Non-specific effects of BCG and DTP vaccination on infant mortality: An analysis of birth cohorts in Ghana and Tanzania

BackgroundVaccines may induce non-specific effects on survival and health outcomes, in addition to protection against targeted pathogens or disease. Observational evidence suggests that infant Baccillus Calmette-Guérin (BCG) vaccination may provide non-specific survival benefits, while diphtheria-tetanus-pertussis (DTP) vaccination may increase the risk of mortality. Non-specific vaccine effects have been hypothesized to modify the effect of neonatal vitamin A supplementation (NVAS) on mortality.Methods22,955 newborns in Ghana and 31,999 newborns in Tanzania were enrolled in two parallel, randomized, double-blind, placebo-controlled trials of neonatal vitamin A supplementation from 2010 to 2014 and followed until 1-year of age. Cox proportional hazard models were used to estimate associations of BCG and DTP vaccination with infant survival.ResultsBCG vaccination was associated with a decreased risk of infant mortality after controlling for confounders in both countries (Ghana adjusted hazard ratio (aHR): 0.51, 95% CI: 0.38–0.68; Tanzania aHR: 0.08, 95% CI: 0.07–0.10). Receiving a DTP vaccination was associated with a decreased risk of death (Ghana aHR: 0.39, 95% CI: 0.26–0.59; Tanzania aHR: 0.19, 95% CI: 0.16–0.22). There was no evidence of interaction between BCG or DTP vaccination status and infant sex or NVAS.ConclusionWe demonstrated that BCG and DTP vaccination were associated with decreased risk of infant mortality in Ghana and Tanzania with no evidence of interaction between DTP or BCG vaccination, NVAS, and infant sex. Our study supports global recommendations on BCG and DTP vaccination and programmatic efforts to ensure all children have access to timely vaccination.Clinical trials registration: Ghana (Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12610000582055) and Tanzania (ANZCTR: ACTRN12610000636055)     

BCG vaccination scar associated with better childhood survival in Guinea-Bissau

BACKGROUND: Recent studies have suggested that Bacille Calmette-Guerin (BCG) vaccination may have a non-specific beneficial effect on infant survival and that a BCG scar may be associated with lower child mortality. No study has previously examined the influence of BCG vaccination on cause of death. METHODS: Two cohorts (A and B) were used to describe the mortality pattern for children with and without BCG scar and to determine specific causes of death. In cohort A (n = 1813), BCG scar was assessed at 6 months of age and as previously described children with a BCG scar had lower mortality over the next 12 months than children with no BCG scar. In cohort B, 1617 children aged 3 months to 5 years of age had their BCG scar status assessed in a household-based survey and mortality was assessed during a 12-month period. Causes of death were determined by verbal autopsy (VA) and related to BCG scar status in a cause-specific hazard function. RESULTS: Controlling for background factors associated with mortality, there was lower mortality for children with a BCG scar than without in cohort B, the mortality ratio (MR) being 0.45 (95% CI 0.21-0.96). Exclusion of children exposed to TB did not have any impact on the result. In a combined analysis of cohorts A and B, the MR was 0.43 (95% CI 0.28-0.65) controlling for background factors. There were no large differences in distribution of the five major causes of death (malaria, pneumonia, acute diarrhoea, chronic diarrhoea, and meningitis/encephalitis) according to BCG scar status in the two cohorts. Having a BCG scar significantly reduced the risk of death from malaria [MR 0.32 (95% CI 0.13-0.76)]. CONCLUSIONS: A BCG scar is a marker of better survival among children in countries with high child mortality. BCG vaccination may affect the response to several major infections including malaria.     

Smallpox and BCG vaccination in childhood and cutaneous malignant melanoma in Danish adults followed from 18 to 49 years

BackgroundEarly smallpox and Bacillus Calmette-Guérin (BCG) vaccinations have been associated with reduced risk of cutaneous malignant melanoma (CMM). We assessed the association between pre-school smallpox vaccination and early-school BCG vaccination and CMM in a young Danish population.MethodsWe conducted a register-based case-cohort study of individuals growing up during the phase-out period of smallpox and BCG vaccination in Denmark (born 1965–1976) utilising the decrease in vaccination during this period. Information on childhood vaccinations and potential confounders from Copenhagen school health records were linked with nationwide registers on cancer (CMM diagnoses), migrations and deaths by personal identification numbers.ResultsThe individuals were followed from age 18 until 31/12/2014 (maximum age at end of follow-up, 49 years). 188 cases of CMM occurred in the background population of 46,239 individuals; 172 CMM cases (91%) had full information and were analysed. The adjusted hazard ratio (HR) for CMM by BCG and/or smallpox vaccination compared with neither vaccine was 1.29 (95% confidence interval (CI) 0.72–2.31). For smallpox vaccination only, HR = 1.23 (95% CI 0.53–2.86) for BCG vaccination only, HR = 1.13 (95% CI 0.61–2.09) and for both smallpox and BCG vaccination, HR = 1.75 (95% CI 0.87–3.48) compared with none of these. Vaccination below the age of one year gave similar results.ConclusionsWe found no strong beneficial effect of smallpox and BCG vaccination against CMM among young adult Danes and with broad confidence intervals our data alone could be compatible with both modest preventive effects, no effects, and modest harmful effects. Our estimates do not contradict a potential modest beneficial effect of neonatal vaccination.     

Human papillomavirus vaccines effectiveness to prevent genital warts: A population-based study using health system integrated databases, 2009–2017

ObjectivesTo assess the effectiveness of the HPV vaccines in preventing genital warts (GW) in women aged 14–23 years and to estimate the incidence of GW in the whole population aged from 14 to 65.DesignPopulation-based retrospective cohort study using real-world data from the Valencia health system Integrated Databases (VID).Study populationAll subjects aged 14–65 years residing in the Valencia Region during 2009–2017 (n = 4,492,724), including a cohort of 563,240 females aged 14–23 years followed-up for the vaccine effectiveness (VE) estimations.Main outcome measuresIncident cases of GW defined as the first activation of GW-related codes (ICD-9-CM 078.11 or ICD-10-CM A63.0) in hospital, primary and specialized care during the study period. Adjusted VE was estimated as (1-Relative Risk (RR)) × 100 by a negative binomial Bayesian model.ResultsThere were 23,049 cases of GW in the overall population and 2,565 in the females’ cohort 14–23 years old. The incidence rate (IR) (in 100,000 persons-year) was 69.1 (95% CI 68.21–69.99) in the population overall, being higher in men (72.73; 95% CI 71.45–74.04). The IR of GW was 104.08 (95% CI 100.79–108.94) in the cohort of young women. The RR of GW increased with age from 14 to 21 years, reaching a plateau from 21 to 23. The VE of a complete schedule was 74% (95% CrI 68–79) for quadrivalent HPV vaccine (HPV4v). No effectiveness was seen with a full vaccination course with the bivalent HPV vaccine (HPV2v) in girls up to 21 years old. GW IR tends to be higher in unvaccinated cohorts covered by HPV4v vaccine than in unvaccinated cohorts not covered by HPV4v vaccine.ConclusionsA complete HPV4v vaccination schedule was 74% effective in reducing GW in our population. Our results also suggest an indirect protection to unvaccinated and HPV2v vaccinated girls.     

Exploring the effects of BCG vaccination in patients diagnosed with tuberculosis: Observational study using the Enhanced Tuberculosis Surveillance system

BackgroundBacillus Calmette–Guérin (BCG) is one of the most widely-used vaccines worldwide. BCG primarily reduces the progression from infection to disease, however there is evidence that BCG may provide additional benefits. We aimed to investigate whether there is evidence in routinely-collected surveillance data that BCG vaccination impacts outcomes for tuberculosis (TB) cases in England.MethodsWe obtained all TB notifications for 2009–2015 in England from the Enhanced Tuberculosis surveillance system. We considered five outcomes: All-cause mortality, death due to TB (in those who died), recurrent TB, pulmonary disease, and sputum smear status. We used logistic regression, with complete case analysis, to investigate each outcome with BCG vaccination, years since vaccination and age at vaccination, adjusting for potential confounders. All analyses were repeated using multiply imputed data.ResultsWe found evidence of an association between BCG vaccination and reduced all-cause mortality (aOR:0.76 (95%CI 0.64–0.89), P:0.001) and weak evidence of an association with reduced recurrent TB (aOR:0.90 (95%CI 0.81–1.00), P:0.056). Analyses using multiple imputation suggested that the benefits of vaccination for all-cause mortality were reduced after 10 years.ConclusionsWe found that BCG vaccination was associated with reduced all-cause mortality in people with TB although this benefit was less pronounced more than 10 years after vaccination. There was weak evidence of an association with reduced recurrent TB.     

Revaccination with measles-mumps-rubella vaccine and hospitalization for infection in Denmark and Sweden – An interrupted time-series analysis

BackgroundIn a previous cohort study of 4-year-old Danish children, revaccination with the live measles-mumps-rubella vaccine (MMR) was associated with a 16% reduction in the rate of hospitalization lasting two days or longer for non-measles-mumps-rubella infections.AimTo examine if the introduction of revaccination with MMR at 4 years of age in Denmark (spring 2008) and at 7–9 years of age in Sweden (autumn 2009), at a time when there was virtually no measles, mumps or rubella cases, was associated with a reduction in the rate of hospitalization-for-infection lasting two days or longer at the population level.MethodsWe included 4-year-olds in Denmark and 7–9-year-olds in Sweden. We obtained the number of hospitalization-for-infection lasting two days or longer from nationwide hospital registers. Person-years at risk were approximated from population statistics for each season and year. We performed an interrupted time series analysis using Poisson regression to estimate the change in hospitalization incidence rates following the introduction of MMR revaccination, adjusting for seasonality. We also performed analyses with control series (3-year-olds in Denmark and 4-year-olds in Sweden).ResultsComparing the incidence of hospitalization-for-infection lasting two days or longer after the introduction of MMR revaccination with the expected level without an introduction of MMR revaccination resulted in an incidence rate ratio of 1.07 (95% confidence interval [CI] = 0.89–1.28) for 4-year-olds in Denmark and 0.89 (95% CI = 0.77–1.02) for 7–9-year-olds in Sweden in analyses without controls. Analyses with controls gave similar results.ConclusionThis population-level study of the introduction of MMR revaccination in Denmark and Sweden had inadequate power to confirm or refute the findings from an individual-level Danish study of an association between MMR revaccination and a lower incidence rate of hospitalization-for-infection lasting two days or longer.     

The impact of HPV multi-cohort vaccination: Real-world evidence of faster control of HPV-related morbidity

BackgroundIn 2009, both Norway and Denmark initiated routine quadrivalent human papillomavirus vaccination (qHPV) for 12-year-old girls; however, Denmark also introduced free-of-charge multi-cohort vaccination for older age groups in 2008. We aim to describe trends in genital warts (GWs) incidence rates (IRs) among men and women and qHPV vaccine coverage among women in Norway and Denmark in 2006–2015.MethodsWe linked multiple national health registries in Norway and Denmark via national personal identifiers to access data on GWs incidence and qHPV vaccination among women and men aged 12–35 years residing in Norway and Denmark in 2006–2015. We calculated age-specific and age-standardized GWs IRs, GWs IR trends before (2006–2009) and after (2009–2015) the implementation of qHPV vaccination, and qHPV vaccine coverage among women.ResultsIn Norway and Denmark together, there were more than 200,000 cases of incident GWs and over 710,000 girls got at least one dose of qHPV vaccine during the study period. The total qHPV coverage in Norway and Denmark in 2015 was among women aged 12–35 years 24% and 70%, respectively. GWs IRs in Norway and Denmark decreased annually in 2009–2015 among women by 4.8% (95% confidence interval: 4.3 to 5.3) and 18.0% (95%CI: 17.5 to 18.6), respectively, and among men 1.9% (95%CI: 1.4 to 2.4) and 10.7% (95%CI: 10.3 to 11.2), respectively. In Denmark, GWs IRs decreased rapidly among both sexes and all age groups after qHPV vaccination, while Norway showed only a modest decrease.ConclusionRapid decline in HPV-related morbidity is feasible with high coverage of multi-cohort vaccination. However, the decision to vaccinate a single cohort of 12-years-old girls only will postpone HPV-related disease control by at least a decade. Thus countries planning HPV vaccination programs should also initiate multi-cohort vaccination for faster disease control.     

COVID-19 vaccination rates among adolescents (12–17 years) by immigrant background and sociodemographic factors: A nationwide registry study in Norway

PurposeLower COVID-19 vaccination rates have been observed among some adult immigrant populations in Norway, and there appears to be an association with sociodemographic factors. However, knowledge is lacking on the distribution of vaccination rates and role of sociodemographic factors among adolescents. This study aims to describe COVID-19 vaccination rates among adolescents according to immigrant background, household income, and parental education.MethodsIn this nationwide registry study, we analyzed individual-level data on adolescents (12–17 years) from the Norwegian Emergency preparedness register for COVID-19 until September 15th, 2022. We estimated incidence rate ratios (IRR) for receiving at least one COVID-19 vaccine dose by country background, household income and parental education, using Poisson regression, adjusting for age, sex, and county.ResultsThe sample comprised 384,815 adolescents. Foreign-born and Norwegian-born with foreign-born parents, had lower vaccination rates (57 % and 58 %) compared to adolescents with at least one Norwegian-born parent (84 %). Vaccination rates by country background varied from 88 % (Vietnam) to 31 % (Russia). Variation and associations by country background, household income, and parental education were greater among 12–15-year-olds than 16–17-year-olds. Household income and parental education were positively associated with vaccination. Compared to the lowest income and education category, IRRs for household income ranged from 1.07 (95 % CI 1.06–1.09) to 1.31 (95 % CI 1.29–1.33) among 12–15-year-olds, and 1.06 (95 % CI 1.04–1.07) to 1.17 (95 % CI 1.15–1.18) among 16–17-year-olds. For parental education, from IRR 1.08 (95 % CI 1.06–1.09) to 1.18 (95 % CI 1.17–1.20) among 12–15-year-olds, and 1.05 (95 % CI 1.04–1.07) to 1.09 (95 % CI 1.07–1.10) among 16–17-year-olds.ConclusionCOVID-19 vaccination rates varied by immigrant background and age group, with lower rates especially among adolescents with background from Eastern Europe and among younger adolescents. Household income and parental education were positively associated with vaccination rates. Our results may help target measures to increase vaccination rates among adolescents.     

BCG vaccine effectiveness in preventing tuberculosis and its interaction with human immunodeficiency virus infection

BACKGROUND: To explore Bacillus Calmette-Guérin vaccine (BCG) as a protective factor against tuberculosis (TB) and how human immunodeficiency virus (HIV) infection modifies the effect of BCG on TB. METHODS: Two matched case-control studies were conducted. One study compared TB cases and controls who were HIV positive. The second compared TB cases and controls who were HIV negative. The study population consisted of 88 TB cases and 88 controls among HIV-positive individuals and 314 TB cases and 310 controls among HIV-negative individuals. Cases were new TB diagnoses, confirmed by either bacteriology, pathology, radiology or clinical response to treatment; controls were selected from people without TB symptoms and who sought medical attention in the same institution where a case was enrolled. BCG was assessed by the presence of a typical scar. RESULTS: The level of protection against all clinical forms of TB was 22% among HIV positive individuals (odds ratio [OR] = 0.78, 95% CI : 0.48-1.26) and 26% among HIV negatives (OR = 0.74, 95% CI : 0.52-1.05). There was a significant difference (P = 0.002) in the level of protection against extrapulmonary TB (ETB) between HIV-negative (OR = 0.54, 95% CI : 0.32-0.93) and HIV-positive individuals (OR = 1.36, 95% CI : 0.72-2.57). CONCLUSION: BCG has a modest protective effect against all forms of TB independent of HIV status, and BCG confers protection against extrapulmonary TB among HIV-negative individuals. However, HIV infection seems to abrogate the protective effect of BCG against extrapulmonary TB. Our data support the public health importance of BCG vaccine in the prevention of extrapulmonary TB among immunocompetent individuals.     

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

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

Pregnancy course,infant outcomes,rehospitalization, and mortality among women with intellectual disability

BackgroundPregnant women with intellectual disability (ID) may have greater levels of comorbidity and decreased care access, social support, or ability to monitor their status and communicate needs, but few studies have examined their pregnancy course and outcome, and little is known about their longer-term maternal and infant health.ObjectiveWe compared pre-pregnancy characteristics, pregnancy outcomes, and rehospitalization <2 years after delivery among women with and without ID.MethodWe identified all women with ID and randomly selected a 10:1 comparison group of women without ID with singleton live birth deliveries in Washington State population-based linked birth-hospital discharge data 1987–2012. Multivariable regressions estimated adjusted odds ratios comparing pre-pregnancy characteristics. In cohort analyses, we estimated relative risks (RR) and 95% confidence intervals (CI) for outcomes.ResultsWomen with ID (N = 103) more often had gestational diabetes (RR 3.39, 95% CI 1.81–6.37), preeclampsia (RR 1.88, 95% CI 1.03–3.42), and inadequate prenatal care (RR 2.48, 95% CI 1.67–3.70). Their infants more often were small for gestational age (RR 1.78, 95% CI 1.10–2.89). Need for rehospitalization postpartum was not increased among women with ID or their infants.ConclusionReasons for increased preeclampsia and gestational diabetes among pregnant women with ID are unclear. Barriers to inadequate prenatal care are multifactorial and warrant further study, with consideration that wellness during pregnancy and other times involves social, familial and clinical support systems responsive to each woman's needs.     

Public health impact of Rotarix vaccination among commercially insured children in the United States

BackgroundThis study (NCT01915888) assessed public health impact of Rotarix, GSK [RV1] vaccination.MethodsChildren born between 2007–2011 were identified from Truven Commercial Claims and Encounters Databases and observed until earlier of plan disenrollment or five years old. Children receiving one or two doses of RV1 during the vaccination window were assigned to incomplete and complete vaccination cohorts, respectively. Children without rotavirus (RV) vaccination (RV1 OR RotaTeq, Merck & Co., Inc. [RV5]) were assigned to the unvaccinated cohort. Claims with International Classification of Disease 9th edition (ICD-9) codes for diarrhea and RV infections were identified. First RV episode incidence, RV-related and diarrhea-related healthcare resource utilization were compared. Multivariate Poisson regression with generalized estimating equations was used to generate 95% confidence intervals (CIs) around incidence rate ratios (IRR) between cohorts while adjusting for gender, age and calendar year. Mean costs for first RV and diarrhea episodes were calculated with adjustment for gender and birth year; bootstrapping was used to determine statistically significant differences between cohorts.ResultsIncidence of first RV episodes was significantly reduced in complete and incomplete vaccination cohorts compared to the unvaccinated cohort (IRR = 0.17 [95%CI: 0.09–0.30] and IRR = 0.19 [95%CI: 0.06–0.58], respectively). RV-related inpatient, outpatient and emergency room (ER) visits were significantly lower for complete vaccination versus unvaccinated cohort. Diarrhea-related inpatient and ER visit rates were significantly lower for complete vaccination versus unvaccinated cohorts; outpatient rates were similar. RV-related and diarrhea-related resource utilization rates were significantly lower or no different for incomplete vaccination versus unvaccinated cohort. Compared with unvaccinated children, adjusted mean cost for first RV episode and first diarrhea episode per 1000 persons was $11,511 (95%CI: $9855-$12,024) and $46,772 (95%CI: $26,268-$66,604) lower, respectively, for completely vaccinated children.ConclusionsRV1 vaccination confers benefits in reduction of RV incidence, RV- and diarrhea-related healthcare resource utilization, and RV- and diarrhea-related healthcare costs.     

Tuberculin reactivity in adults after 50 years of universal bacille Calmette-Guerin vaccination in Taiwan

We aimed to assess whether tuberculin reactivity in adults is affected by bacille Calmette-Guerin (BCG) vaccination after 50 years of universal BCG vaccination with 80-95% coverage. A community-based study on tuberculin reactivity in 619 participants was conducted in February 2000 in Keelung city, Taiwan. Information on BCG vaccination policies and annual risk of infection (ARI) in the underlying population was extracted from consecutive national prevalence surveys relating to the period 1952-1997. Compared with the expected ARI estimate, the standardized morbidity ratio of positive tuberculin response for vaccination in infancy was 2.2 (95% CI 0.3-15.5) for those aged <10 years. The corresponding figures for older age groups ranged from 3.6 (95% CI 2.2-5.9) for those aged 10-12 years to 0.7 (95% CI 0.5-0.9) for those aged 57-67 years. This suggests that the effect of BCG vaccination on positive tuberculin response in adults aged >30 years is probably negligible irrespective of age at vaccination or revaccination and that the tuberculin skin test can be used to diagnose TB in control programmes in countries with moderate or high incidence of TB.     

Modelling the effect of discontinuing universal Bacillus Calmette-Guérin vaccination in an intermediate tuberculosis burden setting

BackgroundBacillus Calmette-Guérin (BCG) vaccination is a widely-used public health intervention for tuberculosis (TB) control. In Taiwan, like other intermediate TB burden settings, steadily declining TB incidence raises important questions on whether universal BCG vaccination should be discontinued. Recent surveys on adverse events following immunisation, such as BCG-induced osteomyelitis/osteitis, also suggest a need to re-evaluate the vaccination programme.MethodsWe developed an age-structured transmission dynamic model, calibrated to population demography and age-specific TB notification rates in Taiwan. We adopted ‘weak-protection’ and ‘strong-protection’ scenarios, representing a range of characteristics including the duration of BCG protection and vaccine efficacies against TB infection and progression. We estimated averted disability-adjusted life years (DALYs) and incremental costs over 10 years after discontinuing universal BCG vaccination in 2018, 2035, and 2050. We also examined the potential impact of ‘surveillance-guided’ discontinuation, triggered once notification rates fall to a given threshold.ResultsIn the weak-protection scenario, discontinuing BCG would result in 2.8 (95% uncertainty range: 2.3, 3.1) additional notified TB cases and −4.1 (−7.7, 0.8) net averted DALYs over 2018–2027. In the strong-protection scenario, 82.9 (72.6, 91.6) additional cases and −402.7 (−506.6, −301.2) averted DALYs would be reported, suggesting a robustly negative health impact. However, in this vaccine scenario, there could be an overall health benefit if BCG is discontinued once TB notification falls below 5 per 100,000 population. The most influential vaccine characteristic for the net health impact is the vaccine efficacy against progression to pulmonary TB. In financial terms, the eliminated cost of the vaccination programme substantially outweighed the incremental cost for TB treatment regardless of BCG protection.ConclusionsBCG discontinuation may be warranted in intermediate burden settings, depending on the quality of vaccine protection, and the potential for refocusing on other TB control activities for earlier detection and treatment.     

Economic evaluation of universal BCG vaccination of Japanese infants

BACKGROUND: The international controversy surrounding the use and effectiveness of the Bacillus Calmette-Guérin (BCG) vaccine and the low incidence of tuberculosis (TB) among Japanese children prompted this study. METHODS: We compared 'universal BCG vaccination' with 'no vaccination at all' using a cost-effectiveness analysis. The study population was a hypothetical cohort comprising a total of 1.2 million infants born in 1996 at locations all over Japan. A model was developed to calculate the number of TB cases prevented by the vaccination programme. Assuming 40-80% overall vaccine efficacy (64-86% for TB-meningitis) and 10 years of protection, we calculated the cost and number of immunizations required to prevent one child from developing TB, the total number of TB cases averted by vaccination and total costs required for the programme. RESULTS: Based on an assumption of flexible vaccine efficacy (40-80%), we estimated that 111-542 TB cases including 10-27 of TB-meningitis would be prevented during the 10 years after BCG vaccination among the cohort of infants born in 1996. About US$35 950-175 862 or 2125-10 399 immunizations would be required to prevent one child from developing TB. Sensitivity analyses covering a wide duration of protection, incidence of TB, vaccine coverage and discount rate, revealed that other than vaccine efficacy, the cost of preventing a single case of TB is highly sensitive to the duration of BCG protection and TB incidence. CONCLUSION: The cost per case of TB prevented is heavily dependent on vaccine efficacy and the duration of protection, and is high compared with the cost of treating one child who has developed TB.     

Medically induced preterm birth and the associations between prenatal care and infant mortality

PurposeDuring the last 30 years, the use of prenatal care, both the proportion of women receiving the recommended number of visits and the average number of visits, has increased substantially. Although infant mortality has decreased, the incidence of preterm birth has increased. We hypothesized that prenatal care may lead to lower infant mortality in part by increasing the detection of obstetrical problems for which the clinical response may be to medically induce preterm birth.MethodsWe examined whether medically induced preterm birth mediates the association between prenatal care and infant mortality by using newly developed methods for mediation analysis. Data are the cohort version of the national linked birth certificate and infant death data for 2003 births. Analyses were adjusted for maternal sociodemographic, geographic, and health characteristics.ResultsReceiving more prenatal care visits than recommended was associated with medically induced preterm birth (odds ratio [OR], 2.44; 95% confidence interval [95% CI], 2.40–2.49) compared with fewer visits than recommended). Medically induced preterm birth was itself associated with greater infant mortality (OR, 5.08; 95% CI, 4.61–5.60) but that association was weaker among women receiving extra prenatal care visits (OR 3.08; 95% CI, 2.88–3.30) compared with women receiving the recommended number of visits or fewer.ConclusionsThese analyses suggest that some of the benefit of prenatal care in terms of infant mortality may be in part due to medically induced preterm birth. If so, the use of preterm birth rates as a metric for tracking birth policy and outcomes could be misleading.     

Identification of subgroups in the Danish population for targeted human papillomavirus vaccination efforts

BackgroundIn the Danish childhood vaccination program, the human papillomavirus (HPV) vaccination coverage is lower than for other vaccines. To tailor a targeted HPV vaccination effort, we aimed to identify girls in Denmark with lower first dose HPV vaccination coverage than girls in general.MethodsA population-based retrospective cohort study was performed of girls born in 2001–2004, residing in Denmark in September 2019 (N = 128,351). Data from the Danish Vaccination Register was linked to sociodemographic data from the Danish Civil Registration System and Statistics Denmark. Cox's proportional hazard regression models were used to compare vaccination uptake rates between subgroups of girls.ResultsHPV vaccination coverage at 14 years of age varied widely by municipality (53.4–80.6%). Girls living with neither of their parents had a lower chance of being vaccinated compared to girls living with both their parents (HR 0.43; 95% CI 0.41–0.46), likewise for girls attending special need education compared with girls attending public schools (HR 0.50; 95% CI 0.42–0.59). The vaccination uptake among immigrants was lower compared to Danish-born girls (HR 0.51; 95% CI 0.49–0.54), especially among immigrant girls whose parents had not passed any Danish exams. Finally, girls who were DTaP-IPV revaccinated had a 50% greater chance of being HPV vaccinated compared to girls who were not (HR 1.61; 95% CI 1.58–1.64).ConclusionTo increase the HPV vaccination uptake, we recommend vaccination efforts targeting girls living without any of their parents, girls attending special need education, immigrants, and girls who are not DTaP-IPV revaccinated. When targeting immigrants, the effort should focus on disseminating sufficient and understandable information about the Danish childhood vaccination program to the parents.     

The impact of two-dose varicella vaccination on varicella and herpes zoster incidence in South Korea using a mathematical model with changing population demographics

BackgroundIn South Korea, one-dose varicella vaccination was introduced to the National Immunization Program in 2005, but varicella outbreaks have continued to occur. Therefore, a two-dose vaccination strategy is considered.MethodsWe developed an age-structured deterministic compartment model using Korean population projection data. The impact of adding a second dose of varicella vaccine on varicella and herpes zoster (HZ) epidemiology was assessed under four different vaccine effectiveness (VE) scenarios (base, moderate, lowest, highest) and the optimal timing of the second vaccine dose (18 months, 4, 5, or 6 years of age) was examined over the period 2020–2065.ResultsA two-dose vaccination schedule reduced the cumulative varicella incidence by > 90% compared to no vaccination, regardless of the VE. The additional reduction attributable to a second dose compared to a single dose was greatest (82%) with the lowest VE scenario. A second dose at 6 years of age reduced the varicella incidence at a population level, whereas a second dose at 18 months of age reduced the varicella incidence primarily in the target birth cohorts. Routine vaccination at the age of 18 months with a catch-up vaccination of 6-year-olds was the optimal strategy for birth cohort and population-level control. HZ incidence continued to increase under no vaccination scenario, which represents the effect of aging population. Under a two-dose scenario, the additional increase in HZ incidence attributable to the reduced exogenous boosting was small relative to a one-dose scenario and a further reduction in HZ cases was observed.ConclusionA two-dose varicella vaccination schedule would significantly reduce varicella and HZ incidence in the long term. A second dose at the age of 18 months with a catch-up vaccination of 6-year-olds would be optimal for controlling varicella in South Korea.     

Determinants of Bacillus Calmette–Guérin (BCG) vaccination among Québec children

ObjectivesTo identify determinants of Bacillus Calmette–Guérin (BCG) vaccination among children born in Québec, Canada, in 1974, the last year of the systematic vaccination campaign.MethodA retrospective birth cohort was assembled in 2011 through probabilistic linkage of administrative databases (n = 81,496). Potential determinants were documented from administrative databases and by interviewing a subset of subjects (n = 1643) in 2012. Analyses were conducted among subjects with complete data, 71,658 (88%) birth cohort subjects and 1154 (70%) interviewed subjects, then redone using multiple imputation. Determinants of BCG vaccination during the organized vaccination program (in 1974), and after the program (1975 onwards) were assessed separately. Logistic regression with backward elimination was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsOverall, 46% of subjects were BCG vaccinated, 43% during the program and 4% after it ended. BCG vaccination during the program was associated with parents' birthplace and urban or rural residence. BCG vaccination after the organized program was only related to ethnocultural origin of the child's grandparents.ConclusionDifferent factors were related to vaccination within and after the organized program. Determinants of BCG vaccination in Québec, Canada, have never been studied and will be useful for future research and vaccination campaigns.     

Birth outcomes for Australian mother-infant pairs who received an influenza vaccine during pregnancy, 2012–2014: The FluMum study

IntroductionIn Australia, influenza vaccination is recommended for all women who will be pregnant during the influenza season. Vaccine safety and effectiveness are key concerns and influencers of uptake for both vaccine providers and families. We assessed the safety of receiving an influenza vaccination during any trimester of pregnancy with respect to preterm births and infant birthweight.MethodsWe conducted a nested retrospective cohort study of ‘FluMum’ participants (2012–2014). Our primary exposure of interest was influenza vaccination during pregnancy. The primary outcomes of interest were infant birthweight and weeks’ gestation at birth for live singleton infants. Analyses included comparisons of these birth outcomes by vaccination status and trimester of pregnancy an influenza vaccine was given. We calculated means, proportions, and relative risks and performed multivariable logistic regression for potential confounding factors.ResultsIn the 7126 mother-infant pairs enrolled in this study, mean maternal age at infant birth was 31.7 years. Influenza vaccine uptake in pregnancy was 34%. Most mothers with a known date of vaccination received a vaccine in the second trimester (51%). Those mothers with a co-morbidity or risk factor were 13% more likely to have influenza vaccine during pregnancy compared to other mothers (RR 1.13, 95% CI 1.04–1.24, p = 0.007). Mean weeks’ gestation at birth was 38.7 for the vaccinated and 38.8 for the unvaccinated group (p = 0.051). Infants in the vaccinated group weighed 15 g less in birthweight compared to the unvaccinated infants (95% CI −12.8 to 42.2, p = 0.29).ConclusionResults arising from this large Australian cohort study are reassuring with respect to two critical safety outcomes; preterm births and low infant birthweights. Studies examining a broader range of birth outcomes following influenza vaccination during pregnancy are required, particularly now that maternal vaccination in pregnancy has expanded to include pertussis as well as influenza.