Evolution, Medicine, and Public Health

Emerging infectious diseases constitute a major health threat and are often associated with zoonotic spillover processes. Pathogen host shifts may involve evolutionary adaptation to new host species, which is of central concern in relation to future pandemics. Evolutionary host shifts require certain conditions to be met, including physiological and ecological factors. A pathogen strain infecting a new host species to which it is not well adapted will generally experience reduced success, which depends on the effective similarity between the new host species and the original reservoir host species from the pathogen's perspective. The adaptation process involves intermediate strains, or phenotypes, that exist at the cost of reduced transmission and replication rates, and the evolutionary outcome depends on factors associated with host species physiology and population interactions. The interplay between host similarity and interaction, and pathogen adaptation trade-offs, is therefore important in steering pathogen evolution and possible evolutionary host-shift outcomes. Here we apply niche-evolution theory to host-pathogen systems to investigate the combined effect of host species similarity and intra- and interspecific interactions on evolutionary host shifts. We identify the conditions under which evolutionary host shifts occur and show, for a two-host-species system, that evolutionary outcomes fall into four distinct categories.

Dormancy is a widespread life-history strategy that enables organisms to persist through periods of adverse environmental conditions. Despite its prevalence, the evolutionary forces shaping dormancy and the timing of reactivation remain poorly understood, particularly in pathogens facing predictable environmental fluctuations. Here, we investigate how seasonal variation can drive the joint evolution of pathogen dormancy and reactivation, and whether these traits are favoured to evolve as fixed or plastic strategies. Using a theoretical model of vector-borne disease transmission, we show when seasonality can promote plasticity in dormancy and reactivation. The optimal timing of transitions between active and dormant states depends critically on the environmental cues available to pathogens and on their reliability for predicting future transmission opportunities. Although motivated by the biology of relapsing malaria parasites, our results provide a general framework for understanding the evolution of dormancy as an adaptive response to periodic environmental fluctuations across diverse pathogen systems.

Early environmental conditions can have long-lasting effects on survival and reproductive fitness. Using a 23 year-long monitoring data set of captive mouse lemur's life history traits, we tested a relationship between maternal allocation to offspring (N = 1365) and their adulthood survival. Maternal characteristics such as age or body condition did not affect allocation to offspring whatever the litter size (1 to 3). Although birth mass depended on size and composition of the litters, mouse lemur survival was highly correlated with body mass acquired after weaning in both sexes, through potential sibling competition. Moreover, female's reproductive success correlated with this body mass and was consistently associated with increased longevity. These findings suggest the presence of a silver spoon effect under constant captive conditions. However, cumulative effects of genetic and adulthood social conditions strongly interact to affect adult survival. Deaths related to intra- or inter-sexes aggressive social interactions may outweigh effect of early environment and therefore minimize the silver-spoon effect on captive mouse lemur's survival. However, having a high body mass after weaning appeared to be a determinant factor in individual survival for mouse lemurs.

Doxycycline post-exposure prophylaxis (doxy-PEP) represents major advancements in sexually transmitted infection prevention for men who have sex with men (MSM), yet the joint long-term population-level impact on Neisseria gonorrhoeae transmission dynamics and antimicrobial resistance (AMR) together with a moderately effective vaccine remains uncertain. Here, we developed a deterministic transmission model calibrated to empirical surveillance data from England to evaluate the 15-year epidemiological interactions of implementing doxy-PEP and vaccination at the population level. The model incorporates the tetracycline- and ceftriaxone-susceptible, tetracycline-resistant (Tet-R), ceftriaxone-resistant (Cef-R), and dual-resistant (Dual-R) strains. Our simulations suggest that the unmitigated deployment of doxy-PEP provides only modest reductions in overall gonorrhoea burden, yielding a net programmatic efficiency of 0.072 (95% CrI: 0.018 - 0.23) averted infections per enrolment over the 15-year horizon. Although doxy-PEP reduces tetracycline- and ceftriaxone-susceptible infections, it consistently selects for Tet-R lineages. Conversely, standalone vaccination yields substantially greater epidemiological benefit, averting 0.73 (95% CrI: 0.17 - 1.63) overall infections per enrolment. When deployed in tandem, the dual intervention strategy achieves the greatest overall effectiveness to 0.83 (95% CrI: 0.22 - 1.71) averted infections per enrolment while mitigating the Tet-R selection pressure observed under standalone doxy-PEP. Long-term strain dynamics were found to be governed by background frontline ceftriaxone treatment failure rates rather than intervention uptake. Under a scenario of compromised ceftriaxone efficacy (20% treatment failure), doxy-PEP is projected to favour expansion of Dual-R strain, yielding 510 (95% CrI: 38 -258600) excess Dual-R infections across the 15-year horizon (146.18% [95% CrI: 31.30 - 920.86%] cumulative increase) and triggering sustained transmission exceeding the no-intervention baseline. Conversely, vaccination standalone or combined strategies consistently suppress overall transmission. By year 15, annual Cef-R and Dual-R infections are restricted to less than or equal to 19 infections under both vaccine-inclusive approaches. These findings suggest that the public health utility of antibiotic prophylaxis is heavily contingent upon the preserved efficacy of frontline therapeutics. Our work demonstrates that single-agent prophylaxis risks localized containment of some pathogens at the cost of driving multidrug-resistant selection in others and underscores the necessity of integrating non-selective tools like vaccines to manage N. gonorrhoeae.

Cancer progression often requires the accumulation of multiple driver mutations, yet the same set of drivers may be acquired in different orders. How these alternative mutation-order pathways jointly shape tumor clonal structure remains unclear. We develop a multitype branching-process model in which malignant transformation requires two driver mutations and distinguish malignant cells both by their mutation order and by the independent transformation event that founded their clone. Under a successive exponential approximation, we establish point-process limits for the pathway-specific clone-size processes and derive a closed-form expression for the limiting expected Simpson's index of the combined malignant population. When the two mutation orders produce malignant cells with the same net growth rate, the limiting index separates into effective pathway weights, determined by mutation rates and birth-death dynamics at preceding stages, and within-pathway concentration terms, determined by intermediate-to-malignant growth-rate ratios. This decomposition shows that a driver's effect on heterogeneity depends critically on when it is acquired. A strong driver acquired early expands the intermediate lineage and increases the supply of independent malignant founders, whereas the same driver acquired at the final transition strengthens the growth and age advantage of early-founded malignant clones. Under additive fitness effects, these counteracting mechanisms can produce a non-monotone relationship between selective advantage and clonal concentration. We further show that threshold-like non-additive fitness effects can generate highly concentrated malignant populations, while order-dependent terminal fitness leads the faster-growing pathway to dominate asymptotically. Together, these results reveal how mutation order, mutational accessibility, selection, and epistasis jointly determine lineage-level intratumor heterogeneity.

Despite its high propensity for host switching, the evolutionary mechanisms underlying influenza host adaptation remain unclear. H3Nx influenza viruses are uniquely generalist, with long-term lineages that circulate in avian, human, swine, equine, and canine hosts. Using 13,295 H3Nx sequences, we quantified host-specific adaptive evolution and developed a pipeline to map reassortment events onto trees with measures of statistical uncertainty. We find that while H3Nx viruses in mammals undergo adaptive evolution in HA and NA, viruses in birds experience very little directional selection. Instead, avian lineages exhibit high rates of reassortment, frequently generating novel reassortant lineages that persist transiently and turn over rapidly. 29.8-47.4% of all avian reassortant lineages are purged within the first year of circulation, and reassortment shows no fitness benefit in birds. In contrast, reassorted lineages in swine are more likely to persist long-term, suggesting that reassortment in swine may be broadly beneficial. Segment-specific reassortment patterns were also distinct between avian and mammalian viruses, with NA reassorting more frequently than expected in birds, but less frequently than expected in swine. Reassortment events are enriched between mammalian, but not avian, host switches, suggesting that reassortment may be most beneficial for mediating host switches among mammalian species. Together, our data suggest that host differences drive fundamentally different evolutionary outcomes for influenza viruses, transitioning from reassortment-dominant evolution in their avian reservoir, to varying degrees of adaptation upon establishment in mammals.

For nearly a century, the physical origin of metabolic scaling has remained unresolved: metabolism is proportional to body mass in small organisms but follows Kleiber's three-quarter-power law in larger animals. We derive both regimes from the Metabolic Holon (MH), a locally optimized capillary-tissue oxygen-supply unit coupling convection, diffusion, and cellular oxygen consumption. Physical similarity predicts that the effective number N of repeated MHs is body-mass invariant within metabolic groups, while independent observations constrain its group-specific magnitude. Without calibration to metabolic-rate or heart-rate data, the theory predicts absolute metabolic rates across 18 orders of magnitude, regime transition, group-specific levels, and heart-rate scaling. One empirical lifetime-heartbeat constraint sets lifespan. Kleiber's law is thus one asymptotic consequence of a general physical theory of organismal aerobic metabolism.

The coexistence of competing pathogen strains is shaped by cross-immunity, the cross-protection that infection with one strain confers against another. Although cross-immunity is often asymmetric between strains, this asymmetry is often neglected in the literature on multi-strain coexistence. The effect on coexistence-exclusion outcomes of waning immunity\textemdash which is particularly relevant for antigenically evolving pathogens\textemdash is also poorly understood. To understand how these factors affect strain coexistence, here we analyze a status-based two-strain SIRS model with asymmetric cross-immunity and strain-specific rates for transmission, recovery, and waning of immunity. We derive explicit invasion thresholds that also determine the feasibility and local stability of a unique coexistence equilibrium. Thus, these thresholds allow us to characterize the region of stable strain coexistence, as a function of the cross-immunities and rates of waning immunity. We also obtain closed-form expressions for the strain prevalences at the coexistence equilibrium, showing that the total prevalence may vary non-monotonically as the basic reproduction number of one strain increases. Finally, we show that a transient reduction in transmission can move a coexisting strain pair across an invasion boundary, driving the weaker strain extinct. Applying this result to influenza B, our analysis offers a parsimonious explanation for the disappearance of the Yamagata lineage during the COVID-19 pandemic.

In the face of an epidemic where a population behaviour both influences disease transmission and reacts to it, social processes can generate norms to support socially beneficial behaviour. Most mathematical models of coupled behaviour disease dynamics treat norms as pre-existing rather than explaining how they are maintained. Here, we investigate whether altruistic punishment can sustain a social distancing norm when individuals may defect, cooperate without punishing, or cooperate while paying a cost to punish defectors. We couple a transmission model to an imitation model for these three strategies. Disease prevalence affects behavioural payoffs, while the behavioural composition modifies transmission. We also compare this coupled system with a control where behavioural decisions respond to a fixed prevalence. We find a wide parameter regime corresponding to the establishment of an injunctive social norm in support of social distancing, where the punisher strategy is widespread. Persistence may occur through stable states where punishers or dominant. Disease behaviour feedback can also create oscillations (where the three strategies succeed one another in response to epidemic waves) or tipping points (sharp transitions between all-defector and cooperative states). These effects do not occur in the uncoupled model, although there are still broad parameter regimes where a social norm persists. Our findings show that costly peer punishment can support persistence of social norms that mitigate disease transmission. More broadly, endogenous epidemic feedback can qualitatively change the conditions under which cooperation and punishment are sustained, producing tipping points and long-term behavioural epidemiological cycles that fixed-payoff models cannot capture.

Heartland virus (HRTV) and Bourbon virus (BRBV) are emerging tick-borne arboviruses transmitted by the lone star tick (Amblyomma americanum) that have caused dozens of cases of human disease in the United States, including multiple fatalities. Despite their significance, entomological, clinical, and molecular surveillance remains sparse, limiting our understanding of HRTV and BRBV distribution and risk. The Nebraska Department of Health and Human Services and the Nebraska Public Health Laboratory expanded tick-borne pathogen surveillance to include HRTV and BRBV in A. americanum ticks beginning in 2024. Here, we report the first detections of HRTV and BRBV in Nebraska and present a multi-segment phylogenetic analysis of complete virus genomes. Using a newly developed amplicon-based whole genome sequencing strategy, we generated complete HRTV genomes from three PCR-positive A. americanum pools collected in two counties in eastern Nebraska. Additionally, we generated a complete BRBV genome from a single PCR-positive A. americanum pool. A time-calibrated phylogenetic analysis of the L segment containing all publicly available HRTV sequences determined that the 3 genomes from Nebraska form a monophyletic cluster that initially diverged from viruses isolated from Missouri in the early 2000s, corresponding with the expansion of A. americanum into Nebraska. A phylogenetic analysis of BRBV segment 2 indicates that the genome from Nebraska sits on a long branch and likely diverged from other genomes sequenced in the early 2010s. Topological concordance across each segment suggests minimal occurrences of reassortment among the HRTV and BRBV genome sequences. These findings document the expansion of HRTV and BRBV to the western margin of the A. americanum range and demonstrate the utility of enhanced surveillance and whole genome sequencing for characterizing the spread of tick-borne arboviruses.

Persistent viral infections arise from complex interactions between viral replication, host cell responses, and ongoing viral evolution. A general framework linking viral fitness to persistence dynamics is lacking. Here, we develop for the first time a mathematical model of viral persistence that takes into consideration viral fitness variations. Essential to the model is the partition of the classical fitness parameter into three components: replicative, infective, and dispersal fitness. The model was initially inspired by a new experiment on hepatitis C virus (HCV) persistence, established in human hepatoma cells, also reported in this work. This experiment documents two strikingly different viral trajectories depending on the initial replicative fitness of the viral population used to establish persistence. The dynamical model describes the interactions among uninfected cells, infected cells, and infectious virions, and it incorporates, through a continuum, two alternative mechanisms of viral release from cells: budding and lysis. Analysis of the model reveals that viral fitness parameters organise infection outcomes into distinct dynamical regimes. Low replicative and dispersal fitness values lead to viral extinction, whereas high values enable persistence through either stable coexistence or recurrent infection waves. The space of fitness discloses a hierarchy among these parameters, with replicative and dispersal fitness being able to trigger important shifts in the outcome of the infection as opposed to infective fitness. The model identifies trade-offs between replication and dispersal that shape viral production and predicts slow dynamical regimes in which infection may persist despite low detectable viral loads. These dynamical transitions provide candidate mechanisms capable of generating the persistence patterns observed experimentally. Our results establish a computational framework linking multidimensional viral fitness to persistence dynamics and suggest general principles by which evolving RNA viruses transition between extinction (cell curing) and sustained persistence.

Infected individuals drive infectious disease transmission, yet empirical data on social interactions during acute infection remain limited. We conducted a prospective longitudinal study of 1,000 medically attended acute gastroenteritis and acute respiratory infection cases and 709 household members in the northwestern United States from 2024 to 2025 to quantify illness-associated changes in social contacts and their implications for transmission modeling. Cases substantially reduced social contacts during peak illness; weighted mean number of contacts increased 2.0-fold (95% confidence interval, 1.8-2.2) over the two-week follow-up. In transmission modeling, the simulated outbreak trajectory and estimated effectiveness of interventions differed substantially between models that did and did not account for temporal reductions in social contacts during acute infection. These findings show that behavioral responses during acute infection could substantially influence transmission dynamics and intervention evaluation, and provide an empirical framework for incorporating illness-associated behavioral change into infectious disease models.

Social relationships are foundational to animal societies, but individual social connections differ hugely in importance and strength. Key relationships, such as those between breeding partners, may be prioritised and more highly invested in by individuals, but a key question is the extent to which social flexibility allows individuals to respond to the loss of these key social relationships. Here, we use a detailed longitudinal dataset of individual breeding and social behaviour in wild great tits (Parus major) to characterise flexibility in social behaviour after the loss of their breeding partner ('widowing'). We show transient increases in two measures of sociality following the widowing event. Individuals' relationships with their replacement partner were initially weaker than those between non-widowed birds, but converged by the breeding season. Hence, we show that birds are robust to the loss of key social relationships and that great tits show a flexible ability to return to social equilibrium. Strong social resilience has implications for the response of populations to change and loss.

Human-to-human transmission of the Andes virus (ANDV), which causes the deadly Hantavirus Pulmonary Syndrome, has been documented in several outbreaks, but remains insufficiently characterized to ensure preparedness against future emergence. Here, we integrate epidemiological data from historical outbreaks and from the 2026 MV Hondius outbreak with a stochastic network-based transmission model to quantify ANDV epidemic potential and control requirements. We estimate a reproduction number of $R_0=2.30$ (95\% CI: 1.33--3.27), supporting sustained human transmission. Uncertainty and sensitivity analysis show that variation in transmissibility and incubation period mainly affects outbreak timing and size, while superspreading events can substantially alter the epidemic evolution. Model analysis and simulations further reveal how contact-network structure strongly modulates outbreak size, with close-contact clustering facilitating containment. Due to the virus characteristics, rapid identification and isolation can effectively suppress outbreaks, even more effectively than in the case of COVID-19, whereas pre-symptomatic transmission or increased mixing could substantially increase risk. Our results provide a quantitative framework for ANDV preparedness and highlight the most critical transmission features for future surveillance.

In temperate regions around the world, bats travel long distances every winter to gather at hibernation sites. A longstanding hypothesis is that each new generation of bats learns about the locations of these sites (called hibernacula) from older individuals, yet clear and compelling evidence demonstrating social transmission of this knowledge has been lacking. Here, we compiled 30,882 observations from 1985 to 2023 of 13,852 Greater mouse-eared bats (Myotis myotis) that were banded and observed at summer roosts, winter hibernacula, or both. Our analyses revealed four lines of evidence that Greater mouse-eared bats find suitable hibernacula using social information acquired at summer roosts. First, naive yearlings were more likely to be seen sharing their first hibernacula with adults from their summer birth colony relative to a null model where bats moved independently. Second, adult bats were also more likely to co-switch together into the same hibernacula across winters than expected from independent movements. Third, bats that roosted together in the summer were more likely to share a different site as a hibernaculum during the winter: being observed together during a summer changed the probability of a pair being observed together during a winter from 5% to 12%. Finally, high-resolution tracking revealed an instance of tandem flights to hibernacula sites during the summer, demonstrating that yearlings can learn from experienced adult bats months before hibernation. Together, our findings show that maternity colonies serve as "information centers" where females acquire knowledge of suitable hibernation sites throughout their long lives.

Metabolic rate is a widely variable trait that reflects organismal energy expenditure. At least half of all arthropod species carry maternally transmitted Wolbachia bacteria, but it is poorly understood how these endosymbionts affect host physiology and fitness. We tested how two central host traits, body mass and standard metabolic rate (SMR), are altered by Wolbachia for nine diverse Drosophila fly species and 13 co-occurring Wolbachia variants diverged roughly 150 million years. Interspecific trait variation was structured according to the host phylogeny, but within each host system, Wolbachia almost always altered body mass and/or SMR. Wolbachia often caused increases or decreases in body mass that, in some cases, also led to mass-dependent effects on whole-organism SMR. Other Wolbachia altered mass-adjusted SMR. These variable effects are plausibly explained by complex interactions among Wolbachia and host genomes, as documented for other traits (e.g., Wolbachia-induced cytoplasmic incompatibility). Endosymbiont effects on body mass and metabolic rate likely have cascading consequences for host biology and evolution, because these central traits are correlated with many aspects of host physiology, behavior, and life history. This also applies to hosts transinfected with Wolbachia from Drosophila to reduce the impacts of pathogens and pests on multiple continents.

In 2022, mpox clade IIb spread globally in men who have sex with men (MSM) via sexual contact. By summer 2022, case numbers declined in Europe and Norther America due to behavior change and immunization, with almost no reported cases in 2023, followed by low-level transmission. By autumn 2022, many susceptible individuals at high risk of transmission may have become immunized. Moreover, because individuals with mpox are infectious for only 2--4 weeks, sustaining transmission chains requires considerable infection throughput. This raises the question: How did mpox persist and transition to endemic circulation? We developed an agent-based model of mpox transmission on the Berlin MSM sexual contact network that incorporates viral shedding kinetics, vaccination, infection-derived immunity, immune waning, and case importations. After calibrating the model, we estimated that the probability of mpox extinction in Berlin exceeded $80\%$ in 2023, when acquired immunity fragmented the transmission network. Extending the analysis to a European MSM metapopulation reduced the extinction probability to less than $60\%$, whereas incorporating global metapopulation dynamics reduced it to nearly zero. We find that mpox persistence was enabled by epidemic asynchrony: When transmission declined in Europe/the Americas, mpox transmission continued in Asia, long enough for immune waning to partially restore transmission potential in Europe, thereby enabling subsequent re-importation and endemic circulation. These model-based findings are supported by phylogenetic evidence indicating that all active German transmission clusters are either linked to (i) re-importation of clade F from the Americas, or (ii) the emergence of clades C and E linked to Asia. Our findings on asynchronous transmission across connected global MSM networks highlight the role of global immuno-epidemiology in enabling mpox persistence and emphasize the importance of coordinated international surveillance and control efforts.

Classic socio-ecological theory predicts that males and females experience different sources and mechanisms of social competition. Whether these differences translate into sex-specific structural properties of dominance hierarchies remains unclear. Here, we compiled 156 dominance interaction matrices from 80 published studies and extracted three commonly used metrics - hierarchy steepness, linearity and the directional consistency index - to investigate the structural characteristics of male and female dominance hierarchies across primates. All three metrics were strongly affected by methodological and demographic variables. Steepness increased with the number of recorded interactions and group size, linearity decreased as matrices became sparser, and directional consistency declined with increasing numbers of interactions. Steepness covaried positively with both linearity and directional consistency, indicating that groups with steeper hierarchies also exhibited more linear and more directionally consistent relationships. We found no sex differences in steepness, linearity or directional consistency. These results suggest that current metrics primarily reflect variation in the sampling effort and the rate of interaction of the recorded behaviour and appear therefore not to capture potential sex differences in the forms of competition. Our findings highlight the need for alternative measures of power asymmetries that are less confounded by sampling effort and demographic variation to better understand how competition and conflict are structured across primate societies.

Viral population dynamics are shaped by production and loss. For viruses of microbes, high standing levels of viral abundances are interpreted as evidence of high rates of viral-induced cellular loss and viral production, followed by rapid extracellular viral decay. Here we reassess assumptions of rapid extracellular decay in 17 curated datasets, finding that biphasic decay either fits better or is statistically indistinguishable from exponential decay in approximately half the datasets. In addition to intrinsic heterogeneity in decay rates, biphasic decay at population scales can arise generically through aggregation mechanisms, where single virions decay and viral aggregates are protected. Integrating aggregation-induced biphasic decay into a virus-host model reveals that accounting for aggregation can recapitulate joint observations of high virion abundances and low infection prevalence, without assuming significant levels of uniformly inefficient infection. Together, our results suggest that durable extracellular virion persistence is environmentally relevant in shaping virus-microbe population dynamics.

SARS-CoV-2 evolution enhanced viral fitness and immune evasion, extending the COVID-19 pandemic and resulting in millions of excess deaths. Viral diversity is generated within infected individuals, yet the timing and interplay of viral and immunological forces that drive transmissible evolution are incompletely understood. We developed a multi-scale within host phylodynamic (WiPhy) model of SARS-CoV-2 infection which couples viral replication, innate and acquired immune responses, and viral mutation. We then validated the model against quantitative viral and phylodynamic metrics. Model output predicts that typical acute infections rapidly generate genetic diversity due to accumulation of minor variants which in most cases do not achieve sufficient concentrations for transmission. Delayed innate immune responses correlate with higher peak viral load and diversification, allowing higher transmission risk of the founder virus or with a novel variant that is equally or less fit. In contrast, the risk of transmitting a fitter variant is highest during the ~10% of infections in which viral loads remain sufficiently high for transmission after 10-14 days. In these cases, non-sustained innate and/or weak acquired immune responses allow sufficient time for selection of a variant with one or more fitness enhancing non-synonymous mutations. Across a simulated cohort of ~1500 individuals, 5% of transmission risk came from variants with enhanced fitness from nonsynonymous mutations, and 13% of simulated infections accounted for 90% of fitter variant transmission risk. Our results highlight how the timing and interplay of viral and immunological forces within a host create bottlenecks that severely limit between host evolution.