Directly transmitted viral diseases: modeling the dynamics of transmission

A key hurdle in understanding the spread and control of infectious diseases is to capture appropriately the dynamics of pathogen transmission. As people and goods travel increasingly rapidly around the world, so do pathogens; we must be prepared to understand their spread, in terms of the contact network between hosts, viral life history and within-host dynamics. This will require collaborative work that takes into account viral life history, strategy and evolution, and host genetics, demographics and immunodynamics. Mathematical models are a useful tool for integrating the data and analyses from diverse fields that contribute to our understanding of viral transmission dynamics in heterogeneous host populations.     

Vector-Borne Pathogen and Host Evolution in a Structured Immuno-Epidemiological System

Vector-borne disease transmission is a common dissemination mode used by many pathogens to spread in a host population. Similar to directly transmitted diseases, the within-host interaction of a vector-borne pathogen and a host’s immune system influences the pathogen’s transmission potential between hosts via vectors. Yet there are few theoretical studies on virulence–transmission trade-offs and evolution in vector-borne pathogen–host systems. Here, we consider an immuno-epidemiological model that links the within-host dynamics to between-host circulation of a vector-borne disease. On the immunological scale, the model mimics antibody-pathogen dynamics for arbovirus diseases, such as Rift Valley fever and West Nile virus. The within-host dynamics govern transmission and host mortality and recovery in an age-since-infection structured host-vector-borne pathogen epidemic model. By considering multiple pathogen strains and multiple competing host populations differing in their within-host replication rate and immune response parameters, respectively, we derive evolutionary optimization principles for both pathogen and host. Invasion analysis shows that the \({\mathcal {R}}_0\) maximization principle holds for the vector-borne pathogen. For the host, we prove that evolution favors minimizing case fatality ratio (CFR). These results are utilized to compute host and pathogen evolutionary trajectories and to determine how model parameters affect evolution outcomes. We find that increasing the vector inoculum size increases the pathogen \({\mathcal {R}}_0\), but can either increase or decrease the pathogen virulence (the host CFR), suggesting that vector inoculum size can contribute to virulence of vector-borne diseases in distinct ways.     

Pathogen persistence in the environment and insect-baculovirus interactions: disease-density thresholds, epidemic burnout, and insect outbreaks

Classical epidemic theory focuses on directly transmitted pathogens, but many pathogens are instead transmitted when hosts encounter infectious particles. Theory has shown that for such diseases pathogen persistence time in the environment can strongly affect disease dynamics, but estimates of persistence time, and consequently tests of the theory, are extremely rare. We consider the consequences of persistence time for the dynamics of the gypsy moth baculovirus, a pathogen transmitted when larvae consume foliage contaminated with particles released from infectious cadavers. Using field-transmission experiments, we are able to estimate persistence time under natural conditions, and inserting our estimates into a standard epidemic model suggests that epidemics are often terminated by a combination of pupation and burnout rather than by burnout alone, as predicted by theory. Extending our models to allow for multiple generations, and including environmental transmission over the winter, suggests that the virus may survive over the long term even in the absence of complex persistence mechanisms, such as environmental reservoirs or covert infections. Our work suggests that estimates of persistence times can lead to a deeper understanding of environmentally transmitted pathogens and illustrates the usefulness of experiments that are closely tied to mathematical models.     

The evolution of virulence in pathogens with frequency-dependent transmission

Frequency-dependent transmission is an important feature of diseases that are sexually transmitted or transmitted by a vector that actively searches for hosts. Here I describe the evolution of virulence in pathogens that have frequency-dependent transmission. I consider two components of virulence--an increase in host mortality due to infection, as is classically described, and a decrease in host fecundity due to infection, because frequency dependence is common among diseases that fully or partially sterilize their hosts. Theoretical predictions pertaining to host-pathogen numerical dynamics can be quite different between pathogens with frequency-dependent transmission and those with density-dependent transmission. In contrast, this study suggests that the principles governing the evolution of virulence that have been established in the context of density-dependent pathogens may also apply (qualitatively) to frequency-dependent pathogens. I examine the evolutionary trajectories of the mortality and sterility components of virulence as well as the role of spatial population structure in the evolution of the sterility component of virulence.     

Horizontal and vertical transmission of viruses in the honey bee, Apis mellifera

The most crucial stage in the dynamics of virus infections is the mode of virus transmission. In general, transmission of viruses can occur through two pathways: horizontal and vertical transmission. In horizontal transmission, viruses are transmitted among individuals of the same generation, while vertical transmission occurs from mothers to their offspring. Because of its highly organized social structure and crowded population density, the honey bee colony represents a risky environment for the spread of disease infection. Like other plant and animal viruses, bee viruses use different survival strategies, including utilization of both horizontal and vertical routes, to transmit and maintain levels in a host population. In this review, we explore the current knowledge about the honey bee viruses and transmission routes of bee viruses. In addition, different transmission strategies on the persistence and dynamics of host-pathogen interactions are also discussed.     

Identifying the age cohort responsible for transmission in a natural outbreak of Bordetella bronchiseptica

Identifying the major routes of disease transmission and reservoirs of infection are needed to increase our understanding of disease dynamics and improve disease control. Despite this, transmission events are rarely observed directly. Here we had the unique opportunity to study natural transmission of Bordetella bronchiseptica--a directly transmitted respiratory pathogen with a wide mammalian host range, including sporadic infection of humans--within a commercial rabbitry to evaluate the relative effects of sex and age on the transmission dynamics therein. We did this by developing an a priori set of hypotheses outlining how natural B. bronchiseptica infections may be transmitted between rabbits. We discriminated between these hypotheses by using force-of-infection estimates coupled with random effects binomial regression analysis of B. bronchiseptica age-prevalence data from within our rabbit population. Force-of-infection analysis allowed us to quantify the apparent prevalence of B. bronchiseptica while correcting for age structure. To determine whether transmission is largely within social groups (in this case litter), or from an external group, we used random-effect binomial regression to evaluate the importance of social mixing in disease spread. Between these two approaches our results support young weanlings--as opposed to, for example, breeder or maternal cohorts--as the age cohort primarily responsible for B. bronchiseptica transmission. Thus age-prevalence data, which is relatively easy to gather in clinical or agricultural settings, can be used to evaluate contact patterns and infer the likely age-cohort responsible for transmission of directly transmitted infections. These insights shed light on the dynamics of disease spread and allow an assessment to be made of the best methods for effective long-term disease control.     

Allocation to sexual versus nonsexual disease transmission

Many diseases have both sexual and nonsexual transmission routes, and closely related diseases often differ in their degree of sexual transmission. We investigate the evolution of transmission mode as a function of host social and mating structure using a model in which disease transmission is explicitly dependent on the numbers of sexual and nonsexual contacts (which are themselves a function of population density) and per-contact infection probabilities. Most generally, and in the absence of trade-offs between the degree of sexual transmission and effects on host fecundity and mortality, nonsexual transmission is favored above the social-sexual crossover point (the host density at which the number of nonsexual contacts exceeds the number of sexual contacts), while sexual transmission is favored below this point. When changes in allocation to the two transmission modes are accompanied by changes in mortality or fecundity, both mixed and pure transmission strategies can be favored. If invading genotypes differ substantially from resident genotypes, genetic polymorphism in transmission mode is possible. The evolutionary outcomes are predictable from a knowledge of the equilibrium population sizes in relation to the social-sexual crossover point. Our results also show that predictions about dynamic outcomes, based on rates of invasion for single pathogens into healthy populations, do not adequately describe the resulting disease prevalence nor predict the subsequent evolutionary dynamics; once invasion of a pathogen has occurred, the conditions for spread of a second pathogen are themselves altered. If the host is considered as a single resource, our results show that two pathogens may coexist on a single resource if they use that resource differentially and have differential feedbacks on resource abundance; such resource feedback effects may be present in other biological systems.     

On the evolutionary dynamics of pathogens with direct and environmental transmission

A number of ecologically and economically important pathogens exhibit a complex transmission dynamics that involves distinct transmission modes. In this paper, we study the evolutionary dynamics of pathogens for which transmission includes direct host-to-host as well as indirect environmental transmission. Different routes of infection spread require specific adaptations of the parasite, which may result in conflicting selection pressures. Using the framework of Adaptive dynamics, we investigate how these conflicting selection pressures are resolved in the course of evolution and determine the conditions for evolutionary diversification of pathogen strains. We show that evolutionary branching and subsequent evolution of specialist strains occurs in wide parameter regions but evolutionary bistability and evolution of generalist pathogens are possible as well. Our analysis reveals that the relative contributions of direct and environmental transmission, as well as the underlying ecological dynamics, play a crucial role in shaping the course of pathogen evolution. Our findings may explain the coexistence of high and low virulence strains observed in several pathogenic organisms using different transmission modes (e.g., influenza viruses) and highlight the importance of considering ecological dynamics in virulence management.     

Virulence and community dynamics of fungal species with vertical and horizontal transmission on a plant with multiple infections

The virulence evolution of multiple infections of parasites from the same species has been modeled widely in evolution theory. However, experimental studies on this topic remain scarce, particularly regarding multiple infections by different parasite species. Here, we characterized the virulence and community dynamics of fungal pathogens on the invasive plant Ageratina adenophora to verify the predictions made by the model. We observed that A. adenophora was highly susceptible to diverse foliar pathogens with mixed vertical and horizontal transmission within leaf spots. The transmission mode mainly determined the pathogen community structure at the leaf spot level. Over time, the pathogen community within a leaf spot showed decreased Shannon diversity; moreover, the vertically transmitted pathogens exhibited decreased virulence to the host A. adenophora, but the horizontally transmitted pathogens exhibited increased virulence to the host. Our results demonstrate that the predictions of classical models for the virulence evolution of multiple infections are still valid in a complex realistic environment and highlight the impact of transmission mode on disease epidemics of foliar fungal pathogens. We also propose that seedborne fungi play an important role in structuring the foliar pathogen community from multiple infections within a leaf spot.     

The dynamics of sexual contact networks: effects on disease spread and control

Sexually transmitted pathogens persist in populations despite the availability of biomedical interventions and knowledge of behavioural changes that would reduce individual-level risk. While behavioural risk factors are shared between many sexually transmitted infections, the prevalence of these diseases across different risk groups varies. Understanding this heterogeneity and identifying better control strategies depends on an improved understanding of the complex social contact networks over which pathogens spread. To date, most efforts to study the impact of sexual network structure on disease dynamics have focused on static networks. However, the interaction between the dynamics of partnership formation and dissolution and the dynamics of transmission plays a role, both in restricting the effective network accessible to the pathogen, and in modulating the transmission dynamics. We present a simple method to simulate dynamical networks of sexual partnerships. We inform the model using survey data on sexual attitudes and lifestyles, and investigate how the duration of infectiousness changes the effective contact network over which disease may spread. We then simulate several control strategies: screening, vaccination and behavioural interventions. Previous theory and research has advanced the importance of core groups for spread and control of STD. Our work is consistent with the importance of core groups, but extends this idea to consider how the duration of infectiousness associated with a particular pathogen interacts with host behaviours to define these high risk subpopulations. Characteristics of the parts of the network accessible to the pathogen, which represent the network structure of sexual contacts from the “point of view” of the pathogen, are substantially different from those of the network as a whole. The pathogen itself plays an important role in determining this effective network structure; specifically, we find that if the pathogen’s duration of infectiousness is short, infection is more concentrated in high-activity, high-concurrency individuals even when all other factors are held constant. Widespread screening programmes would be enhanced by follow-up interventions targeting higher-risk individuals, because screening shortens the expected duration of infectiousness and causes a greater relative decrease in prevalence among lower-activity than in higher-activity individuals. Even for pathogens with longer durations of infectiousness, our findings suggest that targeting vaccination and behavioural interventions towards high-activity individuals provides comparable benefits to population-wide interventions.     

Emerging zoonotic diseases originating in mammals: a systematic review of effects of anthropogenic land-use change

1. Zoonotic pathogens and parasites that are transmitted from vertebrates to humans are a major public health risk with high associated global economic costs. The spread of these pathogens and risk of transmission accelerate with recent anthropogenic land-use changes (LUC) such as deforestation, urbanisation, and agricultural intensification, factors that are expected to increase in the future due to human population expansion and increasing demand for resources.
2. We systematically review the literature on anthropogenic LUC and zoonotic diseases, highlighting the most prominent mammalian reservoirs and pathogens, and identifying avenues for future research.
3. The majority of studies were global reviews that did not focus on specific taxa. South America and Asia were the most-studied regions, while the most-studied LUC was urbanisation. Livestock were studied more within the context of agricultural intensification, carnivores with urbanisation and helminths, bats with deforestation and viruses, and primates with habitat fragmentation and protozoa.
4. Research into specific animal reservoirs has improved our understanding of how the spread of zoonotic diseases is affected by LUC. The behaviour of hosts can be altered when their habitats are changed, impacting the pathogens they carry and the probability of disease spreading to humans. Understanding this has enabled the identification of factors that alter the risk of emergence (such as virulence, pathogen diversity, and ease of transmission). Yet, many pathogens and impacts of LUC other than urbanisation have been understudied.
5. Predicting how zoonotic diseases emerge and spread in response to anthropogenic LUC requires more empirical and data synthesis studies that link host ecology and responses with pathogen ecology and disease spread. The link between anthropogenic impacts on the natural environment and the recent COVID-19 pandemic highlights the urgent need to understand how anthropogenic LUC affects the risk of spillover to humans and spread of zoonotic diseases originating in mammals.

     

Disease transmission by cannibalism: rare event or common occurrence?

Cannibalism has been documented as a possible disease transmission route in several species, including humans. However, the dynamics resulting from this type of disease transmission are not well understood. Using a theoretical model, we explore how cannibalism (i.e. killing and consumption of dead conspecifics) and intraspecific necrophagy (i.e. consumption of dead conspecifics) affect host-pathogen dynamics. We show that group cannibalism, i.e. shared consumption of victims, is a necessary condition for disease spread by cannibalism in the absence of alternative transmission modes. Thus, endemic diseases transmitted predominantly by cannibalism are likely to be rare, except in social organisms that share conspecific prey. These results are consistent with a review of the literature showing that diseases transmitted by cannibalism are infrequent in animals, even though both cannibalism and trophic transmission are very common.     

The role of international transport of equine semen on disease transmission.

Despite the numerous benefits of having the capability to transport semen internationally, there are serious potential ramifications if that semen is contaminated with a communicable disease. BACTERIA: Many commensal bacteria colonize the exterior of the stallion penis and are not regarded as pathogenic. They may be cultured from an ejaculate. Alterations of the normal bacterial flora on the exterior genitalia may cause the growth of opportunistic bacteria such as Klebsiella pneumonia, Pseudomonas aeruginosa, Streptococcus zooepidemicus, which, if inseminated, may cause infertility in susceptible mares. Contagious equine metritis (CEM), a highly transmissible, true venereal disease of horses, is caused by the gram-negative coccobacillis, Taylorella equigenitalis. Even with the use of rigorous testing protocols, the current techniques used may not ensure accuracy of results. VIRUSES: Equine coital exanthema (equine herpes virus type 3; EHV-3) is a highly contagious virus that causes painful lesions on the stallion's penis and mare's vulva. Although it is primarily transmitted through coitus, infected fomites have also been implicated in its spread. Therefore, it is possible that the virus can potentially be transmitted to the ejaculate through penile contact with an artificial vagina or sleeve. Equine arteritis virus appears to be becoming more prevalent in recent years. The most common method of transmission is through respiratory disease, but the organism can also be shed in the semen of asymptomatic stallions. Equine infectious anemia virus has also been found to be present in the semen of an infected stallion, although no evidence exists at this time that there is venereal transmission of this disease. PROTOZOA: Dourine, caused by Trympanosoma equiperidum, is a venereal disease found only in Africa, South and Central America and the Middle East. Serological testing using complement fixation is recommended for diagnosis. Piroplasmosis, a disease caused by Babesia equi or by a less severe strain, Babesia caballi, has received a great deal of attention in recent years due to the increased transfer of horses between countries. It is considered to be enzootic in many areas of the southern US, and is found throughout the world. The protozoal agent is most often spread by ticks, but mechanical transmission has also been documented; therefore, there is concern for venereal transmission if blood from an infected horse contaminates the semen.     

Modelling interference between vectors of non-persistently transmitted plant viruses to identify effective control strategies

Aphids are the primary vector of plant viruses. Transient aphids, which probe several plants per day, are considered to be the principal vectors of non-persistently transmitted (NPT) viruses. However, resident aphids, which can complete their life cycle on a single host and are affected by agronomic practices, can transmit NPT viruses as well. Moreover, they can interfere both directly and indirectly with transient aphids, eventually shaping plant disease dynamics. By means of an epidemiological model, originally accounting for ecological principles and agronomic practices, we explore the consequences of fertilization and irrigation, pesticide deployment and roguing of infected plants on the spread of viral diseases in crops. Our results indicate that the spread of NPT viruses can be i) both reduced or increased by fertilization and irrigation, depending on whether the interference is direct or indirect; ii) counter-intuitively increased by pesticide application and iii) reduced by roguing infected plants. We show that a better understanding of vectors’ interactions would enhance our understanding of disease transmission, supporting the development of disease management strategies.     

Spatial Structure,Transmission Modes and the Evolution of Viral Exploitation Strategies

Spatial structure and local migration are predicted to promote the evolution of less aggressive host exploitation strategies in horizontally transmitted pathogens. Here we explore the effect of spatial structure on the evolution of pathogens that can use both horizontal and vertical routes of transmission. First, we analyse theoretically how vertical transmission can alter evolutionary trajectories and confirm that space can impede the spread of virulent pathogens. Second, we test this prediction using the latent phage λ which transmits horizontally and vertically in Escherichia coli populations. We show that the latent phage λ wins competition against the virulent mutant λcI857 in spatially structured epidemics, but loses when spatial structure is eroded. The vertical transmission of phage λ immunizes its local host pool against superinfection and prevents the spread of the virulent λcI857. This effect breaks down when mixing facilitates horizontal transmission to uninfected hosts. We thus confirm the importance of spatial structure for the evolutionary maintenance of prudent infection strategies in latent viruses.     

Multiple guests in a single host: interactions across symbiotic and phytopathogenic bacteria in phloem‐feeding vectors – a review

Some pathogenic phloem‐limited bacteria are a major threat for worldwide agriculture due to the heavy economic losses caused to many high‐value crops. These disease agents – phytoplasmas, spiroplasmas, liberibacters, and Arsenophonus‐like bacteria – are transmitted from plant to plant by phloem‐feeding Hemiptera vectors. The associations established among pathogens and vectors result in a complex network of interactions involving also the whole microbial community harboured by the insect host. Interactions among bacteria may be beneficial, competitive, or detrimental for the involved microorganisms, and can dramatically affect the insect vector competence and consequently the spread of diseases. Interference is observed among pathogen strains competing to invade the same vector specimen, causing selective acquisition or transmission. Insect bacterial endosymbionts are another pivotal element of interactions between vectors and phytopathogens, because of their central role in insect life cycles. Some symbionts, either obligate or facultative, were shown to have antagonistic effects on the colonization by plant pathogens, by producing antimicrobial substances, by stimulating the production of antimicrobial substances by insects, or by competing for host infection. In other cases, the mutual exclusion between symbiont and pathogen suggests a possible detrimental influence on phytopathogens displayed by symbiotic bacteria; conversely, examples of microbes enhancing pathogen load are available as well. Whether and how bacterial exchanges occurring in vectors affect the relationship between insects, plants, and phytopathogens is still unresolved, leaving room for many open questions concerning the significance of particular traits of these multitrophic interactions. Such complex interplays may have a serious impact on pathogen spread and control, potentially driving new strategies for the containment of important diseases.     

Virulence and transmission modes in metapopulations: when group selection increases virulence

Individuals that are infected by a pathogen can transmit it to unrelated conspecifics (horizontal transmission) or to their progeny when they reproduce (vertical transmission). The mechanisms of these two routes of transmission are different and this difference impacts the way virulence evolves in pathogens. More precisely, horizontal transmission depends on the probability that an infected host contacts susceptible conspecifics, and therefore on its lifespan. Vertical transmission additionally depends on the host's fecundity. This additional dependence in vertically transmitted pathogens results in a decrease in their evolutionarily stable (ES) virulence.Spatial structure is another factor that is often supposed to decrease pathogens’ ES virulence, mostly because it impedes competition for transmission in local populations of hosts. In this paper, using the adaptive dynamics framework, we show that spatial structure can increase ES virulence when pathogens are mostly vertically transmitted. This is due to the difference in how pathogens compete for transmission in local population of hosts, depending on how they are transmitted. We also show that symbionts that are horizontally transmitted should respond more to a change in spatial structure than symbionts that are vertically transmitted.     

Model analysis for plant disease dynamics co-mediated by herbivory and herbivore-borne phytopathogens

Plants are subject to diseases caused by pathogens, many of which are transmitted by herbivorous arthropod vectors. To understand plant disease dynamics, we studied a minimum hybrid model combining consumer-resource (herbivore-plant) and susceptible-infected models, in which the disease is transmitted bi-directionally between the consumer and the resource from the infected to susceptible classes. Model analysis showed that: (i) the disease is more likely to persist when the herbivore feeds on the susceptible plants rather than the infected plants, and (ii) alternative stable states can exist in which the system converges to either a disease-free or an endemic state, depending on the initial conditions. The second finding is particularly important because it suggests that the disease may persist once established, even though the initial prevalence is low (i.e. the R(0) rule does not always hold). This situation is likely to occur when the infection improves the plant nutritive quality, and the herbivore preferentially feeds on the infected resource (i.e. indirect vector-pathogen mutualism). Our results highlight the importance of the eco-epidemiological perspective that integration of tripartite interactions among host plant, plant pathogen and herbivore vector is crucial for the successful control of plant diseases.     

Evolution of virulence in heterogeneous host communities under multiple trade-offs

Many pathogens and parasites are transmitted through hosts that differ in species, sex, genotype, or immune status. In addition, virulence (here defined as disease-induced mortality) and transmission can vary during the infectious period within hosts of different state. Most models of virulence evolution assume that transmission and virulence are constant over the infectious period and that the host population is homogenous. Here, we examine a multispecies susceptible-infected-recovered (SIR) model where transmission occurs within and between species, and transmission and virulence varied during the infectious period. This allows us to understand virulence evolution in a broader range of situations that characterize many emerging diseases. Because emerging pathogens are by definition new to their host populations, they should be expected to rapidly adapt after emergence. We illustrate these evolutionary effects using the framework of adaptive dynamics to examine how virulence evolves after emergence in response to the relative strength of selection on pathogen fitness and mutational variance for virulence. We illustrate the role of evolution by simulating adaptive walks to an evolutionarily stable virulence. We found that the magnitude of between-species transmission and the relative timing of transmission and mortality across species were of primary importance for determining the evolutionarily stable virulence.