Summary Background 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. Methods 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. Findings 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. Interpretation 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. Funding The Foodborne Disease Burden Epidemiology Reference Group (FERG) of WHO and the Government of the Netherlands on behalf of FERG.
Summary Background 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. Methods 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. Findings 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). Interpretation 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. Funding None.
Summary Background In May, 2012, Rwanda became the first low-income African country to introduce pentavalent rotavirus vaccine into its routine national immunisation programme. Although the potential ...health benefits of rotavirus vaccination are huge in low-income African countries that account for more than half the global deaths from rotavirus, concerns remain about the performance of oral rotavirus vaccines in these challenging settings. Methods We conducted a time-series analysis to examine trends in admissions to hospital for non-bloody diarrhoea in children younger than 5 years in Rwanda between Jan 1, 2009, and Dec 31, 2014, using monthly discharge data from the Health Management Information System. Additionally, we reviewed the registries in the paediatric wards at six hospitals from 2009 to 2014 and abstracted the number of total admissions and admissions for diarrhoea in children younger than 5 years by admission month and age group. We studied trends in admissions specific to rotavirus at one hospital that had undertaken active rotavirus surveillance from 2011 to 2014. We assessed changes in rotavirus epidemiology by use of data from eight active surveillance hospitals. Findings Compared with the 2009–11 prevaccine baseline, hospital admissions for non-bloody diarrhoea captured by the Health Management Information System fell by 17–29% from a pre-vaccine median of 4051 to 2881 in 2013 and 3371 in 2014, admissions for acute gastroenteritis captured in paediatric ward registries decreased by 48–49%, and admissions specific to rotavirus captured by active surveillance fell by 61–70%. The greatest effect was recorded in children age-eligible to be vaccinated, but we noted a decrease in the proportion of children with diarrhoea testing positive for rotavirus in almost every age group. Interpretation The number of admissions to hospital for diarrhoea and rotavirus in Rwanda fell substantially after rotavirus vaccine implementation, including among older children age-ineligible for vaccination, suggesting indirect protection through reduced transmission of rotavirus. These data highlight the benefits of routine vaccination against rotavirus in low-income settings. Funding Gavi, the Vaccine Alliance and the Government of Rwanda.
Summary Rotavirus is the most common cause of fatal and severe childhood diarrhoea worldwide. Two new rotavirus vaccines have shown efficacy against severe rotavirus disease in large clinical trials. ...Between 2006 and 2010, 27 countries introduced rotavirus vaccination into national immunisation programmes and, subsequently, the burden of severe rotavirus disease in these countries has decreased substantially in both vaccinated and unvaccinated children. Rotavirus vaccination has led to large, sustained declines in childhood deaths from diarrhoea in Brazil and Mexico, which supports estimates that rotavirus was the leading cause of diarrhoeal deaths in these countries. Studies after licensing have provided new insights into these vaccines, such as the duration of protection, relative effectiveness in poor populations, and strain evolution after vaccine introduction. The challenge for policy makers worldwide is to analyse the effect of vaccination in early adopter countries and to assess whether the benefits outweigh the costs and encourage wider dissemination of these vaccines.
Summary Background The effectiveness of the rotavirus vaccine under conditions of routine use in an African setting with a high prevalence of HIV infection needs to be established. We assessed the ...vaccine effectiveness of monovalent human rotavirus vaccine in preventing admission to hospital for acute rotavirus diarrhoea, after its introduction at age 6 and 14 weeks into South Africa's national immunisation programme. Methods This case-control study was done at seven hospitals in South Africa between April 19, 2010, and Oct 31, 2012. The hospitals were located in a range of urban, peri-urban, and rural settings, with varying rates of population HIV infection. Cases were children aged from 18 weeks to 23 months who were age-eligible to have received at least one dose of the human rotavirus vaccine (ie, those born after June 14, 2009) admitted to hospital with laboratory-confirmed acute rotavirus diarrhoea, and the primary control group was children admitted to hospital with diarrhoea testing negative for rotavirus. A second control group comprised children admitted to a subset of three of the seven hospitals with respiratory illness. The primary endpoint was adjusted vaccine effectiveness (1 – adjusted odds ratio × 100%) in children aged from 18 weeks to 23 months and was calculated by unconditional logistic regression. This study is registered on the South African National Clinical Trial Register, number DOH-27-0512-3247. Findings Of 540 rotavirus-positive cases, 278 children (52%) received two doses, 126 (23%) one dose, and 136 (25%) no doses of human rotavirus vaccine, compared with 1434 rotavirus-negative controls of whom 856 (60%) received two doses, 334 (23%) one dose, and 244 (17%) no doses. Adjusted vaccine effectiveness using rotavirus-negative controls was 57% (95% CI 40–68) for two doses and 40% (16–57) for one dose; estimates were similar when respiratory controls were used as the control group. Adjusted vaccine effectiveness for two doses was similar between age groups 18 weeks–11 months (54%, 95% CI 32–68) and 12–23 months (61%, 35–77), and was similar in HIV-exposed-uninfected (64%, 95% CI 34–80) and HIV-unexposed-uninfected children (54%, 31–69). Interpretation Human rotavirus vaccine provided sustained protection against admission to hospital for acute rotavirus diarrhoea during the first and second years of life. This finding is encouraging and establishes the public health value of rotavirus vaccine in an African setting, especially as rotavirus vaccines are introduced into an increasing number of African countries. Funding GAVI Alliance (with support from PATH).
Although deaths are often reported in the context of norovirus outbreaks, clinical and epidemiologic characteristics of the decedents prior to death are not well established. Through a literature ...review of published reports of deaths associated with norovirus infection, we identified and summarized 158 norovirus-associated deaths in 12 countries from 1988 to 2011.
Objective Using case-control methodology, we measured the vaccine effectiveness (VE) of the 2-dose monovalent rotavirus vaccine (RV1) and 3-dose pentavalent rotavirus vaccine (RV5) series given in ...infancy against rotavirus disease resulting in hospital emergency department or inpatient care. Study design Children were eligible for enrollment if they presented to any 1 of 3 hospitals in Atlanta, Georgia with diarrhea ≤10 days duration during January-June 2013 and were born after RV1 introduction. Stool samples were tested for rotavirus by enzyme immunoassay and immunization records were obtained from providers and the state electronic immunization information system. Case-subjects (children testing rotavirus antigen-positive) were compared with children testing rotavirus antigen-negative. Results Overall, 98 rotavirus-case subjects and 175 rotavirus-negative controls were enrolled. Genotype G12P8 predominated (n = 87, 89%). The VE of 2 RV1 doses was 84% (95% CI 38, 96) among children aged 8-23 months and 82% (95% CI 41, 95) among children aged ≥24 months. For the same age groups, the VE of 3 RV5 doses was 80% (95% CI 27, 95) and 87% (95% CI 22, 98), respectively. Conclusions Under routine use, the RV1 and RV5 series were both effective against moderate-to-severe rotavirus disease during a G12P8 season, and both vaccines demonstrated sustained protection beyond the first 2 years of life.
Rotavirus vaccine use in national immunisation programmes has led to declines in hospital admissions for rotavirus gastroenteritis among children; however, the global impact of rotavirus vaccine ...introduction has not been described using primary data. We describe the impact of rotavirus vaccine introduction on admissions for acute rotavirus gastroenteritis in primarily low-income and middle-income countries, using 9 years of data from the WHO-coordinated Global Rotavirus Surveillance Network (GRSN).
Between Jan 1, 2008, and Dec 31, 2016, children younger than 5 years of age who were admitted to hospital with acute gastroenteritis were prospectively enrolled in GRSN sites. We included sites that enrolled children and collected stool specimens monthly and tested at least 100 specimens annually in the impact analysis, with a separate analysis taking into account site continuity. We compared proportions of acute gastroenteritis cases positive for rotavirus in the pre-vaccine and post-vaccine periods and calculated mean proportion changes for WHO regions, with 95% CIs; these findings were then compared with interrupted time series analyses. We did further sensitivity analyses to account for rotavirus vaccination coverage levels and sites that collected specimens for at least 11 months per year and tested at least 80 specimens per year. We also analysed the age distribution of rotavirus-positive cases before and after vaccine introduction.
403 140 children younger than 5 years of age admitted to hospital with acute gastroenteritis from 349 sites in 82 countries were enrolled over the study period, of whom 132 736 (32·9%) were positive for rotavirus. We included 305 789 children from 198 sites in 69 countries in the impact analysis. In countries that had not introduced rotavirus vaccine in their national immunisation programmes, rotavirus was detected in 38·0% (95% CI 4·8–73·4) of admissions for acute gastroenteritis annually whereas in those that have introduced the vaccine, rotavirus was detected in 23·0% (0·7–57·7) of admissions for acute gastroenteritis, showing a 39·6% (35·4–43·8) relative decline following introduction. Interrupted time series analyses confirmed these findings. Reductions by WHO regions ranged from 26·4% (15·0–37·8) in the Eastern Mediterranean Region to 55·2% (43·0–67·4) in the European Region and were sustained in nine countries (contributing up to 31 sites) for 6–10 years. The age distribution of children with rotavirus gastroenteritis shifted towards older children after rotavirus vaccine introduction.
A significant and sustained reduction in the proportion of hospital admissions for acute gastroenteritis due to rotavirus was seen among children younger than 5 years in GRSN sites following rotavirus vaccine introduction. These findings highlight the need to incorporate rotavirus vaccines into immunisation programmes in countries that have not yet introduced them and underline the importance of high-quality surveillance.
The GRSN receives funding from Gavi, the Vaccine Alliance and the US Centers for Disease Control and Prevention. No specific funding was provided for this Article.
Objective We examined data from 1979-2007 to generate up-to-date baseline estimates of rotavirus intussusception mortality in US infants, to inform policy deliberations of the risks and benefits of ...vaccination. Study design Secular trends in the infant intussusception mortality rate were evaluated using national multiple cause-of-death and natality data from 1979- 2007. Linked birth/infant death data from 1998-2006 were examined to identify risk factors for intussusception deaths. Results After declining from 1979-1996, the average annual intussusception mortality rate stabilized from 1997-2007 at 2.1 per 1 million live births (range, 1.0-3.0). In multivariate analysis, significant variables associated with intussusception deaths included no prenatal care (OR, 5.4; 95% CI, 1.9-15.4) and birth order (≥3rd) (OR, 2.4; 95% CI, 1.4-4.4 reference: birth order (1st)). Conclusions Given the annual variation in intussusceptions mortality and low baseline rates, if a low vaccine-associated risk of death from intussusception exists in the United States, it would be difficult to assess using intussusception mortality trend data alone. Factors associated with intussusception mortality risk may be related to delayed or reduced health care access.
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