BACKGROUND: The underlying causes for lower rotavirus vaccine effectiveness (VE) in high-child-mortality settings are not well understood. Uganda introduced the human monovalent G1P[8] rotavirus vaccine (Rotarix) in June 2018. We determined the effectiveness of Rotarix against rotavirus diarrhea requiring hospital care among Ugandan children. METHODS: We compared the vaccination status of children with laboratory-confirmed rotavirus (cases) and non-rotavirus (controls) diarrhea who were age-eligible to receive Rotarix and admitted to 3 hospitals in Uganda October 2018-December 2022. VE ([1-odds ratio of vaccination among cases and controls] x 100]) was calculated using unconditional logistic regression adjusting for age, birth month-year, and hospital. RESULTS: Among 187 cases and 622 controls, respectively, 93 % (173/187) and 93 % (579/622) had received ≥1 doses of Rotarix. Adjusted full-series (2 dose) VE against rotavirus diarrhea was 29 % (95 % confidence interval: -37 %-63 %) in children 4-59 months of age. Two-dose VE was 62 % (9 %-84 %) in infants 4-11 months of age and - 69 % (-401 %-43 %) in children 12-59 months of age (P = 0.20). VE against strains partially-heterotypic to the vaccine strain (including G3P[8], the most common curculating genotype) was 59 % (1 %-83 %). CONCLUSIONS: Routine Rotarix vaccination was effective in preventing hospital visits for rotavirus diarrhea among Ugandan infants, although protection was not sustained after the first year of life. Protection was demonstrated against partially heterotypic rotavirus strains. These results support the continued use of rotavirus vaccines in Uganda. Additional studies are needed to understand the lower rotavirus VE seen in Uganda and other high-mortality settings.

Rotavirus vaccines have substantially decreased rotavirus hospitalizations in countries where they have been implemented. In some high- and middle-income countries, a low-level of increased risk of intussusception, a type of acute bowel obstruction, has been detected following rotavirus vaccination. However, no increased risk of intussusception was found in India, South Africa, or a network of 7 other African countries. We assessed the association between a 2-dose monovalent rotavirus vaccine (Rotarix) and intussusception in 3 early-adopter low-income Asian countries -- Afghanistan, Myanmar, and Pakistan. Children <12 months of age admitted to a sentinel surveillance hospital with Brighton level 1 intussusception were eligible for enrollment. We collected information about each child's vaccination status and used the self-controlled case series method to calculate the relative incidence of intussusception 1-7 days, 8-21 days, and 1-21 days following each dose of vaccine and derived confidence intervals with bootstrapping. Of the 585 children meeting the analytic criteria, the median age at intussusception symptom onset was 24 weeks (IQR: 19-29). Overall, 494 (84 %) children received the first Rotarix dose and 398 (68 %) received the second dose. There was no increased intussusception risk during any of the risk periods following the first (1-7 days: 1.01 (95 %CI: 0.39, 2.60); 8-21 days: 1.37 (95 %CI: 0.81, 2.32); 1-21 days: 1.28 (95 %CI: 0.78, 2.11)) or second (1-7 days: 0.81 (95 %CI: 0.42, 1.54); 8-21 days: 0.77 (95 %CI: 0.53, 1.16); 1-21 days: 0.78 (95 %CI: 0.53, 1.16)) rotavirus vaccine dose. Our findings are consistent with other data showing no increased intussusception risk with rotavirus vaccination in low-income countries and add to the growing body of evidence demonstrating safety of rotavirus vaccines.

INTRODUCTION: Rotavirus vaccines may provide indirect protection by reducing transmission in the population and thus reducing disease burden. METHODS: This systematic review summarizes estimates of indirect protection from rotavirus vaccines and the methods used to obtain these estimates. RESULTS: We identified 71 studies published between 2009 and 2022 that provided 399 estimates of indirect protection from rotavirus vaccine. Most estimates (73%) evaluated hospitalizations due to rotavirus gastroenteritis as the outcome and unvaccinated children <5 years old as the age group (64%), but there was considerable variability in methods to evaluate indirect protection. For hospitalizations due to rotavirus gastroenteritis among unvaccinated children <5 years old, the median incidence rate ratio was 0.60 (IQR: 0.40-0.87, n = 110 estimates), the median relative percent change in percent positivity was 25% (IQR: 13-44%, n = 49 estimates), and the median relative percent change in absolute number of rotavirus positive tests or rotavirus-specific International Classification of Diseases codes was 42% (IQR: 16-66%, n = 40 estimates). CONCLUSIONS: These findings broadly suggest rotavirus vaccines provide some indirect protection. There is a need to standardize measurement of indirect rotavirus vaccine protection, particularly using consistent outcomes and metrics, and stratifying results by standardized age groups and years since vaccine introduction.

BACKGROUND: Afghanistan introduced monovalent rotavirus vaccine (Rotarix) into its national immunisation schedule in January, 2018. While post-licensure studies have shown substantial declines in rotavirus gastroenteritis cases and deaths globally, there is little evidence of rotavirus vaccine effectiveness and impact from low-income countries in Asia. We aimed to evaluate the effectiveness of the Rotarix vaccine and the impact of Rotarix vaccine on rotavirus gastroenteritis hospitalisations (ie, hospital admissions) among children younger than 5 years in Afghanistan. METHODS: We used a test-negative case-control design embedded in an active sentinel surveillance platform to evaluate vaccine effectiveness. Children born on or after Jan 1, 2018, who had documentation of their rotavirus vaccination status and who were admitted for acute gastroenteritis at one of four sentinel hospitals from May, 2018 to December, 2021 were eligible to be included. We used an unconditional logistic regression model to estimate vaccine effectiveness and 95% CIs for a complete series of doses compared with no rotavirus vaccine doses among patients admitted with acute gastroenteritis. Vaccine effectiveness against hospitalisation was calculated as (1 - [odds of being vaccinated in cases] / [odds of being vaccinated in controls]) × 100%. We compared pre-vaccine (2013-15) and post-vaccine (2019-21) surveillance data from two sites to calculate vaccine impact. FINDINGS: The vaccine effectiveness analysis included 1172 cases and 2173 controls. Approximately 2108 (63·0%) of 3345 cases and controls were male, 1237 (37·0%) were female, and 2171 (65·0%) were aged 6-11 months. Two doses of Rotarix were 45% (95% CI 22-62) effective against rotavirus hospitalisation in children aged 6-59 months, adjusting for age, severity, admission year, and rotavirus season. Rotavirus positivity decreased from 51% pre-vaccine to 39% post-vaccine, resulting in a 39% adjusted reduction in rotavirus positivity among children younger than 5 years admitted with acute gastroenteritis. INTERPRETATION: Rotarix showed moderate effectiveness in preventing rotavirus gastroenteritis hospitalisations, consistent with findings in other low-income countries. These findings support the continued administration of the rotavirus vaccine in Afghanistan. FUNDING: Gavi, the Vaccine Alliance. TRANSLATION: For the Dari translation of the abstract see Supplementary Materials section.

BACKGROUND: Rotavirus vaccine impact on rotavirus hospitalizations is not well documented globally. We performed a systematic review to estimate the number of rotavirus hospitalizations that (1) occur annually, (2) are currently prevented by rotavirus vaccines, and (3) could be prevented with improved vaccine coverage and universal vaccine introduction. METHODS: We systematically reviewed articles indexed in the PubMed database published from January 1, 2000, to December 31, 2019. We included all primary peer-reviewed studies with rotavirus hospitalization rates for children below 5 years that reported data prior to vaccine introduction, utilized at least one continuous year of data collection, and collected hospitalization data after 2000 using active surveillance. We grouped pre-vaccine country estimates by childhood mortality strata and calculated the median rate among each group. We then assigned the mortality stratum-specific hospitalization rates to each country and calculated the number of rotavirus hospitalizations by country, mortality strata, and World Health Organization region. RESULTS: Our search strategy identified 4590 manuscripts, of which 32 were included in the final dataset. In 2019, an estimated 1 760 113 (interquartile range [IQR]: 1 422 645-2 925 372) rotavirus hospitalizations occurred globally, with 524 871 (IQR: 415 987-814 835) prevented by rotavirus vaccination. With universal introduction of rotavirus vaccines and increased vaccine coverage, we estimate that an additional 751 609 (IQR: 607 671-1 318 807) rotavirus hospitalizations can be prevented annually. CONCLUSIONS: This analysis highlights the continued burden of rotavirus hospitalizations among children below 5 years. A large, preventable proportion of this burden could be eliminated by expanding introductions to new countries and increasing rotavirus vaccine coverage to levels seen with other childhood vaccinations.

INTRODUCTION: Diarrhoea is a leading killer of children <5 years old, accounting for 480,000 deaths in 2017. Zimbabwe introduced Rotarix into its vaccination program in 2014. In this evaluation, we estimate direct medical, direct non-medical, and indirect costs attributable to a diarrhea hospitalization in Zimbabwe after rotavirus vaccine introduction. METHODS: Children <5 years old admitted to Harare Central Hospital from June 2018 to April 2019 with acute watery diarrhea were eligible for this evaluation. A 3-part structured questionnaire was used to collect data by interview from the child's family and by review of the medical record. A stool specimen was also collected and tested for rotavirus. Direct medical costs were the sum of medications, consumables, diagnostic tests, and service delivery costs. Direct non-medical costs were the sum of transportation, meals and lodging for caregivers. Indirect costs are the lost income for household members. RESULTS: A total of 202 children were enrolled with a median age of 12 months (IQR: 7-21) and 48 (24%) had malnutrition. Children were sick for a median of 2 days and most had received outpatient medical care prior to admission. The median monthly household income was higher for well-nourished children compared to malnourished children (p < 0.001). The median total cost of a diarrhea illness resulting in hospitalization was $293.74 (IQR: 188.42, 427.89). Direct medical costs, with a median of $251.74 (IQR: 155.42, 390.96), comprised the majority of the total cost. Among children who tested positive for rotavirus, the median total illness cost was $243.78 (IQR: 160.92, 323.84). The median direct medical costs were higher for malnourished than well-nourished children (p < 0.001). CONCLUSION: Direct medical costs are the primary determinant of diarrhea illness costs in Zimbabwe. The descriptive findings from this evaluation are an important first step in calculating the cost effectiveness of rotavirus vaccine.

INTRODUCTION: Latin American countries were among the first to adopt rotavirus vaccines into national immunization programs; we reviewed one decade of their experience with rotavirus vaccination. Areas covered: We systematically reviewed manuscripts published January 1990-January 2018 to assess rotavirus vaccine effectiveness (VE) via meta-analysis; describe trends in rotavirus and acute gastroenteritis (AGE)-associated hospitalizations and mortality before and after vaccine introduction; and estimate annual hospitalizations and deaths averted by rotavirus vaccination in Latin American and Caribbean children <5 years. Rotavirus vaccines demonstrated VE against rotavirus hospitalization of 76% (95% CI: 58-87) in low-mortality countries and 67% (95% CI: 54-76) in high-mortality countries for children <1 year of age. Reductions of 64.0% (IQR: 49.9-69.2) were observed in rotavirus hospitalizations, 32.8% (IQR 29.0-40.3) in AGE hospitalizations, and 53.5% (IQR: 40.4-57.1) in AGE-related mortalities in children <5 years. In 2015, an estimated 125,000 rotavirus-associated hospitalizations and 800 rotavirus-related deaths were prevented in countries that implemented rotavirus vaccines. Expert Commentary: Rotavirus vaccines remain an effective tool against diarrheal disease. The continued success of rotavirus vaccines provides evidence for adoption in Latin American and Caribbean countries that have not yet introduced it, and improvement within those with low coverage.