skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: Spreading processes with mutations over multilayer networks
A key scientific challenge during the outbreak of novel infectious diseases is to predict how the course of the epidemic changes under countermeasures that limit interaction in the population. Most epidemiological models do not consider the role of mutations and heterogeneity in the type of contact events. However, pathogens have the capacity to mutate in response to changing environments, especially caused by the increase in population immunity to existing strains, and the emergence of new pathogen strains poses a continued threat to public health. Further, in the light of differing transmission risks in different congregate settings (e.g., schools and offices), different mitigation strategies may need to be adopted to control the spread of infection. We analyze a multilayer multistrain model by simultaneously accounting for i) pathways for mutations in the pathogen leading to the emergence of new pathogen strains, and ii) differing transmission risks in different settings, modeled as network layers. Assuming complete cross-immunity among strains, namely, recovery from any infection prevents infection with any other (an assumption that will need to be relaxed to deal with COVID-19 or influenza), we derive the key epidemiological parameters for the multilayer multistrain framework. We demonstrate that reductions to existing models that discount heterogeneity in either the strain or the network layers may lead to incorrect predictions. Our results highlight that the impact of imposing/lifting mitigation measures concerning different contact network layers (e.g., school closures or work-from-home policies) should be evaluated in connection with their effect on the likelihood of the emergence of new strains.  more » « less
Award ID(s):
2225513 1813637 1917819
PAR ID:
10467314
Author(s) / Creator(s):
; ; ; ; ; ;
Publisher / Repository:
Proceedings of the National Academy of Sciences
Date Published:
Journal Name:
Proceedings of the National Academy of Sciences
Volume:
120
Issue:
24
ISSN:
0027-8424
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Wallqvist, Anders (Ed.)
    The SARS-CoV-2 pandemic has generated a considerable number of infections and associated morbidity and mortality across the world. Recovery from these infections, combined with the onset of large-scale vaccination, have led to rapidly-changing population-level immunological landscapes. In turn, these complexities have highlighted a number of important unknowns related to the breadth and strength of immunity following recovery or vaccination. Using simple mathematical models, we investigate the medium-term impacts of waning immunity against severe disease on immuno-epidemiological dynamics. We find that uncertainties in the duration of severity-blocking immunity (imparted by either infection or vaccination) can lead to a large range of medium-term population-level outcomes (i.e. infection characteristics and immune landscapes). Furthermore, we show that epidemiological dynamics are sensitive to the strength and duration of underlying host immune responses; this implies that determining infection levels from hospitalizations requires accurate estimates of these immune parameters. More durable vaccines both reduce these uncertainties and alleviate the burden of SARS-CoV-2 in pessimistic outcomes. However, heterogeneity in vaccine uptake drastically changes immune landscapes toward larger fractions of individuals with waned severity-blocking immunity. In particular, if hesitancy is substantial, more robust vaccines have almost no effects on population-level immuno-epidemiology, even if vaccination rates are compensatorily high among vaccine-adopters. This pessimistic scenario for vaccination heterogeneity arises because those few individuals that are vaccine-adopters are so readily re-vaccinated that the duration of vaccinal immunity has no appreciable consequences on their immune status. Furthermore, we find that this effect is heightened if vaccine-hesitants have increased transmissibility (e.g. due to riskier behavior). Overall, our results illustrate the necessity to characterize both transmission-blocking and severity-blocking immune time scales. Our findings also underline the importance of developing robust next-generation vaccines with equitable mass vaccine deployment. 
    more » « less
  2. The multiple immunity responses exhibited in the population and co-circulating variants documented during pandemics show a high potential to generate diverse long-term epidemiological scenarios. Transmission variability, immune uncertainties and human behaviour are crucial features for the predictability and implementation of effective mitigation strategies. Nonetheless, the effects of individual health incentives on disease dynamics are not well understood. We use a behavioural-immuno-epidemiological model to study the joint evolution of human behaviour and epidemic dynamics for different immunity scenarios. Our results reveal a trade-off between the individuals’ immunity levels and the behavioural responses produced. We find that adaptive human behaviour can avoid dynamical resonance by avoiding large outbreaks, producing subsequent uniform outbreaks. Our forward-looking behaviour model shows an optimal planning horizon that minimizes the epidemic burden by balancing the individual risk–benefit trade-off. We find that adaptive human behaviour can compensate for differential immunity levels, equalizing the epidemic dynamics for scenarios with diverse underlying immunity landscapes. Our model can adequately capture complex empirical behavioural dynamics observed during pandemics. We tested our model for different US states during the COVID-19 pandemic. Finally, we explored extensions of our modelling framework that incorporate the effects of lockdowns, the emergence of a novel variant, prosocial attitudes and pandemic fatigue. 
    more » « less
  3. Abstract Pathogen spillover corresponds to the transmission of a pathogen or parasite from an original host species to a novel host species, preluding disease emergence. Understanding the interacting factors that lead to pathogen transmission in a zoonotic cycle could help identify novel hosts of pathogens and the patterns that lead to disease emergence. We hypothesize that ecological and biogeographic factors drive host encounters, infection susceptibility, and cross‐species spillover transmission. Using a rodent–ectoparasite system in the Neotropics, with shared ectoparasite associations as a proxy for ecological interaction between rodent species, we assessed relationships between rodents using geographic range, phylogenetic relatedness, and ectoparasite associations to determine the roles of generalist and specialist hosts in the transmission cycle of hantavirus. A total of 50 rodent species were ranked on their centrality in a network model based on ectoparasites sharing. Geographic proximity and phylogenetic relatedness were predictors for rodents to share ectoparasite species and were associated with shorter network path distance between rodents through shared ectoparasites. The rodent–ectoparasite network model successfully predicted independent data of seven known hantavirus hosts. The model predicted five novel rodent species as potential, unrecognized hantavirus hosts in South America. Findings suggest that ectoparasite data, geographic range, and phylogenetic relatedness of wildlife species could help predict novel hosts susceptible to infection and possible transmission of zoonotic pathogens. Hantavirus is a high‐consequence zoonotic pathogen with documented animal‐to‐animal, animal‐to‐human, and human‐to‐human transmission. Predictions of new rodent hosts can guide active epidemiological surveillance in specific areas and wildlife species to mitigate hantavirus spillover transmission risk from rodents to humans. This study supports the idea that ectoparasite relationships among rodents are a proxy of host species interactions and can inform transmission cycles of diverse pathogens circulating in wildlife disease systems, including wildlife viruses with epidemic potential, such as hantavirus. 
    more » « less
  4. Abstract The immune system is the primary barrier to parasite infection, replication, and transmission following exposure, and variation in immunity can accordingly manifest in heterogeneity in traits that govern population-level infectious disease dynamics. While much work in ecoimmunology has focused on individual-level determinants of host immune defense (e.g., reproductive status and body condition), an ongoing challenge remains to understand the broader evolutionary and ecological contexts of this variation (e.g., phylogenetic relatedness and landscape heterogeneity) and to connect these differences into epidemiological frameworks. Ultimately, such efforts could illuminate general principles about the drivers of host defense and improve predictions and control of infectious disease. Here, we highlight recent work that synthesizes the complex drivers of immunological variation across biological scales of organization and scales these within-host differences to population-level infection outcomes. Such studies note the limitations involved in making species-level comparisons of immune phenotypes, stress the importance of spatial scale for immunology research, showcase several statistical tools for translating within-host data into epidemiological parameters, and provide theoretical frameworks for linking within- and between-host scales of infection processes. Building from these studies, we highlight several promising avenues for continued work, including the application of machine learning tools and phylogenetically controlled meta-analyses to immunology data and quantifying the joint spatial and temporal dependencies in immune defense using range expansions as model systems. We also emphasize the use of organismal traits (e.g., host tolerance, competence, and resistance) as a way to interlink various scales of analysis. Such continued collaboration and disciplinary cross-talk among ecoimmunology, disease ecology, and mathematical modeling will facilitate an improved understanding of the multi-scale drivers and consequences of variation in host defense. 
    more » « less
  5. Close contacts between individuals provide opportunities for the transmission of diseases, including COVID-19. While individuals take part in many different types of interactions, including those with classmates, co-workers and household members, it is the conglomeration of all of these interactions that produces the complex social contact network interconnecting individuals across the population. Thus, while an individual might decide their own risk tolerance in response to a threat of infection, the consequences of such decisions are rarely so confined, propagating far beyond any one person. We assess the effect of different population-level risk-tolerance regimes, population structure in the form of age and household-size distributions, and different interaction types on epidemic spread in plausible human contact networks to gain insight into how contact network structure affects pathogen spread through a population. In particular, we find that behavioural changes by vulnerable individuals in isolation are insufficient to reduce those individuals’ infection risk and that population structure can have varied and counteracting effects on epidemic outcomes. The relative impact of each interaction type was contingent on assumptions underlying contact network construction, stressing the importance of empirical validation. Taken together, these results promote a nuanced understanding of disease spread on contact networks, with implications for public health strategies. 
    more » « less