Heterogeneous aggregation of parasites between individual hosts is common and regarded as an important factor in understanding transmission dynamics of vector-borne diseases. Lyme disease is vectored by generalist tick species, yet we have a limited understanding of how individual heterogeneities within small mammal host populations affect the aggregation of ticks and likelihood of infection. Male hosts often have higher parasite and infection levels than females, but whether this is linked to sexual body size dimorphism remains uncertain. Here, we analysed how host species, sex, and body mass influenced Ixodes ricinus tick infestations and the infection prevalence of Borrelia burgdorferi sensu lato (s.l.) in three species of small mammals involved in the enzootic transmission cycle of Lyme disease in Norway from 2018 to 2022. Larval and nymphal ticks were found on 98% and 34% of all individual hosts, respectively. In bank voles and wood mice, both larval and nymphal tick infestation and infection probability increased with body mass, and it increased more with mass for males than for females. Tick infestation in the common shrew increased with body mass and was higher in males, while pathogen infection was higher in females. Sex-biases in infestation did not correspond with level of sexual body mass dimorphism across species. This study contributes to our understanding of how individual heterogeneity among small mammalian hosts influences I. ricinus tick aggregation and prevalence of B. burgdorferi s.l. at northern latitudes.

Pathogens can elicit high selective pressure on hosts, potentially altering genetic diversity over short evolutionary timescales. Intraspecific variation in immune response is observable as variable survivability from specific infections. The great gerbil (Rhombomys opimus) is a rodent plague host with a heterogenic but highly resistant phenotype. Here, we investigate the genomic basis for plague-resistant phenotypes by exposing wild-caught great gerbils to plague (Yersinia pestis). Whole genome sequencing of 10 survivors and 10 moribund individuals revealed a subset of genomic regions showing elevated differentiation. Gene ontology analysis of candidate genes in these regions demonstrated enrichment of genes directly involved in immune functions, cellular metabolism and the regulation of apoptosis as well as pathways involved in transcription, translation, and gene regulation. Transcriptomic analysis revealed that the early activated great gerbil immune response to plague consisted of classical components of the innate immune system. Our approach combining challenge experiments with transcriptomics and population level sequencing, provides new insight into the genetic background of plague-resistance and confirms its complex nature, most likely involving multiple genes and pathways of both the immune system and regulation of basic cellular functions.

Here we present a developing probabilistic simulation model and tool to assess likely lead times from emergence to detection and arrival for new emerging infectious diseases (EIDs). Key aspects include combining real-world data available on multiple scales with a flexible underlying disease model. As demonstrated by the SARS-CoV-2 pandemic and other emerging infectious diseases, there is a need for scenario exploration for mitigation, surveillance and preparedness strategies. Existing simulation engines have been assessed but found to offer an insufficient set of features with regards to flexibility and control over processes, disease model structure and data sets incorporated for a wider enough range of diseases, circumstances, cofactors and scenarios (Heslop et al. 2017) to suit our aims. We are therefore developing the first version of a simulation model designed to be able to incorporate a diverse range of disease models and data sources including multiple transmission and infectivity stages, multiple host species, varying and evolving virulence, socioeconomic differences, climate events and public health countermeasures. It is designed to be flexible with respect to implementing both improvements in the model structure and data as they become available. It is based on a discrete-time (daily) structure where spatial movement and transition between categories and detection are stochastic rates dependent on spatial data and past states in the model, while being informed by the most suitable data available (Fig. 1). The probability of detection is in itself treated as a probabilistic process and treated as a variable dependent on socioeconomic factors and parameterized by past performance, yet open for manipulation in scenario exploration regarding surveillance and reporting effectiveness. Pathogen hotspot data are sourced from literature and included as a probabilistic assessment of emergence as well as a source of cofactor data (Allen et al. 2017), population data are adressed (Leyk et al. 2019) for utility and combined with data on local connectivity (Nelson et al. 2019) and transnational movement patterns (Recchi et al. 2019Fig. 1), as well as an increasing set of ecological and socioeconomic candidate variables. Model parameterization relies on a machine learning framework with matching to the often partial data available for known relevant disease cases as the training data, and assessing them for plausible ranges of input for new, hypothetical EIDs. As parameterizations improve, the range of scenarios to explore will incorporate effects of climate change and multiple stressors. When a suitable version becomes available it will be shared under a MIT license.

Bacillus anthracis, the etiological agent of anthrax, is a well-established model organism. For B. anthracis and most other infectious diseases, knowledge regarding transmission and infection parameters in natural systems, in large part, comprises data gathered from closely controlled laboratory experiments. Fatal, natural anthrax infections transmit the bacterium through new host-pathogen contacts at carcass sites, which can occur years after death of the previous host. For the period between contact and death, all of our knowledge is based upon experimental data from domestic livestock and laboratory animals. Here we use a noninvasive method to explore the dynamics of anthrax infections, by evaluating the terminal diversity of B. anthracis in anthrax carcasses. We present an application of population genetics theory, specifically, coalescence modeling, to intrainfection populations of B. anthracis to derive estimates for the duration of the acute phase of the infection and effective population size converted to the number of colony-forming units establishing infection in wild plains zebra (Equus quagga). Founding populations are small, a few colony-forming units, and infections are rapid, lasting roughly between 1 d and 3 d in the wild. Our results closely reflect experimental data, showing that small founding populations progress acutely, killing the host within days. We believe this method is amendable to other bacterial diseases from wild, domestic, and human systems.

The great gerbil (Rhombomys opimus) is a social rodent living in permanent, complex burrow systems distributed throughout Central Asia, where it serves as the main host of several important vector-borne infectious pathogens including the well-known plague bacterium (Yersinia pestis). Here, we present a continuous annotated genome assembly of the great gerbil, covering over 96% of the estimated 2.47-Gb genome. Taking advantage of the recent genome assemblies of the sand rat (Psammomys obesus) and the Mongolian gerbil (Meriones unguiculatus), comparative immunogenomic analyses reveal shared gene losses within TLR gene families (i.e., TLR8, TLR10, and the entire TLR11-subfamily) for Gerbillinae, accompanied with signs of diversifying selection of TLR7 and TLR9. Most notably, we find a great gerbil-specific duplication of the MHCII DRB locus. In silico analyses suggest that the duplicated gene provides high peptide binding affinity for Yersiniae epitopes as well as Leishmania and Leptospira epitopes, putatively leading to increased capability to withstand infections by these pathogens. Our study demonstrates the power of whole-genome sequencing combined with comparative genomic analyses to gain deeper insight into the immunogenomic landscape of the great gerbil and its close relatives.

“In order to understand the dynamics of infectious disease outbreaks in humans, we really need to understand the dynamics of the pathogen in nature.”* Over the last decade, I have heard one particular gray-haired ecologist repeat this every chance he gets, for one good reason: It is true. Understanding how pathogens work in natural settings can inform us what consequences may lie ahead if a particular pathogen jumps from one species to another. Outbreaks start with the first or index case in a species. The pathology of the disease agent in that case will determine the fate of that pathogen in its new host species. Mollentze et al. (1) use a meta-analysis of infection challenge data to predict the likely significance, in terms of pathology, of a transspecies infection. This study has particular relevance for rabies and may highlight general implications for other infectious diseases jumping species. At the very least, beyond rabies, it provides an excellent framework for predicting transspecies pathologies for infectious diseases. Successful establishment of the index infection is reliant on complementary host and pathogen attributes. Pathogens have a finite, often streamlined, genetic code, which has evolved to take advantage by evading, attacking, or hijacking the host’s immune system. Coevolution hones the pathogen’s phenotype toward sustainable exploitation of its host’s population. When a pathogen jumps into a new host species, the outcome of that infection and its significance to the new host species is largely cryptic, ranging from benign to disastrous. Some of these outcomes can be predicted using laboratory infection studies across species. Moreover, larger studies or meta-analyses across studies can help us predict and assess risks involving transspecies infections (1). I will discuss some of the other aspects of pathogen biology, ecology, and evolution which precede and follow a pathogen jumping species. Pathogens … [↵][1]1Email: w.r.easterday{at}ibv.uio.no. [1]: #xref-corresp-1-1

Yersinia pestis is transmitted from fleas to rodents when the bacterium develops an extensive biofilm in the foregut of a flea, starving it into a feeding frenzy, or, alternatively, during a brief period directly after feeding on a bacteremic host. These two transmission modes are in a trade-off regulated by the amount of biofilm produced by the bacterium. Here by investigating 446 global isolated Y. pestis genomes, including 78 newly sequenced isolates sampled over 40 years from a plague focus in China, we provide evidence for strong selection pressures on the RNA polymerase ω-subunit encoding gene rpoZ. We demonstrate that rpoZ variants have an increased rate of biofilm production in vitro, and that they evolve in the ecosystem during colder and drier periods. Our results support the notion that the bacterium is constantly adapting-through extended phenotype changes in the fleas-in response to climate-driven changes in the niche.

Bacillus anthracis, the causative agent of anthrax, is a considerable global health threat affecting wildlife, livestock, and the general public. In this study whole-genome sequence analysis of over 350 B. anthracis isolates was used to establish a new high-resolution global genotyping framework that is both biogeographically informative, and compatible with multiple genomic assays. The data presented in this study shed new light on the diverse global dissemination of this species and indicate that many lineages may be uniquely suited to the geographic regions in which they are found. In addition, we demonstrate that plasmid genomic structure for this species is largely consistent with chromosomal population structure, suggesting vertical inheritance in this bacterium has contributed to its evolutionary persistence. This classification methodology is the first based on population genomic structure for this species and has potential use for local and broader institutions seeking to understand both disease outbreak origins and recent introductions. In addition, we provide access to a newly developed genotyping script as well as the full whole genome sequence analyses output for this study, allowing future studies to rapidly employ and append their data in the context of this global collection. This framework may act as a powerful tool for public health agencies, wildlife disease laboratories, and researchers seeking to utilize and expand this classification scheme for further investigations into B. anthracis evolution.

Yersinia pestis , the causative agent of plague, is responsible for about 700 human cases of bubonic and pneumonic plague each year. Yet the disease is far more prevalent within rodent reservoirs than in humans. One of the main means of outbreak prevention is extensive wildlife surveillance, where accurate and rapid detection is essential to prevent spillover into the human population from which, it may otherwise spread more rapidly and over larger distances. Moreover, detection and quantification of the agent aids in investigative studies to understand aspects of the pathogen such as transmission mechanics, pathology, contamination risk and more. Partially based on a previously developed assay by Gabitzsch et al. 2008 we designed a TaqMan ® mismatch amplification mutation assay (TaqMAMA) where a primer leverages a species-specific SNP in the chromosomal single copy ferric uptake regulator gene of Yersinia pestis . The assay allows for specific, rapid detection and quantification of Yersinia pestis using only a single species-specific marker in a highly conserved virulence gene. This low-cost and simple modification of an existing assay eliminates the need for running multiple molecular markers for pathogen detection or performing time-consuming culturing and counting of colonies for quantification.

Environmentally transmitted diseases are comparatively poorly understood and managed, and their ecology is particularly understudied. Here we identify challenges of studying environmental transmission and persistence with a six-sided interdisciplinary review of the biology of anthrax (Bacillus anthracis). Anthrax is a zoonotic disease capable of maintaining infectious spore banks in soil for decades (or even potentially centuries), and the mechanisms of its environmental persistence have been the topic of significant research and controversy. Where anthrax is endemic, it plays an important ecological role, shaping the dynamics of entire herbivore communities. The complex eco-epidemiology of anthrax, and the mysterious biology of Bacillus anthracis during its environmental stage, have necessitated an interdisciplinary approach to pathogen research. Here, we illustrate different disciplinary perspectives through key advances made by researchers working in Etosha National Park, a long-term ecological research site in Namibia that has exemplified the complexities of the enzootic process of anthrax over decades of surveillance. In Etosha, the role of scavengers and alternative routes (waterborne transmission and flies) has proved unimportant relative to the long-term persistence of anthrax spores in soil and their infection of herbivore hosts. Carcass deposition facilitates green-ups of vegetation to attract herbivores, potentially facilitated by the role of anthrax spores in the rhizosphere. The underlying seasonal pattern of vegetation, and herbivores' immune and behavioural responses to anthrax risk, interact to produce regular 'anthrax seasons' that appear to be a stable feature of the Etosha ecosystem. Through the lens of microbiologists, geneticists, immunologists, ecologists, epidemiologists, and clinicians, we discuss how anthrax dynamics are shaped at the smallest scale by population genetics and interactions within the bacterial communities up to the broadest scales of ecosystem structure. We illustrate the benefits and challenges of this interdisciplinary approach to disease ecology, and suggest ways anthrax might offer insights into the biology of other important pathogens. Bacillus anthracis, and the more recently emerged Bacillus cereus biovar anthracis, share key features with other environmentally transmitted pathogens, including several zoonoses and panzootics of special interest for global health and conservation efforts. Understanding the dynamics of anthrax, and developing interdisciplinary research programs that explore environmental persistence, is a critical step forward for understanding these emerging threats.

Background: Emergence of tick-borne diseases is impacting humans and livestock across the Northern Hemisphere. There are, however, large regional variations in number of cases of tick-borne diseases. Some areas have surprisingly few cases of disease compared to other regions. The aim here is to provide a first step towards a better understanding of such contrasting regional patterns of disease emergences at the northern distribution range of Ixodes ricinus in Europe. Methods: We compare disease incidence, vector abundance and pathogen prevalence in eastern and western Norway differing in the number of tick-borne disease cases. First, we analysed the incidence of Lyme borreliosis in humans, tick-borne fever (anaplasmosis) in sheep and anaplasmosis and babesiosis in cattle to verify if incidence differed. Secondly, we analysed extensive field data on questing tick density, pathogen prevalence, as well as the broad spatial pattern of human and livestock distribution as it may relate to tick exposure. Results: The incidences of all diseases were lower in eastern, compared to western, Norway, but this was most marked for the livestock diseases. While the prevalence of Borrelia burgdorferi (sensu lato) in ticks was similar in the two regions, the prevalence of Anaplasma phagocytophilum was markedly lower in eastern, compared to western, Norway. We found overall a lower abundance of questing nymphs in the east. In the east, there were cases of babesiosis in cattle where anaplasmosis was absent, suggesting absence of the pathogen rather than differences in exposure to ticks as part of the explanation for the much lower incidence of anaplasmosis in eastern Norway. Conclusions: Many factors contribute to different disease incidence across ecosystems. We found that regional variation in tick-borne disease incidence may be partly linked to vector abundance and pathogen prevalence, but differently for human and livestock diseases. Further studies are needed to determine if there is also regional variation in specific genospecies and strain frequencies differing in pathogenicity.

BACKGROUND:Anthrax is a globally distributed disease affecting primarily herbivorous mammals. It is caused by the soil-dwelling and spore-forming bacterium Bacillus anthracis. The dormant B. anthracis spores become vegetative after ingestion by grazing mammals. After killing the host, B. anthracis cells return to the soil where they sporulate, completing the lifecycle of the bacterium. Here we present the first study describing temporal microbial soil community changes in Etosha National Park, Namibia, after decomposition of two plains zebra (Equus quagga) anthrax carcasses. To circumvent state-associated-challenges (i.e. vegetative cells/spores) we monitored B. anthracis throughout the period using cultivation, qPCR and shotgun metagenomic sequencing.RESULTS:The combined results suggest that abundance estimation of spore-forming bacteria in their natural habitat by DNA-based approaches alone is insufficient due to poor recovery of DNA from spores. However, our combined approached allowed us to follow B. anthracis population dynamics (vegetative cells and spores) in the soil, along with closely related organisms from the B. cereus group, despite their high sequence similarity. Vegetative B. anthracis abundance peaked early in the time-series and then dropped when cells either sporulated or died. The time-series revealed that after carcass deposition, the typical semi-arid soil community (e.g. Frankiales and Rhizobiales species) becomes temporarily dominated by the orders Bacillales and Pseudomonadales, known to contain plant growth-promoting species.CONCLUSION:Our work indicates that complementing DNA based approaches with cultivation may give a more complete picture of the ecology of spore forming pathogens. Furthermore, the results suggests that the increased vegetation biomass production found at carcass sites is due to both added nutrients and the proliferation of microbial taxa that can be beneficial for plant growth. Thus, future B. anthracis transmission events at carcass sites may be indirectly facilitated by the recruitment of plant-beneficial bacteria.

Bacillus anthracis strains K1 and K2 were isolated from two plains zebra anthrax carcasses in Etosha National Park, Namibia. These are draft genomes obtained by Illumina MiSeq sequencing of isolates collected from culture of blood-soaked soil from each carcass.

Global environmental changes are causing Lyme disease to emerge in Europe. The life cycle of Ixodes ricinus , the tick vector of Lyme disease, involves an ontogenetic niche shift, from the larval and nymphal stages utilizing a wide range of hosts, picking up the pathogens causing Lyme disease from small vertebrates, to the adult stage depending on larger (non-transmission) hosts, typically deer. Because of this complexity the role of different host species for emergence of Lyme disease remains controversial. Here, by analysing long-term data on incidence in humans over a broad geographical scale in Norway, we show that both high spatial and temporal deer population density increase Lyme disease incidence. However, the trajectories of deer population sizes play an overall limited role for the recent emergence of the disease. Our study suggests that managing deer populations will have some effect on disease incidence, but that Lyme disease may nevertheless increase as multiple drivers are involved.

To mitigate the effects of zoonotic diseases on human and animal populations, it is critical to understand what factors alter transmission dynamics. Here we assess the risk of exposure to lethal concentrations of the anthrax bacterium, Bacillus anthracis , for grazing animals in a natural system over time through different transmission mechanisms. We follow pathogen concentrations at anthrax carcass sites and waterholes for five years and estimate infection risk as a function of grass, soil or water intake, age of carcass sites, and the exposure required for a lethal infection. Grazing, not drinking, seems the dominant transmission route, and transmission is more probable from grazing at carcass sites 1–2 years of age. Unlike most studies of virulent pathogens that are conducted under controlled conditions for extrapolation to real situations, we evaluate exposure risk under field conditions to estimate the probability of a lethal dose, showing that not all reservoirs with detectable pathogens are significant transmission pathways.

Data presented here is based on the paper "Climate-driven introduction of the Black Death and successive plague reintroductions into Europe", in PNAS.org Raw datasets of the medieval plague outbreaks, current-day plague reservoirs, and the compilation of medieval traderoutes (based on OWTRAD) available at Zenodo. Note that the maps of current-day plague reservoirs were based on publically available data, are focused on Asia, and are not exhaustive. These were gathered and digitized by W. Ryan Easterday. Source articles for each of the plague foci are available in the Plague Foci Eurasia.kmz at Zenodo Traderoute data: Ciolek, T. Matthew. 1999 - present. Old World Trade Routes (OWTRAD) Project. Canberra: www.ciolek.com - Asia Pacific Research Online. www.ciolek.com/owtrad.html