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Artikel ; Online: Genetic drift and purifying selection shape within-host influenza A virus populations during natural swine infections.

VanInsberghe, David / McBride, Dillon S / DaSilva, Juliana / Stark, Thomas J / Lau, Max S Y / Shepard, Samuel S / Barnes, John R / Bowman, Andrew S / Lowen, Anice C / Koelle, Katia

PLoS pathogens

2024 Band 20, Heft 4, Seite(n) e1012131

Abstract: Patterns of within-host influenza A virus (IAV) diversity and evolution have been described in natural human infections, but these patterns remain poorly characterized in non-human hosts. Elucidating these dynamics is important to better understand IAV ... ...

Abstract	Patterns of within-host influenza A virus (IAV) diversity and evolution have been described in natural human infections, but these patterns remain poorly characterized in non-human hosts. Elucidating these dynamics is important to better understand IAV biology and the evolutionary processes that govern spillover into humans. Here, we sampled an IAV outbreak in pigs during a week-long county fair to characterize viral diversity and evolution in this important reservoir host. Nasal wipes were collected on a daily basis from all pigs present at the fair, yielding up to 421 samples per day. Subtyping of PCR-positive samples revealed the co-circulation of H1N1 and H3N2 subtype swine IAVs. PCR-positive samples with robust Ct values were deep-sequenced, yielding 506 sequenced samples from a total of 253 pigs. Based on higher-depth re-sequenced data from a subset of these initially sequenced samples (260 samples from 168 pigs), we characterized patterns of within-host IAV genetic diversity and evolution. We find that IAV genetic diversity in single-subtype infected pigs is low, with the majority of intrahost Single Nucleotide Variants (iSNVs) present at frequencies of <10%. The ratio of the number of nonsynonymous to the number of synonymous iSNVs is significantly lower than under the neutral expectation, indicating that purifying selection shapes patterns of within-host viral diversity in swine. The dynamic turnover of iSNVs and their pronounced frequency changes further indicate that genetic drift also plays an important role in shaping IAV populations within pigs. Taken together, our results highlight similarities in patterns of IAV genetic diversity and evolution between humans and swine, including the role of stochastic processes in shaping within-host IAV dynamics.
Mesh-Begriff(e)	Animals ; Swine ; Orthomyxoviridae Infections/virology ; Genetic Drift ; Swine Diseases/virology ; Influenza A Virus, H3N2 Subtype/genetics ; Influenza A virus/genetics ; Influenza A Virus, H1N1 Subtype/genetics ; Genetic Variation ; Evolution, Molecular ; Selection, Genetic ; Phylogeny
Sprache	Englisch
Erscheinungsdatum	2024-04-16
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1012131
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Vaccination under uncertainty.

Lau, Max S Y / Grenfell, Bryan T

Nature ecology & evolution

2018 Band 2, Heft 9, Seite(n) 1350–1351

Mesh-Begriff(e)	Africa, Eastern ; Animals ; Foot-and-Mouth Disease ; Uncertainty ; Vaccination
Sprache	Englisch
Erscheinungsdatum	2018-08-04
Erscheinungsland	England
Dokumenttyp	Journal Article ; Comment
ISSN	2397-334X
ISSN (online)	2397-334X
DOI	10.1038/s41559-018-0652-x
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Genetic drift and purifying selection shape within-host influenza A virus populations during natural swine infections.

VanInsberghe, David / McBride, Dillon S / DaSilva, Juliana / Stark, Thomas J / Lau, Max S Y / Shepard, Samuel S / Barnes, John R / Bowman, Andrew S / Lowen, Anice C / Koelle, Katia

bioRxiv : the preprint server for biology

2023

Abstract	Patterns of within-host influenza A virus (IAV) diversity and evolution have been described in natural human infections, but these patterns remain poorly characterized in non-human hosts. Elucidating these dynamics is important to better understand IAV biology and the evolutionary processes that govern spillover into humans. Here, we sampled an IAV outbreak in pigs during a week-long county fair to characterize viral diversity and evolution in this important reservoir host. Nasal wipes were collected on a daily basis from all pigs present at the fair, yielding up to 421 samples per day. Subtyping of PCR-positive samples revealed the co-circulation of H1N1 and H3N2 subtype IAVs. PCR-positive samples with robust Ct values were deep-sequenced, yielding 506 sequenced samples from a total of 253 pigs. Based on higher-depth re-sequenced data from a subset of these initially sequenced samples (260 samples from 168 pigs), we characterized patterns of within-host IAV genetic diversity and evolution. We find that IAV genetic diversity in single-subtype infected pigs is low, with the majority of intra-host single nucleotide variants (iSNVs) present at frequencies of <10%. The ratio of the number of nonsynonymous to the number of synonymous iSNVs is significantly lower than under the neutral expectation, indicating that purifying selection shapes patterns of within-host viral diversity in swine. The dynamic turnover of iSNVs and their pronounced frequency changes further indicate that genetic drift also plays an important role in shaping IAV populations within pigs. Taken together, our results highlight similarities in patterns of IAV genetic diversity and evolution between humans and swine, including the role of stochastic processes in shaping within-host IAV dynamics.
Sprache	Englisch
Erscheinungsdatum	2023-10-25
Erscheinungsland	United States
Dokumenttyp	Preprint
DOI	10.1101/2023.10.23.563581
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Post-lockdown changes of age-specific susceptibility and its correlation with adherence to social distancing measures

Max S. Y. Lau / Carol Liu / Aaron J. Siegler / Patrick S. Sullivan / Lance A. Waller / Kayoko Shioda / Benjamin A. Lopman

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Band 8

Abstract: Abstract Social distancing measures are effective in reducing overall community transmission but much remains unknown about how they have impacted finer-scale dynamics. In particular, much is unknown about how changes of contact patterns and other ... ...

Abstract	Abstract Social distancing measures are effective in reducing overall community transmission but much remains unknown about how they have impacted finer-scale dynamics. In particular, much is unknown about how changes of contact patterns and other behaviors including adherence to social distancing, induced by these measures, may have impacted finer-scale transmission dynamics among different age groups. In this paper, we build a stochastic age-specific transmission model to systematically characterize the degree and variation of age-specific transmission dynamics, before and after lifting the lockdown in Georgia, USA. We perform Bayesian (missing-)data-augmentation model inference, leveraging reported age-specific case, seroprevalence and mortality data. We estimate that overall population-level transmissibility was reduced to 41.2% with 95% CI [39%, 43.8%] of the pre-lockdown level in about a week of the announcement of the shelter-in-place order. Although it subsequently increased after the lockdown was lifted, it only bounced back to 62% [58%, 67.2%] of the pre-lockdown level after about a month. We also find that during the lockdown susceptibility to infection increases with age. Specifically, relative to the oldest age group (> 65+), susceptibility for the youngest age group (0–17 years) is 0.13 [0.09, 0.18], and it increases to 0.53 [0.49, 0.59] for 18–44 and 0.75 [0.68, 0.82] for 45–64. More importantly, our results reveal clear changes of age-specific susceptibility (defined as average risk of getting infected during an infectious contact incorporating age-dependent behavioral factors) after the lockdown was lifted, with a trend largely consistent with reported age-specific adherence levels to social distancing and preventive measures. Specifically, the older groups (> 45) (with the highest levels of adherence) appear to have the most significant reductions of susceptibility (e.g., post-lockdown susceptibility reduced to 31.6% [29.3%, 34%] of the estimate before lifting the lockdown for the 6+ ...
Schlagwörter	Medicine ; R ; Science ; Q
Thema/Rubrik (Code)	300
Sprache	Englisch
Erscheinungsdatum	2022-03-01T00:00:00Z
Verlag	Nature Portfolio
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Comparing and linking machine learning and semi-mechanistic models for the predictability of endemic measles dynamics.

Lau, Max S Y / Becker, Alex / Madden, Wyatt / Waller, Lance A / Metcalf, C Jessica E / Grenfell, Bryan T

PLoS computational biology

2022 Band 18, Heft 9, Seite(n) e1010251

Abstract: Measles is one the best-documented and most-mechanistically-studied non-linear infectious disease dynamical systems. However, systematic investigation into the comparative performance of traditional mechanistic models and machine learning approaches in ... ...

Abstract	Measles is one the best-documented and most-mechanistically-studied non-linear infectious disease dynamical systems. However, systematic investigation into the comparative performance of traditional mechanistic models and machine learning approaches in forecasting the transmission dynamics of this pathogen are still rare. Here, we compare one of the most widely used semi-mechanistic models for measles (TSIR) with a commonly used machine learning approach (LASSO), comparing performance and limits in predicting short to long term outbreak trajectories and seasonality for both regular and less regular measles outbreaks in England and Wales (E&W) and the United States. First, our results indicate that the proposed LASSO model can efficiently use data from multiple major cities and achieve similar short-to-medium term forecasting performance to semi-mechanistic models for E&W epidemics. Second, interestingly, the LASSO model also captures annual to biennial bifurcation of measles epidemics in E&W caused by susceptible response to the late 1940s baby boom. LASSO may also outperform TSIR for predicting less-regular dynamics such as those observed in major cities in US between 1932-45. Although both approaches capture short-term forecasts, accuracy suffers for both methods as we attempt longer-term predictions in highly irregular, post-vaccination outbreaks in E&W. Finally, we illustrate that the LASSO model can both qualitatively and quantitatively reconstruct mechanistic assumptions, notably susceptible dynamics, in the TSIR model. Our results characterize the limits of predictability of infectious disease dynamics for strongly immunizing pathogens with both mechanistic and machine learning models, and identify connections between these two approaches.
Mesh-Begriff(e)	Communicable Diseases/epidemiology ; Disease Outbreaks ; Epidemics ; Humans ; Machine Learning ; Measles/epidemiology ; United States/epidemiology
Sprache	Englisch
Erscheinungsdatum	2022-09-08
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.1010251
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Post-lockdown changes of age-specific susceptibility and its correlation with adherence to social distancing measures.

Lau, Max S Y / Liu, Carol / Siegler, Aaron J / Sullivan, Patrick S / Waller, Lance A / Shioda, Kayoko / Lopman, Benjamin A

Scientific reports

2022 Band 12, Heft 1, Seite(n) 4637

Abstract: Social distancing measures are effective in reducing overall community transmission but much remains unknown about how they have impacted finer-scale dynamics. In particular, much is unknown about how changes of contact patterns and other behaviors ... ...

Abstract	Social distancing measures are effective in reducing overall community transmission but much remains unknown about how they have impacted finer-scale dynamics. In particular, much is unknown about how changes of contact patterns and other behaviors including adherence to social distancing, induced by these measures, may have impacted finer-scale transmission dynamics among different age groups. In this paper, we build a stochastic age-specific transmission model to systematically characterize the degree and variation of age-specific transmission dynamics, before and after lifting the lockdown in Georgia, USA. We perform Bayesian (missing-)data-augmentation model inference, leveraging reported age-specific case, seroprevalence and mortality data. We estimate that overall population-level transmissibility was reduced to 41.2% with 95% CI [39%, 43.8%] of the pre-lockdown level in about a week of the announcement of the shelter-in-place order. Although it subsequently increased after the lockdown was lifted, it only bounced back to 62% [58%, 67.2%] of the pre-lockdown level after about a month. We also find that during the lockdown susceptibility to infection increases with age. Specifically, relative to the oldest age group (> 65+), susceptibility for the youngest age group (0-17 years) is 0.13 [0.09, 0.18], and it increases to 0.53 [0.49, 0.59] for 18-44 and 0.75 [0.68, 0.82] for 45-64. More importantly, our results reveal clear changes of age-specific susceptibility (defined as average risk of getting infected during an infectious contact incorporating age-dependent behavioral factors) after the lockdown was lifted, with a trend largely consistent with reported age-specific adherence levels to social distancing and preventive measures. Specifically, the older groups (> 45) (with the highest levels of adherence) appear to have the most significant reductions of susceptibility (e.g., post-lockdown susceptibility reduced to 31.6% [29.3%, 34%] of the estimate before lifting the lockdown for the 6+ group). Finally, we find heterogeneity in case reporting among different age groups, with the lowest rate occurring among the 0-17 group (9.7% [6.4%, 19%]). Our results provide a more fundamental understanding of the impacts of stringent lockdown measures, and finer evidence that other social distancing and preventive measures may be effective in reducing SARS-CoV-2 transmission. These results may be exploited to guide more effective implementations of these measures in many current settings (with low vaccination rate globally and emerging variants) and in future potential outbreaks of novel pathogens.
Mesh-Begriff(e)	Adolescent ; Age Factors ; Bayes Theorem ; COVID-19/epidemiology ; COVID-19/prevention & control ; Child ; Child, Preschool ; Communicable Disease Control ; Humans ; Infant ; Infant, Newborn ; Physical Distancing ; SARS-CoV-2 ; Seroepidemiologic Studies
Sprache	Englisch
Erscheinungsdatum	2022-03-17
Erscheinungsland	England
Dokumenttyp	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-08566-6
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Characterizing superspreading events and age-specific infectiousness of SARS-CoV-2 transmission in Georgia, USA.

Lau, Max S Y / Grenfell, Bryan / Thomas, Michael / Bryan, Michael / Nelson, Kristin / Lopman, Ben

Proceedings of the National Academy of Sciences of the United States of America

2020 Band 117, Heft 36, Seite(n) 22430–22435

Abstract: ... directly responsible for 20% of all infections. We estimate that the infected nonelderly cases (<60 y ...

Abstract	It is imperative to advance our understanding of heterogeneities in the transmission of SARS-CoV-2 such as age-specific infectiousness and superspreading. To this end, it is important to exploit multiple data streams that are becoming abundantly available during the pandemic. In this paper, we formulate an individual-level spatiotemporal mechanistic framework to integrate individual surveillance data with geolocation data and aggregate mobility data, enabling a more granular understanding of the transmission dynamics of SARS-CoV-2. We analyze reported cases, between March and early May 2020, in five (urban and rural) counties in the state of Georgia. First, our results show that the reproductive number reduced to below one in about 2 wk after the shelter-in-place order. Superspreading appears to be widespread across space and time, and it may have a particularly important role in driving the outbreak in rural areas and an increasing importance toward later stages of outbreaks in both urban and rural settings. Overall, about 2% of cases were directly responsible for 20% of all infections. We estimate that the infected nonelderly cases (<60 y) may be 2.78 [2.10, 4.22] times more infectious than the elderly, and the former tend to be the main driver of superspreading. Our results improve our understanding of the natural history and transmission dynamics of SARS-CoV-2. More importantly, we reveal the roles of age-specific infectiousness and characterize systematic variations and associated risk factors of superspreading. These have important implications for the planning of relaxing social distancing and, more generally, designing optimal control measures.
Mesh-Begriff(e)	Basic Reproduction Number ; Betacoronavirus ; COVID-19 ; Contact Tracing ; Coronavirus Infections/epidemiology ; Coronavirus Infections/prevention & control ; Coronavirus Infections/transmission ; Disease Transmission, Infectious/prevention & control ; Disease Transmission, Infectious/statistics & numerical data ; Georgia/epidemiology ; Humans ; Pandemics/prevention & control ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/prevention & control ; Pneumonia, Viral/transmission ; Risk Factors ; SARS-CoV-2
Schlagwörter	covid19
Sprache	Englisch
Erscheinungsdatum	2020-08-20
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2011802117
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Model diagnostics and refinement for phylodynamic models.

Max S Y Lau / Bryan T Grenfell / Colin J Worby / Gavin J Gibson

PLoS Computational Biology, Vol 15, Iss 4, p e

2019 Band 1006955

Abstract: Phylodynamic modelling, which studies the joint dynamics of epidemiological and evolutionary processes, has made significant progress in recent years due to increasingly available genomic data and advances in statistical modelling. These advances have ... ...

Abstract	Phylodynamic modelling, which studies the joint dynamics of epidemiological and evolutionary processes, has made significant progress in recent years due to increasingly available genomic data and advances in statistical modelling. These advances have greatly improved our understanding of transmission dynamics of many important pathogens. Nevertheless, there remains a lack of effective, targetted diagnostic tools for systematically detecting model mis-specification. Development of such tools is essential for model criticism, refinement, and calibration. The idea of utilising latent residuals for model assessment has already been exploited in general spatio-temporal epidemiological settings. Specifically, by proposing appropriately designed non-centered, re-parameterizations of a given epidemiological process, one can construct latent residuals with known sampling distributions which can be used to quantify evidence of model mis-specification. In this paper, we extend this idea to formulate a novel model-diagnostic framework for phylodynamic models. Using simulated examples, we show that our framework may effectively detect a particular form of mis-specification in a phylodynamic model, particularly in the event of superspreading. We also exemplify our approach by applying the framework to a dataset describing a local foot-and-mouth (FMD) outbreak in the UK, eliciting strong evidence against the assumption of no within-host-diversity in the outbreak. We further demonstrate that our framework can facilitate model calibration in real-life scenarios, by proposing a within-host-diversity model which appears to offer a better fit to data than one that assumes no within-host-diversity of FMD virus.
Schlagwörter	Biology (General) ; QH301-705.5
Thema/Rubrik (Code)	006
Sprache	Englisch
Erscheinungsdatum	2019-04-01T00:00:00Z
Verlag	Public Library of Science (PLoS)
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Model diagnostics and refinement for phylodynamic models.

Lau, Max S Y / Grenfell, Bryan T / Worby, Colin J / Gibson, Gavin J

PLoS computational biology

2019 Band 15, Heft 4, Seite(n) e1006955

Abstract	Phylodynamic modelling, which studies the joint dynamics of epidemiological and evolutionary processes, has made significant progress in recent years due to increasingly available genomic data and advances in statistical modelling. These advances have greatly improved our understanding of transmission dynamics of many important pathogens. Nevertheless, there remains a lack of effective, targetted diagnostic tools for systematically detecting model mis-specification. Development of such tools is essential for model criticism, refinement, and calibration. The idea of utilising latent residuals for model assessment has already been exploited in general spatio-temporal epidemiological settings. Specifically, by proposing appropriately designed non-centered, re-parameterizations of a given epidemiological process, one can construct latent residuals with known sampling distributions which can be used to quantify evidence of model mis-specification. In this paper, we extend this idea to formulate a novel model-diagnostic framework for phylodynamic models. Using simulated examples, we show that our framework may effectively detect a particular form of mis-specification in a phylodynamic model, particularly in the event of superspreading. We also exemplify our approach by applying the framework to a dataset describing a local foot-and-mouth (FMD) outbreak in the UK, eliciting strong evidence against the assumption of no within-host-diversity in the outbreak. We further demonstrate that our framework can facilitate model calibration in real-life scenarios, by proposing a within-host-diversity model which appears to offer a better fit to data than one that assumes no within-host-diversity of FMD virus.
Mesh-Begriff(e)	Animals ; Computational Biology/methods ; Computer Simulation ; Disease Outbreaks/statistics & numerical data ; Humans ; Models, Statistical ; Molecular Epidemiology/methods ; Molecular Epidemiology/statistics & numerical data ; Phylogeny ; Viruses/pathogenicity
Sprache	Englisch
Erscheinungsdatum	2019-04-05
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.1006955
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Characterizing superspreading events and age-specific infectiousness of SARS-CoV-2 transmission in Georgia, USA

Lau, Max S Y / Grenfell, Bryan / Thomas, Michael / Bryan, Michael / Nelson, Kristin / Lopman, Ben

Proc Natl Acad Sci U S A

Abstract: ... directly responsible for 20% of all infections. We estimate that the infected nonelderly cases (<60 y ...

Abstract	It is imperative to advance our understanding of heterogeneities in the transmission of SARS-CoV-2 such as age-specific infectiousness and superspreading. To this end, it is important to exploit multiple data streams that are becoming abundantly available during the pandemic. In this paper, we formulate an individual-level spatiotemporal mechanistic framework to integrate individual surveillance data with geolocation data and aggregate mobility data, enabling a more granular understanding of the transmission dynamics of SARS-CoV-2. We analyze reported cases, between March and early May 2020, in five (urban and rural) counties in the state of Georgia. First, our results show that the reproductive number reduced to below one in about 2 wk after the shelter-in-place order. Superspreading appears to be widespread across space and time, and it may have a particularly important role in driving the outbreak in rural areas and an increasing importance toward later stages of outbreaks in both urban and rural settings. Overall, about 2% of cases were directly responsible for 20% of all infections. We estimate that the infected nonelderly cases (<60 y) may be 2.78 [2.10, 4.22] times more infectious than the elderly, and the former tend to be the main driver of superspreading. Our results improve our understanding of the natural history and transmission dynamics of SARS-CoV-2. More importantly, we reveal the roles of age-specific infectiousness and characterize systematic variations and associated risk factors of superspreading. These have important implications for the planning of relaxing social distancing and, more generally, designing optimal control measures.
Schlagwörter	covid19
Verlag	WHO
Dokumenttyp	Artikel
Anmerkung	WHO #Covidence: #724876
Datenquelle	COVID19

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