Showing papers by "Umesh D. Parashar published in 2005"

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

Abstract: 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.

Rotavirus Vaccines: Targeting the Developing World

Abstract: 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.

Use of active surveillance to validate international classification of diseases code estimates of rotavirus hospitalizations in children.

Abstract: Objective. National estimates of hospi- talizations for rotavirus, the leading cause of acute gas- troenteritis (AGE) in children, have been used to estab- lish the need for rotavirus vaccines. A previous method directly estimated discharges by using the rotavirus-spe- cific International Classification of Diseases (ICD) code, but this method has not been validated. Our study eval- uated the sensitivity of the rotavirus ICD code among children hospitalized for AGE by using active surveil- lance for rotavirus at a tertiary children's hospital. Design. We compared data for rotavirus-coded hospi- tal discharges in 2000-2001 at Cincinnati Children's Hos- pital Medical Center with data on laboratory-confirmed cases of rotavirus obtained from active surveillance. We estimated additional rotavirus hospitalizations by ex- trapolating the proportion of rotavirus-positive results from active-surveillance cases to those with an unknown rotavirus status. Results. Of 767 cases of AGE-related discharge codes, 103 (13%) were coded as rotavirus, 91% (94 of 103) of which were laboratory-confirmed diagnoses. Among all children discharged with an AGE-related illness, 260 (34%) were enrolled in active surveillance, of whom 155 (60%) tested positive for rotavirus. An additional 47 lab- oratory-confirmed rotavirus-case patients not enrolled in active surveillance yielded a total of 202 rotavirus cases and a maximum sensitivity of the rotavirus code of 47%. Extrapolation indicated that an additional 170 untested children might be rotavirus-positive, yielding a total of 372 rotavirus hospitalizations and a minimum sensitivity of the rotavirus code of 25%. Conclusions. Measurement of rotavirus-coded hospi- tal discharges alone seems to greatly underestimate the true burden of rotavirus-associated hospitalizations. The numbers of national rotavirus hospitalization discharges may be substantially greater than previously estimated. Pediatrics 2005;115:78-82; acute gastroenteritis, United States, child, surveillance, hospitalization, ICD codes, sensitivity, specificity.

Incidence of Severe Rotavirus Diarrhea in New Delhi, India, and G and P Types of the Infecting Rotavirus Strains

Abstract: A total of 62,475 children <5 years old from a defined population of approximately 500,000 children and adults from slums in New Delhi, India, were assessed for 1 year by means of passive surveillance, to identify children who were hospitalized for diarrhea. The incidence of severe rotavirus diarrhea was estimated, and the G and P types of the infecting rotavirus strains were determined and were correlated with the clinical severity of diarrhea. Of 584 children who were hospitalized with diarrhea, 137 (23.5%) had rotavirus detected in stool specimens (incidence of rotavirus diarrhea-associated hospitalizations, 337 hospitalizations/100,000 children <5 years of age). Most cases of diarrhea (98%) occurred during the first 2 years of life, peaking at 9-11 months of age. Rotavirus-associated diarrhea occurred year-round but was predominant in winter. Among the strains that could be G-typed, G1 was the most common serotype, followed by G9 and G2; 10% of cases of diarrhea were due to mixed G-type infections. Common strains identified in the present surveillance study were P[8]G1, P[4]G2, P[8]G9, P[6]G1, P[6]G9, and P[6]G3. Children infected with G1 strains had a greater risk of developing more-severe cases of diarrhea than did children infected with other rotavirus strains (odds ratio, 2.95; 95% confidence interval, 1.3-6.67).

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

Abstract: 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. 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. Without a rotavirus vaccination program it is estimated that 171000 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; 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 109000 deaths 1.4 million hospitalizations and 7.7 million outpatient visits among these children. 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. (authors)

Development of Candidate Rotavirus Vaccines Derived from Neonatal Strains in India

Abstract: The need for a rotavirus vaccine in India is based on the enormous burden associated with the 1100,000 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

Update on Rotavirus Vaccines

Abstract: Rotavirus was discovered in 1973, and 10 years later the first report of a rotavirus vaccine clinical trial appeared. This update reviews the epidemiology of rotavirus infections, assesses past and current vaccines and presents ideas for implementation of vaccination programs in developed and developing countries.

Estimates of Rotavirus Disease Burden in Hong Kong: Hospital-Based Surveillance

Abstract: 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.

Estimates of the Burden of Rotavirus Disease in Malaysia

Abstract: 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.

Hospital-Based Study of the Economic Burden Associated with Rotavirus Diarrhea in Hong Kong

Abstract: Rotavirus infection is the most common cause of severe diarrhea in both developed and developing countries. 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. The annual total social cost and total direct medical cost for rotavirus-associated admissions were calculated as US $4.3 and US $4 million respectively by use of data collected during March 2001 to March 2003. The estimate of the direct medical costs was ~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 US $120 when their child’s admission was associated with rotavirus infection; this cost represents ~10% of the monthly salary of an unskilled or service worker. These data emphasize the potential for a safe and effective rotavirus vaccine to reduce the economic burden associated with rotavirus disease. (authors)