Incidence of narcolepsy before and after MF59-adjuvanted influenza A(H1N1)pdm09 vaccination in South Korean soldiers

BackgroundPrevious reports mostly from Europe suggested an association between an occurrence of narcolepsy and an influenza A(H1N1)pdm09 vaccine adjuvanted with AS03 (Pandemrix^®). During the 2009 H1N1 pandemic vaccination campaign, the Korean military performed a vaccination campaign with one type of influenza vaccine containing MF59-adjuvants. This study was conducted to investigate the background incidence rate of narcolepsy in South Korean soldiers and the association of the MF59-adjuvanted vaccine with the occurrence of narcolepsy in a young adult group.MethodsTo assess the incidence of narcolepsy, we retrospectively reviewed medical records of suspicious cases of narcolepsy in 2007–2013 in the whole 20 military hospitals of the Korean military. The screened cases were classified according to the Brighton Collaboration case definition of narcolepsy. After obtaining the number of confirmed cases of narcolepsy per 3 months in 2007–2013, we compared the crude incidence rate of narcolepsy before and after the vaccination campaign.ResultsWe included 218 narcolepsy suspicious cases in the initial review, which were screened by the diagnostic code on the computerized disease registry in 2007–2013. Forty-one cases were finally diagnosed with narcolepsy in 2007–2013 (male sex, 95%; median age, 21 years). The average background incidence rate of narcolepsy in Korean soldiers was 0.91 cases per 100,000 persons per year. During the 9 months before vaccination implementation (April to December 2009), 6 narcolepsy cases occurred, whereas during the next 9 months (January to September 2010) including the 3-month vaccination campaign, 5 cases occurred.ConclusionsThe incidence of narcolepsy in South Korean soldiers was not increased after the pandemic vaccination campaign using the MF59-adjuvanted vaccine. Our results suggest that the MF59-adjuvanted H1N1 vaccine did not contribute to the occurrence of narcolepsy in this young adult group.     

National hospital data for intussusception: Data linkage and retrospective analysis to assess quality and use in vaccine safety surveillance

ObjectivesTo assess the quality of national Hospital Episode Statistics (HES) data for intussusception, and evaluate this routinely collected database for rotavirus vaccine safety surveillance by estimating pre-vaccination trends in intussusception hospitalisation.MethodsData linkage was performed between HES and prospective intussusception data from the British Paediatric Surveillance Unit (BPSU), followed by capture–recapture analysis to verify HES data quality. Inclusion criteria were infants aged less than 12 months and admitted for intussusception to National Health Service (NHS) hospitals in England from March 2008 to March 2009. To estimate pre-vaccination incidence rates of intussusception, we performed a retrospective analysis of HES data. Infants aged less than 12 months and admitted for intussusception to NHS hospitals in England between 1995 and 2009 were included.ResultsData linkage between 254 cases of intussusception identified in HES data and 190 cases reported via the BPSU resulted in 163 cases common to both data sources. Of remaining 91 cases in HES, 37 had confirmed intussusception. HES data accuracy was 78.7% (200 confirmed/254 cases) and completeness for intussusception was 86% (163 matched/190 BPSU cases) compared to 81.5% (163 matched/200 HES cases) for BPSU. A total of 233 (95% CI: 227.4 to 238.8) intussusception cases were estimated for the infant population (2008 to 2009). For retrospective analysis, of 6462 intussusception admissions in HES data (1995 to 2009), 1594 (24.7%) were duplicate admissions. A declining trend in intussusception incidence was observed in the infant population, from 86/100,000 in 1997 to 34/100,000 in 2009 (60% reduction, P < 0.001). Cosinor modelling showed an excess of cases among infants in winter and spring (P < 0.001, n = 4957, 1995 to 2009).ConclusionNational hospital data capture the majority of admissions for intussusception and should be considered for the post-implementation surveillance of rotavirus vaccine safety in England.     

Hepatitis A vaccination coverage among adolescents (13–17 years) in the United States, 2008–2016

BackgroundThe hepatitis A (HepA) vaccine was recommended by the Advisory Committee on Immunization Practices (ACIP) incrementally from 1996 to 1999. In 2006, HepA vaccine was recommended (1) universally for children aged 12–23 months, (2) for persons who are at increased risk for infection, or (3) for any person wishing to obtain immunity. Catch-up vaccination can be considered.ObjectiveTo assess HepA vaccine coverage among adolescents and factors independently associated with vaccination administration in the US.MethodsThe 2008–2016 National Immunization Survey–Teen was utilized to determine 1 and ≥2 dose HepA vaccination coverage among adolescents aged 13–17 years. Factors associated with HepA vaccine series initiation (1 dose) were determined by bivariate and multivariable analyses. Data were stratified by state groups based on ACIP recommendation: universal child vaccination recommended since 1999 (group 1); child vaccination considered since 1999 (group 2); universal child vaccination recommendation since 2006 (group 3).ResultsIn 2016, national vaccination coverage for 1 and ≥2 doses of HepA vaccine among adolescents was 73.9% and 64.4%, respectively. Nationally, a 40 percentage point increase in vaccination coverage occurred among adolescents born in 1995 compared to adolescents born in 2003. Nationally, the independent factors associated with increased vaccine initiation was race/ethnicity (Hispanic, American Indian/Alaskan Native, Asian), military payment source and provider recommendation for HepA vaccination (2008–2013). Living in a suburban or rural region, living in poverty (level <1.33–5.03), and absence of state daycare or school HepA requirement were common factors associated with decreased likelihood of vaccine initiation.ConclusionsEfforts to increase HepA vaccine coverage in adolescents in all regions of the country would strengthen population protection from hepatitis A virus (HAV).     

A follow-up comparative safety analysis of pandemic H1N1 vaccination during pregnancy and risk of infant birth defects among U.S. military mothers

ObjectiveTo update a previous assessment of birth defects among infants born to active duty U.S. military mothers who received the 2009–2010 pandemic H1N1 vaccine, in comparison to the 2008–2009 seasonal influenza vaccine, during pregnancy. Here, we updated the previous comparative analyses with a more refined definition for birth defects using an additional year of follow-up data from both inpatient and outpatient medical encounters.MethodsThe study population included 15,510 live born infants born to active duty mothers vaccinated during pregnancy with either the 2009–2010 pandemic H1N1 vaccine (n = 9033) or the 2008–2009 seasonal influenza vaccine (n = 6477). Birth defect cases were defined as those infants who received a birth defect diagnosis on one inpatient record or two outpatient records on different days within the first year of life. Multivariable logistic regression models were conducted to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between birth defects and maternal vaccination during pregnancy with pandemic H1N1 vaccine versus seasonal influenza vaccine.ResultsInfants born to mothers vaccinated during pregnancy with the pandemic H1N1 vaccine, versus the seasonal influenza vaccine, were not at increased odds of birth defects in univariable (OR: 1.13, 95% CI: 0.95–1.34) or multivariable (OR: 1.14, 95% CI: 0.96–1.35) models. Findings were not significant when further limited to first trimester exposure. Multivariable models were adjusted for infant sex and plurality; maternal age, race/ethnicity, marital status, service branch, military rank, and occupation; timing of vaccination; and receipt of vaccination(s) not routinely recommended during pregnancy.ConclusionComparable to our previous analyses assessing birth defects diagnosed at birth, no significant association was found between the pandemic H1N1 vaccination during pregnancy and birth defects, versus the seasonal influenza vaccine. These findings are reassuring and provide additional support for H1N1-containing seasonal influenza vaccination during pregnancy.     

MMR vaccination status of children exempted from school-entry immunization mandates

BackgroundChild immunizations are one of the most successful public health interventions of the past century. Still, parental vaccine hesitancy is widespread and increasing. One manifestation of this are rising rates of nonmedical or “personal beliefs” exemptions (PBEs) from school-entry immunization mandates. Exemptions have been shown to be associated with increased risk of disease outbreak, but the strength of this association depends critically on the true vaccination status of exempted children, which has not been assessed.ObjectiveTo estimate the true measles-mumps-rubella (MMR) vaccination status of children with PBEs.MethodsWe use administrative data collected by the California Department of Public Health in 2009 and imputation to estimate the MMR vaccination status of children with PBEs under varying scenarios.ResultsResults from 2009 surveillance data indicate MMR1/MMR2 coverage of 18–47% among children with PBEs at typical schools and 11–34% among children with PBEs at schools with high PBE rates. Imputation scenarios point to much higher coverage (64–92% for MMR1 and 25–58% for MMR2 at typical schools; 49–90% for MMR1 and 16–63% for MMR2 at high PBE schools) but still below levels needed to maintain herd immunity against measles.ConclusionsThese coverage estimates suggest that prior analyses of the relative risk of measles associated with vaccine refusal underestimate that risk by an order of magnitude of 2–10 times.     

Mass vaccination with a two-dose oral cholera vaccine in a long-standing refugee camp,Thailand

BackgroundDuring 2005–2012, surveillance in Maela refugee camp, Thailand, identified four cholera outbreaks, with rates up to 10.7 cases per 1000 refugees. In 2013, the Thailand Ministry of Public Health sponsored a two-dose oral cholera vaccine (OCV) campaign for the approximately 46,000 refugees living in Maela.MethodsWe enumerated the target population (refugees living in Maela who are ≥1 year old and not pregnant) in a census three months before the campaign and issued barcoded OCV cards to each individual. We conducted the campaign using a fixed-post strategy during two eight-day rounds plus one two-day round for persons who had missed their second dose and recorded vaccine status for each individual. To identify factors associated with no vaccination (versus at least one dose) and those associated with adverse events following immunization (AEFI), we used separate marginal log-binomial regression models with robust variance estimates to account for household clustering.ResultsA total of 63,057 OCV doses were administered to a target population of 43,485 refugees. An estimated 35,399 (81%) refugees received at least one dose and 27,658 (64%) received two doses. A total of 993 additional doses (1.5%) were wasted including 297 that were spat out. Only 0.05% of refugees, mostly children, could not be vaccinated due to repeated spitting. Characteristics associated with no vaccination (versus at least one dose) included age ≥15 years (versus 1–14 years), Karen ethnicity (versus any other ethnicity) and, only among adults 15–64 years old, male sex. Passive surveillance identified 84 refugees who experienced 108 AEFI including three serious but coincidental events. The most frequent AEFI were nausea (49%), dizziness (38%), and fever (30%). Overall, AEFI were more prevalent among young children and older adults.ConclusionsOur results suggest that mass vaccination in refugee camps with a two-dose OCV is readily achievable and AEFI are few.     

Cost-effectiveness analysis of catch-up hepatitis A vaccination among unvaccinated/partially-vaccinated children

BackgroundSince 2006, the US Centers for Disease Control and Prevention has recommended hepatitis A (HepA) vaccination routinely for children aged 12–23 months to prevent hepatitis A virus (HAV) infection. However, a substantial proportion of US children are unvaccinated and susceptible to infection. We present results of economic modeling to assess whether a one-time catch-up HepA vaccination recommendation would be cost-effective.MethodsWe developed a Markov model of HAV infection that followed a single cohort from birth through death (birth to age 95 years). The model compared the health and economic outcomes from catch-up vaccination interventions for children at target ages from two through 17 years vs. outcomes resulting from maintaining the current recommendation of routine vaccination at age one year with no catch-up intervention.ResultsOver the lifetime of the cohort, catch-up vaccination would reduce the total number of infections relative to the baseline by 741 while increasing doses of vaccine by 556,989. Catch-up vaccination would increase net costs by $10.2 million, or $2.38 per person. The incremental cost of HepA vaccine catch-up intervention at age 10 years, the midpoint of the ages modeled, was $452,239 per QALY gained. Across age-cohorts, the cost-effectiveness of catch-up vaccination is most favorable at age 12 years, resulting in an Incremental Cost-Effectiveness Ratio of $189,000 per QALY gained.ConclusionsGiven the low baseline of HAV disease incidence achieved by current vaccination recommendations, our economic model suggests that a catch-up vaccination recommendation would be less cost-effective than many other vaccine interventions, and that HepA catch-up vaccination would become cost effective at a threshold of $50,000 per QALY only when incidence of HAV rises about 5.0 cases per 100,000 population.     

Waning vaccine protection against influenza A (H3N2) illness in children and older adults during a single season

BackgroundRecent studies have suggested that vaccine-induced protection against influenza may decline within one season. We reanalyzed data from a study of influenza vaccine effectiveness to determine if time since vaccination was an independent predictor of influenza A (H3N2).MethodsPatients with acute respiratory illness were actively recruited during the 2007–2008 season. Respiratory swabs were tested for influenza, and vaccination dates were determined by a validated immunization registry. The association between influenza RT-PCR result and vaccination interval (days) was examined using multivariable logistic regression, adjusting for calendar time, age and other confounders.ResultsThere were 629 vaccinated participants, including 177 influenza A (H3N2) cases and 452 test negative controls. The mean (SD) interval from vaccination to illness onset was 101.7 (25.9) days for influenza cases and 93.0 (29.9) days for controls. There was a significant association between vaccination interval and influenza result in the main effects model. The adjusted odds ratio (aOR) for influenza was 1.12 (CI 1.01, 1.26) for every 14 day increase in the vaccination interval. Age modified the association between vaccination interval and influenza (p = 0.005 for interaction). Influenza was associated with increasing vaccination interval in young children and older adults, but not in adolescents or non-elderly adults. Similar results were found when calendar week of vaccine receipt was assessed as the primary exposure variable.ConclusionsIdentification of influenza A (H3N2) was associated with increasing time since vaccination among young children and older adults during a single influenza season.     

The changing epidemiology of invasive pneumococcal disease after PCV13 vaccination in a country with intermediate vaccination coverage

BackgroundWe studied the impact of 13-valent pneumococcal conjugate vaccine (PCV13) on the incidence of invasive pneumococcal disease (IPD) and serotype distribution in a region with intermediate levels of vaccination (around 64% in children aged <2 years).MethodsSurveillance data on IPD cases reported by microbiologists participating in the Microbiological Reporting System of Catalonia during 2006–2014 were analysed. We compared estimated incidence rate (IR) ratios for serotypes included in PCV7, PCV10non7, PCV13non10 and non-PCV13 between the PCV7 (2006–2009) and PCV13 periods (2010–2014). IR were corrected for missing serotypes according to year and age groups: <2 years, 2–4 years, 5–64 years and ≥65 years.ResultsA total of 9338 IPD cases were reported. Overall IPD incidence declined by 26.2% (from 16.4 to 12.1) in the PCV13 period. The largest decrease was observed in children aged 2–4 years (44.5%, from 37.4 to 20.8). Pneumonia fell in all age groups with the largest reduction in children aged 2–4 years (49.3%) and <2 years (42%). PCV13 serotypes decreased significantly in all age groups, from 52% (31.6 to 15.1) in children aged 2–4 years to 35% (22.8 to 14.8) in adults aged ≥65 years. Non-PCV13 serotypes rose by 13% (14.8 to 16.8) in people aged ≥65 years.ConclusionsIn a region with intermediate vaccination coverage, the introduction of PCV13 has reduced the overall incidence of IPD, mainly due to the decrease in PCV13 serotypes in all age groups, suggesting herd immunity. Non-PCV13 serotypes have increased in adults aged ≥65 years, suggesting serotype replacement. Higher PCV13 vaccination coverage in children will further reduce IPD incidence in all age groups.     

Association of spontaneous abortion with receipt of inactivated influenza vaccine containing H1N1pdm09 in 2010–11 and 2011–12

IntroductionInactivated influenza vaccine is recommended in any stage of pregnancy, but evidence of safety in early pregnancy is limited, including for vaccines containing A/H1N1pdm2009 (pH1N1) antigen. We sought to determine if receipt of vaccine containing pH1N1 was associated with spontaneous abortion (SAB).MethodsWe conducted a case-control study over two influenza seasons (2010–11, 2011–12) in the Vaccine Safety Datalink. Cases had SAB and controls had live births or stillbirths and were matched on site, date of last menstrual period, and age. Of 919 potential cases identified using diagnosis codes, 485 were eligible and confirmed by medical record review. Exposure was defined as vaccination with inactivated influenza vaccine before the SAB date; the primary exposure window was the 1–28 days before the SAB.ResultsThe overall adjusted odds ratio (aOR) was 2.0 (95% CI, 1.1–3.6) for vaccine receipt in the 28-day exposure window; there was no association in other exposure windows. In season-specific analyses, the aOR in the 1–28 days was 3.7 (95% CI 1.4–9.4) in 2010–11 and 1.4 (95% CI 0.6–3.3) in 2011–12. The association was modified by influenza vaccination in the prior season (post hoc analysis). Among women who received pH1N1-containing vaccine in the previous influenza season, the aOR in the 1–28 days was 7.7 (95% CI 2.2–27.3); the aOR was 1.3 (95% CI 0.7–2.7) among women not vaccinated in the previous season. This effect modification was observed in each season.ConclusionSAB was associated with influenza vaccination in the preceding 28 days. The association was significant only among women vaccinated in the previous influenza season with pH1N1-containing vaccine. This study does not and cannot establish a causal relationship between repeated influenza vaccination and SAB, but further research is warranted.     

The impact of expanded program on immunization with live attenuated and inactivated Hepatitis A vaccines in China, 2004–2016

IntroductionSince 2008, two types of hepatitis A (HepA) vaccines were integrated into the expanded program on immunization (EPI) in China. Children were given either one dose of live attenuated HepA (L-HepA) or two doses of inactivated HepA (I-HepA), depending on geographic regions. We sought to evaluate the impact of the EPI on HepA incidence in China.MethodsWe reviewed the epidemiology of HepA during 2004–2016 from National Notifiable Disease Reporting System (NNDRS). We collected data of L-HepA and I-HepA coverage from Children Immunization Information Management System (CIIMS). Based on the regions where two types of HepA vaccines were used, the coverage and incidence of HepA were compared over time.ResultsIn 2008–2016, the HepA vaccine coverage was 98.8% among target children, with 99.6% in I-HepA region and 98.7% in L-HepA region. HepA incidence declined by 78.0% and 82.3% in L-HepA region and I-HepA region, respectively, without significant difference. Dramatic decline were seen in all age groups of both regions.ConclusionThe study suggests that the EPI, with high coverage for both I-HepA and L-HepA, had positive impact on HepA incidence in China.     

Impact of PCV7/PCV13 introduction on community-acquired alveolar pneumonia in children <5 years

BackgroundAlveolar community-acquired pneumonia (A-CAP) is mostly considered a bacterial disease, mainly pneumococcal. This study was conducted to document the impact of sequential 7-valent and the 13-valent pneumococcal conjugate vaccines (PCV7; PCV13) on emergency room and hospitalization for A-CAP among children <5 years of age.MethodsThis is an ongoing prospective population-based study in southern Israel. The current analysis spans over the period July 2002 through June 2013. A-CAP was defined using the World Health Organization (WHO)’s criteria for radiologically-confirmed pneumonia. PCV7 was introduced in Israel in July 2009 and gradually replaced by PCV13 in November 2010. Pneumococcal conjugate vaccine (PCV) impact was calculated by comparing incidences during 3 pre-defined periods: pre-PCV (2002–2008), PCV7 (2010–2011) and PCV13 (2012–2013).ResultsOverall, 10,142 A-CAP episodes occurred. The annual incidences (per 1,000 inhabitants) in children <5 years old declined from a mean (±standard deviation) of 13.8 ± 0.9 in the pre-PCV period to 11.2 ± 2.7 in the PCV7 period and 7.4 in the PCV13 period, representing a reduction of 13% and 47%, respectively. The overall decrease was significantly faster among outpatients than among hospitalized children (42% and −8%, respectively in the PCV7 period; 68% vs. 32% in hospitalized children in the PCV13 period). While in children 12–23 months a significant decline was observed during the PCV7 and PCV13 periods, significant declines in A-CAP rates were observed only during the PCV13 period in the <12 months and 24–59 months age groups (44% and 46%, respectively).ConclusionsA moderate decline in hospital A-CAP visits in children <5 years old was observed after PCV7 introduction. In contrast, after PCV13 introduction a substantial reduction in all visits was evident.     

Immunization of preterm infants with GSK’s hexavalent combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine: A review of safety and immunogenicity

BackgroundInfants with history of prematurity (<37 weeks gestation) and low birth weight (LBW, <2500 g) are at high risk of infection due to functional immaturity of normal physical and immunological defense mechanisms. Despite current recommendations that infants with history of prematurity/LBW should receive routine immunization according to the same schedule and chronological age as full-term infants, immunization is often delayed.MethodsHere we summarize 10 clinical studies and 15 years of post-marketing safety surveillance of GSK’s hexavalent vaccine (DTPa-HBV-IPV/Hib), a combined diphtheria-tetanus-acellular-pertussis-hepatitis-B-inactivated-poliovirus-Haemophilus influenzae-type-b (Hib) conjugate vaccine, when administered alone, or co-administered with pneumococcal conjugate, rotavirus, and meningococcal vaccines and respiratory syncytial virus IgG to infants with history of prematurity/LBW in clinical trials.ResultsAt least 92.5% of infants with history of prematurity/LBW as young as 24 weeks gestation in clinical studies were seropositive to all vaccine antigens after 3-dose primary vaccination with GSK’s hexavalent DTPa-HBV-IPV/Hib vaccine, with robust immune responses to booster vaccination. Seropositivity rates and antibody concentrations to hepatitis B and Hib appeared lower in infants with history of prematurity/LBW than term infants. Between 13–30% of medically stable infants with history of prematurity developed apnea after vaccination with GSK’s hexavalent DTPa-HBV-IPV/Hib vaccine; usually after dose 1. The occurrence of post-immunization cardiorespiratory events appears to be influenced by the severity of any underlying neonatal condition. Most cardiorespiratory events resolve spontaneously or require minimal intervention. GSK’s hexavalent DTPa-HBV-IPV/Hib vaccine was well tolerated in co-administration regimens.ConclusionGSK’s hexavalent DTPa-HBV-IPV/Hib vaccine alone or co-administered with other pediatric vaccines has a clinically acceptable safety and immunogenicity profile when used in infants with history of prematurity/LBW for primary and booster vaccination. Additional studies are needed in very premature and very LBW infants. However, currently available data support using GSK’s hexavalent DTPa-HBV-IPV/Hib vaccine to immunize infants with history of prematurity/LBW according to chronological age.     

Influenza vaccine effectiveness against laboratory confirmed influenza in Greece during the 2013–2014 season: A test-negative study

BackgroundIn 2013–2014 Greece experienced a resurgence of severe influenza cases, coincidental with a shift to H1N1pdm09 predominance. We sought to estimate Vaccine Effectiveness (VE) for this season using available surveillance data from hospitals (including both inpatients and outpatients).MethodsSwab samples were sent by hospital physicians to one of three laboratories, covering the entire country, to be tested for influenza using RT-PCR. The test-negative design was employed, with patients testing positive serving as cases and those testing negative serving as controls. VE was estimated using logistic regression, adjusted for age group, sex, region and calendar time, with further adjustment for unknown vaccination status using inverse response propensity weights. Additional age group stratified estimates and subgroup estimates of VE against H1N1pdm09 and H3N2 were calculated.ResultsOut of 1310 patients with known vaccination status, 124 (9.5%) were vaccinated, and 543 patients (41.5%) tested positive for influenza. Adjusted VE was 34.5% (95% CI: 4.1–55.3%) against any influenza, and 56.7% (95% CI: 22.8–75.7%) against H1N1pdm09. VE estimates appeared to be higher for people aged 60 and older, while in those under 60 there was limited evidence of effectiveness. Isolated circulating strains were genetically close to the vaccine strain, with limited evidence of antigenic drift.ConclusionsThese results suggest a moderate protective effect of the 2013–2014 influenza vaccine, mainly against H1N1pdm09 and in people aged 60 and over. Vaccine coverage was very low in Greece, even among groups targeted for vaccination, and substantial efforts should be made to improve it. VE can and should be routinely monitored, and the results taken into account when deciding on influenza vaccine composition for next season.     

Modeling the long-term antibody response of a hepatitis E vaccine

BackgroundThe first commercialized hepatitis E vaccine, HEV 239, has been shown to be safe and highly immunogenic, the protection as well as the vaccine-induced anti-HEV maintained for at least 4.5 years. However, the longer term persistence of the vaccine-induced anti-HEV responses is unknown.MethodsTwo statistical models, the power-law model and the modified power-law model, were applied to predict the long-term antibody response of the HEV 239 vaccine. The models were fit using the anti-HEV IgG data from a modeling subpopulation of 1278 baseline seronegative vaccinees who seroconverted within one month after finishing the whole vaccination course in the phase 3 trial of HEV 239. In addition, antibody data from a validation subpopulation were used to validate the robustness of the derived models.ResultsIn the vaccinees without pre-vaccination immunity, the power-law model and the modified power-law model estimated that the median duration of the detectable antibody (≥0.077 WU/ml) was 8 years and 13 years, respectively. The power-law model and the modified power-law model estimated that 50% of these vaccinees will maintain detectable levels of anti-HEV IgG for 8 years and >30 years, respectively.ConclusionsThe recombinant hepatitis E vaccine HEV 239 is predicted to provide from 8 years to nearly life-long persistence of anti-HEV IgG above detectable levels. Model predictions are based on conservative mathematical assumptions.(NCT01014845).     

Factors related to vaccine uptake by young adult women in the catch-up phase of the National HPV Vaccination Program in Australia: Results from an observational study

BackgroundAustralia commenced a publically-funded, National Human Papillomavirus (HPV) Vaccination Program in 2007 with a two year catch-up phase for females aged 12–26 years.ObjectiveTo identify the factors associated with the uptake of the HPV vaccine (which has a recommended 3-dose schedule in Australia) by young adult women vaccinated by general practitioners and community-based programs within the catch-up phase.Methods1139 women who were eligible to receive the free HPV vaccine during the catch-up period were recruited in 2008–2009 (age 20–29 years at recruitment), in New South Wales, after having a normal (negative) cervical smear result recorded on the NSW Pap Test Register. Participants completed a self-administered questionnaire providing information on vaccination status, and sociodemographic and other factors.ResultsOverall, 880 (77%) women reported receiving ≥1 dose of the vaccine and 777 women (68%) reported receiving ≥2 doses. In multivariable analysis (adjusting for the period for which each woman was eligible for free HPV vaccination), uptake of ≥1 dose of the vaccine was significantly associated with being born in Australia (p < 0.01), being single (p = 0.02), being nulliparous (p < 0.01), living in a higher socioeconomic status area (p-trend = 0.03), living in more remote areas (p = 0.03), drinking alcohol (p < 0.01) and using hormonal contraceptives (p < 0.01). Although vaccinated women were more likely to have fewer sexual partners than unvaccinated women (p-trend = 0.02), they were also more likely to report a prior sexually transmitted infection (STI) (p = 0.03). Similar factors were associated with receiving ≥2 doses.ConclusionsIn this group, women living in higher socioeconomic status areas were more likely to be vaccinated against HPV in the catch-up phase of the national program. Although vaccinated women tended to have fewer sexual partners, they also reported prior STIs, which may be a marker of increased risk of prior exposure to HPV. The findings of this study reinforce the continuing need to prioritise equitable delivery of vaccination to various population subgroups.     

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.     

The effectiveness of influenza vaccination in preventing hospitalisation in children in Western Australia

BackgroundThere is increasing evidence demonstrating influenza vaccine effectiveness (VE) in the prevention of influenza in children, including the very young. Data demonstrating the effectiveness against severe disease, including hospitalisation, are limited. We aimed to determine the VE of the southern hemisphere trivalent inactivated influenza vaccine (TIV) in preventing laboratory-confirmed influenza-associated hospitalisation in children.Patients and MethodsLaboratory records were used to identify children with confirmed influenza hospitalised (i.e., cases) during a 5 year period (2008, 2010–2013) at the only tertiary paediatric facility in Western Australia. Cases and time, age and ward matched controls were retrospectively reviewed to determine risk factors, vaccination status and outcome. Adjusted odds ratios and VE estimates were derived using conditional logistic regression models.ResultsThree hundred and eighty five cases were identified (Influenza A, 64.9%; Influenza B, 35.1%). Influenza-like illness and pneumonia were the most frequent presentation (74.5% and 23.9%, respectively). The median length of stay was 2 days (Interquartile range 1–4 days). Twenty children (5.2%) required admission to the intensive care unit. Vaccine uptake in cases and controls was low (4.9% and 8.5%, respectively). Three hundred and six case-control pairs were included in the VE analysis, of which 19 pairs were informative with discrepant vaccination status. VE (fully vaccinated vs. unvaccinated) was estimated to be 62.3% (95% CI: −6.6%, 86.7%).ConclusionIn this study, the point estimate for the effectiveness of TIV in preventing influenza-associated hospitalisation in children was similar to that reported for emergency or outpatient attended, laboratory-confirmed influenza, yet confidence intervals were wide. Vaccine uptake remains low. Studies, enroling larger numbers of children, ideally with higher vaccine uptake, are needed to provide additional evidence on TIV protection against influenza hospitalisation in children.     

Immunogenicity and safety of double versus standard dose of the seasonal influenza vaccine in solid-organ transplant recipients: A randomized controlled trial

BackgroundThe use of vaccines with higher doses of antigen is an attractive strategy to improve the immunogenicity of influenza vaccination in transplant recipients. However, the effect of vaccination with a double-dose (DD) containing 30 µg of antigen in this population remains unknown.MethodsWe performed a randomized controlled trial to compare the immunogenicity and safety of DD (30 µg) vs. standard dose (SD, 15 µg) of a trivalent inactivated influenza vaccine in kidney and liver transplant recipients. Immunogenicity was assessed by hemagglutination-inhibition assay. Vaccine response was defined as seroconversion to at least one viral strain 2 weeks after vaccination and seroprotection as a titer ≥40.ResultsSixty-three kidney and 16 liver transplant recipients were enrolled. Forty patients received the DD and 39 the SD vaccine. Overall, 40% of patients in the DD compared to 26% in the SD group (P = 0.174) responded to vaccine. In the DD arm, more patients were seroprotected to all viral strains after vaccination (88% vs 69%, P = 0.048). Post vaccination geometric mean titers of antibodies were 131.9 vs. 89.7 (P = 0.187) for H1N1, 185.4 vs. 138.7 (P = 0.182) for H3N2, and 96.6 vs. 68.8 (P = 0.081) for influenza B with the DD vs. SD. In both groups, most of the adverse events were mild and no vaccine-related severe adverse events were observed.ConclusionDouble-dose influenza vaccine is safe and may increase antibody response in transplant recipients. In this population, DD vaccination could be an alternative when high-dose vaccine is not available. NCT02746783.