Amesh A. Adalja, MD, Project Director, et al., of the Johns Hopkins Bloomberg School of Public Health, Center for Health Security (2018) report that as pandemic preparedness and prediction mature, the integration of data from new technologies will have the potential to have a significant impact on human resilience to global catastrophic biological risk (GCBR)-level threats. Employing new tools in an adaptable framework that seeks to highlight the features of highest priority classes of pathogens will yield new insights. As diagnostic technology rapidly advances, is simplified, and is widely distributed over the next decade, pandemic pathogens will be more readily identified at earlier stages worldwide, allowing preparedness activities to be more proactive.
There are several characteristics likely to be common to GCBR-level pandemic pathogens. Irrespective of the biological class of a pathogen, several attributes are likely to be essential components of any GCBR-level pathogen. These traits include efficient human-to-human transmissibility, an appreciable case fatality rate, the absence of an effective or widely available medical countermeasure, an immunologically naïve population, virulence factors enabling immune system evasion, and respiratory mode of spread. Additionally, the ability to transmit during incubation periods and/or the occurrence of mild illnesses would further augment spread.
Although most classes of microbe could evolve or be manipulated in ways that would cause a catastrophic risk to humans, viruses—especially RNA viruses—are the most likely class of microorganism to have this capacity. Among the various classes of microbes, many possess some or all of the characteristics necessary to be identified as a GCBR. However, several features of viruses make this class of microbial agents the most likely to cause GCBRs. Viruses possess higher capacity for genetic mutability due to both the structure of their genomes and the generation time for replication in which large numbers of progeny virus are created each day. Additionally, the inability of a virus to be countered with a broad-spectrum antiviral—compared with bacteria, fungi, and parasites—makes viruses the more likely cause of a GCBR.
Within the viral class, RNA viruses merit special concern chiefly because of their higher mutability compared to DNA viruses. Efforts to create viral catalogs are not synonymous with nor necessarily effective as tools of pandemic preparedness. Major resource-intensive efforts are currently under way to develop a global virome to catalog as many viral species on the planet as possible. The rationale behind these projects is to develop a full understanding of the breadth of the viral world
and to be able to develop better situational awareness of looming threats. The scientific value of such an undertaking is substantial and without question. However, these efforts will not necessarily translate into better pandemic preparedness, given the sheer numbers of viruses that will be catalogued without a clear means of prioritizing them, the fact that most identified viruses will pose little to no threat to humans, and the recognition that, while a viral cause of the next pandemic is most likely, there is no guarantee it will not be caused by another class of pathogen. The cost effectiveness of a global viral catalog for diminishing pandemic threats may be less than that of systematically pursuing diagnoses of infectious disease syndromes, as discussed below.
Pursuing diagnoses of infectious disease syndromes provides situational awareness of pathogens that could evolve into pandemic threats. Aggressive diagnostic testing of infectious disease syndromes such as atypical pneumonia, central nervous system infections, and septic shock in strategic and sentinel locations around the world and over time may provide insight into new or changing patterns of infection. Such a practice would be a radical departure from standard practices in both the developed and the developing worlds, in which syndromic clinical diagnosis, basic microbiological testing, and empiric
therapy are often the rule.
With the heightened availability of more sophisticated diagnostic testing in both developed and developing nations, it is increasingly possible to have greater insight into the microbiological causes underlying many common infectious syndromes that currently are not routinely pursued to a specific microbiological etiology. Illuminating this biological dark matter that is present in hospitals and clinics worldwide will not only improve treatment but would focus pathogen discovery efforts on established damage-causing microbes.
Human factors and/or the occurrence of complex disasters can elevate pathogens to GCBR levels. During an outbreak situation, early decisions regarding vaccine policy, resource mobilization, and countermeasure deployment made by political and scientific leaders can be decisive in the control of an outbreak and could prevent many
of the downstream cascading effects that affect the healthcare and other sectors. Conversely, decisions—both scientific and political—that lead to harmful or erroneous actions could deepen the consequences of an epidemic or worsen a GCBR. Additionally, as infectious disease outbreaks occur within a larger sociopolitical, geographic, environmental, and economic context, the presence of concomitant complexities can exacerbate an outbreak and confer GCBR-level status on a microbe that is unable, on its own, to possess such destructive capacity. For example, the record-breaking 2017 outbreak of cholera in Yemen, though not rising to the level of a GCBR, was significantly magnified by the presence of war. Therefore, it is important to realize that outbreaks caused by pathogens not categorized as GCBR-level risks could rise to that level through synergy with external factors.
This report is an expert assessment of the traits of GCBR-level pandemic pathogens. We found that it is possible to develop an adaptable open-ended pathogen-agnostic framework of pandemic pathogens that is based on their biologic and epidemiologic traits. We hope that such a framework will shift preparedness activities away from closed list-based approaches and foster a more active-minded approach to this problem that will, in the end, guard against such an event occurring or enable the mitigation of its most severe consequences.
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