Postvaccine Years Research Articles

Impact of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease and pneumonia in The Gambia: 10 years of population-based surveillance

SummaryBackgroundThe Gambia introduced seven-valent pneumococcal conjugate vaccine (PCV7) in August 2009, followed by PCV13 in May, 2011, using a schedule of three primary doses without a booster dose or catch-up immunisation. We aimed to assess the long-term impact of PCV on disease incidence.MethodsWe did 10 years of population-based surveillance for invasive pneumococcal disease (IPD) and WHO defined radiological pneumonia with consolidation in rural Gambia. The surveillance population included all Basse Health and Demographic Surveillance System residents aged 2 months or older. Nurses screened all outpatients and inpatients at all health facilities using standardised criteria for referral. Clinicians then applied criteria for patient investigation. We defined IPD as a compatible illness with isolation of Streptococcus pneumoniae from a normally sterile site (cerebrospinal fluid, blood, or pleural fluid). We compared disease incidence between baseline (May 12, 2008–May 11, 2010) and post-vaccine years (2016–2017), in children aged 2 months to 14 years, adjusting for changes in case ascertainment over time.FindingsWe identified 22 728 patients for investigation and detected 342 cases of IPD and 2623 cases of radiological pneumonia. Among children aged 2–59 months, IPD incidence declined from 184 cases per 100 000 person-years to 38 cases per 100 000 person-years, an 80% reduction (95% CI 69–87). Non-pneumococcal bacteraemia incidence did not change significantly over time (incidence rate ratio 0·88; 95% CI, 0·64–1·21). We detected zero cases of vaccine-type IPD in the 2–11 month age group in 2016–17. Incidence of radiological pneumonia decreased by 33% (95% CI 24–40), from 10·5 to 7·0 per 1000 person-years in the 2–59 month age group, while pneumonia hospitalisations declined by 27% (95% CI 22–31). In the 5–14 year age group, IPD incidence declined by 69% (95% CI −28 to 91) and radiological pneumonia by 27% (95% CI −5 to 49).InterpretationRoutine introduction of PCV13 substantially reduced the incidence of childhood IPD and pneumonia in rural Gambia, including elimination of vaccine-type IPD in infants. Other low-income countries can expect substantial impact from the introduction of PCV13 using a schedule of three primary doses.FundingGavi, The Vaccine Alliance; Bill & Melinda Gates Foundation; UK Medical Research Council; Pfizer Ltd.

Sustained Declines in Age Group-Specific Rotavirus Infection and Acute Gastroenteritis in Vaccinated and Unvaccinated Individuals During the 5 Years Since Rotavirus Vaccine Introduction in England.

The introduction of an oral live-attenuated monovalent rotavirus vaccine (Rotarix®) into the UK infant immunization program in July 2013 was associated with large reductions in laboratory-confirmed rotavirus infections and hospitalizations due to acute gastroenteritis (AGE) within 12 months. Here we report the 5-year impact of the program in England. Individuals with laboratory-confirmed rotavirus infections during 2000-2018 and all-cause hospitalizations for AGE during 2007-2018 were identified using national electronic records. Age-specific incidence rate ratios (IRR) and estimated numbers of cases averted in each of the 5 postvaccination years were calculated. There were 206 389 laboratory-confirmed rotavirus infections and 3 657 651 hospitalizations for all-cause AGE. 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. All-cause AGE hospitalizations were reduced by 12-35% across all age-groups and by 25-48% in <1 year-olds in the 5 postvaccine years, with 24 474-49 278 hospitalizations averted annually. 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. Seasonal changes include a possible shift from annual to biennial peaks with lower peak incidence and longer seasons. There were large and sustained declines in both laboratory-confirmed rotavirus infections and AGE hospitalizations across all age groups in each of the 5 years since the introduction of the UK rotavirus program.

Rotavirus Strain Distribution before and after Introducing Rotavirus Vaccine in India.

In April 2016, an indigenous monovalent rotavirus vaccine (Rotavac) was introduced to the National Immunization Program in India. Hospital-based surveillance for acute gastroenteritis was conducted in five sentinel sites from 2012 to 2020 to monitor the vaccine impact on various genotypes and the reduction in rotavirus positivity at each site. Stool samples collected from children under 5 years of age hospitalized with diarrhea were tested for group A rotavirus using a commercial enzyme immunoassay, and rotavirus strains were characterized by RT-PCR. The proportion of diarrhea hospitalizations attributable to rotavirus at the five sites declined from a range of 56–29.4% in pre-vaccine years to 34–12% in post-vaccine years. G1P[8] was the predominant strain in the pre-vaccination period, and G3P[8] was the most common in the post-vaccination period. Circulating patterns varied throughout the study period, and increased proportions of mixed genotypes were detected in the post-vaccination phase. Continuous long-term surveillance is essential to understand the diversity and immuno-epidemiological effects of rotavirus vaccination.

Indirect impact of rotavirus vaccination on viral causes of acute gastroenteritis in the elderly.

Rotavirus is considered a childhood infection causing acute gastroenteritis however, it also causes disease in adults which may be underestimated due to less frequent testing in this age-group. To determine if paediatric rotavirus vaccination, introduced into Ireland in December 2016, affected the viral aetiology in those aged ≥65 yrs presenting with gastroenteritis in the pre- and post-vaccination years. Additionally, rotavirus genotypes in this age-group will be described. Faecal samples from 2015 to 2019 for the investigation of gastroenteritis were tested by real-time (RT-) PCR for norovirus, adenovirus, rotavirus, Rotarix, astrovirus and sapovirus. Rotaviruses were genotyped by multiplex real-time RT-PCR or hemi-nested RT-PCR and a proportion confirmed by sequencing. 22,593 samples from adults aged ≥65 yrs were tested and 2566 (11 %) had ≥1 virus detected. Of 2566 positive samples, norovirus was detected in 82 %, rotavirus 9 %, sapovirus 6 %, astrovirus 3 % and adenovirus 1 %. Rotavirus and norovirus infections decreased between pre and post-vaccine year groups p < 0.001, whereas sapovirus, astrovirus and adenovirus remained unchanged. Between 2015-16 and 2018-19, G2P[4] increased and G4P[8] decreased, p < 0.001. In 2015-2019 there were 37 rotavirus outbreaks. Five geriatric outbreaks were genotyped and caused by G4P[8] (n = 1), G1P[8] (n = 1), G2P[4] (n = 2) and G12P[8] (n = 1). Rotavirus causes acute gastroenteritis in older people. Paediatric vaccination may have contributed to a decline in infections in the elderly; nevertheless, rotavirus continued to circulate in older people following vaccine introduction. Genotype distribution changed between the pre- and post-vaccine era however genotypes in outbreak and endemic settings were comparable.

Rotavirus vaccine effectiveness and impact in Uzbekistan, the first country to introduce in central Asia

ABSTRACT Uzbekistan, the most populous country in central Asia, was the first in the region to introduce rotavirus vaccine into its national immunization program. Rotarix (GlaxoSmithKline Biologicals, RV1) was introduced in June 2014, with doses recommended at age 2 and 3 months. To evaluate vaccine impact, active surveillance for rotavirus diarrhea was reestablished in 2014 at 2 hospitals in Tashkent and Bukhara which had also performed surveillance during the pre-vaccine period 2005−2009. Children aged <5 y admitted with acute diarrhea had stool specimens collected and tested for rotavirus by enzyme immunoassay. Proportions testing rotavirus-positive in post-vaccine years were compared with the pre-vaccine period. Vaccine records were obtained and effectiveness of 2 RV1 doses vs 0 doses was estimated using rotavirus-case and test-negative design among children enrolled from Bukhara city. In 2015 and 2016, 8%−15% of infants and 10%−16% of children aged<5 y hospitalized with acute diarrhea at the sites tested rotavirus-positive, compared with 26% of infants and 27% of children aged<5 y in pre-vaccine period (reductions in proportion positive of 42%−68%, p <.001). Vaccine effectiveness of 2 RV1 doses vs 0 doses in protecting against hospitalization for rotavirus disease among those aged ≥6 months was 51% (95% CI 2–75) and is based on cases predominantly of genotype G2P[4]. Vaccine effectiveness point estimates tended to be higher against cases with higher illness severity (e.g., clinical severity based on modified Vesikari score ≥11). Our data demonstrate that the monovalent rotavirus vaccine is effective in reducing the likelihood of hospitalization for rotavirus disease in young children in Uzbekistan.

Effects of the rotavirus vaccine program across age groups in the United States: analysis of national claims data, 2001\u20132016

BackgroundThe direct effectiveness of infant rotavirus vaccination implemented in 2006 in the United States has been evaluated extensively, however, understanding of population-level vaccine effectiveness (VE) is still incomplete.MethodsWe analyzed time series data on rotavirus gastroenteritis (RVGE) and all-cause acute gastroenteritis (AGE) hospitalization rates in the United States from the MarketScan® Research Databases for July 2001–June 2016. Individuals were grouped into ages 0–4, 5–9, 10–14, 15–24, 25–44, and 45–64 years. Negative binomial regression models were fitted to monthly RVGE and AGE data to estimate the direct, indirect, overall, and total VE.ResultsA total of 9211 RVGE and 726,528 AGE hospitalizations were analyzed. Children 0–4 years of age had the largest declines in RVGE hospitalizations with direct VE of 87% (95% CI: 83, 90%). Substantial indirect effects were observed across age groups and generally declined in each older group. Overall VE against RVGE hospitalizations for all ages combined was 69% (95% CI: 62, 76%). Total VE was highest among young children; a vaccinated child in the post-vaccine era has a 95% reduced risk of RVGE hospitalization compared to a child in the pre-vaccine era. We observed higher direct VE in odd post-vaccine years and an opposite pattern for indirect VE.ConclusionsVaccine benefits extended to unvaccinated individuals in all age groups, suggesting infants are important drivers of disease transmission across the population. Imperfect disease classification and changing disease incidence may lead to bias in observed direct VE.Trial registrationNot applicable.

The role of the sapovirus infection increased in gastroenteritis after national immunisation was introduced.

This study examined the prevalence and clinical significance of the sapovirus infection in children with acute gastroenteritis before and after the introduction of the rotavirus vaccination in Finland in 2009. We collected 1437 stool samples from children under 16years during three prospective hospital-based surveillance studies of acute gastroenteritis at Tampere University Hospital, Finland. The children were seen in the emergency department (47%) or admitted to the ward (53%). Sapovirus findings from 2006 to 2008 (n=759), before national immunisation, were compared to 2009-2011 (n=330) and 2012-2014 (n=348), after the national programme was launched. The overall incidence of the sapovirus was 3.3%. It was present in 1.4% of acute gastroenteritis cases in 2006-2008 and 5.5% in the post-vaccination years, but the absolute number did not increase. Sapoviruses mainly occurred in the winter and spring, but did not follow the prevalence of the norovirus or rotavirus. Sapovirus GI.1 and GII.1 were the most common genotypes, but the predominant strain was different each season. Many sapovirus lineages appeared during multiple seasons and reappeared later. The sapovirus was uncommonly and sporadically detected in children seen in the hospital for acute gastroenteritis, and its relative role increased after national immunisation was introduced.

Longer-term Direct and Indirect Effects of Infant Rotavirus Vaccination Across All Ages in the United States in 2000-2013: Analysis of a Large Hospital Discharge Data Set.

Rotavirus disease rates dramatically declined among children <5 years of age since the rotavirus vaccine was introduced in 2006; population-level impacts remain to be fully elucidated. Data from the Healthcare Cost and Utilization Project State Inpatient Databases were used to conduct a time-series analysis of monthly hospital discharges across age groups for acute gastroenteritis and rotavirus from 2000 to 2013. Rate ratios were calculated comparing prevaccine and postvaccine eras. Following vaccine introduction, a decrease in rotavirus hospitalizations occurred with a shift toward biennial patterns across all ages. The 0-4-year age group experienced the largest decrease in rotavirus hospitalizations (rate ratio, 0.14; 95% confidence interval, .09-.23). The 5-19-year and 20-59-year age groups experienced significant declines in rotavirus hospitalization rates overall; the even postvaccine calendar years were characterized by progressively lower rates, and the odd postvaccine years were associated with reductions in rates that diminished over time. Those aged ≥60 years experienced the smallest change in rotavirus hospitalization rates overall, with significant reductions in even postvaccine years compared with prevaccine years (rate ratio, 0.51; 95% confidence interval, .39-.66). Indirect impacts of infant rotavirus vaccination are apparent in the emergence of biennial patterns in rotavirus hospitalizations that extend to all age groups ineligible for vaccination. These observations are consistent with the notion that young children are of primary importance in disease transmission and that the initial postvaccine period of dramatic population-wide impacts will be followed by more complex incidence patterns across the age range in the long term.

Sustained impact of rotavirus vaccine on rotavirus hospitalisations in Lusaka, Zambia, 2009–2016

BackgroundMonovalent rotavirus vaccine (RV1) was introduced in Lusaka in February 2012 and rolled out countrywide in November 2013 in the routine Expanded Programme on Immunisation and administered at 6 and 10 weeks with no catch up dose. Reported here is the monitoring of rotavirus acute gastroenteritis hospitalisations at the University Teaching Hospital, Lusaka, Zambia as part of efforts to document the impact of rotavirus vaccine. MethodsChildren <5 years hospitalised for acute gastroenteritis (AGE) from January 2009 to December 2016 were recruited into the rotavirus disease burden active surveillance and had their stools tested for rotavirus by enzyme immunoassay. We compared rotavirus-associated AGE hospitalisations of the pre-vaccine era (2009–2011) with the post-rotavirus vaccine introduction period (2013–2016). ResultsWith the increase in RV1 coverage in Lusaka, rotavirus AGE declined significantly from 40% of diarrhoea hospitalisation in the pre-vaccine era to 29% of diarrhoea hospitalisation in the post-vaccine era (p < 0.001) in children <5 years. After a decreasing trend in rotavirus positivity from 2013 to 2015, positivity increased to 37% in 2016. However, the post-vaccine years (2012–2016) saw substantial decline in the number tested (median decline: 34% (range: 20–43%)) and the number of positive results (median decline: 52% (range: 30–65%). ConclusionA sustained and significant decline in rotavirus AGE hospitalisations was observed in children <5 years since the introduction of RV1 in Lusaka, Zambia. Despite an increase in rotavirus positivity in 2016, the total number of children enrolled and the number of rotavirus positive children remained below baseline. The reason for the increase in rotavirus positivity in 2016 is unknown but could be due to an accumulation of susceptible children and the shifting of disease to children of older age groups. This finding underscores the need for continued monitoring of rotavirus vaccine impact.

Detection of rotavirus before and after monovalent rotavirus vaccine introduction and vaccine effectiveness among children in mainland Tanzania

BackgroundMonovalent rotavirus vaccine (RV1) was introduced in Tanzania in January 2013 under the Reach Every Child initiative, to be given at ages 6 and 10 weeks. We used the sentinel hospital rotavirus surveillance system to examine the rotavirus detection rate before and after vaccine introduction and estimate vaccine effectiveness. MethodsBefore vaccine introduction, rotavirus surveillance was established at two mainland hospitals; children admitted for acute diarrhea were eligible for enrollment and stools were tested for rotavirus antigen. We compared the rotavirus positivity rate in the pre-vaccine period (Tanga Hospital, 2009 and 2011; Bugando Medical Centre, 2012) to that from post-introduction years, 2014–2015. In 2013, surveillance was established at 9 additional hospitals. We examined rotavirus positivity among infants at these sites for 2014–2015. We obtained vaccine records and calculated vaccine effectiveness at 3 sites using case-test-negative control design. ResultsAt Tanga Hospital, the rotavirus positivity rate among infants was 41% (102/251) pre-vaccine and 14% (28/197) in post-vaccine years (rate ratio: 0.35 [95% CI 0.22–0.54]). At Bugando, the positivity rate was 58% (83/143) pre-vaccine, and 18% (49/277) post-introduction (rate ratio 0.30 [95% CI 0.210.44]). Results were similar among children <5 years. At the new sites, the median site rotavirus positivity rate among infants was 26% in 2014 (range 19–44%) and 18% in 2015 (range 16–33%). The effectiveness of ≥1 RV1 dose against rotavirus hospitalization among children 5–23 months was 53% (95% CI: −14, 81), and 66% (95% CI: 9–87) against hospitalization with intravenous rehydration. Following introduction, peak rotavirus activity occurred later in the year and appeared more concentrated in time. ConclusionRotavirus surveillance data from Tanzania indicate that the rotavirus positivity rate among children hospitalized with diarrhea that were enrolled was substantially reduced after vaccine introduction. Low positivity rates among infants were detected at hospitals across the country. Overall, the data support that rotavirus vaccine has been successfully introduced and is effective in Tanzanian children.

Impact of pentavalent rotavirus vaccine against severe rotavirus diarrhoea in The Gambia

IntroductionRotavirus vaccines protect against the leading cause of severe childhood diarrhoea, and have been introduced in many low-income African countries. The Gambia introducedRotateq® (RV5) into their national immunization program in 2013. We revieweddata from an active rotavirus sentinel surveillancesitefor early evidence of vaccine impact. MethodsWe compared rotavirus prevalence in diarrhoeal stool in children< 5 years of age admittedat the Edward Francis Small Teaching Hospital sentinel surveillance site before (2013) andafterRV5 introduction (2015–2016) in the Gambia. The rotavirus-percent positive was separately compared for all diarrhoealhospitalizations and for hospitalizations with severe symptoms. Rotavirus prevalence was compared annually for the pre-vaccine year of 2013 with post-vaccine years of 2015 and 2016 using chi-square or Fisher’s exact tests and the p-value to establish significant relationship was set at p < 0.05. All analyses were completed in SAS 9.3 (SAS Analytics, North Carolina). ResultsRotavirus prevalence among all diarrhoeahospitalizations decreased from 22% in 2013 to 11% in 2015 (p = 0.04), while remaining unchanged in 2016 (18%, p = 0.56). For hospitalizations that were clinically severe and/or treated with intravenous fluids (mean of 46 per year), the rotavirus prevalence decreased from 33% in 2013 to 8% in 2015 (p = 0.04), and to 15% in 2016 (p = 0.08). The children with age <1 year accounted for 45% the population infected with rotavirus in both pre and post rotavirus vaccination periods. ConclusionsRotavirus vaccine introduction in the Gambia could be among factors resulting in decreased diarrhea hospitalizations among children at the Edward Francis Small Teaching Hospital, particularly those with severe disease. These results support the continuation of rotavirus vaccine and additional monitoring of rotavirus hospitalization trends in the country.

Impact of rotavirus vaccination on rotavirus hospitalisation rates among a resource-limited rural population in Mbita, Western Kenya.

A two-dose oral monovalent rotavirus vaccine (RV1) was introduced into the Kenyan National Immunization Program in July 2014. We assessed trends in hospitalisation for rotavirus-specific acute gastroenteritis (AGE) and strain distribution among children <5 years in a rural, resource-limited setting in Kenya before and after the nationwide implementation of the vaccine. Data on rotavirus AGE and strain distribution were derived from a 5-year hospital-based surveillance. We compared rotavirus-related hospitalisations and strain distribution in the 2-year post-vaccine period with the 3-year pre-vaccine baseline. Vaccine administrative data from the Unit of Vaccines and Immunization Services (UVIS) for Mbita sub-county were used to estimate rotavirus immunisation coverage in the study area. We observed a 48% (95% CI: 27-64%) overall decline in rotavirus-related hospitalisations among children aged <5 years in the post-vaccine period. Coverage with the last dose of rotavirus vaccine increased from 51% in year 1% to 72% in year 2 of the vaccine implementation. Concurrently, reductions in rotavirus hospitalisations increased from 40% in the first year to 53% in the second year of vaccine use. The reductions were most pronounced among the vaccine-eligible group, with the proportion of cases in this age group dropping to 14% in post-vaccine years from a high of 51% in the pre-vaccine period. A diversity of rotavirus strains circulated before the introduction of the vaccine with G1P[8] being the most dominant strain. G2P[4] replaced G1P[8] as the dominant strain after the vaccine was introduced. Rotavirus vaccination has resulted in a notable decline in hospital admissions for rotavirus infections in a rural resource-limited population in Kenya. This provides early evidence for continued use of rotavirus vaccines in routine childhood immunisations in Kenya. Our data also underscore the need for expanding coverage on second dose so as to maximise the impact of the vaccine.

Annual changes in rotavirus hospitalization rates before and after rotavirus vaccine implementation in the United States

BackgroundHospitalizations for rotavirus and acute gastroenteritis (AGE) have declined in the US with rotavirus vaccination, though biennial peaks in incidence in children aged less than 5 years occur. This pattern may be explained by lower rotavirus vaccination coverage in US children (59% to 73% from 2010–2015), resulting in accumulation of susceptible children over two successive birth cohorts.MethodsRetrospective cohort analysis of claims data of commercially insured US children aged <5 years. Age-stratified hospitalization rates for rotavirus and for AGE from the 2002–2015 rotavirus seasons were examined. Median age and rotavirus vaccination coverage for biennial rotavirus seasons during pre-vaccine (2002–2005), early post-vaccine (2008–2011) and late post-vaccine (2012–2015) years.ResultsAge-stratified hospitalization rates decreased from pre-vaccine to early post-vaccine and then to late post-vaccine years. The clearest biennial pattern in hospitalization rates is the early post-vaccine period, with higher rates in 2009 and 2011 than in 2008 and 2010. The pattern diminishes in the late post-vaccine period. For rotavirus hospitalizations, the median age and the difference in age between biennial seasons was highest during the early post-vaccine period; these differences were not observed for AGE hospitalizations. There was no significant difference in vaccination coverage between biennial seasons.ConclusionsThese observations provide conflicting evidence that incomplete vaccine coverage drove the biennial pattern in rotavirus hospitalizations that has emerged with rotavirus vaccination in the US. As this pattern is diminishing with higher vaccine coverage in recent years, further increases in vaccine coverage may reach a threshold that eliminates peak seasons in hospitalizations.

Follow-up of hepatitis b virus vaccine response in healthy individuals

Background The long-term protective effect of hepatitis B virus (HBV) vaccine and the need for booster dose vaccination remain unclear. Detection of nonresponders to HBV vaccine and search for factors that lead to nonresponse will help in prevention of HBV infection, hepatocellular carcinoma related to hepatitis B infection and hepatitis D virus infection. Aim The aim of this study was to assess the benefit of follow-up of hepatitis B vaccine response and evaluate the persistence of seroprotection after HBV vaccination to determine the necessity of a booster dose in healthy individuals after 5 and 10 years of vaccination. Patients and methods Serum samples were tested for quantitative detection of hepatitis B surface antibodies (HBsAb) using ELISA for 30 individuals who received HBV vaccine of less than or equal to 5 years (group I) and 30 individuals who received HBV vaccine for more than or equal to 10 years (group II), and if the results were negative or less than 10 IU/ml, evaluations of hepatitis B surface antigen and hepatitis B core antibodies (total) were done. Results HBsAb was positive among 66.7% of each group, and the median HBsAb level was 59.73 and 51.21 in groups I and II, respectively. Conclusion Approximately 33% of the studied groups were nonresponders of HBV vaccine regardless of postvaccination years (5–10). Hepatitis B infection and occult hepatitis B infection results were negative in all of nonresponders. Recommendations Follow-up of HBsAb levels in vaccinated individuals after having completed three doses of hepatitis B vaccination on a large scale is important to detect nonresponses and revaccinate them.

Decline of rotavirus-coded hospitalizations in children under 5 years: A report from Japan where rotavirus vaccines are self-financed

ObjectivesTo estimate the trend in incidence of rotavirus gastroenteritis (RVGE) hospitalization among children aged <5 years in Japan during pre- and post-vaccine periods (2009–2011 and 2012–2015). Study designThis retrospective observational study used a health insurance claims database (constructed by Japan Medical Data Center Co., Ltd.). Rotavirus vaccine became commercially available in 2011. We analyzed data of all children aged <5 years between January 2009 and December 2015. We estimated the incidence rate (IR) of RVGE hospitalization per 1000 person-years from 2009 to 2015 and incidence rate ratio (IRR) of post-vaccine years compared with the averaged pre-vaccine years. IRs and IRRs were also estimated by age group. Primary analysis was limited to the rotavirus season (January to June) of each year. ResultsThe IR was 6.3–9.3 in pre-vaccine years, 2.3 in 2014, and 3.0 in 2015; the decline was estimated to be 71% in 2014 and 61% in 2015 (p<0.01). By age group, reduction in hospitalizations began in 2013 among children <1 year old, followed by children aged 1 to <5 years in 2014. In the 2014 season, a 65% reduction in RVGE hospitalization was observed in children aged 36 to <60 months, although this age group was unlikely to be vaccinated. ConclusionsA substantial decline of RVGE hospitalization in 2014 and its persistence was observed among children aged <5 years in Japan after introduction of rotavirus vaccine, although not included in the national immunization program. Indirect effects of rotavirus vaccination were suggested in the 2014 season.

Intussusception-related Hospitalizations Among Infants Before and After Private Market Licensure of Rotavirus Vaccines in Taiwan, 2001-2013.

Rotavirus is a leading cause of acute gastroenteritis among Taiwanese children. Two globally licensed rotavirus vaccines recommended for inclusion in routine immunization programs that have been available for private market use in Taiwan since 2006 have been associated with a low risk of intussusception in postmarketing studies conducted in several countries. Our objective was to examine trends and characteristics of intussusception hospitalizations in Taiwan among children <12 months of age before and after rotavirus vaccine licensure to provide updated baseline and early postlicensure data. We extracted data on intussusception-related hospitalizations among children <12 months of age during 2001-2013 from the National Health Insurance Research Database. We examined patient demographics, clinical outcome and hospitalization trends, focusing on recommended ages for rotavirus vaccination (6-14, 15-24 and 25-34 weeks). We compared mean hospitalization rates for prevaccine licensure years 2001-2005 with those for postvaccine licensure years 2007-2013 using Poisson regression analysis. During 2001-2013, 1998 intussusceptions hospitalizations were recorded. The mean age of hospitalization was 33 weeks. Almost all children recovered; 3 deaths occurred. The overall intussusception hospitalization rate was 75.1 per 100,000; seasonality was not evident. Hospitalization rates were greatest in children ≥25 weeks of age and occurred more frequently in boys. Prevaccine and postvaccine licensure trends in annual hospitalization rates did not significantly differ. However, mean hospitalization rates were lower during the postvaccine licensure period for children <12 months of age (rate ratio: 0.84, 95% confidence interval: 0.76-0.92) with the greatest decline among children 25-34 weeks of age (rate ratio: 0.66, 95% confidence interval: 0.55-0.78). Infant intussusception in Taiwan occurs at a rate within the range of other Asian countries is rare among children <3 months of age, has a male predominance and does not have a clear seasonality pattern. We did not observe a postlicensure increase in intussusception hospitalization rates in children 6-14 weeks of age.

Long-term impact of self-financed rotavirus vaccines on rotavirus-associated hospitalizations and costs in the Valencia Region, Spain

BackgroundRotavirus vaccines are available in Spain from 2007. They are recommended by the Spanish Pediatric Association, but not funded by the National Health System (NHS) and its coverage rate reached 40-50%. The hospitalization rate reduction of rotavirus caused gastroenteritis (RVAGE) directly attributable to vaccination remains unclear due to the large differences described in published studies, ranging from 14 to 44.5% in children <5 years of age, even with similar vaccination coverage. These results could be partly explained by variability in hospitalization policies, different study designs and the timeframe of observation. In addition, the direct economic impact of the reduction of hospitalizations has never been estimated. Therefore, there is a need to analyze the long-term impact of rotavirus vaccines on RVAGE and all cause gastroenteritis (AGE) hospitalizations and the national health system associated costs, minimizing potential confounders or biases.MethodsA population-based, ecological study using the hospital discharge registry’s Minimum Basic Data Set (MBDS) and the vaccine register (SIV) was performed, among Valencia Region’s children <5 years old, during 2002 - 2015. RVAGE and AGE hospitalization risk was analyzed by vaccine coverage and adjusted by the total hospitalization rate for all causes to avoid external biases. The impact of AGE-associated health care utilization in prevaccine (2003–2006) versus postvaccine (2008–2014) years was also assessed.ResultsAfter vaccines licensure, the incidence of RVAGE-associated hospitalizations decreased markedly. A general vaccine coverage-related reduction in RVAGE or AGE-hospitalizations risk was observed in all age groups. Compared with unvaccinated children, RVAGE hospitalization risk decreased by 67% (95% CI: 55-67), 71% (95% CI: 58-81) and 68% (95% CI: 18-92) in children 0, 1 and 4 years of age, respectively, with a vaccination coverage between 40 and 42%. Overall, the hospital related costs were reduced around EUR 6 Mill per 105 children in 7 years.ConclusionsDespite the low-medium vaccine coverage, the introduction of rotavirus vaccines had a specific coverage-related response impact in the hospitalizations for RVAGE and AGE in children <5 years and their use substantially reduced hospital related costs. The model used reassures that the estimated impact is due to the vaccination and not to other external factors.

Rotavirus vaccine and health-care utilization for rotavirus gastroenteritis in Tsu City, Japan.

BackgroundRotavirus vaccines were introduced in Japan in November 2011. We evaluated the subsequent reduction of the health-care burden of rotavirus gastroenteritis.MethodsWe conducted active surveillance for rotavirus gastroenteritis among children under 5 years old before and after the vaccine introduction. We surveyed hospitalization rates for rotavirus gastroenteritis in children in Tsu City, Mie Prefecture, Japan, from 2007 to 2015 and surveyed the number of outpatient visits at a Tsu City clinic from 2010 to 2015. Stool samples were obtained for rotavirus testing and genotype investigation. We assessed rotavirus vaccine coverage for infants living in Tsu City.ResultsIn the pre-vaccine years (2007–2011), hospitalization rates for rotavirus gastroenteritis in children under 5 years old were 5.5, 4.3, 3.1 and 3.9 cases per 1000 person-years, respectively. In the post-vaccine years (2011–2015), the rates were 3.0, 3.5, 0.8 and 0.6 cases per 1000 person-years, respectively. The hospitalization rate decreased significantly in the 2013–2014 and 2014–2015 seasons compared to the average of the seasons before vaccine introduction (P < 0.0001). In one pre-vaccine year (2010–2011), the number of outpatient visits due to the rotavirus infection was 66. In the post-vaccine years (2011–2015), the numbers for each season was 23, 23, 7 and 5, respectively. The most dominant rotavirus genotype shifted from G3P[8] to G1P[8] and to G2P[4]. The coverage of one dose of rotavirus vaccine in Tsu City was 56.5% in 2014.ConclusionAfter the vaccine introduction, the hospitalization rates and outpatient visits for rotavirus gastroenteritis greatly decreased.

Intussusception Rates Before and After the Introduction of Rotavirus Vaccine

Recent US studies have identified a small increased risk of intussusception after rotavirus vaccination, mainly after the first dose. We examined trends in intussusception hospitalizations before (2000-2005) and after (2007-2013) rotavirus vaccine introduction to assess whether this observed temporal risk translates into more hospitalized cases at the population level. Intussusception hospitalizations in children <12 months of age were abstracted from the State Inpatient Database maintained by the Healthcare Cost and Utilization Project for 26 states that provided data from 2000 to 2013. Rates were calculated using bridged-race postcensal population estimates. Trends were analyzed by age groups (6-14 weeks, 15-24 weeks, and 25-34 weeks) based on the recommended ages for vaccine administration as well as 8-11 weeks when the majority of first doses are given. Rate ratios were calculated by using Poisson regression. No consistent change in intussusception hospitalization rates was observed among all children <12 months of age and among children 15 to 24 weeks and 25 to 34 weeks of age. The intussusception hospitalization rate for children aged 8 to 11 weeks was significantly elevated by 46% to 101% (range: 16.7-22.9 per 100 000) in all postvaccine years except 2011 and 2013 compared with the prevaccine baseline (11.7 per 100 000). The increase in the intussusception hospitalization rate in children 8 to 11 weeks when the majority of first doses of vaccine are given is consistent with recent US postlicensure studies. Given the magnitude of declines in rotavirus disease compared with this small increase in intussusception, the benefits of rotavirus vaccination outweigh the increase risk of intussusception.

Decline in Emergency Department Visits for Acute Gastroenteritis Among Children in 10 US States After Implementation of Rotavirus Vaccination, 2003 to 2013.

Rotavirus vaccination of all infants began in the United States in 2006. Although the effect of vaccination on childhood hospitalizations for rotavirus has been well described, the effects of rotavirus vaccine on emergency department (ED) visits are less well documented. Using the State Emergency Department Databases for 10 US states, we compared the rates of gastroenteritis- and rotavirus-coded ED visits among children <5 years of age in prevaccine (2003 to 2006) with those in postvaccine (2008-2013) years; 2007 was excluded as a transition year. We analyzed ED visit rates by age group, sex, race and rotavirus season. The prevaccine annual gastroenteritis-coded ED visit rate among children <5 years of age of 426 per 10,000 (annual range, 396-477 per 10,000) declined to 382 per 10,000 in postvaccine years, a 10.3% (±0.3%, P < 0.0001) rate reduction overall. Compared with prevaccine years, annual ED visit rates for gastroenteritis decreased by 6.5% (±0.6%) in 2008, 12.3% (±0.6%) in 2010, 14.8% (±0.5%) in 2011, 20.4% (±0.5%) in 2012 and 10.1% (±0.6%) in 2013; a small increase of 1.8% (±0.6%) was seen in 2009 (P < 0.0001 for all individual comparisons). Declines were similar by sex and race and were greater in children <2 years of age (range 14.1%-20.6%, P < 0.0001) than in older children (increase of 3.3% ±0.6%, P < 0.0001). A decline of 21.2% (±0.4%, P < 0.0001) in ED visits was seen during the rotavirus season months from January through June versus an increase of 9.5% (±0.6%, P < 0.0001) during July to December. ED visits specifically coded for rotavirus showed more prominent declines than for all gastroenteritis. ED visits for gastroenteritis in US children have declined since the introduction of rotavirus vaccine.