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.     

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.     

Timeliness and risk factors associated with delay for pneumococcal conjugate 10-valent routine immunization in Brazilian children

BackgroundVaccination coverage is the usual metrics to evaluate the immunization programs performance. For the 10-valent pneumococcal conjugate (PCV10) vaccine, measuring the delay of vaccination is also important, particularly as younger children are at increased risk of disease. Routinely collected administrative data was used to assess the timeliness of PCV10 vaccination, and the factors associated with delay to receive the first and second doses, and the completion of the PCV10 3 + 1 schedule.MethodsA population-based retrospective cohort study was conducted with children born in 2012 in Central Brazil. Children who received the PCV10 first dose in public health services were followed-up until 23 months of age. Timeliness of receiving each PCV10 dose at any given age was defined as receiving the dose within 28 days grace period from the recommended age by the National Immunization Program. Log-binomial regression models were used to examine risk factors for delays of the first dose and the completion PCV10 3 + 1 schedule.ResultsIn total, 14,282 children were included in the cohort of study. Delayed vaccination occurred in 9.4%, 23.8%, 36.8% and 39.9% children for the first, second, third and the booster doses, respectively. A total of 1912 children (12.8% of the cohort) were not adequately vaccinated at the 6 months of life; 1,071 (7%) received the second dose after 6 months of age, 784 (5.4%) did not receive the second dose, and 57 (0.4%) received the first dose after six months of life.ConclusionA considerable delay was found in PCV10 third and booster doses. Almost 2 thousand children had not received the recommended PCV10 doses at 6 months of age. Timeliness of vaccination is an issue in Brazil although high vaccination coverages.     

No evidence of an increase of bacterial and viral infections following Measles,Mumps and Rubella vaccine

The suggestion that multi-antigen vaccines might overload the immune system has led to calls for single antigen vaccines. In 2003 we showed that rather than an increase there appeared to be a reduced risk of severe bacterial infection in the three months following Measles, Mumps and Rubella vaccine (MMR). The present analysis of illnesses in a general population is based on an additional 10 years of data for bacterial infections and also includes admissions with viral infections. Analyses were carried out using the self-controlled case-series method and separately for bacterial and viral infection cases, using risk periods of 0–30 days, 31–60 days and 61–90 days post MMR vaccine. An analysis was also carried out for those cases which were given MMR and Meningococcal serogroup C (MCC) vaccines concomitantly.A reduced risk was seen in the 0–30-day period for both bacterial infection (relative incidence = 0.68, 95% CI 0.54–0.86) and viral infections (relative incidence = 0.68, 95% CI 0.49–0.93). There was no increased risk in any period when looking at combined viral or bacterial infections or for individual infections with the single exception of an increased risk in the 31–60 days post vaccination period for herpes infections (relative incidence = 1.69, 95% CI 1.06–2.70). For the children given Meningococcal group C vaccines concomitantly no significantly increased risk was seen in either the bacterial (relative incidence = 0.54, 95% CI 0.26–1.13) or viral cases (relative incidence = 0.46, 95% CI 0.11–1.93).Our study confirms that the MMR vaccine does not increase the risk of invasive bacterial or viral infection in the 90 days after the vaccination and does not support the hypothesis that there is an induced immune deficiency due to overload from multi-antigen vaccines.     

Barriers to timely administration of birth dose vaccines in The Gambia,West Africa

ObjectiveAlthough vaccine coverage in infants in sub-Saharan Africa is high, this is estimated at the age of 6–12 months. There is little information on the timely administration of birth dose vaccines. The objective of this study was to assess the timing of birth dose vaccines (hepatitis B, BCG and oral polio) and reasons for delayed administration in The Gambia.MethodsWe used vaccination data from the Farafenni Health and Demographic Surveillance System (FHDSS) between 2004 and 2014. Coverage was calculated at birth (0–1 day), day 7, day 28, 6 months and 1 year of age. Logistic regression models were used to identify demographic and socio-economic variables associated with vaccination by day 7 in children born between 2011 and 2014.ResultsMost of the 10,851 children had received the first dose of hepatitis B virus (HBV) vaccine by the age of 6 months (93.1%). Nevertheless, only 1.1% of them were vaccinated at birth, 5.4% by day 7, and 58.4% by day 28. Vaccination by day 7 was associated with living in urban areas (West rural: adjusted OR (AOR) = 6.13, 95%CI: 3.20–11.75, east rural: AOR = 6.72, 95%CI: 3.66–12.33) and maternal education (senior-educations: AOR = 2.43, 95%CI: 1.17–5.06); and inversely associated with distance to vaccination delivery points (≧2 km: AOR = 0.41, 95%CI: 0.24–0.70), and Fula ethnicity (AOR = 0.60, 95%CI: 0.40–0.91).ConclusionVaccine coverage in The Gambia is high but infants are usually vaccinated after the neonatal period. Interventions to ensure the implementation of national vaccination policies are urgently needed.     

Travel medicine consultation: An opportunity to improve coverage for routine vaccinations

BackgroundTravelers may be responsible for the spread of vaccine-preventable diseases upon return. Travel physicians and family physicians may play a role in checking and updating vaccinations before traveling. Our aim was to evaluate the vaccine coverage for mandatory and recommended vaccination in travelers attending a travel medicine clinic (TMC).MethodsVaccine coverage was measured using the current French immunization schedule as reference for correct immunization, in travelers providing a vaccination certificate during the TMC visit (university hospital of Saint-Étienne), between August 1, 2013 and July 31, 2014.ResultsIn total, 2336 travelers came to the TMC during the study period. Among the 2019 study participants, only 1216 (60.3%) provided a vaccination certificate. Travelers who provided a vaccination certificate were significantly younger than travelers who did not (mean age: 34.8 ± 17.8 vs. 46 ± 18.4 years, P < 0.005) and were less likely to be Hajj pilgrims. Vaccine coverage against Tetanus, Diphtheria, and Poliomyelitis (Td/IPV vaccine) was 91.8%, 78.6% against Measles, Mumps, and Rubella (MMR), and 59.4% against Viral Hepatitis B (HBV). BCG vaccine coverage was 71.9%. Older travelers were less likely to be correctly vaccinated, except against HBV as vaccinated travelers were significantly older than unvaccinated travelers.ConclusionObtaining information about immunization in travelers is difficult. Coverage for routine vaccines should be improved in this population. Travel medicine consultations could be the opportunity to vaccinate against MMR, HBV, and Td/IPV.     

Estimates of pertussis vaccine effectiveness in United States air force pediatric dependents

BackgroundPertussis vaccination compliance is critical for reduction in the prevalence of disease; however, the current acellular pertussis vaccine may not provide sufficient protection from infection. This study examined acellular pertussis vaccine effectiveness (VE) for Air Force dependents less than 12 years of age.MethodsWe conducted a case-control study among Air Force pediatric dependents from 2011 to 2013, comparing cases with positive pertussis test results to controls who received the same lab tests with a negative result. Our study population was categorized by age group and vaccination status based on the Centers for Disease Control and Prevention recommended pertussis vaccination schedule. VE was calculated with respect to vaccination status and pertussis lab results.ResultsWe compared 27 pertussis laboratory positive cases with 974 pertussis laboratory negative controls, 2 months to <12 years old. Comparing completely vaccinated to non-vaccinated patients, the overall VE was 78.3% (95% confidence interval (CI): 48.6, 90.8; p < 0.001). VE was highest among those 15 months to <6 years old: 97.6% (95% CI: 78.5, 99.7; p < 0.001). Children 6 to <12 years old had the lowest VE: 48.5% (95% CI: −74.0, 84.7; p = 0.28). Comparing partially vaccinated patients to nonvaccinated patients yielded 64.2% (95% CI: −7.2, 88.1; p = 0.06) overall VE.ConclusionsAcellular pertussis vaccination was effective at preventing laboratory confirmed pertussis among our Air Force pediatric dependent population, with highest protection among completely vaccinated, young children. Older children received the lowest amount of protection. Partial vaccination had near significant protection. Our overall calculated pertussis VE corroborates other pertussis VE studies looking at similar age groups.     

Severity of mumps disease is related to MMR vaccination status and viral shedding

BackgroundDuring recent years, various mumps outbreaks have occurred among measles, mumps, and rubella (MMR) vaccinated persons in various countries worldwide, including the Netherlands. We studied mumps virus shedding in MMR vaccinated and unvaccinated mumps patients and related these findings to clinical data.MethodsIn this study, we included 1112 mumps patients of whom diagnostic samples were tested positive in our laboratory between 1 January 2007 and 31 December 2014. We compared mumps virus shedding and severity of disease between patients who had received 2 doses of MMR (n = 592) and unvaccinated mumps patients (n = 195). Mumps virus shedding in saliva and urine specimens was measured by qPCR. Severity of disease was studied in a subset of patients with clinical data available.ResultsMumps patients who had received 2 MMR doses shed less often mumps virus in their urine than unvaccinated patients. Salivary viral loads were higher at day of onset of disease in twice MMR vaccinated patients with viruria than in twice MMR vaccinated patients without viruria. However, salivary viral loads did not significantly differ between patients who had received 2 MMR doses and unvaccinated patients. Bilateral parotitis and orchitis were less often reported in patients who had received 2 MMR doses than in unvaccinated patients. Furthermore, the prevalence of bilateral parotitis and orchitis was higher among twice MMR vaccinated patients with viruria than among twice MMR vaccinated patients without viruria.ConclusionsMMR vaccination was associated with less severe disease among mumps patients. Systemic spread of virus was associated with more severe disease. The elevated salivary viral loads in patients with systemic mumps disease suggest that these patients pose a higher risk for mumps virus transmission. Our study contributes to the understanding of mumps virus pathogenesis and shows the protective effect of MMR vaccination on severity of disease.     

Assessing misclassification of vaccination status: Implications for studies of the safety of the childhood immunization schedule

BackgroundTo address public concern about the safety of the childhood immunization schedule, the Institute of Medicine recommended observational studies comparing adverse health outcomes of fully vaccinated children to children under-vaccinated due to parental choice. Misclassification of vaccination status could bias such studies.ObjectiveTo assess risk of misclassification of vaccination status within the Vaccine Safety Datalink (VSD).Design/methodsA retrospective cohort study was conducted in three phases. In phase 1, electronic health record (EHR) data were used to identify patterns of under-vaccination during the first 24 months of life potentially due to parental choice. In phase 2, a random sample of records of under-vaccinated children was manually reviewed. In phase 3, a separate sample of parents were surveyed to assess whether EHR data accurately reflected their child’s vaccination status. Phases 1 and 2 were conducted at 6 VSD sites, phase 3 at 1 site.ResultsThe study cohort included 361,901 children born 2004 through 2012. By 24 months of age, 198,249 (54.8%) were fully vaccinated with no delays, 84,698 (23.4%) experienced delays but were fully vaccinated by 24 months of age, 4865 (1.3%) received no vaccines, 3789 (1.0%) delayed starting vaccination until ≥4 months of age, 4781 (1.3%) had consistent vaccine-limiting (≤2 vaccines per visit), and the remaining 65,519 (18.1%) were missing vaccine series or doses. When a diagnosis code for vaccine refusal was present in EHR data, encounter notes confirmed vaccine refusal as the reason for under-vaccination for nearly 100% of sampled records. Parent surveys confirmed these findings. Parents of under-vaccinated children were more likely to report visiting an alternative medical provider than parents of fully vaccinated children.ConclusionsSpecific groups of children, under-vaccinated due to parental choice, can be identified with relatively low likelihood of misclassification of vaccination status using EHR-based vaccine data and diagnosis codes.     

Contrasting female-male mortality ratios after routine vaccinations with pentavalent vaccine versus measles and yellow fever vaccine. A cohort study from urban Guinea-Bissau

BackgroundIn addition to protection against the target diseases, vaccines may have non-specific effects (NSEs). Measles vaccine (MV) has beneficial NSEs, providing protection against non-measles deaths, most so for girls. By contrast, though protecting against diphtheria, tetanus and pertussis, DTP vaccine is associated with increased female mortality relative to male mortality. In 2008, Guinea-Bissau replaced DTP with the DTP-containing pentavalent vaccine (Penta; DTP-H. influenza type B-Hepatitis B) at 6, 10 and 14 weeks and yellow fever vaccine (YF) was to be given with MV. We investigated possible sex-differential mortality rates following Penta and MV+YF vaccination.MethodsBandim Health Project (BHP) registers vaccines given by the three government health centres in the study area and vital status through demographic surveillance. We assessed the association between sex and mortality by vaccination status in Cox proportional hazards models with age as underlying timescale. Follow-up was censored at a subsequent vaccination contact or after 6 months of follow-up.ResultsBetween September 2008 and April 2011, we registered 23,448 vaccination contacts for children aged 42–365 days; 17,313 were for Penta and 3028 for MV (2907 co-administered with YF). During follow-up 112 children died. The female/male mortality rate ratio was 1.73 (1.11–2.70) following Penta and 0.38 (0.12–1.19) after MV (p = 0.02 for same effect). Adjusting for maternal education or weight-for-age at the time of vaccination did not change the estimates.ConclusionPenta appears to have the same negative effects on mortality as those seen for DTP. Assessing post-vaccination mortality for boys and girls is necessary to improve the vaccination programme.     

A general measles vaccination campaign in urban Guinea-Bissau: Comparing child mortality among participants and non-participants

BackgroundMeasles vaccination campaigns targeting children aged 9–59 months are conducted every three years in Guinea-Bissau. Studies have demonstrated beneficial non-specific effects of measles vaccine. We compared mortality one year after the December 2012 measles vaccination campaign in Bissau city for children who received campaign measles vaccine with children who did not receive campaign measles vaccine.MethodsField workers from Bandim Health Project registered all children living in the Bandim Health Project’s study area who received measles vaccination at the campaign posts. Children not seen during the campaign were visited at home and campaign participation status was assessed. We compared mortality rates of participants vs. non-participants in Cox regression models.Results5633 children aged 9–59 months (85%) received campaign measles vaccination and 1006 (15%) did not. During the subsequent year 16 children died. Adjusted for background factors, the hazard ratio (HR) comparing measles vaccinated versus unvaccinated was 0.28 (95% CI: 0.10–0.77). The benefit was larger for girls (HR: 0.17 (0.05–0.59)) and for children who had received routine measles vaccine before the campaign (HR: 0.15 (0.04–0.63)).ConclusionsWe found indications of strong beneficial non-specific effects of receiving measles vaccine during the 2012 campaign, especially for girls and children with previous routine measles vaccination. Measles vaccination campaigns may be an effective way of improving child survival.     

Influenza vaccination coverage of Vaccine for Children (VFC)-entitled versus privately insured children,United States, 2011–2013

BackgroundThe Vaccines for Children (VFC) program provides vaccines at no cost to children who are Medicaid-eligible, uninsured, American Indian or Alaska Native (AI/AN), or underinsured and vaccinated at Federally Qualified Health Centers or Rural Health Clinics. The objective of this study was to compare influenza vaccination coverage of VFC-entitled to privately insured children in the United States, nationally, by state, and by selected socio-demographic variables.MethodsData from the National Immunization Survey-Flu (NIS-Flu) surveys were analyzed for the 2011–2012 and 2012–2013 influenza seasons for households with children 6 months–17 years. VFC-entitlement and private insurance status were defined based upon questions asked of the parent during the telephone interview. Influenza vaccination coverage estimates of children VFC-entitled versus privately insured were compared by t-tests, both nationally and within state, and within selected socio-demographic variables.ResultsFor both seasons studied, influenza coverage for VFC-entitled children did not significantly differ from coverage for privately insured children (2011–2012: 52.0% ± 1.9% versus 50.7% ± 1.2%; 2012–2013: 56.0% ± 1.6% versus 57.2% ± 1.2%). Among VFC-entitled children, uninsured children had lower coverage (2011–2012: 38.9% ± 4.7%; 2012–2013: 44.8% ± 3.5%) than Medicaid-eligible (2011–2012: 55.2% ± 2.1%; 2012–2013: 58.6% ± 1.9%) and AI/AN children (2011–2012: 54.4% ± 11.3%; 2012–2013: 54.6% ± 7.0%). Significant differences in vaccination coverage among VFC-entitled and privately insured children were observed within some subgroups of race/ethnicity, income, age, region, and living in a metropolitan statistical area principle city.ConclusionsAlthough finding few differences in influenza vaccination coverage among VFC-entitled versus privately insured children was encouraging, nearly half of all children were not vaccinated for influenza and coverage was particularly low among uninsured children. Additional public health interventions are needed to ensure that more children are vaccinated such as a strong recommendation from health care providers, utilization of immunization information systems, provider reminders, standing orders, and community-based interventions such as educational activities and expanded access to vaccination services.     

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.     

The Roma vaccination gap: Evidence from twelve countries in Central and South-East Europe

AimTo investigate differences in vaccination coverage between Roma and otherwise comparable non-Roma children, including factors associated with the vaccination gap, health care access and discrimination faced by Roma.MethodsWe analyse data from the Roma Regional Survey 2011 implemented in twelve countries of Central and South-East Europe. Our sample comprises 8233 children aged up to 6 with 7072 Roma children and 1161 non-Roma children. Estimates of the Roma vaccination gap are estimated using Logit regressions.ResultsWe find that the Roma children have a lower probability of being vaccinated compared to non-Roma (odds ratio = 0.325). The odds of being vaccinated for a Roma child is 33.9% that of a non-Roma child for DPT, 34.4% for Polio, 38.6% for MMR and 45.7% for BCG. These differences do not appear to be explained entirely by their worse socio-economic status. The ethnic gap narrows by about 50% once individual characteristics are controlled for, with odds ratios of 0.548 for DPT, 0.559 for Polio, 0.598 for MMR and 0.704 for BCG. The probability of being vaccinated increases with access to health care, especially when Roma have a doctor to approach when needed.ConclusionsOur findings point out a large difference in vaccination coverage between Roma and non-Roma and support the need for better understanding of factors influencing vaccination among Roma as well as policies that might improve services for Roma in Central and South-East Europe.     

Delayed BCG vaccination results in minimal alterations in T cell immunogenicity of acellular pertussis and tetanus immunizations in HIV-exposed infants

BackgroundBacille Calmette–Guerin (BCG) is effective in preventing disseminated tuberculosis (TB) in children but may also have non-specific benefits, and is thought to improve immunity to unrelated antigens through trained innate immunity. In HIV-infected infants, there is a risk of BCG-associated adverse events. We aimed to explore whether delaying BCG vaccination by 8 weeks, in utero or perinatal HIV infection is excluded, affected T-cell responses to B. pertussis (BP) and tetanus toxoid (TT), in HIV-exposed, uninfected infants.MethodsInfants were randomized to receive BCG vaccination at birth or 8 weeks of age. At 8 and 14 weeks, T cell proliferation and intracellular cytokine (IL-2, IL-13, IL-17, and IFN-γ) expression was analyzed in response to BP, TT and Staphylococcal enterotoxin B (SEB) antigens.ResultsDelaying BCG vaccination did not alter T-cell proliferation to BP or TT antigens. Infants immunized with BCG at birth had higher CD4+ T cell proliferation to SEB at 14 weeks of age (p = 0.018). Birth-vaccinated infants had increased CD8+ IL-2 expression in response to BP, but not TT or SEB, at 8 weeks. Infants vaccinated with BCG at 8 weeks had significantly lower IL-13 expression by BP-specific CD4+ and CD8+ T cells at 14 weeks (p = 0.032 and p = 0.0035, respectively). There were no observed differences in multifunctional cytokine response to TT, BP or SEB between infants vaccinated with BCG at birth versus 8 weeks of age.ConclusionDelaying BCG vaccination until 8 weeks of age results in robust T-cellular responses to BP and TT in HIV-exposed infants.Clinical Trial Registry: NCT02062580.     

Different effects of BCG strains – A natural experiment evaluating the impact of the Danish and the Russian BCG strains on morbidity and scar formation in Guinea-Bissau

BackgroundDifferent Bacillus Calmette-Guerin (BCG) vaccine strains may have different non-specific effects. We assessed the effect of two BCG strains (Danish and Russian) on childhood morbidity and BCG scarification in Guinea-Bissau.MethodsDuring 2011–2013, infants in the Bandim Health Project’s urban study area received the Danish or Russian BCG in a natural experiment. Health center consultations were registered at point of care and scar status and size at age 4½ months. We assessed the effect of strain on consultation rates between vaccination and age 45 days in Cox proportional hazards models. Scar prevalence and size were compared using binomial regression and ranksum tests.ResultsAmong 1206 children, 18% received Danish BCG (n = 215) and 82% Russian BCG (n = 991). The adjusted hazard ratio (aHR) for consultations was 0.94 (95% CI 0.60–1.46) for Danish BCG compared with Russian BCG. Girls vaccinated with Danish BCG tended to have lower consultation rates compared with girls vaccinated with Russian BCG (aHR 0.56 (0.25–1.24)), whereas the effect was opposite for boys (aHR 1.24 (0.74–2.11)), p = 0.09. Children vaccinated with Danish BCG were more likely to develop a scar (97%) than children vaccinated with Russian BCG (87%), the relative risk (RR) being 1.11 (1.06–1.16). The effect was stronger in girls, and BCG scar size was larger among infants vaccinated with the Danish strain.ConclusionBCG strain influences scar prevalence and scar size, and may have sex differential effects on morbidity. BCG strains are currently used interchangeably, but BCG scarring has been linked to subsequent survival. Hence, more research into the health effects of different BCG strains is warranted. Small adjustments of BCG production could potentially lower childhood morbidity and mortality at low cost.     

Seroprevalence of antibodies against serogroup C meningococci in the region of Valencia,Spain: Impact of meningococcal C conjugate vaccination

Background and aimsMeningococcal C conjugate (MCC) vaccination programs provide direct and indirect protection against meningococcal disease. However, a decrease in the antibodies could affect herd immunity. We conducted a seroprevalence study to assess the immunity in subjects 8–12 years after different MCCV vaccination programs were launched and evaluated the impact of vaccination on seroprotection.MethodsSeroepidemiological study conducted from October 2010 to April 2012 in the region of Valencia, Spain. Sample size was not proportional to the population but to the expected seroprotection by age group. Sera from subjects that were ≥ 3 years old were tested using a standardized complement-mediated serum bactericidal antibodies (SBA) assay. Age-stratified proportions of subjects with SBA titers ≥ 8 were considered seroprotected and evaluated. A multivariate logistic regression model was performed to evaluate the impact of vaccination on the seroprotection.ResultsSerum samples from 1880 subjects were collected. In total, 523 (27.8%) of the 1880 subjects and 446 (31.2%) of the 1430 subjects < 30 years (targeted to any vaccination campaign) showed protective SBA titers. The highest percentage of seroprotected subjects (67.8%, 95%CI 56.9–77.4) was observed in those that were vaccinated in a catch-up campaign at 10–13 years of age (20–21 years old at the time of blood sampling). Those scheduled for immunization in infancy at 2, 4 and 6 months of age (7–8 years at blood sample) represented the lowest (7.1%, 95% CI 3.3–13.1) number of seroprotected subjects. Having received one vaccine dose after 12 months of age was associated with increased seroprotection. The present study revealed a positive correlation between the increasing age at vaccination and longer duration of seroprotection.ConclusionOnly one in three subjects who were vaccinated with MCC vaccine was seroprotected after 8–12 years. These findings emphasize that seroprevalence studies are essential to identify susceptible cohorts and to inform vaccine policy.     

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.     

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.     

Vaccination rates and adherence in premature infants before and after pneumococcal conjugate vaccine schedule change for term infants – A claims database analysis in Germany

BackgroundIn 2015, the German Standing Committee on Vaccination (STIKO) changed the pneumococcal conjugate vaccination (PCV) schedule for mature infants from a 3+1 scheme (2, 3, 4, and 11–14 months of age) to a 2+1 scheme (2, 4, and 11–14 months of age). For premature infants, the 3+1 scheme remained. The aim of this study was to assess vaccination rates, completeness, and timeliness for PCV in premature infants before and after the modified recommendation.MethodsA retrospective claims data analysis using the “Institut für angewandte Gesundheitsforschung Berlin” Research Database was conducted. Premature infants born in 2013 and 2016 with an individual follow-up of 24 months were included. Hexavalent combination (HEXA) vaccination with a consistent 3+1 recommendation for mature and premature infants was analyzed as reference vaccination.ResultsAfter 24 months, the PCV rate for at least one dose remained stable in premature newborns of 2016 compared to 2013, while the HEXA vaccination rate increased slightly. However, a significant decrease of a completed PCV schedule (4 doses) in premature infants was noted, whereas the completeness of HEXA vaccination did not change. The timeliness of PCV in premature newborns increased for the first and the booster PCV, while the timeliness of HEXA immunization did not change from 2013 to 2016.ConclusionAlthough STIKO still recommends a 3+1 PCV schedule for premature infants in Germany, premature infants were vaccinated according to the changed recommendations for mature born infants. A substantial share of premature infants remained unvaccinated, and their vaccinations were often delayed.