In the current vaccine paradigm, it is usually assumed that vaccines only protect against the target infection, that effective vaccines reduce mortality corresponding to the target infection's share of mortality, and that vaccine effects are similar for boys and girls. However, epidemiological vaccine research has generated observations, which contradict these assumptions and suggest that vaccines have important non-specific effects (NSEs).We list eleven contradictory observations, including the observations that several live vaccines reduce mortality far more than can be explained by protection against the target infections, and that several non-live vaccines are associated with increased female mortality.We suggest six principles, which may explain these observations: 1) live vaccines enhance resistance towards unrelated infections; 2) non-live vaccines enhance susceptibility towards unrelated infections for females; 3) the most recent vaccination has the strongest NSEs; 4) combinations of live and non-live vaccines given together have variable NSEs; 5) vaccinating with live vaccines in the presence of existing immunity enhances beneficial NSEs; and 6) vaccines may interact with other interventions affecting the immune system.These principles may characterise a new paradigm: they may help resolve the contradictory observations, they raise new questions which could not have been seen from the existing paradigm, and they correctly predict new observations, which cannot be explained within the current paradigm. Pursuing these principles could lead to an optimised understanding and use of vaccines.

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Background: When vaccinations with vaccinia against smallpox and Bacillus Calmette-Guérin (BCG) against tuberculosis were phased out in some high-income countries around 1980, the impact on overall mortality was not examined. Recent studies from low-income countries have suggested that these vaccines are associated with mortality reductions, not explained by specific disease protection. We examined whether vaccinia and BCG administered in childhood were associated with long-term mortality reductions in a high-income population. Methods: In this case-cohort study, we followed 47 622 schoolchildren from Copenhagen, Denmark, born 1965 to 1976, from their first health examination to 2010. This cohort experienced the phase-out of vaccinia and BCG vaccination programmes. Results: A sub-cohort of 5 316 individuals (699 excluded) was followed for 164 450 person-years (0.2% were lost to follow-up), and 401 deaths due to natural causes (841 deaths in total) occurred in the full cohort. Compared with individuals who had not received vaccinia or BCG, those who had received both vaccinia and BCG had an adjusted hazard ratio (aHR) of 0.54 [95% confidence interval (CI): 0.36–0.81] for mortality due to natural causes of death; those who only received BCG had an aHR of 0.58 (95% CI: 0.39–0.85). Vaccinia and BCG were not associated with any protection against deaths by accidents, suicide or murder, the combined aHR being 0.94 (95% CI: 0.62–1.42). Conclusions: Vaccinia and BCG vaccinations were associated with better long-term survival, which was not explained by specific protection. Vaccines with beneficial non-specific effects may reduce overall mortality even after the target diseases are eradicated.

Abstract.Cholera outbreaks in Africa have been attributed to both droughts and floods, but whether the risk of a cholera outbreak is elevated during droughts is unknown. We estimated the risk of cholera outbreaks during droughts and floods compared with drought- and flood-free periods in 40 sub-Saharan African countries during 1990–2010 based on data from Emergency Events Database: the Office of Foreign Disaster Assistance /Centre for Research on the Epidemiology of Disasters International Disaster Database (www.emdat.be). A cholera outbreak was registered in one of every three droughts and one of every 15 floods. We observed an increased incidence rate of cholera outbreaks during drought periods (incidence rate ratio [IRR] = 4.3, 95% confidence interval [CI] = 2.9–7.2) and during flood periods (IRR = 144, 95% CI = 101–208) when compared with drought/flood-free periods. Floods are more strongly associated with cholera outbreaks, yet the prevalence of cholera outbreaks is higher during droughts because of droughts’ long durations. The results suggest that droughts in addition to floods call for increased cholera preparedness.

Background Children who are exposed to adversities might be more susceptible to disease development during childhood and in later life due to impaired physiological and mental development. To explore this hypothesis, we assessed hospitalisation patterns through childhood and into adult life among those exposed to different trajectories of adversities during childhood.Methods For this population-based cohort study, we used annually updated data from Danish nationwide registers covering more than half a million children (aged 0-15 years) born between 1994 and 2001. Children who were alive and resident in Denmark on their 16th birthday were included in the analysis. Cluster analysis was used to divide children into five distinct trajectories according to their experience of childhood adversities, including poverty and material deprivation, loss or threat of loss within the family, and aspects of family dynamics. To describe comprehensively the disease patterns experienced by these groups of children, we assessed the associations of each adversity trajectory with hospital admission patterns according to the entire spectrum of disease diagnoses in the International Classification of Diseases 10th edition, from birth to 24 years of age, using survival models.

BackgroundThe live smallpox and Bacillus Calmette-Guérin (BCG) vaccinations have been associated with better adult survival in both Guinea-Bissau and Denmark. In Guinea-Bissau, human immunodeficiency virus (HIV)-1 became an important cause of death after smallpox vaccination was phased out globally in 1980. We hypothesised that smallpox and BCG vaccinations were associated with a lower prevalence of HIV-1 infection, and we tested this hypothesis in both Guinea-Bissau and Denmark.MethodsWe conducted 2 studies: (1) a cross-sectional study of HIV infection and vaccination scars in Guinea-Bissau including 1751 individuals and (2) a case-base study with a background population of 46239 individuals in Denmark. In Guinea-Bissau, HIV-1 transmission was almost exclusively sexually transmitted. In Denmark, we excluded intravenous drug users. Data were analyzed using logistic regression.ResultsBacillus Calmette-Guérin and/or smallpox vaccination compared with neither of these vaccines was associated with an adjusted odds ratio (aOR) for HIV-1 of 0.62 (95% confidence interval [CI], 0.36–1.07) in Guinea-Bissau and 0.70 (95% CI, 0.43–1.15) in Denmark. We combined the results from both settings in a meta-analysis (aOR = 0.66; 95% CI, 0.46–0.96). Data from Guinea-Bissau indicated a stronger effect of multiple smallpox vaccination scars (aOR = 0.27; 95% CI, 0.10–0.75) as follows: women, aOR = 0.18 (95% CI, 0.05–0.64); men, aOR = 0.52 (95% CI, 0.12–2.33); sex-differential effect, P = .29.ConclusionsThe studies from Guinea-Bissau and Denmark, 2 very different settings, both suggest that the BCG and smallpox vaccines could be associated with a decreased risk of sexually transmitted HIV-1. It might be informative to pursue this observation and explore possible protective mechanisms as part of the search for an HIV-1 vaccine.

PurposeThe DANish LIFE course (DANLIFE) cohort is a prospective register-based study set up to investigate the complex life course mechanisms linking childhood adversities to health and well-being in childhood, adolescence and young adulthood including cumulative and synergistic actions and potentially sensitive periods in relation to health outcomes.ParticipantsAll children born in Denmark in 1980 or thereafter have successively been included in the cohort totalling more than 2.2 million children. To date, the study population has been followed annually in the nationwide Danish registers for an average of 16.8 years with full data coverage in the entire follow-up period. The information is currently updated until 2015.Findings to dateDANLIFE provides information on a wide range of family-related childhood adversities (eg, parental separation, death of a parent or sibling, economic disadvantage) with important psychosocial implications for health and well-being in childhood, adolescence and young adulthood. Measurement of covariates indicating demographic (eg, age, sex), social (eg, parental education) and health-related factors (eg, birth weight) has also been included from the nationwide registers. In this cohort profile, we provide an overview of the childhood adversities and covariates included in DANLIFE. We also demonstrate that there is a clear social gradient in the exposure to childhood adversities confirming clustering of adverse experiences within individuals.Future plansDANLIFE provides a valuable platform for research into early life adversity and opens unique possibilities for testing new research ideas on how childhood adversities affect health across the life course.

Background The third dose of diphtheria-tetanus-pertussis (DTP3) is used to monitor immunization programs. DTP has been associated with higher female mortality. Methods We updated previous literature searches for DTP-studies of mortality by sex. We examined the female/male (F/M) mortality rate ratio (MRR) with increasing number of doses of DTP and for subsequent doses of measles vaccine (MV) after DTP and of DTP after MV. Results Eight studies had information on both DTP1 and DTP3. The F/M MRR was 1.17 (0.88-1.57) after DTP1 and increased to 1.66 (1.32-2.09) after DTP3. Following receipt of MV the F/M MRR declined to 0.63 (0.42-0.96). In 11 studies the F/M MRR increased to 1.73 (1.33-2.27) when DTP-containing vaccine was administered after MV. Conclusions The F/M MRR increased with increasing doses of DTP. After MV, females had lower mortality than males. If DTP was provided after MV, mortality increased again for females relative to males. No bias can explain these changes in the F/M MRR. DTP does not improve male survival substantially in situations with herd immunity to pertussis and the higher F/M MRR after DTP may therefore reflects an absolute increase in female mortality.