Interactions between zoonotic pathogens and infectious disease spread: Why understanding mechanisms and modelling matters more than ever

Even though extreme containment and mitigation strategies were implemented by numerous governments around the world to slow down the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the number of critically ill patients and fatalities keeps rising. This crisis has highlighted the socioeconomic disparities of health care systems within and among countries. As new CoVID policies and responses are implemented to lessen the impact of the virus, it is imperative (1) to consider additional mitigation strategies critical for the development of effective countermeasures, (2) to promote long-term policies and strict regulations of the trade of wildlife and live animal markets, and (3) to advocate for necessary funding and investments in global health, specifically for the prevention of and response to natural and manmade pandemics. This document considers some of these challenges.

The emergence and spread of infectious diseases with pandemic potential occurred regularly throughout history. Major pandemics and epidemics such as plague, cholera, flu, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have already afflicted humanity. The world is now facing the new coronavirus disease 2019 (COVID-19) pandemic. Many infectious diseases leading to pandemics are caused by zoonotic pathogens that were transmitted to humans due to increased contacts with animals through breeding, hunting and global trade activities. The understanding of the mechanisms of transmission of pathogens to humans allowed the establishment of methods to prevent and control infections. During centuries, implementation of public health measures such as isolation, quarantine and border control helped to contain the spread of infectious diseases and maintain the structure of the society. In the absence of pharmaceutical interventions, these containment methods have still been used nowadays to control COVID-19 pandemic. Global surveillance programs of water-borne pathogens, vector-borne diseases and zoonotic spillovers at the animal-human interface are of prime importance to rapidly detect the emergence of infectious threats. Novel technologies for rapid diagnostic testing, contact tracing, drug repurposing, biomarkers of disease severity as well as new platforms for the development and production of vaccines are needed for an effective response in case of pandemics.

Syndemics, the adverse interaction of two or more coterminous diseases or other negative health conditions, have probably existed since human settlement, plant and animal domestication, urbanization, and the growth of social inequality beginning about 10-12,000 years ago. These dramatic changes in human social evolution significantly increased opportunities for the spread of zoonotic infectious diseases in denser human communities with increased sanitation challenges. In light of a growing body of research that indicates that anthropogenic air pollution causes numerous threats to health and is taking a far greater toll on human life and wellbeing than had been reported, this paper proposes the possibility that air pollution is now the primary driver of infectious disease syndemics. In support of this assertion, this paper reviews the growth and health impacts of air pollution, the relationship of air pollution to the development and spread of infectious diseases, and reported cases of air pollution-driven infectious disease syndemics, and presents public health recommendations for leveraging the biosocial insight of syndemic theory in responding to infectious disease.

Space matters: host spatial structure and the dynamics of plague transmission

AimWe present a mechanistic niche model that integrates the demography of competing plant species in a metabolic, stochastic framework. In order to explore the model's ability to generate multiple species and community patterns, we assessed trait composition, richness gradients and spatial distributions of species ranges and abundances of simulated communities.LocationHypothetical, sloped plane.MethodsStage‐structured populations of species differing in traits and habitat requirements competed for space in a grid‐based model. Demographic processes (recruitment, reproduction, mortality, dispersal) and resource competition were explicitly simulated. Demographic rates and carrying capacity followed metabolic constraints. We simulated 50 species pools until reaching stable communities. Species pools were initialized with 400 species that had random traits and habitat requirements. The habitat requirements generated potential distributions of richness, range and abundance, whereas the simulations yielded realized distributions.ResultsThe communities assembled in the simulations consisted of species spread non‐randomly within trait space. Potential species richness peaked at mid‐elevations, whereas realized richness was slightly shifted towards higher elevations. For 11% of all species, the highest local abundances were found not in the most suitable habitat, but in suboptimal conditions. 53% of all species could not fill the climatically determined potential range. The ability to fill the potential range was significantly influenced by species traits (e.g. body mass and Allee effects) and species richness.Main conclusionsSpatial and trait properties of surviving species and of equilibrium communities diverged from the potential distributions. Realized richness gradients were consistent both with patterns observed in nature and those expected from null models based on geometrical constraints. However, the divergences between potential and realized patterns of richness, ranges and abundances indicate the importance of demography and biotic interaction for generating patterns at species and community levels. Consequently, bias in correlative habitat models and single‐species mechanistic models may arise if competition and demography are neglected. Additionally, competitive exclusion provides a mechanistic explanation for the low transferability of single‐species niche models. These results confirm the usefulness of mechanistic niche models for guiding further research integrating ecological niche, community ecology and biogeography.

We study the impact of non-pharmaceutical policy interventions (NPIs) like “stay-at-home” orders on the spread of infectious disease. Local policies have little impact on the economy nor on local public health. Stay-at-home is only weakly associated with slower growth of Covid-19 cases. Reductions in observed “mobility” are not associated with slower growth of Covid-19 cases. Stay-at-home is associated with lower workplace and more residential activity, but common shocks matter much more. Moreover, job losses have been no higher in US states that implemented stay-at-home during the Covid-19 pandemic than in states that did not have stay-at-home. All of these results demonstrate that the Covid-19 pandemic is a common economic and public health shock. They also show that policy spillovers and behavioral responses are important. The tradeoff between the economy and public health in a pandemic depends strongly on what is happening elsewhere. This underscores the importance of coordinated economic and public health responses.

Multistable switches are ubiquitous building blocks in both systems and synthetic biology. Given their central role, it is thus imperative to understand how their fundamental properties depend not only on the tunable biophysical properties of the switches themselves, but also on their genetic context. To this end, we reveal in this article how these factors shape the essential characteristics of toggle switches implemented using leaky promoters such as their stability and robustness to noise, both at single-cell and population levels. In particular, our results expose the roles that competition for scarce transcriptional and translational resources, promoter leakiness, and cell-to-cell heterogeneity collectively play. For instance, the interplay between protein expression from leaky promoters and the associated cost of relying on shared cellular resources can give rise to tristable dynamics even in the absence of positive feedback. Similarly, we demonstrate that while promoter leakiness always acts against multistability, resource competition can be leveraged to counteract this undesirable phenomenon. Underpinned by a mechanistic model, our results thus enable the context-aware rational design of multistable genetic switches that are directly translatable to experimental considerations, and can be further leveraged during the synthesis of large-scale genetic systems using computer-aided biodesign automation platforms.

Advancing therapies for viral infections using mechanistic computational models of the dynamic interplay between the virus and host immune response

Dynamic and integrative approaches to understanding pathogen spillover.

Wild birds are important in the maintenance and transmission of many zoonotic pathogens. With increasing urbanization and the resulting emergence of zoonotic diseases, it is critical to understand the relationships among birds, vectors, zoonotic pathogens, and the urban landscape. Here, we use wild birds as sentinels across a gradient of urbanization to understand the relative risk of diseases caused by three types of zoonotic pathogens: Salmonella pathogens, mosquito-borne West Nile virus (WNV) and tick-borne pathogens, including the agents of Lyme disease and human anaplasmosis. Wild birds were captured using mist nets at five sites throughout greater Chicago, Illinois, and blood, faecal and ectoparasite samples were collected for diagnostic testing. A total of 289 birds were captured across all sites. A total of 2.8% of birds harboured Ixodes scapularis--the blacklegged tick--of which 54.5% were infected with the agent of Lyme disease, and none were infected with the agent of human anaplasmosis. All infested birds were from a single site that was relatively less urban. A single bird, captured at the only field site in which supplemental bird feeding was practised within the mist netting zone, was infected with Salmonella enterica subspecies enterica. While no birds harboured WNV in their blood, 3.5% of birds were seropositive, and birds from more urban sites had higher exposure to the virus than those from less urban sites. Our results demonstrate the presence of multiple bird-borne zoonotic pathogens across a gradient of urbanization and provide an assessment of potential public health risks to the high-density human populations within the area.

The re-emergence of mpox as a global public health threat has once again brought the viral disease to the attention of the international community. As mpox cases increase and spread beyond the shores of Africa, public health experts face the challenge of implementing effective measures to contain the disease. This review aims to examine the significance of mpox in public health, with a particular focus on recent outbreaks and understanding the public health response. The review explores recent approaches, including vaccination strategies, risk communication, and emergency preparedness. The paper also critically analyses limitations and offers possible future directions for improving the management of current and future outbreaks. Google and Google Scholar search engines as well as PubMed database were searched to identify literature concerning mpox public health impact and response. Websites of the WHO and similar organizations were also searched. The key search terms used were ‘‘mpox,’’ ‘‘public health,’’ ‘‘impact,’’ ‘‘response,’’ and ‘‘outbreak.’’ The review findings highlighted the challenges and gaps in the ongoing mpox outbreak response, ranging from vaccine shortage to limited surveillance and testing capacity and infrastructure, as well as inequitable access to vaccines and medical countermeasures. Other challenges include logistical issues and ongoing conflicts. This article emphasized the urgent need for multi-sectoral collaboration among key stakeholders, including embracing a One Health approach in case detection and investigation. The prevention and control of mpox require a more effective response that prioritizes rapid and equitable access to vaccines, diagnostics, and other necessary countermeasures.

Mpox virus (MPXV) is the only pathogen that triggered two Public Health Emergency of International Concern (PHEIC) declarations, first in July 2022 and then again in August 2024. The 2022 outbreak was attributed primarily to clade IIb MPXV, specifically lineage B.1. However, the 2024 global outbreak was largely due to the emergence of clade Ib MPXV, which was first identified in the Sud Kivu region of the Democratic Republic of the Congo in 2023. During this period, the transmission route of MPXV transitioned from primarily zoonotic spillovers to sustained human-to-human transmission, disproportionately affecting vulnerable groups such as men-who-have-sex-with-men, immunocompromised individuals and marginalized populations with limited access to healthcare. This shift has been driven by critical mutations in genes associated with viral fitness, immune evasion, and transmission dynamics. Moreover, these changes correspond with atypical and often milder yet more transmissible clinical presentations, complicating the detection and management of cases. Despite these challenges, health system preparedness has remained uneven. High-income countries leverage existing infrastructure to facilitate rapid responses through proactive policies and financial commitments. However, many low- and middle-income countries struggle with delayed case detection, limited surge capacity, community unawareness and fragmented outbreak governance. Although diagnostics, vaccines and antivirals have advanced, issues such as accessibility, affordability and distribution have persisted, hindering global solidarity efforts. This narrative review integrates evidence on the evolution of MPXV clades, clinical heterogeneity and public health responses. Furthermore, by learning from past outbreaks, this review proposes actionable, time-sensitive recommendations to strengthen surveillance, ensure equitable deployment of countermeasures, secure supply chains, and embed One Health approaches for increased resilience.

The globe on the spotlight: Coronavirus disease 2019 (Covid-19)

This research explored the role of air travel in the spread of infectious diseases, specifically severe acute respiratory syndrome (SARS), H1N1, Ebola, and pneumonic plague. Air travel provides the means for such diseases to spread internationally at extraordinary rates because infected passengers jump from coast to coast and continent to continent within hours. Outbreaks of diseases that spread from person to person test the effectiveness of current public health responses. This research used a mixed methods approach, including use of the Spatiotemporal Epidemiological Modeler, to model the spread of diseases, evaluate the impact of air travel on disease spread, and analyze the effectiveness of different public health strategies and travel policies. Modeling showed that the spread of Ebola and pneumonic plague is minimal and should not be a major air travel concern if an individual becomes infected. H1N1 and SARS have higher infection rates and air travel will facilitate the spread of disease nationally and internationally. To contain the spread of infectious diseases, aviation and public health authorities should establish tailored preventive measures at airports, capture contact information for ticketed passengers, expand the definition of “close contact,” and conduct widespread educational programs. The measures will put in place a foundation for containing the spread of infectious diseases via air travel and minimize the panic and economic consequences that may occur during an outbreak.

Rodents and shrews are major reservoirs of various pathogens that are related to zoonotic infectious diseases. The purpose of this study was to investigate co-infections of zoonotic pathogens in rodents and shrews trapped in four provinces of China. We sampled different rodent and shrew communities within and around human settlements in four provinces of China and characterised several important zoonotic viral, bacterial, and parasitic pathogens by PCR methods and phylogenetic analysis. A total of 864 rodents and shrews belonging to 24 and 13 species from RODENTIA and EULIPOTYPHLA orders were captured, respectively. For viral pathogens, two species of hantavirus (Hantaan orthohantavirus and Caobang orthohantavirus) were identified in 3.47% of rodents and shrews. The overall prevalence of Bartonella spp., Anaplasmataceae, Babesia spp., Leptospira spp., Spotted fever group Rickettsiae, Borrelia spp., and Coxiella burnetii were 31.25%, 8.91%, 4.17%, 3.94%, 3.59%, 3.47%, and 0.58%, respectively. Furthermore, the highest co-infection status of three pathogens was observed among Bartonella spp., Leptospira spp., and Anaplasmataceae with a co-infection rate of 0.46%. Our results suggested that species distribution and co-infections of zoonotic pathogens were prevalent in rodents and shrews, highlighting the necessity of active surveillance for zoonotic pathogens in wild mammals in wider regions.