Maternal pertussis immunization and the blunting of routine vaccine effectiveness: a meta-analysis and modeling study.

A key goal of pertussis control is to protect infants too young to be vaccinated, the age group most vulnerable to this highly contagious respiratory infection. In the last decade, maternal immunization has been deployed in many countries, successfully reducing pertussis in this age group. Because of immunological blunting, however, this strategy may erode the effectiveness of primary vaccination at later ages. Here, we systematically reviewed the literature on the relative risk (RR) of pertussis after primary immunization of infants born to vaccinated vs. unvaccinated mothers. The four studies identified had ≤6 years of follow-up and large statistical uncertainty (meta-analysis weighted mean RR: 0.71, 95% CI: 0.38-1.32). To interpret this evidence, we designed a new mathematical model with explicit blunting mechanisms and evaluated maternal immunization's short- and long-term impact on pertussis transmission dynamics. We show that transient dynamics can mask blunting for at least a decade after rolling out maternal immunization. Hence, the current epidemiological evidence may be insufficient to rule out modest reductions in the effectiveness of primary vaccination. Irrespective of this potential collateral cost, we predict that maternal immunization will remain effective at protecting unvaccinated newborns, supporting current public health recommendations.

Grandmother presence improved grandchild survival against childhood infections but not vaccination coverage in historical Finns.

Grandmother presence can improve the number and survival of their grandchildren, but what grandmothers protect against and how they achieve it remains poorly known. Before modern medical care, infections were leading causes of childhood mortality, alleviated from the nineteenth century onwards by vaccinations, among other things. Here, we combine two individual-based datasets on the genealogy, cause-specific mortality and vaccination status of eighteenth- and nineteenth-century Finns to investigate two questions. First, we tested whether there were cause-specific benefits of grandmother presence on grandchild survival from highly lethal infections (smallpox, measles, pulmonary and diarrhoeal infections) and/or accidents. We show that grandmothers decreased all-cause mortality, an effect which was mediated through smallpox, pulmonary and diarrhoeal infections, but not via measles or accidents. Second, since grandmothers have been suggested to increase vaccination coverage, we tested whether the grandmother effect on smallpox survival was mediated through increased or earlier vaccination, but we found no evidence for such effects. Our findings that the beneficial effects of grandmothers are in part driven by increased survival from some (but not all) childhood infections, and are not mediated via vaccination, have implications for public health, societal development and human life-history evolution.

The interactions of SARS-CoV-2 with cocirculating pathogens: Epidemiological implications and current knowledge gaps.

Despite the availability of effective vaccines, the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggests that cocirculation with other pathogens and resulting multiepidemics (of, for example, COVID-19 and influenza) may become increasingly frequent. To better forecast and control the risk of such multiepidemics, it is essential to elucidate the potential interactions of SARS-CoV-2 with other pathogens; these interactions, however, remain poorly defined. Here, we aimed to review the current body of evidence about SARS-CoV-2 interactions. Our review is structured in four parts. To study pathogen interactions in a systematic and comprehensive way, we first developed a general framework to capture their major components: sign (either negative for antagonistic interactions or positive for synergistic interactions), strength (i.e., magnitude of the interaction), symmetry (describing whether the interaction depends on the order of infection of interacting pathogens), duration (describing whether the interaction is short-lived or long-lived), and mechanism (e.g., whether interaction modifies susceptibility to infection, transmissibility of infection, or severity of disease). Second, we reviewed the experimental evidence from animal models about SARS-CoV-2 interactions. Of the 14 studies identified, 11 focused on the outcomes of coinfection with nonattenuated influenza A viruses (IAVs), and 3 with other pathogens. The 11 studies on IAV used different designs and animal models (ferrets, hamsters, and mice) but generally demonstrated that coinfection increased disease severity compared with either monoinfection. By contrast, the effect of coinfection on the viral load of either virus was variable and inconsistent across studies. Third, we reviewed the epidemiological evidence about SARS-CoV-2 interactions in human populations. Although numerous studies were identified, only a few were specifically designed to infer interaction, and many were prone to multiple biases, including confounding. Nevertheless, their results suggested that influenza and pneumococcal conjugate vaccinations were associated with a reduced risk of SARS-CoV-2 infection. Finally, fourth, we formulated simple transmission models of SARS-CoV-2 cocirculation with an epidemic viral pathogen or an endemic bacterial pathogen, showing how they can naturally incorporate the proposed framework. More generally, we argue that such models, when designed with an integrative and multidisciplinary perspective, will be invaluable tools to resolve the substantial uncertainties that remain about SARS-CoV-2 interactions.

From January to June: Birth seasonality across two centuries in a rural Polish community.

Seasonality of births is a worldwide phenomenon, but the mechanisms behind it remain insufficiently explored. Birth seasonality is likely to be driven by seasonal changes in women's fecundity (i.e. ability to conceive), which is strongly influenced by their energetic status. We tested whether birth seasonality is driven by high workload and/or low access to food using 200 years of birth data, from 1782 until 2004, in an agricultural rural Polish community. First, we analysed the time series of births and within-annual variance in births, a proxy for the extent of seasonality. Secondly, we tested the hypothesis that a high agricultural workload and/or low access to food decreases number of births. We found seasonality of births throughout more than 200 years of observation in an agricultural Polish population, with a dominant birth seasonality in January and February which gradually shifted towards June in the late twentieth century. The observed pattern does not support the hypothesis that birth seasonality resulted from women's energetic status. We discuss the possible reasons why our results do not support the tested hypothesis and some implications for our understanding of the birth seasonality.

Glucose tolerance predicts survival in old zebra finches.

The capacity to deal with external and internal challenges is thought to affect fitness, and the age-linked impairment of this capacity defines the ageing process. Using a recently developed intra-peritoneal glucose tolerance test (GTT), we tested for a link between the capacity to regulate glucose levels and survival in zebra finches. We also investigated for the effects of ambient factors, age, sex, and manipulated developmental and adult conditions (i.e. natal brood size and foraging cost, in a full factorial design) on glucose tolerance. Glucose tolerance was quantified using the incremental 'area under the curve' (AUC), with lower values indicating higher tolerance. Glucose tolerance predicted survival probability in old birds, above the median age, with individuals with higher glucose tolerance showing better survival than individuals with low or intermediate glucose tolerance. In young birds there was no association between glucose tolerance and survival. Experimentally induced adverse developmental conditions did not affect glucose tolerance, but low ambient temperature at sampling and hard foraging conditions during adulthood induced a fast return to baseline levels (i.e. high glucose tolerance). These findings can be interpreted as an efficient return to baseline glucose levels when energy requirements are high, with glucose presumably being used for energy metabolism or storage. Glucose tolerance was independent of sex. Our main finding that old birds with higher glucose tolerance had better survival supports the hypothesis that the capacity to efficiently cope with a physiological challenge predicts lifespan, at least in old birds.

Sex-specific body mass ageing trajectories in adult Asian elephants.

In species with marked sexual dimorphism, the classic prediction is that the sex which undergoes stronger intrasexual competition ages earlier or quicker. However, more recently, alternative hypotheses have been put forward, showing that this association can be disrupted. Here, we utilize a unique, longitudinal data set of a semi-captive population of Asian elephants (Elephas maximus), a species with marked male-biased intrasexual competition, with males being larger and having shorter lifespans, and investigate whether males show earlier and/or faster body mass ageing than females. We found evidence of sex-specific body mass ageing trajectories: adult males gained weight up to the age of 48 years old, followed by a decrease in body mass until natural death. In contrast, adult females gained body mass with age until a body mass decline in the last year of life. Our study shows sex-specific ageing patterns, with an earlier onset of body mass declines in males than females, which is consistent with the predictions of the classical theory of ageing.

The Long-Term Success of Mandatory Vaccination Laws After Implementing the First Vaccination Campaign in 19th Century Rural Finland.

In high-income countries, childhood infections are on the rise, a phenomenon attributed in part to persistent hesitancy toward vaccines. To combat vaccine hesitancy, several countries recently made vaccinating children mandatory, but the effect of such vaccination laws on vaccination coverage remains debated, and the long-term consequences are unknown. Here we quantified the consequences of vaccination laws on vaccination coverage, monitoring for a period of 63 years (1837-1899) rural Finland's first vaccination campaign against the highly lethal childhood infection smallpox. We found that annual vaccination campaigns were focused on children up to 1 year old and that their vaccination coverage was low and declined over time until the implementation of the vaccination law, which stopped the declining trend and was associated with an abrupt coverage increase, of 20%, to cover >80% of all children. Our results indicate that vaccination laws can have a long-term beneficial effect of increasing the vaccination coverage and will help public health practitioners to make informed decisions on how to act against vaccine hesitancy and optimize the impact of vaccination programs.

Within-individual repeatability in telomere length: A meta-analysis in nonmammalian vertebrates.

Telomere length is increasingly used as a biomarker of long-term somatic state and future survival prospects. While most studies have overlooked this aspect, biological interpretations based on a given telomere length will benefit from considering the level of within-individual repeatability of telomere length through time. Therefore, we conducted a meta-analysis on 74 longitudinal studies in nonmammalian vertebrates, with the aim to establish the current pattern of within-individual repeatability in telomere length and to identify the methodological (e.g., qPCR/TRF) and biological factors (e.g., age class, phylogeny) that may affect it. While the median within-individual repeatability of telomere length was moderate to high (R = 0.55; 95% CI: 0.05-0.95; N = 82), marked heterogeneity between studies was evident. Measurement method affected the repeatability estimate strongly, with TRF-based studies exhibiting high repeatability (R = 0.80; 95% CI: 0.34-0.96; N = 25), while repeatability of qPCR-based studies was markedly lower and more variable (R = 0.46; 95% CI: 0.04-0.82; N = 57). While phylogeny explained some variance in repeatability, phylogenetic signal was not significant (λ = 0.32; 95% CI: 0.00-0.83). None of the biological factors investigated here significantly explained variation in the repeatability of telomere length, being potentially obscured by methodological differences. Our meta-analysis highlights the high variability in within-individual repeatability estimates between studies and the need to put more effort into separating technical and biological explanations. This is important to better understand to what extent biological factors can affect the repeatability of telomere length and thus the interpretation of telomere length data.

Town population size and structuring into villages and households drive infectious disease risks in pre-healthcare Finland.

Social life is often considered to cost in terms of increased parasite or pathogen risk. However, evidence for this in the wild remains equivocal, possibly because populations and social groups are often structured, which affects the local transmission and extinction of diseases. We test how the structuring of towns into villages and households influenced the risk of dying from three easily diagnosable infectious diseases-smallpox, pertussis and measles-using a novel dataset covering almost all of Finland in the pre-healthcare era (1800-1850). Consistent with previous results, the risk of dying from all three diseases increased with the local population size. However, the division of towns into a larger number of villages decreased the risk of dying from smallpox and to some extent of pertussis but it slightly increased the risk for measles. Dividing towns into a larger number of households increased the length of the epidemic for all three diseases and led to the expected slower spread of the infection. However, this could be seen only when local population sizes were small. Our results indicate that the effect of population structure on epidemics, disease or parasite risk varies between pathogens and population sizes, hence lowering the ability to generalize the consequences of epidemics in spatially structured populations, and mapping the costs of social life, via parasites and diseases.

Glucose regulation is a repeatable trait affected by successive handling in zebra finches.

The capacity to adequately respond to (physiological) perturbations is a fundamental aspect of physiology, and may affect health and thereby Darwinian fitness. However, little is known of the degree of individual variation in this capacity in non-model organisms. The glucose tolerance test evaluates the individual's ability to regulate circulating glucose levels, and is a widely used tool in medicine and biomedical research, because glucose regulation is thought to play a role in the ageing process, among other reasons. Here, we developed an application of the intraperitoneal glucose tolerance test (IP-GTT) to be used in small birds, to test whether individuals can be characterized by their regulation of glucose levels and the effect of successive handling on such regulation. Since the IP-injection (intraperitoneal glucose injection), repeated handling and blood sampling may trigger a stress response, which involves a rise in glucose levels, we also evaluated the effects of handling protocols on glucose response. Blood glucose levels decreased immediately following an IP-injection, either vehicle or glucose loaded, and increased with successive blood sampling. Blood glucose levels peaked, on average, at 20 min post-injection (PI) and had not yet returned back to initial levels at 120 min PI. Glucose measurements taken during the IP-GTT were integrated to estimate magnitude of changes in glucose levels over time using the incremental area under the curve (AUC) up to 40 min PI. Glucose levels integrated in the AUC were significantly repeatable within individuals over months (r = 50%; 95% CI 30-79%), showing that the ability to regulate glucose differs consistently between individuals.

Child volunteers in a women's paramilitary organization in World War II have accelerated reproductive schedules.

Understanding how conditions experienced during development affect reproductive timing is of considerable cross-disciplinary interest. Life-history theory predicts that organisms will accelerate reproduction when future survival is unsure. In humans, this can be triggered by early exposure to mortality. Previous studies, however, have been inconclusive due to several confounds that are also likely to affect reproduction. Here we take advantage of a natural experiment in which a population is temporarily divided by war to analyze how exposure to mortality affects reproduction. Using records of Finnish women in World War II, we find that young girls serving in a paramilitary organization wait less time to reproduce, have shorter inter-birth intervals, and have more children than their non-serving peers or sisters. These results support the hypothesis that exposure to elevated mortality rates during development can result in accelerated reproductive schedules and adds to our understanding of how participation in warfare affects women.

Coupling lifespan and aging? The age at onset of body mass decline associates positively with sex-specific lifespan but negatively with environment-specific lifespan.

Whether lifespan scales to age-associated changes in health and disease is an urgent question in societies with increasing lifespan. Body mass is associated with organismal functioning in many species, and often changes with age. We here tested in zebra finches whether two factors that decreased lifespan, sex and poor environmental quality, accelerated the onset of body mass declines. We subjected 597 birds for nine years to experimentally manipulated foraging costs (harsh = H, benign = B) during development (small vs large brood size) and in adulthood (easy vs hard foraging conditions) in a 2 × 2 design. This yielded four treatment combinations (HH, HB, BH, BB) for each sex. Harsh environments during development and in adulthood decreased average body mass additively. The body mass aging trajectory showed a short steep increase in early adulthood, followed by a plateau and then a decline after 5 years. This decline occurred in all groups except for HB females, which gained mass until death. Surprisingly, the onset of body mass decline was earlier in experimental groups with a longer lifespan. In contrast, the onset of body mass decline was one year earlier in females, which lived two months (4%) shorter than males. Thus, the onset of body mass aging associated positively with the sex-specific differences in lifespan, but negatively with the environmental modulation of lifespan. Thus, body mass aging trajectories did not generally scale to lifespan, and we discuss the possible causes and implications of this finding.

Baseline glucose level is an individual trait that is negatively associated with lifespan and increases due to adverse environmental conditions during development and adulthood.

High baseline glucose levels are associated with pathologies and shorter lifespan in humans, but little is known about causes and consequences of individual variation in glucose levels in other species. We tested to what extent baseline blood glucose level is a repeatable trait in adult zebra finches, and whether glucose levels were associated with age, manipulated environmental conditions during development (rearing brood size) and adulthood (foraging cost), and lifespan. We found that: (1) repeatability of glucose levels was 30%, both within and between years. (2) Having been reared in a large brood and living with higher foraging costs as adult were independently associated with higher glucose levels. Furthermore, the finding that baseline glucose was low when ambient temperature was high, and foraging costs were low, indicates that glucose is regulated at a lower level when energy turnover is low. (3) Survival probability decreased with increasing baseline glucose. We conclude that baseline glucose is an individual trait negatively associated with survival, and increases due to adverse environmental conditions during development (rearing brood size) and adulthood (foraging cost). Blood glucose may be, therefore, part of the physiological processes linking environmental conditions to lifespan.

What have humans done for evolutionary biology? Contributions from genes to populations.

Many fundamental concepts in evolutionary biology were discovered using non-human study systems. Humans are poorly suited to key study designs used to advance this field, and are subject to cultural, technological, and medical influences often considered to restrict the pertinence of human studies to other species and general contexts. Whether studies using current and recent human populations provide insights that have broader biological relevance in evolutionary biology is, therefore, frequently questioned. We first surveyed researchers in evolutionary biology and related fields on their opinions regarding whether studies on contemporary humans can advance evolutionary biology. Almost all 442 participants agreed that humans still evolve, but fewer agreed that this occurs through natural selection. Most agreed that human studies made valuable contributions to evolutionary biology, although those less exposed to human studies expressed more negative views. With a series of examples, we discuss strengths and limitations of evolutionary studies on contemporary humans. These show that human studies provide fundamental insights into evolutionary processes, improve understanding of the biology of many other species, and will make valuable contributions to evolutionary biology in the future.

Individual variation in metabolic reaction norms over ambient temperature causes low correlation between basal and standard metabolic rate.

Basal metabolic rate (BMR) is often assumed to be indicative of the energy turnover at ambient temperatures (Ta) below the thermoneutral zone (SMR), but this assumption has remained largely untested. Using a new statistical approach, we quantified the consistency in nocturnal metabolic rate across a temperature range in zebra finches (N=3213 measurements on 407 individuals) living permanently in eight outdoor aviaries. Foraging conditions were either benign or harsh, and body mass and mass-adjusted BMR (BMRm) and SMR (SMRm) were lower in individuals living in a harsh foraging environment. The correlation between SMRm at different Ta was high (r=0.91), independent of foraging environment, showing that individuals are consistently ranked according to their SMRm However, the correlations between BMRm and SMRm were always lower (average: r=0.29; range: 0

Effects of developmental conditions on glucocorticoid concentrations in adulthood depend on sex and foraging conditions.

Developmental conditions in early life frequently have long-term consequences on the adult phenotype, but the adult environment can modulate such long-term effects. Glucocorticoid hormones may be instrumental in mediating developmental effects, but the permanency of such endocrine changes is still debated. Here, we manipulated environmental conditions during development (small vs. large brood size, and hence sibling competition) and in adulthood (easy vs. hard foraging conditions) in a full factorial design in zebra finches, and studied effects on baseline (Bas-CORT) and stress-induced (SI-CORT) corticosterone in adulthood. Treatments affected Bas-CORT in females, but not in males. Females reared in small broods had intermediate Bas-CORT levels as adults, regardless of foraging conditions in adulthood, while females reared in large broods showed higher Bas-CORT levels in hard foraging conditions and lower levels in easy foraging conditions. Female Bas-CORT was also more susceptible than male Bas-CORT to non-biological variables, such as ambient temperature. In line with these results, repeatability of Bas-CORT was higher in males (up to 51%) than in females (25%). SI-CORT was not responsive to the experimental manipulations in either sex and its repeatability was high in both sexes. We conclude that Bas-CORT responsiveness to intrinsic and extrinsic conditions is higher in females than in males, and that the expression of developmental conditions may depend on the adult environment. The latter finding illustrates the critical importance of studying of causes and consequences of long-term developmental effects in other environments in addition to standard laboratory conditions.

Food availability affects adult survival trajectories depending on early developmental conditions.

Food availability modulates survival in interaction with (for example) competition, disease and predators, but to what extent food availability in natural populations affects survival independent of these factors is not well known. We tested the effect of food availability on lifespan and actuarial senescence in a large population of captive zebra finches by increasing the effort required to obtain food, reflecting natural contrasts in food availability. Food availability may not affect all individuals equally and we therefore created heterogeneity in phenotypic quality by raising birds with different numbers of siblings. Low food availability had no effect on lifespan for individuals from benign developmental conditions (raised in small broods), but shortened lifespan for individuals from harsh developmental conditions. The lifespan difference arose through higher baseline mortality rate of individuals from harsh developmental conditions, despite a decrease in the rate of actuarial senescence. We found no evidence for sex-specific environmental sensitivity, but females lived shorter than males due to increased actuarial senescence. Thus, low food availability by itself shortens lifespan, but only in individuals from harsh developmental conditions. Our food availability manipulation resembles dietary restriction as applied to invertebrates, where it extends lifespan in model organisms and we discuss possible reasons for the contrasting results.

Large diurnal temperature range increases bird sensitivity to climate change.

Climate variability is changing on multiple temporal scales, and little is known of the consequences of increases in short-term variability, particularly in endotherms. Using mortality data with high temporal resolution of zebra finches living in large outdoor aviaries (5 years, 359.220 bird-days), we show that mortality rate increases almost two-fold per 1°C increase in diurnal temperature range (DTR). Interestingly, the DTR effect differed between two groups with low versus high experimentally manipulated foraging costs, reflecting a typical laboratory 'easy' foraging environment and a 'hard' semi-natural environment respectively. DTR increased mortality on days with low minimum temperature in the easy foraging environment, but on days with high minimum temperature in the semi-natural environment. Thus, in a natural environment DTR effects will become increasingly important in a warming world, something not detectable in an 'easy' laboratory environment. These effects were particularly apparent at young ages. Critical time window analyses showed that the effect of DTR on mortality is delayed up to three months, while effects of minimum temperature occurred within a week. These results show that daily temperature variability can substantially impact the population viability of endothermic species.

What can long-lived mutants tell us about mechanisms causing aging and lifespan variation in natural environments?

Long-lived mutants of model organisms have brought remarkable progress in our understanding of aging mechanisms. However, long-lived mutants are usually maintained in optimal standardized laboratory environments (SLEs), and it is not obvious to what extent insights from long-lived mutants in SLEs can be generalized to more natural environments. To address this question, we reviewed experiments that compared the fitness and lifespan advantage of long-lived mutants relative to wild type controls in SLEs and more challenging environments in various model organisms such as yeast Saccharomyces cerevisiae, the nematode worm Caenorhabditis elegans, the fruitfly Drosophila melanogaster and the mouse Mus musculus. In competition experiments over multiple generations, the long-lived mutants had a lower fitness relative to wild type controls, and this disadvantage was the clearest when the environment included natural challenges such as limited food (N=6 studies). It is well known that most long-lived mutants have impaired reproduction, which provides one reason for the fitness disadvantage. However, based on 12 experiments, we found that the lifespan advantage of long-lived mutants is diminished in more challenging environments, often to the extent that the wild type controls outlive the long-lived mutants. Thus, it appears that information on aging mechanisms obtained from long-lived mutants in SLEs may be specific to such environments, because those same mechanisms do not extend lifespan in more natural environments. This suggests that different mechanisms cause variation in aging and lifespan in SLEs compared to natural populations.