NAS : Diagnostic Tools, Gaps, and Collaborative Pathways in Human H5N1 Detection (Rapid Expert Consultation)

 
#18,896

While the abrupt drop in human H5N1 cases reported over the past 8 months by the United States is encouraging, it must be tempered by the knowledge that our ability to detect community cases is actually quite limited.  

Even under the best of circumstances (see CDC graphic above), only a percentage of cases (of any infectious disease) will end up officially recognized; aka `The tip of the pyramid'. 

Officially, since early 2024 the United States has reported 70 human infections with HPAI H5N1, with 67 (95.7%) linked directly to livestock (cattle or poultry) or animal (wild bird) exposure. In 3 cases, the exposure has not been determined.

This doesn't include 7 additional cases - locally confirmed but not verified by the CDC's labs - which are listed as `probable' cases'.

Nor does it include the 2nd, strongly suspected case in Missouri - the 8 asymptomatic and/or mild cases retrospectively identified by serological testing of dairy workers - or the 3 asymptomatic veterinarians (out of 150 tested) who volunteered for testing at a veterinary conference last September and showed antibodies to the H5N1 virus.

Previous studies have estimated fewer than 1-in-100 novel swine flu infections are picked up by passive surveillance (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012).

We've seen similar estimates with other novel viruses, including H7N9 in China and MERS-CoV in Saudi Arabia, while seroprevalence studies have indicated that spillovers of H9N2 - and even H5N1 - often go unreported.

This isn't only true in the United States, but around the globe. 

A little over a year ago the ECDC issued guidance for member nations on Enhanced Influenza Surveillance to Detect Avian Influenza Virus Infections in the EU/EEA During the Inter-Seasonal Period., which cautioned:

Sentinel surveillance systems are important for the monitoring of respiratory viruses in the EU/EEA, but these systems are not designed and are not sufficiently sensitive to identify a newly emerging virus such as avian influenza in the general population early enough for the purpose of implementing control 
measures in a timely way. 

Similarly, in 2023's analysis from the UKHSA (see TTD (Time to Detect): Revisited), they estimated there could be dozens or even hundreds of undetected human H5N1 infections before public health surveillance would likely detect them, potentially over a period of weeks or months.

We've seen several cases (see here, here, and here) where someone has been hospitalized, treated, and either died - or was released from the hospital - only to learn days or weeks later that they had actually been infected with a novel H5 virus. 

During this time hospital staff, families, and even visitors may be been unwittingly exposed. The `window' for PCR testing for H5N1 is notoriously short, and opportunities for contract tracing become less viable with each day that passes. 

In response, we've seen documents issued by the CDC (see CDC HAN: Accelerated Subtyping of Influenza A in Hospitalized Patients) and the ECDC (see ECDC: Updated Reporting Protocol for Zoonotic Influenza Virus) urging more aggressive testing; although these represent advisory - not regulatory - guidance. 

 

All of which brings us to a new, 36-page Expert Consultation (by Nahid Bhadelia; Rick A. Bright; Vanessa Moeder) - published by the National Academies Press - on the current shortfalls in diagnostic tools for detecting H5N1 in the community, and ways to improve these systems. 

The authors point out that H5N1 subtyping capacity in the United States remains `limited and fragmented'. 

• most influenza A tests do not provide subtype identification  
• subtyping is often limited to public health labs or a few commercial LDTs, with results often taking days 
• No FDA-authorized rapid point-of-care or at-home H5N1 tests exist.

The authors argue that `Diagnostics are the first line of defense' against any novel virus, and that current gaps in our testing and surveillance leave us unprepared to deal with a large-scale outbreak. 

The download is free (with registration), and this makes a good Sunday morning long-read. Given its copyright status, I've only provided the link and synopsis below.  

Diagnostic Tools, Gaps, and Collaborative Pathways in Human H5N1 Detection
Rapid Expert Consultation
(2025)

Diagnostics are the first line of defense to infectious disease outbreaks. The rapid spread of Influenza A (H5N1) or "Bird Flu" into U.S. dairy cattle, poultry, and humans underscores the urgent need for stronger diagnostic readiness. While sustained human-to-human transmission has not yet occurred with H5N1, the risk is growing. Currently there are knowledge gaps around early case identification measures, clinical management, and coordinated public health efforts.