Evaluation of perceived threat differences posed by filovirus variants

Abstract

In the United States, filoviruses (ebolaviruses and marburgviruses) are listed as National Institute of Allergy and Infectious Diseases (NIAID) Category A Priority Pathogens, Select Agents, and Centers for Disease Control and Prevention (CDC) Category A Bioterrorism Agents. In recent months, U.S. biodefense professionals and policy experts have initiated discussions on how to optimize filovirus research in regard to medical countermeasure (ie, diagnostics, antiviral, and vaccine) development. Standardized procedures and reagents could accelerate the independent verification of research results across government agencies and establish baselines for the development of animal models acceptable to regulatory entities, such as the Food and Drug Administration (FDA), while being fiscally responsible. At the root of standardization lies the question of which filovirus strains, variants, or isolates ought to be the prototypes for product development, evaluation, and validation. Here we discuss a rationale for their selection. We conclude that, based on currently available data, filovirus biodefense research ought to focus on the classical taxonomic filovirus prototypes: Marburg virus Musoke in the case of marburgviruses and Ebola virus Mayinga in the case of Zaire ebolaviruses. Arguments have been made in various committees in favor of other variants, such as Marburg virus Angola, Ci67 or Popp, or Ebola virus Kikwit, but these rationales seem to be largely based on anecdotal or unpublished and unverified data, or they may reflect a lack of awareness of important facts about the variants' isolation history and genomic properties.

Figure 1.

Plotting of the case-fatality rates (black dots on a scale from 0.0 [0%] to 1.0 [100%]) for each human filovirus disease outbreak broken down by virus [EBOV, MARV/RAVV, SUDV, BDBV], location [country]/year, and overall case numbers/deaths, along with 99% confidence intervals (black horizontal lines). The vertical lines represent the overall case-fatality rate for a particular virus (bold lines), with corresponding 99% confidence intervals (dashed lines). The case-fatality rate of EBOV disease outbreaks is 78% (99.5% CI: 71%, 84%), for MARV/RAVV 82% (99% CI: 68%, 91%), for SUDV 53% (99% CI: 42%, 64%), and for BDBV 34% (99% CI: 13%, 63%). Statistically significant differences in overall case-fatality rates are found in the case of EBOV vs. SUDV (p=<0.0001), MARV vs. SUDV (p=<0.0001), EBOV vs. BDBV (p=<0.0001), and MARV vs. BDBV (p=<0.0001), but not in the case of EBOV vs. MARV, or SUDV vs. BDBV. TAFV is not included in the figure because only one nonlethal human case has been described. DRC, Democratic Republic of Congo; RC, Republic of Congo. Color graphics available online at www.liebertonline.com/bsp