Two Human H5N1 Cases Detected via Expanded Subtyping
A new study published in ASM Case Reports describes an expanded surveillance protocol for highly pathogenic avian influenza A(H5N1) in humans. The report details the detection of two H5 RNA-positive individuals in Alameda County, California, neither of whom had documented exposure to infected animals. These findings highlight the limitations of current exposure-based testing strategies in the United States. Between August 2024 and April 2025, researchers implemented universal H5 subtyping on 4,488 influenza A-positive respiratory samples collected within their hospital system, irrespective of patient exposure history. This expanded screening yielded an H5 positivity rate of 0.04%.
Case 1 (Confirmed): A 14-month-old female presented with mild respiratory symptoms (fever, congestion) and acute otitis media. She had no known H5N1 exposure risks, such as the consumption of unpasteurized milk or contact with symptomatic animals. The clinical sample tested positive for H5 (Ct= 34.0) and pan-influenza A (Ct = 32.8); these results were reproducible upon repeat testing. Partial sequencing of the hemagglutinin (HA) gene demonstrated that the H5 sequence was closely related to the clade 2.3.4.4b, genotype B3.13 viruses currently circulating in U.S. dairies and previously identified in other California human cases.
Case 2 (Potential): A 79-year-old male with a history of chronic comorbidities presented with cough and dyspnea and was diagnosed with community-acquired pneumonia. He similarly reported no known high-risk exposures. The sample tested positive for H5 (Ct = 40.1) and pan-influenza A (Ct = 38.1), and these high cycle threshold signals were reproducible. However, subsequent confirmatory testing at both the California Department of Public Health (CDPH) and the CDC was negative for both pan-influenza A and the H5 subtype. Consequently, this case does not strictly fulfill the CDC criteria for "confirmed," "probable," or "suspect" novel influenza A infection.
The detection of these two cases in patients without high-risk exposures suggests that infections resulting from potential human-to-human transmission or cryptic circulation may be overlooked under current, stringent testing criteria.
