Evolution, Medicine, and Public Health

A central question in Geroscience is whether early-life mortality, which declines from birth to sexual maturity, and late-life mortality, which grows exponentially in time, can be understood within a shared conceptual framework. We show that stochastic threshold models can explain both phases by incorporating heterogeneity in neonatal vulnerability. Using U.S. National Center for Health Statistics data, we find that infant mortality risk is strongly associated with neonatal clinical markers such as Apgar scores, gestational age, and birth weight, suggesting that initial physiological differences persist across early life. We show that the [~]1/t mortality decline generically arises in stochastic threshold models via depletion of the most vulnerable, across a wide range of model specifications. Incorporating this mechanism into the Saturating-Removal model captures both the early decline and the later Gompertz acceleration, reproducing the full J-shaped mortality curve. Together, our findings link neonatal vulnerability to late-life mortality dynamics within a shared stochastic framework, supporting a life-course perspective on aging and longevity.

Parasites can alter host populations in fundamentally different ways depending on whether exposure results in infection. Yet, most epidemiological and evolutionary inference focuses on established infections, leaving the fitness consequences of parasite exposure comparatively understudied. This gap is consequential because hosts are frequently exposed to diverse parasite genotypes, and these encounters can impose substantial fitness costs even when infection does not occur. Theory predicts that hosts may mitigate these costs when interacting with commonly encountered parasite genotypes, such that exposure to sympatric parasites incurs lower fitness consequences than exposure to novel, allopatric parasites. Here, we examine the fitness consequences of exposure and infection in the first intermediate host of the trophically transmitted tapeworm Schistocephalus solidus, a cyclopoid copepod that serves as the first host in a three-host life cycle. Using sympatric (Vancouver Island, Canada) and allopatric (Norway) host-parasite combinations, we found a striking reciprocal asymmetry. Sympatric parasites were significantly more infective, yet exposure to sympatric parasites imposed weaker fitness costs when infection did not establish. In contrast, allopatric parasites were less infective, but exposed females produced fewer eggs and had lower hatching success than both controls and females exposed to sympatric parasites, indicating substantial genotype-dependent costs of exposure. Moreover, we found that infection was highly virulent across all genotypes: a single parasite caused near-complete reproductive suppression and reduced host survival across all host-parasite pairings, confirming S. solidus as a castrating parasite in copepods. Together, these results demonstrate that exposure, not just infection, acts as a critical ecological filter with potentially large and underappreciated consequences for host population dynamics and parasite transmission.

While SARS-CoV-2 and influenza continue to place a significant burden on population health, within-household differences in decisions towards vaccination and seeking care across these two pathogens, and across sociodemographic groups, remain largely unexplored. By conducting a household-level survey in Illinois, we found that many individuals made inconsistent decisions about vaccination: among all adults, 29% were vaccinated for only one of COVID-19 or influenza, and among those with children in the home, 39% lived with a child whose influenza or COVID-19 vaccination status differed from their own. A higher proportion of adults were vaccinated against COVID-19 compared to influenza, while the opposite was true for those younger than 18 years old. These differences hold even when accounting for disparities in coverage by age, race/ethnicity, political affiliation, and socioeconomic status. While vaccinated individuals consistently reported wanting to protect themselves or others, those who declined vaccination reported highly heterogeneous reasons ranging from resource constraints to distrust or misconceptions about vaccination. These differences are even more pronounced for COVID-19, with larger partisan gaps and higher refusal driven by safety concerns, lack of trust, or religious reasons than those who decide not to get the influenza vaccine. In contrast to vaccination, the decision to seek medical care when sick showed opposite sociodemographic trends, that are likely attributable to illness severity. Our findings highlight that closing gaps in COVID-19 and influenza vaccination coverage will require an integrative strategy that accounts for diverse motivations, fears, and barriers to access, while addressing social inequalities common to both diseases.

Background: Wearing facemasks and practising social distancing slow the spread of respiratory pathogens. However, in the event of a new pandemic emerging, the willingness of populations to voluntarily adopt these behaviours is unclear. Methods: A discrete choice experiment was conducted among 2,006 UK-based adults. Participants were presented with hypothetical scenarios describing the emergence of a respiratory virus pandemic and were asked to choose when they would wear facemasks and practise social distancing. A mixed multinomial logit model was used to jointly estimate how disease severity and prevalence, uncertainty in these quantities, and individual-level characteristics influence behavioural choices. Findings: Participants were averse to facemasks and social distancing in the absence of pandemic risk. For each ten-unit increase in severity (10 additional hospitalisations/1,000 infections), the odds of always wearing a facemask outside the home increased by 15.9% (95%CI: 14.3%, 17.5%), relative to rarely/never, and the odds of avoiding all people as much as possible increased by 16.4% (14.6%, 18.2%), relative to not avoiding anyone. Greater disease prevalence, uncertainty in disease severity or disease prevalence, a university education, prior COVID-19 vaccination and non-white ethnicity were also associated with choosing to always wear facemasks and avoid all people as much as possible. The probability of participants choosing to rarely/never wear facemasks varied from 13.4% (11.9%, 14.9%) in the lowest-risk scenario to 1.4% (1.2%, 1.7%) in the highest-risk scenario. Interpretation: Perceived risks of disease and associated uncertainty drive intention of UK adults to adapt their behaviour in a future pandemic.

A quarter of the world's population has immunologic evidence of past or present Mycobacterium tuberculosis (Mtb) infection (MTBI) detected as TST or IGRA positivity. Community-based preventive treatment of individuals with MTBI has resulted in transient decreases in TB cases, but its long-term effectiveness has been controversial. Due to the likelihood that many of those with immune responses to Mtb antigens may no longer harbor Mtb, widespread treatment of all such individuals may result in unnecessary exposure to antibiotics. We raise an additional concern that preventive treatment of individuals with MTBI, who are not at the risk of disease progression, may result in loss of protective immunity, provided by the persistent infection, and enhanced risk of TB upon re-exposure to Mtb. There is evidence from human cohorts and animal studies that prior exposure to Mtb confers protection against TB development upon re-exposure, and that treatment of Mtb-infected animals often results in loss of this protection. We build a novel epidemiological model of Mtb dynamics and progression to TB in a community allowing for protection afforded by MTBI against exogenous reinfection-driven disease progression. We show that implementation of treatment of MTBI in the whole community will result in reduction of TB cases but stopping the program may result in an increase in new TB cases that may offset (or even exceed) benefits of the preventive treatment program. Our results suggest that better understanding protective effects provided by MTBI against progression to TB upon Mtb re-exposure and identification of Mtb-infected individuals who most benefit from preventive treatment must be a priority before preventive treatment of asymptomatic MTBI is widely implemented.

Research on under-vaccination often segments populations using demographic or administrative variables that are operationally useful but fail to capture identity dimensions relevant to vaccination decisions. Drawing on social identity theory, we propose an identity-landscape approach distinguishing identity membership, identity centrality, and multidimensional identity structure. Using a cross-sectional survey of 1,000 UK parents, we measured 65 identity indicators, identity-importance ratings, and their association with attitudinal and behavioural hesitancy toward childhood vaccination using validated scales. Beyond established socio-demographic predictors, alternative-medicine and natural-lifestyle identities, as well as affiliation with social media networks, were linked to greater hesitancy. Greater centrality of religion and political affiliation within personal identity was also associated with higher hesitancy. Principal component analysis suggested that individuals actively engaged across multiple societal issues were more hesitant, whereas stereotypically male-gendered engagement was associated with lower hesitancy. An identity-focused population segmentation may identify previously unrecognized undervaccinated groups and inform innovative tailored immunization campaigns.

The Red Queen Hypothesis proposes that genetic variation is maintained in populations through antagonistic coevolution of hosts and parasites. A major assumption of the Red Queen Hypothesis is tight genetic specificity for infection. However, it has been argued that this genetic interaction of host and parasite (GHxGP) is sensitive to environmental context (GHxGPxE). Environmental change could accordingly disrupt coevolutionary oscillations on relevant time scales, calling into question antagonistic coevolution as a general and robust explanation for the maintenance of genetic diversity. To evaluate this critique, we used the plant-parasitic nematode Meloidogyne arenaria and its natural bacterial parasite Pasteuria penetrans to determine if specificity is altered by temperature. We exposed six isofemale host lines to five parasite sources at three ecologically relevant temperatures. We found that, at two of three temperatures, susceptibility to infection depended on the specific combination of host line and parasite source (GHxGP). This specificity varied across temperatures, consistent with a GHxGPxE effect. This three-way interaction was driven both by quantitative changes in the strength of specificity across temperatures and shifts in the susceptibility rankings of host-parasite combinations. Our study contributes a rare experimental test of a proposed challenge to the Red Queen Hypothesis and suggests the potential for environmental context to change host-parasite specificity.

Intrinsic capacity (IC) summarizes functional health across multiple domains in healthy aging research, yet evidence on whether IC can be measured and tracked before older age remains limited. Using data from the 1958 British birth cohort at ages 50 and 62 (N = 7,804), we examined whether IC could be measured as a coherent, valid and longitudinally comparable construct from midlife to early old age. A second-order model applied to 30 indicators across sensory, cognitive, physical, psychological and vitality domains supported a five-domain IC construct, with scalar invariance across sweeps enabling comparison of scores over time. IC scores showed graded associations with self-rated health and chronic disease burden in the expected directions. Mean IC declined by 6.3 points on a 0-100 scale from age 50 to 62. These findings establish a basis for studying IC trajectories from midlife, before functional decline is usually clinically apparent.

When only some hosts are protected from disease vectors, disease spread may be inhibited through a net reduction in vector visits or amplified as vectors redirect their attention to unprotected hosts. Two factors that determine which outcome prevails are host microbiota that alter vector host-seeking behavior and natural enemies that redistribute or suppress vector populations. Because both shape the frequency and distribution of vector visits, they are essential for understanding how individual-level protection scales to population-level disease dynamics. Yet, how these processes interact across scales remains poorly understood. Pea aphids are major virus vectors in pea crops and are commonly managed using parasitoid wasps. Recent evidence suggests that epiphytic bacteria in the genus Pseudomonas can also repel or kill pea aphids, yet whether Pseudomonas complements or undermines parasitoid-based vector control remains unknown. We used a mathematical model to show when and why Pseudomonas complements versus undermines biocontrol of aphid-vectored virus outbreaks. The effect of Pseudomonas on virus outbreaks depends most strongly on how successful parasitoids are at tracking aphid densities: When parasitoids effectively track aphids, Pseudomonas inhibits virus outbreaks by reducing aphid densities. With poor parasitoid tracking of aphids, Pseudomonas-induced aphid mortality generates spatial variability in aphid densities that slows parasitoid population growth. The net result is amplified crowding in plants not protected by Pseudomonas, increasing winged aphid production and accelerating viral spread. Counterintuitively, the more effective Pseudomonas is at killing aphids, the more strongly it generates spatial variability and promotes virus spread. The only other factor that can change the direction of Pseudomonas effects on virus outbreaks is whether the virus starts on a Pseudomonas-protected plant, which can cause Pseudomonas to inhibit virus outbreaks when it would otherwise promote them. Our results show how community and spatial context dictate whether microbiota protective to individual hosts will accelerate viral outbreaks.

Reproductive strategies vary widely among vertebrates, yet the selective drivers of life history trait evolution remain unresolved. Viviparity is typically associated with a slower life history syndrome of larger bodies, increased lifespans, and reduced fecundity. However, viviparity is often coupled to increased matrotrophic investment, which according to the Disposable Soma Theory (DST) should reduce longevity. Conversely, the Selfish Mother Hypothesis (SMH) suggests that matrotrophic mothers withhold nutrients for the sake of their own future survival and reproduction. These opposing frameworks imply conflicting life history outcomes, and it remains unclear whether such dynamics operate primarily among individuals of the same species or shape higher-level clade-wide divergence. Here, we used a phylogenetically controlled comparative analysis of chondrichthyan (n = 162) and mammalian (n = 620) species to show that both the convergent origin and quantitative degree of matrotrophy is associated with reduced longevity across two major vertebrate clades. Our results decouple parity mode and nutrient provisioning to show that matrotrophy reduces maternal longevity, which counteracts the slower life history strategy of viviparity. We provide evolutionary support for the DST, and not the SMH, in reproductive strategy diversification. Using a simple stochastic simulation, we propose a unified Sacrificial Mother framework, in which increased matrotrophic investment specifically reduces maternal longevity through the accumulation of somatic costs. Our work identifies the somatic costs of viviparous matrotrophy as a fundamental, but previously unrecognised, evolutionary trade-off against individual embryonic fitness which shapes the diversification of vertebrate life history strategies beyond resource allocation in intraspecific individuals.

Cancer progression following treatment failure is an evolutionary process in which therapy acts as a selection pressure driving Darwinian selection on heritable variation to favor resistant clones. This ability to generate variation, i.e., the cancers evolvability, is a key determinant of how rapidly tumors adapt to therapy. Here, we present an evolutionary game-theoretic model to evaluate how evolvability shapes resistance dynamics under two treatment modalities: targeted therapy and chemotherapy. We first compare cancer populations with fixed evolvabilities: low or high. Targeted therapy imposes a steep selection gradient, enabling rapid resistance evolution, while chemotherapy exerts a flatter gradient but drives tumors toward more extreme resistance strategies. We show that targeted therapy works better in low-evolvability cancers, whereas chemotherapy better controls high-evolvability populations. We then extend the model to incorporate facultative evolvability in which cancer cells dynamically adjust their evolvability in response to therapy-induced stress in which cells fine-tune the trade-off between acquiring higher resistance and limiting the costs of resistance and evolvability. The latter strategy sustains a higher tumor burden than fixed-evolvability populations. To address the challenges of facultative evolvability for therapy efficacy, we develop and simulate an evolutionary double bind using sequential cycles of chemotherapy and targeted therapy. With an appropriate sequence and timing, this strategy can drive cancer cells with facultative evolvability to extinction. Our results highlight the importance of evolvability in shaping treatment response and underscore the need to incorporate evolutionary principles into therapy design.

Reproductive seasonality offsets the energetic costs of reproduction by synchronizing births with peak resources and is traditionally expected to increase with latitude and environmental seasonality. However, life-history and behavioural strategies may also buffer energetic shortages and reduce dependency on environmental cycles. Here, we propose and test an integrative framework integrating climatic, life-history and behavioural factors using high-resolution measures of reproductive seasonality for 132 wild primate populations from 94 species. As expected, reproductive seasonality declines at lower latitudes, in less seasonal and in less predictable environments, even after controlling for productivity. It also decreases in species that spread reproductive costs by extending developmental periods, or when a higher infant mortality urges females to resume fertility shortly after loss. Unexpectedly, reproductive seasonality increases with environmental productivity and is not reduced by cognitive (foraging innovations), social (allomaternal care), or ecological (dietary breadth) buffering. Broader diets even enhance seasonality. These findings suggest that reproductive seasonality emerges from opportunity more than from constraints in productive environments, where females exploit abundant resources to accelerate their reproductive pace. Together, our results shed light on the diverse selective pressures shaping primate reproductive seasonality, including climate, life-history pace, and infanticide risk, and help to explain why humans reproduce year-round.

Many primates exhibit female philopatry and live in stable, female-bonded social groups. Permanent group fusions are rarely documented in these populations. We present a case study on a fusion of two social groups from a hybrid population of baboons (Papio cynocephalus x P. anubis) living in the Amboseli basin of Kenya. The fusion occurred following a period of increased human-induced mortality in one of the two social groups. After the fusion, females from the smaller group became the lowest ranking. We compared female behavior in the months following the fusion to the behavior of females in groups that had not fused and also compared pre- and post-fusion fitness outcomes. Following the fusion, the groups activity budget and patterns of agonistic interactions were typical for the study population. Females preferred familiar grooming partners for a short period following the fusion; however, after three months, patterns in female grooming were comparable to other groups, indicating rapid social integration. With the caveat that our sample size was limited, we observed no detectable fitness-related costs of group fusion in terms of birth rates or offspring survival, and adult female mortality was low following the fusion. These results demonstrate the flexibility of female baboons in navigating exposure to novel same-sex conspecifics despite a species-typic pattern of female philopatry. Based on this and previous examples of group fusions, we propose that group fusions may be most likely to occur when groups are too small to retain adult males, defend against predators, or compete with other groups.

The ecological and evolutionary dynamics of populations, including viral populations, are known to be jointly shaped by deterministic and stochastic processes. While the impact of stochastic processes has been rigorously explored for viral dynamics at the level of the host population, most dynamic models for acutely-infecting respiratory viral pathogens at the within-host scale remain deterministic in their formulation. While this may be reasonable for identifying key processes shaping their within-host viral population dynamics, recent studies indicate that stochastic processes need to be invoked for understanding patterns of within-host viral evolution. Specifically, several studies have shown that viral allele frequencies can change dramatically over the time course of days in acute infections. Here, we use stochastic dynamic models to explore the role of environmental noise in shaping observed patterns of virus evolution in acute respiratory virus infections. We summarize ways in which environmental stochasticity can be biologically realized in these acute viral infections and describe within-host models that can be implemented to jointly yield viral population dynamics and evolutionary dynamics. We further develop a statistical approach to estimate the extent of environmental noise from observed within-host allele frequency changes. We test this approach on simulated data and apply it to existing influenza A virus and SARS-CoV-2 within-host data. With these applications, we show that environmental stochasticity can parsimoniously reproduce key features of empirically observed allele frequency changes without needing to invoke demographic stochasticity or to adopt Wright-Fisher model formulations with a constant effective population size. Finally, we show that purifying selection and positive selection can both still contribute to within-host viral evolution in the context of a noisy environment, providing theoretical support for studies that have found purifying and positive selection in acutely-infecting respiratory virus populations.

Many mobile animals move to locate and consume resources, making energy gain and growth dependent on activity. Yet the role of activity in shaping predator-prey interactions in food webs has not been broadly considered. Here, we synthesize empirical examples to examine how three activity traits (mean, variance, and timing) vary among taxa (fish, mammals, birds) and between predators and prey across temporal scales. We then use predator-prey models to explore how these diverse activity patterns influence stability. Motivated by emerging activity patterns, our theory shows that fluctuating activity rates can drive predator-prey interaction strengths with major consequences for stability. Future research is needed on activity trait patterning, links between activity and attack rates, and the consequences of activity for predator-prey interactions to whole food webs. This is especially critical as human-driven changes to abiotic cues increasingly alter animal activity rates and may rewire food webs.

Prolonged association between mothers and their offspring is common in ungulates, with the level of maternal investment likely to play a central role in shaping this trait. Here we examined patterns of association between mothers and offspring over time, the apparent benefits of association to offspring, and costs to mothers. We analyzed 40 years worth of census data from an individually-monitored, food-limited population of red deer (Cervus elaphus) on the Isle of Rum, Scotland. Starting from birth, female calves associated more frequently with their mothers than male calves in their first year. Calves also associated less with their mothers if the mother did not conceive a new calf. Association frequency decreased with mothers age and population density, and survival over the first year was not related to mother-calf association. Yearlings, now in their second year, were more often associated with their mothers if they were female, if there was no subsequent calf (or the subsequent calf died as a neonate), and if they were still being suckled. Increased association between mothers and yearlings was associated with increased survival to adulthood at 28 months, but suckling a yearling did not improve its probability of survival. For individuals that reached maturity, increased association in the yearling year was associated with slightly shorter adult life spans. The level of association between a calf and mother was not associated with the mothers immediate survival or fecundity. Our findings suggest that juveniles born to poor-condition mothers benefit from prolonged association through improved yearling survival.

Cell tropism, or the preference of a virus for particular cell types, has major implications for viral transmission, pathogenesis, and evolution. An increase in viral fitness -- increased within-host replication, also leading to increased transmission between hosts -- can result from a virus changing its cell tropism. This is illustrated in the context of influenza, where adaptation to infect cells expressing 2-6 linked sialic acid receptors enhances human-to-human transmissibility. Target cell populations differ not only in abundance but also in intrinsic properties such as susceptibility, viral production, and interferon responses, rendering the relationship between tropism and viral fitness multi-faceted and complex. Understanding how different cell tropisms quantitatively change fitness remains an important open question in virology and quantitative biology. Here, we present a within-host mathematical model that incorporates distinct target cell types differing in key properties, and examine how cell tropism affects viral fitness, as measured by metrics such as peak viral load, infection duration, or total virus produced. Our analysis reveals that tradeoffs may arise when cell types differ by multiple characteristics. We further demonstrate that model parameters describing heterogeneity between cell types can be more accurately inferred when cell type proportions are measured alongside viral load. Our findings provide a framework for assessing the links between viral evolution, cell tropism, and within-host fitness, and motivate the design of experiments to collect quantitative data on between-cell heterogeneity.

Birds provide a unique model for ageing research, as they exhibit higher mass-adjusted metabolic rates and blood glucose levels than other vertebrate groups, yet demonstrate greater longevity and slower senescence compared to mammals of similar body size. This challenges the "pace of life syndrome" hypothesis, which predicts that high metabolic rates and elevated glucose should correlate with shorter lifespans. While the effects of glucose, glycation, and advanced glycation end-products (AGEs) on ageing are well-documented in humans and the conventional models used in biomedical research, their impact on avian physiology and ageing remains poorly understood. Some evidence suggests that birds possess adaptations mitigating the potential detrimental effects of glucose levels, which are much higher than those of all other vertebrate groups. However, previous studies indicate that elevated glucose predicts reduced lifespan, and protein glycation--varying with age--can influence survival and some fitness-related traits. This implies that glycation or AGE accumulation may have relevant effects on avian longevity. In this study, we experimentally investigated how one year of dietary supplementation with glucose or methylglyoxal affects survival and ageing markers (metabolic rate, flying performance, and beak coloration) in captive zebra finches (Taeniopygia guttata). Our results reveal a significant increase in mortality exclusively in glucose-supplemented birds. Although glucose treatment elevated albumin glycation rate and AGE formation--the latter also observed with methylglyoxal supplementation--these variables did not directly explain the increased mortality in glucose-treated birds, which was absent in methylglyoxal-treated individuals despite similar AGE accumulation. Additionally, we observed some effects on the assessed senescence markers, with an age-related constraint on seasonal metabolic adjustment, and a treatment-influenced age decline in secondary sexual traits expression. These findings support the use of these markers as proxies for senescence in zebra finches. We also discuss alternative mechanisms, independent of the glycation cascade, which may contribute to mortality. A seasonal decline in flight performance, particularly during peak mortality periods, suggests a broader deterioration of health. Thus, although we demonstrate glucose supplementation to be more deleterious than methylglyoxal, the underlying mechanisms for the observed increase in mortality induced by the treatment remain unresolved.

BackgroundEnvironmental conditions shape the evolutionary trajectories of RNA viruses, yet little is known about how complex physical stressors such as microgravity influence host-virus interactions and viral evolution. Here, we investigated the short-term evolutionary consequences of simulated microgravity on the Caenorhabditis elegans - Orsay virus (OrV) system. MethodsOrV was subjected to six serial passages in hosts acclimated to low-shear modeled microgravity, with parallel evolution under standard-gravity. Evolutionary outcomes were evaluated using virulence, transmission, and replication traits, all measured under standard-gravity conditions. ResultsViral load fluctuated across passages in both environments, with lower mean accumulation in microgravity-evolved lineages. After evolution, we detected no significant changes in virulence. Transmission increased in standard-gravity lineages but not in microgravity-evolved ones, while viral replication decreased in all lineages, with a stronger decline in those evolved under microgravity. However, the magnitude of phenotypic changes was generally modest. DiscussionThese results indicate that evolution under microgravity can alter viral phenotypic trajectories over short timescales. However, because all traits were assayed under standard-gravity conditions, we cannot directly assess local adaptation to microgravity, and the observed differences may reflect environment-specific trade-offs rather than reduced fitness per se. Furthermore, the limited number of passages and the modest magnitude of phenotypic change suggest that evolutionary responses may still be in an early stage. ConclusionOverall, our findings provide initial evidence that simulated microgravity can influence the evolutionary dynamics of an RNA virus, while highlighting the need for reciprocal fitness assays and longer-term experiments to fully characterize adaptation to altered gravitational environments.

The multinational Andes virus outbreak linked to the MV Hondius has exposed contacts across several countries, but the absence of further confirmed cases remains difficult to interpret given the long incubation period. We estimate the probability that secondary clusters may emerge using a stratified branching-process model parameterized with country-level tracing and isolation indicators. The risk of sustained spread is low, but secondary clusters remain plausible under imperfect isolation or pre-symptomatic transmission. These results support coordinated contact tracing and effective isolation while exposed contacts remain within the risk window.