One confirmed and one potential human case of influenza A(H5N1) detected through an expanded subtyping protocol

Sep 29, 2026

Uploaded by Jasmine

Current U.S. surveillance for highly pathogenic avian influenza A(H5N1) in humans prioritizes people with known animal exposures, potentially missing community-acquired infections. To close this gap, universal H5 subtyping was applied to all influenza A-positive respiratory samples collected at one hospital system, independent of exposure history. From Aug 2024 to Apr 2025, 4,488 samples were subtyped and two H5 RNA-positive cases were identified in Alameda County. The report supports broader, geographically targeted screening for early detection.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages7

Reading Time18 min

AccessFree to download

Abstract

Keywords

Highly pathogenic avian influenza A(H5N1) and current surveillance

Materials and Methods

H5 subtyping protocol

Sequencing

| Editor’s Pick | Clinical Microbiology | Case Series One confirmed and one potential human case of influenza A(H5N1) detected through an expanded subtyping protocol Grant P. Higerd-Rusli,1 Abraar Karan,2 Seth A. Hoffman,2 Ingrid E. A. Morante,3 ChunHong Huang,1 Malaya K. Sahoo,3 Matthew M. Hernandez,1 Benjamin A. Pinsky1,2,3 AUTHOR AFFILIATIONS See affiliation list on p. 6. ABSTRACT Current U.S. surveillance for highly pathogenic avian influenza A(H5N1) in humans prioritizes individuals with known animal exposures, potentially missing community-acquired infections. To address this gap, we implemented universal H5 subtyping of all influenza A-positive respiratory samples collected within our hospital system, regardless of patient exposure history. Between August 2024 and April 2025, we subtyped 4,488 influenza A-positive samples and identified two cases positive for H5 RNA in Alameda County, California, USA. The first case was a 14-month-old girl with mild respiratory symptoms and no H5N1 exposure risks; sequencing of the sample revealed an H5 gene closely related to clade [2.3.4.4](2.3.4.4)b, genotype B3.13 viruses circulating in U.S. dairies. The second case was a 79-year-old male, also with no known exposures, whose sample reproducibly tested positive with a high cycle threshold value but could not be confirmed by public health laboratories. Both patients had evidence of co-infection with other common respiratory viruses. These findings, while requiring cautious interpretation due to low virus levels and the presence of potential confounding factors, highlight limitations in exposure-based testing and demonstrate the potential for cryptic H5N1 circulation. This report underscores that broader, geographically targeted surveillance may be a critical tool for early detection of potential community transmission of pandemic-capable pathogens. KEYWORDS avian influenza, influenza, H5, HPAI H ighly pathogenic avian influenza A H5N1 has spread globally in wild birds and led to outbreaks in increasingly diverse mammalian species (1) . Since March 2024, an outbreak of H5N1 clade [2.3.4.4](2.3.4.4)b has spread among dairy cows across the United States (1) . Given that there is little to no pre-existing immunity in the human population, acquisition of efficient human-to-human transmissibility by H5N1 could lead to rapid global dissemination, resulting in substantial morbidity and mortality (2, 3) . As of August 2025, 70 confirmed human cases have been detected in the United States, 65 of which have reported high-risk exposures to infected dairy cows or poultry and two of which reported exposure to backyard flocks, wild birds, or other mammals (4) . There have been three reported infections in individuals without known exposures: one in Missouri, one in San Francisco, California, and another in British Columbia, Canada (1, 5, 6) . There has been one fatal case in Louisiana (1) . Current influenza surveillance efforts in the United States include “routine surveillance,” where a finite subset of human influenza A-positive samples undergo additional testing (7) . This may include H5 testing but only for samples without an identifiable seasonal influenza A subtype (8) . As of 18 August 2025, routine surveillance demonstrated an H5 case positivity rate of ~0.003%(6/204,843) (4) . Targeted subtyping for H5 is currently limited by strict testing criteria that prioritize individuals with known animal exposure (9, 10) . Consequently, human cases, particularly those arising from potential Editor Nicholas M. Moore, Rush University Medical Center, Chicago, Illinois, USA Address correspondence to Benjamin A. Pinsky, [bpinsky@stanford.edu](bpinsky@stanford.edu). human-to-human spread, may be missed. To evaluate whether cases may be going undiagnosed, we implemented universal H5 subtype screening of all influenza A-positive samples within our hospital system, regardless of patient exposure history. Here wereport that this expanded

FAQs

What limitation in current U.S. H5N1 surveillance does the study address?

Routine surveillance prioritizes individuals with known animal exposures, which may miss community-acquired infections.

How was universal H5 subtyping implemented in the hospital system?

All influenza A-positive respiratory samples were subtyped for influenza A H5 regardless of patient exposure history.

What were the main findings regarding H5 RNA cases in Alameda County?

Two cases were identified as H5 RNA-positive: a 14-month-old girl with mild symptoms and no exposure risks, and a 79-year-old male with reproducible positivity but not confirmed by public health laboratories.

Sep 29, 2026

Uploaded by Jasmine