Rotavirus vaccines: successes and challenges.

Since 2006, the availability of two new rotavirus vaccines has raised enthusiasm to consider the eventual control and elimination of severe rotavirus diarrhea through the global use of vaccines. Rotavirus remains the most severe cause of acute diarrhea in children worldwide responsible for several hundred thousands of deaths in low income countries and up to half of hospital admissions for diarrhea around the world. The new vaccines have been recommended by WHO for all infants and in more than 47 countries, their introduction into routine childhood immunization programs has led to a remarkable decline in hospital admissions and even deaths within 3 years of introduction. Challenges remain with issues of vaccine finance globally and the problem that these live oral vaccines perform less well in low income settings where they are needed most. Ongoing research that will accompany vaccine introduction might help address these issues of efficacy and new vaccines and novel financing schemes may both help make these vaccines universally available and affordable in the decade.

Remaining issues and challenges for rotavirus vaccine in preventing global childhood diarrheal morbidity and mortality.

Rotavirus vaccines have had a dramatic impact on morbidity and mortality from diarrhea among children in high- and middle-income countries that have introduced the vaccine into their national immunization programs. Widespread introduction of rotavirus vaccine in developing countries is imminent and their full potential in reducing the global burden from severe childhood diarrhea may soon be realized. The objectives of this paper are to describe the remaining issues and challenges in ensuring the success of the global rotavirus vaccination program and to discuss further research needed to help address them.

Rotavirus infection in hospitalized children and estimates of disease burden in Kyrgyzstan, 2005-2007.

To estimate the rotavirus-associated burden in Kyrgyzstan, we conducted hospital surveillance among children <5 years old with diarrhoea during 2005-2007. Of 3756 children hospitalized with diarrhoea, 26% had rotavirus detected in stool samples by an enzyme immunoassay. The virus genotype G1P[8] was identified in 60% of 190 characterized samples from 2005 to 2006. The estimated risk for rotavirus hospitalization by age 5 years was 1 in 28 children. One quarter of all gastroenteritis hospitalizations in children <5 years old in Kyrgyzstan may be attributable to rotavirus. Rotavirus vaccination could be an important health intervention to reduce the burden of rotavirus gastroenteritis.

Rotavirus gastroenteritis in uzbekistan: implications for vaccine policy in central Asia.

BACKGROUND: To determine the value of rotavirus vaccines in Central Asia, we conducted surveillance of rotavirus in Uzbekistan, the country with the largest birth cohort in the region. Uzbekistan is eligible for international funds to introduce new vaccines. METHODS: We screened stool samples for rotavirus that were collected from children aged <5 years with gastroenteritis in 2 hospitals during 2005-2006. Using surveillance information and other data, we estimated national numbers of rotavirus-associated events per year. RESULTS: Of 3537 enrolled children, 1046 (30%) had rotavirus detected in stool specimens. Children aged <2 years accounted for 841 (80%) of all rotavirus infections. The G1P[8] genotype was identified in 27 (52%) of 52 typed samples collected in 2005. Rotavirus is estimated to cause 1174-1857 deaths and 6394-6558 hospitalizations among children aged <5 years annually. The cumulative risk of hospitalization for rotavirus by age 5 years is 1 in 94-96 children, and the risk of rotavirus-related death is 1 in 330-524 children. CONCLUSIONS: One-third of all hospitalizations for gastroenteritis and almost 5% of all deaths among children aged <5 years in Uzbekistan may be attributable to rotavirus. Introduction of rotavirus vaccines into the national immunization program at the current subsidized prices could be cost-effective.

Rotavirus disease and its prevention.

PURPOSE OF REVIEW: Rotavirus infection is the foremost cause of severe gastroenteritis of young children worldwide. Efforts to develop safe and effective vaccines resulted in licensure of the first live oral vaccine, tetravalent, rhesus-based rotavirus vaccine (RRV-TV), which was incorporated into the US immunization schedule in 1998. Less than 1 year later, however, the vaccine was withdrawn when reports of cases of intussusception were linked to recent vaccination. This setback created significant hurdles as well as new opportunities for the development of the next generation of rotavirus vaccines. This review focuses on new information related to the clinical presentation and pathogenesis of rotavirus infection, the associated global disease burden, and the ongoing efforts to develop and introduce the next generation of rotavirus vaccines for widespread use. RECENT FINDINGS: Recent studies have confirmed that rotavirus infection is not confined only to the gut but can have extraintestinal manifestations, including viremia. Estimates of the global disease burden of rotavirus diarrhea have been refined and suggest that mortality has not declined, and that among hospitalized cases of diarrhea, the fraction associated with rotavirus has increased in many countries. In the United States, the estimated number of hospitalizations attributed to rotavirus has increased. Debate continues about the magnitude of the attributable risk of the association between RRV-TV and intussusception. Several new rotavirus vaccines are in late stages of development. One vaccine was licensed in Mexico in 2004 and a second has completed clinical trials in the United States and Europe and may be licensed within 2 to 3 years. SUMMARY: The tremendous burden of rotavirus diarrhea among children all over the world continues to drive the remarkable pace of vaccine development and the variety of approaches to creating rotavirus vaccines.

Assessment of the epidemic potential of a new strain of rotavirus associated with the novel G9 serotype which caused an outbreak in the United States for the first time in the 1995-1996 season.

Rotavirus causes severe morbidity in developed countries and frequent deaths (> or = 500,000 per year) in less-developed countries. Historically, four serotypes--G1, G2, G3, and G4-have predominated; they are distinguished by one of two surface neutralization antigens (VP7). However, in 1983 and 1984 we described a new rotavirus serotype, designated G9, in five children hospitalized for diarrhea in Philadelphia, Pa. G9 rotavirus was not identified again in the Western Hemisphere until it caused ca. 50% of the rotavirus disease detected in Philadelphia in the 1995-1996 season. This outbreak allowed us to question whether a rotavirus strain completely new to a well-studied community would target either very young infants or older children, cause especially severe disease, or completely displace previously extant serotypes. We observed a significant excess of G9 infections in younger infants (especially in those < 6 months old) that might be attributed to the lack of G9-specific antibodies in mothers. Of further note, six of the seven oldest patients with rotavirus diarrhea were infected with the G9 strains (not significant). However, the age distribution of children with rotavirus did not differ over a 5-year study period regardless of the infecting serotype. Patients with diarrhea associated with G9 strains did not have disease more severe than that caused by the G1, G2, or G3 serotype. G9 strains did not displace the other serotypes but were virtually completely replaced by G1 or G2 serotypes in the three subsequent rotavirus seasons. We conclude that the abrupt appearance of this novel rotavirus serotype did not present a special threat to public health in the community.