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Leon AE, Fleming-Davies AE, Adelman JS, Hawley DM. Pathogen priming alters host transmission potential and predictors of transmissibility in a wild songbird species. mSphere 2025; 10:e0088624. [PMID: 40062847 PMCID: PMC12039224 DOI: 10.1128/msphere.00886-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 02/05/2025] [Indexed: 03/19/2025] Open
Abstract
Pathogen reinfections occur widely, but the extent to which reinfected hosts contribute to ongoing transmission is often unknown despite its implications for host-pathogen dynamics. House finches (Haemorhous mexicanus) acquire partial protection from initial exposure to the bacterial pathogen Mycoplasma gallisepticum (MG), with hosts readily reinfected with homologous or heterologous strains on short timescales. However, the extent to which reinfected hosts contribute to MG transmission has not been tested. We used three pathogen priming treatments-none, intermediate (repeated low-dose priming), or high (single high-dose priming)-to test how prior pathogen priming alters the likelihood of transmission to a cagemate during index bird reinfection with a homologous or heterologous MG strain. Relative to unprimed control hosts, the highest priming level strongly reduced maximum pathogen loads and transmission success of index birds during reinfections. Reinfections with the heterologous strain, previously shown to be more virulent and transmissible than the homologous strain used, resulted in higher pathogen loads within high-primed index birds and showed higher overall transmission success regardless of host priming treatment. This suggests that inherent differences in strain transmissibility are maintained in primed hosts, leading to the potential for ongoing transmission during reinfections. Finally, among individuals, transmission was most likely from hosts harboring higher within-host pathogen loads. However, associations between disease severity and transmission probability were dependent on a given bird's priming treatment. Overall, our results indicate that reinfections can result in ongoing transmission, particularly where reinfections result from a highly transmissible strain, with potential implications for virulence evolution.IMPORTANCEAs COVID-19 dramatically illustrated, humans and other animals can become infected with the same pathogen multiple times. Because individuals already have defenses against pathogens that their immune systems encountered before, reinfections are likely less contagious to others, but this is rarely directly tested. We used a songbird species and two strains of its common bacterial pathogen to study how contagious hosts are when their immune systems have some degree of prior experience with a pathogen. We found that reinfected hosts are not as contagious as initially infected ones. However, the more transmissible of the two strains, which also causes more harm to its hosts, was able to multiply more readily than the other strain within reinfected hosts and was more contagious in both reinfected and first-infected hosts. This suggests that reinfections might favor more harmful pathogen strains that are better able to overcome immune defenses.
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Affiliation(s)
- A. E. Leon
- Department of Biological Sciences, Virginia Tech, Blacksburg, Virginia, USA
| | | | - J. S. Adelman
- Department of Biological Sciences, University of Memphis, Memphis, Tennessee, USA
| | - D. M. Hawley
- Department of Biological Sciences, Virginia Tech, Blacksburg, Virginia, USA
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2
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Pooladvand P, Kendal JR, Tanaka MM. How cultural innovations trigger the emergence of new pathogens. Proc Natl Acad Sci U S A 2024; 121:e2322882121. [PMID: 39556748 PMCID: PMC11621466 DOI: 10.1073/pnas.2322882121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 08/14/2024] [Indexed: 11/20/2024] Open
Abstract
Cultural practices perceived to be adaptive-from clearing land for food production to medical innovations-can disseminate quickly through human populations. However, these same practices often have unintended maladaptive effects. A particularly consequential effect is the emergence of diseases. In numerous instances, a cultural change is followed by the appearance of a new pathogen. Here, we develop mathematical models to analyze the population processes through which cultural evolution precipitates the emergence of a new disease. We find that when a risk-bearing cultural practice spreads, emergence can be an unavoidable cost even if a safer alternative practice eventually evolves from the original. Social learning and a fitness advantage associated with the evolving practice drive early disease emergence but the two factors have distinct effects on the time to mutation of the pathogen and significant stochastic variation is observed. For example, a disease can take longer to emerge in a population that adopts the risk-bearing practice quickly than in a population that is slow to transition. Extending the model to explore the effects of an alternative practice evolving from the original, we find a nonmonotonic relationship between relative risk of the two practices and the median time to disease emergence. Our findings contribute to understanding how cultural evolution can shape pathogen evolution and highlight the unpredictability of disease emergence.
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Affiliation(s)
- Pantea Pooladvand
- School of Biotechnology and Biomedical Sciences, University of New South Wales, Sydney, NSW2052, Australia
- Evolution and Ecology Research Centre, University of New South Wales, Sydney, NSW2052, Australia
| | - Jeremy R. Kendal
- Department of Anthropology, Durham University, Durham DH1 3LE, United Kingdom
| | - Mark M. Tanaka
- School of Biotechnology and Biomedical Sciences, University of New South Wales, Sydney, NSW2052, Australia
- Evolution and Ecology Research Centre, University of New South Wales, Sydney, NSW2052, Australia
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3
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Bouros I, Hill EM, Keeling MJ, Moore S, Thompson RN. Prioritising older individuals for COVID-19 booster vaccination leads to optimal public health outcomes in a range of socio-economic settings. PLoS Comput Biol 2024; 20:e1012309. [PMID: 39116038 PMCID: PMC11309497 DOI: 10.1371/journal.pcbi.1012309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 07/09/2024] [Indexed: 08/10/2024] Open
Abstract
The rapid development of vaccines against SARS-CoV-2 altered the course of the COVID-19 pandemic. In most countries, vaccinations were initially targeted at high-risk populations, including older individuals and healthcare workers. Now, despite substantial infection- and vaccine-induced immunity in host populations worldwide, waning immunity and the emergence of novel variants continue to cause significant waves of infection and disease. Policy makers must determine how to deploy booster vaccinations, particularly when constraints in vaccine supply, delivery and cost mean that booster vaccines cannot be administered to everyone. A key question is therefore whether older individuals should again be prioritised for vaccination, or whether alternative strategies (e.g. offering booster vaccines to the individuals who have most contacts with others and therefore drive infection) can instead offer indirect protection to older individuals. Here, we use mathematical modelling to address this question, considering SARS-CoV-2 transmission in a range of countries with different socio-economic backgrounds. We show that the population structures of different countries can have a pronounced effect on the impact of booster vaccination, even when identical booster vaccination targeting strategies are adopted. However, under the assumed transmission model, prioritising older individuals for booster vaccination consistently leads to the most favourable public health outcomes in every setting considered. This remains true for a range of assumptions about booster vaccine supply and timing, and for different assumed policy objectives of booster vaccination.
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Affiliation(s)
- Ioana Bouros
- Department of Computer Science, University of Oxford, Oxford, United Kingdom
| | - Edward M. Hill
- Mathematics Institute, University of Warwick, Coventry, United Kingdom
- Zeeman Institute for Systems Biology and Infectious Disease Epidemiology Research (SBIDER), University of Warwick, Coventry, United Kingdom
- School of Life Sciences, University of Warwick, Coventry, United Kingdom
| | - Matt J. Keeling
- Mathematics Institute, University of Warwick, Coventry, United Kingdom
- Zeeman Institute for Systems Biology and Infectious Disease Epidemiology Research (SBIDER), University of Warwick, Coventry, United Kingdom
- School of Life Sciences, University of Warwick, Coventry, United Kingdom
| | - Sam Moore
- Lancaster Medical School, Lancaster University, Lancaster, United Kingdom
| | - Robin N. Thompson
- Mathematical Institute, University of Oxford, Oxford, United Kingdom
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4
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Huang CQ, Vishwanath S, Carnell GW, Chan ACY, Heeney JL. Immune imprinting and next-generation coronavirus vaccines. Nat Microbiol 2023; 8:1971-1985. [PMID: 37932355 DOI: 10.1038/s41564-023-01505-9] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 09/13/2023] [Indexed: 11/08/2023]
Abstract
Vaccines based on historical virus isolates provide limited protection from continuously evolving RNA viruses, such as influenza viruses or coronaviruses, which occasionally spill over between animals and humans. Despite repeated booster immunizations, population-wide declines in the neutralization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have occurred. This has been compared to seasonal influenza vaccinations in humans, where the breadth of immune responses induced by repeat exposures to antigenically distinct influenza viruses is confounded by pre-existing immunity-a mechanism known as imprinting. Since its emergence, SARS-CoV-2 has evolved in a population with partial immunity, acquired by infection, vaccination or both. Here we critically examine the evidence for and against immune imprinting in host humoral responses to SARS-CoV-2 and its implications for coronavirus disease 2019 (COVID-19) booster vaccine programmes.
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Affiliation(s)
- Chloe Qingzhou Huang
- Laboratory of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK
| | - Sneha Vishwanath
- Laboratory of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK
| | - George William Carnell
- Laboratory of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK
| | - Andrew Chun Yue Chan
- Laboratory of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK
| | - Jonathan Luke Heeney
- Laboratory of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
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5
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Hart WS, Park H, Jeong YD, Kim KS, Yoshimura R, Thompson RN, Iwami S. Analysis of the risk and pre-emptive control of viral outbreaks accounting for within-host dynamics: SARS-CoV-2 as a case study. Proc Natl Acad Sci U S A 2023; 120:e2305451120. [PMID: 37788317 PMCID: PMC10576149 DOI: 10.1073/pnas.2305451120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 09/07/2023] [Indexed: 10/05/2023] Open
Abstract
In the era of living with COVID-19, the risk of localised SARS-CoV-2 outbreaks remains. Here, we develop a multiscale modelling framework for estimating the local outbreak risk for a viral disease (the probability that a major outbreak results from a single case introduced into the population), accounting for within-host viral dynamics. Compared to population-level models previously used to estimate outbreak risks, our approach enables more detailed analysis of how the risk can be mitigated through pre-emptive interventions such as antigen testing. Considering SARS-CoV-2 as a case study, we quantify the within-host dynamics using data from individuals with omicron variant infections. We demonstrate that regular antigen testing reduces, but may not eliminate, the outbreak risk, depending on characteristics of local transmission. In our baseline analysis, daily antigen testing reduces the outbreak risk by 45% compared to a scenario without antigen testing. Additionally, we show that accounting for heterogeneity in within-host dynamics between individuals affects outbreak risk estimates and assessments of the impact of antigen testing. Our results therefore highlight important factors to consider when using multiscale models to design pre-emptive interventions against SARS-CoV-2 and other viruses.
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Affiliation(s)
- William S. Hart
- Mathematical Institute, University of Oxford, OxfordOX2 6GG, United Kingdom
- lnterdisciplinary Biology Laboratory, Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya464-8602, Japan
| | - Hyeongki Park
- lnterdisciplinary Biology Laboratory, Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya464-8602, Japan
| | - Yong Dam Jeong
- lnterdisciplinary Biology Laboratory, Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya464-8602, Japan
- Department of Mathematics, Pusan National University, Busan46241, South Korea
| | - Kwang Su Kim
- lnterdisciplinary Biology Laboratory, Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya464-8602, Japan
- Department of Scientific Computing, Pukyong National University, Busan48513, South Korea
| | - Raiki Yoshimura
- lnterdisciplinary Biology Laboratory, Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya464-8602, Japan
| | - Robin N. Thompson
- Mathematical Institute, University of Oxford, OxfordOX2 6GG, United Kingdom
- Mathematics Institute, University of Warwick, CoventryCV4 7AL, United Kingdom
- Zeeman Institute for Systems Biology and Infectious Disease Epidemiology Research, University of Warwick, CoventryCV4 7AL, United Kingdom
| | - Shingo Iwami
- lnterdisciplinary Biology Laboratory, Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya464-8602, Japan
- Institute of Mathematics for Industry, Kyushu University, Fukuoka819-0395, Japan
- Institute for the Advanced Study of Human Biology, Kyoto University, Kyoto606-8501, Japan
- Interdisciplinary Theoretical and Mathematical Sciences Program, RIKEN, Saitama351-0198, Japan
- NEXT-Ganken Program, Japanese Foundation for Cancer Research, Tokyo135-8550, Japan
- Science Groove Inc., Fukuoka810-0041, Japan
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Southall E, Ogi-Gittins Z, Kaye AR, Hart WS, Lovell-Read FA, Thompson RN. A practical guide to mathematical methods for estimating infectious disease outbreak risks. J Theor Biol 2023; 562:111417. [PMID: 36682408 DOI: 10.1016/j.jtbi.2023.111417] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 01/13/2023] [Accepted: 01/16/2023] [Indexed: 01/21/2023]
Abstract
Mathematical models are increasingly used throughout infectious disease outbreaks to guide control measures. In this review article, we focus on the initial stages of an outbreak, when a pathogen has just been observed in a new location (e.g., a town, region or country). We provide a beginner's guide to two methods for estimating the risk that introduced cases lead to sustained local transmission (i.e., the probability of a major outbreak), as opposed to the outbreak fading out with only a small number of cases. We discuss how these simple methods can be extended for epidemiological models with any level of complexity, facilitating their wider use, and describe how estimates of the probability of a major outbreak can be used to guide pathogen surveillance and control strategies. We also give an overview of previous applications of these approaches. This guide is intended to help quantitative researchers develop their own epidemiological models and use them to estimate the risks associated with pathogens arriving in new host populations. The development of these models is crucial for future outbreak preparedness. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics".
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Affiliation(s)
- E Southall
- Mathematics Institute, University of Warwick, Coventry, UK; Zeeman Institute for Systems Biology and Infectious Disease Epidemiology Research, University of Warwick, Coventry, UK
| | - Z Ogi-Gittins
- Mathematics Institute, University of Warwick, Coventry, UK; Zeeman Institute for Systems Biology and Infectious Disease Epidemiology Research, University of Warwick, Coventry, UK
| | - A R Kaye
- Mathematics Institute, University of Warwick, Coventry, UK; Zeeman Institute for Systems Biology and Infectious Disease Epidemiology Research, University of Warwick, Coventry, UK
| | - W S Hart
- Mathematical Institute, University of Oxford, Oxford, UK
| | | | - R N Thompson
- Mathematics Institute, University of Warwick, Coventry, UK; Zeeman Institute for Systems Biology and Infectious Disease Epidemiology Research, University of Warwick, Coventry, UK.
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7
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Impact of MERS-CoV and SARS-CoV-2 Viral Infection on Immunoglobulin-IgG Cross-Reactivity. Vaccines (Basel) 2023; 11:vaccines11030552. [PMID: 36992136 DOI: 10.3390/vaccines11030552] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 02/15/2023] [Accepted: 02/23/2023] [Indexed: 03/03/2023] Open
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has posed a considerable threat to public health and global economies. SARS-CoV-2 has largely affected a vast world population and was declared a COVID-19 pandemic outbreak, with a substantial surge of SARS-CoV-2 infection affecting all aspects of the virus’ natural course of infection and immunity. The cross-reactivity between the different coronaviruses is still a knowledge gap in the understanding of the SARS-CoV-2 virus. This study aimed to investigate the impact of MERS-CoV and SARS-CoV-2 viral infections on immunoglobulin-IgG cross-reactivity. Our retrospective cohort study hypothesized the possible reactivation of immunity in individuals with a history of infection to Middle East Respiratory Syndrome coronavirus (MERS-CoV) when infected with SARS-CoV-2. The total number of participants included was 34; among them, 22 (64.7%) were males, and 12 (35.29%) were females. The mean age of the participants was 40.3 ± 12.9 years. This study compared immunoglobulin (IgG) levels against SARS-CoV-2 and MERS-CoV across various groups with various histories of infection. The results showed that a reactive borderline IgG against both MERS-CoV and SARS-CoV-2 in participants with past infection to both viruses was 40% compared with 37.5% among those with past infection with MERS-CoV alone. Our study results establish that individuals infected with both SARS-CoV-2 and MERS-CoV showed higher MERS-CoV IgG levels compared with those of individuals infected previously with MERS-CoV alone and compared with those of individuals in the control. The results further highlight cross-adaptive immunity between MERS-CoV and SARS-CoV. Our study concludes that individuals with previous infections with both MERS-CoV and SARS-CoV-2 showed significantly higher MERS-CoV IgG levels compared with those of individuals infected only with MERS-CoV and compared with those of individuals in the control, suggesting cross-adaptive immunity between MERS-CoV and SARS-CoV.
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