Effectiveness of rotavirus vaccines in an Australian population: A case-control study

ObjectiveTwo rotavirus vaccines (RV1 and RV5) were included in the publicly funded National Immunisation Program in Australia from July 2007. The programme in Western Australia initially provided RV1 (at ages 2 and 4 months) and then switched to RV5 (at ages 2, 4 and 6 months) from July 2009. This retrospective case-control study was conducted to assess the effectiveness of rotavirus vaccine against laboratory confirmed and notified cases of rotavirus infection among children aged <5 years.MethodsCase-subjects were identified as vaccine-eligible children (born from 1 May 2007) who were notified as having rotavirus infection during the period 2009–2011. The control group was vaccine-eligible children notified as having Campylobacter or Salmonella infection during the same period. Individual rotavirus immunisation status was ascertained from a population-based immunisation register. Full-dose and partial-dose vaccine effectiveness (VE) were calculated for both vaccines using the adjusted odds ratio (OR) of vaccination for cases versus controls (VE = (1 − OR)*100%).ResultsOverall, 282 cases and 883 controls were included. The adjusted VE for a full course of either rotavirus vaccine was 72% (95% CI: 56–82) and 71% (95% CI: 50–84) for partial vaccination (one dose of RV1 or one/two doses of RV5). The VE for a complete 3-dose course of RV5 was 82% (95% CI: 59–92) and for a full 2-dose course of RV1 was 73% (95% CI: 55–83).ConclusionsRV1 and RV5 were both effective in preventing laboratory confirmed and notified rotavirus infections among children aged <5 years. Even incomplete courses of vaccination conferred good protection.     

Long-term effectiveness of pentavalent and monovalent rotavirus vaccines against hospitalization in Taiwan children

BackgroundTwo rotavirus vaccines (RV1 and RV5) are available on the private market in Taiwan, not included in national immunization program. Scanty reports evaluated the rotavirus vaccine effectiveness (VE) in Asian countries.MethodsFrom February 2014-July 2017, we conducted a prospective case-control study in ten hospitals in Taiwan. Case-patients included children aged 8–59 months, and hospitalized with laboratory-confirmed rotavirus acute gastroenteritis (AGE). For each case patient, up to four controls, rotavirus-negative AGE or non-AGE illnesses, respectively, were matched by gender, age and enrolled date. Vaccination history was confirmed through vaccination card or hospital record. VE was calculated as (1 − odds ratio of vaccination) × 100%.ResultsTotally 4248 AGE patients and 2242 non-AGE controls were enrolled. A total of 330 case-patients with rotavirus AGE, 1226 rotavirus-negative AGE controls and 1122 non-AGE controls were included for analysis. Unvaccinated rate was 85.15% for rotavirus-positive cases, 42.9% for rotavirus-negative controls, and 34.31% for non-AGE controls. VE of two-dose RV1 was 84.9% (95% confidence interval [CI]:77.7%, 90.1%) for rotavirus-negative AGE and 88.9% (95% CI: 83.4%, 92.8%) for non-AGE controls, while VE of three-dose RV5 was 92.5% (95% CI: 85.1%, 96.7%) and 96.4% (95% CI: 91.9%, 98.6%), respectively. For respective vaccine, VEs were not significantly different in term of rotavirus genotypes. VEs of both vaccines declined <80% in children aged three years by combined controls.ConclusionsBoth vaccines provided excellent and sustained protection against rotavirus AGE hospitalization in children in Taiwan, but the effectiveness declined slightly in children aged three years.     

Long-term surveillance of rotavirus vaccination after implementation of a national immunization program in Finland (2008–2018)

BackgroundRotavirus (RV) vaccination was included in the Finnish National immunization Program (NIP) in 2009. RotaTeq (RV5) has been used exclusively with a national average vaccination coverage rate (VCR) of > 90%. While previous studies have demonstrated that inpatient rotavirus gastroenteritis (RVGE) admissions declined by as much as 96% in Finnish children ≤ 5 years old following RV vaccination introduction, no study has evaluated long-term protection after vaccination in Finland. In this study, we analyze incidence of hospital outpatient visits and inpatient admissions of gastroenteritis in children up to 7 years of age.MethodsWe first describe the incidence of RVGE, viral gastroenteritis (VGE), and acute gastroenteritis (AGE) for all Finnish children born during 2008–2011. Children were stratified by the year of birth into not-eligible, partially eligible and rotavirus vaccine-eligible (born in 2008, 2009, 2010 and 2011, respectively). Hospital inpatient and outpatient data was collected from the National Care Register for all children from birth until December 31st, 2018. We also studied RVGE incidence during 2014–2017 for children<3 years of age in municipalities with VCRs of 90% and above and municipalities with VCRs below 90%.ResultsRVGE incidence decreased significantly soon after implementation of RV vaccination in the NIP. In vaccine-eligible cohorts, no clear peak incidence in the youngest age groups could be observed, and no RVGE cases were observed beyond 6 years after vaccination, in contrast to vaccine ineligible and partially eligible cohorts. Despite an overall high VCR in Finland, regions with high VCR had lower incidence of RVGE than regions with lower VCR.ConclusionIncidence of RVGE has remained low in all age groups during the 10 years following introduction of RV vaccine in the Finnish NIP. Differences in RVGE incidence were observed in regions with high as compared with lower VCR, highlighting the importance of maintaining high vaccination coverage.     

Impact of rotavirus vaccination on intussusception hospital admissions in England

BackgroundAn increased risk of intussusception has been reported following rotavirus vaccination. We sought to determine whether introduction of rotavirus vaccination in England in July 2013 was associated with a change in the burden of total and age group-specific childhood hospital admissions for intussusception.MethodsWe identified all children aged 0–36 months admitted to hospitals in England with intussusception using the Hospital Episode Statistics dataset. We performed a retrospective ecological analysis comparing hospital admission rates for intussusception during the periods before (2008/2009–2012/2013) and after (2014/2015–2017/2018) introduction of rotavirus vaccination using modified Poisson regression and interrupted time series analysis. Length of hospital stay and clinical outcomes were also examined.ResultsThe mean annual admission rate for intussusception in infants over the ten-year study period was 31.5 per 100,000 person-years. An increase in the admission rate in the 8–16 weeks age group (RR 1.46, 95% CI 1.12–1.91), those receiving vaccination, was compensated for by decreases in the 17–24 weeks (RR 0.77, 0.63–0.94), 25–32 weeks (RR 0.71, 0.59–0.86) and 41–52 weeks (RR 0.80, 0.66–0.98) age groups. Using interrupted time series analysis, we observed a significant decrease in incidence in the 0–12 months age group (RR 0.80, 0.67–0.96), but not in the overall 0–36 months age group (RR 1.09, 0.98–1.20). There was no significant change in the proportion of children requiring surgical intervention or with major complications of intussusception. Length of hospital stay decreased among infants receiving surgery for intussusception.ConclusionsOur results suggest that introduction of rotavirus vaccination in England has resulted in a downward shift in the age at which intussusception occurs in infants, with no overall increase in hospital admission rate or disease severity. These findings support the view that the benefits of rotavirus vaccination outweigh the small increased risk of intussusception in the early post-vaccination period.     

Impact of rotavirus vaccine on paediatric rotavirus hospitalisation and intussusception in New Zealand: A retrospective cohort study

BackgroundRotavirus results in a significant burden of hospitalisations and deaths globally. Rotavirus vaccine has been used in New Zealand since July 2014. The aim of this study was to assess the safety and effectiveness of RotaTeq® vaccine in New Zealand between 2006 and 2016.MethodsA national cohort study of 723,695 children aged less than 6 years was carried out using linked administrative datasets. Study outcomes were hospitalisation for intussusception, rotavirus, and all-cause gastroenteritis. Intussusception hospitalisation rates were calculated from 2006 to 2016, and rotavirus and all-cause gastroenteritis hospitalisation rates from 2011 to 2016. We examined the effect of RotaTeq® vaccination on rotavirus and all-cause gastroenteritis hospitalisation rates using Poisson regression. Adjusted incidence rate ratios controlled for sex, year of birth, ethnicity, socioeconomic deprivation, and district health board area.ResultsSignificant reductions in the incidence of rotavirus hospitalisation were seen in all age groups, ethnicities, and deprivation following the introduction of RotaTeq®. There was a 92.6% reduction in hospitalisation incidence in the vaccinated cohort (p < 0.0001). There was also a 48% reduction in all-cause gastroenteritis hospitalisation incidence in the vaccinated cohort (p < 0.0001). The average annual intussusception rate in children aged less than 3 years was 26.2 per 100,000, with no significant change over time (p = 0.847).ConclusionsIn New Zealand the introduction of RotaTeq® resulted in a significant reduction in rotavirus hospitalisation, and a halving in all-cause gastroenteritis hospitalisation. There has been no change in the overall incidence of intussusception or clear change in patterns of cases, although intussusception cases did occur within risk period immediately post vaccine.     

Catching-up with pentavalent vaccine: Exploring reasons behind lower rotavirus vaccine coverage in El Salvador

Rotavirus vaccine was introduced in El Salvador in 2006 and is recommended to be given concomitantly with DTP–HepB–Haemophilus influenzae type b (pentavalent) vaccine at ages 2 months (upper age limit 15 weeks) and 4 months (upper age limit 8 months) of age. However, rotavirus vaccination coverage continues to lag behind that of pentavalent vaccine, even in years when national rotavirus vaccine stock-outs have not occurred. We analyzed factors associated with receipt of oral rotavirus vaccine among children who received at least 2 doses of pentavalent vaccine in a stratified cluster survey of children aged 24–59 months conducted in El Salvador in 2011. Vaccine doses included were documented on vaccination cards (94.4%) or in health facility records (5.6%). Logistic regression and survival analysis were used to assess factors associated with vaccination status and age at vaccination. Receipt of pentavalent vaccine by age 15 weeks was associated with rotavirus vaccination (OR: 5.1; 95% CI 2.7, 9.4), and receipt of the second pentavalent dose by age 32 weeks was associated with receipt of two rotavirus vaccine doses (OR: 5.0; 95% CI 2.1–12.3). Timely coverage with the first pentavalent vaccine dose was 88.2% in the 2007 cohort and 91.1% in the 2008 cohort (p = 0.04). Children born in 2009, when a four-month national rotavirus vaccine stock-out occurred, had an older median age of receipt of rotavirus vaccine and were less likely to receive rotavirus on the same date as the same dose of pentavalent vaccine than children born in 2007 and 2008. Upper age limit recommendations for rotavirus vaccine administration contributed to suboptimal vaccination coverage. Survey data suggest that late rotavirus vaccination and co-administration with later doses of pentavalent vaccine among children born in 2009 helped increase rotavirus vaccine coverage following shortages.     

Impact of rotavirus vaccination on diarrheal hospitalizations in children younger than 5 years of age in a rural southern Mozambique

BackgroundRotavirus vaccine (Rotarix®) was introduced in Mozambique through its Expanded Program of Immunization in September 2015. We assessed the impact of rotavirus vaccination on childhood gastroenteritis-associated hospitalizations post-vaccine introduction in a high HIV prevalence rural setting of southern Mozambique.MethodsWe reviewed and compared the trend of hospitalizations (prevalence) and incidence rates of acute gastroenteritis (AGE), and rotavirus associated-diarrhea (laboratory confirmed rotavirus) in pre- (January 2008–August 2015) and post-rotavirus vaccine introduction periods (September 2015–December 2020), among children <5 years of age admitted to Manhiça District Hospital.ResultsFrom January 2008 to December 2020, rotavirus vaccination was found to contribute to the decline of the prevalence of AGE from 19% (95% CI: 18.14–20.44) prior to the vaccine introduction to 10% (95% CI: 8.89–11.48) in the post-introduction period, preventing 40% (95 % IE: 38–42) and 84% (95 % IE: 80–87) of the expected AGE and laboratory confirmed rotavirus cases, respectively, among infants. Similarly, the overall incidence of rotavirus was 11.8-fold lower in the post-vaccine introduction period (0.4/1000 child-years-at-risk [CYAR]; 95% CI: 0.3–0.6) compared with the pre-vaccination period (4.7/1000 CYAR; 95% CI: 4.2–5.1) with the highest reduction being observed among infants (16.8-fold lower from the 15.1/1000 CYAR in the pre-vaccine to 0.9/1000 CYAR in the post-vaccine eras).ConclusionsWe documented a significant reduction in all-cause diarrhea hospitalizations and rotavirus positivity after vaccine introduction demonstrating the beneficial impact of rotavirus vaccination in a highly vulnerable population.     

Effectiveness of quadrivalent influenza vaccination in the first year of a funded childhood program in Queensland,Australia, 2018

BackgroundFollowing high influenza activity in 2017, the state of Queensland, Australia, funded a quadrivalent inactivated influenza vaccination program for children aged 6 months to <5 years in 2018. We calculated influenza vaccine effectiveness (VE) among children eligible for this program.MethodsA matched case-control study was conducted. Cases were identified using Queensland 2018 influenza notification data among children age-eligible for funded vaccination. Controls were drawn from Australian Immunisation Register records of Queensland resident children age-eligible for funded influenza vaccine. Up to 10 controls per case were matched for location and birthdate. First dose vaccination was valid if received ≥14 days prior to specimen collection; a second dose was valid if received ≥28 days after first dose receipt. VE was calculated for vaccine doses and adherence to national recommendations for two doses in the first season (schedule completeness) and adjusted (VE_adj) for sex and First Nations status.ResultsThere were 1,125 cases and 10,645 matched controls analysed. Overall VE_adj against laboratory-confirmed influenza was 51% (95% confidence interval (CI) 41–60). VE_adj was 60% (95% CI 46–70) for children who received two doses in 2018, and 60% (95% CI 48–69) for children vaccinated appropriately according to schedule completeness. VE increased with age.ConclusionsModerate vaccine effectiveness was observed for children eligible for the funded program in Queensland in 2018, adding to the sparse evidence for influenza vaccine use in Australian children. Adhering to the national first season two dose schedule for influenza vaccine receipt in children ensures maximum protection.     

A population based study comparing changes in rotavirus burden on the Island of Ireland between a highly vaccinated population and an unvaccinated population

BackgroundRotavirus infection is a leading cause of gastroenteritis in infants and children globally. Reductions in rotavirus activity have been observed following introduction of rotavirus vaccination programmes, however a reductions have also been reported in some unvaccinated countries.The Island of Ireland incorporates the two jurisdictions Northern Ireland (NI) and the Republic of Ireland (IE). Both have similarities in climate, demography, morbidity and mortality but distinct health administrations and vaccination policies. Rotarix was added to the childhood immunisation programme in NI on the 1 July 2013. IE have not introduced routine rotavirus vaccination to date.The aim of this population based ecological study was to evaluate the impact of the rotavirus vaccine on burden of rotavirus disease in NI, and to compare with IE as an unvaccinated control population. This will help determine if the changes seen were due to the rotavirus vaccine, or due to confounding factors.MethodsA number of population based measures of disease burden were compared in both jurisdictions pre-vaccine (six years; 2007/08–2012/13) and post-vaccine (two years; 2013/14–2014/15). The data sources included national rotavirus surveillance data based on laboratory reports/notifications; hospital admission data; and notifications of gastroenteritis in under 2 year olds.ResultsIn the post-vaccination period, rotavirus incidence in NI dropped by 54% while in IE it increased by 19% compared to the pre-vaccine period. Notifications of gastroenteritis in under 2 s in NI declined by 53% and hospital admissions in under 5 year olds in NI declined by 40% in the post vaccine period.ConclusionsThis natural experiment demonstrated a significant reduction in rotavirus disease activity post-vaccine introduction in NI with associated reductions in healthcare utilisation, with a concurrent increase in rotavirus disease activity in the non-vaccinated population in IE. These findings support rotavirus vaccination as an effective measure to reduce childhood morbidity.     

Effectiveness of typhoid conjugate vaccine in Zimbabwe used in response to an outbreak among children and young adults: A matched case control study

BackgroundZimbabwe suffers from regular outbreaks of typhoid fever (TF), worse since 2017. Most cases were in Harare and a vaccination campaign with Typhoid Conjugate Vaccine (TCV) was conducted in March 2019. The vaccine effectiveness (VE) was assessed against culture-confirmed S. Typhi in children six months to 15 years and in individuals six months to 45 years in Harare.MethodsA matched case-control study was conducted in three urban suburbs of Harare targeted by the TCV vaccination campaign. Suspected TF cases were enrolled prospectively in four health facilities and were matched to facility (1:1) and community (1:5) controls.FindingsOf 504 suspected cases from July 2019 to March 2020, 148 laboratory-confirmed TF cases and 153 controls confirmed-negative were identified. One hundred and five (47 aged six months to 15 years) cases were age, sex, and residence matched with 105 facility-based controls while 96 cases were matched 1:5 by age, sex, and immediate-neighbour with 229 community controls.The adjusted VE against confirmed TF was 75% (95%CI: 1–94, p = 0.049) compared to facility controls, and 84% (95%CI: 57–94, p < 0.001) compared to community controls in individuals six months to 15 years. The adjusted VE against confirmed TF was 46% (95%CI: 26–77, p = 0.153) compared to facility controls, and 67% (95%CI: 35–83, p = 0.002) compared to community controls six months to 45 years old.InterpretationThis study confirms that one vaccine dose of TCV is effective to control TF in children between six months and 15 years old in an African setting.     

Beyond expectations: Post-implementation data shows rotavirus vaccination is likely cost-saving in Australia

BackgroundUniversal vaccination against rotavirus was included in the funded Australian National Immunisation Program in July 2007. Predictive cost-effectiveness models assessed the program before introduction.MethodsWe conducted a retrospective economic evaluation of the Australian rotavirus program using national level post-implementation data on vaccine uptake, before-after measures of program impact and published estimates of excess intussusception cases. These data were used as inputs into a multi-cohort compartmental model which assigned cost and quality of life estimates to relevant health states, adopting a healthcare payer perspective. The primary outcome was discounted cost per quality adjusted life year gained, including or excluding unspecified acute gastroenteritis (AGE) hospitalisations.ResultsRelative to the baseline period (1997–2006), over the 6 years (2007–2012) after implementation of the rotavirus program, we estimated that ∼77,000 hospitalisations (17,000 coded rotavirus and 60,000 unspecified AGE) and ∼3 deaths were prevented, compared with an estimated excess of 78 cases of intussusception. Approximately 90% of hospitalisations prevented were in children <5 years, with evidence of herd protection in older age groups. The program was cost-saving when observed changes (declines) in both hospitalisations coded as rotavirus and as unspecified AGE were attributed to the rotavirus vaccine program. The adverse impact of estimated excess cases of intussusception was far outweighed by the benefits of the program.ConclusionThe inclusion of herd impact and declines in unspecified AGE hospitalisations resulted in the value for money achieved by the Australian rotavirus immunisation program being substantially greater than predicted by pre-implementation models, despite the potential increased cases of intussusception. This Australian experience is likely to be relevant to high-income countries yet to implement rotavirus vaccination programs.     

Effectiveness of monovalent rotavirus vaccine against hospitalizations due to all rotavirus and equine-like G3P[8] genotypes in Haiti 2014–2019

BackgroundRotavirus vaccines are effective in preventing severe rotavirus. Haiti introduced 2-dose monovalent (G1P[8]) rotavirus vaccine recommended for infants at 6 and 10 weeks of age in 2014. We calculated the effectiveness of rotavirus vaccine against hospitalization for acute gastroenteritis in Haiti.MethodsWe enrolled children 6–59 months old admitted May 2014-September 2019 for acute watery diarrhea at any sentinel surveillance hospital. Stool was tested for rotavirus using enzyme immunoassay (EIA) and genotyped with multiplex one-step RT-PCR assay and Sanger sequencing for stratification by genotype. We used a case-negative design where cases were children positive for rotavirus and controls were negative for rotavirus. Only children eligible for vaccination were included and a child was considered vaccinated if vaccine was given ≥ 14 days before enrollment. We used unconditional logistic regression to calculate odds ratios and calculated 2-dose and 1-dose vaccine effectiveness (VE) as (1 - odds ratio) * 100.ResultsWe included 129 (19%) positive cases and 543 (81%) negative controls. Among cases, 77 (60%) were positive for equine-like G3P[8]. Two doses of rotavirus vaccine were 66% (95% CI: 44, 80) effective against hospitalizations due to any strain of rotavirus and 64% (95% CI: 33, 81) effective against hospitalizations due to the equine-like G3P[8] genotype.ConclusionsThese findings are comparable to other countries in the Americas region. To the best of our knowledge, this is the first VE estimate both against the equine-like G3P[8] genotype and from a Caribbean country. Overall, these results support rotavirus vaccine use and demonstrate the importance of complete vaccination.     

Epidemiology of varicella in Haidian district,Beijing, China—2007–2015

Background1-Dose varicella vaccination was recommended for children in Beijing before November 2012. To further control school-based outbreaks and decrease incidence, a 2-dose vaccination was implemented in 2013. We described the varicella epidemiology and assessed impact of the 2-dose vaccination in Haidian district, Beijing, 2007–2015.MethodsWe examined the estimated incidence and disease characteristics of varicella during 2007–2015 and obtained the 1-dose vaccination coverage for children born during 2005–2013. Number of vaccine doses given was used to indirectly reflect the second-dose vaccination coverage. Overall and age-specific estimated incidences were compared between 2007–2012 and 2013–2015.ResultsA total of 23,497 cases were reported during 2007–2015. Of the 23,497 cases, 13,440 (57.20%) were male, and 68.40% were <20 years of age and 70.02% were students and children in kindergarten. The estimated incidence increased from 82 cases per 100,000 population in 2007 to 104 in 2011, before substantially decreasing from 86 in 2012 to 56 in 2015. The median age increased from 14 years in 2007 to 18 years in 2015. The 1-dose varicella coverage for children at ≥2 years of age gradually increased from 74.21% in 2007 to 90.06% in 2015. Compared with 2007–2012, two-fold average vaccine doses were given during 2013–2015, and the overall estimated incidence declined by 34.4%, particularly in children aged 5–9 years, with a significantly declined trend in children aged 1–9 years and older adolescents aged 15–19 years and non-significantly declined trend in adults aged ≥20 years, but a significant increasing trend in infants.ConclusionsThe overall incidence of varicella has decreased substantially in Haidian district since 2013, with largest decline in children aged 5–9 years. The 2-dose varicella vaccination might not lead to increase in incidence in adults. Long-term surveillance is needed to fully evaluate the long-term impact of the 2-dose varicella vaccination.     

Use of the state immunization information system to assess rotavirus vaccine effectiveness in Connecticut, 2006-2008

Immunization information systems (IIS) contain individual vaccination records and have potential use for evaluating post-licensure vaccine effectiveness (VE). A matched case-control study was performed by using the Connecticut state IIS to calculate rotavirus VE against hospitalization; results were compared with pre-licensure efficacy and with estimates previously obtained by traditional case-control methods using matched controls from medical sources and medical chart abstracted data. Case-patients (n = 54) were vaccine-eligible children with IIS entry and hospitalized for rotavirus gastroenteritis during July 2006-December 2008; each was matched to five control subjects (n = 270) who were randomly selected from IIS based on case-patient's birth date and town of residence. VE of at least one dose was 90.6%, comparable to the pre-licensure efficacy of 96% and to the unadjusted 83.5-90.7% estimates by using traditional case-control methods. IIS can be a convenient and potentially accurate tool for calculating VE.     

Cost-effectiveness and budget impact analyses for the prioritisation of the four available rotavirus vaccines in the national immunisation programme in Thailand

BackgroundRotavirus is a major cause of diarrhoea in children less than five years old in Thailand. Vaccination has been shown to be an effective intervention to prevent rotavirus infections but has yet to be enlisted in the national immunisation programme. This study aimed to assess the cost-utility of introducing rotavirus vaccines, taking all WHO-prequalified vaccines into consideration.MethodsA cost-utility analysis was performed using a transmission dynamic model to estimate, from a societal perspective, the costs and outcomes of four WHO-prequalified rotavirus vaccines: Rotarix®, RotaTeq®, ROTAVAC® and ROTASIIL®. The model was used to simulate the impact of introducing the vaccines among children aged < 1 year and compare this with no rotavirus vaccination. The vaccination programme was considered to be cost-effective if the incremental cost-effectiveness ratio was less than a threshold of USD 5,110 per QALY gained.ResultsOverall, without the vaccine, the model predicted the average annual incidence of rotavirus to be 312,118 cases. With rotavirus vaccination at a coverage of more than 95%, the average number of rotavirus cases averted was estimated to be 144,299 per year. All rotavirus vaccines were cost-saving. ROTASIIL® was the most cost-saving option, followed by ROTAVAC®, Rotarix® and RotaTeq®, providing average cost-savings of USD 32, 31, 23 and 22 million per year, respectively, with 999 QALYs gained. All vaccines remained cost-saving with lower QALYs gained, even when ignoring indirect beneficial effects. The net saving to the healthcare system when implementing any one of these vaccines would be between USD 13 and 33 million per year.ConclusionRotavirus vaccines should be included in the national vaccination programme in Thailand. Implementing any one of these four WHO-prequalified vaccines would reduce government healthcare spending while yielding health benefits to the population.     

Intussusception among Norwegian children: What to expect after introduction of rotavirus vaccination?

BackgroundTo reduce the risk of vaccine-associated intussusception, rotavirus vaccination in Norway was implemented under strict age limits (the first dose given by 12 weeks of age and the second dose by 16 weeks of age) in 2014. We estimated the incidence of intussusception in children <2 years old before vaccine introduction and the number of vaccine-associated cases under current and extended age limits for vaccine administration in Norway.MethodsTo estimate the baseline incidence, we validated all diagnoses in children <2 years old registered in the national hospital registry during the pre-vaccine period of 2008–2013. Using national vaccine coverage data and international estimates of intussusception risk after rotavirus vaccination, we calculated the numbers of expected vaccine-associated intussusception cases to compare with the estimated numbers of averted rotavirus cases. Uncertainty was accounted for by several scenario analyses using current and extended age limits for vaccine administration.ResultsThe pre-vaccine incidence of intussusception was 26.7 (95% CI 23.1–30.6) cases/year per 100,000 children <2 years old and 37.1 (95% CI 31.2–43.8) cases/year per 100,000 children <1 year old. In the 2016 birth cohort (approx. 60,000) vaccinated under the current age limits, 1.3 (95% CI 0.7–2.0) vaccine-associated intussusception cases were expected to occur. If age limits were extended to 16 weeks for the first vaccine dose and 24 weeks for the second dose, leading to more children vaccinated at an older age, 2.2 (95% CI 1.2–3.5) excess cases would be expected in the same cohort. Simultaneously, an estimated 1768 rotavirus hospitalizations/year in children <5 years old would be averted under current age limits, with 98 additional rotavirus hospitalizations averted under extended age limits.ConclusionsAdministering rotavirus vaccines beyond current age limits in Norway would lead to a marginal increase in the number of intussusception cases, which would be offset by the benefits of vaccination.     

Vaccination rate and immunity of children and adolescents with inflammatory bowel disease or autoimmune hepatitis in Germany

Background and aimsImmunosuppressed patients are at risk of severe infections with vaccination preventable diseases. We evaluated vaccination rate and immunity of children and adolescents with inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH).MethodsImmunization rate of 329 children with IBD (n = 300) and AIH (n = 29) was assessed in seven German centres using vaccination certificates, history of chicken pox and by determining anti-varicella zoster virus (VZV) and anti-measles IgG antibodies.ResultsOf the total cohort 86% received long-term immunosuppression. Four doses of a hexavalent vaccine were documented in 89%, at least one dose of measles, mumps, and rubella (MMR) vaccination was documented in 325 (99%), with 300 (92%) receiving two doses. Anti-measles IgG concentrations were insufficient in 11% of the immunized patients.VZV vaccination was officially recommended in Germany since 2004, and implemented in 88% born from 2005 onwards. In patients born earlier VZV catch up vaccination only reached 25% (n = 67). Of 118 patients with documented VZV vaccination 25 (21%) did not display sufficient anti-VZV IgG. Of 198 patients with a history of chicken pox, six had undetectable anti-VZV IgG. Of 29 patients having neither had chicken pox nor VZV vaccination, 20 were found to have sufficient anti-VZV IgG.ConclusionsIn our cohort vaccination coverage for hexavalent and MMR vaccinations was good, but insufficient for VZV vaccination in patients born before 2005. Neither the vaccination certificate nor the history of chicken pox is reliable to predict VZV immunity indicating a need for serologic investigations and if needed vaccination before initiating immunosuppressive therapy.     

Effectiveness of Lanzhou lamb rotavirus vaccine in preventing gastroenteritis among children younger than 5 years of age

BackgroundLanzhou Lamb rotavirus (LLR) vaccine was licensed in China in 2000. It was the only vaccine available in private market before 2018. However, the data about the post-marketing effectiveness is very limited. To assess the vaccine effectiveness (VE), we conducted a case-control study based on the hospital surveillance system in Beijing from 2015 to 2017.MethodsSeven hospitals located in seven districts in Beijing, from October 1, 2015, to March 31, 2017, were included. The VE of LLR vaccine was assessed in laboratory-confirmed rotavirus infection among children younger than five years old through a case-control design, using rotavirus-negative cases as controls. LLR vaccination was documented from a vaccination registry. VE was estimated adjusting for age group, gender, study site, the month of illness onset and interval days between illness onset to sampling through a logistic regression model.ResultsA total of 598 cases and 1766 controls were included in this study. The vaccine average coverage rate during 2015–2017 among children younger than five years old was 10.8% in Beijing. The adjusted VE for LLR vaccine of 1 dose versus 0 dose was 34.9% (95%CI, 5.3–55.3). We also obtained the adjusted VE of 87.7% (95%CI, 32.7–97.8) for patients with the severity score ≥11, 36.2% (95%CI, 4.7–57.3) for children of 2–35 months age group and 40.8% (95%CI, 7.8–61.9) against G9 rotavirus infection. Vaccinated cases were less likely to have watery stool (OR = 0.42) and have diarrhea longer than 5 days (OR = 0.47) than unvaccinated cases.DiscussionLLR vaccine conferred protection against rotavirus disease. Children who were vaccinated presented with less severe clinical manifestations. An immunization schedule of receiving all three doses in the first year should be preferred.     

Lower incidence of hospital-treated infections in infants under 3 months of age vaccinated with BCG

BackgroundLive vaccines potentially have non-specific effects that protect against other infections than those the vaccines are targeted against. The national vaccination program (NVP) in Finland was changed on September 1st, 2006: before BCG vaccine was given to all newborn babies and afterwards to babies in risk groups only. We used this natural experiment to study the non-specific effects of BCG in the frame of NVP using before-after design.MethodsWe compared the incidence of several outcomes obtained from Finnish health registers between children born between July 1st, 2004, and June 30th, 2006 (BCG-eligible) and an age- and season-matched reference cohort born between July 1st, 2007, and June 30th, 2009 (BCG-non-eligible) using Poisson regression. These cohorts were restricted to full-term children whose parents were born in Finland. Follow-up began at birth and lasted 3 months, which is the scheduled age for DTaP-IPV-Hib vaccination, and from 4 months until first birthday. The outcomes included all infections, pneumonia and injuries as a negative control outcome.ResultsThe incidence rate ratio (IRR) of the BCG-eligible cohort (N = 93,658) compared to BCG-non-eligible cohort (N = 94,712) for hospital-diagnosed infections was 0.89 (95 %Cl 0.86–0.93) for the 3-month follow-up. The decrease was mainly caused by respiratory infections. In 4–12 months follow-up the BCG-eligible had slightly more infections than BCG-non-eligible children (IRR 1.03, 1.01–1.06).ConclusionsBCG vaccination was associated with a lower incidence of all hospital-diagnosed infections during the first three months of life. The difference cannot be attributed to lung tuberculosis, since only few paediatric cases occurred in Finland during 2000s. The disappearance of non-specific effect after administration of an inactivated vaccine is compatible with previous studies.     

Association between mixed rotavirus vaccination types of infants and rotavirus acute gastroenteritis

IntroductionRotavirus remains the leading cause of severe diarrhea in children under 5 years worldwide. In the US, Rotarix^® (RV1) and RotaTeq^® (RV5), have been associated with reductions in and severity of rotavirus disease. Studies have evaluated the impact of RV1 or RV5 but little is known about the impact of incomplete or mixed vaccination upon vaccine effectiveness.MethodsCase control study to examine association of combined RV1 and RV5 and rotavirus acute gastroenteritis, factoring severity of diarrheal disease. Children born after March 1, 2009 with acute gastroenteritis from three pediatric hospitals in Atlanta, Georgia were approached for enrollment. Survey was administered, stool specimen was collected, and vaccination records were obtained.Results891 of 1127 children with acute gastroenteritis were enrolled. Stool specimens were collected from 708 for rotavirus testing; 215 stool samples tested positively for rotavirus. Children >12 months of age were more likely to have rotavirus. Children categorized with Vesikari score of >11 were almost twice as likely to be rotavirus positive. Prior rotavirus vaccination decreased the mean Vesikari score, p < 0.0001. Children with complete single type vaccination were protected against rotavirus (OR 0.21, 95% CI: 0.14–0.31, p < 0.0001).ConclusionComplete rotavirus vaccination with a single vaccine type resulted in protection against rotavirus diarrhea and decrease in severity of rotavirus gastroenteritis. Incomplete rotavirus vaccination either with a single vaccine or mixed vaccination types also provided some protection.