Burden

Study Design:^4,5

1. Objective
   Compares global and regional genotype distributions between vaccine-introducing and non introducing countries and evaluates how these comparisons changed after consideration of temporal trends.
2. Methods
   This systematic review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Embase, Medline, CAB Abstracts, and Global Health databases were searched for studies reporting rotavirus genotypes among children aged <5 years with rotavirus gastroenteritis. Article screening and full-text review were conducted independently by reviewers using Covidence. Genotype data were extracted for each country-specific study period, and vaccine introduction status was determined based on the date of rotavirus vaccine introduction into the national immunization program. Genotype counts were pooled to estimate genotype proportions, and mixed-effect logistic regression models were used to compare genotype detection odds according to vaccine introduction status and time since vaccine introduction.
3. Number of Patients
   The analysis included 24 821 genotyped stool specimens from vaccine-introducing settings and 123 255 specimens from non introducing settings across 361 studies.
4. Inclusion Criteria
   Studies reporting rotavirus genotypes among children <5 years with rotavirus gastroenteritis and sufficient genotype data collected after 2000 were included.
5. Exclusion Criteria
   Clinical trials, duplicate data, studies with insufficient genotype data, asymptomatic children, hospital-acquired infections, and studies with samples collected before 2000 were excluded.
6. Outcomes
   The study assessed rotavirus genotype distributions, temporal genotype trends, and genotype detection odds according to vaccine introduction status and time since vaccine introduction.

Study Design:⁶

1. Objective
   Describes the incidence and mortality of rotavirus infection among children younger than 5 years and reveals the urgent need for interventions to reduce diarrhea risk, treat severe diarrhea episodes, and prevent rotavirus diarrhea.
2. Methods
   A cross-sectional modeling analysis based on findings from the Global Burden of Disease Study 2016 (GBD 2016). The researchers used Bayesian hierarchical models, including the Cause of Death Ensemble model (CODEm) and DisMod-MR version 2.1, to estimate rotavirus-associated mortality and morbidity across countries, age groups, sexes, and years. Data sources included scientific literature, surveillance systems, vital registration data, verbal autopsy data, population surveys, and healthcare records. Rotavirus-attributable burden was estimated using population attributable fractions (PAFs), while vaccine impact was assessed using modeled vaccine coverage and vaccine efficacy estimates.
3. Number of Patients
   The study did not include a single patient cohort because it was a global burden estimation analysis using aggregated international datasets and surveillance systems. The analysis focused on children younger than 5 years worldwide and estimated that rotavirus caused more than 258 million diarrhea episodes and 128,500 deaths globally in 2016.
4. Inclusion Criteria
   The study included global data sources used in the Global Burden of Disease Study 2016, including surveillance data, scientific literature, healthcare records, verbal autopsy data, and population-based studies related to diarrhea and rotavirus infection among children younger than 5 years of age.
5. Outcomes
   The primary outcomes were rotavirus-associated mortality and morbidity among children younger than 5 years by country and year, as well as the number of deaths prevented by rotavirus vaccination. Rotavirus vaccination was estimated to have prevented approximately 28,800 deaths worldwide in the same year.

Study Design:⁷

1. Objective
   Estimate the global number of rotavirus hospitalizations among children younger than 5 years in 2019, determine how many hospitalizations were prevented by current rotavirus vaccination programs, and estimate the additional number of hospitalizations that could be prevented through universal vaccine introduction and improved vaccine coverage worldwide.
2. Methods
   A systematic review and global burden estimation analysis. The authors systematically reviewed PubMed articles published between January 1, 2000, and December 31, 2019, following PRISMA guidelines. Studies reporting annual rotavirus hospitalization rates in children younger than 5 years before vaccine introduction were included. Data were grouped according to childhood mortality strata and WHO regions. Median hospitalization rates were calculated and applied to country-specific population estimates to estimate global hospitalization burden. Vaccine coverage data from WHO/UNICEF and vaccine effectiveness estimates were then used to estimate hospitalizations prevented by vaccination and the potential additional reductions achievable with universal vaccine introduction and higher coverage.
3. Number of Patients
   The study did not involve a single patient cohort because it was a systematic review and modeling study using aggregated population-based surveillance data from multiple countries. The analysis estimated that approximately 1,760,113 rotavirus hospitalizations occurred globally among children younger than 5 years in 2019.
4. Inclusion Criteria
   The study included primary peer-reviewed studies that: Reported annual rotavirus hospitalization rates among children younger than 5 years before rotavirus vaccine introduction, Included at least one continuous year of surveillance data, Collected hospitalization data after the year 2000, used active surveillance methods to identify laboratory-confirmed rotavirus hospitalizations.
5. Exclusion Criteria
   Studies including nosocomial infections, focused on special populations such as military-base populations, involving nonhuman rotavirus, using hospital discharge coding alone to calculate hospitalization rates, conducted in non-WHO member countries, with passive surveillance methods or without hospitalization rate data.
6. Outcomes
   The primary outcomes were the estimated number of global rotavirus hospitalizations among children younger than 5 years in 2019, the number of hospitalizations prevented by current rotavirus vaccination programs, the number of additional hospitalizations potentially preventable through universal vaccine introduction and improved vaccine coverage.

Study Design:⁸

1. Objective
   Explore the global burden and 30-year change patterns of rotavirus infection-associated deaths.
2. Methods
   Based on the Global Burden of Disease 2019 Study (GBD 2019), the study analyzed the age-standardized death rate (ASDR) of rotavirus infection by sex, geographical region, and sociodemographic index (SDI) from 1990 to 2019. A Joinpoint regression model was used to analyze global trends in rotavirus infection over the 30 years, SaTScan software was used to detect spatial and temporal aggregations, and a generalized linear model was used to explore the relationship between sociodemographic factors and death rates of rotavirus infection.
3. Number of Patients
   GBD 2019 included 204 countries and territories divided into 21 regions based on epidemiological similarities and geographical proximity and five groups according to SDI quintiles (low, low-middle,middle, high-middle, and high SDI).
4. Inclusion Criteria
   The study included data from GBD 2019, which provided comprehensive and standardized assessments of the world’s health for 369 diseases, injuries, and impairments from 1990 to 2019. The study extracted the number of deaths, death rates, and ASDRs of rotavirus infection with 95% UIs from 1990 to 2019, and analyses were stratified by age, sex, location, and year.
5. Outcomes
   The study assessed the age-standardized death rates (ASDRs), number of deaths, and temporal trends of rotavirus infection-associated deaths from 1990 to 2019 according to sex, age group, geographical region, and sociodemographic index (SDI).