Reaffirming a Positive Correlation Between Number of Vaccine Doses and Infant Mortality Rates: A Response to Critics (original) (raw)

Infant mortality rates regressed against number of vaccine doses routinely given: Is there a biochemical or synergistic toxicity

The infant mortality rate (IMR) is one of the most important indicators of the socioeconomic well-being and public health conditions of a country. The US childhood immunization schedule specifies 26 vaccine doses for infants aged less than 1 year—the most in the world—yet 33 nations have lower IMRs. Using linear regression, the immunization schedules of these 34 nations were examined and a correlation coefficient of r ¼ 0.70 (p < 0.0001) was found between IMRs and the number of vaccine doses routinely given to infants. Nations were also grouped into five different vaccine dose ranges: 12–14, 15–17, 18–20, 21–23, and 24–26. The mean IMRs of all nations within each group were then calculated. Linear regression analysis of unweighted mean IMRs showed a high statistically significant correlation between increasing number of vaccine doses and increasing infant mortality rates, with r ¼ 0.992 (p ¼ 0.0009). Using the Tukey-Kramer test, statistically significant differences in mean IMRs were found between nations giving 12–14 vaccine doses and those giving 21–23, and 24–26 doses. A closer inspection of correlations between vaccine doses, biochemical or synergistic toxicity, and IMRs is essential.

Neonatal, Infant, and Under Age Five Vaccine Doses Routinely Given in Developed Nations and Their Association With Mortality Rates

Cureus, 2023

In 2011, using 2009 data, we published a study demonstrating that among the most highly developed nations, those requiring the most vaccine doses for their infants tended to have the least favorable infant mortality rates (r = 0.70, p < .0001). Twelve years later, we replicated our original study using 2019 data. Linear regression analysis corroborated the positive trend reported in our initial paper (r = 0.45; p < .002). Herein, we broaden our analyses to consider the effect of vaccines on neonatal and under age five mortality rates. Objective We performed several investigations to explore potential relationships between the number of early childhood vaccine doses required by nations and their neonatal, infant, and under age five mortality rates. Methods In this ecological study, we conducted linear regression analyses of neonatal, infant, and under age five vaccine doses required by nations and their neonatal, infant, and under age five mortality rates. All analyses were based on 2019 and 2021 data. We also stratified nations by the number of neonatal vaccine doses required and conducted a one-way ANOVA test and a post hoc Tukey-Kramer test to determine if there were statistically significant differences in the group mean neonatal, infant, and under age five mortality rates of nations that administered zero, one, or two neonatal vaccine doses. Results Linear regression analyses of neonatal vaccine doses required by nations in our 2021 dataset yielded statistically significant positive correlations to rates of neonatal mortality (r = 0.34, p = .017), infant mortality (r = 0.46, p = .0008), and under age five mortality (r = 0.48, p = .0004). Similar results were reported using 2019 data. Utilizing 2021 data, a post hoc Tukey-Kramer test indicated a statistically significant pairwise difference between the mean neonatal mortality rates, mean infant mortality rates, and mean under age five mortality rates of nations requiring zero vs. two neonatal vaccine doses. There was a statistically significant difference of 1.28 deaths per 1000 live births (p < .002) between the mean infant mortality rates among nations that did not give their neonates any vaccine doses and those that required two vaccine doses. Using 2019 and 2021 data, 17 of 18 analyses (12 bivariate linear regressions and six ANOVA and Tukey-Kramer tests) achieved statistical significance and corroborated the findings reported in our original study of a positive association between the number of vaccine doses required by developed nations and their infant mortality rates. Conclusions There are statistically significant positive correlations between mortality rates of developed nations and the number of early childhood vaccine doses that are routinely given. Further investigations of the hypotheses generated by this study are recommended to confirm that current vaccination schedules are achieving their intended objectives.

Methodological challenges in measuring vaccine effectiveness using population cohorts in low resource settings

Vaccine, 2015

Post-licensure real world evaluation of vaccine implementation is important for establishing evidence of vaccine effectiveness (VE) and programme impact, including indirect effects. Large cohort studies offer an important epidemiological approach for evaluating VE, but have inherent methodological challenges. Since March 2012, we have conducted an open prospective cohort study in two sites in rural Malawi to evaluate the post-introduction effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) against all-cause post-neonatal infant mortality and monovalent rotavirus vaccine (RV1) against diarrhoea-related post-neonatal infant mortality. Our study sites cover a population of 500,000, with a baseline post-neonatal infant mortality of 25 per 1000 live births. We conducted a methodological review of cohort studies for vaccine effectiveness in a developing country setting, applied to our study context. Based on published literature, we outline key considerations when defining the denominator (study population), exposure (vaccination status) and outcome ascertainment (mortality and cause of death) of such studies. We assess various definitions in these three domains, in terms of their impact on power, effect size and potential biases and their direction, using our cohort study for illustration. Based on this iterative process, we discuss the pros and cons of our final perprotocol analysis plan. Since no single set of definitions or analytical approach accounts for all possible biases, we propose sensitivity analyses to interrogate our assumptions and methodological decisions. In the poorest regions of the world where routine vital birth and death surveillance are frequently unavailable and the burden of disease and death is greatest We conclude that provided the balance between definitions and their overall assumed impact on estimated VE are acknowledged, such large scale real-world cohort studies can provide crucial information to policymakers by providing robust and compelling evidence of total benefits of newly introduced vaccines on reducing child mortality.

Correlates of Complete Childhood Vaccination in East African Countries

PLoS ONE, 2014

Background: Despite the benefits of childhood vaccinations, vaccination rates in low-income countries (LICs) vary widely. Increasing coverage of vaccines to 90% in the poorest countries over the next 10 years has been estimated to prevent 426 million cases of illness and avert nearly 6.4 million childhood deaths worldwide. Consequently, we sought to provide a comprehensive examination of contemporary vaccination patterns in East Africa and to identify common and countryspecific barriers to complete childhood vaccination.

Assessing the characteristics of un- and under-vaccinated children in low- and middle-income countries: A multi-level cross-sectional study

PLOS global public health, 2022

Achieving equity in vaccination coverage has been a critical priority within the global health community. Despite increased efforts recently, certain populations still have a high proportion of un-and under-vaccinated children in many low-and middle-income countries (LMICs). These populations are often assumed to reside in remote-rural areas, urban slums and conflict-affected areas. Here, we investigate the effects of these key community-level factors, alongside a wide range of other individual, household and community level factors, on vaccination coverage. Using geospatial datasets, including cross-sectional data from the most recent Demographic and Health Surveys conducted between 2008 and 2018 in nine LMICs, we fitted Bayesian multi-level binary logistic regression models to determine key community-level and other factors significantly associated with non-and under-vaccination. We analyzed the odds of receipt of the first doses of diphtheria-tetanus-pertussis (DTP1) vaccine and measles-containing vaccine (MCV1), and receipt of all three recommended DTP doses (DTP3) independently, in children aged 12-23 months. In bivariate analyses, we found that remoteness increased the odds of non-and under-vaccination in nearly all the study countries. We also found evidence that living in conflict and urban slum areas reduced the odds of vaccination, but not in most cases as expected. However, the odds of vaccination were more likely to be lower in urban slums than formal urban areas. Our multivariate analyses revealed that the key community variables-remoteness, conflict and urban slumwere sometimes associated with non-and under-vaccination, but they were not frequently predictors of these outcomes after controlling for other factors. Individual and household factors such as maternal utilization of health services, maternal education and ethnicity, were more common predictors of vaccination. Reaching the Immunisation Agenda 2030 target of reducing the number of zero-dose children by 50% by 2030 will require country tailored PLOS GLOBAL PUBLIC HEALTH

Randomized Trials to Study the Nonspecific Effects of Vaccines in Children in Low-Income Countries

The Pediatric Infectious Disease Journal, 2010

Background: Studies from Africa have suggested marked non-specific effects (NSEs) of routine vaccinations with effects on child survival. There have been few studies from Asia. We re-analyzed a study from Maharashtra, India, which had collected information on vaccinations during infancy and survival until 5 years of age. Design: 4138 children born between 1987 and 1989 were visited at home every three months to collect information on nutritional status and vaccinations. Since nutritional status was a determinant of time to vaccinations, we adjusted for nutritional status in the analyzes of the association between vaccinations and mortality. Setting: 45 contiguous villages in Shirur Administrative Block in Pune District. Main outcome measures: Mortality rate ratios (MRR) for different vaccination status groups. Results: The study area has male preferential treatment, but the female-male mortality ratio varied between age groups with different pre-dominant vaccines; it was high in the age group in which diphtheria-tetanus-pertussis (DTP) vaccine predominates and low in the age group in which measles vaccine (MV) is given. Children who followed the WHO recommended schedule of first BCG and then DTP vaccination were vaccinated earlier than other children (p < 0.01). Two-thirds of the children had received BCG and DTP out-of-sequence, i.e. BCG and DTP simultaneously or BCG after DTP. Children who received BCG and DTP simultaneously or BCG as most recent vaccination had significantly lower mortality than children having DTP as the most recent vaccination, the mortality rate ratio being 0.15 (0.03-0.70). Conclusions: BCG out-of-sequence may be associated with lower mortality than DTP as the most recent vaccination. Given the public health implications, this possibility should be tested in randomized trials. Excess female mortality may also be related to vaccination policy.

Systematic review of studies evaluating the broader economic impact of vaccination in low and middle income countries

BMC Public Health, 2012

Background: Most health economic evaluations of childhood vaccination only capture the health and short-term economic benefits. Measuring broader, long-term effects of vaccination on productivity and externalities could provide a more complete picture of the value of vaccines. Method: MEDLINE, EconLit and NHS-EED databases were searched for articles published between January 1990 and July 2011, which captured broader economic benefits of vaccines in low and middle income countries. Studies were included if they captured at least one of the following categories on broader economic impact: outcome-related productivity gains, behaviour-related productivity gains, ecological externalities, equity gains, financial sustainability gains or macroeconomic benefits. Results: Twenty-six relevant studies were found, including observational studies, economic models and contingent valuation studies. Of the identified broader impacts, outcome-related productivity gains and ecological externalities were most commonly accounted for. No studies captured behaviour-related productivity gains or macroeconomic effects. There was some evidence to show that vaccinated children 8-14 years of age benefit from increased cognitive ability. Productivity loss due to morbidity and mortality was generally measured using the human capital approach. When included, herd immunity effects were functions of coverage rates or based on reduction in disease outcomes. External effects of vaccines were observed in terms of equitable health outcomes and contribution towards synergistic and financially sustainable healthcare programs.

The Equity Impact Vaccines May Have On Averting Deaths And Medical Impoverishment In Developing Countries

Health affairs (Project Hope), 2018

With social policies increasingly directed toward enhancing equity through health programs, it is important that methods for estimating the health and economic benefits of these programs by subpopulation be developed, to assess both equity concerns and the programs' total impact. We estimated the differential health impact (measured as the number of deaths averted) and household economic impact (measured as the number of cases of medical impoverishment averted) of ten antigens and their corresponding vaccines across income quintiles for forty-one low- and middle-income countries. Our analysis indicated that benefits across these vaccines would accrue predominantly in the lowest income quintiles. Policy makers should be informed about the large health and economic distributional impact that vaccines could have, and they should view vaccination policies as potentially important channels for improving health equity. Our results provide insight into the distribution of vaccine-preve...