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The Essential Elements of Pandemic Pathogens

Amesh A. Adalja, MD, FACP, FACEP, FIDSA, May 21, 2018

To optimally prepare for pandemics, it is essential to possess some understanding of what types of pathogens are most likely to cause a pandemic. Traditionally, lists derived from prior outbreaks and biological weapons development are used to guide preparedness activities. However, such list-based approaches can lead to static thinking about biological threats, making an already surprise-laden field even more so. Reflecting this uncertainty and the need to be prepared for unknown and unlisted agents, the World Health Organization (WHO) has developed the concept of “Disease X.”1

It was in this context that my colleagues and I undertook a project to develop a framework to determine which traits any pathogen that constitutes a global catastrophic biological risk (GCBR) is most likely to possess. GCBRs are a distinct form of pandemic more akin to the 1918 influenza pandemic than to more recent outbreaks of SARS, MERS, and Ebola.  A report detailing the project was just released.2


More than 120 Experts Interviewed

The methodology of this project included an extensive literature review, coupled with interviews with more than 120 experts. Interviewees were drawn not only from the field of human infectious disease but also from astrobiology, plant pathology, veterinary medicine, amphibian biology, and mycology. The aim of including such diverse fields was to understand successful pathogens per se and apply that knowledge to human infectious diseases. As such, the project was explicitly pathogen-agnostic at the start, with consideration given to all classes of infectious agents, from prions to protozoa, with multiple mechanisms of spread ranging from zoonotic to sexual.


Respiratory-borne RNA Viruses

In the final analysis, which was informed by expert interviews, a literature review, and an in-person roundtable meeting, we concluded that respiratory-borne RNA viruses were the most likely pathogens to constitute a GCBR. The rationale behind that conclusion is based on several facts, including:

  • The transmission of a respiratory-spread microorganism is much harder to stop using standard public health measures, which are more effective with infections spread by fecal-oral, body fluid, or vector-borne routes.
  • Viruses have more rapid generation times, on balance, than other classes of microbes, allowing much faster amplification of cases.
  • There is no currently available “broad-spectrum” antiviral agent akin to a broad-spectrum antibacterial agent.
  • Viruses that have RNA genomes are more mutable and more likely to evolve relevant genetic changes to increase pandemic potential.


Several Recommendations

Given the conclusion regarding respiratory-borne RNA viruses, we offer several recommendations to help augment pandemic preparedness:

  • Expand respiratory virus surveillance beyond influenza to encompass more viruses that fit this criterion (eg, parainfluenza, rhinoviruses, enteroviruses, etc).
  • Increase diagnostic capacity worldwide for respiratory virus detection; many respiratory viruses can cause a spectrum of illness that will include simple upper respiratory infections, the majority of which are nonspecifically diagnosed in both resource-rich and resource-poor areas.
  • Increase investments in therapeutics and vaccines against respiratory-borne RNA viruses.
  • Develop a clinical research agenda to answer key questions regarding optimal treatment, including supportive care, for these infections.



  1. World Health Organization. List of blueprint priority diseases. WHO website. 2018. Accessed May 21, 2018.

  2. Adalja AA, Watson M, Toner ES, Cicero A, Inglesby TV. The Characteristics of Pandemic Pathogens. Baltimore, MD: Johns Hopkins Center for Health Security; 2018. Accessed May 21, 2018.