Microbiology & Cell Biology

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    Comparative Aerosol and Surface Stability of SARS-CoV-2 Variants of Concern
    (Centers for Disease Control and Prevention, 2023-05) Bushmaker, Trenton; Kwe Yinda, Claude; Morris, Dylan H.; Holbrook, Myndi G.; Gamble, Amandine; Adney, Danielle; Bushmaker, Cara; van Doremalen, Neeltje; Fischer, Robert J.; Plowright, Raina K.; Lloyd-Smith, James O.; Munster, Vincent J.
    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.
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    Severe Acute Respiratory Syndrome Coronavirus 2 Is Detected in the Gastrointestinal Tract of Asymptomatic Endoscopy Patients but Is Unlikely to Pose a Significant Risk to Healthcare Personnel
    (Elsevier, 2022-06) Cherne, Michelle D.; Gentry, Andrew B.; Nemudraia, Anna; Nemudryi, Artem; Hedges, Jodi F.; Walk, Heather; Blackwell, Karlin; Snyder, Deann T.; Jerome, Maria; Madden, Wyatt; Hashimi, Marziah; Sebrell, T. Andrew; King, David B.; Plowright, Raina K.; Jutila, Mark A.; Wiedenheft, Blake; Bimczok, Diane
    Background and aims. Recent evidence suggests that the gut is an additional target for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection. However, whether SARS-CoV-2 spreads via gastrointestinal secretions remains unclear. To determine the prevalence of gastrointestinal SARS-CoV-2 infection in asymptomatic subjects, we analyzed gastrointestinal biopsy and liquid samples from endoscopy patients for the presence of SARS-CoV-2. Methods. We enrolled 100 endoscopic patients without known SARS-CoV-2 infection (cohort A) and 12 patients with a previous COVID-19 diagnosis (cohort B) in a cohort study performed at a regional hospital. Gastrointestinal biopsies and fluids were screened for SARS-CoV-2 by polymerase chain reaction (PCR), immunohistochemistry, and virus isolation assay, and the stability of SARS CoV-2 in gastrointestinal liquids in vitro was analyzed. Results. SARS-CoV-2 ribonucleic acid was detected by PCR in the colonic tissue of 1/100 patients in cohort A. In cohort B, 3 colonic liquid samples tested positive for SARS-CoV-2 by PCR and viral nucleocapsid protein was detected in the epithelium of the respective biopsy samples. However, no infectious virions were recovered from any samples. In vitro exposure of SARS-CoV-2 to colonic liquid led to a 4-log-fold reduction of infectious SARS-CoV-2 within 1 hour (P ≤ .05). Conclusion. Overall, the persistent detection of SARS-CoV-2 in endoscopy samples after resolution of COVID-19 points to the gut as a long term reservoir for SARS-CoV-2. Since no infectious virions were recovered and SARS-CoV-2 was rapidly inactivated in the presence of colon liquids, it is unlikely that performing endoscopic procedures is associated with a significant infection risk due to undiagnosed asymptomatic or persistent gastrointestinal SARS-CoV-2 infections.
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    Prioritizing surveillance of Nipah virus in India
    (2019-06) Plowright, Raina K.; Becker, Daniel J.; Crowley, Daniel E.; Washburne, Alex D.; Huang, Tao; Nameer, P. O.; Gurley, Emily S.; Han, Barbara A.
    The 2018 outbreak of Nipah virus in Kerala, India, highlights the need for global surveillance of henipaviruses in bats, which are the reservoir hosts for this and other viruses. Nipah virus, an emerging paramyxovirus in the genus Henipavirus, causes severe disease and stuttering chains of transmission in humans and is considered a potential pandemic threat. In May 2018, an outbreak of Nipah virus began in Kerala, > 1800 km from the sites of previous outbreaks in eastern India in 2001 and 2007. Twenty-three people were infected and 21 people died (16 deaths and 18 cases were laboratory confirmed). Initial surveillance focused on insectivorous bats (Megaderma spasma), whereas follow-up surveys within Kerala found evidence of Nipah virus in fruit bats (Pteropus medius). P. medius is the confirmed host in Bangladesh and is now a confirmed host in India. However, other bat species may also serve as reservoir hosts of henipaviruses. To inform surveillance of Nipah virus in bats, we reviewed and analyzed the published records of Nipah virus surveillance globally. We applied a trait-based machine learning approach to a subset of species that occur in Asia, Australia, and Oceana. In addition to seven species in Kerala that were previously identified as Nipah virus seropositive, we identified at least four bat species that, on the basis of trait similarity with known Nipah virus-seropositive species, have a relatively high likelihood of exposure to Nipah or Nipah-like viruses in India. These machine-learning approaches provide the first step in the sequence of studies required to assess the risk of Nipah virus spillover in India. Nipah virus surveillance not only within Kerala but also elsewhere in India would benefit from a research pipeline that included surveys of known and predicted reservoirs for serological evidence of past infection with Nipah virus (or cross reacting henipaviruses). Serosurveys should then be followed by longitudinal spatial and temporal studies to detect shedding and isolate virus from species with evidence of infection. Ecological studies will then be required to understand the dynamics governing prevalence and shedding in bats and the contacts that could pose a risk to public health.
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    A bioinformatic pipeline for identifying informative SNP panels for parentage assignment from RADseq data
    (2018-06) Andrews, Kimberly R.; Adams, Jennifer R.; Cassirer, E. Frances; Plowright, Raina K.; Gardner, Colby; Dwire, Maggie; Hohenlohe, Paul A.; Waits, Lisette P.
    The development of high-throughput sequencing technologies is dramatically increasing the use of single nucleotide polymorphisms (SNPs) across the field of genetics, but most parentage studies of wild populations still rely on microsatellites. We developed a bioinformatic pipeline for identifying SNP panels that are informative for parentage analysis from restriction site-associated DNA sequencing (RADseq) data. This pipeline includes options for analysis with or without a reference genome, and provides methods to maximize genotyping accuracy and select sets of unlinked loci that have high statistical power. We test this pipeline on small populations of Mexican gray wolf and bighorn sheep, for which parentage analyses are expected to be challenging due to low genetic diversity and the presence of many closely related individuals. We compare the results of parentage analysis across SNP panels generated with or without the use of a reference genome, and between SNPs and microsatellites. For Mexican gray wolf, we conducted parentage analyses for 30 pups from a single cohort where samples were available from 64% of possible mothers and 53% of possible fathers, and the accuracy of parentage assignments could be estimated because true identities of parents were known a priori based on field data. For bighorn sheep, we conducted maternity analyses for 39 lambs from five cohorts where 77% of possible mothers were sampled, but true identities of parents were unknown. Analyses with and without a reference genome produced SNP panels with ≥95% parentage assignment accuracy for Mexican gray wolf, outperforming microsatellites at 78% accuracy. Maternity assignments were completely consistent across all SNP panels for the bighorn sheep, and were 74.4% consistent with assignments from microsatellites. Accuracy and consistency of parentage analysis were not reduced when using as few as 284 SNPs for Mexican gray wolf and 142 SNPs for bighorn sheep, indicating our pipeline can be used to develop SNP genotyping assays for parentage analysis with relatively small numbers of loci.
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    Environmental persistence of influenza H5N1 is driven by temperature and salinity: insights from a Bayesian meta-analysis
    (2018-09) Martin, Gerardo A.; Becker, Daniel J.; Plowright, Raina K.
    Environmental persistence of zoonotic pathogens is a key trait that influences the probability of zoonotic spillover. Pathogen survival outside of the host determines the window available for contact with the new recipient host species and the dose of pathogen available to that host. The longer a pathogen survives in the environment, the more disconnected the reservoir and recipient hosts can be in space and time, and the more likely that an infective dose will be available to recipient hosts. Therefore, environmental persistence is a key parameter for mechanistic models needed to predict pathogen spillover. Avian influenza can be transmitted from wildlife to poultry and people in part due to its ability to persist in the environment. Considerable work has been done to quantify trends in avian influenza persistence across environmental conditions, often published in separate studies with separate datasets. In this paper, we quantify the trends and variability of avian influenza viral persistence across environmental conditions by collating disjoint experimental data on viral particle persistence in water across many studies and a range of environmental conditions. The collated data represent 120 estimates from three different studies of the decay rates of highly pathogenic avian influenza H5N1 (90 estimates from Asia and 30 from Europe) in response to temperature, pH, and salinity. We analyzed these data with a Bayesian model to control for biases with random effects and used experimental replicates and R2 estimates of the publication's regression procedures as statistical weights. We found temperature significantly decreases persistence of H5N1 virus in water, and this effect is stronger than that of salinity alone. Salinity interacts with temperature and probably drives the most contrasting persistence scenarios between cold-saline and warm-saline water bodies, where highest and lowest persistence times could occur respectively. Our work provides needed parameters for models that examine the risk of spillover of avian influenza viruses.
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    Persistent infections support maintenance of a coronavirus in a population of Australian bats (Myotis macropus)
    (2017-07) Jeong, J.; Smith, C. S.; Peel, Alison J.; Plowright, Raina K.; Kerlin, D. H.; McBroom, J.; McCallum, Hamish I.
    Understanding viral transmission dynamics within populations of reservoir hosts can facilitate greater knowledge of the spillover of emerging infectious diseases. While bat-borne viruses are of concern to public health, investigations into their dynamics have been limited by a lack of longitudinal data from individual bats. Here, we examine capture-mark-recapture (CMR) data from a species of Australian bat (Myotis macropus) infected with a putative novel Alphacoronavirus within a Bayesian framework. Then, we developed epidemic models to estimate the effect of persistently infectious individuals (which shed viruses for extensive periods) on the probability of viral maintenance within the study population. We found that the CMR data analysis supported grouping of infectious bats into persistently and transiently infectious bats. Maintenance of coronavirus within the study population was more likely in an epidemic model that included both persistently and transiently infectious bats, compared with the epidemic model with non-grouping of bats. These findings, using rare CMR data from longitudinal samples of individual bats, increase our understanding of transmission dynamics of bat viral infectious diseases.
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    Principles and Patterns of Bat Movements: From Aerodynamics to Ecology
    (2017-09) Voigt, Christian C.; Frick, Winifred F.; Holderied, Marc W.; Holland, Richard; Kerth, Gerald; Mello, Marco A. R.; Plowright, Raina K.; Swartz, Sharon; Yovel, Yossi
    Movement ecology as an integrative discipline has advanced associated fields because it presents not only a conceptual framework for understanding movement principles but also helps formulate predictions about the consequences of movements for animals and their environments. Here, we synthesize recent studies on principles and patterns of bat movements in context of the movement ecology paradigm. The motion capacity of bats is defined by their highly articulated, flexible wings. Power production during flight follows a U-shaped curve in relation to speed in bats yet, in contrast to birds, bats use mostly exogenous nutrients for sustained flight. The navigation capacity of most bats is dominated by the echolocation system, yet other sensory modalities, including an iron-based magnetic sense, may contribute to navigation depending on a bat\'s familiarity with the terrain. Patterns derived from these capacities relate to antagonistic and mutualistic interactions with food items. The navigation capacity of bats may influence their sociality, in particular, the extent of group foraging based on eavesdropping on conspecifics' echolocation calls. We infer that understanding the movement ecology of bats within the framework of the movement ecology paradigm provides new insights into ecological processes mediated by bats, from ecosystem services to diseases.
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    Contact and contagion: Probability of transmission given contact varies with demographic state in bighorn sheep
    (2017-05) Manlove, Kezia R.; Cassirer, E. Frances; Plowright, Raina K.; Cross, Paul C.; Hudson, Peter J.
    Understanding both contact and probability of transmission given contact are key to managing wildlife disease. However, wildlife disease research tends to focus on contact heterogeneity, in part because the probability of transmission given contact is notoriously difficult to measure. Here, we present a first step towards empirically investigating the probability of transmission given contact in free-ranging wildlife. We used measured contact networks to test whether bighorn sheep demographic states vary systematically in infectiousness or susceptibility to Mycoplasma ovipneumoniae, an agent responsible for bighorn sheep pneumonia. We built covariates using contact network metrics, demographic information and infection status, and used logistic regression to relate those covariates to lamb survival. The covariate set contained degree, a classic network metric describing node centrality, but also included covariates breaking the network metrics into subsets that differentiated between contacts with yearlings, ewes with lambs, and ewes without lambs, and animals with and without active infections. Yearlings, ewes with lambs, and ewes without lambs showed similar group membership patterns, but direct interactions involving touch occurred at a rate two orders of magnitude higher between lambs and reproductive ewes than between any classes of adults or yearlings, and one order of magnitude higher than direct interactions between multiple lambs. Although yearlings and non-reproductive bighorn ewes regularly carried M. ovipneumoniae, our models suggest that a contact with an infected reproductive ewe had approximately five times the odds of producing a lamb mortality event of an identical contact with an infected dry ewe or yearling. Consequently, management actions targeting infected animals might lead to unnecessary removal of young animals that carry pathogens but rarely transmit. This analysis demonstrates a simple logistic regression approach for testing a priori hypotheses about variation in the odds of transmission given contact for free-ranging hosts, and may be broadly applicable for investigations in wildlife disease ecology.
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    Null expectations for disease dynamics in shrinking habitat: dilution or amplification?
    (2017-06) Faust, Christina L.; Dobson, Andrew P.; Gottdenker, Nicole; Bloomfield, Laura S. P.; McCallum, Hamish I.; Gillespie, Thomas R.; Diuk-Wasser, Maria; Plowright, Raina K.
    As biodiversity declines with anthropogenic land-use change, it is increasingly important to understand how changing biodiversity affects infectious disease risk. The dilution effect hypothesis, which points to decreases in biodiversity as critical to an increase in infection risk, has received considerable attention due to the allure of a win-win scenario for conservation and human well-being. Yet some empirical data suggest that the dilution effect is not a generalizable phenomenon. We explore the response of pathogen transmission dynamics to changes in biodiversity that are driven by habitat loss using an allometrically scaled multi-host model. With this model, we show that declining habitat, and thus declining biodiversity, can lead to either increasing or decreasing infectious-disease risk, measured as endemic prevalence. Whether larger habitats, and thus greater biodiversity, lead to a decrease (dilution effect) or increase (amplification effect) in infection prevalence depends upon the pathogen transmission mode and how host competence scales with body size. Dilution effects were detected for most frequency-transmitted pathogens and amplification effects were detected for density-dependent pathogens. Amplification effects were also observed over a particular range of habitat loss in frequency-dependent pathogens when we assumed that host competence was greatest in large-bodied species. By contrast, only amplification effects were observed for density-dependent pathogens; host competency only affected the magnitude of the effect. These models can be used to guide future empirical studies of biodiversity-disease relationships across gradients of habitat loss. The type of transmission, the relationship between host competence and community assembly, the identity of hosts contributing to transmission, and how transmission scales with area are essential factors to consider when elucidating the mechanisms driving disease risk in shrinking habitat.
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    Microclimates Might Limit Indirect Spillover of the Bat Borne Zoonotic Hendra Virus
    (2017-01) Martin, Gerardo A.; Webb, Rebecca J.; Chen, Carla; Plowright, Raina K.; Skerratt, Lee F.
    Infectious diseases are transmitted when susceptible hosts are exposed to pathogen particles that can replicate within them. Among factors that limit transmission, the environment is particularly important for indirectly transmitted parasites. To try and assess a pathogens' ability to be transmitted through the environment and mitigate risk, we need to quantify its decay where transmission occurs in space such as the microclimate harbouring the pathogen. Hendra virus, a Henipavirus from Australian Pteropid bats, spills-over to horses and humans, causing high mortality. While a vaccine is available, its limited uptake has reduced opportunities for adequate risk management to humans, hence the need to develop synergistic preventive measures, like disrupting its transmission pathways. Transmission likely occurs shortly after virus excretion in paddocks; however, no survival estimates to date have used real environmental conditions. Here, we recorded microclimate conditions and fitted models that predict temperatures and potential evaporation, which we used to simulate virus survival with a temperature-survival model and modification based on evaporation. Predicted survival was lower than previously estimated and likely to be even lower according to potential evaporation. Our results indicate that transmission should occur shortly after the virus is excreted, in a relatively direct way. When potential evaporation is low, and survival is more similar to temperature dependent estimates, transmission might be indirect because the virus can wait several hours until contact is made. We recommend restricting horses' access to trees during night time and reducing grass under trees to reduce virus survival.
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