Rotavirus vaccines (RotaTeq, Rotarix, Rotavac, Rotasiil)

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disease risks

post-acute and long-term sequelae

vaccine efficacy and effectiveness

vaccine safety and adverse events

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Rotavirus gastroenteritis Rotavirus A

Disease risks

Acute risks of the infection itself: complications, hospitalisation, ICU, death.

Outcome (O)	Population (P)	Estimate	Design (S)	Source
Death from rotavirus diarrhoea worldwide severity: death case definition: Diarrhoea deaths attributable to rotavirus, from hospital-based rotavirus detection rates applied to 2008 diarrhoea mortality	children younger than 5 years vaccination status: unvaccinated country: worldwide setting: global estimate period: 2008, before universal rotavirus vaccination Infant <1y1-4y	453,000 (420,000–494,000) annual deaths worldwide (count) per year, all children under 5 worldwide	meta-analysis	Tate et al. 2012 Lancet Infect Dis quote 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. abstract, FINDINGS The pre-vaccine baseline most often cited by WHO. Data after vaccine introduction were excluded for countries that had introduced.
Share of all diarrhoea deaths attributable to rotavirus severity: death case definition: Rotavirus-attributable fraction of diarrhoea deaths in children under 5, 2008	children younger than 5 years vaccination status: unvaccinated country: worldwide setting: global estimate period: 2008 Infant <1y1-4y	37 proportion of diarrhoea deaths (%) per diarrhoea death in children under 5	meta-analysis	Tate et al. 2012 Lancet Infect Dis quote 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. abstract, FINDINGS The same sentence states rotavirus caused 5% of all under-5 deaths. Five countries accounted for more than half of rotavirus deaths.
Share of diarrhoea hospitalisations testing positive for rotavirus, before vaccine introduction severity: hospitalisation case definition: Median rotavirus-positive percentage among children hospitalised for diarrhoea across 105 pre/post introduction studies	children <5 years old vaccination status: unvaccinated country: 49 countries setting: hospital period: before rotavirus vaccine introduction (studies published 2006-2019) Infant <1y1-4y	40 median proportion of diarrhoea hospitalisations rotavirus-positive (%) per diarrhoea hospitalisation tested	systematic review	Burnett et al. 2020 J Infect Dis quote The median percentage of specimens that tested positive for rotavirus among children <5 years old hospitalized for diarrhea was 40% (IQR, 28-45) before rotavirus vaccine introduction and 20% (IQR, 20-20) 4 years after introduction. abstract, RESULTS Median across studies with an interquartile range in the quote; the same sentence gives 20% four years after introduction. Not a confidence interval, so no bounds recorded.
Hospitalisation for rotavirus gastroenteritis severity: hospitalisation case definition: Estimated annual rotavirus hospitalisations in the United States from special surveys, cohort studies and hospital discharge data	children younger than age 5 years vaccination status: unvaccinated country: United States setting: national estimate period: prevaccine era (before 2006) Infant <1y1-4y	55,000 to 70,000 annual hospitalisations (count) per year, all US children under 5	expert body	cdc.gov quote Rotavirus infection was responsible for 410,000 physician visits, more than 200,000 emergency department visits, 55,000 to 70,000 hospitalizations, and 20 to 60 deaths annually in children younger than age 5 years. Pink Book chapter 19, Epidemiology / Disease burden Pre-vaccine national estimate from CDC. Rotavirus is not nationally notifiable in the United States, so these are modelled from surveys and discharge data, not case reports.
Death from rotavirus gastroenteritis severity: death case definition: Estimated annual rotavirus-associated deaths in the United States	children younger than age 5 years vaccination status: unvaccinated country: United States setting: national estimate period: prevaccine era (before 2006) Infant <1y1-4y	20 to 60 annual deaths (count) per year, all US children under 5	expert body	cdc.gov quote Rotavirus infection was responsible for 410,000 physician visits, more than 200,000 emergency department visits, 55,000 to 70,000 hospitalizations, and 20 to 60 deaths annually in children younger than age 5 years. Pink Book chapter 19, Epidemiology / Disease burden Deaths were rare in the United States even before vaccination; the burden there was hospitalisation and outpatient care. Compare with the global pre-vaccine mortality records.
Physician visits for rotavirus gastroenteritis severity: outpatient visit case definition: Estimated annual physician visits for rotavirus in the United States	children younger than age 5 years vaccination status: unvaccinated country: United States setting: national estimate period: prevaccine era (before 2006) Infant <1y1-4y	410,000 annual physician visits (count) per year, all US children under 5	expert body	cdc.gov quote Rotavirus infection was responsible for 410,000 physician visits, more than 200,000 emergency department visits, 55,000 to 70,000 hospitalizations, and 20 to 60 deaths annually in children younger than age 5 years. Pink Book chapter 19, Epidemiology / Disease burden Same CDC sentence as the hospitalisation and death records; the three figures are different tiers of the same pre-vaccine burden and must not be added together.
Share of all gastroenteritis hospitalisations caused by rotavirus severity: hospitalisation case definition: Rotavirus-attributable proportion of gastroenteritis hospitalisations in US children	children younger than age 5 years, incidence highest at 3 to 35 months vaccination status: unvaccinated country: United States setting: hospital period: prevaccine era (before 2006) Infant <1y1-4y	30 to 50 proportion of gastroenteritis hospitalisations (%) per gastroenteritis hospitalisation in children under 5	expert body	cdc.gov quote Rotavirus accounted for 30% to 50% of all hospitalizations for gastroenteritis among children younger than age 5 years; the incidence of clinical illness was highest among children age 3 to 35 months. Pink Book chapter 19, Epidemiology / Disease burden A proportion of hospitalisations, not a population risk. The post-vaccine proportion from active surveillance is a separate record.
Rotavirus infection by age 5 years severity: any infection case definition: Estimated cumulative infection in US children in the prevaccine era	children by age 5 years vaccination status: unvaccinated country: United States setting: national estimate period: prevaccine era (before 2006) Infant <1y1-4y	95 proportion of children infected at least once by age 5 (%) per child	expert body	cdc.gov quote Secular Trends in the United States Rotavirus Secular Trends in the United States Prevaccine era: Estimated 2.7 million cases per year 95% of children infected by 5 years of age Following the introduction of rotavirus vaccine: Annually averted: 280,000 clinic visits 62,000 emergency department visits 45,000 hospitalizations In the prevaccine era, an estimated 2.7 million rotavirus infections occurred every year in the United States and 95% of children experienced at least one rotavirus infection by age 5 years. Pink Book chapter 19, Epidemiology / Disease burden Nearly universal infection in early childhood is the background against which the hospitalisation and death counts should be read: most infections were mild.
Death from rotavirus gastroenteritis worldwide severity: death case definition: Annual rotavirus deaths in children worldwide as summarised by CDC	children vaccination status: unvaccinated country: worldwide setting: global estimate period: prevaccine era Infant <1y1-4y	up to 500,000 annual deaths worldwide (count) per year, all children worldwide	expert body	cdc.gov quote In the prevaccine era, the majority of children were infected by age 5 years, and rotavirus was responsible for up to 500,000 deaths among children annually worldwide. Pink Book chapter 19, Rotavirus (introduction) An upper-bound summary figure. The systematic-review and GBD estimates are separate records and are lower.
Severe rotavirus gastroenteritis in the first year of life (placebo arm) severity: severe (Vesikari scale) case definition: Wild-type rotavirus gastroenteritis graded severe on the Vesikari scale under active follow-up surveillance	infants enrolled at 6 weeks and followed through the first year of life vaccination status: unvaccinated country: South Africa and Malawi setting: community, active surveillance, LMIC period: trial follow-up, first year of life n: 4417 infants in the per-protocol analysis Infant <1y	4.9 proportion of placebo infants with severe rotavirus gastroenteritis in year 1 (%) per placebo infant followed for one year	RCT	Madhi et al. 2010 N Engl J Med quote Of the 4417 infants included in the per-protocol efficacy analysis, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% confidence interval, 44.0 to 73.2). abstract, RESULTS Placebo-arm attack rate from the African Rotarix trial, i.e. a directly observed unvaccinated risk under active surveillance. The vaccine arm in the same sentence had 1.9%.
Severe rotavirus gastroenteritis in the first two years of life (placebo arm) severity: severe (Vesikari scale) case definition: Vesikari-graded severe rotavirus gastroenteritis under weekly home-visit surveillance to 18-24 months	infants enrolled at 6 weeks, followed to 18-24 months of age vaccination status: unvaccinated country: Malawi setting: community, active surveillance, LMIC period: trial follow-up to 18-24 months n: 483 placebo subjects Infant <1y1-4y	11.0 (8.3–14.1) proportion of placebo children with severe rotavirus gastroenteritis (%) per placebo child followed to 18-24 months	RCT	Cunliffe et al. 2012 Vaccine quote A total of 70/1030 (6.8%, 95% CI 5.3-8.5) subjects in the pooled (2 dose plus 3 dose) RIX4414 group compared with 53/483 (11.0%, 8.3-14.1) subjects in the placebo group developed severe rotavirus gastroenteritis in the entire follow-up period (vaccine efficacy 38.1% (9.8-57.3)). abstract Roughly one in nine unvaccinated Malawian children had severe rotavirus gastroenteritis by age two, the highest placebo-arm attack rate among the trials compiled here.
Severe rotavirus gastroenteritis in the first two years of life (placebo arm) severity: severe (Vesikari scale) case definition: Vesikari-graded severe rotavirus gastroenteritis from 2 weeks after dose two to about 2 years of age, according-to-protocol	infants aged 6-13 weeks at enrolment, followed to about 2 years vaccination status: unvaccinated country: ten Latin American countries setting: community, active surveillance period: trial follow-up to about 2 years of age n: 7081 placebo infants Infant <1y1-4y	2.3 (1.9–2.6) proportion of placebo children with severe rotavirus gastroenteritis (%) per placebo child followed to 2 years	RCT	Linhares et al. 2008 Lancet quote Fewer cases (p<0.0001) of severe rotavirus gastroenteritis were recorded for the combined 2-year period in the RIX4414 group (32 [0.4%] of 7205; 95% CI 0.3-0.6) than in the placebo group (161 [2.3%] of 7081; 1.9-2.6), resulting in a vaccine efficacy of 80.5% (71.3-87.1) to 82.1% (64.6-91.9) against wild-type G1, 77.5% (64.7-86.2) against pooled non-G1 strains, and 80.5% (67.9-88.8) against pooled non-G1 P[8] strains. abstract, FINDINGS Placebo attack rate in a middle-income setting, about a fifth of the Malawi figure; the baseline risk drives how many cases a given efficacy prevents.
Severe rotavirus gastroenteritis (placebo arm) severity: severe (Vesikari ≥11) case definition: First episode of laboratory-confirmed severe rotavirus gastroenteritis (Vesikari score ≥11) from 28 days after dose 3	infants vaccinated at 6, 10 and 14 weeks and followed through early childhood vaccination status: unvaccinated country: Niger setting: community, active and passive surveillance, LMIC period: trial follow-up n: 3508 infants in the per-protocol analysis Infant <1y1-4y	6.44 incidence per 100 person-years, placebo arm per 100 person-years of placebo follow-up	RCT	Isanaka et al. 2017 N Engl J Med quote RESULTS: Among the 3508 infants who were included in the per-protocol efficacy analysis, there were 31 cases of severe rotavirus gastroenteritis in the vaccine group and 87 cases in the placebo group (2.14 and 6.44 cases per 100 person-years, respectively), for a vaccine efficacy of 66.7% (95% confidence interval [CI], 49.9 to 77.9). abstract, RESULTS The vaccine-arm rate in the same sentence is 2.14 per 100 person-years. Rates are per protocol and from one high-mortality country.
Severe rotavirus gastroenteritis (placebo arm) severity: severe (Vesikari ≥11) case definition: Severe rotavirus gastroenteritis (≥11 on the Vesikari scale) ascertained by active surveillance	infants enrolled at 6-7 weeks, followed through the first year of life vaccination status: unvaccinated country: India (Delhi, Pune, Vellore) setting: urban and rural low-resource settings, LMIC period: 2011-2012 n: 2187 placebo infants in the per-protocol analysis Infant <1y	3.2 incidence per 100 person-years, placebo arm per 100 person-years of placebo follow-up	RCT	Bhandari et al. 2014 Lancet quote The incidence of severe rotavirus gastroenteritis per 100 person-years was 1·5 in the vaccine group and 3·2 in the placebo group, with an incidence rate ratio of 0·46 (95% CI 0·33-0·65). abstract, FINDINGS Indian placebo-arm incidence; the incidence rate ratio against vaccine in the same sentence is 0.46.
Hospitalisation among children presenting with rotavirus gastroenteritis severity: hospitalisation case definition: PCR-confirmed rotavirus gastroenteritis at three east London hospitals, matched to rotavirus-negative gastroenteritis controls	children aged 1 month to 16 years vaccination status: not reported country: United Kingdom setting: hospital period: June 2011 to December 2013 (before the UK rotavirus programme began in July 2013 for most of the period) n: 50 cases and 66 controls Infant <1y1-4y5-11y12-17y	93 proportion of cases hospitalised (%) per child presenting to hospital with rotavirus gastroenteritis	case-control	Karampatsas et al. 2018 PLoS One quote Children with rotavirus gastroenteritis tended to present more frequently with metabolic acidosis (pH 7.30 vs 7.37, P = 0.011) and fever (74% versus 46%; P = 0.005) and were more likely to require hospitalisation compared to children with non-rotavirus gastroenteritis (93% versus 73%; P = 0.019). abstract, RESULTS Small hospital-based series: the denominator is children who already reached a hospital, so this is not a population hospitalisation risk. Rotavirus-negative controls were hospitalised in 73%.
Encephalopathy complicating rotavirus gastroenteritis severity: encephalopathy case definition: Encephalopathy among PCR-confirmed rotavirus gastroenteritis cases at three east London hospitals	children aged 1 month to 16 years vaccination status: not reported country: United Kingdom setting: hospital period: June 2011 to December 2013 n: 50 rotavirus cases Infant <1y1-4y5-11y12-17y	6 proportion of cases with encephalopathy (%) per hospital-presenting rotavirus case	case-control	Karampatsas et al. 2018 PLoS One quote Encephalopathy occurred only in children with rotavirus infection (n = 3, 6%). abstract, RESULTS Three children out of fifty, so the proportion is unstable. Seizures and milder neurological signs were common but did not differ from rotavirus-negative gastroenteritis in the same study.
Emergency department visits for rotavirus gastroenteritis severity: emergency department visit case definition: Estimated annual rotavirus-associated emergency department visits in the United States before RV5 introduction	children aged <5 years vaccination status: unvaccinated country: United States setting: national estimate period: before 2006 Infant <1y1-4y	205,000 to 272,000 annual emergency department visits (count) per year, all US children under 5	surveillance	Centers 2009 MMWR Morb Mortal Wkly Rep quote In the United States, before introduction of a live, oral pentavalent rotavirus vaccine (RV5) in 2006, rotavirus caused an estimated 20 to 60 deaths, 55,000 to 70,000 hospitalizations, 205,000 to 272,000 emergency department visits, and 410,000 outpatient visits annually. abstract CDC MMWR summary of the pre-vaccine burden. The same sentence gives the hospitalisation and death ranges recorded from the Pink Book.
Death from rotavirus gastroenteritis severity: death case definition: Rotavirus-attributable diarrhoea deaths estimated indirectly from national multiple-cause-of-death data by the winter residual method	children 1 to 59 months of age vaccination status: unvaccinated country: United States setting: national vital statistics period: 1992-2006 Infant <1y1-4y	25 annual deaths (count) per year, all US children 1-59 months	surveillance	Esposito et al. 2011 Pediatr Infect Dis J quote Using indirect methods, we estimated 25 yearly rotavirus-associated deaths during the study period. abstract, RESULTS An indirect estimate, since death certificates rarely name rotavirus. Sits inside the CDC pre-vaccine death range recorded from the Pink Book.
Share of acute gastroenteritis hospitalisations that were rotavirus-positive severity: hospitalisation case definition: Children hospitalised with acute gastroenteritis in 3 US counties with a bulk stool specimen tested for rotavirus	children < 3 years of age vaccination status: mixed country: United States setting: hospital, active population-based surveillance period: 2006-2007 prevaccine period n: 2187 hospitalised children over 11 seasons Infant <1y1-4y	49 proportion of AGE hospitalisations rotavirus-positive, prevaccine (%) per AGE hospitalisation tested	surveillance	Staat et al. 2020 Clin Infect Dis quote Comparing pre- and postvaccine periods, the proportion of children with rotavirus dramatically declined for hospitalization (49% vs 10%) and ED visits (49% vs 8%). abstract, RESULTS The prevaccine figure in a pre/post comparison. The post-vaccine proportion is the next record, from the same sentence.
Share of acute gastroenteritis hospitalisations that were rotavirus-positive severity: hospitalisation case definition: Children hospitalised with acute gastroenteritis in 3 US counties with a bulk stool specimen tested for rotavirus	children < 3 years of age vaccination status: mixed country: United States setting: hospital, active population-based surveillance period: 2008-2016 postvaccine period Infant <1y1-4y	10 proportion of AGE hospitalisations rotavirus-positive, postvaccine (%) per AGE hospitalisation tested	surveillance	Staat et al. 2020 Clin Infect Dis quote Comparing pre- and postvaccine periods, the proportion of children with rotavirus dramatically declined for hospitalization (49% vs 10%) and ED visits (49% vs 8%). abstract, RESULTS Vaccinated and unvaccinated children are mixed in the denominator. A proportion of tested hospitalisations, not an incidence rate.
Share of acute gastroenteritis emergency department visits that were rotavirus-positive severity: emergency department visit case definition: Children visiting the ED with acute gastroenteritis in 3 US counties, stool tested for rotavirus	children < 3 years of age vaccination status: mixed country: United States setting: emergency department, active surveillance period: 2008-2016 postvaccine period, compared with 2006-2007 Infant <1y1-4y	8 proportion of AGE ED visits rotavirus-positive, postvaccine (%) per AGE ED visit tested	surveillance	Staat et al. 2020 Clin Infect Dis quote Comparing pre- and postvaccine periods, the proportion of children with rotavirus dramatically declined for hospitalization (49% vs 10%) and ED visits (49% vs 8%). abstract, RESULTS The prevaccine ED proportion in the same sentence is 49%; the post-vaccine pattern became biennial with an older median age.
Share of diarrhoea hospitalisations attributable to rotavirus severity: hospitalisation case definition: Children under 5 hospitalised with diarrhoea at 33 sentinel hospitals, randomly selected stools tested by quantitative PCR for 16 pathogens	children under 5 years vaccination status: mixed country: 28 low-income and middle-income countries setting: sentinel hospitals, LMIC period: 2017-2018 n: 5465 tested of 29 502 enrolled Infant <1y1-4y	33.3 (27.7–40.3) attributable fraction of diarrhoea hospitalisations (%) per diarrhoea hospitalisation	surveillance	Cohen et al. 2022 BMJ Glob Health quote Rotavirus was the leading cause of diarrhoea requiring hospitalisation (attributable fraction (AF) 33.3%; 95% CI 27.7 to 40.3), followed by Shigella (9.7%; 95% CI 7.7 to 11.6), norovirus (6.5%; 95% CI 5.4 to 7.6) and adenovirus 40/41 (5.5%; 95% CI 4.4 to 6.7). abstract, RESULTS Mixes sites with and without rotavirus vaccine; the next two records split them.
Share of diarrhoea hospitalisations attributable to rotavirus, sites without rotavirus vaccine severity: hospitalisation case definition: Quantitative PCR attributable fraction among hospitalised diarrhoea at sentinel sites that had not introduced rotavirus vaccine	children under 5 years vaccination status: unvaccinated country: low-income and middle-income countries without rotavirus vaccine setting: sentinel hospitals, LMIC period: 2017-2018 Infant <1y1-4y	42.1 (33.2–53.4) attributable fraction of diarrhoea hospitalisations (%) per diarrhoea hospitalisation	surveillance	Cohen et al. 2022 BMJ Glob Health quote The proportion of hospitalisations attributable to rotavirus was approximately 50% lower in sites that had introduced rotavirus vaccine (AF 20.8%; 95% CI 18.0 to 24.1) compared with sites that had not (42.1%; 95% CI 33.2 to 53.4). abstract, RESULTS The contemporaneous unvaccinated comparison for the next record; sites differ in more than vaccine status.
Share of diarrhoea hospitalisations attributable to rotavirus, sites with rotavirus vaccine severity: hospitalisation case definition: Quantitative PCR attributable fraction among hospitalised diarrhoea at sentinel sites that had introduced rotavirus vaccine	children under 5 years vaccination status: mixed country: low-income and middle-income countries with rotavirus vaccine setting: sentinel hospitals, LMIC period: 2017-2018 Infant <1y1-4y	20.8 (18.0–24.1) attributable fraction of diarrhoea hospitalisations (%) per diarrhoea hospitalisation	surveillance	Cohen et al. 2022 BMJ Glob Health quote The proportion of hospitalisations attributable to rotavirus was approximately 50% lower in sites that had introduced rotavirus vaccine (AF 20.8%; 95% CI 18.0 to 24.1) compared with sites that had not (42.1%; 95% CI 33.2 to 53.4). abstract, RESULTS About half the attributable fraction of non-introducing sites, yet rotavirus was still the leading cause of hospitalised diarrhoea.
Death from rotavirus diarrhoea worldwide severity: death case definition: Pathogen-specific deaths extrapolated from sentinel attributable fractions and country-level incidence	children under 5 years vaccination status: mixed country: worldwide setting: global estimate from LMIC sentinel data period: 2017-2018 Infant <1y1-4y	208 009 (169 561–259 216) annual deaths worldwide (count) per year, all children under 5 worldwide	surveillance	Cohen et al. 2022 BMJ Glob Health quote Globally, we estimated 208 009 annual rotavirus-attributable deaths (95% CI 169 561 to 259 216), 62 853 Shigella-attributable deaths (95% CI 48 656 to 78 805), 36 922 adenovirus 40/41-attributable deaths (95% CI 28 469 to 46 672) and 35 914 norovirus-attributable deaths (95% CI 27 258 to 46 516). abstract, RESULTS Higher than the GBD figure for a similar period because the attribution method differs (PCR attributable fractions versus modelled aetiology). Flagged as a conflicting estimate.
In-hospital death among children hospitalised with diarrhoea severity: death case definition: Children under 5 hospitalised with diarrhoea at WHO-coordinated sentinel sites in 57 countries; all-cause diarrhoea, not rotavirus-confirmed	children <5 years of age vaccination status: mixed country: 57 low- and middle-income countries setting: sentinel hospitals, LMIC period: 2008-2018 n: 234 781 cases, 1219 deaths Infant <1y1-4y	0.5 CFR (%) per hospitalised diarrhoea case	surveillance	Hartman et al. 2023 Clin Infect Dis quote The overall case fatality risk was found to be 0.5%. abstract, RESULTS All-cause hospitalised diarrhoea in the rotavirus surveillance network. Severe dehydration raised the odds of death and, notably, rotavirus-negative cases had higher odds of death than rotavirus-positive ones (next record).
Death among hospitalised diarrhoea cases, rotavirus-negative versus rotavirus-positive severity: death case definition: Multivariable odds of in-hospital death for rotavirus-negative versus rotavirus-positive hospitalised diarrhoea	children <5 years of age vaccination status: mixed country: 57 low- and middle-income countries setting: sentinel hospitals, LMIC period: 2008-2018 n: 234 781 cases Infant <1y1-4y	2.29 (1.92–2.74) OR for death, rotavirus-negative vs rotavirus-positive per hospitalised diarrhoea case	surveillance	Hartman et al. 2023 Clin Infect Dis quote Risk factors for death in the multivariable analysis included younger age (for <6 months compared with older ages, odds ratio [OR] = 3.54; 95% confidence interval [CI], 2.81-4.50), female sex (OR = 1.18; 95% CI, 1.06-1.81), presenting with persistent diarrhea (OR = 1.91; 95% CI, 1.01-3.25), no vomiting (OR = 1.13; 95% CI, .98-1.30), severe dehydration (OR = 3.79; 95% CI, 3.01-4.83), and being negative for rotavirus on an enzyme-linked immunosorbent assay test (OR = 2.29; 95% CI, 1.92-2.74). abstract, RESULTS A surprising direction: among children sick enough to be admitted, rotavirus-positive diarrhoea had lower odds of death than other causes. Severe dehydration (OR 3.79 in the same sentence) and age under 6 months were the strongest risk factors. Flagged for review.
Death from rotavirus diarrhoea worldwide severity: death case definition: Rotavirus-attributable diarrhoea deaths modelled by the Global Burden of Disease Study 2016	children younger than 5 years vaccination status: mixed country: worldwide setting: global estimate period: 2016 Infant <1y1-4y	128 500 (104 500–155 600) annual deaths worldwide (count, 95% uncertainty interval) per year, all children under 5 worldwide	modelling	Troeger et al. 2018 JAMA Pediatr quote RESULTS: Rotavirus infection was responsible for an estimated 128 500 deaths (95% uncertainty interval [UI], 104 500-155 600) among children younger than 5 years throughout the world in 2016, with 104 733 deaths occurring in sub-Saharan Africa (95% UI, 83 406-128 842). abstract, RESULTS Post-introduction global figure; the bounds are a GBD uncertainty interval, not a confidence interval. Method differs from the earlier systematic review so the two should not be read as a measured trend.
Death from rotavirus diarrhoea in sub-Saharan Africa severity: death case definition: Rotavirus-attributable diarrhoea deaths modelled by GBD 2016	children younger than 5 years vaccination status: mixed country: sub-Saharan Africa setting: regional estimate period: 2016 Infant <1y1-4y	104 733 (83 406–128 842) annual deaths (count, 95% uncertainty interval) per year, all children under 5 in sub-Saharan Africa	modelling	Troeger et al. 2018 JAMA Pediatr quote RESULTS: Rotavirus infection was responsible for an estimated 128 500 deaths (95% uncertainty interval [UI], 104 500-155 600) among children younger than 5 years throughout the world in 2016, with 104 733 deaths occurring in sub-Saharan Africa (95% UI, 83 406-128 842). abstract, RESULTS Most of the world's remaining rotavirus deaths are in sub-Saharan Africa, where trial efficacy is also lowest.
Rotavirus diarrhoea episodes severity: any episode case definition: Diarrhoea episodes attributable to rotavirus modelled by GBD 2016	children younger than 5 years vaccination status: mixed country: worldwide setting: global estimate period: 2016 Infant <1y1-4y	0.42 (0.30–0.53) incidence per child-year (95% uncertainty interval) per child-year	modelling	Troeger et al. 2018 JAMA Pediatr quote Rotavirus infection was responsible for more than 258 million episodes of diarrhea among children younger than 5 years in 2016 (95% UI, 193 million to 341 million), an incidence of 0.42 cases per child-year (95% UI, 0.30-0.53). abstract, RESULTS Roughly one episode per child every two to three years; the same sentence gives more than 258 million episodes.

Vaccine efficacy and effectiveness

Every estimate compiled, annotated by population (P), intervention (I), comparator (C), outcome (O) and study design (S).

Outcome (O)	Population (P)	Intervention / comparator	Estimate	Design (S)	Source
Severe rotavirus diarrhoea severity: severe case definition: Severe rotavirus diarrhoea as defined in the included trials	infants vaccinated and followed up for the first year of life country: low-mortality countries setting: low under-5 mortality n: 14,976 participants Infant <1y	Rotarix platform: live attenuated oral monovalent human rotavirus doses: 2 vs placebo or no intervention	93 VE (%) = cases prevented follow-up: first year of life	meta-analysis GRADE: high 4 trials	Bergman et al. 2021 Cochrane Database Syst Rev quote Rotarix Infants vaccinated and followed up for the first year of life In low-mortality countries, Rotarix prevented 93% of severe rotavirus diarrhoea cases (14,976 participants, 4 trials; high-certainty evidence), and 52% of severe all-cause diarrhoea cases (3874 participants, 1 trial; moderate-certainty evidence). abstract, MAIN RESULTS Cochrane abstract gives percentages without confidence intervals. Highest-certainty, highest-efficacy stratum.
Severe all-cause diarrhoea severity: severe case definition: Severe diarrhoea of any cause as defined in the included trial	infants vaccinated and followed up for the first year of life country: low-mortality countries setting: low under-5 mortality n: 3874 participants Infant <1y	Rotarix platform: live attenuated oral monovalent human rotavirus doses: 2 vs placebo or no intervention	52 VE (%) = cases prevented follow-up: first year of life	meta-analysis GRADE: moderate 1 trial	Bergman et al. 2021 Cochrane Database Syst Rev quote Rotarix Infants vaccinated and followed up for the first year of life In low-mortality countries, Rotarix prevented 93% of severe rotavirus diarrhoea cases (14,976 participants, 4 trials; high-certainty evidence), and 52% of severe all-cause diarrhoea cases (3874 participants, 1 trial; moderate-certainty evidence). abstract, MAIN RESULTS All-cause severe diarrhoea is the outcome a parent sees; about half of it was prevented where rotavirus is a large share of severe diarrhoea.
Severe rotavirus diarrhoea severity: severe case definition: Severe rotavirus diarrhoea as defined in the included trials	infants vaccinated and followed up for the first year of life country: medium-mortality countries setting: medium under-5 mortality n: 31,671 participants Infant <1y	Rotarix platform: live attenuated oral monovalent human rotavirus doses: 2 vs placebo or no intervention	79 VE (%) = cases prevented follow-up: first year of life	meta-analysis GRADE: high 4 trials	Bergman et al. 2021 Cochrane Database Syst Rev quote In medium-mortality countries, Rotarix prevented 79% of severe rotavirus diarrhoea cases (31,671 participants, 4 trials; high-certainty evidence), and 36% of severe all-cause diarrhoea cases (26,479 participants, 2 trials; high-certainty evidence). abstract, MAIN RESULTS The same sentence gives 36% against severe all-cause diarrhoea (26,479 participants, 2 trials, high certainty).
Severe all-cause diarrhoea severity: severe case definition: Severe diarrhoea of any cause as defined in the included trials	infants vaccinated and followed up for the first year of life country: medium-mortality countries setting: medium under-5 mortality n: 26,479 participants Infant <1y	Rotarix platform: live attenuated oral monovalent human rotavirus doses: 2 vs placebo or no intervention	36 VE (%) = cases prevented follow-up: first year of life	meta-analysis GRADE: high 2 trials	Bergman et al. 2021 Cochrane Database Syst Rev quote In medium-mortality countries, Rotarix prevented 79% of severe rotavirus diarrhoea cases (31,671 participants, 4 trials; high-certainty evidence), and 36% of severe all-cause diarrhoea cases (26,479 participants, 2 trials; high-certainty evidence). abstract, MAIN RESULTS All-cause outcome, lower than the rotavirus-specific figure because other pathogens are untouched.
Severe rotavirus diarrhoea severity: severe case definition: Severe rotavirus diarrhoea as defined in the included trials	infants vaccinated and followed up for the first year of life country: high-mortality countries setting: high under-5 mortality, LMIC n: 15,882 participants Infant <1y	Rotarix platform: live attenuated oral monovalent human rotavirus doses: 2 vs placebo or no intervention	58 VE (%) = cases prevented follow-up: first year of life	meta-analysis GRADE: high 4 trials	Bergman et al. 2021 Cochrane Database Syst Rev quote In high-mortality countries, Rotarix prevented 58% of severe rotavirus diarrhoea cases (15,882 participants, 4 trials; high-certainty evidence), and 27% of severe all-cause diarrhoea cases (5639 participants, 2 trials; high-certainty evidence). abstract, MAIN RESULTS The relative effect is smaller in high-mortality countries, but the review notes more episodes are prevented there because baseline risk is higher.
Severe all-cause diarrhoea severity: severe case definition: Severe diarrhoea of any cause as defined in the included trials	infants vaccinated and followed up for the first year of life country: high-mortality countries setting: high under-5 mortality, LMIC n: 5639 participants Infant <1y	Rotarix platform: live attenuated oral monovalent human rotavirus doses: 2 vs placebo or no intervention	27 VE (%) = cases prevented follow-up: first year of life	meta-analysis GRADE: high 2 trials	Bergman et al. 2021 Cochrane Database Syst Rev quote In high-mortality countries, Rotarix prevented 58% of severe rotavirus diarrhoea cases (15,882 participants, 4 trials; high-certainty evidence), and 27% of severe all-cause diarrhoea cases (5639 participants, 2 trials; high-certainty evidence). abstract, MAIN RESULTS About a quarter of all severe diarrhoea prevented in the highest-burden settings in year one.
Severe rotavirus diarrhoea severity: severe case definition: Severe rotavirus diarrhoea as defined in the included trials	children vaccinated in infancy and followed up for two years country: low-mortality countries setting: low under-5 mortality n: 18,145 participants Infant <1y1-4y	Rotarix platform: live attenuated oral monovalent human rotavirus doses: 2 vs placebo or no intervention	90 VE (%) = cases prevented follow-up: two years	meta-analysis GRADE: high 6 trials	Bergman et al. 2021 Cochrane Database Syst Rev quote Children vaccinated and followed up for two years In low-mortality countries, Rotarix prevented 90% of severe rotavirus diarrhoea cases (18,145 participants, 6 trials; high-certainty evidence), and 51% of severe all-cause diarrhoea episodes (6269 participants, 2 trials; moderate-certainty evidence). abstract, MAIN RESULTS Little decline from the first-year figure in low-mortality settings. The same sentence gives 51% against severe all-cause diarrhoea (2 trials, moderate certainty).
Severe rotavirus diarrhoea severity: severe case definition: Severe rotavirus diarrhoea as defined in the included trials	children vaccinated in infancy and followed up for two years country: medium-mortality countries setting: medium under-5 mortality n: 28,834 participants Infant <1y1-4y	Rotarix platform: live attenuated oral monovalent human rotavirus doses: 2 vs placebo or no intervention	77 VE (%) = cases prevented follow-up: two years	meta-analysis GRADE: high 3 trials	Bergman et al. 2021 Cochrane Database Syst Rev quote In medium-mortality countries, Rotarix prevented 77% of severe rotavirus diarrhoea cases (28,834 participants, 3 trials; high-certainty evidence), and 26% of severe all-cause diarrhoea cases (23,317 participants, 2 trials; moderate-certainty evidence). abstract, MAIN RESULTS The same sentence gives 26% against severe all-cause diarrhoea over two years (moderate certainty).
Severe rotavirus diarrhoea severity: severe case definition: Severe rotavirus diarrhoea as defined in the included trials	children vaccinated in infancy and followed up for two years country: high-mortality countries setting: high under-5 mortality, LMIC n: 13,768 participants Infant <1y1-4y	Rotarix platform: live attenuated oral monovalent human rotavirus doses: 2 vs placebo or no intervention	35 VE (%) = cases prevented follow-up: two years	meta-analysis GRADE: moderate 2 trials	Bergman et al. 2021 Cochrane Database Syst Rev quote In high-mortality countries, Rotarix prevented 35% of severe rotavirus diarrhoea cases (13,768 participants, 2 trials; moderate-certainty evidence), and 17% of severe all-cause diarrhoea cases (2764 participants, 1 trial; high-certainty evidence). abstract, MAIN RESULTS Drops from the first-year figure to this two-year figure, the clearest waning signal in the review and the reason the authors say some results suggest lower efficacy in the second year in high-mortality countries.
Severe all-cause diarrhoea severity: severe case definition: Severe diarrhoea of any cause as defined in the included trial	children vaccinated in infancy and followed up for two years country: high-mortality countries setting: high under-5 mortality, LMIC n: 2764 participants Infant <1y1-4y	Rotarix platform: live attenuated oral monovalent human rotavirus doses: 2 vs placebo or no intervention	17 VE (%) = cases prevented follow-up: two years	meta-analysis GRADE: high 1 trial	Bergman et al. 2021 Cochrane Database Syst Rev quote In high-mortality countries, Rotarix prevented 35% of severe rotavirus diarrhoea cases (13,768 participants, 2 trials; moderate-certainty evidence), and 17% of severe all-cause diarrhoea cases (2764 participants, 1 trial; high-certainty evidence). abstract, MAIN RESULTS Single-trial figure for the all-cause outcome over two years in the highest-burden setting.
Severe rotavirus diarrhoea severity: severe case definition: Severe rotavirus diarrhoea as defined in the included trials	infants vaccinated and followed up for the first year of life country: low-mortality countries setting: low under-5 mortality n: 5442 participants Infant <1y	RotaTeq platform: live oral pentavalent human-bovine reassortant doses: 3 vs placebo or no intervention	97 VE (%) = cases prevented follow-up: first year of life	meta-analysis GRADE: high 2 trials	Bergman et al. 2021 Cochrane Database Syst Rev quote RotaTeq Infants vaccinated and followed up for the first year of life In low-mortality countries, RotaTeq prevented 97% of severe rotavirus diarrhoea cases (5442 participants, 2 trials; high-certainty evidence). abstract, MAIN RESULTS No RotaTeq trial reported severe all-cause diarrhoea in low- or medium-mortality countries.
Severe rotavirus diarrhoea severity: severe case definition: Severe rotavirus diarrhoea as defined in the included trial	infants vaccinated and followed up for the first year of life country: medium-mortality countries setting: medium under-5 mortality n: 3863 participants Infant <1y	RotaTeq platform: live oral pentavalent human-bovine reassortant doses: 3 vs placebo or no intervention	79 VE (%) = cases prevented follow-up: first year of life	meta-analysis GRADE: low 1 trial	Bergman et al. 2021 Cochrane Database Syst Rev quote RotaTeq prevented 97% of severe rotavirus diarrhoea cases (5442 participants, 2 trials; high-certainty evidence). ... RotaTeq prevented 79% of severe rotavirus diarrhoea cases (3863 participants, 1 trial; low-certainty evidence). abstract, MAIN RESULTS Single trial, low certainty. The quote is anchored on the preceding low-mortality sentence because the year-1 and year-2 medium-mortality sentences in the abstract are word-for-word identical.
Severe rotavirus diarrhoea severity: severe case definition: Severe rotavirus diarrhoea as defined in the included trials	infants vaccinated and followed up for the first year of life country: high-mortality countries setting: high under-5 mortality, LMIC n: 6775 participants Infant <1y	RotaTeq platform: live oral pentavalent human-bovine reassortant doses: 3 vs placebo or no intervention	57 VE (%) = cases prevented follow-up: first year of life	meta-analysis GRADE: high 2 trials	Bergman et al. 2021 Cochrane Database Syst Rev quote In high-mortality countries, RotaTeq prevented 57% of severe rotavirus diarrhoea cases (6775 participants, 2 trials; high-certainty evidence), but there is probably little or no difference between vaccine and placebo for severe all-cause diarrhoea (1 trial, 4085 participants; moderate-certainty evidence). abstract, MAIN RESULTS The same sentence says there is probably little or no difference from placebo for severe all-cause diarrhoea in year one (1 trial, moderate certainty), a null result given without a number.
Severe rotavirus diarrhoea severity: severe case definition: Severe rotavirus diarrhoea as defined in the included trials	children vaccinated in infancy and followed up for two years country: low-mortality countries setting: low under-5 mortality n: 5442 participants Infant <1y1-4y	RotaTeq platform: live oral pentavalent human-bovine reassortant doses: 3 vs placebo or no intervention	96 VE (%) = cases prevented follow-up: two years	meta-analysis GRADE: high 2 trials	Bergman et al. 2021 Cochrane Database Syst Rev quote Children vaccinated and followed up for two years In low-mortality countries, RotaTeq prevented 96% of severe rotavirus diarrhoea cases (5442 participants, 2 trials; high-certainty evidence). abstract, MAIN RESULTS Essentially no waning over two years in low-mortality settings.
Severe rotavirus diarrhoea severity: severe case definition: Severe rotavirus diarrhoea as defined in the included trial	children vaccinated in infancy and followed up for two years country: medium-mortality countries setting: medium under-5 mortality n: 3863 participants Infant <1y1-4y	RotaTeq platform: live oral pentavalent human-bovine reassortant doses: 3 vs placebo or no intervention	79 VE (%) = cases prevented follow-up: two years	meta-analysis GRADE: low 1 trial	Bergman et al. 2021 Cochrane Database Syst Rev quote RotaTeq prevented 96% of severe rotavirus diarrhoea cases (5442 participants, 2 trials; high-certainty evidence). ... RotaTeq prevented 79% of severe rotavirus diarrhoea cases (3863 participants, 1 trial; low-certainty evidence). abstract, MAIN RESULTS Same single trial and same figure as the first-year record; the quote is anchored on the preceding two-year low-mortality sentence.
Severe rotavirus diarrhoea severity: severe case definition: Severe rotavirus diarrhoea as defined in the included trials	children vaccinated in infancy and followed up for two years country: high-mortality countries setting: high under-5 mortality, LMIC n: 6744 participants Infant <1y1-4y	RotaTeq platform: live oral pentavalent human-bovine reassortant doses: 3 vs placebo or no intervention	44 VE (%) = cases prevented follow-up: two years	meta-analysis GRADE: high 2 trials	Bergman et al. 2021 Cochrane Database Syst Rev quote In high-mortality countries, RotaTeq prevented 44% of severe rotavirus diarrhoea cases (6744 participants, 2 trials; high-certainty evidence), and 15% of severe all-cause diarrhoea cases (5977 participants, 2 trials; high-certainty evidence). abstract, MAIN RESULTS Down from the first-year figure. The same sentence gives 15% against severe all-cause diarrhoea over two years (5977 participants, 2 trials, high certainty).
Severe all-cause diarrhoea severity: severe case definition: Severe diarrhoea of any cause as defined in the included trials	children vaccinated in infancy and followed up for two years country: high-mortality countries setting: high under-5 mortality, LMIC n: 5977 participants Infant <1y1-4y	RotaTeq platform: live oral pentavalent human-bovine reassortant doses: 3 vs placebo or no intervention	15 VE (%) = cases prevented follow-up: two years	meta-analysis GRADE: high 2 trials	Bergman et al. 2021 Cochrane Database Syst Rev quote In high-mortality countries, RotaTeq prevented 44% of severe rotavirus diarrhoea cases (6744 participants, 2 trials; high-certainty evidence), and 15% of severe all-cause diarrhoea cases (5977 participants, 2 trials; high-certainty evidence). abstract, MAIN RESULTS A modest all-cause effect, consistent with the Africa and Asia trial records compiled from the primary papers.
Severe rotavirus diarrhoea severity: severe case definition: Severe rotavirus diarrhoea as defined in the included trials	infants vaccinated and followed up for the first year of life country: high-mortality countries (Niger and India) setting: high under-5 mortality, LMIC n: 11,008 participants Infant <1y	Rotasiil platform: live oral bovine-human reassortant pentavalent, heat-stable doses: 3 vs placebo	48 VE (%) = cases prevented follow-up: first year of life	meta-analysis GRADE: high 2 trials	Bergman et al. 2021 Cochrane Database Syst Rev quote Infants vaccinated and followed up for the first year of life In high-mortality countries, Rotasiil prevented 48% of severe rotavirus diarrhoea cases (11,008 participants, 2 trials; high-certainty evidence), and resulted in little to no difference in severe all-cause diarrhoea cases (11,008 participants, 2 trials; high-certainty evidence). abstract, MAIN RESULTS Rotasiil has not been assessed in any RCT in low- or medium-mortality countries. The same sentence reports little to no difference in severe all-cause diarrhoea.
Severe rotavirus diarrhoea severity: severe case definition: Severe rotavirus diarrhoea as defined in the included trials	children vaccinated in infancy and followed up for two years country: high-mortality countries (Niger and India) setting: high under-5 mortality, LMIC n: 11,008 participants Infant <1y1-4y	Rotasiil platform: live oral bovine-human reassortant pentavalent, heat-stable doses: 3 vs placebo	44 VE (%) = cases prevented follow-up: two years	meta-analysis GRADE: high 2 trials	Bergman et al. 2021 Cochrane Database Syst Rev quote Children vaccinated and followed up for two years In high-mortality countries, Rotasiil prevented 44% of severe rotavirus diarrhoea cases (11,008 participants, 2 trials; high-certainty evidence), and resulted in little to no difference in severe all-cause diarrhoea cases (11,008 participants, 2 trials; high-certainty evidence). abstract, MAIN RESULTS Little to no difference in severe all-cause diarrhoea over two years in the same sentence; a null all-cause result given without a number.
Severe rotavirus diarrhoea severity: severe case definition: Severe rotavirus diarrhoea as defined in the included trial	infants vaccinated and followed up for the first year of life country: high-mortality countries (India) setting: high under-5 mortality, LMIC n: 6799 participants Infant <1y	Rotavac platform: live oral monovalent human-bovine natural reassortant (116E) doses: 3 vs placebo	57 VE (%) = cases prevented follow-up: first year of life	meta-analysis GRADE: moderate 1 trial	Bergman et al. 2021 Cochrane Database Syst Rev quote Infants vaccinated and followed up for the first year of life In high-mortality countries, Rotavac prevented 57% of severe rotavirus diarrhoea cases (6799 participants, 1 trial; moderate-certainty evidence), and 16% of severe all-cause diarrhoea cases (6799 participants, 1 trial; moderate-certainty evidence). abstract, MAIN RESULTS The same sentence gives 16% against severe all-cause diarrhoea (moderate certainty).
Severe all-cause diarrhoea severity: severe case definition: Severe diarrhoea of any cause as defined in the included trial	infants vaccinated and followed up for the first year of life country: high-mortality countries (India) setting: high under-5 mortality, LMIC n: 6799 participants Infant <1y	Rotavac platform: live oral monovalent human-bovine natural reassortant (116E) doses: 3 vs placebo	16 VE (%) = cases prevented follow-up: first year of life	meta-analysis GRADE: moderate 1 trial	Bergman et al. 2021 Cochrane Database Syst Rev quote Infants vaccinated and followed up for the first year of life In high-mortality countries, Rotavac prevented 57% of severe rotavirus diarrhoea cases (6799 participants, 1 trial; moderate-certainty evidence), and 16% of severe all-cause diarrhoea cases (6799 participants, 1 trial; moderate-certainty evidence). abstract, MAIN RESULTS Single-trial all-cause estimate.
Severe rotavirus diarrhoea severity: severe case definition: Severe rotavirus diarrhoea as defined in the included trial	children vaccinated in infancy and followed up for two years country: high-mortality countries (India) setting: high under-5 mortality, LMIC n: 6541 participants Infant <1y1-4y	Rotavac platform: live oral monovalent human-bovine natural reassortant (116E) doses: 3 vs placebo	54 VE (%) = cases prevented follow-up: two years	meta-analysis GRADE: moderate 1 trial	Bergman et al. 2021 Cochrane Database Syst Rev quote Children vaccinated and followed up for two years In high-mortality countries, Rotavac prevented 54% of severe rotavirus diarrhoea cases (6541 participants, 1 trial; moderate-certainty evidence); no Rotavac studies have reported on severe all-cause diarrhoea at two-years follow-up. abstract, MAIN RESULTS No Rotavac study reported severe all-cause diarrhoea at two years.
Laboratory-confirmed rotavirus severity: as reported (mostly medically attended) case definition: Laboratory-confirmed rotavirus as the endpoint in observational post-licensure studies	children younger than 12 months country: low-mortality countries (31 studies in this stratum overall) setting: low under-5 mortality Infant <1y	Rotarix platform: live attenuated oral monovalent doses: as reported (full series) vs test-negative or unvaccinated controls as in the included studies	86 (81–90) VE (%)	meta-analysis random-effects regression over 60 studies from 32 countries	Burnett et al. 2020 Lancet Glob Health quote Rotarix vaccine effectiveness against laboratory-confirmed rotavirus among children younger than 12 months old was 86% (95% CI 81-90) in low-mortality countries, 77% (66-85) in medium-mortality countries, and 63% (54-70) in high-mortality countries. abstract, FINDINGS The same sentence gives 77% (66-85) in medium-mortality and 63% (54-70) in high-mortality countries for under-12-month-olds.
Laboratory-confirmed rotavirus severity: as reported (mostly medically attended) case definition: Laboratory-confirmed rotavirus in observational post-licensure studies	children younger than 12 months country: high-mortality countries (21 studies in this stratum overall) setting: high under-5 mortality, LMIC Infant <1y	Rotarix platform: live attenuated oral monovalent doses: as reported (full series) vs test-negative or unvaccinated controls as in the included studies	63 (54–70) VE (%)	meta-analysis	Burnett et al. 2020 Lancet Glob Health quote Rotarix vaccine effectiveness against laboratory-confirmed rotavirus among children younger than 12 months old was 86% (95% CI 81-90) in low-mortality countries, 77% (66-85) in medium-mortality countries, and 63% (54-70) in high-mortality countries. abstract, FINDINGS Real-world effectiveness in high-mortality countries, close to the Cochrane first-year trial efficacy in the same stratum.
Laboratory-confirmed rotavirus severity: as reported (mostly medically attended) case definition: Laboratory-confirmed rotavirus in observational post-licensure studies	children aged 12-23 months country: low-mortality countries setting: low under-5 mortality 1-4y	Rotarix platform: live attenuated oral monovalent doses: as reported (full series) time since vaccination: second year of life vs test-negative or unvaccinated controls as in the included studies	86 (81–90) VE (%)	meta-analysis	Burnett et al. 2020 Lancet Glob Health quote Rotarix vaccine effectiveness among children aged 12-23 months was 86% (81-90) in low-mortality countries, 54% (23-73) in medium-mortality countries, and 58% (38-72) in high-mortality countries. abstract, FINDINGS No waning in the second year of life in low-mortality countries: identical to the under-12-month estimate.
Laboratory-confirmed rotavirus severity: as reported (mostly medically attended) case definition: Laboratory-confirmed rotavirus in observational post-licensure studies	children aged 12-23 months country: medium-mortality countries setting: medium under-5 mortality 1-4y	Rotarix platform: live attenuated oral monovalent doses: as reported (full series) time since vaccination: second year of life vs test-negative or unvaccinated controls as in the included studies	54 (23–73) VE (%)	meta-analysis	Burnett et al. 2020 Lancet Glob Health quote Rotarix vaccine effectiveness among children aged 12-23 months was 86% (81-90) in low-mortality countries, 54% (23-73) in medium-mortality countries, and 58% (38-72) in high-mortality countries. abstract, FINDINGS Down from the under-12-month figure in the same stratum; the same sentence gives 58% (38-72) at 12-23 months in high-mortality countries.
Laboratory-confirmed rotavirus severity: as reported (mostly medically attended) case definition: Laboratory-confirmed rotavirus in observational post-licensure studies	children aged 12-23 months country: high-mortality countries setting: high under-5 mortality, LMIC 1-4y	Rotarix platform: live attenuated oral monovalent doses: as reported (full series) time since vaccination: second year of life vs test-negative or unvaccinated controls as in the included studies	58 (38–72) VE (%)	meta-analysis	Burnett et al. 2020 Lancet Glob Health quote Rotarix vaccine effectiveness among children aged 12-23 months was 86% (81-90) in low-mortality countries, 54% (23-73) in medium-mortality countries, and 58% (38-72) in high-mortality countries. abstract, FINDINGS Pooled second-year effectiveness in high-mortality countries; individual studies such as Malawi show much lower point estimates with wide intervals.
Laboratory-confirmed rotavirus severity: as reported (mostly medically attended) case definition: Laboratory-confirmed rotavirus in observational post-licensure studies	children younger than 12 months country: low-mortality countries setting: low under-5 mortality Infant <1y	RotaTeq platform: live oral pentavalent reassortant doses: as reported (full series) vs test-negative or unvaccinated controls as in the included studies	86 (76–92) VE (%)	meta-analysis	Burnett et al. 2020 Lancet Glob Health quote RotaTeq vaccine effectiveness among children younger than 12 months was 86% (76-92) in low-mortality countries and 66% (51-76) in high-mortality countries. abstract, FINDINGS The same sentence gives 66% (51-76) in high-mortality countries for RotaTeq under 12 months.
Laboratory-confirmed rotavirus severity: as reported (mostly medically attended) case definition: Laboratory-confirmed rotavirus in observational post-licensure studies	children younger than 12 months country: high-mortality countries setting: high under-5 mortality, LMIC Infant <1y	RotaTeq platform: live oral pentavalent reassortant doses: as reported (full series) vs test-negative or unvaccinated controls as in the included studies	66 (51–76) VE (%)	meta-analysis	Burnett et al. 2020 Lancet Glob Health quote RotaTeq vaccine effectiveness among children younger than 12 months was 86% (76-92) in low-mortality countries and 66% (51-76) in high-mortality countries. abstract, FINDINGS Real-world RotaTeq effectiveness in high-mortality settings, above its pooled trial efficacy there.
Laboratory-confirmed rotavirus severity: as reported (mostly medically attended) case definition: Laboratory-confirmed rotavirus in observational post-licensure studies	children aged 12-23 months country: low-mortality countries setting: low under-5 mortality 1-4y	RotaTeq platform: live oral pentavalent reassortant doses: as reported (full series) time since vaccination: second year of life vs test-negative or unvaccinated controls as in the included studies	84 (79–89) VE (%)	meta-analysis	Burnett et al. 2020 Lancet Glob Health quote RotaTeq vaccine effectiveness among children aged 12-23 months was 84% (79-89) in low-mortality countries. abstract, FINDINGS No RotaTeq 12-23-month pooled estimate for medium- or high-mortality countries is given.
Rotavirus disease under routine use severity: as reported case definition: Rotavirus disease as defined in 48 post-licensure studies from 24 countries	children in post-licensure studies, mostly under 2-3 years country: 24 countries, stratified by child mortality Infant <1y1-4y	Rotarix (RV1) platform: live attenuated oral monovalent doses: as reported vs as in the included studies	57 median VE (%), high-mortality countries	systematic review	Jonesteller et al. 2017 Clin Infect Dis quote 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. abstract The same sentence gives medians of 84% in low- and 75% in medium-mortality countries for RV1, and 90% and 45% for RV5 in low- and high-mortality countries. Medians across studies, no pooled interval.
Rotavirus disease under routine use severity: as reported case definition: Rotavirus disease as defined in 48 post-licensure studies from 24 countries	children in post-licensure studies, mostly under 2-3 years country: 24 countries, stratified by child mortality Infant <1y1-4y	RotaTeq (RV5) platform: live oral pentavalent reassortant doses: as reported vs as in the included studies	45 median VE (%), high-mortality countries	systematic review	Jonesteller et al. 2017 Clin Infect Dis quote 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. abstract Lowest median in the review. The review also notes a partial series gave considerable but lower protection, VE tended to decline in the second year in medium- and high-mortality settings, and VE was greater against more severe disease.
Rotavirus disease caused by homotypic strains severity: as reported strain: homotypic (fully matched to vaccine) case definition: Strain-specific effectiveness from post-licensure studies, strains classified by antigen matching to the vaccine	children in post-licensure studies country: high-income countries Infant <1y1-4y	Rotarix (RV1) platform: live attenuated oral monovalent doses: as reported vs as in the included studies	94 (80–98) VE (%)	meta-analysis	Leshem et al. 2014 Lancet Infect Dis quote FINDINGS: In high-income countries, RV1 pooled vaccine effectiveness was 94% (95% CI 80-98) against homotypic strains, 71% (39-86) against partly heterotypic strains, and 87% (76-93) against fully heterotypic strains. abstract, FINDINGS The same sentence gives 71% (39-86) against partly heterotypic and 87% (76-93) against fully heterotypic strains in high-income countries; no significant difference between strain groups.
Rotavirus disease caused by fully heterotypic strains severity: as reported strain: fully heterotypic (no antigen match to vaccine) case definition: Strain-specific effectiveness from post-licensure studies	children in post-licensure studies country: high-income countries Infant <1y1-4y	Rotarix (RV1) platform: live attenuated oral monovalent doses: as reported vs as in the included studies	87 (76–93) VE (%)	meta-analysis	Leshem et al. 2014 Lancet Infect Dis quote FINDINGS: In high-income countries, RV1 pooled vaccine effectiveness was 94% (95% CI 80-98) against homotypic strains, 71% (39-86) against partly heterotypic strains, and 87% (76-93) against fully heterotypic strains. abstract, FINDINGS Heterotypic protection from the monovalent vaccine is nearly as high as homotypic in high-income settings.
Rotavirus disease caused by fully heterotypic strains severity: as reported strain: fully heterotypic (no antigen match to vaccine) case definition: Strain-specific effectiveness from post-licensure studies	children in post-licensure studies country: middle-income countries Infant <1y1-4y	Rotarix (RV1) platform: live attenuated oral monovalent doses: as reported vs as in the included studies	47 (28–61) VE (%)	meta-analysis	Leshem et al. 2014 Lancet Infect Dis quote In middle-income settings, respective pooled data were 59% (36-73), 72% (58-81), and 47% (28-61). abstract, FINDINGS Homotypic 59% (36-73) and partly heterotypic 72% (58-81) in the same sentence; all lower than in high-income countries and not significantly different from each other.
Rotavirus disease caused by homotypic strains severity: as reported strain: homotypic (fully matched to vaccine) case definition: Strain-specific effectiveness from post-licensure studies	children in post-licensure studies country: high-income countries Infant <1y1-4y	RotaTeq (RV5) platform: live oral pentavalent reassortant doses: as reported vs as in the included studies	83 (78–87) VE (%)	meta-analysis	Leshem et al. 2014 Lancet Infect Dis quote In high-income countries, RV5 vaccine effectiveness was 83% (78-87) against homotypic strains, 82% (70-89) against single-antigen vaccine type strains, 82% (70-89) against partly heterotypic strains, and 75% (47-88) against single-antigen non-vaccine type strains. abstract, FINDINGS The same sentence gives 82% (70-89) for partly heterotypic and 75% (47-88) for single-antigen non-vaccine-type strains.
Rotavirus disease caused by partly heterotypic strains severity: as reported strain: partly heterotypic case definition: Strain-specific effectiveness from post-licensure studies	children in post-licensure studies country: middle-income countries Infant <1y1-4y	RotaTeq (RV5) platform: live oral pentavalent reassortant doses: as reported vs as in the included studies	37 (10–56) VE (%)	meta-analysis	Leshem et al. 2014 Lancet Infect Dis quote In middle-income settings, RV5 vaccine effectiveness was 70% (58-78) against single-antigen vaccine type strains, 37% (10-56) against partly heterotypic strains, and 87% (38-97) against single-antigen non-vaccine type strains. abstract, FINDINGS The lowest strain-specific estimate in the review; single-antigen vaccine-type strains gave 70% (58-78) and single-antigen non-vaccine-type 87% (38-97) in the same sentence, so the pattern is not a simple homotypic advantage.
Rotavirus hospitalisations after vaccine introduction severity: hospitalisation case definition: Relative reduction in rotavirus hospitalisations with at least 12 months of data before and after introduction	children <5 years old country: 49 countries setting: national and sentinel programmes period: studies published 2006-2019 Infant <1y1-4y	Rotarix or RotaTeq national programmes platform: live oral doses: national schedule vs pre-introduction period	59 median relative reduction (%)	systematic review	Burnett et al. 2020 J Infect Dis quote Among children <5 years old, there was a median reduction of 59% (IQR, 46-74) in rotavirus hospitalizations, 36% (IQR, 23-47) in AGE hospitalizations, and 36% (IQR, 28-46) AGE mortality. abstract, RESULTS Interquartile range in the quote, not a confidence interval. The same sentence gives 36% for all-cause AGE hospitalisations and 36% for AGE mortality; reductions were larger with low child mortality, younger age and higher coverage.
Acute gastroenteritis deaths after vaccine introduction severity: death case definition: Relative reduction in all-cause AGE mortality with at least 12 months of data before and after introduction	children <5 years old country: 49 countries setting: national programmes period: studies published 2006-2019 Infant <1y1-4y	Rotarix or RotaTeq national programmes platform: live oral doses: national schedule vs pre-introduction period	36 median relative reduction in AGE mortality (%)	systematic review	Burnett et al. 2020 J Infect Dis quote Among children <5 years old, there was a median reduction of 59% (IQR, 46-74) in rotavirus hospitalizations, 36% (IQR, 23-47) in AGE hospitalizations, and 36% (IQR, 28-46) AGE mortality. abstract, RESULTS Ecological before/after comparisons; secular declines in diarrhoea mortality can contribute. The Latin America record with control countries addresses that partly.
Rotavirus AGE hospitalisations and ED visits after vaccine introduction severity: hospitalisation or ED visit case definition: Relative reduction with at least 12 months of pre- and post-introduction surveillance	children <5 years of age country: 27 countries setting: national and sentinel programmes period: first 10 years since licensure Infant <1y1-4y	Rotarix or RotaTeq national programmes platform: live oral doses: national schedule vs pre-introduction period	67 median relative reduction (%)	systematic review	Burnett et al. 2017 J Infect Dis quote 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. abstract By child mortality stratum the medians were 71% (low), 59% (medium) and 60% (high) in the same sentence; all-cause AGE hospitalisations fell by a smaller median.
Severe rotavirus gastroenteritis in children under one year (herd effect) severity: severe case definition: Herd immunity effect on rotavirus-specific severe gastroenteritis estimated from pre/post studies published 2008-2014	children less than one year of age country: mostly United States (four of five studies) Infant <1y	Rotarix or RotaTeq programmes platform: live oral doses: national schedule vs expected rates without indirect protection	22 median herd effect (%)	meta-analysis	Pollard et al. 2015 Vaccine quote RESULTS: In studies reporting a rotavirus-specific GE outcome, four of five of which were conducted in the United States, the median herd effect across all study years was 22% [19-25%]. abstract, RESULTS The bracketed 19-25% in the quote is a range across study years, not a confidence interval. Latin American all-cause studies gave a similar median herd effect.
Rotavirus hospitalisations averted by routine vaccination severity: hospitalisation case definition: Claims-based estimate of average annual rotavirus hospitalisations averted among commercially insured US children	children younger than age 5 years country: United States setting: commercially insured claims data period: 2007-2011 Infant <1y1-4y	RotaTeq and Rotarix routine programme platform: live oral doses: routine series vs expected pre-vaccine rates	45,000 average annual hospitalisations averted (count)	expert body	cdc.gov quote An evaluation of claims data of commercially insured children estimated that an average annual 280,000 clinic visits, 62,000 emergency department visits, and 45,000 hospitalizations for rotavirus disease were averted among U.S. children younger than age 5 years during 2007–2011 by routine vaccination. Pink Book chapter 19, Epidemiology / Disease burden Commercially insured children only. The same sentence gives 280,000 clinic visits and 62,000 ED visits averted per year.
Hospitalisation or emergency department visit for G1-G4 rotavirus gastroenteritis severity: hospitalisation or ED visit strain: G1-G4 case definition: Hospitalisations and ED visits related to G1-G4 rotavirus gastroenteritis occurring 14 or more days after the third dose	healthy infants approximately 6 to 12 weeks old at first dose country: multinational (REST), mainly United States and Finland n: 68,038 infants Infant <1y1-4y	RotaTeq (RV5) platform: live oral pentavalent human-bovine (WC3) reassortant doses: 3 schedule: 4-to-10-week intervals vs placebo	94.5 (91.2–96.6) VE (%)	RCT	Vesikari et al. 2006 N Engl J Med quote The vaccine reduced hospitalizations and emergency department visits related to G1-G4 rotavirus gastroenteritis occurring 14 or more days after the third dose by 94.5 percent (95 percent confidence interval, 91.2 to 96.6 percent). abstract, RESULTS The Rotavirus Efficacy and Safety Trial, the licensure trial for RotaTeq in high-income settings.
Rotavirus gastroenteritis of any severity severity: any strain: G1-G4 case definition: Any G1-G4 rotavirus gastroenteritis through the first full rotavirus season after vaccination, nested substudy	healthy infants approximately 6 to 12 weeks old at first dose country: multinational (REST), nested efficacy substudy Infant <1y1-4y	RotaTeq (RV5) platform: live oral pentavalent human-bovine (WC3) reassortant doses: 3 vs placebo	74.0 (66.8–79.9) VE (%) follow-up: first full rotavirus season	RCT	Vesikari et al. 2006 N Engl J Med quote In a nested substudy, efficacy against any G1-G4 rotavirus gastroenteritis through the first full rotavirus season after vaccination was 74.0 percent (95 percent confidence interval, 66.8 to 79.9 percent); efficacy against severe gastroenteritis was 98.0 percent (95 percent confidence interval, 88.3 to 100 percent). abstract, RESULTS Efficacy against any rotavirus gastroenteritis is well below efficacy against severe disease (next record); the vaccine mainly prevents severe illness.
Severe G1-G4 rotavirus gastroenteritis severity: severe strain: G1-G4 case definition: Severe rotavirus gastroenteritis through the first full rotavirus season, nested substudy	healthy infants approximately 6 to 12 weeks old at first dose country: multinational (REST), nested efficacy substudy Infant <1y1-4y	RotaTeq (RV5) platform: live oral pentavalent human-bovine (WC3) reassortant doses: 3 vs placebo	98.0 (88.3–100) VE (%) follow-up: first full rotavirus season	RCT	Vesikari et al. 2006 N Engl J Med quote In a nested substudy, efficacy against any G1-G4 rotavirus gastroenteritis through the first full rotavirus season after vaccination was 74.0 percent (95 percent confidence interval, 66.8 to 79.9 percent); efficacy against severe gastroenteritis was 98.0 percent (95 percent confidence interval, 88.3 to 100 percent). abstract, RESULTS Upper bound reaches 100 because few severe cases occurred in the vaccine arm.
Clinic visits for G1-G4 rotavirus gastroenteritis severity: outpatient visit strain: G1-G4 case definition: Office or clinic visits for G1-G4 rotavirus gastroenteritis	healthy infants approximately 6 to 12 weeks old at first dose country: multinational (REST) Infant <1y1-4y	RotaTeq (RV5) platform: live oral pentavalent human-bovine (WC3) reassortant doses: 3 vs placebo	86.0 (73.9–92.5) VE (%)	RCT	Vesikari et al. 2006 N Engl J Med quote The vaccine reduced clinic visits for G1-G4 rotavirus gastroenteritis by 86.0 percent (95 percent confidence interval, 73.9 to 92.5 percent). abstract, RESULTS Health-care utilisation endpoint from the large REST cohort.
Severe rotavirus gastroenteritis and rotavirus-associated hospitalisation severity: severe and hospitalisation strain: G1P[8] vaccine strain era case definition: Severe gastroenteritis identified by active surveillance and graded on the 20-point Vesikari scale	healthy infants dosed at approximately two and four months of age country: 11 Latin American countries and Finland n: 20,169 infants in the efficacy subgroup Infant <1y	Rotarix (RIX4414) platform: live attenuated oral monovalent G1P[8] human rotavirus doses: 2 schedule: about 2 and 4 months of age vs placebo	85 VE (%) follow-up: to age 1 year	RCT	Ruiz-Palacios et al. 2006 N Engl J Med quote RESULTS: The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent (P<0.001 for the comparison with placebo) and reached 100 percent against more severe rotavirus gastroenteritis. abstract, RESULTS The pivotal Rotarix trial. The abstract gives P<0.001 but no confidence interval. The same sentence reports 100 percent efficacy against more severe disease.
Hospitalisation for diarrhoea of any cause severity: hospitalisation case definition: All-cause diarrhoea hospitalisation under active surveillance	healthy infants dosed at approximately two and four months of age country: 11 Latin American countries and Finland n: 63,225 infants Infant <1y	Rotarix (RIX4414) platform: live attenuated oral monovalent G1P[8] human rotavirus doses: 2 vs placebo	42 (29–53) VE (%) follow-up: to age 1 year	RCT	Ruiz-Palacios et al. 2006 N Engl J Med quote Hospitalization for diarrhea of any cause was reduced by 42 percent (95 percent confidence interval, 29 to 53 percent; P<0.001). abstract, RESULTS All-cause outcome: roughly two in five diarrhoea admissions prevented in the first year.
Severe rotavirus gastroenteritis over the first 2 years of life severity: severe case definition: Vesikari-graded severe rotavirus gastroenteritis from 2 weeks after dose two to about 2 years of age, according-to-protocol	infants aged 6-13 weeks at enrolment, followed to about 2 years country: ten Latin American countries n: 14,286 infants in the according-to-protocol analysis Infant <1y1-4y	Rotarix (RIX4414) platform: live attenuated oral monovalent G1P[8] human rotavirus doses: 2 vs placebo	80.5 (71.3–87.1) VE (%) follow-up: about 2 years	RCT	Linhares et al. 2008 Lancet quote Fewer cases (p<0.0001) of severe rotavirus gastroenteritis were recorded for the combined 2-year period in the RIX4414 group (32 [0.4%] of 7205; 95% CI 0.3-0.6) than in the placebo group (161 [2.3%] of 7081; 1.9-2.6), resulting in a vaccine efficacy of 80.5% (71.3-87.1) to 82.1% (64.6-91.9) against wild-type G1, 77.5% (64.7-86.2) against pooled non-G1 strains, and 80.5% (67.9-88.8) against pooled non-G1 P[8] strains. abstract, FINDINGS Two-year follow-up of the Latin American arm of the pivotal trial. The same sentence gives strain-specific estimates (next records).
Severe rotavirus gastroenteritis caused by wild-type G1 severity: severe strain: G1 (homotypic to vaccine) case definition: Vesikari-graded severe rotavirus gastroenteritis, genotype by RT-PCR	infants aged 6-13 weeks at enrolment, followed to about 2 years country: ten Latin American countries Infant <1y1-4y	Rotarix (RIX4414) platform: live attenuated oral monovalent G1P[8] human rotavirus doses: 2 vs placebo	82.1 (64.6–91.9) VE (%) follow-up: about 2 years	RCT	Linhares et al. 2008 Lancet quote Fewer cases (p<0.0001) of severe rotavirus gastroenteritis were recorded for the combined 2-year period in the RIX4414 group (32 [0.4%] of 7205; 95% CI 0.3-0.6) than in the placebo group (161 [2.3%] of 7081; 1.9-2.6), resulting in a vaccine efficacy of 80.5% (71.3-87.1) to 82.1% (64.6-91.9) against wild-type G1, 77.5% (64.7-86.2) against pooled non-G1 strains, and 80.5% (67.9-88.8) against pooled non-G1 P[8] strains. abstract, FINDINGS Homotypic strain estimate for the two-year period.
Severe rotavirus gastroenteritis caused by non-G1 strains severity: severe strain: pooled non-G1 strains (heterotypic) case definition: Vesikari-graded severe rotavirus gastroenteritis, genotype by RT-PCR	infants aged 6-13 weeks at enrolment, followed to about 2 years country: ten Latin American countries Infant <1y1-4y	Rotarix (RIX4414) platform: live attenuated oral monovalent G1P[8] human rotavirus doses: 2 vs placebo	77.5 (64.7–86.2) VE (%) follow-up: about 2 years	RCT	Linhares et al. 2008 Lancet quote Fewer cases (p<0.0001) of severe rotavirus gastroenteritis were recorded for the combined 2-year period in the RIX4414 group (32 [0.4%] of 7205; 95% CI 0.3-0.6) than in the placebo group (161 [2.3%] of 7081; 1.9-2.6), resulting in a vaccine efficacy of 80.5% (71.3-87.1) to 82.1% (64.6-91.9) against wild-type G1, 77.5% (64.7-86.2) against pooled non-G1 strains, and 80.5% (67.9-88.8) against pooled non-G1 P[8] strains. abstract, FINDINGS Heterotypic protection from a monovalent vaccine; the intervals for G1 and non-G1 overlap.
Hospital admission for rotavirus gastroenteritis severity: hospitalisation case definition: Hospital admission with rotavirus gastroenteritis over about 2 years	infants aged 6-13 weeks at enrolment, followed to about 2 years country: ten Latin American countries Infant <1y1-4y	Rotarix (RIX4414) platform: live attenuated oral monovalent G1P[8] human rotavirus doses: 2 vs placebo	83.0 (73.1–89.7) VE (%) follow-up: about 2 years	RCT	Linhares et al. 2008 Lancet quote Vaccine efficacy for hospital admission for rotavirus gastroenteritis was 83.0% (73.1-89.7) and for admission for diarrhoea of any cause was 39.3% (29.1-48.1). abstract, FINDINGS The same sentence gives 39.3% (29.1-48.1) against admission for diarrhoea of any cause.
Rotavirus gastroenteritis of any severity, first rotavirus season severity: any case definition: Any rotavirus gastroenteritis episode confirmed by ELISA from 2 weeks post-dose two to the end of the first rotavirus season	infants enrolled from six European countries, first season after vaccination country: six European countries n: 3874 infants in the according-to-protocol analysis Infant <1y	Rotarix (RIX4414) platform: live attenuated oral monovalent G1P[8] human rotavirus doses: 2 vs placebo	87.1 (79.6–92.1) VE (%) follow-up: first efficacy period, mean 5.7 months	RCT	Vesikari et al. 2007 Lancet quote During the first efficacy follow-up period (mean duration 5.7 months [SD 1.2]), 24 of 2572 infants allocated RIX4414 versus 94 of 1302 given placebo had rotavirus gastroenteritis episodes of any severity, resulting in a vaccine efficacy of 87.1% (95% CI 79.6-92.1; p<0.0001). abstract, FINDINGS Coadministered with routine childhood vaccines. The European efficacy trial.
Severe rotavirus gastroenteritis over two seasons severity: severe (Vesikari ≥11) case definition: Episodes scoring 11 or greater on the 20-point Vesikari scale during two consecutive rotavirus seasons	infants vaccinated in early infancy and followed through two rotavirus seasons country: six European countries Infant <1y1-4y	Rotarix (RIX4414) platform: live attenuated oral monovalent G1P[8] human rotavirus doses: 2 vs placebo	90.4 (85.1–94.1) VE (%) follow-up: combined period, mean 17 months	RCT	Vesikari et al. 2007 Lancet quote For the combined efficacy follow-up period, vaccine efficacy against severe rotavirus gastroenteritis was 90.4% (85.1-94.1; p<0.0001), for admission owing to rotavirus gastroenteritis 96.0% (83.8-99.5; p<0.0001), and for rotavirus-related medical attention 83.8% (76.8-88.9; p<0.0001), and significant protection against severe rotavirus gastroenteritis by circulating G1, G2, G3, G4, and G9 rotavirus types was shown. abstract, FINDINGS The same sentence gives 96.0% (83.8-99.5) against admission and 83.8% (76.8-88.9) against rotavirus-related medical attention.
Hospital admission for rotavirus gastroenteritis over two seasons severity: hospitalisation case definition: Admission owing to rotavirus gastroenteritis during two consecutive rotavirus seasons	infants vaccinated in early infancy and followed through two rotavirus seasons country: six European countries Infant <1y1-4y	Rotarix (RIX4414) platform: live attenuated oral monovalent G1P[8] human rotavirus doses: 2 vs placebo	96.0 (83.8–99.5) VE (%) follow-up: combined period, mean 17 months	RCT	Vesikari et al. 2007 Lancet quote For the combined efficacy follow-up period, vaccine efficacy against severe rotavirus gastroenteritis was 90.4% (85.1-94.1; p<0.0001), for admission owing to rotavirus gastroenteritis 96.0% (83.8-99.5; p<0.0001), and for rotavirus-related medical attention 83.8% (76.8-88.9; p<0.0001), and significant protection against severe rotavirus gastroenteritis by circulating G1, G2, G3, G4, and G9 rotavirus types was shown. abstract, FINDINGS Protection against admission was shown for circulating G1, G2, G3, G4 and G9 types in the same study.
Severe rotavirus gastroenteritis in the first year of life severity: severe case definition: Wild-type rotavirus gastroenteritis graded severe on the Vesikari scale, active follow-up	infants dosed at 6, 10 and 14 weeks, followed through the first year of life country: South Africa and Malawi setting: LMIC n: 4417 infants in the per-protocol analysis Infant <1y	Rotarix (RIX4414) platform: live attenuated oral monovalent G1P[8] human rotavirus doses: 2 or 3 (pooled) schedule: 6, 10 and 14 weeks vs placebo	61.2 (44.0–73.2) VE (%) follow-up: first year of life	RCT	Madhi et al. 2010 N Engl J Med quote Of the 4417 infants included in the per-protocol efficacy analysis, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% confidence interval, 44.0 to 73.2). abstract, RESULTS Pooled two- and three-dose arms. Country-specific estimates are the next record.
Severe rotavirus gastroenteritis in the first year of life, Malawi severity: severe case definition: Vesikari-graded severe rotavirus gastroenteritis, active follow-up	infants dosed at 6, 10 and 14 weeks, followed through the first year of life country: Malawi setting: LMIC, high mortality Infant <1y	Rotarix (RIX4414) platform: live attenuated oral monovalent G1P[8] human rotavirus doses: 2 or 3 (pooled) vs placebo	49.4 VE (%) follow-up: first year of life	RCT	Madhi et al. 2010 N Engl J Med quote Vaccine efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9%); however, the number of episodes of severe rotavirus gastroenteritis that were prevented was greater in Malawi than in South Africa (6. abstract, RESULTS South Africa in the same sentence was 76.9%. Despite lower efficacy, more cases were prevented in Malawi than in South Africa because baseline risk was higher; the next sentence of the abstract gives the cases prevented per hundred infants.
Severe gastroenteritis of any cause in the first year of life severity: severe case definition: All-cause severe gastroenteritis under active follow-up	infants dosed at 6, 10 and 14 weeks, followed through the first year of life country: South Africa and Malawi setting: LMIC Infant <1y	Rotarix (RIX4414) platform: live attenuated oral monovalent G1P[8] human rotavirus doses: 2 or 3 (pooled) vs placebo	30.2 VE (%) follow-up: first year of life	RCT	Madhi et al. 2010 N Engl J Med quote Efficacy against all-cause severe gastroenteritis was 30.2%. abstract, RESULTS No confidence interval in the abstract.
Severe rotavirus gastroenteritis over the first two years of life severity: severe case definition: Vesikari-graded severe rotavirus gastroenteritis, weekly home visits to 1 year then follow-up to 18-24 months	infants enrolled at 6 weeks and followed to 18-24 months of age country: Malawi setting: LMIC, high mortality n: 1513 in the pooled analysis Infant <1y1-4y	Rotarix (RIX4414) platform: live attenuated oral monovalent G1P[8] human rotavirus doses: 2 or 3 (pooled) vs placebo	38.1 (9.8–57.3) VE (%) follow-up: entire follow-up to 18-24 months	RCT	Cunliffe et al. 2012 Vaccine quote A total of 70/1030 (6.8%, 95% CI 5.3-8.5) subjects in the pooled (2 dose plus 3 dose) RIX4414 group compared with 53/483 (11.0%, 8.3-14.1) subjects in the placebo group developed severe rotavirus gastroenteritis in the entire follow-up period (vaccine efficacy 38.1% (9.8-57.3)). abstract Fewer than a fifth of circulating strains were the vaccine genotype G1P[8]; non-vaccine genotypes predominated.
Severe rotavirus gastroenteritis in the second year of life severity: severe case definition: Vesikari-graded severe rotavirus gastroenteritis during the second year of follow-up	children in the second year of life country: Malawi setting: LMIC, high mortality 1-4y	Rotarix (RIX4414) platform: live attenuated oral monovalent G1P[8] human rotavirus doses: 2 or 3 (pooled) time since vaccination: second year of life vs placebo	17.6 (-59.2–56.0) VE (%) follow-up: second year of life	RCT	Cunliffe et al. 2012 Vaccine quote The point estimate of efficacy in the second year of life (17.6%; -59.2 to 56.0) was lower than in the first year of life (49.4%; 19.2-68.3). abstract A point estimate near null with a wide interval, versus 49.4% (19.2-68.3) in the first year in the same sentence. The clearest waning signal from an RCT in a high-mortality setting.
Severe rotavirus gastroenteritis (Vesikari ≥11) severity: severe (Vesikari ≥11) case definition: Severe rotavirus gastroenteritis arising 14 days or more after the third dose to about 21 months of age, per protocol	infants dosed at about 6, 10 and 14 weeks, followed to around 21 months country: Bangladesh and Vietnam setting: rural Matlab and urban Nha Trang, LMIC n: 1969 infants in the per-protocol analysis Infant <1y1-4y	RotaTeq (RV5) platform: live oral pentavalent human-bovine reassortant doses: 3 schedule: 6, 10 and 14 weeks with oral poliovirus vaccine vs placebo	48.3 (22.3–66.1) VE (%) follow-up: median 498 days	RCT	Zaman et al. 2010 Lancet quote 38 cases of severe rotavirus gastroenteritis (Vesikari score >or=11) were reported during more than 1197 person-years of follow up in the vaccine group, compared with 71 cases in more than 1156 person years in the placebo group, resulting in a vaccine efficacy of 48.3% (95% CI 22.3-66.1) against severe disease (p=0.0005 for efficacy >0%) during nearly 2 years of follow-up. abstract, FINDINGS First RotaTeq efficacy trial in developing Asia; about half the efficacy seen in Europe and the United States.
Severe rotavirus gastroenteritis (Vesikari ≥11) severity: severe (Vesikari ≥11) case definition: Severe rotavirus gastroenteritis detected by enzyme immunoassay from 14 days after the third dose to around 21 months, per protocol	infants dosed at about 6, 10 and 14 weeks, followed to around 21 months country: Ghana, Kenya and Mali setting: rural Ghana and Kenya, urban Mali; LMIC, high mortality; HIV-infected infants not excluded n: 4705 infants in the per-protocol analysis Infant <1y1-4y	RotaTeq (RV5) platform: live oral pentavalent human-bovine reassortant doses: 3 schedule: 6, 10 and 14 weeks vs placebo	39.3 (19.1–54.7) VE (%) follow-up: median 527 days	RCT	Armah et al. 2010 Lancet quote 79 cases of severe rotavirus gastroenteritis were reported in 2610.6 person-years in the vaccine group, compared with 129 cases in 2585.9 person-years in the placebo group, resulting in a vaccine efficacy against severe rotavirus gastroenteritis of 39.3% (95% CI 19.1-54.7, p=0.0003 for efficacy >0%). abstract, FINDINGS The lowest pivotal-trial efficacy for RotaTeq; the Mali site contributed an unreliable first-year estimate (see the Mali records).
Rotavirus gastroenteritis of any severity, first year of life severity: any case definition: Rotavirus gastroenteritis of any severity through the first year of life, post hoc	infants dosed at approximately 6, 10 and 14 weeks, through the first year of life country: Ghana, Kenya and Mali setting: LMIC, high mortality Infant <1y	RotaTeq (RV5) platform: live oral pentavalent human-bovine reassortant doses: 3 vs placebo	49.2 (29.9–63.5) VE (%) follow-up: first year of life	RCT	Tapia et al. 2012 Vaccine quote VE against RVGE of any severity was 49.2% (95%CI: 29.9, 63.5) through the first year of life and 30.5% (95%CI: 16.7, 42.2) through the complete follow-up period. abstract The same sentence gives 30.5% (16.7-42.2) through the complete follow-up period, so protection against any-severity disease fell in year two.
Severe gastroenteritis of any aetiology, first year of life severity: severe case definition: Severe gastroenteritis of any cause through the first year of life, post hoc	infants dosed at approximately 6, 10 and 14 weeks, through the first year of life country: Ghana, Kenya and Mali setting: LMIC, high mortality Infant <1y	RotaTeq (RV5) platform: live oral pentavalent human-bovine reassortant doses: 3 vs placebo	21.5 (–38.4) VE (%) follow-up: first year of life	RCT	Tapia et al. 2012 Vaccine quote VE against severe-gastroenteritis of any etiology was 21.5% (95%CI: <0, 38.4) through the first year of life and 10.6% (95%CI: <0, 24.9) through the complete follow-up period. abstract The lower confidence bound is printed as "<0" in the source, so only the upper bound is recorded; the interval includes zero. Through complete follow-up the figure was 10.6% (<0, 24.9).
Severe rotavirus gastroenteritis caused by vaccine-contained G and P types severity: severe strain: G1-G4, P1A[8] (vaccine-contained) case definition: Severe RVGE caused by G1-G4, P1A[8] strains through complete follow-up	infants dosed at approximately 6, 10 and 14 weeks, followed nearly 2 years country: Ghana, Kenya and Mali setting: LMIC, high mortality Infant <1y1-4y	RotaTeq (RV5) platform: live oral pentavalent human-bovine reassortant doses: 3 vs placebo	34.0 (11.2–51.2) VE (%) follow-up: complete follow-up, nearly 2 years	RCT	Tapia et al. 2012 Vaccine quote Through the complete follow-up period, VE against severe-RVGE caused by (i) vaccine-contained G and P types (G1-G4, P1A[8]), (ii) non-vaccine G types (G8, G9, G10), and (iii) non-vaccine P types (P1B[4], P2A[6]) was 34.0% (95%CI:11.2, 51.2), 81.8% (95%CI:16.5, 98.0) and 40.7% (95%CI:8.4, 62.1), respectively. abstract The same sentence gives 81.8% (16.5-98.0) against non-vaccine G types and 40.7% (8.4-62.1) against non-vaccine P types: in Africa protection was not confined to vaccine genotypes, with small numbers.
Severe rotavirus gastroenteritis, first year of follow-up, Mali site severity: severe (Vesikari ≥11) case definition: Severe RVGE (Vesikari ≥11) from 14 days after dose 3 through the first year, per protocol	infants dosed at approximately 6, 10 and 14 weeks, first year of follow-up country: Mali setting: urban Bamako, LMIC, high mortality n: 1960 infants enrolled at the Mali site Infant <1y	RotaTeq (RV5) platform: live oral pentavalent human-bovine reassortant doses: 3 vs placebo	1 (-431.7–81.6) VE (%) follow-up: first year	RCT	Sow et al. 2012 Vaccine quote In the first year of follow-up, largely due to cultural practices to visit traditional healers as the first point of care, the point estimate of efficacy was unreliable: the per protocol vaccine efficacy against severe RVGE was 1% (95% confidence interval [CI]: -431.7, 81.6); the intention-to-treat vaccine efficacy was 42.9% (95% CI: -125.7, 87.7). abstract The authors call this point estimate unreliable: families visited traditional healers first, so cases were missed by surveillance. An essentially null, uninformative estimate recorded as reported.
Severe rotavirus gastroenteritis, second year of follow-up, Mali site severity: severe (Vesikari ≥11) case definition: Severe RVGE (Vesikari ≥11) during the second year after surveillance was adapted to local care-seeking	children in the second year of life country: Mali setting: urban Bamako, LMIC, high mortality 1-4y	RotaTeq (RV5) platform: live oral pentavalent human-bovine reassortant doses: 3 time since vaccination: second year of life vs placebo	19.2 VE (%) follow-up: second year	RCT	Sow et al. 2012 Vaccine quote During the second year of follow-up, after the surveillance system was modified to adapt to local customs and health care seeking practices, the point estimate of per-protocol vaccine efficacy was 19.2% (95% CI: -23.1,47.3%). abstract The source prints the interval as -23.1,47.3 with no space, which the number gate cannot parse, so the bounds are not recorded; the interval spans zero. Low and non-significant in the second year even after surveillance was improved. Not all vaccinees seroconverted; the abstract gives the seroresponse rate.
Severe rotavirus gastroenteritis (Vesikari ≥11) severity: severe (Vesikari ≥11) case definition: Severe rotavirus gastroenteritis (≥11 on the Vesikari scale) by active surveillance, per protocol	infants aged 6-7 weeks at first dose country: India (Delhi, Pune, Vellore) setting: low-resource urban and rural, LMIC n: 6541 infants in the per-protocol analysis Infant <1y	Rotavac (116E) platform: live oral monovalent human-bovine natural reassortant doses: 3 schedule: 6-7, 10 and 14 weeks vs placebo	53.6 (35.0–66.9) VE (%)	RCT	Bhandari et al. 2014 Lancet quote 71 events of severe rotavirus gastroenteritis were reported in 4752 person-years in infants in the vaccine group compared with 76 events in 2360 person-years in those in the placebo group; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0-66·9; p=0·0013) and 56·4% (36·6-70·1; p<0·0001) in the first year of life. abstract, FINDINGS The licensure trial for Rotavac. The same sentence gives 56.4% (36.6-70.1) in the first year of life and the number needed to immunise to prevent one severe episode.
Severe rotavirus gastroenteritis in the second year of life severity: severe (Vesikari ≥11) case definition: Severe rotavirus gastroenteritis (≥11 on the Vesikari scale), per protocol	children in the second year of life country: India setting: low-resource urban and rural, LMIC 1-4y	Rotavac (116E) platform: live oral monovalent human-bovine natural reassortant doses: 3 time since vaccination: second year of life vs placebo	48.9 (17.4–68.4) VE (%) follow-up: second year of life	RCT	Bhandari et al. 2014 Vaccine quote Vaccine efficacy against severe rotavirus gastroenteritis in children up to 2 years of age was 55.1% (95% CI 39.9 to 66.4; p<0.0001); vaccine efficacy in the second year of life of 48.9% (95% CI 17.4 to 68.4; p=0.0056) was only marginally less than in the first year of life [56.3% (95% CI 36.7 to 69.9; p<0.0001)]. abstract Only marginally below the first-year figure of 56.3% (36.7-69.9) in the same sentence, so unlike Malawi, no clear waning in India. Up to 2 years the overall efficacy was 55.1% (39.9-66.4).
Severe rotavirus gastroenteritis (Vesikari ≥11) severity: severe (Vesikari ≥11) case definition: First episode of laboratory-confirmed severe rotavirus gastroenteritis beginning 28 days after dose 3, per protocol	infants dosed at 6, 10 and 14 weeks country: Niger setting: LMIC, high mortality n: 3508 infants in the per-protocol analysis Infant <1y1-4y	Rotasiil (BRV-PV) platform: live oral bovine-human reassortant pentavalent, heat-stable doses: 3 schedule: 6, 10 and 14 weeks vs placebo	66.7 (49.9–77.9) VE (%)	RCT	Isanaka et al. 2017 N Engl J Med quote RESULTS: Among the 3508 infants who were included in the per-protocol efficacy analysis, there were 31 cases of severe rotavirus gastroenteritis in the vaccine group and 87 cases in the placebo group (2.14 and 6.44 cases per 100 person-years, respectively), for a vaccine efficacy of 66.7% (95% confidence interval [CI], 49.9 to 77.9). abstract, RESULTS Intention-to-treat efficacy was similar. Higher than the Rotasiil India trial, which the Cochrane pooled estimate averages across.
Severe rotavirus gastroenteritis to two years of age severity: severe case definition: Severe rotavirus gastroenteritis detected by home-visit surveillance until two years of age, per protocol	infants 6 to 8 weeks at first dose, followed to two years country: India (six sites) setting: LMIC n: 7500 infants randomised Infant <1y1-4y	Rotasiil (BRV-PV) platform: live oral bovine-human reassortant pentavalent, heat-stable doses: 3 schedule: 6, 10 and 14 weeks with routine vaccines vs placebo	39.5 (26.7–50) VE (%) follow-up: to two years of age	RCT	Kulkarni et al. 2017 Vaccine quote Vaccine efficacy over the entire follow-up period (until children reached two years of age) was 39.5% (95% CI 26.7, 50, p<0.0001) in the PP analysis and 38.8% (95% CI, 26.4, 49, p<0.0001) in the ITT analysis. abstract At the primary end-point the per-protocol efficacy was lower still. Lower than the same product in Niger.
Very severe rotavirus gastroenteritis (Vesikari ≥16) severity: very severe (Vesikari ≥16) case definition: Very severe rotavirus gastroenteritis, Vesikari score ≥16, per protocol, complete follow-up	infants 6 to 8 weeks at first dose, followed to two years country: India (six sites) setting: LMIC Infant <1y1-4y	Rotasiil (BRV-PV) platform: live oral bovine-human reassortant pentavalent, heat-stable doses: 3 vs placebo	54.7 (29.7–70.8) VE (%) follow-up: to two years of age	RCT	Kulkarni et al. 2017 Vaccine quote Vaccine efficacy against the very severe rotavirus cases (VSRVGE, Vesikari score≥16) was 60.5% (95% CI 17.7, 81, p=0.0131) at the time of the primary analysis and 54.7% (95% CI 29.7, 70.8, p=0.0004) for the complete follow-period in the PP population. abstract Efficacy rises with severity: higher against very severe disease than against severe disease in the same trial.
Rotavirus-associated inpatient visit severity: hospitalisation case definition: Laboratory-confirmed rotavirus among children seeking care for acute gastroenteritis at 7 US paediatric institutions	children younger than 5 years, median 21 months country: United States setting: inpatient and ED, 7 paediatric medical institutions period: November 2009 to June 2016 n: 1193 rotavirus-positive cases and 9620 rotavirus-negative controls Infant <1y1-4y	RotaTeq or Rotarix (any) platform: live oral doses: at least 1 vs rotavirus-negative acute gastroenteritis controls	82 (77–86) VE (%)	test-negative	Payne et al. 2019 JAMA Netw Open quote Among 1193 rotavirus-positive cases and 9620 rotavirus-negative controls, at least 1 dose of any rotavirus vaccine was 82% (95% CI, 77%-86%) protective against rotavirus-associated inpatient visits and 75% (95% CI, 71%-79%) protective against rotavirus-associated ED visits. abstract, RESULTS The same sentence gives 75% (71-79) against ED visits, so protection is stronger for the more severe care tier.
Rotavirus-associated inpatient or ED visit severity: inpatient or ED visit case definition: Laboratory-confirmed rotavirus among children seeking care for acute gastroenteritis	children younger than 5 years country: United States setting: inpatient and ED, 7 paediatric medical institutions period: 2009-2016 Infant <1y1-4y	RotaTeq (RV5) platform: live oral pentavalent reassortant doses: 3 vs rotavirus-negative acute gastroenteritis controls	81 (78–84) VE (%)	test-negative	Payne et al. 2019 JAMA Netw Open quote Vaccine effectiveness against inpatient and ED visits was 81% (95% CI, 78%-84%) for RV5 (3 doses) and 78% (95% CI, 72%-82%) for RV1 (2 doses) among the study population. abstract, RESULTS Full RV5 series; the same sentence gives 78% (72-82) for a full 2-dose RV1 series, with no significant difference between products over the 7 years.
Rotavirus-associated inpatient or ED visit severity: inpatient or ED visit case definition: Laboratory-confirmed rotavirus among children seeking care for acute gastroenteritis	children younger than 5 years country: United States setting: inpatient and ED, 7 paediatric medical institutions period: 2009-2016 Infant <1y1-4y	Rotarix (RV1) platform: live attenuated oral monovalent doses: 2 vs rotavirus-negative acute gastroenteritis controls	78 (72–82) VE (%)	test-negative	Payne et al. 2019 JAMA Netw Open quote Vaccine effectiveness against inpatient and ED visits was 81% (95% CI, 78%-84%) for RV5 (3 doses) and 78% (95% CI, 72%-82%) for RV1 (2 doses) among the study population. abstract, RESULTS Full RV1 series. A mixed course of both vaccines gave a similar estimate in the next sentence.
Severe rotavirus infection severity: severe case definition: Laboratory-confirmed rotavirus graded severe by clinical severity score	children younger than 5 years country: United States setting: inpatient and ED, 7 paediatric medical institutions period: 2009-2016 Infant <1y1-4y	RotaTeq or Rotarix (any) platform: live oral doses: any dose vs rotavirus-negative acute gastroenteritis controls	91 (85–95) VE (%)	test-negative	Payne et al. 2019 JAMA Netw Open quote Rotavirus patients who were not vaccinated had severe infections 4 times more often than those who were vaccinated (74 of 426 [17.4%] vs 28 of 605 [4.6%]; P < .001), and any dose of rotavirus vaccine was 65% (95% CI, 56%-73%) effective against mild infections, 81% (95% CI, 76%-84%) against moderate infections, and 91% (95% CI, 85%-95%) against severe infections. abstract, RESULTS Effectiveness rises with severity: 65% (56-73) against mild and 81% (76-84) against moderate infection in the same sentence. Unvaccinated rotavirus patients had severe infection four times as often (17.4% vs 4.6%).
Mild rotavirus infection severity: mild case definition: Laboratory-confirmed rotavirus graded mild by clinical severity score	children younger than 5 years country: United States setting: inpatient and ED, 7 paediatric medical institutions period: 2009-2016 Infant <1y1-4y	RotaTeq or Rotarix (any) platform: live oral doses: any dose vs rotavirus-negative acute gastroenteritis controls	65 (56–73) VE (%)	test-negative	Payne et al. 2019 JAMA Netw Open quote Rotavirus patients who were not vaccinated had severe infections 4 times more often than those who were vaccinated (74 of 426 [17.4%] vs 28 of 605 [4.6%]; P < .001), and any dose of rotavirus vaccine was 65% (95% CI, 56%-73%) effective against mild infections, 81% (95% CI, 76%-84%) against moderate infections, and 91% (95% CI, 85%-95%) against severe infections. abstract, RESULTS The lowest severity tier; vaccinated children who do get rotavirus mostly get mild disease.
Rotavirus acute gastroenteritis hospitalisation or ED visit severity: hospitalisation or ED visit case definition: Laboratory-confirmed rotavirus AGE in inpatient and ED settings in 3 US counties, matched case-control	age-eligible children under active surveillance, first 3 seasons after introduction country: United States setting: inpatient and ED, 3 counties period: January 2006 to June 2009 Infant <1y1-4y	RotaTeq (RV5) platform: live oral pentavalent reassortant doses: 1 vs rotavirus-negative AGE controls	74 (37–90) VE (%)	case-control	Staat et al. 2011 Pediatrics quote The VE of RV5 for 1, 2, and 3 doses against all rotavirus genotypes with the use of rotavirus-negative AGE controls was 74% (95% confidence interval [CI]: 37%-90%), 88% (95% CI: 66%-96%), and 87% (95% CI: 71%-94%), respectively, and with the use of ARI controls was 73% (95% CI: 43%-88%), 88% (95% CI: 68%-95%), and 85% (95% CI: 72%-91%), respectively. abstract, RESULTS Partial series of one dose. Two doses gave 88% (66-96) and three doses 87% (71-94) in the same sentence; the ARI-control analysis gave 73%, 88% and 85%.
Rotavirus acute gastroenteritis hospitalisation or ED visit severity: hospitalisation or ED visit case definition: Laboratory-confirmed rotavirus AGE in inpatient and ED settings in 3 US counties, matched case-control	age-eligible children under active surveillance, first 3 seasons after introduction country: United States setting: inpatient and ED, 3 counties period: January 2006 to June 2009 Infant <1y1-4y	RotaTeq (RV5) platform: live oral pentavalent reassortant doses: 2 vs rotavirus-negative AGE controls	88 (66–96) VE (%)	case-control	Staat et al. 2011 Pediatrics quote The VE of RV5 for 1, 2, and 3 doses against all rotavirus genotypes with the use of rotavirus-negative AGE controls was 74% (95% confidence interval [CI]: 37%-90%), 88% (95% CI: 66%-96%), and 87% (95% CI: 71%-94%), respectively, and with the use of ARI controls was 73% (95% CI: 43%-88%), 88% (95% CI: 68%-95%), and 85% (95% CI: 72%-91%), respectively. abstract, RESULTS Partial series of two doses, not distinguishable from the full three-dose series (87%, 71-94) in this study. Estimates were comparable in the first and second years of life.
Rotavirus gastroenteritis (medically attended) and hospitalisation severity: medically attended case definition: Confirmed rotavirus among children seeking medical care for gastroenteritis with a stool sample, test-negative design	children 3-59 months of age country: Spain (Navarre) setting: primary care and hospital period: January 2008 to June 2011 n: 756 cases and 6036 controls Infant <1y1-4y	RotaTeq or Rotarix (complete vaccination, pooled) platform: live oral doses: complete series vs rotavirus-negative gastroenteritis controls	78 (68–85) VE (%)	test-negative	Castilla et al. 2012 Vaccine quote The adjusted effectiveness of complete vaccination was 78% (95% CI: 68-85%) in preventing rotavirus gastroenteritis and 83% (95% CI: 65-93%) in preventing hospitalization for rotavirus gastroenteritis. abstract The same sentence gives 83% (65-93) against hospitalisation; no difference between the two vaccines was detected. Low uptake since the vaccines are not in the Spanish programme.
Rotavirus hospitalisation, first year of life severity: hospitalisation case definition: Rotavirus-positive diarrhoeal admissions versus test-negative controls in Blantyre	children in the first year of life country: Malawi setting: urban hospital, LMIC, high mortality period: 3 years after introduction in 2012 n: 241 rotavirus cases and 692 test-negative controls Infant <1y	Rotarix (RV1) platform: live attenuated oral monovalent doses: 2 time since vaccination: first year of life vs test-negative controls	70.6 (33.6–87.0) VE (%)	test-negative	Bar-Zeev et al. 2016 Clin Infect Dis quote Comparing 241 rotavirus cases with 692 test-negative controls, VE was 70.6% (95% CI, 33.6%-87.0%) and 31.7% (95% CI, -140.6% to 80.6%) in the first and second year of life, respectively, whereas mean age of rotavirus cases increased from 9.3 to 11.8 months. abstract, RESULTS First-year effectiveness under routine use in Malawi, higher than the trial efficacy there; the second year is the next record.
Rotavirus hospitalisation, second year of life severity: hospitalisation case definition: Rotavirus-positive diarrhoeal admissions versus test-negative controls in Blantyre	children in the second year of life country: Malawi setting: urban hospital, LMIC, high mortality period: 3 years after introduction in 2012 1-4y	Rotarix (RV1) platform: live attenuated oral monovalent doses: 2 time since vaccination: second year of life vs test-negative controls	31.7 (-140.6–80.6) VE (%)	test-negative	Bar-Zeev et al. 2016 Clin Infect Dis quote Comparing 241 rotavirus cases with 692 test-negative controls, VE was 70.6% (95% CI, 33.6%-87.0%) and 31.7% (95% CI, -140.6% to 80.6%) in the first and second year of life, respectively, whereas mean age of rotavirus cases increased from 9.3 to 11.8 months. abstract, RESULTS A low point estimate with an interval spanning null, mirroring the trial's second-year result. Population rotavirus admissions fell in infants but did not fall in older children.
Rotavirus hospitalisation among stunted children severity: hospitalisation case definition: Rotavirus-positive admissions versus test-negative controls, stratified by nutritional status	children under 5 years risk group: stunted children country: Malawi setting: urban hospital, LMIC, high mortality n: 205 stunted children Infant <1y1-4y	Rotarix (RV1) platform: live attenuated oral monovalent doses: 2 vs test-negative controls	27.8 (-99.5–73.9) VE (%)	test-negative	Bar-Zeev et al. 2016 Clin Infect Dis quote VE did not differ significantly by nutritional status (78.1% [95% CI, 5.6%-94.9%] in 257 well-nourished and 27.8% [95% CI, -99.5% to 73.9%] in 205 stunted children;P= .12), or by HIV exposure (60.5% [95% CI, 13.3%-82.0%] in 745 HIV-unexposed and 42.2% [95% CI, -106.9% to 83.8%] in 174 exposed children;P= .91). abstract, RESULTS Well-nourished children in the same sentence had 78.1% (5.6-94.9); the difference was not statistically significant (P = .12) and both intervals are wide.
Rotavirus hospitalisation among HIV-exposed children severity: hospitalisation case definition: Rotavirus-positive admissions versus test-negative controls, stratified by maternal HIV exposure	children under 5 years immune status: HIV-exposed (maternal HIV) country: Malawi setting: urban hospital, LMIC, high mortality n: 174 HIV-exposed children Infant <1y1-4y	Rotarix (RV1) platform: live attenuated oral monovalent doses: 2 vs test-negative controls	42.2 (-106.9–83.8) VE (%)	test-negative	Bar-Zeev et al. 2016 Clin Infect Dis quote VE did not differ significantly by nutritional status (78.1% [95% CI, 5.6%-94.9%] in 257 well-nourished and 27.8% [95% CI, -99.5% to 73.9%] in 205 stunted children;P= .12), or by HIV exposure (60.5% [95% CI, 13.3%-82.0%] in 745 HIV-unexposed and 42.2% [95% CI, -106.9% to 83.8%] in 174 exposed children;P= .91). abstract, RESULTS HIV-unexposed children in the same sentence had 60.5% (13.3-82.0); no significant difference by HIV exposure (P = .91), but the exposed-group interval is very wide.
First-ever seizure requiring hospitalisation or ED care severity: hospitalisation or ED visit case definition: Seizure hospitalisation or ED visit 4 to 55 weeks after the last rotavirus dose in the Vaccine Safety Datalink, Cox model adjusted for site, age at last dose, sex and calendar month	children in the year following infant vaccination country: United States setting: Vaccine Safety Datalink, 7 health care organisations period: born after 28 February 2006, enrolled to November 2009 n: 250 601 infants Infant <1y1-4y	RotaTeq or Rotarix (full course) platform: live oral doses: full course vs unvaccinated children	0.82 (.73–.91) RR, fully vaccinated vs unvaccinated follow-up: 4 to 55 weeks after last dose	cohort	Payne et al. 2014 Clin Infect Dis quote After adjusting for covariates (VSD site, age at last dose, sex, and calendar month of the index date), a statistically significant protective association was observed between a full course of rotavirus vaccination vs no vaccination for both first-ever seizures (risk ratio [RR] = 0.82; 95% confidence interval [CI], .73-.91) and all seizures (RR = 0.79; 95% CI, .71-.88). abstract, RESULTS A non-diarrhoeal benefit: rotavirus infection is linked to childhood seizures. The same sentence gives RR 0.79 (.71-.88) for all seizures. Observational, so unvaccinated children may differ in care-seeking. The bounds are printed without a leading zero in the source.
Laboratory-confirmed rotavirus infections, all ages severity: laboratory-confirmed infection case definition: Laboratory-confirmed rotavirus in national electronic records, age-specific incidence rate ratios versus pre-vaccine years	all age groups country: England setting: national laboratory surveillance period: each of the 5 years after introduction in July 2013 n: 206 389 laboratory-confirmed infections 2000-2018 All ages	Rotarix national programme platform: live attenuated oral monovalent doses: 2 vs pre-vaccine years	69-83 relative reduction (%), range across 5 post-vaccine years	surveillance	Gower et al. 2022 Clin Infect Dis quote Reductions of 69-83% in laboratory-confirmed rotavirus infections in all age groups and 77-88% in infants aged <1 year in each of the 5 postvaccine years are reported, with 11 386-11 633 cases averted annually. abstract, RESULTS The same sentence gives 77-88% in infants under 1 year. Reductions in all age groups, most of which are unvaccinated, show indirect protection.
All-cause gastroenteritis hospitalisations averted in unvaccinated age groups (indirect protection) severity: hospitalisation case definition: Share of averted all-cause AGE hospitalisations falling in age groups not eligible for vaccination, primarily older adults	unvaccinated age groups, primarily older adults vaccination status: unvaccinated country: England setting: national hospital records period: 5 years after introduction in July 2013 5-11y12-17y18-49y50-64y65+	Rotarix national infant programme platform: live attenuated oral monovalent doses: 2 (given to infants, not to this population) vs pre-vaccine years	at least 50% and up to 80% share of averted AGE hospitalisations in unvaccinated age groups (%)	surveillance	Gower et al. 2022 Clin Infect Dis quote There was strong evidence of indirect (herd) protection, with at least 50% and up to 80% of the non-specific end point of all-cause gastroenteritis (AGE) hospitalizations averted being in unvaccinated age-groups, primarily older adults. abstract, RESULTS Herd protection: the people benefiting here did not receive the vaccine. All-cause AGE hospitalisations fell across all age groups and most in under-1-year-olds.
All-cause diarrhoea deaths after vaccine introduction severity: death case definition: All-cause diarrhoea deaths from the PAHO mortality database, 2002-2009, in vaccine-adopter versus control countries	children under 5 years of age country: Brazil, El Salvador, Mexico and Nicaragua setting: national vital statistics period: 2006-2009 post-vaccination period Infant <1y1-4y	rotavirus vaccine national programmes introduced in 2006 platform: live oral doses: national schedule vs pre-vaccine trend and four control countries that had not introduced	1777 annual under-5 deaths avoided (count)	ecological	Paternina-Caicedo et al. 2015 Vaccine quote An estimatedtotal of 1777 of annual under-5 deaths were avoided in Brazil, El Salvador, Mexico, and Nicaragua during the post-vaccination period. abstract, RESULTS Time-trend analysis with contemporaneous control countries that showed no decline; Panama did not show a significant decrease. The source prints "estimatedtotal" without a space.

Vaccine safety and adverse events

Harms measured after vaccination against an unvaccinated or baseline comparator. Kept separate from post-acute sequelae, which follow the disease, not the vaccine.

Outcome (O)	Population (P)	Intervention / comparator	Estimate	Design (S)	Source
Intussusception within 21 days of the first dose (pooled) severity: intussusception case definition: Meta-analysis of SCCS studies using RV1 on a 2, 4 month schedule in England, Australia, Mexico, Brazil and Singapore	infants on a 2 and 4 month schedule country: England, Australia, Mexico, Brazil and Singapore Infant <1y	Rotarix (RV1) platform: live attenuated oral monovalent doses: 1 vs all other time in the same infants (self-controlled)	2.35 (1.45–3.8) pooled relative incidence, 21 days after dose 1 follow-up: 21 days after dose 1	meta-analysis	Stowe et al. 2016 Vaccine quote The RIs in a meta-analysis combing our results with Australia, Mexico, Brazil and Singapore using RV1, a 2, 4 month schedule and SCCS gave pooled RI estimates of 2.35 (1.45-3.8) and 1.77 (1.29-2.43) in the 21 day period after the 1st and 2nd doses, respectively. abstract, RESULTS The same sentence gives 1.77 (1.29-2.43) after the second dose.
Excess intussusception after rotavirus vaccination severity: intussusception case definition: CDC summary of US post-licensure evaluations of RV1 and RV5	vaccinated infants country: United States Infant <1y	RotaTeq (RV5) and Rotarix (RV1) platform: live oral doses: routine series vs background intussusception rate	1 per 20,000 to 100,000 excess cases per vaccinated infants	expert body	cdc.gov quote In the United States, the risk is estimated as 1 excess case of intussusception per 20,000 to 100,000 vaccinated infants. Pink Book chapter 19, Vaccine safety / Intussusception CDC's summary of the US risk; mostly in the first week after the first or second dose, possibly up to three weeks after dose one. A history of intussusception is a contraindication.
Intussusception within 42 days after any dose severity: intussusception case definition: Intussusception cases identified by active surveillance within 42 days after any dose	healthy infants approximately 6 to 12 weeks old at first dose country: multinational (REST) n: 34,035 vaccine and 34,003 placebo recipients Infant <1y	RotaTeq (RV5) platform: live oral pentavalent human-bovine (WC3) reassortant doses: 3 vs placebo	1.6 (0.4–6.4) RR vs placebo follow-up: 42 days after any dose	RCT	Vesikari et al. 2006 N Engl J Med quote Intussusception occurred in 12 vaccine recipients and 15 placebo recipients within one year after the first dose including six vaccine recipients and five placebo recipients within 42 days after any dose (relative risk, 1.6; 95 percent confidence interval, 0.4 to 6.4). abstract, RESULTS Six vaccine and five placebo cases. The trial was sized to exclude a risk like Rotashield's, not the much smaller risk later found in post-licensure studies.
Definite intussusception within 31 days after each dose severity: intussusception case definition: Definite intussusception during the 31-day window after each dose	healthy infants dosed at approximately two and four months of age country: 11 Latin American countries and Finland n: 63,225 infants Infant <1y	Rotarix (RIX4414) platform: live attenuated oral monovalent G1P[8] human rotavirus doses: 2 vs placebo	-0.32 (-2.91–2.18) risk difference per 10,000 infants vs placebo follow-up: 31 days after each dose	RCT	Ruiz-Palacios et al. 2006 N Engl J Med quote During the 31-day window after each dose, six vaccine recipients and seven placebo recipients had definite intussusception (difference in risk, -0.32 per 10,000 infants; 95 percent confidence interval, -2.91 to 2.18; P=0.78). abstract, RESULTS Six vaccine and seven placebo cases: no excess detected in the trial. Post-licensure SCCS and cohort studies with far more doses did detect a small excess (records below).
Intussusception admission within 1-21 days of the first dose severity: intussusception case definition: Confirmed intussusception admissions in infants aged 48-183 days from Hospital Episode Statistics, SCCS with age adjustment	infants aged 48-183 days country: England setting: national hospital records period: March 2013 to October 2014 n: 95 confirmed cases, 39 vaccinated 1-21 days before onset Infant <1y	Rotarix (RV1) platform: live attenuated oral monovalent doses: 1 vs all other time in the same infants (self-controlled)	4.53 (2.34–8.58) relative incidence, 1-21 days after dose 1 follow-up: 1-21 days after vaccination	SCCS	Stowe et al. 2016 Vaccine quote An increased relative incidence (RI) in this period was found, 4.53 (95% confidence interval 2.34-8.58) and 2.60 (1.43-4.81) respectively after the 1st and 2nd doses with an attributable risk of 1.91 and 1.49 per 100,000 doses respectively. abstract, RESULTS The same sentence gives RI 2.60 (1.43-4.81) after the second dose, with attributable risks of 1.91 and 1.49 per 100,000 doses. The authors estimate a few dozen vaccine-caused admissions a year in England against tens of thousands of gastroenteritis admissions prevented.
Intussusception admission within 1-7 days of the first dose severity: intussusception case definition: Confirmed intussusception admissions, SCCS	infants aged 48-183 days country: England setting: national hospital records period: March 2013 to October 2014 Infant <1y	Rotarix (RV1) platform: live attenuated oral monovalent doses: 1 vs all other time in the same infants (self-controlled)	13.81 (6.44–28.32) relative incidence, 1-7 days after dose 1 follow-up: 1-7 days after dose 1	SCCS	Stowe et al. 2016 Vaccine quote The peak risk was 1-7 days after the first dose, RI 13.81 (6.44-28.32), with an estimated 93% of the 15 cases being vaccine-attributable. abstract, RESULTS The highest-risk window; an estimated 93% of the 15 cases in it were vaccine-attributable. A large relative incidence on a small baseline rate.
Chart-confirmed intussusception within 7 days of monovalent vaccination severity: intussusception case definition: Chart-confirmed intussusception within 7 days after RV1 in the Vaccine Safety Datalink, compared with a concurrent RV5 cohort	infants between 4 and 34 weeks of age country: United States setting: Vaccine Safety Datalink, six integrated health care organisations period: April 2008 to March 2013 n: 207,955 RV1 doses; 1,301,810 RV5 doses Infant <1y	Rotarix (RV1) platform: live attenuated oral monovalent doses: 2 (both doses combined) vs concurrent infants receiving RotaTeq (RV5)	9.4 (1.4–103.8) RR, RV1 vs RV5 follow-up: 7 days after either dose	cohort	Weintraub et al. 2014 N Engl J Med quote The relative risk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination, as compared with the risk after pentavalent rotavirus vaccination, was 9.4 (95% confidence interval, 1.4 to 103.8). abstract, RESULTS Six cases observed against under one expected from historical rates; the abstract also gives an attributable risk per infants vaccinated. Very wide interval because of few events.
Excess intussusception after the first RotaTeq dose, 21-day window severity: intussusception case definition: Chart-confirmed intussusception in three US health plans (FDA Mini-Sentinel), self-controlled risk interval	infants 5.0 to 36.9 weeks of age country: United States setting: three US health plans, Mini-Sentinel period: 2004 to mid-2011 n: 507,874 first doses of RV5 Infant <1y	RotaTeq (RV5) platform: live oral pentavalent reassortant doses: 1 vs self-controlled risk interval in vaccinated infants	1.5 (0.2–3.2) attributable risk per 100,000 first-dose recipients (21-day window) follow-up: 21 days after dose 1	SCCS	Yih et al. 2014 N Engl J Med quote CONCLUSIONS: RV5 was associated with approximately 1.5 (95% CI, 0.2 to 3.2) excess cases of intussusception per 100,000 recipients of the first dose. abstract, CONCLUSIONS The 7-day window gave a slightly lower attributable risk. No significant increase after dose 2 or 3. RV1 analysis was underpowered; the secondary analysis suggested a risk after dose 2.
Intussusception within 1-7 days of the first Rotavac dose severity: intussusception case definition: Brighton level 1 intussusception at 27 Indian hospitals, SCCS in infants 28 to 365 days	infants 28 to 365 days of age country: India setting: 27 hospitals, active surveillance period: April 2016 to June 2019 n: 589 infants in the SCCS analysis Infant <1y	Rotavac platform: live oral monovalent human-bovine natural reassortant (116E) doses: 1 vs all other time in the same infants (self-controlled)	0.83 (0.00–3.00) relative incidence, 1-7 days after dose 1 follow-up: 1-7 days after dose 1	SCCS	Reddy et al. 2020 N Engl J Med quote The relative incidence of intussusception after the first dose was 0.83 (95% confidence interval [CI], 0.00 to 3.00) in the 1-to-7-day risk window and 0.35 (95% CI, 0.00 to 1.09) in the 8-to-21-day risk window. abstract, RESULTS No increased risk after any dose; the later window after dose 1 and all windows after doses 2 and 3 also had intervals including 1. A matched case-control analysis also found no increase.
Intussusception within 8-21 days of the third Rotavac dose severity: intussusception case definition: Brighton level 1 intussusception at 22 hospitals in 16 Indian states, SCCS	children aged 28-364 days at onset country: India setting: 22 hospitals, active surveillance period: April 2016 to September 2017 n: 52 vaccinated intussusception cases Infant <1y	Rotavac platform: live oral monovalent human-bovine natural reassortant (116E) doses: 3 vs all other time in the same infants (self-controlled)	2.52 (0.78–5.61) relative incidence, 8-21 days after dose 3 follow-up: 8-21 days after dose 3	SCCS	INCLEN 2021 Vaccine quote Similarly, no increased risk during 8-21 days after the dose 1 (zero cases observed), dose 2 (RI, 0.71 [95% CI, 0.0-3.28]) or dose 3 (RI, 2.52 [95% CI, 0.78-5.61]). abstract, RESULTS The highest point estimate in a small analysis; zero cases were observed within 21 days of dose 1 and the interval includes 1. Not an increased risk by the authors' reading.
Intussusception within 1-21 days of the first Rotarix dose severity: intussusception case definition: Brighton level 1 intussusception in children under 12 months at sentinel hospitals, SCCS with bootstrapped intervals	children <12 months, median 24 weeks at onset country: Afghanistan, Myanmar and Pakistan setting: sentinel hospitals, low-income n: 585 children Infant <1y	Rotarix platform: live attenuated oral monovalent doses: 1 vs all other time in the same infants (self-controlled)	1.28 (0.78–2.11) relative incidence, 1-21 days after dose 1 follow-up: 1-21 days after dose 1	SCCS	Burnett et al. 2023 Vaccine quote 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. abstract No increased risk in three low-income Asian countries, consistent with India and African networks and unlike England, Australia and the United States. The 1-21-day window after dose 2 gave 0.78 (0.53-1.16).
Type 1 diabetes from 8 months to 11 years of age severity: type 1 diabetes case definition: Type 1 diabetes identified by ICD codes in the Vaccine Safety Datalink, Cox model adjusted for demographics, birth characteristics and well-child visits	children followed from 8 months to 11 years, median 5.4 years country: United States setting: 7 health care organisations, Vaccine Safety Datalink period: born 2006-2014, followed to 2017 n: 386 937 children, 464 cases Infant <1y1-4y5-11y	RotaTeq or Rotarix (all recommended doses by 8 months) platform: live oral doses: full series vs children who received no rotavirus vaccine	1.03 (0.62–1.72) adjusted HR vs unvaccinated follow-up: median 5.4 years	cohort	Glanz et al. 2020 JAMA Pediatr quote Compared with children unexposed to rotavirus vaccination, the adjusted hazard ratio was 1.03 (95% CI, 0.62-1.72) for children fully exposed to rotavirus vaccination and 1.50 (95% CI, 0.81-2.77) for children partially exposed to rotavirus vaccination. abstract, RESULTS Null association: neither an increase nor the protective effect reported in some ecological studies. Partially vaccinated children had a higher but non-significant hazard ratio. Very few children were unvaccinated, so the comparison group is small and may differ in health care use.
Type 1 diabetes between 6 months and 5 years of age severity: type 1 diabetes case definition: Type 1 diabetes diagnosis in national registers, all children born in Norway 2007-2019	children from 6 months to 5 years country: Norway setting: national registers period: born 2007-2019 n: 740,744 children, 846 cases Infant <1y1-4y	rotavirus vaccine (Norwegian programme, introduced September 2014) platform: live oral doses: full series vs non-vaccinated children	1.17 (0.78–1.77) adjusted HR vs non-vaccinated follow-up: to 5 years of age	cohort	Östman et al. 2026 Diabetologia quote In a secondary analysis comparing fully vaccinated with non-vaccinated children, the adjusted HR was 1.17 (95% CI 0.78, 1.77). abstract, RESULTS No evidence of a reduced risk of type 1 diabetes after rotavirus vaccination. The interrupted time series showed a slight increasing trend that was not significant after excluding transition cohorts.

Gaps

No post-acute record is compiled: searches for long-term sequelae after rotavirus gastroenteritis (post-infectious syndromes, long-term follow-up) returned nothing usable, and the only candidate long-term outcome, type 1 diabetes, is studied as an association with vaccination rather than as a sequela of infection; those studies are filed under safety.
The WHO rotavirus position paper (WER 2021) could not be snapshotted: the who.int publication page returned 404 and two IRIS PDF handles returned an empty DSpace page, so the WHO recommendation text and its own burden summary are not quoted. The Cochrane review and CDC Pink Book stand in for the expert-body tier.
No rotavirus-specific case-fatality ratio among hospitalised rotavirus-confirmed children in LMICs was found in an abstract; the sentinel-network CFR compiled here is for all-cause hospitalised diarrhoea.
No pre-vaccine burden record was found for Europe in an abstract with usable numbers; the European burden review (PMID 16397431) surfaced in search but was not fetched.
Cochrane 2021 reports efficacy percentages without confidence intervals in its abstract, so the stratified Cochrane records carry no bounds; the trial records supply the intervals.
Cochrane 2021 states that RotaTeq probably makes little or no difference to severe all-cause diarrhoea in high-mortality countries in the first year, but gives no number, so that null finding has no record.
No efficacy record was found for infants of HIV-infected mothers or HIV-infected infants from an RCT abstract (search returned nothing); the Malawi case-control HIV-exposed estimate is the only special-population record.
Rotasiil has no real-world effectiveness record: the real-world meta-analysis excluded vaccines other than Rotarix and RotaTeq for lack of post-licensure data.

Flags for review

The WHO 2021 rotavirus position paper could not be reached (who.int 404; IRIS handles 10665/342841 and 10665/342909 returned empty pages). A reviewer should snapshot the correct WER PDF and add the WHO burden and recommendation sentences.
Three global mortality figures disagree by method and year: 453,000 (2008, hospital detection rates x diarrhoea deaths), 128 500 (GBD 2016 modelling) and 208 009 (2017-2018, PCR attributable fractions from sentinel sites). They must not be shown as a single trend line; label each with its method.
rotavirus-bur-022 reports higher odds of death among rotavirus-NEGATIVE hospitalised diarrhoea than rotavirus-positive. This is a surprising finding that will read as "rotavirus is less deadly than other diarrhoea"; it is conditional on hospital admission and does not speak to population mortality. Show it with that caveat or not at all.
The placebo-arm attack rates (rotavirus-bur-023 to 027) are per-protocol trial figures under active surveillance in specific countries; they are not national incidence rates and must not be multiplied by population counts.
US pre-vaccine burden records (bur-001 to 004) are CDC estimate ranges with no confidence intervals; the Pink Book and the 2009 MMWR give slightly different ED-visit figures ("more than 200,000" vs "205,000 to 272,000"), which is why the MMWR is used for ED visits.
Cochrane 2021 gives two textually identical sentences for RotaTeq in medium-mortality countries (year 1 and year 2 both 79%, 3863 participants, 1 trial). The compiler resolves them by anchoring on the preceding low-mortality sentence, so the quotes for those two records span two sentences joined by ' ... '.
Intussusception evidence splits by setting: SCCS and cohort studies in England, the United States and other high- and middle-income countries find a small excess risk after dose 1 (roughly 1-5 per 100,000), whereas SCCS studies in India and three low-income Asian countries find none. A page should show both and not pool them. Each is a relative incidence or attributable risk on a rare baseline; do not present the large relative incidences (e.g. 13.81) without the absolute attributable risk in the same sentence.
The programme-impact and herd-effect records (rotavirus-eff-080 to 087) are before/after or ecological comparisons, not individual-level effectiveness. They are filed as efficacy with comparator = pre-introduction period, and should be labelled as impact rather than VE on the page.
The type 1 diabetes records (rotavirus-saf-012, saf-013) are null findings filed as safety because they measure an outcome after vaccination; no record claims a protective effect, although some ecological studies (not compiled) report one. A reviewer may prefer to omit them from a safety section if the site reserves that section for harms.
Several efficacy records carry no confidence interval because the abstract gives none (Cochrane strata, Rotarix pivotal 85%, Madhi country-specific and all-cause figures, Jonesteller medians). Two sources print bounds in forms the number gate cannot accept ("-23.1,47.3" without a space in Sow 2012; "<0" in Tapia 2012), so those bounds are dropped and explained in notes rather than retyped.

Search log (33 searches)

rotavirus vaccines preventing rotavirus diarrhoea Cochrane · PubMed → Found PMID 34788488 (Bergman 2021 Cochrane, 60 trials); compiled as the stratified Cochrane efficacy records.
pentavalent human-bovine reassortant rotavirus vaccine safety efficacy trial REST · PubMed → Found PMID 16394299 (Vesikari 2006 NEJM REST); compiled as RotaTeq pivotal efficacy and intussusception records.
attenuated human rotavirus vaccine severe gastroenteritis Latin America Finland trial Ruiz-Palacios · PubMed → First query returned only a review; a second query (Ruiz-Palacios intussusception) found PMID 16394298 (Rotarix pivotal NEJM), PMID 18395579 (Linhares 2008 two-year Latin America) and PMID 20692031 (Zaman 2010 RotaTeq Asia).
rotavirus vaccine efficacy African infants randomized trial Malawi South Africa · PubMed → Found PMID 20107214 (Madhi 2010 NEJM) and PMID 22520135 (Cunliffe 2012 Malawi second year); compiled as efficacy and placebo-arm burden records.
rotavirus deaths children younger than 5 years global estimates · PubMed → Found PMID 22030330 (Tate 2012, 2008 estimate) and PMID 30105384 (Troeger 2018 GBD 2016); compiled as global mortality burden records.
rotavirus hospitalizations United States children prevaccine era burden · PubMed → Found PMID 32060546 (Staat 2020 NVSN 2006-2016); compiled as pre/post proportion records.
rotavirus disease burden United States children hospitalizations deaths before vaccine introduction · PubMed → Found PMID 21691244 (Esposito 2011 baseline diarrhoea mortality) and PMID 19847149 (CDC MMWR 2009); compiled as US burden records.
CDC Pink Book chapter 19 rotavirus · websource (cdc.gov) → Snapshotted as web_id cdc-gov-92e1fad9e8; used for US pre-vaccine burden, worldwide deaths and intussusception excess-risk records.
rotavirus vaccine intussusception self-controlled case series risk · PubMed → Found PMID 27286641 (Stowe 2016 England SCCS), PMID 33176083 (Reddy 2020 India NEJM), PMID 32972735 (INCLEN 2021), PMID 37884416 (Burnett 2023 Asia); compiled as safety records.
Bhandari oral rotavirus vaccine 116E efficacy Indian infants · PubMed → Found PMID 24629994 (Bhandari 2014 Lancet) and PMID 25091663 (second year); compiled as Rotavac efficacy records.
Isanaka bovine rotavirus pentavalent vaccine Niger efficacy · PubMed → Found PMID 28328346 (Isanaka 2017 NEJM); compiled as Rotasiil Niger efficacy and placebo-arm burden.
Kulkarni phase III bovine-human reassortant pentavalent rotavirus vaccine BRV-PV India efficacy · PubMed → Found PMID 28967523 (Kulkarni 2017); compiled as Rotasiil India efficacy records.
Burnett global impact rotavirus vaccination diarrhea hospitalizations deaths · PubMed → Found PMID 32095831 (Burnett 2020 JID) and PMID 28430997 (Burnett 2017 JID); compiled as impact records.
real-world effectiveness of rotavirus vaccines 2006-19 literature review meta-analysis · PubMed → Found PMID 32827481 (Burnett 2020 Lancet Glob Health); compiled as real-world VE by mortality stratum and age.
effectiveness of rotavirus vaccination systematic review first decade global postlicensure data · PubMed → Found PMID 28444323 (Jonesteller 2017); compiled as median VE records.
Payne association of rotavirus vaccination inpatient emergency department visits acute gastroenteritis 2010-2016 · PubMed → Found PMID 31560386 (Payne 2019 JAMA Netw Open); compiled as US VE by product, severity and setting.
Payne rotavirus vaccine effectiveness case-control United States partial series dose · PubMed → Found PMID 21768317 (Staat 2011 Pediatrics); compiled as dose-count VE records.
rotavirus vaccine effectiveness Malawi case-control second year of life Bar-Zeev · PubMed → Found PMID 27059359 (Bar-Zeev 2016); compiled as waning, stunting and HIV-exposure VE records.
Leshem distribution of rotavirus strains and strain-specific effectiveness of the rotavirus vaccine after introduction · PubMed → Found PMID 25082561 (Leshem 2014 Lancet Infect Dis); compiled as genotype-specific VE records.
Armah efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis infants developing countries sub-Saharan Africa · PubMed → Found PMID 20692030 (Armah 2010 Lancet); also PMID 22520141 (Tapia 2012 secondary endpoints) and PMID 22520140 (Sow 2012 Mali) from the Asia/Africa query; compiled as efficacy records.
Vesikari efficacy human rotavirus vaccine first 2 years of life European infants randomized · PubMed → Found PMID 18037080 (Vesikari 2007 Lancet); compiled as European Rotarix efficacy records.
rotavirus vaccine indirect protection older children adults hospitalizations decline · PubMed → Found PMID 34043765 (Gower 2022 England 5-year impact) and PMID 26116250 (Pollard 2015 herd effect meta-analysis); compiled as indirect-effect records.
rotavirus vaccine effectiveness child mortality diarrhea deaths reduction Mexico Brazil · PubMed → Found PMID 26116247 (Paternina-Caicedo 2015); compiled as a mortality-impact record.
rotavirus vaccination seizures reduction children cohort · PubMed → Found PMID 24265355 (Payne 2014 VSD seizures); compiled as efficacy against seizures.
Weintraub risk of intussusception after monovalent rotavirus vaccination; Yih intussusception risk after rotavirus vaccination U.S. infants · PubMed → Found PMID 24422678 (Weintraub 2014 VSD) and PMID 24422676 (Yih 2014 Mini-Sentinel); compiled as US intussusception safety records.
rotavirus vaccination type 1 diabetes incidence children · PubMed → Found PMID 32150236 (Glanz 2020 VSD cohort) and PMID 42663626 (Östman 2026 Norway); compiled as null safety records. PMID 31961393 (Burke 2020) has no abstract numbers and was not used.
rotavirus vaccine effectiveness Europe hospitalisation test-negative design · PubMed → Found PMID 22122860 (Castilla 2012 Navarre); compiled as European real-world VE.
rotavirus severe dehydration case fatality hospitalized children low-income country · PubMed → Found PMID 35797157 (Hartman 2023 WHO surveillance networks); compiled as CFR and risk-factor records.
rotavirus gastroenteritis seizures encephalopathy complications children extraintestinal · PubMed → Found PMID 29565992 (Karampatsas 2018 east London); compiled as hospitalisation and encephalopathy burden records.
rotavirus deaths children global LMIC hospitalised diarrhoea aetiology surveillance network · PubMed → Found PMID 36660904 (Cohen 2022 Global Pediatric Diarrhea Surveillance); compiled as attributable-fraction and death records.
rotavirus gastroenteritis long-term sequelae post-infectious children follow-up · PubMed → Nothing usable returned; recorded as a gap (no post-acute records).
Rotavirus vaccines WHO position paper 2021 · PubMed and websource (who.int, iris.who.int) → PubMed returned only Chinese expert-consensus papers; the who.int publication page returned 404 and two IRIS PDF URLs returned empty pages. Recorded as a gap and flag.
rotavirus vaccine efficacy HIV-infected infants South Africa Steele · PubMed → Nothing returned; recorded as a gap.