Pandemic risk stemming from the bovine H5N1 outbreak: an account of the knowns and unknowns

Abstract

H5N1 subtype influenza A viruses represent a long-standing pandemic concern. Owing to their global occurrence in poultry, humans are routinely exposed to these viruses, and hundreds of human cases have been documented worldwide since 2003. The relevant viral lineages are not static, however, and have recently undergone a massive expansion of host range and geographic distribution. Within this expansion, the introduction of H5N1 viruses into dairy cattle in the United States has spawned a novel animal-human interface. In response, public health agencies have sought to evaluate the risk of an H5N1 pandemic stemming from the bovine outbreak. These assessments draw on evidence from the field and the laboratory to score a series of recognized risk factors. As such, their utility hinges on fundamental understanding of the processes that drive pandemic emergence and the availability of relevant data. Advancing this understanding and gathering data prior to and during an outbreak are primary missions of the NIAID Centers of Excellence for Influenza Research and Response (CEIRR) Network. To further these goals and highlight the need for an invigorated response across US agencies, here, we review gaps in understanding of the dairy cattle outbreak and identify constraints on efforts to close these gaps.

Keywords: H5N1; bird flu; bovine; influenza A virus; pandemic preparedness; risk assessment.

Fig 1

The CEIRR risk assessment pipeline seeks to advance understanding of pandemic risk through well-integrated viral surveillance, genomic characterization, phylogenetic analyses, phenotypic analyses, and evaluation of viral susceptibility to human defenses.

Fig 2

Critical open questions relate to the processes that triggered the dairy cattle outbreak present and that drive its expansion.

Fig 3

Critical open questions relate to the potential for viral evolution in different host species to increase the potential for human-to-human transmission via a respiratory route.

Fig 4

Limitations on key research that would advance assessment of H5N1 pandemic risk.