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Background. Rotavirus vaccine is recommended for routine use in all countries globally. To facilitate decision making on rotavirus vaccine adoption by countries, help donors prioritize investments in health interventions, and monitor vaccine impact, we estimated rotavirus mortality for children <5 years of age from 2000 to 2013. Methods. We searched PubMed using the keyword \"rotavirus\" to identify studies that met each of the following criteria: data collection midpoint in year 1998 or later, study period of a 12-month increment, and detection of rotavirus infection by enzyme immunoassay in at least 100 children <5 years of age who were hospitalized with diarrhea and systematically enrolled through active surveillance. We also included data from countries that participated in the World Health Organization (WHO)-coordinated rotavirus surveillance network between 2008 and 2013 that met these criteria. To predict the proportion of diarrhea due to rotavirus, we constructed a multiple linear regression model. To determine the number of rotavirus deaths in children <5 years of age from 2000 to 2013, we multiplied annual, country-specific estimates of the proportion of diarrhea due to rotavirus from the regression model by the annual number of WHO-estimated child deaths caused by diarrhea in each country. Results. Globally, we estimated that the number of rotavirus deaths in children <5 years of age declined from 528 000 (range, 465 000–591 000) in 2000 to 215 000 (range, 197 000–233 000) in 2013. The predicted annual rotavirus detection rate from these studies declined slightly over time from 42.5% (95% confidence interval [CI], 37.4%–47.5%) in 2000 to 37.3% (95% CI, 34.2%–40.5%) in 2013 globally. In 2013, an estimated 47 100 rotavirus deaths occurred in India, 22% of all rotavirus deaths that occurred globally. Four countries (India, Nigeria, Pakistan, and Democratic Republic of Congo) accounted for approximately half (49%) of all estimated rotavirus deaths in 2013. Discussion. While rotavirus vaccine had been introduced in >60 countries worldwide by the end of 2013, the majority of countries using rotavirus vaccine during the review period were low-mortality countries and the impact of rotavirus vaccine on global estimates of rotavirus mortality has been limited. Continued monitoring of rotavirus mortality rates and deaths through rotavirus surveillance will aid in monitoring the impact of vaccination.

In 2006, 2 rotavirus vaccines were licensed. We summarize the impact of rotavirus vaccination on hospitalizations and deaths from rotavirus and all-cause acute gastroenteritis (AGE) during the first 10 years since vaccine licensure, including recent evidence from countries with high child mortality. We used standardized guidelines (PRISMA) to identify observational evaluations of rotavirus vaccine impact among children <5 years of age that presented at least 12 months of pre– and post–vaccine introduction surveillance data. We identified 57 articles from 27 countries. Among children <5 years of age, the median percentage reduction in AGE hospitalizations was 38% overall and 41%, 30%, and 46% in countries with low, medium, and high child mortality, respectively. Hospitalizations and emergency department visits due to rotavirus AGE were reduced by a median of 67% overall and 71%, 59%, and 60% in countries with low, medium, and high child mortality, respectively. Implementation of rotavirus vaccines has substantially decreased hospitalizations from rotavirus and all-cause AGE.

Two rotavirus vaccines, Rotarix (RV1) and RotaTeq (RV5), were licensed for global use in 2006. A systematic review of 48 peer-reviewed articles with postlicensure data from 24 countries showed a median RV1 vaccine effectiveness (VE) of 84%, 75%, and 57% in countries with low, medium, and high child mortality, respectively, and RV5 VE of 90% and 45% in countries with low and high child mortality, respectively. A partial vaccine series provided considerable protection, but not to the same level as a full series. VE tended to decline in the second year of life, particularly in medium- and high-mortality settings, and tended to be greater against more severe rotavirus disease. Postlicensure data from countries across geographic regions and with different child mortality levels demonstrate that under routine use, both RV1 and RV5 are effective against rotavirus disease, supporting the World Health Organization recommendation that all countries introduce rotavirus vaccine into their national immunization program.

Despite substantial decreases in recent decades, acute gastroenteritis causes the second greatest burden of all infectious diseases worldwide. Noroviruses are a leading cause of sporadic cases and outbreaks of acute gastroenteritis across all age groups. We aimed to assess the role of norovirus as a cause of endemic acute gastroenteritis worldwide. We searched Embase, Medline, and Global Health databases from Jan 1, 2008, to March 8, 2014, for studies that used PCR diagnostics to assess the prevalence of norovirus in individuals with acute gastroenteritis. We included studies that were done continuously for 1 year or more from a specified catchment area (geographical area or group of people), enrolled patients who presented with symptoms of acute gastroenteritis, and used PCR-based diagnostics for norovirus on all stool specimens from patients with acute gastroenteritis. The primary outcome was prevalence of norovirus among all cases of gastroenteritis. We generated pooled estimates of prevalence by fitting linear mixed-effect meta-regression models. Of 175 articles included, the pooled prevalence of norovirus in 187 336 patients with acute gastroenteritis was 18% (95% CI 17–20). Norovirus prevalence tended to be higher in cases of acute gastroenteritis in community (24%, 18–30) and outpatient (20%, 16–24) settings compared with inpatient (17%, 15–19, p=0·066) settings. Prevalence was also higher in low-mortality developing (19%, 16–22) and developed countries (20%, 17–22) compared with high-mortality developing countries (14%, 11–16; p=0·058). Patient age and whether the study included years of novel strain emergence were not associated with norovirus prevalence. Norovirus is a key gastroenteritis pathogen associated with almost a fifth of all cases of acute gastroenteritis, and targeted intervention to reduce norovirus burden, such as vaccines, should be considered. The Foodborne Disease Burden Epidemiology Reference Group (FERG) of WHO and the Government of the Netherlands on behalf of FERG.

WHO recommends routine use of rotavirus vaccines in all countries, particularly in those with high mortality attributable to diarrhoeal diseases. To establish the burden of life-threatening rotavirus disease before the introduction of a rotavirus vaccine, we aimed to update the estimated number of deaths worldwide in children younger than 5 years due to diarrhoea attributable to rotavirus infection. We used PubMed to identify studies of at least 100 children younger than 5 years who had been admitted to hospital with diarrhoea. Additionally, we required the studies to have a data collection midpoint of the year 2000 or later, to be done in full-year increments, and to assesses diarrhoea attributable to rotavirus with EIAs or polyacrylamide gel electrophoresis. We also included data from countries that participated in the WHO-coordinated Global Rotavirus Surveillance Network (consisting of participating member states during 2009) and that met study criteria. For countries that have introduced a rotavirus vaccine into their national immunisation programmes, we excluded data subsequent to the introduction. We classified studies into one of five groups on the basis of region and the level of child mortality in the country in which the study was done. For each group, to obtain estimates of rotavirus-associated mortality, we multiplied the random-effect mean rotavirus detection rate by the 2008 diarrhoea-related mortality figures for countries in that group. We derived the worldwide mortality estimate by summing our regional estimates. Worldwide in 2008, diarrhoea attributable to rotavirus infection resulted in 453 000 deaths (95% CI 420 000–494 000) in children younger than 5 years—37% of deaths attributable to diarrhoea and 5% of all deaths in children younger than 5 years. Five countries accounted for more than half of all deaths attributable to rotavirus infection: Democratic Republic of the Congo, Ethiopia, India, Nigeria, and Pakistan; India alone accounted for 22% of deaths (98 621 deaths). Introduction of effective and available rotavirus vaccines could substantially affect worldwide deaths attributable to diarrhoea. Our new estimates can be used to advocate for rotavirus vaccine introduction and to monitor the effect of vaccination on mortality once introduced. None.

BackgroundAs new rotavirus vaccines are being introduced in immunization programs, global and national estimates of disease burden, especially rotavirus-associated mortality, are needed to assess the potential health benefits of vaccination and to monitor vaccine impact MethodsWe identified 76 studies that were initiated after 1990, lasted at least 1 full year, and examined rotavirus among >100 children hospitalized with diarrhea. The studies were assigned to 5 groups (A-E) with use of World Health Organization classification of countries by child mortality and geography. For each group, the mean rotavirus detection rate was multiplied by diarrhea-related mortality figures from 2004 for countries in that group to yield estimates of rotavirus-associated mortality ResultsOverall, rotavirus accounted for 527,000 deaths (95% confidence interval, 475,000–580,000 deaths) annually or 29% of all deaths due to diarrhea among children <5 years of age. Twenty-three percent of deaths due to rotavirus disease occurred in India, and 6 countries (India, Nigeria, Congo, Ethiopia, China, and Pakistan) accounted for more than one-half of deaths due to rotavirus disease ConclusionsThe high mortality associated with rotavirus disease underscores the need for targeted interventions, such as vaccines. To realize the full life-saving potential of vaccines, it will be vital to ensure that they reach children in countries with high mortality. These baseline figures will allow future assessment of vaccine impact on rotavirus-associated mortality

Two rotavirus vaccines have been licensed in >100 countries worldwide since 2006. As of October 2105, these vaccines have been implemented in the national immunization programs of 79 countries, including 36 low-income countries that are eligible for support for vaccine purchase from Gavi, the Vaccine Alliance. Rotavirus vaccines were initially introduced in Australia and countries of the Americas and Europe after completion of successful clinical trials in these regions, and the impact of routine vaccination in reducing the health burden of severe childhood gastroenteritis in these regions has been well documented. Because of concerns around the performance of orally administered rotavirus vaccines in developing countries, vaccine implementation in these settings only began after additional clinical trials were completed and the World Health Organization issued a global recommendation for use of rotavirus vaccines in 2009. This supplementary issue of Clinical Infectious Diseases includes a collection of articles describing the impact and effectiveness of routine rotavirus vaccination in developing countries that were among the early adopters of rotavirus vaccine. The data highlight the benefits of vaccination and should provide valuable evidence to sustain vaccine use in these countries and encourage other countries to adopt routine rotavirus vaccination to reduce the health burden of severe childhood gastroenteritis.

► Prevalence data on ∼110,000 rotavirus strains identified from 100 countries worldwide during a 12-year period preceding introduction of rotavirus vaccines were collected and presented in this systematic review ► The paper summarizes (i) baseline strain prevalence data for the pre-vaccine era, (ii) analyzes spatiotemporal trends in distribution of circulating strains, and (iii) provides a weighted model to describe a more reliable estimate on the medical importance of individual rotavirus strains. Recently, two rotavirus vaccines have been recommended for routine immunization of infants worldwide. These vaccines proved efficacious during clinical trials and field use in both developing and developed countries, and appear to provide good protection against a range of rotavirus genotypes, including some that are not included in the vaccines. However, since conclusive data that the vaccines will protect against a wide variety of rotavirus strains are still lacking and since vaccines may exert some selection pressure, a detailed picture of global strain prevalence from the pre-rotavirus vaccine era is important to evaluate any potential changes in circulating strains observed after widespread introduction of rotavirus vaccines. Thus, we systematically reviewed rotavirus genotyping studies spanning a 12-year period from 1996 to 2007. In total, ∼110,000 strains were genotyped from 100 reporting countries. Five genotypes (G1–G4, and G9) accounted for 88% of all strains, although extensive geographic and temporal differences were observed. For example, the prevalence of G1 strains declined from 2000 onward, while G3 strains re-emerged, and G9 and G12 strains emerged during the same period. When crude strain prevalence data were weighted by region based on the region's contribution to global rotavirus mortality, the importance of genotypes G1 and G9 strains that were more prevalent in regions with low mortality was reduced and conversely the importance of G8 strains that were more prevalent in African settings with greater contribution to global rotavirus mortality was increased. This study provides the most comprehensive, up-to-date information on rotavirus strain surveillance in the pre-rotavirus vaccine era and will provide useful background to examine the impact of rotavirus vaccine introduction on future strain prevalence.

With the advent of the rotavirus vaccine, the causes of acute gastroenteritis in children are evolving. In this report from three sentinel U.S. sites, norovirus is identified as a leading causal organism in acute gastroenteritis in children. Norovirus-associated acute gastroenteritis is characterized by the sudden onset of intense vomiting and dehydrating diarrhea, typically lasting 1 to 3 days, with high rates of transmission to persons of all ages. 1 Norovirus is a leading etiologic pathogen implicated in severe gastroenteritis outbreaks in the United States. 2 , 3 However, the endemic burden of norovirus-associated acute gastroenteritis identified through active, laboratory-confirmed surveillance of U.S. pediatric populations has not been fully characterized. Given the substantial decline in pediatric rotavirus-associated acute gastroenteritis in the United States since the introduction of rotavirus vaccines, 4 – 8 and given recent advances in the development of candidate norovirus vaccines, . . .