Impact of a twelve-year rotavirus vaccine program on acute diarrhea mortality and hospitalization in Brazil: 2006-2018.

BACKGROUND: Monitoring the impact of vaccine programs is necessary to identify changes in vaccine efficacy. We report the impact of the 12-year rotavirus vaccine program on diarrhea mortality and hospitalizations and their correlation to socioeconomic indicators. METHODS: this ecological study describes diarrhea hospitalizations and deaths from 2006 to 2018 in Brazil and correlates rotavirus vaccine coverage, hospitalizations and deaths to socioeconomic indicators and social vulnerability index (SVI) by state and region. Hospitalizations, deaths, and vaccine coverage trends were analyzed using Joinpoint regression models. Associations between hospitalizations, mortality and rotavirus vaccination coverage and socioeconomic and SVI indicators were established using Ordinary Least Square regressions. RESULTS: Rotavirus vaccine coverage remained stable between 2006 and 2018 (annual percentage changes (APC) [95%CI]: 4.4% [-0.3%, 9.2%]). Diarrhea hospitalization rates decreased 52.5% (-5.7% [-7.5%, -3.8%]), from 68.4 to 32.5 hospitalizations per 10,000 children <5 years-old between 2006 and 2018, with significant decreases in diarrhea mortality (-9.8% [-11.2%, -8.5%]). The Northeast region experienced the largest reductions (-13.9% [-15.7%, -12.2%]). Vaccination coverage and diarrhea-mortality were inversely correlated with the SVI. CONCLUSION: The burden of childhood diarrhea has decreased over an extended period. States with high SVI, but high vaccination coverage had the largest reductions in hospitalizations and deaths.

Effects of geographic and economic heterogeneity on the burden of rotavirus diarrhea and the impact and cost-effectiveness of vaccination in Nigeria.

Child mortality from rotavirus gastroenteritis remains high in Nigeria, representing 14% of all rotavirus deaths worldwide. Here, we examine the potential impact and cost-effectiveness of national rotavirus vaccine introduction in geographic and economic subpopulations of Nigeria. We projected the health and economic outcomes of rotavirus vaccination in children over the first five years of life using a spreadsheet-based model. We modeled child populations using national survey data on rotavirus mortality risk factors and vaccination coverage to predict burden and impact across regional and wealth quintile subpopulations within Nigeria. Our base case considered introduction of a general rotavirus vaccine, modeled to encompass characteristics of existing vaccines, versus no vaccine. Base case costs were estimated from the government perspective, assuming Gavi subsidies, over the first five years. We also present estimates from the cost of vaccination from the perspective of Gavi. We explored uncertainty in model parameters through probabilistic uncertainty, one-way sensitivity, and scenario analyses. According to our estimates, rotavirus enteritis was responsible for 47,898 [95% Uncertainty Limits: 35,361; 63,703] child deaths per year, with approximately 80% of the national burden concentrated in the three northern regions of Nigeria. Rotavirus vaccination was estimated to prevent 6,454 [3,960; 9,721] deaths, 13% [9%; 18%] of the national annual RV burden. National ICERs for rotavirus vaccination from the Nigerian government and Gavi perspectives were US$47 [$18; $105] and $62 [$29; $130] per DALY averted, respectively. General rotavirus vaccination was projected to reduce rotavirus mortality by only 6% [4%; 9%] in the North West region compared to 35% [24%; 47%] in the South East region. Base case ICERs ranged from US$25 [10; 56] per DALY averted in North West to US$64 [18; 157] per DALY averted in South South. Gavi perspective ICERs ranged from US$33 [$15; $68] in North West to US$88 [35; 191] per DALY averted in South South. According to one-way sensitivity analyses, ICERs were most sensitive to vaccine efficacy, followed by estimated administrative costs and rotavirus mortality. Disparities in mortality reduction were largely driven by inequality in vaccination coverage across regions and between socioeconomic subpopulations. Due to high, persistent, and inequitable burden of rotavirus in Nigeria, routine vaccination with any of these rotavirus vaccines would be an high impact and cost-effective strategy in reducing child mortality.

Temporal decline in diarrhea episodes and mortality in Kiribati children two years following rotavirus vaccine introduction, despite high malnutrition rates: a retrospective review.

BACKGROUND: Kiribati introduced rotavirus vaccine in 2015. To estimate the impact of rotavirus vaccine on acute gastroenteritis (AGE) and severe acute malnutrition (SAM) among children under 5 in Kiribati, a retrospective review of inpatient and outpatient AGE and hospitalized SAM was undertaken. METHODS: Inpatient data for admissions and hospital deaths due to AGE, SAM and all-causes were collected for children under 5 from all hospitals on the main island, Tarawa, from January 2010-December 2013 (pre-rotavirus vaccine) and January 2016-September 2017 (post-rotavirus vaccine). National outpatient diarrhea data were collected from January 2010 to August 2017 for under 5. An interrupted time-series analysis was undertaken to estimate the effect of rotavirus vaccine on the rates of inpatient and outpatient AGE, inpatient SAM; and inpatient case fatality rates for AGE and SAM, were calculated pre- and post-rotavirus vaccine introduction. RESULTS: The incidence rate of AGE admissions from Tarawa and national AGE outpatient presentations significantly declined by 37 and 44%, respectively, 2 years following rotavirus vaccine introduction. There was a significant decline in the percentage of AGE contributing to all-cause under 5 admissions (12·8% vs. 7·2%, p < 0·001) and all-cause under-five mortality (15·9% vs. 5·7%, p = 0·006) pre- and post-rotavirus vaccine introduction. The estimated incidence rate of inpatient SAM decreased by 24% in under 5 s, 2 years following rotavirus vaccine introduction. CONCLUSIONS: AGE morbidity and mortality and hospitalized SAM rates have declined following rotavirus vaccine introduction in Kiribati children.

Impacto poblacional a 10 años de la vacunación contra rotavirus en México / Population impact of rotavirus vaccination in Mexico after 10 years

Resumen: Objetivo: Evaluar el impacto de la vacunación contra rotavirus (RV) a 10 años de su universalización sobre la morbimortalidad por enfermedad diarreica aguda (EDA) en niños mexicanos menores de cinco años. Material y métodos: Se compararon las medianas anuales de casos nuevos, defunciones y hospitalizaciones por EDA del periodo pre y posuniversalización; se calcularon reducciones absolutas y relativas, considerando significativos valores de p<0.05. Resultados: La mortalidad, hospitalizaciones y casos nuevos por EDA en menores de cinco años disminuyeron 52.6, 46 y 15.5% respectivamente, en el periodo posuniversalización. Durante la temporada de RV las reducciones en la mortalidad, hospitalizaciones y casos nuevos fueron de 66.9, 64.7 y 28.7%, respectivamente. Conclusiones: A partir de la universalización de la vacuna de RV en México, se aprecian reducciones importantes y sostenidas en la mortalidad, hospitalizaciones e incidencia por EDA, con menor impacto en esta última. El mayor impacto se observa durante la temporada de RV.

Abstract: Objective: To evaluate the impact of rotavirus (RV) vaccination after 10 years of it´s universalization on morbidity and mortality from Acute Diarrheal Disease (ADD) in mexican children under five years of age. Materials and methods: Annual median numbers for ADD new cases, hospitalizations and deaths were compared between pre and post universalization periods; absolute and relative reductions were calculated, considering p<0.05 values as significant. Results: Mortality, hospitalizations and new cases from ADD in children under five decreased 52.6, 46, and 15.5% respectively, in the posuniversalization period. During rotavirus seasons, reduction in mortality, hospitalizations and new cases was 66.9, 64.7, and 28.7% respectively. Conclusions: As of the universal introduction of RV vaccination in Mexico, significant and sustained reductions are appreciated for mortality and hospitalizations from ADD, less so for incidence. A most prominent effect is observed during the winter season.

[Population impact of rotavirus vaccination in Mexico after 10 years]. / Impacto poblacional a 10 años de la vacunación contra rotavirus en México.

OBJECTIVE: To evaluate the impact of rotavirus (RV) vaccination after 10 years of it´s universalization on morbidity and mortality from Acute Diarrheal Disease (ADD) in mexican children under five years of age. MATERIALS AND METHODS: Annual median numbers for ADD new cases, hospitalizations and deaths were compared between pre and post universalization periods; absolute and relative reductions were calculated, considering p<0.05 values as significant. RESULTS: Mortality, hospitalizations and new cases from ADD in children under five decreased 52.6, 46, and 15.5% respectively, in the posuniversalization period. During rotavirus seasons, reduction in mortality, hospitalizations and new cases was 66.9, 64.7, and 28.7% respectively. CONCLUSIONS: As of the universal introduction of RV vaccination in Mexico, significant and sustained reductions are appreciated for mortality and hospitalizations from ADD, less so for incidence. A most prominent effect is observed during the winter season.

OBJETIVO: Evaluar el impacto de la vacunación contra rotavirus (RV) a 10 años de su universalización sobre la morbimortalidad por enfermedad diarreica aguda (EDA) en niños mexicanos menores de cinco años. MATERIAL Y MÉTODOS: Se compararon las medianas anuales de casos nuevos, defunciones y hospitalizaciones por EDA del periodo pre y posuniversalización; se calcularon reducciones absolutas y relativas, considerando significativos valores de p<0.05. RESULTADOS: La mortalidad, hospitalizaciones y casos nuevos por EDA en menores de cinco años disminuyeron 52.6, 46 y 15.5% respectivamente, en el periodo posuniversalización. Durante la temporada de RV las reducciones en la mortalidad, hospitalizaciones y casos nuevos fueron de 66.9, 64.7 y 28.7%, respectivamente. CONCLUSIONES: A partir de la universaliza- ción de la vacuna de RV en México, se aprecian reducciones importantes y sostenidas en la mortalidad, hospitalizaciones e incidencia por EDA, con menor impacto en esta última. El mayor impacto se observa durante la temporada de RV.

Re-evaluating the potential impact and cost-effectiveness of rotavirus vaccination in 73 Gavi countries: a modelling study.

BACKGROUND: Previous studies have found rotavirus vaccination to be highly cost-effective in low-income countries. However, updated evidence is now available for several inputs (ie, rotavirus disease mortality rates, rotavirus age distributions, vaccine timeliness, and vaccine efficacy by duration of follow-up), new rotavirus vaccines have entered the market, vaccine prices have decreased, and cost-effectiveness thresholds have been re-examined. We aimed to provide updated cost-effectiveness estimates to inform national decisions about the new introduction and current use of rotavirus vaccines in Gavi countries. METHODS: We calculated the potential costs and effects of rotavirus vaccination for ten successive birth cohorts in 73 countries previously and currently eligible for Gavi support, compared with no vaccination. We used a deterministic cohort model to calculate numbers of rotavirus gastroenteritis cases, outpatient visits, hospitalisations, and deaths between birth and 5 years, with and without rotavirus vaccination. We calculated treatment costs from the government and societal perspectives. The primary outcome measure was the incremental cost-effectiveness ratio (discounted US$ per disability-adjusted life-year averted). Country-specific model input parameters were based on the scientific literature, published meta-analyses, and international databases. We ran deterministic and probabilistic uncertainty analyses. FINDINGS: Over the period 2018-27, rotavirus vaccination has the potential to prevent nearly 600 000 deaths in Gavi countries. Averted outpatient visits and hospitalisations could lead to treatment savings of approximately $484·1 million from the government perspective and $878·0 million from the societal perspective. The discounted dollars per disability-adjusted life-year averted has a very high probability (>90%) of being less than 0·5 times the gross domestic product per capita in 54 countries, and less than 1·0 times gross domestic product per capita in 63 countries. INTERPRETATION: Rotavirus vaccination continues to represent good value for money across most Gavi countries despite lower rotavirus mortality estimates and more stringent willingness-to-pay thresholds. FUNDING: Bill & Melinda Gates Foundation.

Burden of rotavirus infection in hospitalized elderly individuals prior to the introduction of rotavirus vaccination in Sweden.

BACKGROUND: Rotavirus gastroenteritis (GE) in the elderly has been much less studied than in children. OBJECTIVES: The aim of this study was to determine the morbidity and mortality for elderly hospitalized patients with rotavirus GE prior to the introduction of rotavirus vaccination in Sweden, and to investigate the epidemiology of rotavirus genotypes in these patients. STUDY DESIGN: All patients 60 years or older who were hospitalized at Sahlgrenska University Hospital, Gothenburg, Sweden, and were rotavirus positive in a clinical diagnostic test from 2009 to 2016, were included. Medical records were reviewed and rotavirus genotyping real-time PCR was performed. RESULTS: One hundred and fifty-nine patients were included, corresponding to an annual incidence of hospitalization due to rotavirus GE of 16/100 000 inhabitants aged 60 years or older. G2P[4] was the most common genotype, followed by G1P[8] and G4P[8]. The majority of patients had community-onset of symptoms and no or few pre-existing health disorders. Four patients (2.5%) died within 30 days of sampling. Patients with hospital-onset rotavirus GE had a longer median length of stay following diagnosis compared with patients with community-onset of symptoms (19 vs. 5 days, p = 0.001) and higher 30-day mortality (8.6% (3/35) vs. < 1% (1/124), p = 0.03). CONCLUSIONS: Hospitalization due to rotavirus GE among the elderly seems to mainly affect otherwise healthy individuals and is associated with low 30-day mortality.

Efficacy of live oral rotavirus vaccines by duration of follow-up: a meta-regression of randomised controlled trials.

BACKGROUND: The duration of protection offered by rotavirus vaccines varies across the world, and this variation is important to understanding and predicting the effects of the vaccines. There is now a large body of evidence on the efficacy of live oral rotavirus vaccines in different settings, but these data have never been synthesised to obtain robust estimates of efficacy by duration of follow-up. Our aim is to estimate the efficacy of live oral rotavirus vaccines at each point during follow-up and by mortality stratum. METHODS: In our meta-regression study, we identified all randomised controlled trials of rotavirus vaccines published until April 4, 2018, using the results of a Cochrane systematic review, and cross checked these studies against those identified by another systematic review. We excluded trials that were based on special populations, trials without an infant schedule, and trials without clear reporting of numbers of enrolled infants and events in different periods of follow-up. For all reported periods of follow-up, we extracted the mean duration of follow-up (time since administration of the final dose of rotavirus vaccination), the number of enrolled infants, and case counts for rotavirus-positive severe gastroenteritis in both non-vaccinated and vaccinated groups. We used a Bayesian hierarchical Poisson meta-regression model to estimate the pooled cumulative vaccine efficacy (VE) and its waning with time for three mortality strata. We then converted these VE estimates into instantaneous VE (iVE). FINDINGS: In settings with low mortality (15 observations), iVE pooled for infant schedules of Rotarix and RotaTeq was 98% (95% credibility interval 93-100) 2 weeks following the final dose of vaccination and 94% (87-98) after 12 months. In medium-mortality settings (11 observations), equivalent estimates were 82% (74-92) after 2 weeks and 77% (67-84) after 12 months. In settings with high mortality (24 observations), there were five different vaccines with observation points for infant schedules. The pooled iVE was 66% (48-81) after 2 weeks of follow-up and 44% (27-59) after 12 months. INTERPRETATION: Rotavirus vaccine efficacy is lower and wanes more rapidly in high-mortality settings than in low-mortality settings, but the earlier peak age of disease in high-mortality settings means that live oral rotavirus vaccines are still likely to provide substantial benefit. FUNDING: Bill & Melinda Gates Foundation.

Rotavirus vaccine impact assessment surveillance in India: protocol and methods.

INTRODUCTION: Rotavirus infection accounts for 39% of under-five diarrhoeal deaths globally and 22% of these deaths occur in India. Introduction of rotavirus vaccine in a national immunisation programme is considered to be the most effective intervention in preventing severe rotavirus disease. In 2016, India introduced an indigenous rotavirus vaccine (Rotavac) into the Universal Immunisation Programme in a phased manner. This paper describes the protocol for surveillance to monitor the performance of rotavirus vaccine following its introduction into the routine childhood immunisation programme. METHODS: An active surveillance system was established to identify acute gastroenteritis cases among children less than 5 years of age. For all children enrolled at sentinel sites, case reporting forms are completed and a copy of vaccination record and a stool specimen obtained. The forms and specimens are sent to the referral laboratory for data entry, analysis, testing and storage. Data from sentinel sites in states that have introduced rotavirus vaccine into their routine immunisation schedule will be used to determine rotavirus vaccine impact and effectiveness. ETHICS AND DISSEMINATION: The Institutional Review Board of Christian Medical College, Vellore, and all the site institutional ethics committees approved the project. Results will be disseminated in peer-reviewed journals and with stakeholders of the universal immunisation programme in India.

Risk factors for death among children 0-59 months of age with moderate-to-severe diarrhea in Manhiça district, southern Mozambique.

BACKGROUND: Despite major improvements in child survival rates, the number of deaths due to diarrhea remains unacceptably high. We aimed to describe diarrhea-associated mortality and evaluate risk factors for death among Mozambican children with moderate-to-severe diarrhea (MSD). METHODS: Between December 2007 and November 2012, children under-five with MSD were enrolled in Manhiça district, as part of the Global Enteric Multicenter study (GEMS). Clinical, epidemiological, and socio-demographic characteristics were collected. Anthropometric measurements were performed and stool samples collected upon recruitment. A follow-up visit ~ 60 days post-enrolment was conducted and verbal autopsies performed in all death cases. RESULTS: Of the 916 MSD-cases analyzed; 90% (821/916) completed 60 days follow-up and 69 patients died. The case fatality rate at follow-up was 8% (69/821), and the mortality rate 10.2 (95%CI: 7.75-13.59) deaths per 1000 persons-week at risk. Nearly half of the deaths 48% (33/69) among study participants clustered within 2 weeks of the onset of diarrhea. Typical enteropathogenic Escherichia coli (typical EPEC) and Cryptosporidium were the two pathogens associated to an increased risk of death in the univariate analysis with (HR = 4.16, p = 0.0461) and (H = 2.84, p = 0.0001) respectively. Conversely, Rotavirus infection was associated to a decreased risk of death (HR = 0.52, p = 0.0198). According to the multivariate analysis, risk factors for death included co-morbidities such as malnutrition (HR = 4.13, p <  0.0001), pneumonia/lower respiratory infection (HR = 3.51, p <  0.0001) or invasive bacterial disease (IBD) (HR = 6.80, p = 0.0009), presenting on arrival with lethargy or overt unconsciousness (HR = 1.73, p = 0.0302) or wrinkled skin (HR = 1.71, p = 0.0393), and cryptosporidium infection (HR = 2.14, p = 0.0038). When restricting the analysis to those with available HIV results (n = 191, 22% of the total study sample), HIV was shown to be a significant risk factor for death (HR = 5.05, p = 0.0009). Verbal autopsies were conducted in 100% of study deaths, and highlighted diarrhea as the main underlying cause of death 39%, (27/69); followed by HIV/AIDS related deaths 29.0% (20/69) and sepsis 11.6% (8/69). CONCLUSION: Preventive strategies targeting Cryptosporidium, malnutrition and early identification and treatment of associated co-morbidities could contribute to the prevention of the majority of diarrhea associated deaths in Mozambican children.

Talk to Patients About: Rotavirus.

Rotavirus is a highly contagious viral infection that inflames the lining of the stomach and intestines, and especially affects children 2 years old and younger. In the United States, the introduction of a vaccine in 2006 helped arrest rotavirus illnesses and deaths.

Rates of hospitalization and death for all-cause and rotavirus acute gastroenteritis before rotavirus vaccine introduction in Kenya, 2010-2013.

BACKGROUND: Rotavirus vaccine was introduced in Kenya immunization program in July 2014. Pre-vaccine disease burden estimates are important for assessing vaccine impact. METHODS: Children with acute gastroenteritis (AGE) (≥3 loose stools and/or ≥ 1 episode of unexplained vomiting followed by loose stool within a 24-h period), hospitalized in Siaya County Referral Hospital (SCRH) from January 2010 through December 2013 were enrolled. Stool specimens were tested for rotavirus (RV) using an enzyme immunoassay (EIA). Hospitalization rates were calculated using person-years of observation (PYO) from the Health Demographic Surveillance System (HDSS) as a denominator, while adjusting for healthcare utilization at household level and proportion of stool specimen collected from patients who met the case definition at the surveillance hospital. Mortality rates were calculated using PYO as the denominator and number of deaths estimated using total deaths in the HDSS, proportion of deaths attributed to diarrhoea by verbal autopsy (VA) and percent positive for rotavirus AGE (RVAGE) hospitalizations. RESULTS: Of 7760 all-cause hospitalizations among children < 5 years of age, 3793 (49%) were included in the analysis. Of these, 21% (805) had AGE; RV was detected in 143 (26%) of 541 stools tested. Among children < 5 years, the estimated hospitalization rates per 100,000 PYO for AGE and RVAGE were 2413 and 429, respectively. Mortality rate associated with AGE and RVAGE were 176 and 45 per 100,000 PYO, respectively. CONCLUSION: AGE and RVAGE caused substantial health care burden (hospitalizations and deaths) before rotavirus vaccine introduction in Kenya.

Effects of geographic and economic heterogeneity on the burden of rotavirus diarrhea and the impact and cost-effectiveness of vaccination in Pakistan.

Globally, rotavirus is a leading cause of childhood diarrhea and related mortality. Although rotavirus vaccination has been introduced in many countries worldwide, there are numerous low- to middle-income countries that have not yet introduced. Pakistan is one of the countries with the highest number of rotavirus deaths in children under five years. Although rotavirus infection is almost universal among children, mortality is often a result of poor nutrition and lack of access to health care and other aspects of poverty. We assess the impact and cost-effectiveness of introducing childhood rotavirus vaccination in Pakistan. We use household data from the 2012-2013 Demographic Health survey in Pakistan to estimate heterogeneity in rotavirus mortality risk, vaccination benefits, and cost-effectiveness across geographic and economic groups. We estimate two-dose rotavirus vaccination coverage that would be distributed through a routine vaccination program. In addition, we estimate rotavirus mortality (burden), and other measures of vaccine cost-effectiveness and impact by subpopulations of children aggregated by region and economic status. Results indicate that the highest estimated regional rotavirus burden is in Sindh (3.3 rotavirus deaths/1000 births) and Balochistan (3.1 rotavirus deaths/1000 births), which also have the lowest estimated vaccination coverage, particularly for children living in the poorest households. In Pakistan, introduction could prevent 3061 deaths per year with current routine immunization patterns at an estimated $279/DALY averted. Increases in coverage to match the region with highest coverage (Islamabad) could prevent an additional 1648 deaths per year. Vaccination of children in the highest risk regions could result in a fourfold mortality reduction as compared to low risk children, and children in the poorest households have a three to four times greater mortality reduction benefit than the richest. Based on the analysis presented here, the benefits and cost-effectiveness of rotavirus vaccination can be maximized by reaching economically and geographically vulnerable children.

Effects of geographic and economic heterogeneity on rotavirus diarrhea burden and vaccination impact and cost-effectiveness in the Lao People's Democratic Republic.

Rotavirus enteritis is responsible for nearly 200,000 child deaths worldwide in 2015. Globally, many low- and middle-income countries have introduced rotavirus vaccine, resulting in documented reductions in hospitalizations and child mortality. We examined the potential impact and cost-effectiveness of introducing rotavirus vaccination in Lao People's Democratic Republic using an Excel-based spreadsheet model. We estimated mortality risk factors, patterns of care seeking, and vaccination access to predict outcomes for regional, provincial, and socioeconomic subpopulations for one birth cohort through their first five years of life and life course in Disability-Adjusted Life Years estimates. Socioeconomic status was defined by categorizing households into regional wealth quintiles based on a national asset index. We modeled a two-dose ROTARIX vaccine under current Gavi pricing and efficacy estimates from Bangladesh and Vietnam. DPT1 and DPT2 coverages were used to estimate rotavirus vaccination coverage. Probabilistic sensitivity analysis was used to assess the impact of uncertainty on model parameters on predicted incremental cost-effectiveness ratios (ICERs), including scenarios of increases in vaccination coverage. Rotavirus vaccination would prevent 143 child deaths/year, or 28% of annual rotavirus burden. The estimated national level ICER for rotavirus vaccination was $140/DALY, with regional socioeconomic subpopulation estimates ranging from $72/DALY for the poorest in the Central region to $353/DALY for the richest in the North region, indicating high cost-effectiveness. Within regions, ICERs are most favorable for children in the poorer and poorest quintiles. However, the full benefits of rotavirus vaccination will only be realized by reducing disparities in vaccination coverage, access to treatment, and environmental health. Improving vaccination coverage to equitable levels alone would prevent 87 additional child deaths per year.

Safety of a heat-stable rotavirus vaccine among children in Niger: Data from a phase 3, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Rotavirus remains a major cause of diarrhea among children under 5 years of age. The efficacy of RotaSIIL, a pentavalent rotavirus vaccine, was shown in an event-driven trial in Niger. We describe the two-year safety follow-up of this trial. METHODS: Follow-up of safety outcomes began upon administration of the first dose of RotaSIIL or placebo. Adverse events were followed until 28 days after the third dose, and serious adverse events were followed until 2 years of age. Suspected cases of intussusception were evaluated at first point of contact and then referred to hospital for surgical evaluation. Causes of death were obtained by chart review and verbal autopsy. Passive surveillance was carried out in health centers. Community health workers carried out active surveillance in villages. Between-group differences were evaluated using the chi-squared test and Fisher's exact test. RESULTS: A total of 4092 children were randomized, and 4086 received at least one dose of RotaSIIL or placebo, constituting the intention-to-treat population, who accrued a total of 7385 child-years of follow-up time. At two years of follow-up, 58 (2.8%) participants who received RotaSIIL and 49 (2.4%) participants who received placebo had died (p = 0.38). Most deaths were due to infectious causes common to the study area. One participant had confirmed intussusception, 542 days after receiving the third dose of RotaSIIL. A total of 395 (19.3%) participants receiving RotaSIIL and 419 (20.5%) participants receiving placebo experienced any serious adverse event (p = 0.36). Most serious adverse events were hospitalizations due to infection (malaria, lower respiratory tract infection and gastroenteritis) or marasmus. Overall, 1474 (72.1%) participants receiving RotaSIIL and 1456 (71.1%) participants receiving placebo had at least one adverse event (p = 0.49) in the follow-up period. CONCLUSIONS: At two years of follow-up, RotaSIIL was found to be safe. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02145000.

Impact of rotavirus vaccine on diarrheal hospitalization and outpatient consultations in the Philippines: First evidence from a middle-income Asian country.

BACKGROUND: Monovalent rotavirus (RV) vaccine was introduced in the Philippines in a phased manner beginning in 2012. To assess the impact of RV vaccine, we conducted a retrospective review of diarrheal admissions in two hospitals. METHODS: Records of physician-diagnosed diarrheal admissions were reviewed in D.O. Plaza Hospital (DOPH) from 2009 to 2016 in Agusan del Sur where RV vaccine was introduced in the immunization program; and in Cotabato Regional Medical Center (CRMC) from 2011 to 2016 in a region where the vaccine was not introduced. Reports from consultations in public health clinics in Agusan Del Sur and RV vaccine coverage were obtained. RESULTS: All-cause diarrheal admissions among children <5 years old in DOPH declined from 2013 to 2016 following RV vaccine introduction in 2012. Using the 2009-2011 mean number of hospitalizations as baseline (X‾ = 1,141), the reductions were 28% (n = 821), 56% (n = 507), 63% (n = 417) and 59% (n = 466) in 2013, 2014, 2015 and 2016, respectively. In comparison, no substantial declines in diarrheal hospitalizations were seen in CRMC from 2011 to 2016. A declining trend was also seen in outpatient consultations in Agusan del Sur following RV vaccine introduction with declines of 27% (n = 2,333), 33% (n = 2,143), 45% (n = 1,764) and 67% (n = 1,059) in 2013, 2014, 2015 and 2016. From September 2012 to December 2016, the 1 and 2-dose RV vaccine coverage gradually increased from 5% and 4% in 2012 to 92% and 88% in 2015, but decreased in 2016 to 53% and 52%, respectively. DISCUSSION: RV vaccine introduction was associated with a substantial decline in diarrheal hospitalizations and outpatient consultations for diarrhea in Agusan del Sur, Philippines.

The economic burden of rotavirus infection in South Korea from 2009 to 2012.

Rotavirus is a common cause of diarrhea worldwide, and vaccination prevents rotaviral gastroenteritis. Since the rotavirus vaccine was introduced in Korea in 2007, the prevalence of rotaviral gastroenteritis has decreased. However, little is known on the economic burden of rotavirus infection and its variations in Korea. Here, we estimated the economic costs of rotavirus infection from 2009 to 2012 using nationwide data from the National Health Insurance Service (NHIS) claims. Socioeconomic costs were subdivided into direct and indirect and measured with a prevalence-based approach. Costs were converted from Won to United States dollars (US$). The number of children <5 years old infected with rotavirus decreased from 21,437 to 10,295 during the study period, representing a decrease in prevalence from 947 to 443 per 100,000. The sum of direct and indirect costs also decreased, from $17.3 million to $9.6 million, and the days of admission decreased from 76,000 to 38,000. However, per capita expenditures slightly increased, from $809 to $934. Thus, the economic burden of rotavirus infection decreased after implementation of rotavirus vaccination. Including the vaccine as part of the national essential vaccination program could reduce the prevalence of and economic loss from rotavirus infection in Korea.

Estimated impact of rotavirus vaccine on hospitalizations and deaths from rotavirus diarrhea among children <5 in Asia.

BACKGROUND: Of the 215,000 global deaths from rotavirus estimated in 2013, 41% occur in Asian countries. However, despite a recommendation for global rotavirus vaccination since 2009, only eight countries in Asia have introduced the rotavirus vaccine into their national immunization program as of September 2017. To help policy makers assess the potential value of vaccination, we projected the reduction in rotavirus hospitalizations and deaths following a hypothetical national introduction of rotavirus vaccines in all countries in Asia using data on national-level rotavirus mortality, <5 population, rotavirus hospitalizations rates, routine vaccination coverage, and vaccine effectiveness. METHODS: To quantify uncertainty, we generated 1,000 simulations of these inputs. RESULTS: Our model predicted 710,000 fewer rotavirus hospitalizations, a 49% decrease from the 1,452,000 baseline hospitalizations and 35,000 fewer rotavirus deaths, a 40% decrease from the 88,000 baseline deaths if all 43 Asian countries had introduced rotavirus vaccine. Similar reductions were projected in subanalyses by vaccine introduction status, subregion, and birth cohort size. CONCLUSION: Rotavirus vaccines will substantially reduce morbidity and mortality due to rotavirus infections in Asia.

Potential impact and cost-effectiveness of rotavirus vaccination in Afghanistan.

INTRODUCTION: Despite progress made in child survival in the past 20 years, 5.9 million children under five years died in 2015, with 9% of these deaths due to diarrhea. Rotavirus is responsible for more than a third of diarrhea deaths. In 2013, rotavirus was estimated to cause 215,000 deaths among children under five years, including 89,000 in Asia. As of April 2017, 92 countries worldwide have introduced rotavirus vaccination in their national immunization program. Afghanistan has applied for Gavi support to introduce rotavirus vaccination nationally. This study estimates the potential impact and cost-effectiveness of a national rotavirus immunization program in Afghanistan. METHODS: This study examined the use of Rotarix® (RV1) administered using a two-dose schedule at 6 and 10 weeks of age. We used the ProVac Initiative's UNIVAC model (version 1.2.09) to evaluate the impact and cost-effectiveness of a rotavirus vaccine program compared with no vaccine over ten birth cohorts from 2017 to 2026 with a 3% annual discount rate. All monetary units are adjusted to 2017 US$. RESULTS: Rotavirus vaccination in Afghanistan has the potential to avert more than one million cases; 660,000 outpatient visits; approximately 50,000 hospital admissions; 650,000 DALYs; and 12,000 deaths, over 10 years. Not accounting for any Gavi subsidy, rotavirus vaccination can avert DALYs at US$82/DALY from the government perspective and US$80/DALY from the societal perspective. With Gavi support, DALYs can be averted at US$29/DALY and US$31/DALY from the societal and government perspective, respectively. The average yearly cost of a rotavirus vaccination program would represent 2.8% of the total immunization budget expected in 2017 and 0.1% of total health expenditure. CONCLUSION: The introduction of rotavirus vaccination would be highly cost-effective in Afghanistan, and even more so with a Gavi subsidy.