#19,115
This morning we've an open access review published in CHEST® - the monthly clinical research journal of the American College of Chest Physicians - which looks at the continued evolution of HPAI H5N1's threat to human health.At a time when many government agencies appear to have reduced their coverage of HPAI (the CDC's last Avian Flu News & Spotlights update was Sept 8th, 2025), this review for clinicians is particularly timely.
This article covers a lot of ground, starting with a a literature search and evidence review which documents HPAI's shift from being primarily a disease of birds to increased mammalian adaptation.
While focusing primarily on H5N1 clade 2.3.4.4b, this review also briefly discusses the Cambodian 2.3.2.1e clade. While H5N5 is mentioned, this article went to press prior to last year's announced human infection in Washington state.
Much of this review is focused on practical concerns for clinicians, including testing, treatment, and isolation of cases. A few `pearls' from the narrative include:
- Exposure to cattle or commercial poultry operations thus may be indicative of potential clade 2.3.4.4b A(H5N1) infection; however, lack of exposure cannot rule out potential infection, as observed in 5 patients with unknown exposure or exposure to other animals.39,41
- Timely identification and isolation of infected patients is essential and is enabled by a low threshold of suspicion for patients with consistent clinical presentations and epidemiologic factors, including exposure to sick birds or cattle within 10 days of symptom onset.
- Patients with positive findings may go undetected if they do not seek diagnosis or treatment in the absence of access to health care or because they experience only mild symptoms.
Future Directions
At this time, the risk posed to the general public from AIV is considered low.29 However, that reality could change at any time given the rapidly evolving situation involving infection in mammals and substantial knowledge gaps surrounding clade 2.3.4.4b A(H5N1) and human infections.
This is an excellent review for clinicians, and makes for a good Sunday morning read for anyone interested in the topic.
Highly recommended.
Open access
Examining the Threat of H5N1 Highly Pathogenic Avian Influenza to Human Health
Juliette Blais-Savoie, Emily Halajian, Kuganya Nirmalarajah, Andra Banete, Juan C. Corredor, Jonathon D. Kotwa,Yaejin Lee, Sugandha Raj, Shayan Sharif ,Nicole Mideo, Samira Mubareka
Publication: CHEST
Publisher: Elsevier
Date: April 2026
Abstract
Topic Importance
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.
Review Findings
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.
Summary
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
While HPAI H5Nx remains our biggest concern, recents human infections with other subtypes (see Taiwan CDC Update: Novel H7 Infection Identified as H7N7 and WHO DON: Avian Influenza A(H9N2) - Italy (Ex Senegal)) remind us that Nature's laboratory is open 24/7, and we could easily be blindsided by something unexpected coming out of left field.
