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The global demand and potential public health impact of oral antiviral treatment stockpile for influenza pandemics.

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Title: The global demand and potential public health impact of oral antiviral treatment stockpile for influenza pandemics.
Authors: Han AX; Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Center, University of Amsterdam, Amsterdam 1105 AZ, The Netherlands., Hulme KD; Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Center, University of Amsterdam, Amsterdam 1105 AZ, The Netherlands., Russell CA; Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Center, University of Amsterdam, Amsterdam 1105 AZ, The Netherlands.
Source: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2026 Aug 04; Vol. 123 (31), pp. e2524161123. Date of Electronic Publication: 2026 Jul 28.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
Imprint Name(s): Original Publication: Washington, DC : National Academy of Sciences
MeSH Terms: Antiviral Agents*/supply & distribution , Antiviral Agents*/therapeutic use , Influenza, Human*/drug therapy , Influenza, Human*/epidemiology , Influenza, Human*/mortality , Influenza, Human*/prevention & control , Pandemics*/prevention & control , Public Health* , Strategic Stockpile*, Triazines/supply & distribution ; Triazines/therapeutic use ; Oseltamivir/therapeutic use ; Oseltamivir/supply & distribution ; Morpholines/supply & distribution ; Morpholines/therapeutic use ; Dibenzothiepins/supply & distribution ; Dibenzothiepins/therapeutic use ; Pyridones/supply & distribution ; Pyridones/therapeutic use ; COVID-19/epidemiology ; Thiepins/supply & distribution ; Thiepins/therapeutic use ; Humans ; Administration, Oral ; SARS-CoV-2 ; Pandemic Preparedness ; Global Health
Abstract: Antiviral drugs are among the few countermeasures available during the critical interval between the emergence of a novel influenza pandemic and vaccine availability. Antiviral stockpiling is a key pandemic preparedness measure, yet existing stockpiling estimates vary widely and rest on outdated assumptions about healthcare-seeking behavior and drug-specific effectiveness-limitations that the COVID-19 pandemic and recent clinical trial evidence have made untenable. We developed a multiscale transmission model incorporating heterogeneous healthcare-seeking behavior and direct clinical estimates of antiviral transmission risk reduction to estimate country-specific demand and mortality impact across four pandemic scenarios in 186 countries. We find that baloxavir marboxil (BXM), due to its transmission-reducing potential, could avert 37 to 68% of mean pandemic deaths in the first epidemic wave, approximately double the impact of oseltamivir, while requiring a mean stockpile approximately 5 to 10% smaller (7 to 34% of the population, compared to 28 to 36% for oseltamivir). Uncertainty in viral load dynamics and transmission reduction benefits from clinical trials means that BXM's impact could vary, but sensitivity analyses consistently suggest that BXM is likely to be more effective than oseltamivir. Under limited drug availability, priority should be given to treatment over postexposure prophylaxis. Although drug rationing for high-mortality populations (e.g., elderly) can substantially reduce BXM demand, doing so leads to greater total pandemic deaths. Critically, each week of delay in initiating antiviral distribution erodes impact by up to 3% of averted deaths, meaning that antiviral stockpiles must be accompanied by rapid deployment infrastructure to deliver their potential impact.
Competing Interests: Competing interests statement:The authors declare no competing interest.
Grant Information: 818353 EC | European Research Council (ERC); 10710062310004 ZonMw (Netherlands Organisation for Health Research and Development); 09150162210121 ZonMw (Netherlands Organisation for Health Research and Development); 09150182010027 ZonMw (Netherlands Organisation for Health Research and Development)
Contributed Indexing: Keywords: antiviral stockpiling; influenza pandemic; oral antivirals; pandemic preparedness; public health
Substance Nomenclature: 0 (Antiviral Agents)
0 (Triazines)
20O93L6F9H (Oseltamivir)
4G86Y4JT3F (baloxavir)
0 (Morpholines)
0 (Dibenzothiepins)
0 (Pyridones)
0 (Thiepins)
Entry Date(s): Date Created: 20260728 Date Completed: 20260729 Latest Revision: 20260807
Update Code: 20260807
PubMed Central ID: PMC13439088
DOI: 10.1073/pnas.2524161123
PMID: 42520120
Database: MEDLINE
FullText Text:
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DbLabel: MEDLINE
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AccessLevel: 3
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
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  Data: The global demand and potential public health impact of oral antiviral treatment stockpile for influenza pandemics.
– Name: Author
  Label: Authors
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  Data: <searchLink fieldCode="AU" term="%22Han+AX%22">Han AX</searchLink>; Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Center, University of Amsterdam, Amsterdam 1105 AZ, The Netherlands.<br /><searchLink fieldCode="AU" term="%22Hulme+KD%22">Hulme KD</searchLink>; Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Center, University of Amsterdam, Amsterdam 1105 AZ, The Netherlands.<br /><searchLink fieldCode="AU" term="%22Russell+CA%22">Russell CA</searchLink>; Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Center, University of Amsterdam, Amsterdam 1105 AZ, The Netherlands.
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  Data: <searchLink fieldCode="JN" term="%227505876%22">Proceedings of the National Academy of Sciences of the United States of America</searchLink> [Proc Natl Acad Sci U S A] 2026 Aug 04; Vol. 123 (31), pp. e2524161123. <i>Date of Electronic Publication: </i>2026 Jul 28.
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  Data: English
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22National+Academy+of+Sciences%22">National Academy of Sciences </searchLink><i>Country of Publication: </i>United States <i>NLM ID: </i>7505876 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1091-6490 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2200278424%22">00278424 </searchLink><i>NLM ISO Abbreviation: </i>Proc Natl Acad Sci U S A <i>Subsets: </i>MEDLINE
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  Data: <i>Original Publication</i>: Washington, DC : National Academy of Sciences
– Name: SubjectMESH
  Label: MeSH Terms
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  Data: <searchLink fieldCode="MM" term="%22Antiviral+Agents%22">Antiviral Agents*</searchLink>/<searchLink fieldCode="MM" term="%22Antiviral+Agents+supply+%26+distribution%22">supply & distribution</searchLink> <br /><searchLink fieldCode="MM" term="%22Antiviral+Agents%22">Antiviral Agents*</searchLink>/<searchLink fieldCode="MM" term="%22Antiviral+Agents+therapeutic+use%22">therapeutic use</searchLink> <br /><searchLink fieldCode="MM" term="%22Influenza%2C+Human%22">Influenza, Human*</searchLink>/<searchLink fieldCode="MM" term="%22Influenza%2C+Human+drug+therapy%22">drug therapy</searchLink> <br /><searchLink fieldCode="MM" term="%22Influenza%2C+Human%22">Influenza, Human*</searchLink>/<searchLink fieldCode="MM" term="%22Influenza%2C+Human+epidemiology%22">epidemiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Influenza%2C+Human%22">Influenza, Human*</searchLink>/<searchLink fieldCode="MM" term="%22Influenza%2C+Human+mortality%22">mortality</searchLink> <br /><searchLink fieldCode="MM" term="%22Influenza%2C+Human%22">Influenza, Human*</searchLink>/<searchLink fieldCode="MM" term="%22Influenza%2C+Human+prevention+%26+control%22">prevention & control</searchLink> <br /><searchLink fieldCode="MM" term="%22Pandemics%22">Pandemics*</searchLink>/<searchLink fieldCode="MM" term="%22Pandemics+prevention+%26+control%22">prevention & control</searchLink> <br /><searchLink fieldCode="MM" term="%22Public+Health%22">Public Health*</searchLink> <br /><searchLink fieldCode="MM" term="%22Strategic+Stockpile%22">Strategic Stockpile*</searchLink><br /><searchLink fieldCode="MH" term="%22Triazines%22">Triazines</searchLink>/<searchLink fieldCode="MH" term="%22Triazines+supply+%26+distribution%22">supply & distribution</searchLink> ; <searchLink fieldCode="MH" term="%22Triazines%22">Triazines</searchLink>/<searchLink fieldCode="MH" term="%22Triazines+therapeutic+use%22">therapeutic use</searchLink> ; <searchLink fieldCode="MH" term="%22Oseltamivir%22">Oseltamivir</searchLink>/<searchLink fieldCode="MH" term="%22Oseltamivir+therapeutic+use%22">therapeutic use</searchLink> ; <searchLink fieldCode="MH" term="%22Oseltamivir%22">Oseltamivir</searchLink>/<searchLink fieldCode="MH" term="%22Oseltamivir+supply+%26+distribution%22">supply & distribution</searchLink> ; <searchLink fieldCode="MH" term="%22Morpholines%22">Morpholines</searchLink>/<searchLink fieldCode="MH" term="%22Morpholines+supply+%26+distribution%22">supply & distribution</searchLink> ; <searchLink fieldCode="MH" term="%22Morpholines%22">Morpholines</searchLink>/<searchLink fieldCode="MH" term="%22Morpholines+therapeutic+use%22">therapeutic use</searchLink> ; <searchLink fieldCode="MH" term="%22Dibenzothiepins%22">Dibenzothiepins</searchLink>/<searchLink fieldCode="MH" term="%22Dibenzothiepins+supply+%26+distribution%22">supply & distribution</searchLink> ; <searchLink fieldCode="MH" term="%22Dibenzothiepins%22">Dibenzothiepins</searchLink>/<searchLink fieldCode="MH" term="%22Dibenzothiepins+therapeutic+use%22">therapeutic use</searchLink> ; <searchLink fieldCode="MH" term="%22Pyridones%22">Pyridones</searchLink>/<searchLink fieldCode="MH" term="%22Pyridones+supply+%26+distribution%22">supply & distribution</searchLink> ; <searchLink fieldCode="MH" term="%22Pyridones%22">Pyridones</searchLink>/<searchLink fieldCode="MH" term="%22Pyridones+therapeutic+use%22">therapeutic use</searchLink> ; <searchLink fieldCode="MH" term="%22COVID-19%22">COVID-19</searchLink>/<searchLink fieldCode="MH" term="%22COVID-19+epidemiology%22">epidemiology</searchLink> ; <searchLink fieldCode="MH" term="%22Thiepins%22">Thiepins</searchLink>/<searchLink fieldCode="MH" term="%22Thiepins+supply+%26+distribution%22">supply & distribution</searchLink> ; <searchLink fieldCode="MH" term="%22Thiepins%22">Thiepins</searchLink>/<searchLink fieldCode="MH" term="%22Thiepins+therapeutic+use%22">therapeutic use</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Administration%2C+Oral%22">Administration, Oral</searchLink> ; <searchLink fieldCode="MH" term="%22SARS-CoV-2%22">SARS-CoV-2</searchLink> ; <searchLink fieldCode="MH" term="%22Pandemic+Preparedness%22">Pandemic Preparedness</searchLink> ; <searchLink fieldCode="MH" term="%22Global+Health%22">Global Health</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Antiviral drugs are among the few countermeasures available during the critical interval between the emergence of a novel influenza pandemic and vaccine availability. Antiviral stockpiling is a key pandemic preparedness measure, yet existing stockpiling estimates vary widely and rest on outdated assumptions about healthcare-seeking behavior and drug-specific effectiveness-limitations that the COVID-19 pandemic and recent clinical trial evidence have made untenable. We developed a multiscale transmission model incorporating heterogeneous healthcare-seeking behavior and direct clinical estimates of antiviral transmission risk reduction to estimate country-specific demand and mortality impact across four pandemic scenarios in 186 countries. We find that baloxavir marboxil (BXM), due to its transmission-reducing potential, could avert 37 to 68% of mean pandemic deaths in the first epidemic wave, approximately double the impact of oseltamivir, while requiring a mean stockpile approximately 5 to 10% smaller (7 to 34% of the population, compared to 28 to 36% for oseltamivir). Uncertainty in viral load dynamics and transmission reduction benefits from clinical trials means that BXM's impact could vary, but sensitivity analyses consistently suggest that BXM is likely to be more effective than oseltamivir. Under limited drug availability, priority should be given to treatment over postexposure prophylaxis. Although drug rationing for high-mortality populations (e.g., elderly) can substantially reduce BXM demand, doing so leads to greater total pandemic deaths. Critically, each week of delay in initiating antiviral distribution erodes impact by up to 3% of averted deaths, meaning that antiviral stockpiles must be accompanied by rapid deployment infrastructure to deliver their potential impact.
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: Competing interests statement:The authors declare no competing interest.
– Name: GrantInfo
  Label: Grant Information
  Group: Grant
  Data: 818353 EC | European Research Council (ERC); 10710062310004 ZonMw (Netherlands Organisation for Health Research and Development); 09150162210121 ZonMw (Netherlands Organisation for Health Research and Development); 09150182010027 ZonMw (Netherlands Organisation for Health Research and Development)
– Name: SubjectMinor
  Label: Contributed Indexing
  Group:
  Data: <i>Keywords: </i>antiviral stockpiling; influenza pandemic; oral antivirals; pandemic preparedness; public health
– Name: NumberCAS
  Label: Substance Nomenclature
  Group: ID
  Data: 0 (Antiviral Agents)<br />0 (Triazines)<br />20O93L6F9H (Oseltamivir)<br />4G86Y4JT3F (baloxavir)<br />0 (Morpholines)<br />0 (Dibenzothiepins)<br />0 (Pyridones)<br />0 (Thiepins)
– Name: DateEntry
  Label: Entry Date(s)
  Group: Date
  Data: <i>Date Created: </i>20260728 <i>Date Completed: </i>20260729 <i>Latest Revision: </i>20260807
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  Data: 20260807
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  Data: PMC13439088
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  Data: 10.1073/pnas.2524161123
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  Data: 42520120
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42520120
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        Value: 10.1073/pnas.2524161123
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      – Code: eng
        Text: English
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        StartPage: e2524161123
    Subjects:
      – SubjectFull: Triazines supply & distribution
        Type: general
      – SubjectFull: Triazines therapeutic use
        Type: general
      – SubjectFull: Oseltamivir therapeutic use
        Type: general
      – SubjectFull: Oseltamivir supply & distribution
        Type: general
      – SubjectFull: Morpholines supply & distribution
        Type: general
      – SubjectFull: Morpholines therapeutic use
        Type: general
      – SubjectFull: Dibenzothiepins supply & distribution
        Type: general
      – SubjectFull: Dibenzothiepins therapeutic use
        Type: general
      – SubjectFull: Pyridones supply & distribution
        Type: general
      – SubjectFull: Pyridones therapeutic use
        Type: general
      – SubjectFull: COVID-19 epidemiology
        Type: general
      – SubjectFull: Thiepins supply & distribution
        Type: general
      – SubjectFull: Thiepins therapeutic use
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        Type: general
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      – SubjectFull: Global Health
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      – SubjectFull: Antiviral Agents supply & distribution
        Type: general
      – SubjectFull: Antiviral Agents therapeutic use
        Type: general
      – SubjectFull: Influenza, Human drug therapy
        Type: general
      – SubjectFull: Influenza, Human epidemiology
        Type: general
      – SubjectFull: Influenza, Human mortality
        Type: general
      – SubjectFull: Influenza, Human prevention & control
        Type: general
      – SubjectFull: Pandemics prevention & control
        Type: general
      – SubjectFull: Public Health
        Type: general
      – SubjectFull: Strategic Stockpile
        Type: general
    Titles:
      – TitleFull: The global demand and potential public health impact of oral antiviral treatment stockpile for influenza pandemics.
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              Text: 2026 Aug 04
              Type: published
              Y: 2026
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