Examining the Threat of H5N1 Highly Pathogenic Avian Influenza to Human Health

The clade 2.3.4.4b highly pathogenic avian influenza (HPAI) virus H5N1 is the etiologic agent for an ongoing panzootic with a rapidly increasing number of human infections. Although morbidity and mortality in humans with this clade seems to be limited to date, previous HPAI H5N1 viruses have been associated with mortality rates of approximately 50% in humans. Not all cases of clade 2.3.4.4b influenza A(H5N1) HPAI in humans have been associated with known exposure to infected animals. Therefore, clinicians must be aware of the changing viral ecology, human risk factors, and clinical presentations associated with H5N1 viruses to facilitate early case recognition and management of clade 2.3.4.4b A(H5N1) HPAI infection in humans.

Historic H5N1 presentations have involved multiorgan systemic disease, notably including severe neurological disease. Common symptoms associated with clade 2.3.4.4b A(H5N1) HPAI include conjunctivitis, fever, and upper respiratory tract infection. Exposure to infected dairy cattle is a novel risk factor.

The rapid global spread of clade 2.3.4.4b A(H5N1) viruses has been associated with severe disease and high mortality in many farmed animal species and wildlife. The composite picture of emerging risk to human health comprises an unprecedented number of mammalian infections, viral adaptations to mammalian hosts, severe neuroinvasive disease in naturally infected mammals, and spillover into novel species such as dairy cows with forward transmission to humans. Preparedness measures are crucial to mitigating significant human health impacts from this virus and must include a Canadian One Health Training Program in Emerging Zoonoses approach that promotes both animal and human health.