Pacific Institute on Pathogens, Pandemics and Society

Humanity is now facing what may be the biggest challenge to its existence: irreversible climate change brought about by human activity. Our planet is in a state of emergency, and we only have a short window of time (7-8 years) to enact meaningful change. The goal of this systematic literature review is to summarize the peer-reviewed literature on proposed solutions to climate change in the last 20 years (2002-2022), and to propose a framework for a unified approach to solving this climate change crisis. Solutions reviewed include a transition toward use of renewable energy resources, reduced energy consumption, rethinking the global transport sector, and nature-based solutions. This review highlights one of the most important but overlooked pieces in the puzzle of solving the climate change problem - the gradual shift to a plant-based diet and global phaseout of factory (industrialized animal) farming, the most damaging and prolific form of animal agriculture. The gradual global phaseout of industrialized animal farming can be achieved by increasingly replacing animal meat and other animal products with plant-based products, ending government subsidies for animal-based meat, dairy, and eggs, and initiating taxes on such products. Failure to act will ultimately result in a scenario of irreversible climate change with widespread famine and disease, global devastation, climate refugees, and warfare. We therefore suggest an "All Life" approach, invoking the interconnectedness of all life forms on our planet. The logistics for achieving this include a global standardization of Environmental, Social, and Governance (ESG) or similar measures and the introduction of a regulatory body for verification of such measures. These approaches will help deliver environmental and sustainability benefits for our planet far beyond an immediate reduction in global warming.

Rattus spp. may acquire and disseminate antimicrobial resistant bacteria or antimicrobial resistance (AMR) genes. We conducted a scoping review to synthesize available research findings on AMR in Rattus spp. and to describe the size and scope of available literature on AMR epidemiology in Rattus spp. The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR). The search focused on scientific peer-reviewed publications focusing on AMR in peridomestic Rattus spp. The review was limited to publications in English available in PubMed, Web of Science and Scopus between 2000 and 2021. The results were summarized descriptively. Thirty-four studies conducted in twenty-one countries were included in this scoping review. Twelve bacterial species with AMR were identified with Escherichia coli and Staphylococcus aureus being the two most commonly reported. The resistant bacteria were isolated from species of peridomestic Rattus spp. in which R. norvegicus and R. rattus were the two most commonly studied. Rats were also found to carry multi-drug resistant (MDR) bacteria including extended-spectrum beta (β)-lactamase (ESBL), methicillin-resistant Staphylococcus aureus (MRSA), colistin-resistant Enterobacteriaceae (CoRE), and vancomycin-resistant Enterococci (VRE). This scoping review suggests that peridomestic Rattus spp. can carry multiple antimicrobial resistant bacteria, indicating their potential to serve as reservoirs and spreaders of AMR thus posing a threat to human and animal health.

Non-pharmaceutical interventions (NPIs), such as social distancing and contact tracing, are important public health measures that can reduce pathogen transmission. In addition to playing a crucial role in suppressing transmission, NPIs influence pathogen evolution by mediating mutation supply, restricting the availability of susceptible hosts, and altering the strength of selection for novel variants. Yet it is unclear how NPIs might affect the emergence of novel variants that are able to escape pre-existing immunity (partially or fully), are more transmissible or cause greater mortality. We analyse a stochastic two-strain epidemiological model to determine how the strength and timing of NPIs affect the emergence of variants with similar or contrasting life-history characteristics to the wild type. We show that, while stronger and timelier NPIs generally reduce the likelihood of variant emergence, it is possible for more transmissible variants with high cross-immunity to have a greater probability of emerging at intermediate levels of NPIs. This is because intermediate levels of NPIs allow an epidemic of the wild type that is neither too small (facilitating high mutation supply), nor too large (leaving a large pool of susceptible hosts), to prevent a novel variant from becoming established in the host population. However, since one cannot predict the characteristics of a variant, the best strategy to prevent emergence is likely to be an implementation of strong, timely NPIs.

Defensive symbionts in the host microbiome can confer protection from infection or reduce the harms of being infected by a parasite. Defensive symbionts are therefore promising agents of biocontrol that could be used to control or ameliorate the impact of infectious diseases. Previous theory has shown how symbionts can evolve along the parasitism-mutualism continuum to confer greater or lesser protection to their hosts and in turn how hosts may coevolve with their symbionts to potentially form a mutualistic relationship. However, the consequences of introducing a defensive symbiont for parasite evolution and how the symbiont may coevolve with the parasite have received relatively little theoretical attention. Here, we investigate the ecological and evolutionary implications of introducing a tolerance-conferring defensive symbiont into an established host-parasite system. We show that while the defensive symbiont may initially have a positive impact on the host population, parasite and symbiont evolution tend to have a net negative effect on the host population in the long term. This is because the introduction of the defensive symbiont always selects for an increase in parasite virulence and may cause diversification into high- and low-virulence strains. Even if the symbiont experiences selection for greater host protection, this simply increases selection for virulence in the parasite, resulting in a net negative effect on the host population. Our results therefore suggest that tolerance-conferring defensive symbionts may be poor biocontrol agents for population-level infectious disease control.

BACKGROUND: Vaccine homophily describes non-heterogeneous vaccine uptake within contact networks. This study was performed to determine observable patterns of vaccine homophily, as well as the impact of vaccine homophily on disease transmission within and between vaccination groups under conditions of high and low vaccine efficacy. METHODS: Residents of British Columbia, Canada, aged ≥ 16 years, were recruited via online advertisements between February and March 2022, and provided information about vaccination status, perceived vaccination status of household and non-household contacts, compliance with COVID-19 prevention guidelines, and history of COVID-19. A deterministic mathematical model was used to assess transmission dynamics between vaccine status groups under conditions of high and low vaccine efficacy. RESULTS: Vaccine homophily was observed among those with 0, 2, or 3 doses of the vaccine. Greater homophily was observed among those who had more doses of the vaccine (p < 0.0001). Those with fewer vaccine doses had larger contact networks (p < 0.0001), were more likely to report prior COVID-19 (p < 0.0001), and reported lower compliance with COVID-19 prevention guidelines (p < 0.0001). Mathematical modelling showed that vaccine homophily plays a considerable role in epidemic growth under conditions of high and low vaccine efficacy. Furthermore, vaccine homophily contributes to a high force of infection among unvaccinated individuals under conditions of high vaccine efficacy, as well as to an elevated force of infection from unvaccinated to suboptimally vaccinated individuals under conditions of low vaccine efficacy. INTERPRETATION: The uneven uptake of COVID-19 vaccines and the nature of the contact network in the population play important roles in shaping COVID-19 transmission dynamics.

Many organisms experience an increase in disease resistance as they age, but the time of life at which this change occurs varies. Increases in resistance are partially due to prior exposure and physiological constraints, but these cannot fully explain the observed patterns of age-related resistance. An alternative explanation is that developing resistance at an earlier age incurs costs to other life-history traits. Here, we explore how trade-offs with host reproduction or mortality affect the evolution of the onset of resistance, depending on when during the host's life cycle the costs are paid (only when resistance is developing, only when resistant or throughout the lifetime). We find that the timing of the costs is crucial to determining evolutionary outcomes, often making the difference between resistance developing at an early or late age. Accurate modelling of biological systems therefore relies on knowing not only the shape of trade-offs but also when they take effect. We also find that the evolution of the rate of onset of resistance can result in evolutionary branching. This provides an alternative, possible evolutionary history of populations which are dimorphic in disease resistance, where the rate of onset of resistance has diversified rather than the level of resistance.

Hyperparasites (species which parasitize other parasites) are common in natural populations, affecting many parasitic taxa, including: eukaryotic parasites; bacterial and fungal pathogens. Hyperparasitism is therefore likely to shape the ecology and evolution of many host-parasite systems, representing a promising method for biocontrol (e.g., treating antimicrobial resistant infections). However, the eco-evolutionary consequences of hyperparasitism have received little attention. We use a host-parasite-hyperparasite model to explore how introducing a hyperparasite drives the evolution of parasite virulence, and what impact this has on the host population. We show when the introduction of a hyperparasite selects for higher or lower parasite virulence, and the changes in virulence experienced by the host population. Crucially, we show that variation in the direct effects of hyperparasites on virulence and transmission, and the probability of cotransmission, can lead to a previously unseen hysteresis effect, whereby small shifts in hyperparasite characteristics can lead to sudden shifts in parasite virulence. We also show that hyperparasites can induce diversification in parasite virulence, leading to the coexistence of high and low virulence strains. Our results show hyperparasites can have dramatic effects on the evolution of parasite virulence, and that the use of hyperparasites in biocontrol should be approached with caution.

This study explores the health-related quality of life (HRQoL) experienced by patients with Long COVD-19 using data from British Columbia's post-COVID-19 Recovery Clinics. A retrospective cohort of 3463 patients was analyzed to assess HRQoL through the EQ-5D-5L questionnaire which includes five dimensions (mobility, self-care, usual activities, physical health, and mental health) administered to patients; responses were analyzed using the Visual Analogue Score (VAS). Notably, 95% of participants reported HRQoL scores below 90, with 50% scoring under 60, indicating significant impacts on their well-being. The analysis revealed that HRQoL is significantly influenced by various social determinants of health (SDoH), including age, sex, employment status, and ethnicity, each showing distinct correlations with HRQoL dimensions and overall VAS scores. Specifically, older age was associated with decreased mobility and increased pain/discomfort but less anxiety and depression, highlighting varying impacts across the age spectrum. The study highlights the multifaceted impacts of Long COVID on the lives of patients and underscores the necessity of targeted strategies to improve HRQoL among diverse groups, considering specific SDoH. Such a comprehensive approach could lead to more equitable health outcomes and support the development of tailored public health policies aimed at the recovery and rehabilitation of Long COVID sufferers.

A bstract Hyperparasites (species which parasitise other parasites) are common in natural populations, affecting many parasitic taxa, including: eukaryotic parasites; bacterial and fungal pathogens. Hyperparasitism is therefore likely to shape the ecology and evolution of many host-parasite systems, representing a promising method for biocontrol (e.g., treating antimicrobial resistant infections). However, the eco-evolutionary consequences of hyperparasitism have received little attention. We use a host-parasite-hyperparasite model to explore how introducing a hyperparasite drives the evolution of parasite virulence, and what impact this has on the host population. We show when the introduction of a hyperparasite selects for higher or lower parasite virulence, and the changes in virulence experienced by the host population. Crucially, we show that variation in the direct effects of hyperparasites on virulence and transmission, and the probability of co-transmission, can lead to a previously unseen hysteresis effect, whereby small shifts in hyperparasite characteristics can lead to sudden shifts in parasite virulence. We also show that hyperparasites can induce diversification in parasite virulence, leading to the coexistence of high and low virulence strains. Our results show hyperparasites can have dramatic effects on the evolution of parasite virulence, and that the use of hyperparasites in biocontrol should be approached with caution.

Rats are an important issue in cities globally. Despite their ubiquity, perceptions and concerns about rats vary with circumstance and the context in which a person interacts with them. Municipal rat management programs are a service to communities and therefore must be responsive to the varied concerns of their residents. Understanding why communities are concerned about rats can help inform rat management programs to meet the specific needs of their residents. The objective of this study was to identify why the residents of Vancouver, Canada care about rats and what they want done to address them. To do this, we qualitatively analyzed 6,158 resident complaints about rats made to the city's municipal government between January 2014 and May 2020. Using a qualitative descriptive coding process, we found that rats were a priority in a minority of cases. In general, people were more concerned about broader community issues, such as neighborhood disorder, of which rats were one part. Complaints tended to be made when problems were highly visible, nearby, and when the complainant wanted the city to take action to alleviate this issue, particularly when they were in and around their living spaces. The rates of complaints were highest in the most economically and socially deprived neighborhoods and lowest in the most privileged neighbourhoods. We synthesize this information with a view towards understanding how to develop objectives and actions for municipal management strategies that are grounded in community concerns.

This article describes a novel molecular method to show relatedness between bacterial infections, which may not be able to grow in the laboratory due to treatment with antibiotics or for bacteria requiring unique conditions to grow well. Uniquely, we applied this technique to Shigella isolates from human cases associated with a local cluster in an underserved community, as well as rat samples from the same community. We believe that this novel approach can serve as a complementary method to support outbreak/cluster investigation for Shigella spp.

Many coevolutionary processes, including host-parasite and host-symbiont interactions, involve one species or trait which evolves much faster than the other. Whether or not a coevolutionary trajectory converges depends on the relative rates of evolutionary change in the two species, and so current adaptive dynamics approaches generally either determine convergence stability by considering arbitrary (often comparable) rates of evolutionary change or else rely on necessary or sufficient conditions for convergence stability. We propose a method for determining convergence stability in the case where one species is expected to evolve much faster than the other. This requires a second separation of timescales, which assumes that the faster evolving species will reach its evolutionary equilibrium (if one exists) before a new mutation arises in the more slowly evolving species. This method, which is likely to be a reasonable approximation for many coevolving species, both provides straightforward conditions for convergence stability and is less computationally expensive than traditional analysis of coevolution models, as it reduces the trait space from a two-dimensional plane to a one-dimensional manifold. In this paper, we present the theory underlying this new separation of timescales and provide examples of how it could be used to determine coevolutionary outcomes from models.

Abstract Living in cities creates One Health challenges because urban environments can promote pathogen transmission in wildlife and human-wildlife interactions with commensal species such as rats. In this study, we examined social and ecological processes that lead to an elevated risk of leptospirosis, a fatal rat-associated disease transmitted through Leptospira interrogans bacteria in urine. We examined rat and human factors associated with (1) human exposure to rat urine in the home environment, (2) the presence of rats carrying L. interrogans on the block, and (3) environmental conditions associated with rat infection. We surveyed residents and trapped rats on the same 16 blocks in four neighbourhoods in Chicago. Survey respondents were more likely to observe rat urine in their homes if they had lower incomes. Blocks where rats were carrying L. interrogans had higher rat abundance and respondents with higher incomes, who reported dogs dying from leptospirosis, children playing in yards with rat waste, flooded yards, and gardens with rat burrows. Rats were more likely to be infected with L. interrogans if they were trapped on a block with more accessible garbage and if they were older. Our results highlight that rat presence alone does not determine the risk of close contact with rat-associated pathogens; socio-economics can affect an individual’s ability to exclude animals from living spaces. In addition, improved waste management may help mitigate disease risks for humans, wildlife, and domestic animals. We also discuss opportunities for public education about rat-associated zoonoses and lessons learned about meaningful community engagement in One Health work. Information © The Authors 2024

Mathematical models of infectious disease transmission typically neglect within-host dynamics. Yet within-host dynamics - including pathogen replication, host immune responses, and interactions with microbiota - are crucial not only for determining the progression of disease at the individual level, but also for driving within-host evolution and onwards transmission, and therefore shape dynamics at the population level. Various approaches have been proposed to model both within- and between-host dynamics, but these typically require considerable simplifying assumptions to couple processes at contrasting scales (e.g., the within-host dynamics quickly reach a steady state) or are computationally intensive. Here we propose a novel, readily adaptable and broadly applicable method for modelling both within- and between-host processes which can fully couple dynamics across scales and is both realistic and computationally efficient. By individually tracking the deterministic within-host dynamics of infected individuals, and stochastically coupling these to continuous host state variables at the population-level, we take advantage of fast numerical methods at both scales while still capturing individual transient within-host dynamics and stochasticity in transmission between hosts. Our approach closely agrees with full stochastic individual-based simulations and is especially useful when the within-host dynamics do not rapidly reach a steady state or over longer timescales to track pathogen evolution. By applying our method to different pathogen growth scenarios we show how common simplifying assumptions fundamentally change epidemiological and evolutionary dynamics.

Abstract Background Vaccine homophily describes non-heterogeneous vaccine uptake within contact networks. This study was performed to determine observable patterns of vaccine homophily, associations between vaccine homophily, self-reported vaccination, COVID-19 prevention behaviours, contact network size, and self-reported COVID-19, as well as the impact of vaccine homophily on disease transmission within and between vaccination groups under conditions of high and low vaccine efficacy. Methods Residents of British Columbia, Canada, aged ≥16 years, were recruited via online advertisements between February and March 2022, and provided information about vaccination status, perceived vaccination status of household and non-household contacts, compliance with COVID-19 prevention guidelines, and history of COVID-19. A deterministic mathematical model was used to assess transmission dynamics between vaccine status groups under conditions of high and low vaccine efficacy. Results Vaccine homophily was observed among the 1304 respondents, but was lower among those with fewer doses ( p &lt;0.0001). Unvaccinated individuals had larger contact networks ( p &lt;0.0001), were more likely to report prior COVID-19 ( p &lt;0.0001), and reported lower compliance with COVID-19 prevention guidelines ( p &lt;0.0001). Mathematical modelling showed that vaccine homophily plays a considerable role in epidemic growth under conditions of high and low vaccine efficacy. Further, vaccine homophily contributes to a high force of infection among unvaccinated individuals under conditions of high vaccine efficacy, as well as elevated force of infection from unvaccinated to vaccinated individuals under conditions of low vaccine efficacy. Interpretation The uneven uptake of COVID-19 vaccines and the nature of the contact network in the population play important roles in shaping COVID-19 transmission dynamics.

Defensive symbionts-organisms that confer protection to their hosts against natural enemies such as parasites, predators, or herbivores-are found throughout the natural world. Theoretical and empirical studies have shown that defensive symbionts can both interfere with ecological interactions between hosts and exploiters, as well as drive exploiter evolution. Defensive symbionts are also potential candidates for biocontrol agents to help manage infectious diseases or agricultural pests. The impact of defensive symbionts on parasite ecology and evolution has therefore recently received increased empirical and theoretical attention. In this theoretical study, we investigate the impact that a defensive symbiont which protects hosts from infection (conferred resistance) has on the evolution of parasite virulence. We also explore how the extent of protection conferred by the defensive symbiont coevolves with parasite virulence, and how symbiont and parasite evolution affect the ecology of the host population in both the short- and long-term. We show that, while costly resistance-conferring defensive symbionts always select for increased parasite virulence, the overall long-term ecological effect on the host population may still be positive due to reductions in disease prevalence. This contrasts with tolerance-conferring symbionts (which protect against virulence), where the long-term ecological effects on the host population are always negative. We also show when the defensive symbiont can successfully eliminate the parasite. Resistance-conferring defensive symbionts therefore offer more promise as evolutionarily robust biocontrols than those that only confer tolerance.

Hosts can evolve a variety of defences against parasitism, including resistance (which prevents or reduces the spread of infection) and tolerance (which protects against virulence). Some organisms have evolved different levels of tolerance at different life-stages, which is likely to be the result of coevolution with pathogens, and yet it is currently unclear how coevolution drives patterns of age-specific tolerance. Here, we use a model of tolerance-virulence coevolution to investigate how age structure influences coevolutionary dynamics. Specifically, we explore how coevolution unfolds when tolerance and virulence (disease-induced mortality) are age-specific compared to when these traits are uniform across the host lifespan. We find that coevolutionary cycling is relatively common when host tolerance is age-specific, but cycling does not occur when tolerance is the same across all ages. We also find that age-structured tolerance can lead to selection for higher virulence in shorter-lived than in longer-lived hosts, whereas non-age-structured tolerance always leads virulence to increase with host lifespan. Our findings therefore suggest that age structure can have substantial qualitative impacts on host-pathogen coevolution.

Abstract Diagnostic testing is a key tool in the fight against many infectious diseases. The emergence of pathogen variants that are able to avoid detection by diagnostic testing therefore represents a key challenge for public health. In recent years, variants for multiple pathogens have emerged which escape diagnostic testing, including mutations in Plasmodium falciparum (malaria), Chlamydia trachomatis (chlamydia) and SARS-Cov-2 (Severe acute respiratory syndrome coronavirus 2) (Coronavirus disease 2019). However, little is currently known about when and the extent to which diagnostic test escape will evolve. Here we use a mathematical model to explore how the frequency of diagnostic testing, combined with variation in compliance and efficacy of isolating, together drive the evolution of detection avoidance. We derive key thresholds under which a testing regime will (i) select for diagnostic test avoidance, or (ii) drive the pathogen extinct. Crucially, we show that imperfect compliance with diagnostic testing regimes can have marked effects on selection for detection avoidance, and consequently, for disease control. Yet somewhat counterintuitively, we find that an intermediate level of testing can select for the highest level of detection avoidance. Our results, combined with evidence from various pathogens, demonstrate that the evolution of diagnostic testing avoidance should be carefully considered when designing diagnostic testing regimes.

A bstract Many organisms experience an increase in disease resistance as they age but the time of life at which this change occurs varies. Increases in resistance are partially due to prior exposure and physiological constraints but these cannot fully explain the observed patterns of age-related resistance. An alternative explanation is that developing resistance at an earlier age incurs costs to other life-history traits. Here, we explore how trade-offs with host reproduction or mortality affect the evolution of the onset of resistance, depending on when during the host’s life-cycle the costs are paid (only when resistance is developing, only when resistant or throughout the lifetime). We find that the timing of the costs is crucial to determining evolutionary outcomes, often making the difference between resistance developing at an early or late age. Accurate modelling of biological systems therefore relies on knowing not only the shape of trade-offs but also when they take effect. We also find that the evolution of the rate of onset of resistance can result in evolutionary branching. This provides an alternative, possible evolutionary history of populations which are dimorphic in disease resistance, where the rate of onset of resistance has diversified rather than the level of resistance.

A bstract Hosts can evolve a variety of defences against parasitism, including resistance (which prevents or reduces the spread of infection) and tolerance (which protects against virulence). Some organisms have evolved different levels of tolerance at different life-stages, which is likely to be the result of coevolution with pathogens, and yet it is currently unclear how coevolution drives patterns of age-specific tolerance. Here, we use a model of tolerance-virulence coevolution to investigate how age structure influences coevolutionary dynamics. Specifically, we explore how coevolution unfolds when tolerance and virulence (disease-induced mortality) are age-specific compared to when these traits are uniform across the host lifespan. We find that coevolutionary cycling is relatively common when host tolerance is age-specific, but cycling does not occur when tolerance is the same across all ages. We also find that age-structured tolerance can lead to selection for higher virulence in shorter-lived than in longer-lived hosts, whereas non-age-structured tolerance always leads virulence to increase with host lifespan. Our findings therefore suggest that age structure can have substantial qualitative impacts on host-pathogen coevolution.