Religious affiliation as a driver of immunization coverage: Analyses of zero-dose vaccine prevalence in 66 low- and middle-income countries.

Background: The literature on the association between religion and immunization coverage is scant, mostly consisting of single-country studies. Analyses in low and middle-income countries (LMICs) to assess whether the proportions of zero-dose children vary according to religion remains necessary to better understand non-socioeconomic immunization barriers and to inform interventions that target zero-dose children. Methods: We included 66 LMICs with standardized national surveys carried out since 2010, with information on religion and vaccination. The proportion of children who failed to receive any doses of a diphtheria-pertussis-tetanus (DPT) containing vaccine - a proxy for no access to routine vaccination or "zero-dose" status - was the outcome. Differences among religious groups were assessed using a test for heterogeneity. Additional analyses were performed controlling for the fixed effect of country, household wealth, maternal education, and urban-rural residence to assess associations between religion and immunization. Findings: In 27 countries there was significant heterogeneity in no-DPT prevalence according to religion. Pooled analyses adjusted for wealth, maternal education, and area of residence showed that Muslim children had 76% higher no-DPT prevalence than Christian children. Children from the majority religion in each country tended to have lower no-DPT prevalence than the rest of the population except in Muslim-majority countries. Interpretation: Analyses of gaps in coverage according to religion are relevant to renewing efforts to reach groups that are being left behind, with an important role in the reduction of zero-dose children.

Subnational Gender Inequality and Childhood Immunization: An Ecological Analysis of the Subnational Gender Development Index and DTP Coverage Outcomes across 57 Countries.

The role of gender inequality in childhood immunization is an emerging area of focus for global efforts to improve immunization coverage and equity. Recent studies have examined the relationship between gender inequality and childhood immunization at national as well as individual levels; we hypothesize that the demonstrated relationship between greater gender equality and higher immunization coverage will also be evident when examining subnational-level data. We thus conducted an ecological analysis examining the association between the Subnational Gender Development Index (SGDI) and two measures of immunization-zero-dose diphtheria-tetanus-pertussis (DTP) prevalence and 3-dose DTP coverage. Using data from 2010-2019 across 702 subnational regions within 57 countries, we assessed these relationships using fractional logistic regression models, as well as a series of analyses to account for the nested geographies of subnational regions within countries. Subnational regions were dichotomized to higher gender inequality (top quintile of SGDI) and lower gender inequality (lower four quintiles of SGDI). In adjusted models, we find that subnational regions with higher gender inequality (favoring men) are expected to have 5.8 percentage points greater zero-dose prevalence than regions with lower inequality [16.4% (95% confidence interval (CI) 14.5-18.4%) in higher-inequality regions versus 10.6% (95% CI 9.5-11.7%) in lower-inequality regions], and 8.2 percentage points lower DTP3 immunization coverage [71.0% (95% CI 68.3-73.7%) in higher-inequality regions versus 79.2% (95% CI 77.7-80.7%) in lower-inequality regions]. In models accounting for country-level clustering of gender inequality, the magnitude and strength of associations are reduced somewhat, but remain statistically significant in the hypothesized direction. In conjunction with published work demonstrating meaningful associations between greater gender equality and better childhood immunization outcomes in individual- and country-level analyses, these findings lend further strength to calls for efforts towards greater gender equality to improve childhood immunization and child health outcomes broadly.

Conditional probability and ratio-based approaches for mapping the coverage of multi-dose vaccines.

Many vaccines are often administered in multiple doses to boost their effectiveness. In the case of childhood vaccines, the coverage maps of the doses and the differences between these often constitute an evidence base to guide investments in improving access to vaccination services and health system performance in low and middle-income countries. A major problem often encountered when mapping the coverage of multi-dose vaccines is the need to ensure that the coverage maps decrease monotonically with successive doses. That is, for doses i $$ i $$ and j $$ j $$ , i < j ⇒ p i ( s ) ≥ p j ( s ) $$ i

The Association between Childhood Immunization and Gender Inequality: A Multi-Country Ecological Analysis of Zero-Dose DTP Prevalence and DTP3 Immunization Coverage.

This study explores the association between childhood immunization and gender inequality at the national level. Data for the study include annual country-level estimates of immunization among children aged 12-23 months, indicators of gender inequality, and associated factors for up to 165 countries from 2010-2019. The study examined the association between gender inequality, as measured by the gender development index and the gender inequality index, and two key outcomes: prevalence of children who received no doses of the DTP vaccine (zero-dose children) and children who received the third dose of the DTP vaccine (DTP3 coverage). Unadjusted and adjusted fractional logit regression models were used to identify the association between immunization and gender inequality. Gender inequality, as measured by the Gender Development Index, was positively and significantly associated with the proportion of zero-dose children (high inequality AOR = 1.61, 95% CI: 1.13-2.30). Consistently, full DTP3 immunization was negatively and significantly associated with gender inequality (high inequality AOR = 0.63, 95% CI: 0.46-0.86). These associations were robust to the use of an alternative gender inequality measure (the Gender Inequality Index) and were consistent across a range of model specifications controlling for demographic, economic, education, and health-related factors. Gender inequality at the national level is predictive of childhood immunization coverage, highlighting that addressing gender barriers is imperative to achieve universal coverage in immunization and to ensure that no child is left behind in routine vaccination.

Predicting HPV vaccination among Tdap vaccinated adolescents in Georgia at the county level☆.

PURPOSE: Vaccinations are reported at the state level, but services are delivered at the county level through health departments (HD). This research contributes statistical models to predict county level HPV vaccination. METHODS: Using a cross sectional study design, secondary data were analyzed for the years 2016-2018 for all counties of GA. Study population was male and female adolescents aged 13-17 who received the tetanus, diphtheria and pertussis (Tdap) vaccine. The number of administered HPV vaccine doses and HPV vaccination coverage rate were modeled using indicators of HD clinic access, age, sex, race/ethnicity, socioeconomic status, education, median household income, health insurance, and urban/rural residence. RESULTS: By county the number of administered HPV vaccine doses showed a statistically significant positive association with indicators of HD clinic access: public transit and the number of HD private clinics. HPV vaccination coverage showed a statistically significant negative association with White race and rural residency. CONCLUSION: Examining Tdap vaccinated adolescents conservatively predicted HPV vaccination and controlled for multiple confounders such as vaccination ineligibility, vaccine exemption, and vaccine opposition. Within this population, public health professionals and clinicians could use these statistical models to target HPV vaccination efforts among non-Hispanic whites and rural communities at the county level.

Retesting the hypothesis that early Diphtheria-Tetanus-Pertussis vaccination increases female mortality: An observational study within a randomised trial.

BACKGROUND: There are worrying indications that diphtheria-tetanus-pertussis (DTP) vaccine has negative non-specific effects for females. We previously found, in a trial of early-Bacillus Calmette-Guérin (BCG) to low weight (LW) neonates, that receiving early-DTP (before 2 months of age), was associated with increased female mortality compared with no-DTP/delayed-DTP. Within a subsequent LW trial, we aimed to retest this observation. METHODS: Between 2010 and 2014, in Guinea-Bissau, 2,398 infants were randomised 1:1 to early-BCG (intervention) or delayed-BCG (standard practice for LW neonates) and visited at 2, 6 and 12 months of age to assess nutritional and vaccination status. DTP is recommended at 6 weeks of age. We examined the effect of having "early-DTP" versus "no-DTP" at the time of the 2-month visit on all-cause mortality between the 2- and 6-month visits in Cox models stratified by sex and adjusted for BCG-group and 2-month-weight-for-age (z-scores) providing adjusted mortality rate ratios (aMRRs). We analysed to which extent conditions varied between the present and the previous LW trials and how that might have affected the overall result of comparing the early-DTP and the no-DTP groups. RESULTS: At the time of the 2-month visit, 75% (1,795/2,398) had received DTP. Those vaccinated had better anthropometric indices than no-DTP infants at birth and by 2 months of age. Between the 2- and 6-month visits, 29 deaths occurred. The early-DTP/no-DTP aMRR was 1.09 (95% CI: 0.44-2.69); 1.19 (0.45-3.15) for females and 0.77 (0.14-4.19) for males. Compared to the previous study, the present study cohort had 56% (30-72%) lower overall mortality, fewer no-DTP infants, higher BCG vaccination coverage and several more oral polio vaccine campaigns. CONCLUSION: We did not find that early-DTP was associated with increased female mortality as found in a previous study; differences in results may partly be due to a decline in overall mortality and changes in vaccination practices.

Tétanos generalizado en un niño parcialmente inmunizado

Resumen El tétanos continúa siendo un problema de salud pública, y que afecta a todas las edades. La mortalidad aumenta por bajas coberturas de vacunación y escasez de recursos para un tratamiento temprano. Es causado por la toxina de Clostridium tetani (tetanoespasmina) el cual ingresa al organismo a través de heridas contaminadas por cuerpos extraños. La clínica más frecuente del tétanos es del tipo generalizado y se caracteriza por la contracción tónica de músculos esqueléticos, espasmos musculares intensos, dolorosos, e hiperactividad autonómica. El diagnóstico es principalmente clínico. Se presenta el caso clínico de un tétanos generalizado en un niño con vacunación incompleta. Se discute la importancia de la vacunación y el diagnóstico y tratamiento precoz para mejorar el pronóstico de la enfermedad.

Abstract Tetanus continues to be a public health problem, which affects all age groups. Mortality increases when immunization programs have low coverage and there is a lack of resources for early treatment. This disease is caused by the toxin of Clostridium tetani (tetanospasmin) which enters the body via wounds contaminated by foreign bodies. The most common symptoms of tetanus are of the generalized type and are characterized by tonic contraction of skeletal muscles, intense, painful muscle spasms, and autonomic hyperactivity. The diagnosis is clinical and the previous vaccination history becomes important. We report the case of generalized tetanus in a child with incomplete immunizations. Highlight the importance of vaccination and early diagnosis and treatment.

Impact of Recommended Maternal Vaccination Programs on the Clinical Presentation of SARS-CoV-2 Infection: A Prospective Observational Study.

The COVID-19 pandemic has raised questions about the possible cross immunity resulting from common vaccination programs and SARS-CoV-2 infection. Therefore, the Spanish Obstetric Emergency group performed a multicenter prospective study on the vaccination status of Influenza and Tdap (diphtheria, tetanus and pertussis vaccine boost administered in adulthood) in consecutive cases of SARS-CoV-2 infection in a pregnancy cohort, in order to assess its possible association with the clinical presentation and severity of symptoms of SARS-CoV-2 infection, as well as to determine the factors that may affect vaccination adherence. A total of 1150 SARS-CoV-2 positive pregnant women from 78 Spanish hospitals were analyzed: 183 had not received either vaccine, 23 had been vaccinated for Influenza only, 529 for Tdap only and 415 received both vaccines. No association was observed between the vaccination status and the clinical presentation of SARS-CoV-2 infection and/or the severity of symptoms. However, a lower adherence to the administration of both vaccines was observed in the Latin-American subgroup. Based on the results above, we reinforce the importance of maternal vaccination programs in the actual pandemic. Health education campaigns should be specially targeted to groups less likely to participate in these programs, as well as for a future SARS-CoV-2 vaccination campaign.

Effect of educational and financial incentive-based interventions on immunization attitudes, beliefs, intentions and receipt among close contacts of pregnant women.

INTRODUCTION: Cocooning, the vaccination of close contacts of a newborn, is a strategy to limit the risk of pertussis and influenza infection among vulnerable infants. METHODS: Pregnant women in Colorado and Georgia referred close contacts to an app that provided tailored educational videos about vaccines along with a small pharmacy-based financial incentive for vaccine receipt. The primary objective of this study was to determine the feasibility of implementing this app-based cocooning intervention. RESULTS: Two hundred seventy seven contacts were enrolled in this study. Of those who received the educational videos, 96% found them interesting, 100% found them clear to understand, 97% found them helpful, and 99% trusted them. Completion of the videos led to significant increases in influenza vaccine knowledge (p = 0.025), Tdap vaccine knowledge (p < 0.001), and intention to receive these vaccines (p = 0.046). Of the 136 participants who reported receiving influenza vaccine, 41 (30%) reported receiving it at a pharmacy, and of the 66 who reported receiving Tdap vaccine, 15 (23%) reported receiving it at a pharmacy. Of all participants, 80% reported being comfortable receiving vaccines at a pharmacy instead of a doctor's office. The provision of small pharmacy-based financial incentives combined with individually-tailored educational videos about vaccines led to 6.97 (95%CI: 2.25-21.64) times higher odds of self-reported receipt of influenza vaccine than providing small pharmacy-based financial incentives without these videos. No significant difference was found for Tdap vaccine. CONCLUSIONS: Tailored vaccine education can positively impact vaccine knowledge and intentions among adults. An app-based referral program providing education and financial incentives for cocooning vaccination at pharmacies is feasible.

Out-of-Sequence Vaccinations With Measles Vaccine and Diphtheria-Tetanus-Pertussis Vaccine: A Reanalysis of Demographic Surveillance Data From Rural Bangladesh.

BACKGROUND: Due to delays in vaccinations, diphtheria-tetanus-whole-cell-pertussis (DTP) is often given with or after measles vaccine (MV)-out of sequence. We reanalyzed data from Matlab, Bangladesh, to examine how administration of MV and DTP out-of-sequence was associated with child survival. METHODS: In sum, 36 650 children born between 1986 and 1999 were followed with registration of vaccinations and survival. Controlling for background factors using Cox proportional hazards models, survival was analyzed between 9 and 24 months of age. We measured the mortality rate ratio (MRR) to compare vaccination groups. Oral polio vaccine (OPV) campaigns, which started in 1995, reduced the mortality rate and reduced the difference between vaccination groups. In the main analysis, we therefore censored for OPV campaigns; there were 151 nonaccident deaths before the OPV campaigns. RESULTS: Compared with MV administered alone (MV-only), DTP administered with or after MV had MRR 2.20 (1.31-3.70), and DTP-only had MRR 1.78 (1.01-3.11). Compared with MV-only, DTP administered with MV had a female-male MRR 0.56 (0.13-2.38), significantly different to DTP administered after MV, which had MRR 14.83 (1.88-117.1), test of interaction P = .011. Compared with having DTP (no MV) as most recent vaccination, MV-only had a nonaccident MRR of 0.56 (0.32-0.99). CONCLUSION: The negative effects of non-live DTP with or after live MV are not explained merely by selection bias. These observations support a live-vaccine-last policy where DTP should not be given with or after MV.

Reduced Mortality After Oral Polio Vaccination and Increased Mortality After Diphtheria-tetanus-pertussis Vaccination in Children in a Low-income Setting.

PURPOSE: The diphtheria-tetanus-pertussis vaccine (DTP) and oral polio vaccine (OPV) were introduced in children 3 of 5 months of age in 1981-1983 in Bandim, in the capital of Guinea-Bissau. Because DTP has been linked to deleterious nonspecific effects (NSEs) and OPV to beneficial NSEs, we followed up this cohort to 3 years of age and examined the effects of DTP with OPV on all-cause mortality and the interactions of DTP and OPV with the measles vaccine (MV). METHODS: DTP and OPV were offered at 3 monthly community weighing sessions. Vaccination groups were defined by the last vaccine received. We compared overall mortality for different groups in Cox proportional hazards regression models, reporting hazards ratios (HRs) with 95% CIs. FINDINGS: The study cohort included 1491 children born in Bandim from December 1980 to December 1983. From 3 to 35 months of age, with censoring for MV, children vaccinated with DTP and/or OPV had higher mortality than both unvaccinated children (HR = l.66; 95% CI, 1.03-2.69) and OPV-only vaccinated children (HR = 2.81; 95% CI, 1.02-7.69); DTP-only vaccinated children had higher mortality than OPV-only vaccinated children (HR = 3.38; 95% CI, 1.15--9.93). In the age group of 3-8 months, before MV is administered, DTP-only vaccination was associated with a higher mortality than DTP with OPV (HR = 3.38; 95% CI, 1.59-7.20). Between 9 and 35 months of age, when MV is given, DTP-vaccinated and MV-unvaccinated children had higher mortality (HR = 2.76; 95% CI, 1.36-5.59) than children who had received MV after DTP, and among children who received DTP with MV or after MV, DTP-only vaccination was associated with a higher mortality than DTP with OPV (HR = 6.25; 95% CI, 2.55-15.37). IMPLICATIONS: Because the 2 vaccines had differential effects and the healthiest children were vaccinated first, selection biases are unlikely to explain the estimated impact on child survival. OPV had beneficial NSEs, and administration of OPV with DTP may have reduced the negative effects of DTP.

Infant, maternal and demographic predictors of delayed vaccination: A population-based cohort study.

BACKGROUND: Receiving vaccines at or close to their due date (vaccination timeliness) is a now key measure of program performance. However, studies comprehensively examining predictors of delayed infant vaccination are lacking. We aimed to identify predictors of short and longer-term delays in diphtheria-tetanus-pertussis (DTP) vaccination by dose number and ethnicity. METHODS: Perinatal, notification, death and immunisation databases were linked for 1.3 million births in 2000-11 from two Australian states (Western Australia and New South Wales), with follow-up data until 2013. Ordinal logistic regression was used to estimate adjusted relative risks (RR) by degree of delay. Separate models were constructed for each vaccine dose and for Aboriginal and non-Aboriginal children. RESULTS: Each dose-specific cohort included at least 49,000 Aboriginal and 1.1 million non-Aboriginal children. Delayed receipt was more common among Aboriginal than non-Aboriginal children (eg for the first dose of DTP [DTP1] 19.4 v 8.1%). Risk factors for delayed vaccination were strongest for DTP1, and delayed receipt of DTP1 was a key driver of subsequent delays; every week DTP1 was delayed was associated with a 1.6 to 2-fold increased risk of delayed DTP2 receipt. For DTP1, ≥3 previous pregnancies (the only factor more strongly associated with longer than shorter delays; RR ≥5 compared to no previous pregnancies), and children born to mothers <20 years of age (RR ≥2 compared to ≥35 years) were at highest risk of delay. Other independent predictors were prematurity, maternal smoking during pregnancy, and being born in Western Australia (if Aboriginal) or another country in the Oceania region. CONCLUSION: The sub-populations at risk for delayed vaccination we have identified are likely generalisable to other high-income settings. Measures to improve their dose 1 timeliness, particularly for children with older siblings, are likely to have significant flow-on benefits for timeliness of later doses.

Shaping markets to benefit global health - A 15-year history and lessons learned from the pentavalent vaccine market.

Market shaping for health products used in lower-income countries strives to benefit public health. As a funder of vaccines, Gavi, The Vaccine Alliance (Gavi) has goals for its market shaping efforts, achieved through a strategy developed and implemented by the Gavi Secretariat, UNICEF, the World Health Organization (WHO) and the Bill & Melinda Gates Foundation (BMGF). A case-study of Gavi's fifteen-year engagement with a vaccine against diphtheria, tetanus, pertussis, hepatitis B and haemophilus influenzae type b (pentavalent) provides evidence of the benefits and potential risks of trying to influence markets. During 2001-18, Gavi disbursed US$3.5 billion to support use of 50 million pentavalent doses annually before 2005, increasing to ∼300 million doses annually by 2016. During this time, eight manufacturers invested in vaccine development and manufacturing and the first two manufacturers have subsequently ceased production. Following its strategy, Gavi implemented coordinated market interventions including technical assistance to manufacturers, improving market information transparency, risk-sharing agreements and innovative procurement aiming to stimulate and capitalize on a competitive market. In 2018 supply allows ∼80 million children per year to be immunised, a sixteen-fold increase from 2005, with vaccine-related costs per child for donors and countries of one-quarter the 2005 level. Lessons learned include the importance of frameworks and strategies; the need to adjust interventions with changing conditions; the important role of manufacturers; and the potentially powerful effects of interconnected markets. This case study is limited by its focus on a single health product in a specific market, however the lessons can inform other market shaping efforts when taken in context. While countries and children have improved vaccine access, risks of financial sustainability and continued manufacturer investment in Gavi vaccine markets are being monitored. Gavi should continue implementing a market shaping strategy, adjust with market conditions and expect and measure unintended consequences.

Lessons Learned from the Testing of Neonatal Vitamin A Supplementation.

A total of 12 trials have tested the effect of neonatal vitamin A supplementation (NVAS) on mortality. Overall, NVAS had no effect on mortality, but results were heterogeneous. Two competing hypotheses have been put forward to explain the divergent effects: A) NVAS works by preventing vitamin A deficiency (VAD) and not all countries have VAD; B) NVAS interacts negatively with subsequent diphtheria-tetanus-pertussis (DTP) vaccine, increasing mortality in females; in countries with low DTP coverage NVAS may have a beneficial effect. Only hypothesis A was tested in a recent meta-analysis; there is no strong empirical support for hypothesis A and it would not explain observed negative effects in some settings. Hypothesis B accounts for most observations. However, so far it has only been tested properly in a few trials. If hypothesis B is correct, it has major consequences for the understanding of the effects of vitamin A, and for the VAS policy in older children. As a WHO priority, the DTP coverage is bound to increase, and therefore hypothesis B urgently needs to be tested.

A systematic review of adult tetanus-diphtheria-acellular (Tdap) coverage among healthcare workers.

During the last decades pertussis incidence raised globally. Several vaccination strategies targeting adults to reduce pertussis among young infants have been proposed, including vaccination of healthcare workers (HCWs). The aim of this study was to analyse, by performing a systematic review of literature, published papers that evaluated Tdap coverage among HCWs, variables associated with vaccine uptake and efforts implemented to raise vaccination rates. We searched the MedLine, Embase, SCOPUS, LILACS, Web of Science and Cochrane for full-text studies that evaluated Tdap coverage in HCW. Two independent reviewers screened the articles and extracted the data.Twenty-eight studies published from 2009 to 2018 were reviewed. Most studies were conducted in the USA. Initial Tdap coverage varied from 6.1% to 63.9%. USA and France are the only two countries with studies evaluating Tdap coverage within HCWs using national data. In the USA, Tdap coverage in HCWs raised from 6.1% to 45.1% from 2007 to 2015. In the analysis of French national data, a Tdap coverage of 63.9% was observed. Five studies used interventions to raise Tdap coverage in HCWs. Two intervention studies implemented mandatory vaccination and three used educational strategies. All of them achieved coverages over 86%. Only eleven studies analysed the association of Tdap vaccination with variables of interest. Previous immunization with other vaccines recommended for HCWs (like influenza, hepatitis B and MMR) was positively associated with Tdap uptake in four studies. In conclusion, overall Tdap coverage among HCWs is low, but seems to increase over the years after the vaccine introduction and with implementation of interventions to increase coverage.

Evidence of Increase in Mortality After the Introduction of Diphtheria-Tetanus-Pertussis Vaccine to Children Aged 6-35 Months in Guinea-Bissau: A Time for Reflection?

BACKGROUND: Whole-cell diphtheria-tetanus-pertussis (DTP) and oral polio vaccine (OPV) were introduced to children in Guinea-Bissau in 1981. We previously reported that DTP in the target age group from 3 to 5 months of age was associated with higher overall mortality. DTP and OPV were also given to older children and in this study we tested the effect on mortality in children aged 6-35 months. METHODS: In the 1980s, the suburb Bandim in the capital of Guinea-Bissau was followed with demographic surveillance and tri-monthly weighing sessions for children under 3 years of age. From June 1981, routine vaccinations were offered at the weighing sessions. We calculated mortality hazard ratio (HR) for DTP-vaccinated and DTP-unvaccinated children aged 6-35 months using Cox proportional hazard models. Including this study, the introduction of DTP vaccine and child mortality has been studied in three studies; we made a meta-estimate of these studies. RESULTS: At the first weighing session after the introduction of vaccines, 6-35-month-old children who received DTP vaccination had better weight-for-age z-scores (WAZ) than children who did not receive DTP; one unit increase in WAZ was associated with an odds ratio of 1.32 (95% CI = 1.13-1.55) for receiving DTP vaccination. Though lower mortality compared with not being DTP-vaccinated was, therefore, expected, DTP vaccination was associated with a non-significant trend in the opposite direction, the HR being 2.22 (0.82-6.04) adjusted for WAZ. In a sensitivity analysis, including all children weighed at least once before the vaccination program started, DTP (±OPV) as the most recent vaccination compared with live vaccines or no vaccine was associated with a HR of 1.89 (1.00-3.55). In the three studies of the introduction of DTP in rural and urban Guinea-Bissau, DTP-vaccinated children had an HR of 2.14 (1.42-3.23) compared to DTP-unvaccinated children; this effect was separately significant for girls [HR = 2.60 (1.57-4.32)], but not for boys [HR = 1.71 (0.99-2.93)] (test for interaction p = 0.27). CONCLUSION: Although having better nutritional status and being protected against three infections, 6-35 months old DTP-vaccinated children tended to have higher mortality than DTP-unvaccinated children. All studies of the introduction of DTP have found increased overall mortality.

IgG antibody prevalence suggests high immunization needs in newcomers to Luxembourg, 2012.

Vaccine coverage of the general population in Luxembourg is high, but refugees or asylum seekers may be incompletely vaccinated and susceptible to vaccine-preventable diseases. In order to assess protection rates, serum and oral fluid samples were collected from 406 newcomers aged between 13 and 70 years arriving between May and September 2012. Sera were screened for IgG antibodies against measles, rubella, mumps, hepatitis B, tetanus, diphtheria and pertussis. Oral fluid samples were screened for antibodies against measles, mumps and rubella virus to investigate their suitability for antibody prevalence studies. More than 90% of the participants had IgG antibodies against rubella, 73% against measles and 56% against mumps. Less than 19% had anti-HBs antibodies. Nearly 84% of the participants had an adequate protection against tetanus, 73% against diphtheria and 40% had pertussis antibodies. 93%, 95% and 78% of the measles, rubella and mumps test results obtained with serum and oral fluid were concordant. The majority of the participants lacked antibodies against at least one of the measles/mumps/rubella (58%) and diphtheria/tetanus/pertussis (72%) vaccine components and against hepatitis B virus (82%) and might thus profit from vaccination. Oral fluid is a suitable alternative and non-invasive specimen for measles/rubella antibody prevalence studies.

Sex-differential effects of diphtheria-tetanus-pertussis vaccine for the outcome of paediatric admissions? A hospital based observational study from Guinea-Bissau.

BACKGROUND: In spite of protection against the targeted infections, a large volume of observational data indicates that diphtheria-tetanus-pertussis (DTP) vaccine may have a negative impact on overall childhood mortality in low-income countries, especially in girls. METHODS: In an observational study using data from Bandim Health Project's continuous registration of all admissions to the paediatric ward at the National Hospital Simão Mendes in Bissau, we investigated whether DTP was associated with higher female than male in-hospital mortality (female/male case fatality ratio (F/M CFR)) and whether the CFR comparing DTP-vaccinated and DTP-unvaccinated children differed by sex. We included children aged 6 weeks to 8 months (274 days) admitted to the paediatric ward with a vaccination card seen during admission. RESULTS: From May 2001 to January 2008, 4230 children aged 6 weeks to 8 months were admitted and 3450 (82%; 1997 boys, 1453 girls) presented a vaccination card. The proportion presenting a vaccination card and DTP coverage did not differ by sex. During admission, 16% (200/1250) of the girls and 13% (220/1694) of the boys who had received DTP died. The F/M CFR among the 2944 DTP-vaccinated children was 1.23 (1.03-1.46); while it was 0.95 (0.66-1.38) among the 506 children who had not received DTP. DTP-vaccinated children were older and had better socioeconomic status. Adjusted for age, BCG-vaccination, residence, and maternal education the CFR comparing DTP-vaccinated boys with DTP-unvaccinated boys was 0.84 (0.63-1.11), while the CFR comparing DTP-vaccinated girls with DTP-unvaccinated girls was 1.28 (0.90-1.83) (p = .07 for same effect in boys and girls). CONCLUSION: Among DTP-vaccinated children, female in-hospital mortality was higher than male in-hospital mortality and DTP-vaccination tended to be associated with higher mortality in girls. The data are consistent with DTP having negative effects on mortality for girls. Further studies are necessary to design the optimal vaccination programme for both sexes.

Long-term sex-differential effects of neonatal vitamin A supplementation on in vitro cytokine responses.

High-dose vitamin A supplementation (VAS) may affect mortality to infectious diseases in a sex-differential manner. Here, we analysed the long-term immunological effects of neonatal vitamin A supplementation (NVAS) in 247 children, who had been randomly allocated to 50 000 or 25 000 IU vitamin A (15mg and 7·5mg retinol equivalents, respectively) or placebo at birth. At 4-6 months of age, we assessed bacille Calmette-Guérin (BCG) scarification, and we analysed in vitro responses of TNF-α, IL-5, IL-10, IL-13 and IFN-γ in whole blood stimulations to phytohaemagglutinin (PHA), purified protein derivative (PPD), tetanus toxoid and lipopolysaccharide. There were no differences between the two doses of NVAS, and thus they were analysed combined as NVAS (any dose) v. placebo. All analyses were performed unstratified and by sex. NVAS increased the chance of having a scar after BCG vaccination in females (NVAS v. placebo: 96 v. 71 %, proportion ratio: 1·24; 95 % CI 1·09, 1·42), but not in males (P for interaction=0·012). NVAS was associated with significant sex-differential effects on the pro- to anti-inflammatory cytokine ratios (TNF-α:IL-10) to PPD, tetanus toxoid and medium alone, which were increased in females but decreased in males. In addition, IL-17 responses tended to be increased in NVAS v. placebo recipients in males but not in females, significantly so for the PHA stimulation. The study corroborates sex-differential effects of VAS on the immune system, emphasising the importance of analysing VAS effects by sex.