccine?

OBJECTIVES: Our objective was to determine the following among US pediatricians: (1) perceptions regarding burden of rotavirus disease and need for a vaccine; (2) intentions for recommending a newly licensed rotavirus vaccine; (3) perceived barriers to implementation; and (4) factors associated with plans for vaccine adoption. PATIENTS AND METHODS: A network of 431 pediatricians was recruited from a random sample of American Academy of Pediatrics' members. The network was designed to be representative of the American Academy of Pediatrics with respect to region of the country, practice type, and practice setting. During January and February 2006, physicians were surveyed by Internet or mail. The survey contained a paragraph summarizing results of the new rotavirus vaccine trial. Respondents were asked about intentions to use the vaccine and anticipated barriers. RESULTS: The survey response rate was 71%. Of the respondents, 52% strongly agreed and 37% somewhat agreed with the need for a rotavirus vaccine. If recommended for routine use, 50% would strongly recommend and 34% would recommend but not strongly; 52% would begin to use within 6 months and 27% from 6 months to 1 year. The top 3 "definite" barriers to implementation included concerns about uniform coverage of vaccine by insurers, lack of adequate reimbursement, and parental reluctance because of withdrawal of previous rotavirus vaccine. In multivariate analysis, factors associated with very likely adoption of the vaccine included perception of a high burden of rotavirus disease and a high level of confidence in prelicensure studies of vaccine safety. The presence of physician concerns about safety of the new vaccine and the perception of parental concerns about vaccine safety in general were negatively associated with adoption. CONCLUSIONS: The majority of pediatricians reported willingness to implement the new rotavirus vaccine, most within 6 months. Major barriers to optimal implementation included provider concerns about reimbursement issues and parental acceptance of the vaccine.

Attitude of Health Personnel↗

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↗

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↗

Rotavirus vaccines.

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Developed Countries↗

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↗

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↗

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↗

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↗

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↗

Projected cost-effectiveness of rotavirus vaccination for children in Asia.

BACKGROUND: New rotavirus vaccines may soon be licensed, and decisions regarding implementation of their use will likely be based on the health and economic benefits of vaccination. METHODS: We estimated the benefits and cost-effectiveness of rotavirus vaccination in Asia by using published estimates of rotavirus disease incidence, health care expenditures, vaccine coverage rates, and vaccine efficacy. RESULTS: Without a rotavirus vaccination program, it is estimated that 171,000 Asian children will die of rotavirus diarrhea, 1.9 million will be hospitalized, and 13.5 million will require an outpatient visit by the time the Asian birth cohort reaches 5 years of age. The medical costs associated with these events are approximately 191 million US dollars; however, the total burden would be higher with the inclusion of such societal costs as lost productivity. A universal rotavirus vaccination program could avert approximately 109,000 deaths, 1.4 million hospitalizations, and 7.7 million outpatient visits among these children. CONCLUSIONS: A rotavirus vaccine could be cost-effective, depending on the income level of the country, the price of the vaccine, and the cost-effectiveness standard that is used. Decisions regarding implementation of vaccine use should be based not only on whether the intervention provides a cost savings but, also, on the value of preventing rotavirus disease-associated morbidity and mortality, particularly in countries with a low income level (according to 2004 World Bank criteria for the classification of countries into income groups on the basis of per capita gross national income) where the disease burden is great.

Asia↗