70 Confirmed H5N1 Cases - 7 Probable
#18,864
While the sharp decline in human infections with HPAI H5N1 in the United States over the past 7 months is somewhat reassuring, the reality is it requires a combination of both diligence and luck to detect community cases of novel influenza infection.
It has been estimated in the past that less 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).
Many with mild or moderate symptoms will not seek a doctor's advice, and among those who do, most will not be tested for novel influenza. And of course, asymptomatic cases are almost certain to be missed.
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.
While a little over two years ago, a study from the HKHSA (see UK Novel Flu Surveillance: Quantifying TTD) warned that it could take between 3 and 10 weeks - and anywhere between a few dozen to a few thousand community cases - before community spread would become apparent to authorities.
So, while the recent lull in human cases may be reassuring, it may not fully reflect the situation on the ground.Yesterday the CDC's MMWR published a long-awaited report on the investigation into a child's infection last December with HPAI H5N1 in California (see Presumptive Bird Flu Case Identified In San Francisco).
This is one of four cases (3 confirmed, 1 Probable) in the United States since mid-2024 where the source of infection remains unknown (i.e. no known exposure to dairy cows, poultry, wild birds, or other infected animals).
While this investigation found `no laboratory evidence of human-to-human transmission among close contacts', the devil is always in the details.
- Confirmation of the child's H5N1 infection was delayed nearly 4 weeks (27 days) after the onset of illness, and contact tracing and testing occurred well past the time where valid PCR results would be expected.
- Of 84 potential contacts, 67 met the CDC close-contact definition. But of those, only a small number were actually tested via PCR or serology (n=14). In all, only 9 contacts were tested for post-exposure antibodies.
FIGURE 2. Network analysis of human A(H5N1) influenza cases and possible contacts (N = 84)* — San Francisco, California, January 2025
In their analysis, the authors discuss these (and other) limitations - none of which are unique to this investigation - as we've seen previously:
WHO DON Update On Mexico's Fatal H5N1 Infection
In January of 2025, we looked at a CDC HAN: Accelerated Subtyping of Influenza A in Hospitalized Patients - and while some progress appears to have been made - it is unclear what the level of compliance is to these guidelines across the nation.
And of course, these are only likely to capture hospitalized patients. Those attending clinics or private physicians are less apt to be tested for novel flu.
While I've only posted some excerpts, the following MMWR report is well worth reading in its entirety, particularly for its detailed look at the challenges related to contact tracing and testing in the wake of a delayed diagnosis.
Highly Pathogenic Avian Influenza A(H5N1) Virus Infection in a Child with No Known Exposure — San Francisco, California, December 2024–January 2025
Weekly / September 4, 2025 / 74(33);522–527
Farrell A. Tobolowsky, DO1; Eric Morris, MPH1; Lina Castro, MPH1; Tina Schaff1; Monica Jacinto1; Joseph P. Clement, MS1; Min Z. Levine, PhD2; Julia C. Frederick, PhD2; Feng Liu, PhD2; Crystal Holiday, PhD2; Marie K. Kirby, PhD2; C. Todd Davis, PhD2; Krista Kniss, MPH2; Sonja J. Olsen, PhD2; Rahil Ryder, MS3; Debra A. Wadford, PhD3; Godfred Masinde, PhD1; George Han, MD1; A. Danielle Iuliano, PhD2; Seema Jain, MD1
Summary
What is already known about this topic?
As of January 1, 2025, 37 human cases of highly pathogenic avian influenza (HPAI) A(H5N1) had been detected in California, none of which occurred in San Francisco.
What is added by this report?
On January 9, 2025, a case of HPAI A(H5N1) infection was identified in a school-aged child in San Francisco through enhanced surveillance (influenza A virus subtyping of a sample of specimens weekly). No source of exposure was identified, and investigations found no laboratory evidence of human-to-human transmission among close contacts.
What are the implications for public health practice?
Enhanced surveillance and timely subtyping of a subset of influenza A–positive specimens, including specimens from persons without known A(H5N1) exposure, are important to detect avian influenza A virus infections. Public health investigations are critical to monitoring for human-to-human transmission.Article PDF
Abstract
In response to a highly pathogenic avian influenza (HPAI) A(H5N1) outbreak in U.S. dairy cows detected in March 2024, with subsequent identification of human cases, the San Francisco Department of Public Health instituted enhanced influenza surveillance (influenza A virus subtyping of a sample of specimens weekly) in June 2024. As of January 1, 2025, 37 human cases of influenza A(H5N1) had been detected in California, none of which occurred in San Francisco.On January 9, 2025, enhanced surveillance detected a human influenza A(H5N1) virus genotype B3.13 infection in a school-aged child in San Francisco with mild illness. Case investigation and contact tracing were conducted to ascertain exposures and detect possible human-to-human transmission. Activities comprised a household visit that included an environmental assessment, close contact interviews and surveys, and molecular and serologic testing.Sixty-seven close contacts (household, school, and health care) were identified. Upper respiratory tract specimens collected from seven asymptomatic household contacts and four symptomatic school contacts all tested negative for influenza virus by real-time reverse transcription–polymerase chain reaction (rRT-PCR). Although antibodies against influenza A(H5N1) were detected in the index patient, serologic testing of a convenience sample of nine close contacts identified no detectable A(H5)-specific antibodies.Despite an extensive investigation, the infection source remains unknown; no human-to-human transmission was identified among close contacts by rRT-PCR and serologic testing. Continued enhanced surveillance and timely subtyping of a subset of influenza A–positive specimens are essential components of a comprehensive strategy to detect human novel influenza A virus infections, including among persons without known exposures to A(H5N1) viruses.
(SNIP)
Index Case Investigation
The index patient lived in an urban environment, did not travel, and had no reported exposure to dairy cows, cats, poultry, birds or other wild animals in the 10 days prior to the illness onset; the family had a pet dog. There were no animals at school, and the patient’s family did not work in occupations that increase risk for A(H5N1) virus infection (handling, slaughtering, defeathering, butchering, culling, caring for, or milking infected animals). A member of the patient’s family purchased raw poultry at a live bird market 2 weeks before the child’s illness onset; the poultry was cooked and consumed the same day it was purchased.
Investigation of Close Contacts
Among 84 persons identified as possible contacts of the index patient (seven household, 53 school, and 24 health care), 67 (80%) met the close contact definition (Figure 2). No household contacts reported illness. School absences were reported for 34 (64.2%) school contacts, 26 (76.5%) of whom were interviewed (one teacher and parents of 25 children). All interviewed parents reported respiratory illnesses in their children, including seven who were symptomatic at the time of interview. The teacher had had influenza-compatible symptoms but was asymptomatic at the time of interview. Four persons were tested for one or more respiratory viruses (COVID-19, RSV, or influenza) previously while ill; all test results for influenza were negative. Among the 24 health care worker contacts from three facility visits (two urgent care, one emergency department), 11 (45.8%) completed a survey, including seven who had close contact with the patient; none reported influenza-compatible symptoms. All 11 available respiratory (oropharyngeal and nasal) specimens from close contacts (seven household and four school) were A(H5)-negative by rRT-PCR.
Serum specimens were collected from the index patient (32 days from onset to convalescent serum collection), three adult household contacts, two school contacts, and four health care contacts. Among these nine contacts, the median interval between their first exposure to the index patient and serum collection was 45 days (range = 9–47 days), and the median interval between their last exposure and serum collection was 26 days (range = 0–46 days). The patient had antibodies to all three wild-type A(H5N1) viruses, with elevated antibody titers in all assays, consistent with recent H5N1 infection: A/Texas/37/2024 (B3.13) (MN titer = 160, HI titer = 320); A/Michigan/90/2024 (B3.13) (MN titer = 320, HI titer = 226); and A/Washington/240/2024 (D1.1) (MN titer = 113, HI titer = 320). All nine close contacts’ serology results were negative for all three wild-type A(H5N1) viruses.
Discussion
Although no exposure was identified, clinical presentation, molecular testing, and positive serology with elevated antibody titers confirmed HPAI A(H5N1) infection in this child. The absence of laboratory (molecular and serologic) evidence of current or recent A(H5N1) virus infection among close contacts suggests no human-to-human transmission. At least two other U.S. patients with confirmed A(H5N1) infection, including another unrelated pediatric patient in the San Francisco Bay Area, had no known exposure to A(H5N1) virus–infected domestic poultry, wild birds, dairy cows, or other infected animals (3,4).
Although no dairy processing facilities are located in San Francisco, the city is situated on a migratory bird route, and in 2024, A(H5) virus was detected in a live bird market, wild birds, and San Francisco wastewater (H5N1 bird flu detected in SF, first in California city wastewater). Although the family purchased poultry at a live bird market (the child did not accompany them to the market), the parents were confident that the child was not exposed to raw poultry, recent A(H5) testing in the market was negative, the cooked poultry consumption occurred more than 2 weeks before the child’s symptom onset, and neither parent had evidence of infection, arguing against infected poultry exposure as the source. Although no wild bird exposure was reported, the child did spend time outside at school; therefore, environmental exposure is theoretically possible. As there were no clear risk factors or exposure to A(H5N1) virus, the infectious source remains unknown.
The genetic differences between the patient’s two positive specimens collected at separate time points likely reflect replication in the child during the intervening 25 days. Persistently positive influenza PCR test results have been previously reported, yet the duration of A(H5N1) viral nucleic acid detection and infection in humans is unknown and likely varies with virus and host factors (9). Although the second (oropharyngeal) swab collected from the patient was positive for A(H5N1) 4 weeks after the first, sequencing did not reveal mutations indicating mammalian adaptation.
Limitations
The findings in this report are subject to at least three limitations. First, because this case was identified through enhanced surveillance, which at the time included batch testing, there was a delay between specimen collection and the influenza A virus subtyping that led to detection of the case: as a result, the investigation occurred after the patient’s illness had resolved and at the end of the 10-day monitoring period for close contacts, subjecting interviews to recall bias and limiting public health interventions such as real-time testing, isolation, antiviral treatment, and postexposure antiviral prophylaxis.Second, it was not possible to interview or collect respiratory and serum specimens from all close contacts; therefore, assessment of signs and symptoms and immunologic response was not comprehensive.Lastly, although household and health care contacts were assessed for asymptomatic infection, only symptomatic school contacts received molecular or serologic testing; thus, asymptomatic infection might have been missed.Implications for Public Health Practice
A(H5N1) virus infections in humans without a clear animal exposure have rarely occurred in the United States (CDC Confirms H5N1 Bird Flu Infection in a Child in California) but have been documented in other countries where A(H5N1) viruses have circulated in wild birds for years. Continued enhanced surveillance and real-time subtyping of a subset of influenza A positive specimens at public health laboratories, including among persons without known risk for exposure to A(H5N1) virus, is an important part of comprehensive novel influenza surveillance strategies (Summer 2025 Influenza Surveillance).
Although the child had no known dairy cow exposure, sequencing results indicated that this case was associated with the 2024–2025 California dairy cow outbreak. The B3.13 genotype associated with this outbreak has also been detected in birds and felines (10), highlighting the continued transmissibility of the virus across susceptible species. Given the wild and domestic animal reservoirs for A(H5N1), a continued One Health approach supports surveillance of wild and domestic animal reservoirs for identification of additional animal cases and risk factors for cross-species and animal-to-human transmission.