On the Relationship between Asymptomatic Infections and Diseases

Authors

  • Martin Zach Department of Analytic Philosophy, Institute of Philosophy of the Czech Academy of Sciences, Prague, Czechia https://orcid.org/0000-0001-7181-0391

DOI:

https://doi.org/10.5195/pom.2023.171

Keywords:

Host-microbe interaction, Immunology, Philosophy of science, Asymptomatic infection, Disease

Abstract

Many microbes responsible for infectious diseases are known to run an asymptomatic course in a significant portion of the population. By highlighting the conceptual complexities of host-microbe interactions, this paper elucidates the fact that while many infections remain asymptomatic, this does not necessarily mean that such infections are of no concern for health. The paper builds on the so-called damage-response framework and considers several developments required to gain a more comprehensive perspective on infections and their relationship to diseases. Irrespective of their (short-term) clinical manifestation, infections leave an imprint with consequences for health. Finally, these considerations regarding host-microbe interactions must be incorporated into policy decisions and public understanding of health if we hope to handle future pandemics such as Covid-19 better.

References

Akdis, Cezmi A. 2021. “Does the Epithelial Barrier Hypothesis Explain the Increase in Allergy, Autoimmunity and Other Chronic Conditions?” Nature Reviews Immunology 21, no. 11: 739–751. https://doi.org/10.1038/s41577-021-00538-7.

Altmann, Daniel M., Emily M. Whettlock, Siyi Liu, Deepa J. Arachchillage, and Rosemary J. Boyton. 2023. “The Immunology of Long COVID.” Nature Reviews Immunology, 11 July: 1–17. https://doi.org/10.1038/s41577-023-00904-7.

Amoretti, Maria Cristina and Elisabetta Lalumera. 2020. “The Concept of Disease in the Time of COVID-19.” Theoretical Medicine and Bioethics 41, nos. 5–6: 203–221. https://doi.org/10.1007/s11017-021-09540-5.

Ayres, Janelle. 2016. "Ending the Arms Race with Infectious Diseases." TEDxSanDiego, 23 November. https://www.youtube.com/watch?v=7ZWTG0-eCEg.

———. 2020. “Surviving COVID-19: A Disease Tolerance Perspective.” Science Advances 6, no. 18, eabc1518. https://doi.org/10.1126/sciadv.abc1518.

Broadbent, Alex. 2014. “Disease as a Theoretical Concept: The Case of ‘HPV-Itis.’” Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences 48 (Part B): 250–257. https://doi.org/10.1016/j.shpsc.2014.07.010.

CDC (Centers for Disease Control and Prevention). 2022. “What Is Polio?” https://www.cdc.gov/polio/what-is-polio/index.htm.

Chen, Ingrid, Siân E. Clarke, Roly Gosling, Busiku Hamainza, Gerry Killeen, Alan Magill, Wendy O’Meara, Ric N. Price, and Eleanor M. Riley. 2016. “‘Asymptomatic’ Malaria: A Chronic and Debilitating Infection that Should Be Treated.” PLOS Medicine 13, no. 1, e1001942. https://doi.org/10.1371/journal.pmed.1001942.

Choutka, Jan, Viraj Jansari, Mady Hornig, and Akiko Iwasaki. 2022. “Unexplained Post-Acute Infection Syndromes.” Nature Medicine 28, no. 5: 911–923. https://doi.org/10.1038/s41591-022-01810-6.

Da Fonseca, Denise Morais, Timothy W. Hand, Seong Ji Han, Michael Y. Gerner, Arielle Glatman Zaretsky, Allyson L. Byrd, Oliver J. Harrison, et al. 2015. “Microbiota-Dependent Sequelae of Acute Infection Compromise Tissue-Specific Immunity.” Cell 163, no. 2: 354–366. https://doi.org/10.1016/j.cell.2015.08.030.

De Steenhuijsen Piters, Wouter A.A., Rebecca L. Watson, Emma M. de Koff, Raiza Hasrat, Kayleigh Arp, Mei Ling J.N. Chu, Pieter C.M. de Groot, et al. 2022. “Early-Life Viral Infections Are Associated with Disadvantageous Immune and Microbiota Profiles and Recurrent Respiratory Infections.” Nature Microbiology 7, no. 2: 224–237. https://doi.org/10.1038/s41564-021-01043-2.

Didierlaurent, Arnaud, John Goulding, Seema Patel, Robert Snelgrove, Lionel Low, Magali Bebien, Toby Lawrence, et al. 2008. “Sustained Desensitization to Bacterial Toll-Like Receptor Ligands after Resolution of Respiratory Influenza Infection.” Journal of Experimental Medicine 205, no. 2: 323–329. https://doi.org/10.1084/jem.20070891.

Divangahi, Maziar, Peter Aaby, Shabaana Abdul Khader, Luis B. Barreiro, Siroon Bekkering, Triantafyllos Chavakis, Reinout van Crevel, et al. 2020. “Trained Immunity, Tolerance, Priming and Differentiation: Distinct Immunological Processes.” Nature Immunology 22, no. 1: 2–6. https://doi.org/10.1038/s41590-020-00845-6.

Doolan, Denise L., Carlota Dobaño, and J. Kevin Baird. 2009. “Acquired Immunity to Malaria.” Clinical Microbiology Reviews 22, no. 1: 13–36. https://doi.org/10.1128/cmr.00025-08.

Eberl, Gérard. 2016. “Immunity by Equilibrium.” Nature Reviews Immunology 16, no. 8: 524–532. https://doi.org/10.1038/nri.2016.75.

Feehan, Karen T. and Derek W. Gilroy. 2019. “Is Resolution the End of Inflammation?” Trends in Molecular Medicine 25, no. 3: 198–214. https://doi.org/10.1016/j.molmed.2019.01.006.

Fuller, Jonathan. 2018. “What Are Chronic Diseases?” Synthese 195, 7: 3197–3220. https://doi.org/10.1007/s11229-017-1368-1.

Goulding, John, Robert Snelgrove, José Saldana, Arnaud Didierlaurent, Mary Cavanagh, Emily Gwyer, Jeremy Wales, Erika L. Wissinger, and Tracy Hussell. 2007. “Respiratory Infections: Do We Ever Recover?” Proceedings of the American Thoracic Society 4,no. 8: 618–625. https://doi.org/10.1513/pats.200706-066TH.

Griffin, Diane E. 2022. “Why Does Viral RNA Sometimes Persist after Recovery from Acute Infections?” PLOS Biology 20, no. 6, e3001687. https://doi.org/10.1371%2Fjournal.pbio.3001687.

Hayes, Kelly S., Laura J. Cliffe, Alison J. Bancroft, Simon P. Forman, Seona Thompson, Cath Booth, and Richard K. Grencis. 2017. “Chronic Trichuris Muris Infection Causes Neoplastic Change in the Intestine and Exacerbates Tumour Formation in APC Min/+ Mice.” PLOS Neglected Tropical Diseases 11, no. 6, e0005708. https://doi.org/10.1371/journal.pntd.0005708.

Hesslow, Germund. 1993. “Do We Need a Concept of Disease?” Theoretical Medicine 14, no. 1: 1–14. http://dx.doi.org/10.1007/BF00993984.

Hussell, Tracy. 2016. “Heterologous Immunity Meets Tissue-Specific Training.” Nature Reviews Immunology 16, no. 5, 275. https://doi.org/10.1038/nri.2016.41.

Jenkins, Stephen J. and Judith E. Allen. 2021. “The Expanding World of Tissue-Resident Macrophages.” European Journal of Immunology 51, no. 8: 1882–1896. https://doi.org/10.1002/eji.202048881.

Leavitt, Judith W. 1992. “‘Typhoid Mary’ Strikes Back: Bacteriological Theory and Practice in Early Twentieth-Century Public Health.” Isis 83, no. 4: 608–629. https://doi.org/10.1086/356292.

Lemoine, Maël. 2013. “Defining Disease beyond Conceptual Analysis: An Analysis of Conceptual Analysis in Philosophy of Medicine.” Theoretical Medicine and Bioethics 34, no. 4: 309–325. https://doi.org/10.1007/s11017-013-9261-5.

———. Forthcoming 2024. Basic Concepts of Medical Science. Cambridge: Cambridge University Press.

Maizels, Rick M. and Henry J. McSorley. 2016. “Regulation of the Host Immune System by Helminth Parasites.” Journal of Allergy and Clinical Immunology 138, no. 3: 666–675. https://doi.org/10.1016%2Fj.jaci.2016.07.007.

Maziarz, Mariusz and Martin Zach. 2020. “Agent‐Based Modelling for SARS‐ CoV‐2 Epidemic Prediction and Intervention Assessment: A Methodological Appraisal.” Journal of Evaluation in Clinical Practice 26, no. 5: 1352–1360. https://doi.org/10.1111/jep.13459.

———. 2021. “Assessing the Quality of Evidence from Epidemiological Agent-Based Models for the COVID-19 Pandemic.” History and Philosophy of the Life Sciences 43, no. 1, 10. https://doi.org/10.1007/s40656-020-00357-4.

Medzhitov, Ruslan, David S. Schneider, and Miguel P. Soares. 2012. “Disease Tolerance as a Defense Strategy.” Science 335, no. 6071: 936–941. https://doi.org/10.1126/science.1214935.

Méthot, Pierre-Olivier and Samuel Alizon. 2014. “What Is a Pathogen? Toward a Process View of Host-Parasite Interactions.” Virulence 5, no. 8: 775–785. https://doi.org/10.4161/21505594.2014.960726.

Meyerowitz, Eric A., Aaron Richterman, Isaac I. Bogoch, Nicola Low, and Muge Cevik. 2021. “Towards an Accurate and Systematic Characterisation of Persistently Asymptomatic Infection with SARS-CoV-2.” Lancet Infectious Diseases 21, no. 6: e163–e169. https://doi.org/10.1016/S1473-3099(20)30837-9.

Motwani, Madhur P., Justine Newson, Simon Kwong, Angela Richard-Loendt, Romain Colas, Jesmond Dalli, and Derek W. Gilroy. 2017. “Prolonged Immune Alteration Following Resolution of Acute Inflammation in Humans.” PLOS ONE 12, no. 10, e0186964. https://doi.org/10.1371/journal.pone.0186964.

Murphy, Dominic. 2020. “Concepts of Disease and Health.” In The Stanford Encyclopedia of Philosophy (Spring 2021 Edition), edited by Edward N. Zalta. https://plato.stanford.edu/archives/spr2021/entries/health-disease/.

Naik, Shruti and Elaine Fuchs. 2022. “Inflammatory Memory and Tissue Adaptation in Sickness and in Health.” Nature 607, no. 7918: 249–255. https://doi.org/10.1038/s41586-022-04919-3.

Netea, Mihai G., Jorge Domínguez-Andrés, Luis B. Barreiro, Triantafyllos Chavakis, Maziar Divangahi, Elaine Fuchs, Leo A.B. Joosten, et al. 2020. “Defining Trained Immunity and Its Role in Health and Disease.” Nature Reviews Immunology 20, no. 6: 375–388. https://doi.org/10.1038/s41577-020-0285-6.

Olive, Andrew J. and Christopher M. Sassetti. 2018. “Tolerating the Unwelcome Guest: How the Host Withstands Persistent Mycobacterium Tuberculosis.” Frontiers in Immunology 9 (September), 2094. https://doi.org/10.3389%2Ffimmu.2018.02094.

Pirofski, Liise-anne and Arturo Casadevall. 2002. “The Meaning of Microbial Exposure, Infection, Colonisation, and Disease in Clinical Practice.” Lancet Infectious Diseases 2, no. 10: 628–635. https://doi.org/10.1016/s1473-3099(02)00398-5.

Rakoff-Nahoum, Seth, Justin Paglino, Fatima Eslami-Varzaneh, Stephen Edberg, and Ruslan Medzhitov. 2004. “Recognition of Commensal Microflora by Toll-Like Receptors Is Required for Intestinal Homeostasis.” Cell 118, no. 2: 229–241. https://doi.org/10.1016/j.cell.2004.07.002.

Reiss, Julian and Rachel A. Ankeny. 2016. “Philosophy of Medicine.” In The Stanford Encyclopedia of Philosophy, edited by Edward N. Zalta. https://plato.stanford.edu/archives/spr2022/entries/medicine/.

Sachs, David H. 2003. “Tolerance: Of Mice and Men.” Journal of Clinical Investigation 111, no. 12: 1819–1821. https://doi.org/10.1172/JCI18926.

Schneider, David S. 2021. “Immunology’s Intolerance of Disease Tolerance.” Nature Reviews Immunology 21, no. 10: 624–625. https://doi.org/10.1038/s41577-021-00619-7.

Schneider, David S. and Janelle S. Ayres. 2008. “Two Ways to Survive Infection: What Resistance and Tolerance Can Teach Us about Treating Infectious Diseases.” Nature Reviews Immunology 8, no. 11: 889–895. https://doi.org/10.1038/nri2432.

Sholl, Jonathan. 2015. “Escaping the Conceptual Analysis Straitjacket: Pathological Mechanisms and Canguilhem’s Biological Philosophy.” Perspectives in Biology and Medicine 58, no. 4: 395–418. https://doi.org/10.1353/pbm.2015.0032.

Snelgrove, Robert J., Alexandra Godlee, and Tracy Hussell. 2011. “Airway Immune Homeostasis and Implications for Influenza-Induced Inflammation.” Trends in Immunology 32, no. 7: 328–334. https://doi.org/10.1016/j.it.2011.04.006.

Soares, Miguel P., Luis Teixeira, and Luis F. Moita. 2017. “Disease Tolerance and Immunity in Host Protection against Infection.” Nature Reviews Immunology 17, no. 2: 83–96. https://doi.org/10.1038/nri.2016.136.

Sollid, Ludvig M. 2022. “Epstein-Barr Virus as a Driver of Multiple Sclerosis.” Science Immunology 7, 70, eabo7799. https://doi.org/10.1126/sciimmunol.abo7799.

Sollid, Ludvig M. and Bana Jabri. 2013. “Triggers and Drivers of Autoimmunity: Lessons from Coeliac Disease.” Nature Reviews Immunology 13, no. 4: 294–302. https://doi.org/10.1038/nri3407.

Spinney, Laura. 2022. “Pandemics Disable People: The History Lesson that Policymakers Ignore.” Nature 602, no. 7897: 383–385. https://doi.org/10.1038/d41586-022-00414-x.

Swenson, Kai E., Stephen J. Ruoss, and Erik R. Swenson. 2021. “The Pathophysiology and Dangers of Silent Hypoxemia in COVID-19 Lung Injury.” Annals of the American Thoracic Society 18, no. 7: 1098–1105. https://doi.org/10.1513/annalsats.202011-1376cme.

Urbanowski, Michael E., Elizabeth A. Ihms, Kristina Bigelow, André Kübler, Paul T. Elkington, and William R. Bishai. 2018. “Repetitive Aerosol Exposure Promotes Cavitary Tuberculosis and Enables Screening for Targeted Inhibitors of Extensive Lung Destruction.” Journal of Infectious Diseases 218, no. 1: 53–63. https://doi.org/10.1093/infdis/jiy127.

Weinberg, Robert A. 2014. The Biology of Cancer. 2nd ed. New York: Garland Science.

Welsh, Raymond M. and Liisa K. Selin. 2002. “No One Is Naive: The Significance of Heterologous T-Cell Immunity.” Nature Reviews Immunology 2, no. 6: 417–426. https://doi.org/10.1038/nri820.

Yong, Ed. 2020. “Immunology Is Where Intuition Goes to Die.” The Atlantic, 5 August. https://www.theatlantic.com/health/archive/2020/08/covid-19-immunity-is-the-pandemics-central-mystery/614956.

Zach, Martin and Gregor P. Greslehner. 2022. “Towards an Extended View of Immunity: A Philosophical Perspective.” Anaesthesia Critical Care & Pain Medicine 41, no. 6, 101156. https://doi.org/10.1016/j.accpm.2022.101156.

———. 2023. “Understanding Immunity: An Alternative Framework beyond Defense and Strength.” Biology & Philosophy 38, no. 1: 1–25. https://doi.org/10.1007/s10539-023-09893-2.

Downloads

Published

2023-10-02

How to Cite

Zach, M. (2023). On the Relationship between Asymptomatic Infections and Diseases . Philosophy of Medicine, 4(1). https://doi.org/10.5195/pom.2023.171

Issue

Vol. 4 No. 1 (2023)

Section

The Examination Room

License

Copyright (c) 2023 Martin Zach

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors who publish with this journal agree to the following terms:

  1. The Author retains copyright in the Work, where the term “Work” shall include all digital objects that may result in subsequent electronic publication or distribution.
  2. Upon acceptance of the Work, the author shall grant to the Publisher the right of first publication of the Work.
  3. The Author shall grant to the Publisher and its agents the nonexclusive perpetual right and license to publish, archive, and make accessible the Work in whole or in part in all forms of media now or hereafter known under a Creative Commons Attribution 4.0 International License or its equivalent, which, for the avoidance of doubt, allows others to copy, distribute, and transmit the Work under the following conditions:
    1. Attribution—other users must attribute the Work in the manner specified by the author as indicated on the journal Web site;
    with the understanding that the above condition can be waived with permission from the Author and that where the Work or any of its elements is in the public domain under applicable law, that status is in no way affected by the license.
  4. The Author is able to enter into separate, additional contractual arrangements for the nonexclusive distribution of the journal's published version of the Work (e.g., post it to an institutional repository or publish it in a book), as long as there is provided in the document an acknowledgement of its initial publication in this journal.
  5. Authors are permitted and encouraged to post online a prepublication manuscript (but not the Publisher’s final formatted PDF version of the Work) in institutional repositories or on their Websites prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work. Any such posting made before acceptance and publication of the Work shall be updated upon publication to include a reference to the Publisher-assigned DOI (Digital Object Identifier) and a link to the online abstract for the final published Work in the Journal.
  6. Upon Publisher’s request, the Author agrees to furnish promptly to Publisher, at the Author’s own expense, written evidence of the permissions, licenses, and consents for use of third-party material included within the Work, except as determined by Publisher to be covered by the principles of Fair Use.
  7. The Author represents and warrants that:
    1. the Work is the Author’s original work;
    2. the Author has not transferred, and will not transfer, exclusive rights in the Work to any third party;
    3. the Work is not pending review or under consideration by another publisher;
    4. the Work has not previously been published;
    5. the Work contains no misrepresentation or infringement of the Work or property of other authors or third parties; and
    6. the Work contains no libel, invasion of privacy, or other unlawful matter.
  8. The Author agrees to indemnify and hold Publisher harmless from Author’s breach of the representations and warranties contained in Paragraph 6 above, as well as any claim or proceeding relating to Publisher’s use and publication of any content contained in the Work, including third-party content.
  9. The Author agrees to digitally sign the Publisher’s final formatted PDF version of the Work.