NOT JUST DISEASE X
In the 21st century, there have been several major outbreaks of novel pathogens, such as SARS-CoV-1, Middle Eastern respiratory virus, severe fever with thrombocytopenia syndrome virus, and SARS-CoV-2.1–4 Novel pathogens continue to pose a significant threat, especially as the global community continues to be more interconnected and as human activities drive us and animal populations to closer interaction, increasing the risk for spillover events.5,6 In 2018, the WHO codified this concept of an unknown threat when it included “Disease X” on its list of priority pathogens.
The WHO formally defined Disease X as representing “the knowledge that a serious international epidemic could be caused by a pathogen currently unknown to cause human disease.”7 This unprecedented move acknowledged that the pathogenome of the world still held many unknowns, and encouraged initiatives aimed at enhanced surveillance and preparedness. By including Disease X on the priority pathogen list, the WHO signaled that research and development should account for the unknown threat. As SARS-CoV-2 and previously emergent novel pathogens have shown us, the novel pathogen poses more than just a theoretical threat. The pandemic has brought increased references to Disease X in preparing the global community for subsequent threats. But calls to action for pandemic preparedness under the banner of Disease X are too narrowly focused, and a balance must be struck between accounting for unknown dangers and maintaining focus on already identified, often neglected infectious diseases of public health importance.
In fact, some of the most significant outbreaks in the past 20 years have been from previously identified pathogens, such as cholera in Zimbabwe 2008; pandemic swine flu in 2009; chikungunya and Zika viruses in South and Central America 2014 and 2015, respectively; Ebola virus in West Africa 2014–2015; and yellow fever virus in Brazil 2016.8–13 In addition, during the writing of this piece, there has been identification of monkeypox virus in the Europe and elsewhere and detection of polio virus in Mozambique after 30 years, detection in the UK after 40 years as well as the United States (New York).14–17 Introductions, expansions, and reemergence events highlight that discreet characterization of known pathogens is also not sufficient. Some pathogens seem to be adequately characterized, but what we know may in fact become insufficient given significant changes to the ecology of the pathogen. For example, changes due to urbanization and deforestation encourage spillovers and introductions into new geographies; climate change leads to expansion of vectors and their associated pathogens; and social issues (e.g., the rise in antivaccination movements or forced migration) alter the demographics of human communities.18 All these factors essentially provide more opportunities for pathogen contact with susceptible hosts, affording the means for emergence and the potential for fulminant outbreaks. Thus, although there is an important need for virus hunters to continue to discover the identities of potential Disease X pathogens, prospective and steady basic research and public health preparedness needs a broader framing for efficient and expedient allocation of resources and ultimately translation of results into programmatic development and optimization.
A broader, One Health-aligned framework.
One Health is the understanding that health of humans, animals, and the environment are interconnected and is a critical paradigm for framing future research for optimized planetary health.19 One Health is the context in which specific problems should be set to formulate holistic and balanced solutions. One Health encompasses myriad things currently threatening global health, including (but not limited to) infectious diseases, noncommunicable diseases, environmental disasters, and climate change. Disease X as a focus for surveillance does not intuitively put things into the One Health paradigm because it focuses on the identity of a pathogen and, in some respects, whether it has been previously identified or not.
Developing subframeworks that are One Health aligned but that address specific aspects of health focuses efforts, identifies the most relevant stakeholders, and leads to balanced and efficient responses. As an example, we discuss one such subframework to address emerging infectious threats specifically and associated preparedness and response. We propose the framework of Disease
We propose defining Disease
In addition to specific therapeutics development, pandemic research and development should include and prioritize the transmission ecology of pathogens, both natural and anthropogenic. As SARS-CoV-2 has demonstrated, social and political pressures, as well as global equity issues have all contributed to the persistence of the virus, even when therapeutics were deployed in record time.20,21 Deficiencies in understanding of the transmission mode(s) early in the pandemic delayed masking and other nonpharmaceutical intervention recommendations which were further exacerbated by delayed and/or poor science communication.22,23 Further, there are a multitude of viruses for which diagnostic capabilities are currently non-existent or severely lagging, as was highlighted by the West African Ebola virus (2014–2015) outbreak and the Zika virus outbreak in South America (2015–2016).24 Additionally, a lack of quickly available, sensitive, and specific diagnostics may create a reliance on clinical syndrome for diagnosis, which creates an additional issue of possible misdiagnosis.25
Critically, by shifting the novelty of the “next big thing” from Disease X, potential threats from already identified (possibly neglected) pathogens will not be discounted. Additionally, Disease
Finally, Disease
Championing a broad framework for preparedness that is One Health aligned allows for development of flexible programs that are progressively specific, as necessary, but exploits common aspects of pathogen transmission to allow for generic planning programs and response protocols.
Citation: The American Journal of Tropical Medicine and Hygiene 107, 6; 10.4269/ajtmh.22-0341
Although perhaps intuitive, the framework of Disease
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