Febrile seizures following measles and varicella vaccines in young children in Australia

BackgroundFebrile seizures (FS) are common in childhood with incidence peaking in the second year of life when measles and varicella-containing vaccines are administered. This study aimed to examine the vaccine-attributable risk of FS following separate administration of MMR and monovalent varicella vaccines (VV) prior to a planned change to MMRV as the second dose of measles-containing vaccine at 18 months of age.MethodsAll FS cases in children aged <5 years from 1st January 2012 to 30th April 2013 were identified from emergency department (ED) and inpatient databases at five Australian tertiary paediatric hospitals participating in PAEDS (Paediatric Active Enhanced Disease Surveillance). Immunization records were obtained from the Australian Childhood Immunization Register (ACIR). The relative incidence (RI) of FS following MMR dose 1 (MMR1) and VV in children aged 11–23 months was determined using the self-controlled case series (SCCS) method and used to calculate attributable risk.ResultsThere were 2013 FS episodes in 1761 children. The peak age at FS was 18 months. The risk of FS was significantly increased 5–12 days post receipt of MMR1 at 12 months (RI = 1.9 [95% CI: 1.3–2.9]), but not after VV at 18 months (RI = 0.6 [95% CI: 0.3–1.2]. The estimated excess annual number of FS post MMR1 was 24 per 100,000 vaccinated children aged 11–23 months (95% CI = 7–49 cases per 100,000) or 1 per 4167 doses.ConclusionsOur study detected the expected increased FS risk post MMR1 vaccine at 12 months, but monovalent varicella vaccine at age 18 months was not associated with increased risk of FS. This provides baseline data to assess the risk of FS post MMRV, introduced in Australia as the second dose of measles-containing vaccine at 18 months of age in July 2013.     

Determinants of under-immunization and cumulative time spent under-immunized in a Quebec cohort

BackgroundUnder-immunization refers to a state of sub-optimal protection against vaccine preventable diseases. Vaccine coverage for age may not capture intentional or non-intentional spacing of vaccines in the recommended provincial immunization guidelines. We aimed to identify factors associated with coverage and under-immunization and to determine the number of days during which children were under-immunized during their first 24 months of life.MethodsSecondary analysis of children ≤3 years recruited through active surveillance for gastroenteritis from three Quebec pediatric emergency departments from 2012 to 2014. Vaccination status for children at least 24 months of age was determined using provincial immunization guidelines. Cumulative days under-immunized were calculated for DTaP-VPI-Hib, PCV, MMR, and Men-C-C. Factors associated with up-to-date (UTD) status at 24 months of life and for under-immunization ≥6 months were analyzed using logistic regression.ResultsOf 246 eligible children, 180 (73%) were UTD by 24 months of life. The mean cumulative days under-immunized for MMR was 107 days, for PCV 209 days, for Men-C-C 145 days, and for DTaP-VPI-Hib 227 days. Overall, 149 children (60%) experienced delay for at least 1 vaccine. Factors associated with both an UTD status at 24 months and concurrently associated with being under-immunization ≥6 months, included timely initiation of immunization (OR = 5.85; 95% CI: 2.80–12.22) and (OR = 0.13; 95% CI: 0.07–0.24), failure to co-administer 18-month vaccines (OR = 0.15; 95% CI: 0.10–0.21) and (OR = 3.29; 95% CI: 2.47–4.39), and having a household with ≥3 children under 18 years ((OR = 0.50; 0.28–0.86) and (OR = 2.99; 1.45–6.22), respectively.ConclusionPaired with an unexpected low level of coverage at 24 months of life, the majority of our cohort also experienced a state of under-immunization for a least one vaccine. Estimates of coverage do not capture intentional or non-intentional gaps in protection from vaccine preventable illnesses. Timely preventive care should be prioritized.     

Simultaneous vaccination with MMR and DTaP-IPV-Hib and rate of hospital admissions with any infections: A nationwide register based cohort study

BackgroundIn Denmark, live measles, mumps, and rubella vaccine (MMR) is associated with a reduced risk of infectious disease admissions, particularly for lower respiratory tract infections. In low-income countries, simultaneous vaccination (i.e. vaccination at the same visit) with live and inactivated vaccines may increase child mortality compared with the live vaccine alone. We examined the hypothesis that simultaneous administration of MMR and the inactivated DTaP-IPV-Hib vaccine compared with MMR alone is associated with higher incidence of infectious disease admissions.MethodsNationwide, retrospective, register based cohort study of 520,859 children born in Denmark 1997–2006, who were followed from 15 months to 4 years of age. Incidence rate ratios (IRRs) of hospital admissions were estimated by Cox regression and adjusted for background factors including exact age.ResultsBy 2 years of age, 4965 children had simultaneous MMR and DTaP-IPV-Hib as their most recent vaccination. Compared with MMR alone, simultaneous administration was associated with a higher rate of lower respiratory tract infections (adjusted incidence rate ratio (IRR), 1.27; 95% confidence interval (CI), 1.13–1.42). There was no effect on other infections. Overall, simultaneous administration was associated with a 7% (95% CI, 0–15%) increase in infectious disease admissions.ConclusionsSimultaneous administration of MMR and DTaP-IPV-Hib compared with MMR alone may increase the rate of hospital admissions related to lower respiratory tract infections. These findings require replication in other high-income settings.     

Guillain-Barré syndrome and influenza vaccines: A meta-analysis

Cases of Guillain-Barré syndrome (GBS) have been occasionally associated with influenza vaccines; this possible risk, even if rare, is a matter of much concern. To investigate the strength of this association, a systematic review and a meta-analysis have been conducted; for the purpose, controlled observational studies addressing the risk of GBS associated with different influenza vaccines were sought. We finally selected 39 studies of interest published between 1981 and 2014 (seasonal influenza vaccines, 22; pandemic influenza vaccines, 16; both vaccines simultaneously administered, 1); funnel plot did not identify publication bias. At the association between any influenza vaccine – whether seasonal or pandemic – with GBS, the overall relative risk was 1.41 (95% CI, 1.20–1.66). Pandemic vaccines presented a higher risk (RR = 1.84; 95% CI, 1.36–2.50) compared to seasonal vaccines (RR = 1.22; 95% CI, 1.01–1.48); the latter should be considered as marginally statistically significant. Pandemic adjuvanted vaccines were not found to be related to a higher risk compared to non-adjuvanted vaccines. The results of the present meta-analysis point to a small but statistically significant association between influenza vaccines, particularly the pandemic ones, and GBS, which is consistent with current explanations upon possible mechanisms for this condition to appear.     

Risk factors and familial clustering for fever 7–10 days after the first dose of measles vaccines

BackgroundSeven to ten days after a first dose of a measles-containing vaccine (MCV; i.e., MMR or MMRV), children have elevated fever risk which can be associated with febrile seizures. This study investigated individual and familial factors associated with fever 7–10 days after MCV.MethodsRetrospective cohort study among children who were <36 months of age at receipt of MCV in six sites of the Vaccine Safety Datalink from 1/1/2000 to 12/31/2012. We evaluated medically-attended clinic or emergency department visits with a code for fever 7–10 days after any MCV (“MCV- associated”). We evaluated factors associated with MCV-associated fever using χ² and multivariable logistic regression analyses.ResultsAmong 946,806 children vaccinated with MCV, we identified 7480 (0.8%) MCV-associated fever visits. Compared with children without fever after MCV, children with MCV-associated fever were more likely to have received MMRV than MMR (OR 1.3 95% CI 1.2, 1.5), have had medically attended fever both following previous vaccines (OR 1.3 95% CI 1.1, 1.6) and at any other previous time (OR 1.7 95% CI 1.6, 1.8), have had at least 1 prior seizure (OR 2.2 95% CI 1.7, 2.7), and have had >3 medical visits within the 6 months before MCV (OR 1.7 95% CI 1.6, 1.8). In families with multiple MCV-immunized children, after adjusting for healthcare seeking behavior care for fever, those whose siblings had MCV-associated fever were more likely to also have MCV-associated fever (OR 3.5 95% CI 2.5, 4.8).DiscussionChildren who received MMRV vaccine or who had prior medically-attended fevers and seizures during the first year of life had increased risk of fever after a first dose of measles vaccine. After adjusting for familial propensity to seek care, MCV-associated fever still clustered within families, suggesting a possible genetic basis for susceptibility to developing fever due to measles vaccines.     

Correlates of receiving recommended adolescent vaccines among youth with special health care needs: Findings from a statewide survey

BackgroundMany youth with special health care needs (YSHCN) have not received recommended adolescent vaccines, yet data are lacking on correlates of vaccination among this population. Such information can identify subgroups of YSHCN that may be at risk for under-immunization and strategies for increasing vaccination.MethodsWe analyzed weighted data from a population-based sample of parents with an 11- to 17-year-old child with a special health care need from the 2010–2012 North Carolina Child Health Assessment and Monitoring Program (n = 604). We used ordinal logistic regression to identify correlates of how many recommended vaccines (tetanus booster, meningococcal, and HPV [at least one dose] vaccines) adolescents had received.ResultsOnly 12% of YSHCN (18% of females and 7% of males) had received all three vaccines. More YSHCN had received tetanus booster vaccine (91%) than meningococcal (28%) or HPV vaccines (32%). In multivariable analyses, YSHCN who were female (OR = 2.59, 95% CI: 1.57–4.24), ages 16–17 (OR = 2.06, 95% CI: 1.10–3.87), or who had a preventive check-up in the past year (OR = 2.98, 95% CI: 1.24–7.21) had received a greater number of the vaccines. YSHCN from households that contained a person with at least some college education had received fewer of the vaccines (OR = 0.57, 95% CI: 0.33–0.96). Vaccine coverage did not differ by type of special health care need.ConclusionsVaccine coverage among YSHCN is lacking and particularly low among those who are younger or male. Reducing missed opportunities for vaccination at medical visits and concomitant administration of adolescent vaccines may help increase vaccine coverage among YSHCN.     

A retrospective nationwide register-based study to evaluate the non-specific effects of first MMR vaccination among children in Finland

BackgroundAccording to earlier studies, live vaccines like measles-mumps-rubella (MMR) vaccine could reduce also other infections than only the infections they are targeted against. This non-specific effect has been seen especially in studies in low-income countries and results from high-income countries have not been unambiguous. In 2011 Finland changed the recommended schedule for the first MMR vaccination from 18 months to 12 months of age. This change created a natural experiment for evaluating the potential non-specific effects.MethodsThis is a retrospective nationwide register-based cohort study of Finnish children born between 2008 and 2012. Children were divided into two cohorts by age at MMR vaccination: children administered early MMR vaccination (11 through 12 months of age) and late MMR vaccination (18 through 19 months of age). Morbidity was evaluated during the main follow-up period (from 13 to 17 months of age) and before any MMR vaccination (3 to 10 months) and after all were vaccinated with MMR (20 to 35 months) as control follow-up periods. We analyzed all infections and did additional analyzes for urinary tract infections (UTI) and bronchitis. Injuries were analyzed as a control outcome.ResultsEarly MMR vaccinated children (N = 79 949) had fewer infections compared to late MMR vaccinated (N = 60 965) during the main follow-up period. The incidence rate ratio (IRR) was 0.84 (95 % confidence interval (95 % CI) 0.81–0.87). However, similar differences were also observed during the control follow-up periods. MMR vaccinated children had less UTI in the main follow-up period (IRR 0.73, 0.60–0.89) but not in the control follow-up periods. When stratified by sex, the difference was observed among girls but not in boys.ConclusionNo clear evidence was found for non-specific effects in infectious diseases morbidity. However, there could be a nonspecific effect on UTI. Confirmation is needed from other studies, especially from high-income countries.     

Interchangeability of meningococcal group C conjugate vaccines with different carrier proteins in the United Kingdom infant immunisation schedule

An open, non-randomised study was undertaken in England during 2011–12 to evaluate vaccine antibody responses in infants after completion of the routine primary infant immunisation schedule, which included two doses of meningococcal group C (MenC) conjugate (MCC) vaccine at 3 and 4 months. Any of the three licensed MCC vaccines could be used for either dose, depending on local availability. Healthy term infants registered at participating general practices (GPs) in Hertfordshire and Gloucestershire, UK, were recruited prospectively to provide a single blood sample four weeks after primary immunisation, which was administered by the GP surgery. Vaccination history was obtained at blood sampling. MenC serum bactericidal antibody (SBA) and IgG antibodies against Haemophilus influenzae b (Hib), pertussis toxin (PT), diphtheria toxoid (DT), tetanus toxoid (TT) and thirteen pneumococcal serotypes were analysed according to MCC vaccines received. MenC SBA responses differed significantly (P < 0.001) according to MCC vaccine schedule as follows: MenC SBA geometric mean titres (GMTs) were significantly lower in infants receiving a diphtheria cross-reacting material-conjugated MCC (MCC-CRM) vaccine followed by TT-conjugated MCC (MCC-TT) vaccine (82.0; 95% CI, 39–173; n = 14) compared to those receiving two MCC-CRM (418; 95% CI, 325–537; n = 82), two MCC-TT (277; 95% CI, 223–344; n = 79) or MCC-TT followed by MCC-CRM (553; 95% CI, 322–949; n = 18). The same group also had the lowest Hib geometric mean concentrations (0.60 μg/mL, 0.27–1.34) compared to 1.85 μg/mL (1.23–2.78), 2.86 μg/mL (2.02–4.05) and 4.26 μg/mL (1.94–9.36), respectively. Our results indicate that MCC vaccines with different carrier proteins are not interchangeable. When several MCC vaccines are available, children requiring more than one dose should receive MCC vaccines with the same carrier protein or, alternatively, receive MCC-TT first wherever possible.     

Tularemia vaccine: Safety,reactogenicity, “Take” skin reactions,and antibody responses following vaccination with a new lot of the Francisella tularensis live vaccine strain – A phase 2 randomized clinical Trial

BackgroundTularemia is caused by Francisella tularensis, a gram-negative bacterium that has been weaponized as an aerosol. For protection of personnel conducting biodefense research, the United States Army required clinical evaluation of a new lot of tularemia live vaccine strain manufactured in accordance with Current Good Manufacturing Practices.MethodsA phase 2 randomized clinical trial compared the new lot (DVC-LVS) to the existing vaccine that has been in use for decades (USAMRIID-LVS). The vaccines were delivered by scarification to 228 participants. Safety, reactogenicity, take and/or antibody levels were assessed on days 0, 1, 2, 8, 14, 28, 56, and 180.Principal ResultsBoth vaccines were safe and had acceptable reactogenicity profiles during six months of follow-up. There were no serious or grade 3 and 4 laboratory adverse events. Moderate systemic reactogenicity (mostly headache or feeling tired) was reported by ∼23% of participants receiving either vaccine. Injection site reactogenicity was mostly mild itchiness and pain. The frequencies of vaccine take skin reactions were 73% (95% CI, 64, 81) for DVC-LVS and 80% (95% CI, 71, 87) for USAMRIID-LVS. The 90% CI for the difference in proportions was −6.9% (−16.4, 2.6). The rates of seroconversion measured by microagglutination assay on days 28 or 56 were 94% (95% CI, 88, 98; n = 98/104) for DVC-LVS and 94% (95% CI, 87, 97; n = 103/110) for USAMRIID-LVS (p = 1.00). Day 14 sera revealed more rapid seroconversion for DVC-LVS relative to USAMRIID-LVS: 82% (95% CI, 73, 89) versus 55% (95% CI, 45, 65), respectively (p < 0.0001).Major conclusionsThe DVC-LVS vaccine had similar safety, reactogenicity, take and antibody responses compared to the older USAMRIID vaccine, and was superior for early (day 14) antibody production. Vaccination take was not a sensitive surrogate for seroconversion in a multi-center study where personnel at five research clinics performed assessments.ClinicalTrials.gov identifier NCT01150695     

HPV vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis: A nationwide register-based study from Norway

BackgroundVaccination has been suggested to be involved in the aetiology of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). HPV vaccine was introduced in the Norwegian Childhood Immunisation Programme and offered 12 year old girls from 2009. We studied the association between HPV vaccination and risk of CFS/ME and also assessed medical history in relation to both risk of CFS/ME and HPV vaccine uptake.MethodsIndividual data from national registries, including the Norwegian Population Registry, the Norwegian Patient Registry and the Norwegian Immunisation Registry were linked using the unique personal identification number. Yearly incidence rates of CFS/ME for 2009–2014 were calculated among the 824,133 boys and girls, aged 10–17 living in Norway during these 6 years. A total of 176,453 girls born 1997–2002 were eligible for HPV vaccination and included in further analyses. Hazard ratios (HRs) of CFS/ME were estimated using Cox regression. Risk differences (RDs) of vaccine uptake were estimated with binomial regression.ResultsA similar yearly increase in incidence rate of CFS/ME was observed among girls and boys, IRR = 1.15 (95% confidence interval (CI) 1.10–1.19) and 1.15 (95% CI 1.09–1.22), respectively. HPV vaccination was not associated with CFS/ME, HR = 0.86 (95% CI 0.69–1.08) for the entire follow-up period and 0.96 (95% CI 0.64–1.43) for the first two years after vaccination. The risk of CFS/ME increased with increasing number of previous hospital contacts, HR = 5.23 (95% CI 3.66–7.49) for 7 or more contacts as compared to no contacts. Girls with 7 or more hospital contacts were less likely to be vaccinated than girls with no previous hospital contacts, RD = −5.5% (95% CI −6.7% to −4.2%).ConclusionsNo indication of increased risk of CFS/ME following HPV vaccination was observed among girls in the first 6 birth cohorts offered HPV vaccine through the national immunisation programme in Norway.     

Clearance of Tritrichomonas foetus in experimentally infected heifers protected with vaccines based on killed-T. foetus with different adjuvants

Tritrichomonas foetus is a flagellated protozoan that causes a sexually transmitted disease in cattle. Trichomonosis is characterized by early abortions, subfertility and a significant decrease in productivity. Vaccine preparations containing whole T. foetus can reduce the time of residence of the pathogen in the host cervix after experimental infection. Here, T. foetus vaccines prepared with different adjuvants were tested, in parallel with a commercial vaccine, for their efficacy to clear the infection. The median time for clearance of infection was 69 days in non-immunized animals, 55 days in animals treated with aluminum hydroxide, 41 days with oil-in-water or saponin based vaccines or with a commercial vaccine and 27 days in animals treated with saponin plus aluminum hydroxide. A slight increase in the risk of T. foetus clearance from the genital tract was found with the saponin based vaccine (hazard ratio, 2.52; 95% confidence interval, 1.03–6.17) or the commercial vaccine (hazard ratio, 2.61; 95% confidence interval, 1.07–6.38). A significant increase in the risk of T. foetus clearance was found with the combination of saponin plus aluminum hydroxide based vaccine (hazard ratio, 5.12; 95% confidence interval, 2.04–12.83).     

Text message reminders for timely routine MMR vaccination: A randomized controlled trial

ObjectiveMeasles–mumps–rubella (MMR) vaccination is important for preventing disease outbreaks, yet pockets of under-vaccination persist. Text message reminders have been employed successfully for other pediatric vaccines, but studies examining their use for MMR vaccination are limited. This study assessed the impact of text message reminders on timely MMR vaccination.Study designParents (n = 2054) of 9.5–10.5-month-old children from four urban academically-affiliated pediatric clinics were randomized to scheduling plus appointment text message reminders, appointment text message reminder-only, or usual care. The former included up to three text reminders to schedule the one-year preventive care visit. Both text messaging arms included a text reminder sent 2 days before that visit. Outcomes included appointment scheduling, appointment attendance, and MMR vaccination by age 13 months, the standard of care at study sites.ResultsChildren of parents in the scheduling plus appointment text message reminders arm were more likely to have a scheduled one-year visit than those in the other arms (71.9% vs. 67.4%, relative risk ratio (RRR) 1.07 [95% CI 1.005–1.13]), particularly if no appointment was scheduled before randomization (i.e., no baseline appointment) (62.1% vs. 54.7%, RRR 1.14 [95% CI 1.04–1.24]). One-year visit attendance and timely MMR vaccination were similar between arms. However, among children without a baseline appointment, those with parents in the scheduling plus appointment text message reminders arm were more likely to undergo timely MMR vaccination (61.1% vs. 55.1%, RRR 1.11 [95% CI 1.01–1.21]).ConclusionText message reminders improved timely MMR vaccination of high-risk children without a baseline one-year visit.     

Effectiveness of 2009 pandemic influenza A(H1N1) vaccines: A systematic review and meta-analysis

BackgroundThe clinical effectiveness of monovalent influenza A(H1N1)pdm09 vaccines has not been comprehensively summarised. We undertook a systematic review and meta-analysis to assess vaccine effectiveness (VE) for adjuvanted and unadjuvanted vaccines.MethodsWe searched healthcare databases and grey literature from 11 June 2009 to 12 November 2014. Two researchers independently assessed titles and abstracts to identify studies for full review. Random effects meta-analyses estimated the pooled effect size of vaccination compared to placebo or no vaccination for crude and adjusted odds ratios (OR) to prevent laboratory confirmed influenza illness (LCI) and related hospitalization. VE was calculated as (1-pooled OR) 1 100. Narrative synthesis was undertaken where meta-analysis was not possible.ResultsWe identified 9229 studies of which 38 at moderate risk of bias met protocol eligibility criteria; 23 were suitable for meta-analysis. Pooled adjusted VE against LCI with adjuvanted and unadjuvanted vaccines both reached statistical significance (adjuvanted: VE = 80%; 95% confidence interval [CI] 59–90%; unadjuvanted: VE = 66%; 95% CI 47–78%); in planned secondary analyses, VE in adults often failed to reach statistical significance and pooled point estimates were lower than observed in children. Overall pooled adjusted VE against hospitalization was 61% (95% CI 14–82%); in planned secondary analyses, adjusted VE attained statistical significance in adults aged 18–64 years and children for adjuvanted vaccines. Adjuvanted vaccines were significantly more effective in children compared to adults for both outcomes.ConclusionsAdjuvanted and unadjuvanted monovalent influenza A(H1N1)pdm09 vaccines were both effective in preventing LCI. Overall, the vaccines were also effective against influenza-related hospitalization. For both outcomes adjuvanted vaccines were more effective in children than in adults.     

Risk factors for severe outcomes among members of the United States military hospitalized with pneumonia and influenza, 2000–2012

BackgroundThe progression from hospitalization for a respiratory infection to requiring substantial supportive therapy is a key stage of the influenza severity pyramid. Respiratory infections are responsible for 300,000–400,000 medical encounters each year among US military personnel, some of which progress to severe acute respiratory infections.MethodsWe obtained data on 11,086 hospitalizations for pneumonia and influenza (P&I) among non-recruit US military service members during the period of 1 January 2000 through 31 December 2012. From these, we identified 512 P&I hospitalizations that progressed to severe episodes using standard case definitions. We evaluated the effect of demographic and occupational characteristics, co-morbid conditions, and history of influenza vaccination on the risk of a hospitalized P&I case becoming a severe case. We also evaluated the risk of a severe outcome and the length of time since influenza vaccination (within 180, 60, and 30 days).ResultsThe median age of subjects at the time of the P&I episode was 32 years (range, 28–40) and subjects were predominantly male (89.5%). In a univariate analysis, demographic risk factors for a severe episode included service in the US Air Force (RR = 1.6 relative to US Army, 95%CI 1.3–2.1), US Coast Guard (RR = 2.1, 1.2–3.7) or US Navy (RR = 1.4, 1.1–1.8). Being born in the US and recent influenza vaccination (within 180 days of episode) were protective against developing severe disease. Among co-morbid conditions, univariate risk factors for severe disease included chronic renal or liver disease (RR = 4.98, 95%CI 4.1–6.1), diseases of the circulatory system (RR = 3.1, 95%CI 2.6–3.7), diabetes mellitus (RR = 2.3, 95%CI 1.5–3.6), obesity (RR = 1.6, 95%CI 1.2–2.1), cancer (RR = 1.6, 95%CI 1.3–2.0), and chronic obstructive pulmonary disease (RR = 1.4, 95%CI 1.1–1.7). Although many of the risk factors found to be significant in univariate analysis were no longer significant under a multivariate analysis, receipt of any influenza vaccine within 180 days of episode remained protective (RR = 0.81, 95%CI 0.67–0.99), while serving in the US Coast Guard (RR = 1.9, 95%CI 1.1–3.4) or US Air Force (RR = 1. 5, 95%CI 1.2–2.0), presence of renal or liver disease (RR = 3.6, 95%CI 2.9–4.6), and diseases of the circulatory system (RR = 2.2, 95%CI 1.8–2.8), remained significantly associated with a higher risk of developing severe disease.ConclusionsIn a large cohort, after adjusting for many possible risk factors, influenza vaccination was protective against severe episodes among P&I hospitalizations. The service-specific (US Coast Guard or US Air Force) increased risk may represent some differences in data (e.g., coding or reporting practices) as opposed to genuine differences in physiological outcome. Our findings suggest that renal and liver disease as well as diseases of the circulatory system may contribute to influenza severity in this population independently of age and other potential comorbidities. These findings provide additional evidence for the prioritization of specific risk groups within the US military for influenza vaccination     

Parental perceptions of childhood seasonal influenza vaccination in Singapore: A cross-sectional survey

PurposeSeasonal influenza vaccination is recommended in children aged 6–59 months, but little is known about child vaccination coverage and determinants in Asian settings. We report the results of a survey of knowledge, attitudes, practices, and determinants of child influenza vaccination in Singapore.MethodsIn December 2015-March 2016, we conducted a survey of 332 parents of children aged 6 months to 5 years attending pre-schools. We assessed child influenza vaccine coverage and parental knowledge, attitudes, and practices of child influenza vaccination. We used multivariable regression and structural equation models to identify factors associated with child influenza vaccination.ResultsKnowledge about influenza, perceived benefit of vaccination, and willingness to vaccinate were high. However, only 32% of children had ever received influenza vaccine, and only 15% in the past year. Factors independently associated with child influenza vaccination included: being recommended influenza vaccine by a child’s doctor (prevalence ratio (PR) = 2.47, 95% CI: 1.75–3.48); receiving influenza vaccine information from a private general practitioner (PR = 1.47, 95% CI: 1.05–2.04); regularly receiving pre-travel influenza vaccine (PR = 1.64, 95% CI: 1.19–2.25); higher willingness to vaccinate (PR = 1.58, 95% CI:1.24–2.04 per unit increase in willingness score); and feeling well-informed about influenza vaccine (PR = 1.44, 95% CI: 1.04–1.99). Parents who obtained influenza vaccine information from television were less likely to have vaccinated their child (PR = 0.44, 95% CI: 0.23–0.85). Path analysis indicated that being recommended vaccination by a child's doctor increased willingness to vaccinate and self-efficacy (feeling well-informed about influenza vaccine). Median willingness-to-pay for a dose of influenza vaccine was SGD30 (interquartile range: SGD20-SGD50), and was higher in parents of vaccinated compared with unvaccinated children (SGD45 vs SGD30, p = 0.0012).ConclusionKnowledge and willingness to vaccinate was high in this parent population, but influenza vaccine uptake in children was low. Encouraging medical professionals to recommend vaccination of eligible children is key to improving uptake.     

Impact of the national targeted Hepatitis A immunisation program in Australia: 2000–2014

In November 2005, hepatitis A vaccine was funded under the Australian National Immunisation Program for Aboriginal and Torres Strait Islander (Indigenous) children aged 12–24 months in the targeted jurisdictions of Queensland, South Australia, Western Australia and the Northern Territory.We reviewed the epidemiology of hepatitis A from 2000 to 2014 using data from the Australian National Notifiable Diseases Surveillance System, the National Hospital Morbidity Database, and Australian Bureau of Statistics causes-of-death data. The impact of the national hepatitis A immunisation program was assessed by comparison of pre-vaccine (2000–2005) and post-vaccine time periods (2006–2014), by age group, Indigenous status and jurisdiction using incidence rate ratios (IRR) per 100,000 population and 95% confidence intervals (CI).The national pre-vaccine notification rate in Indigenous people was four times higher than the non-Indigenous rate, and declined from 8.41 per 100,000 (95% CI 5.03–11.79) pre-vaccine to 0.85 per 100,000 (95% CI 0.00–1.99) post-vaccine, becoming similar to the non-Indigenous rate. Notification and hospitalisation rates in Indigenous children aged <5 years from targeted jurisdictions declined in the post-vaccine period when compared to the pre-vaccine period (notifications: IRR = 0.07; 95% CI 0.04–0.13; hospitalisations: IRR = 0.04; 95% CI 0.01–0.16). As did notification rates in Indigenous people aged 5–19 (IRR = 0.08; 95% CI 0.05–0.13) and 20–49 years (IRR = 0.06; 95% CI 0.02–0.15) in targeted jurisdictions. For non-Indigenous people from targeted jurisdictions, notification rates decreased significantly in children aged <5 years (IRR 0.47; 95% CI 0.31–0.71), and significantly more overall (IRR = 0.43; 95% CI 0.39–0.47) compared to non-Indigenous people from non-targeted jurisdictions (IRR = 0.60; 95% CI 0.56–0.64).The national hepatitis A immunisation program has had a significant impact in the targeted population with relatively modest vaccine coverage, with evidence suggestive of substantial herd protection effects.     

Concomitant administration of a fully liquid,ready-to-use DTaP-IPV-HB-PRP-T hexavalent vaccine with a meningococcal serogroup C conjugate vaccine in infants

DTaP-IPV-HB-PRP-T or hexavalent vaccines are indicated for primary and booster vaccination of infants and toddlers against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive diseases caused by Haemophilus influenzae type b (Hib). The present study evaluates the safety and immunogenicity of a ready-to-use hexavalent vaccine when co-administered with a meningococcal serogroup C conjugate (MenC) vaccine in infants.This was a phase III, open-label, randomised, multicentre study conducted in Finland. Healthy infants, aged 46–74 days (n = 350), were randomised in a ratio of 1:1 to receive DTaP-IPV-HB-PRP-T vaccine at two, three and four months, either with a MenC vaccine co-administered at two and four months (Group 1; n = 175) or without MenC vaccine (Group 2; n = 175). All infants also received routine rotavirus and 13-valent pneumococcal conjugate vaccines.The proportion of participants with an anti-HBs concentration ⩾10 mIU/mL assessed one month after the third dose of DTaP-IPV-HB-PRP-T vaccine was 97.5% [95%CI: 93.1–99.3] in the coadministration group and 96.1% [95%CI: 91.8–98.6] in the group without MenC vaccine. The proportion of participants with an anti-MenC SBA titre ⩾8 assessed one month after the second dose of MenC vaccine was 100% in the coadministration group. Both primary objectives were achieved.Secondary immunogenicity and safety analyses showed that co-administration of DTaP-IPV-HB-PRP-T and MenC vaccines did not impact the immune response to the antigens of each of the two vaccines. All vaccines were well tolerated and the safety profile of DTaP-IPV-HB-PRP-T vaccine was similar in both groups.ClinicalTrials.gov identifier: NCT01839175; EudraCT number: 2012-005547-24.     

Hospitalizations within 14 days of vaccination among pediatric recipients of the live attenuated influenza vaccine,United States 2010–2012

BackgroundLive attenuated influenza vaccine (LAIV) is safe in healthy children ⩾2 years. The original clinical trials excluded individuals with underlying conditions; however, post-marketing data suggest LAIV may be safe for these populations.MethodsWe analyzed MarketScan Commercial Claims Databases from 2010 to 2012 to describe hospitalizations within 14 days of vaccination among LAIV recipients. We evaluated LAIV recipients aged 2–18 years and defined underlying conditions by presence of inpatient or outpatient ICD-9 code during the previous calendar year. We excluded asthma and immunocompromising conditions. We defined risk windows as 1–7 days and 8–14 days after vaccination; the control period was 12–4 days prior to and 15–23 days after vaccination. We conducted a self-controlled case series analysis using a conditional Poisson regression model to estimate incidence-rate ratios (IRR).Results1,216,123 children aged 2–18 years received LAIV from 2010 to 2012. 634 children met our inclusion criteria and were hospitalized during the observation period (12 days prior to vaccination to 23 days after vaccination). Of those hospitalized, 72 (11.4%) had non-asthma, non-immunocompromising underlying conditions. Children with non-asthma, non-immunocompromising underlying conditions had an all-cause hospitalization IRR of 1.1 (95% CI 0.6–2.0, p = 0.83) in the 1–7 day risk period and 0.9 (95% CI 0.4–1.7, p = 0.67) in the 8–14 day risk period. Children with no underlying conditions had an all-cause hospitalization IRR of 0.9 (0.8–1.2, p = 0.60) in the 1–7 day risk period and 1.1 (95% CI 0.9–1.3, p = 0.53) in the 8–14 day risk period. There were no differences in all-cause hospitalization risk in individuals with non-asthma, non-immunocompromising underlying conditions compared to those without underlying conditions in the 1–7 day (p = 0.88) or 8–14 day (p = 0.24) risk period.ConclusionsWe found no evidence of differences in post-LAIV hospitalization risk among children with non-asthma, non-immunocompromising underlying conditions compared to healthy children.     

A native outer membrane vesicle vaccine confers protection against meningococcal colonization in human CEACAM1 transgenic mice

BackgroundThe effect of protein-based meningococcal vaccines on prevention of nasopharyngeal colonization has been difficult to investigate experimentally because a reliable animal colonization model did not exist.MethodsHuman CEACAM1 transgenic mice, which can be colonized by meningococci, were immunized IP with one of two meningococcal native outer membrane vesicle (NOMV) vaccines prepared from mutants with attenuated endotoxin (lpxL1 knockout) and over-expressed sub-family B Factor H-binding proteins (FHbp). Animals were challenged intranasally two weeks after the third dose with wild-type strain H44/76, or were treated IP with anti-NOMV serum before and during the bacterial challenge.ResultsThe NOMV-1 vaccine, prepared from the serogroup B H44/76 mutant, elicited ∼40-fold higher serum bactericidal antibody titers against the wild-type H44/76 challenge strain than the NOMV-2 vaccine prepared from a heterologous serogroup W mutant strain with different PorA and FHbp amino acid sequence variants. Compared to aluminum hydroxide-immunized control mice, the efficacy for prevention of any H44/76 colonization was 93% (95% confidence interval, 52–99, P < 0.0001) for the NOMV-1 vaccine, and 19% (−3–36, P = 0.23) for NOMV-2. NOMV-2-vaccinated mice had a 5.6-fold decrease in geometric mean CFU of bacteria per animal in tracheal washes compared to control mice (P = 0.007). The efficacy of passive administration of serum from NOMV-1-vaccinated mice to immunologically naïve mice against colonization was 44% (17–61; P = 0.002).ConclusionsBoth NOMV vaccines protected against meningococcal colonization but there was greater protection by the NOMV-1 vaccine with antigens matched with the challenge strain. Meningococcal vaccines that target protein antigens have potential to decrease colonization.