To Identify Pandemic Pathogens, Diagnose Every Case

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Of the roughly 1,400 bacterial, viral, protozoan, and fungal pathogens that are known to infect people, only a few have demonstrated the potential to cause a “sudden, extraordinary, widespread disaster beyond the collective capability of national and international governments and the private sector to control” – what my colleagues and I define as ‘Global Catastrophic Biological Risks’ (GCBRs). The members of this infamous club include some of humanity’s greatest scourges, including plague, smallpox, and pandemic influenza. While the current threat posed by these pathogens has been attenuated somewhat due to the modern infectious disease armamentarium (e.g., basic sanitation and hygiene, vaccines, and modern medical care), these and other pathogens nevertheless have the potential to cause mass death and the chaos and suffering that would inevitably follow.

In response, governments and health authorities have attempted to bound the problem by compiling both formal and informal lists of the pathogens most likely to cause severe epidemics or pandemics. Notable examples include the WHO’s R&D Blueprint and the CDC’s Bioterrorism Agents list. While these lists serve important planning or regulatory functions, they also can inhibit a comprehensive understanding of the biological threat landscape. As the 2009 emergence of the pandemic H1N1 influenza virus in Mexico (rather than Southeast Asia) and the importation of Zika virus to the Americas demonstrate, surprise has been the norm.

We believe this stems, in part, from list-based thinking. That’s why we were so pleased to see WHO include “Disease X” in this year’s update of the R&D Blueprint, as a reminder of the importance of constant vigilance and preparedness. This theme will feature prominently in the Clade X tabletop exercise that our Center is conducting this week.

For the past several months, my colleagues and I have been working to identify some common characteristics of pandemic pathogens. We hope our findings will spur more nuanced assessments of biological threats. I encourage you to check out our recently released final report.

There is one major finding from that report I want to highlight here.

The fact is, the vast majority of illnesses and deaths from infectious causes are never definitively diagnosed. This is true regardless of where in the world care is rendered. Instead, clinicians primarily rely on constellations of signs and symptoms, what are called ‘syndromes’, to whittle down the list of things that could conceivably cause the illness. While far less labor intensive than tracking each and every case down to its root cause, this aspect of medical practice makes it far more likely that index cases or clusters of known or unknown pathogens will go unnoticed.

We believe that clinicians the world over should be making routine use of classical clinical microbiology, clinical applications of next-generation sequencing, and point-of-care molecular diagnostics that are starting to become available. That information, once gleaned, should be rapidly and seamlessly transmitted to public health authorities. This improved flow of information would dramatically boost our ability to identify pandemic pathogens in a timely fashion.