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We assessed evidence of exposure to viruses and bacteria in an unmanaged and long-isolated population of Soay sheep (Ovis aries) inhabiting Hirta, in the St Kilda archipelago, 65 km west of Benbecula in the Outer Hebrides of Scotland. The sheep harbour many metazoan and protozoan parasites but their exposure to viral and bacterial pathogens is unknown. We tested for herpes viral DNA in leucocytes and found that 21 of 42 tested sheep were infected with ovine herpesvirus 2 (OHV-2). We also tested 750 plasma samples collected between 1997 and 2010 for evidence of exposure to seven other viral and bacterial agents common in domestic Scottish sheep. We found evidence of exposure to Leptospira spp., with overall seroprevalence of 6·5%. However, serological evidence indicated that the population had not been exposed to border disease, parainfluenza, maedi-visna, or orf viruses, nor to Chlamydia abortus. Some sheep tested positive for antibodies against Mycobacterium avium subsp. paratuberculosis (MAP) but, in the absence of retrospective faecal samples, the presence of this infection could not be confirmed. The roles of importation, the pathogen-host interaction, nematode co-infection and local transmission warrant future investigation, to elucidate the transmission ecology and fitness effects of the few viral and bacterial pathogens on Hirta.

Evolution is a key aspect of the biology of many pathogens, driving processes ranging from immune escape to changes in virulence. Because evolution is inherently subject to feedbacks, and because pathogen evolution plays out at scales ranging from within-host to between-host and beyond, evolutionary questions provide special challenges to the modelling community. In this article, we provide an overview of five challenges in modelling the evolution of pathogens and their hosts, and point to areas for development, focussing in particular on the issue of linking theory and data.

Many disease systems exhibit complexities not captured by current theoretical and empirical work. In particular, systems with multiple host species and multiple infectious agents (i.e., multi-host, multi-agent systems) require novel methods to extend the wealth of knowledge acquired studying primarily single-host, single-agent systems. We outline eight challenges in multi-host, multi-agent systems that could substantively increase our knowledge of the drivers and broader ecosystem effects of infectious disease dynamics.

The population dynamics of infectious disease is a mature field in terms of theory and to some extent, application. However for microparasites, the theory and application of models of the dynamics within a single infected host is still an open field. Further, connecting across the scales - from cellular to host level, to population level - has potential to vastly improve our understanding of pathogen dynamics and evolution. Here, we highlight seven challenges in the following areas: transmission bottlenecks, heterogeneity within host, dynamic fitness landscapes within hosts, making use of next-generation sequencing data, capturing superinfection and when and how to model more than two scales.

Studying the emergence of novel infectious agents involves many processes spanning host species, spatial scales, and scientific disciplines. Mathematical models play an essential role in combining insights from these investigations and drawing robust inferences from field and experimental data. We describe nine challenges in modelling the emergence of novel pathogens, emphasizing the interface between models and data.

Many diseases exhibit subcritical transmission (i.e. 0

Population-level analyses often use average quantities to describe heterogeneous systems, particularly when variation does not arise from identifiable groups. A prominent example, central to our current understanding of epidemic spread, is the basic reproductive number, R(0), which is defined as the mean number of infections caused by an infected individual in a susceptible population. Population estimates of R(0) can obscure considerable individual variation in infectiousness, as highlighted during the global emergence of severe acute respiratory syndrome (SARS) by numerous 'superspreading events' in which certain individuals infected unusually large numbers of secondary cases. For diseases transmitted by non-sexual direct contacts, such as SARS or smallpox, individual variation is difficult to measure empirically, and thus its importance for outbreak dynamics has been unclear. Here we present an integrated theoretical and statistical analysis of the influence of individual variation in infectiousness on disease emergence. Using contact tracing data from eight directly transmitted diseases, we show that the distribution of individual infectiousness around R(0) is often highly skewed. Model predictions accounting for this variation differ sharply from average-based approaches, with disease extinction more likely and outbreaks rarer but more explosive. Using these models, we explore implications for outbreak control, showing that individual-specific control measures outperform population-wide measures. Moreover, the dramatic improvements achieved through targeted control policies emphasize the need to identify predictive correlates of higher infectiousness. Our findings indicate that superspreading is a normal feature of disease spread, and to frame ongoing discussion we propose a rigorous definition for superspreading events and a method to predict their frequency.

Recognition is a prerequisite for non-random association amongst individuals. We explore how non-random association patterns (i.e. who spends time with whom) affect disease dynamics. We estimated the amount of time individuals spent together per month using radio-tracking data from African buffalo and incorporated these data into a dynamic social network model. The dynamic nature of the network has a strong influence on simulated disease dynamics particularly for diseases with shorter infectious periods. Cluster analyses of the association data demonstrated that buffalo herds were not as well defined as previously thought. Associations were more tightly clustered in 2002 than 2003, perhaps due to drier conditions in 2003. As a result, diseases may spread faster during drought conditions due to increased population mixing. Association data are often collected but this is the first use of empirical data in a network disease model in a wildlife population.

We explore the transmission process for sexually transmitted diseases (STDs). We derive the classical frequency-dependent incidence mechanistically from a pair-formation model, using an approximation that applies to populations with rapid pairing dynamics (such as core groups or non-pair-bonding animals). This mechanistic derivation provides a framework to assess how accurately frequency-dependent incidence portrays the pair-based transmission known to underlie STD dynamics. This accuracy depends strongly on the disease being studied: frequency-dependent formulations are more suitable for chronic less-transmissible infections than for transient highly transmissible infections. Our results thus support earlier proposals to divide STDs into these two functional classes, and we suggest guidelines to help assess under what conditions each class can be appropriately modelled using frequency-dependent incidence. We then extend the derivation to include situations where infected individuals exhibit altered pairing behaviour. For four cases of increasing behavioural complexity, analytic expressions are presented for the generalized frequency-dependent incidence rate, basic reproductive number (R0) and steady-state prevalence (i∞) of an epidemic. The expression for R0is identical for all cases, giving refined insights into determinants of invasibility of STDs. Potentially significant effects of infection-induced changes in contact behaviour are illustrated by simulating epidemics of bacterial and viral STDs. We discuss the application of our results to STDs (in humans and animals) and other infectious diseases.

Severe acute respiratory syndrome (SARS) has been transmitted extensively within hospitals, and healthcare workers (HCWs) have comprised a large proportion of SARS cases worldwide. We present a stochastic model of a SARS outbreak in a community and its hospital. For a range of basic reproductive numbers (R0) corresponding to conditions in different cities (but with emphasis on R0∼ 3 as reported for Hong Kong and Singapore), we evaluate contact precautions and case management (quarantine and isolation) as containment measures. Hospital-based contact precautions emerge as the most potent measures, with hospital-wide measures being particularly important if screening of HCWs is inadequate. For R0= 3, case isolation alone can control a SARS outbreak only if isolation reduces transmission by at least a factor of four and the mean symptom-onset-to-isolation time is less than 3 days. Delays of a few days in contact tracing and case identification severely degrade the utility of quarantine and isolation, particularly in high-transmission settings. Still more detrimental are delays between the onset of an outbreak and the implementation of control measures; for given control scenarios, our model identifies windows of opportunity beyond which the efficacy of containment efforts is reduced greatly. By considering pathways of transmission in our system, we show that if hospital-based transmission is not halted, measures that reduce community-HCW contact are vital to preventing a widespread epidemic. The implications of our results for future emerging pathogens are discussed.

Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Serology (the detection of antibodies formed by the host against an infecting pathogen) is frequently used to assess current infections and past exposure to specific pathogens. However, the presence of cross-reactivity among host antibodies in serological data makes it challenging to interpret the patterns and draw reliable conclusions about the infecting pathogen or strain., Methodology/principal Findings: In our study, we use microscopic agglutination test (MAT) serological data from three host species [California sea lion (Zalophus californianus), island fox (Urocyon littoralis), and island spotted skunk (Spilogale gracilis)] with confirmed infections to assess differences in cross-reactivity by host species and diagnostic laboratory. All host species are known to be infected with the same serovar of Leptospira interrogans. We find that absolute and relative antibody titer magnitudes vary systematically across host species and diagnostic laboratories. Despite being infected by the same Leptospira serovar, three host species exhibit different cross-reactivity profiles to a 5-serovar diagnostic panel. We also observe that the cross-reactive antibody titer against a non-infecting serovar can remain detectable after the antibody titer against the infecting serovar declines below detectable levels., Conclusions/significance: Cross-reactivity in serological data makes interpretation difficult and can lead to common pitfalls. Our results show that the highest antibody titer is not a reliable indicator of infecting serovar and highlight an intriguing role of host species in shaping reactivity patterns. On the other side, seronegativity against a given serovar does not rule out that serovar as the cause of infection. We show that titer magnitudes can be influenced by both host species and diagnostic laboratory, indicating that efforts to interpret absolute titers (e.g., as indicators of recent infection) must be calibrated to the system under study. Thus, we implore scientists and health officials using serological data for surveillance to interpret the data with caution., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Influenza A viruses (IAV) have caused more documented global pandemics in human history than any other pathogen 1,2 . High pathogenicity avian influenza (HPAI) viruses belonging to the H5N1 subtype are a leading pandemic risk. Two decades after H5N1 "bird flu" became established in poultry in Southeast Asia, its descendants have resurged 3 , setting off an H5N1 panzootic in wild birds that is fueled by (a) rapid intercontinental spread, reaching South America and Antarctica for the first time 4,5 ; (b) fast evolution via genomic reassortment 6 ; and (c) frequent spillover into terrestrial 7,8 and marine mammals 9 . The virus has sustained mammal-to-mammal transmission in multiple settings, including European fur farms 10,11 , South American marine mammals 12-15 , and US dairy cattle 16-19 , raising questions about whether humans are next. Historically, swine are considered optimal intermediary hosts that help avian influenza viruses (AIV) adapt to mammals before jumping to humans 20 . However, the altered ecology of H5N1 has opened the door to new evolutionary pathways. Could dairy cattle, farmed mink, or South American sea lions serve as new mammalian gateways to humans? Here we explore the molecular and ecological factors driving H5N1's sudden expansion in host range and assess the likelihood of different zoonotic pathways leading to an H5N1 pandemic., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

In the centuries following Christopher Columbus's 1492 voyage to the Americas, transoceanic travel opened unprecedented pathways in global pathogen circulation. Yet no biological transfer is a single, discrete event. We use mathematical modeling to quantify historical risk of shipborne pathogen introduction, exploring the respective contributions of journey time, ship size, population susceptibility, transmission intensity, density dependence, and pathogen biology. We contextualize our results using port arrivals data from San Francisco, 1850 to 1852, and from a selection of historically significant voyages, 1492 to 1918. We offer numerical estimates of introduction risk across historically realistic ranges of journey time and ship population size, and show that both steam travel and shipping regimes that involved frequent, large-scale movement of people substantially increased risk of transoceanic pathogen circulation., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Pathogenic Leptospira species are globally important zoonotic pathogens capable of infecting a wide range of host species. In marine mammals, reports of Leptospira have predominantly been in pinnipeds, with isolated reports of infections in cetaceans., Case Presentation: On 28 June 2021, a 150.5 cm long female, short-beaked common dolphin (Delphinus delphis delphis) stranded alive on the coast of southern California and subsequently died. Gross necropsy revealed multifocal cortical pallor within the reniculi of the kidney, and lymphoplasmacytic tubulointerstitial nephritis was observed histologically. Immunohistochemistry confirmed Leptospira infection, and PCR followed by lfb1 gene amplicon sequencing suggested that the infecting organism was L.kirschneri. Leptospira DNA capture and enrichment allowed for whole-genome sequencing to be conducted. Phylogenetic analyses confirmed the causative agent was a previously undescribed, divergent lineage of L.kirschneri., Conclusions: We report the first detection of pathogenic Leptospira in a short-beaked common dolphin, and the first detection in any cetacean in the northeastern Pacific Ocean. Renal lesions were consistent with leptospirosis in other host species, including marine mammals, and were the most significant lesions detected overall, suggesting leptospirosis as the likely cause of death. We identified the cause of the infection as L.kirschneri, a species detected only once before in a marine mammal - a northern elephant seal (Mirounga angustirostris) of the northeastern Pacific. These findings raise questions about the mechanism of transmission, given the obligate marine lifestyle of cetaceans (in contrast to pinnipeds, which spend time on land) and the commonly accepted view that Leptospira are quickly killed by salt water. They also raise important questions regarding the source of infection, and whether it arose from transmission among marine mammals or from terrestrial-to-marine spillover. Moving forward, surveillance and sampling must be expanded to better understand the extent to which Leptospira infections occur in the marine ecosystem and possible epidemiological linkages between and among marine and terrestrial host species. Generating Leptospira genomes from different host species will yield crucial information about possible transmission links, and our study highlights the power of new techniques such as DNA enrichment to illuminate the complex ecology of this important zoonotic pathogen., (© 2024. The Author(s).)

Researchers and clinicians often rely on molecular assays like PCR to identify and monitor viral infections, instead of the resource-prohibitive gold standard of viral culture. However, it remains unclear when (if ever) PCR measurements of viral load are reliable indicators of replicating or infectious virus. The recent popularity of PCR protocols targeting subgenomic RNA for SARS-CoV-2 has caused further confusion, as the relationships between subgenomic RNA and standard total RNA assays are incompletely characterized and opinions differ on which RNA type better predicts culture outcomes. Here, we explore these issues by comparing total RNA, subgenomic RNA, and viral culture results from 24 studies of SARS-CoV-2 in non-human primates (including 2167 samples from 174 individuals) using custom-developed Bayesian statistical models. On out-of-sample data, our best models predict subgenomic RNA positivity from total RNA data with 91% accuracy, and they predict culture positivity with 85% accuracy. Further analyses of individual time series indicate that many apparent prediction errors may arise from issues with assay sensitivity or sample processing, suggesting true accuracy may be higher than these estimates. Total RNA and subgenomic RNA showed equivalent performance as predictors of culture positivity. Multiple cofactors (including exposure conditions, host traits, and assay protocols) influence culture predictions, yielding insights into biological and methodological sources of variation in assay outcomes-and indicating that no single threshold value applies across study designs. We also show that our model can accurately predict when an individual is no longer infectious, illustrating the potential for future models trained on human data to guide clinical decisions on case isolation. Our work shows that meta-analysis of in vivo data can overcome longstanding challenges arising from limited sample sizes and can yield robust insights beyond those attainable from individual studies. Our analytical pipeline offers a framework to develop similar predictive tools in other virus-host systems, including models trained on human data, which could support laboratory analyses, medical decisions, and public health guidelines., Competing Interests: The authors declare there are no competing interests., (Copyright: © 2024 Snedden, Lloyd-Smith. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

It remains poorly understood how SARS-CoV-2 infection influences the physiological host factors important for aerosol transmission. We assessed breathing pattern, exhaled droplets, and infectious virus after infection with Alpha and Delta variants of concern (VOC) in the Syrian hamster. Both VOCs displayed a confined window of detectable airborne virus (24-48 hr), shorter than compared to oropharyngeal swabs. The loss of airborne shedding was linked to airway constriction resulting in a decrease of fine aerosols (1-10 µm) produced, which are suspected to be the major driver of airborne transmission. Male sex was associated with increased viral replication and virus shedding in the air. Next, we compared the transmission efficiency of both variants and found no significant differences. Transmission efficiency varied mostly among donors, 0-100% (including a superspreading event), and aerosol transmission over multiple chain links was representative of natural heterogeneity of exposure dose and downstream viral kinetics. Co-infection with VOCs only occurred when both viruses were shed by the same donor during an increased exposure timeframe (24-48 hr). This highlights that assessment of host and virus factors resulting in a differential exhaled particle profile is critical for understanding airborne transmission., Competing Interests: JP, DM, JR, CY, VA, MH, TB, JS, TS, KB, CR, RP, CS, CM, JL, RF, VM No competing interests declared

Introduction: Methamphetamine use is highly prevalent among men who have sex with men (MSM), but knowledge of the long-term dynamics, and how they are affected by substance use treatment, is limited. This study aimed to describe trajectories of methamphetamine use among MSM, and to evaluate the impact of treatment for any kind of substance use on frequency of methamphetamine use., Methods: This analysis used data from a cohort of MSM in Los Angeles, CA, who participated in semi-annual study visits from 2014 to 2022. The study characterized trajectories of methamphetamine use using a continuous time multistate Markov model with three states. States were defined using self-reported frequency of methamphetamine use in the past six months: frequent (daily), occasional (weekly or less), and never. The model estimated the association between receiving treatment for any kind of substance use and changes in state of frequency of methamphetamine use., Results: This analysis included 2348 study visits among 285 individuals who were followed-up for an average of 4.4 years. Among participants who were in the frequent use state, 65 % (n = 26) of those who were receiving any kind of substance use treatment at a study visit had reduced their methamphetamine use at their next visit, compared to 33 % (n = 95) of those who were not receiving treatment. Controlling for age, race/ethnicity, and HIV-status, those who reported receiving current treatment for substance use were more likely to transition from occasional to no use (HR: 1.63, 95 % CI: 1.10-2.42) and frequent to occasional use (HR: 4.25, 95 % CI: 2.11-8.59) in comparison to those who did not report receiving current treatment for substance use., Conclusions: Findings from this dynamic modeling study provide a new method for assessing longitudinal methamphetamine use outcomes and add important evidence outside of clinical trials that substance use treatment may reduce methamphetamine use., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023. Published by Elsevier Inc.)

An outbreak of human mpox infection in nonendemic countries appears to have been driven largely by transmission through body fluids or skin-to-skin contact during sexual activity. We evaluated the stability of monkeypox virus (MPXV) in different environments and specific body fluids and tested the effectiveness of decontamination methodologies. MPXV decayed faster at higher temperatures, and rates varied considerably depending on the medium in which virus was suspended, both in solution and on surfaces. More proteinaceous fluids supported greater persistence. Chlorination was an effective decontamination technique, but only at higher concentrations. Wastewater was more difficult to decontaminate than plain deionized water; testing for infectious MPXV could be a helpful addition to PCR-based wastewater surveillance when high levels of viral DNA are detected. Our findings suggest that, because virus stability is sufficient to support environmental MPXV transmission in healthcare settings, exposure and dose-response will be limiting factors for those transmission routes.

Leptospirosis, the most widespread zoonotic disease in the world, is broadly understudied in multi-host wildlife systems. Knowledge gaps regarding Leptospira circulation in wildlife, particularly in densely populated areas, contribute to frequent misdiagnoses in humans and domestic animals. We assessed Leptospira prevalence levels and risk factors in five target wildlife species across the greater Los Angeles region: striped skunks (Mephitis mephitis), raccoons (Procyon lotor), coyotes (Canis latrans), Virginia opossums (Didelphis virginiana), and fox squirrels (Sciurus niger). We sampled more than 960 individual animals, including over 700 from target species in the greater Los Angeles region, and an additional 266 sampled opportunistically from other California regions and species. In the five target species seroprevalences ranged from 5 to 60%, and infection prevalences ranged from 0.8 to 15.2% in all except fox squirrels (0%). Leptospira phylogenomics and patterns of serologic reactivity suggest that mainland terrestrial wildlife, particularly mesocarnivores, could be the source of repeated observed introductions of Leptospira into local marine and island ecosystems. Overall, we found evidence of widespread Leptospira exposure in wildlife across Los Angeles and surrounding regions. This indicates exposure risk for humans and domestic animals and highlights that this pathogen can circulate endemically in many wildlife species even in densely populated urban areas., (© 2023. Springer Nature Limited.)

Respiratory viruses can be transmitted by multiple modes, including contaminated surfaces, commonly referred to as fomites. Efficient fomite transmission requires that a virus remain infectious on a given surface material over a wide range of environmental conditions, including different relative humidities. Prior work examining the stability of influenza viruses on surfaces has relied upon virus grown in media or eggs, which does not mimic the composition of virus-containing droplets expelled from the human respiratory tract. In this study, we examined the stability of the 2009 pandemic H1N1 (H1N1pdm09) virus on a variety of nonporous surface materials at four different humidities. Importantly, we used virus grown in primary human bronchial epithelial cell (HBE) cultures from different donors to recapitulate the physiological microenvironment of expelled viruses. We observed rapid inactivation of H1N1pdm09 on copper under all experimental conditions. In contrast to copper, viruses were stable on polystyrene plastic, stainless steel, aluminum, and glass, at multiple relative humidities, but greater decay on acrylonitrile butadiene styrene (ABS) plastic was observed at short time points. However, the half-lives of viruses at 23% relative humidity were similar among noncopper surfaces and ranged from 4.5 to 5.9 h. Assessment of H1N1pdm09 longevity on nonporous surfaces revealed that virus persistence was governed more by differences among HBE culture donors than by surface material. Our findings highlight the potential role of an individual's respiratory fluid on viral persistence and could help explain heterogeneity in transmission dynamics. IMPORTANCE Seasonal epidemics and sporadic pandemics of influenza cause a large public health burden. Although influenza viruses disseminate through the environment in respiratory secretions expelled from infected individuals, they can also be transmitted by contaminated surfaces where virus-laden expulsions can be deposited. Understanding virus stability on surfaces within the indoor environment is critical to assessing influenza transmission risk. We found that influenza virus stability is affected by the host respiratory secretion in which the virus is expelled, the surface material on which the droplet lands, and the ambient relative humidity of the environment. Influenza viruses can remain infectious on many common surfaces for prolonged periods, with half-lives of 4.5 to 5.9 h. These data imply that influenza viruses are persistent in indoor environments in biologically relevant matrices. Decontamination and engineering controls should be used to mitigate influenza virus transmission., Competing Interests: The authors declare a conflict of interest. This work was funded by the National Institutes of Health (NIH) CEIRS (HHSN272201400007C) and New Innovator Award to L.C.M. (1-DP2-A1112243), the American Lung Association Biomedical Research Grant (RG-575688), the Tsinghua Education Foundation of North America, and the China Scholarship Council (CSC). Work by D.H.M. and J.O.L.-S. was supported by the UCLA AIDS Institute and Charity Treks, and National Science Foundation (NSF) Grants DEB-1557022 and DEB-2245631.

SARS-CoV-2 transmits principally by air; contact and fomite transmission may also occur. Variants of concern are more transmissible than ancestral SARS-CoV-2. We found indications of possible increased aerosol and surface stability for early variants of concern, but not for the Delta and Omicron variants. Stability changes are unlikely to explain increased transmissibility.

Background: More than four decades after the eradication of smallpox, the ongoing 2022 monkeypox outbreak and increasing transmission events of other orthopoxviruses necessitate a greater understanding of the global distribution of susceptibility to orthopoxviruses. We aimed to characterise the current global landscape of smallpox vaccination history and orthopoxvirus susceptibility., Methods: We characterised the global landscape of smallpox vaccination at a subnational scale by integrating data on current demography with historical smallpox vaccination programme features (coverage and cessation dates) from eradication documents and published literature. We analysed this landscape to identify the factors that were most associated with geographical heterogeneity in current vaccination coverage. We considered how smallpox vaccination history might translate into age-specific susceptibility profiles for orthopoxviruses under different vaccination effectiveness scenarios., Findings: We found substantial global spatial heterogeneity in the landscape of smallpox vaccination, with vaccination coverage estimated to range from 7% to 60% within admin-1 regions (ie, regions one administrative level below country) globally, with negligible uncertainty (99·6% of regions have an SD less than 5%). We identified that geographical variation in vaccination coverage was driven mostly by differences in subnational demography. Additionally, we found that susceptibility for orthopoxviruses was highly age specific based on age at cessation and age-specific coverage; however, the age profile was consistent across vaccine effectiveness values., Interpretation: The legacy of smallpox eradication can be observed in the current landscape of smallpox vaccine protection. The strength and longevity of smallpox vaccination campaigns globally, combined with current demographic heterogeneity, have shaped the epidemiological landscape today, revealing substantial geographical variation in orthopoxvirus susceptibility. This study alerts public health decision makers to non-endemic regions that might be at greatest risk in the case of widespread and sustained transmission in the 2022 monkeypox outbreak and highlights the importance of demography and fine-scale spatial dynamics in predicting future public health risks from orthopoxviruses., Funding: US National Institutes of Health and US National Science Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The explosive outbreaks of COVID-19 seen in congregate settings such as prisons and nursing homes, has highlighted a critical need for effective outbreak prevention and mitigation strategies for these settings. Here we consider how different types of control interventions impact the expected number of symptomatic infections due to outbreaks. Introduction of disease into the resident population from the community is modeled as a stochastic point process coupled to a branching process, while spread between residents is modeled via a deterministic compartmental model that accounts for depletion of susceptible individuals. Control is modeled as a proportional decrease in the number of susceptible residents, the reproduction number, and/or the proportion of symptomatic infections. This permits a range of assumptions about the density dependence of transmission and modes of protection by vaccination, depopulation and other types of control. We find that vaccination or depopulation can have a greater than linear effect on the expected number of cases. For example, assuming a reproduction number of 3.0 with density-dependent transmission, we find that preemptively reducing the size of the susceptible population by 20% reduced overall disease burden by 47%. In some circumstances, it may be possible to reduce the risk and burden of disease outbreaks by optimizing the way a group of residents are apportioned into distinct residential units. The optimal apportionment may be different depending on whether the goal is to reduce the probability of an outbreak occurring, or the expected number of cases from outbreak dynamics. In other circumstances there may be an opportunity to implement reactive disease control measures in which the number of susceptible individuals is rapidly reduced once an outbreak has been detected to occur. Reactive control is most effective when the reproduction number is not too high, and there is minimal delay in implementing control. We highlight the California state prison system as an example for how these findings provide a quantitative framework for understanding disease transmission in congregate settings. Our approach and accompanying interactive website (https://phoebelu.shinyapps.io/DepopulationModels/) provides a quantitative framework to evaluate the potential impact of policy decisions governing infection control in outbreak settings., Competing Interests: The authors have declared that no competing interests exist.

Infectious zoonotic diseases are a threat to wildlife conservation and global health. They are especially a concern for wild apes, which are vulnerable to many human infectious diseases. As ecotourism, deforestation, and great ape field research increase, the threat of human-sourced infections to wild populations becomes more substantial and could result in devastating population declines. The endangered mountain gorillas (Gorilla beringei beringei) of the Virunga Massif in east-central Africa suffer periodic disease outbreaks and are exposed to infections from human-sourced pathogens. It is important to understand the possible risks of disease introduction and spread in this population and how human contact may facilitate disease transmission. Here we present and evaluate an individual-based, stochastic, discrete-time disease transmission model to predict epidemic outcomes and better understand health risks to the Virunga mountain gorilla population. To model disease transmission we have derived estimates for gorilla contact, interaction, and migration rates. The model shows that the social structure of gorilla populations plays a profound role in governing disease impacts with subdivided populations experiencing less than 25% of the outbreak levels of a single homogeneous population. It predicts that gorilla group dispersal and limited group interactions are strong factors in preventing widespread population-level outbreaks of infectious disease after such diseases have been introduced into the population. However, even a moderate amount of human contact increases disease spread and can lead to population-level outbreaks., (© 2021 Wiley Periodicals LLC.)

In the past two decades, three coronaviruses with ancestral origins in bats have emerged and caused widespread outbreaks in humans, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the first SARS epidemic in 2002-2003, the appreciation of bats as key hosts of zoonotic coronaviruses has advanced rapidly. More than 4,000 coronavirus sequences from 14 bat families have been identified, yet the true diversity of bat coronaviruses is probably much greater. Given that bats are the likely evolutionary source for several human coronaviruses, including strains that cause mild upper respiratory tract disease, their role in historic and future pandemics requires ongoing investigation. We review and integrate information on bat-coronavirus interactions at the molecular, tissue, host and population levels. We identify critical gaps in knowledge of bat coronaviruses, which relate to spillover and pandemic risk, including the pathways to zoonotic spillover, the infection dynamics within bat reservoir hosts, the role of prior adaptation in intermediate hosts for zoonotic transmission and the viral genotypes or traits that predict zoonotic capacity and pandemic potential. Filling these knowledge gaps may help prevent the next pandemic., (© 2021. Springer Nature Limited.)

Cross-species transmission of pathogens is intimately linked to human and environmental health. With limited healthcare and challenging living conditions, people living in poverty may be particularly susceptible to endemic and emerging diseases. Similarly, wildlife is impacted by human influences, including pathogen sharing, especially for species in close contact with people and domesticated animals. Here we investigate human and animal contacts and human health in a community living around the Bwindi Impenetrable National Park (BINP), Uganda. We used contact and health survey data to identify opportunities for cross-species pathogen transmission, focusing mostly on people and the endangered mountain gorilla. We conducted a survey with background questions and self-reported diaries to investigate 100 participants' health, such as symptoms and behaviours, and contact patterns, including direct contacts and sightings over a week. Contacts were revealed through networks, including humans, domestic, peri-domestic, and wild animal groups for 1) contacts seen in the week of background questionnaire completion, and 2) contacts seen during the diary week. Participants frequently felt unwell during the study, reporting from one to 10 disease symptoms at different intensity levels, with severe symptoms comprising 6.4% of the diary records and tiredness and headaches the most common symptoms. After human-human contacts, direct contact with livestock and peri-domestic animals were the most common. The contact networks were moderately connected and revealed a preference in contacts within the same taxon and within their taxa groups. Sightings of wildlife were much more common than touching. However, despite contact with wildlife being the rarest of all contact types, one direct contact with a gorilla with a timeline including concerning participant health symptoms was reported. When considering all interaction types, gorillas mostly exhibited intra-species contact, but were found to interact with five other species, including people and domestic animals. Our findings reveal a local human population with recurrent symptoms of illness in a location with intense exposure to factors that can increase pathogen transmission, such as direct contact with domestic and wild animals and proximity among animal species. Despite significant biases and study limitations, the information generated here can guide future studies, such as models for disease spread and One Health interventions., Competing Interests: The authors have declared that no competing interests exist.

Decontamination helps limit environmental transmission of infectious agents. It is required for the safe reuse of contaminated medical, laboratory, and personal protective equipment, and for the safe handling of biological samples. Heat treatment is a common decontamination method, notably used for viruses. We show that for liquid specimens (here, solution of SARS-CoV-2 in cell culture medium), the virus inactivation rate under heat treatment at 70°C can vary by almost two orders of magnitude depending on the treatment procedure, from a half-life of 0.86 min (95% credible interval [CI] 0.09, 1.77) in closed vials in a heat block to 37.04 min (95% CI 12.64, 869.82) in uncovered plates in a dry oven. These findings suggest a critical role of evaporation in virus inactivation via dry heat. Placing samples in open or uncovered containers may dramatically reduce the speed and efficacy of heat treatment for virus inactivation. Given these findings, we reviewed the literature on temperature-dependent coronavirus stability and found that specimen container types, along with whether they are closed, covered, or uncovered, are rarely reported in the scientific literature. Heat-treatment procedures must be fully specified when reporting experimental studies to facilitate result interpretation and reproducibility, and must be carefully considered when developing decontamination guidelines. IMPORTANCE Heat is a powerful weapon against most infectious agents. It is widely used for decontamination of medical, laboratory, and personal protective equipment, and for biological samples. There are many methods of heat treatment, and methodological details can affect speed and efficacy of decontamination. We applied four different heat-treatment procedures to liquid specimens containing SARS-CoV-2. Our results show that the container used to store specimens during decontamination can substantially affect inactivation rate; for a given initial level of contamination, decontamination time can vary from a few minutes in closed vials to several hours in uncovered plates. Reviewing the literature, we found that container choices and heat treatment methods are only rarely reported explicitly in methods sections. Our study shows that careful consideration of heat-treatment procedure-in particular the choice of specimen container and whether it is covered-can make results more consistent across studies, improve decontamination practice, and provide insight into the mechanisms of virus inactivation.