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46 cases Highly Pathogenic Avian Influenza A(H5N1) Virus Infections in Humans
BACKGROUND
Highly pathogenic avian influenza A(H5N1) viruses have caused widespread infections in dairy cows and poultry in the United States, with sporadic human cases. We describe characteristics of human A(H5N1) cases identified from March through October 2024 in the United States.
METHODS
We analyzed data from persons with laboratory-confirmed A(H5N1) virus infection using a standardized case-report form linked to laboratory results from the Centers for Disease Control and Prevention influenza A/H5 subtyping kit.
RESULTS
Of 46 case patients, 20 were exposed to infected poultry, 25 were exposed to infected or presumably infected dairy cows, and 1 had no identified exposure; that patient was hospitalized with nonrespiratory symptoms, and A(H5N1) virus infection was detected through routine surveillance. Among the 45 case patients with animal exposures, the median age was 34 years, and all had mild A(H5N1) illness; none were hospitalized, and none died. A total of 42 patients (93%) had conjunctivitis, 22 (49%) had fever, and 16 (36%) had respiratory symptoms; 15 (33%) had conjunctivitis only. The median duration of illness among 16 patients with available data was 4 days (range, 1 to 8). Most patients (87%) received oseltamivir; oseltamivir was started a median of 2 days after symptom onset. No additional cases were identified among the 97 household contacts of case patients with animal exposures. The types of personal protective equipment (PPE) that were most commonly used by workers exposed to infected animals were gloves (71%), eye protection (60%), and face masks (47%).
CONCLUSIONS
In the cases identified to date, A(H5N1) viruses generally caused mild illness, mostly conjunctivitis, of short duration, predominantly in U.S. adults exposed to infected animals; most patients received prompt antiviral treatment. No evidence of human-to-human A(H5N1) transmission was identified. PPE use among occupationally exposed persons was suboptimal, which suggests that additional strategies are needed to reduce exposure risk. (Funded by the Centers for Disease Control and Prevention.)
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The Emerging Threat of H5N1 to Human Health
Highly pathogenic avian influenza (HPAI) A(H5N1) emerged in 1997.1 Since then, it has spread globally by migratory birds, resulting in infections in animals on every continent. HPAI A(H5N1) clade 2.3.4.4b emerged in 2021 and resulted in fatal infections in poultry as well as terrestrial and marine mammals.1 In early 2024, influenza A infection was first recognized in dairy cows with mastitis in Texas. Infection in dairy cows is now widespread in the United States, affecting more than 875 herds in 16 states. Most cow infections are genotype B3.13, whereas most outbreaks in wild birds and poultry are genotype D1.1.
Against this background, more humans have come into contact with HPAI A(H5N1). Investigators now report in the Journal a series of human cases from the United States and Canada.2,3 The former series involves 46 case patients with generally mild, self-limited infection with A(H5N1): 20 with exposure to poultry, 25 with exposure to dairy cows, and 1 with undefined exposure.2 Among case patients with occupational exposure, the use of personal protective equipment (PPE) was not universal. Most case patients presented with conjunctivitis, almost half with fever, and a minority with mild respiratory symptoms, and all recovered. The only hospitalization occurred in the case patient with undefined exposure, although hospitalization was not for respiratory illness. Of cases with sequenceable virus, most were B3.13; four cases in patients with poultry exposure were D1.1.
In Canada, a 13-year-old girl with mild asthma and obesity presented with conjunctivitis and fever and had progression to respiratory failure.3 She received intubation and venovenous extracorporeal membrane oxygenation. After treatment that included oseltamivir, amantadine, and baloxavir, she recovered. Notably, genotype D1.1 was detected; sequencing of one isolate from the lower airways that was collected 8 days after the onset of symptoms showed three mutations potentially associated with enhanced virulence and human adaptation: E627K in the polymerase basic 2 gene and E186D and Q222H in the H5 hemagglutinin gene. It is unclear whether these mutations were present in the infecting virus or emerged during the course of the patient’s illness.
These reports show several critical features of the threat of HPAI to human health, and how we might respond. First, collaboration among investigators in human and veterinary medicine, public health leadership, health care providers, and occupational authorities (especially agricultural), exemplified by the case series in United States, is paramount. Cases of H5N1 respiratory illness have been detected because of a standard surveillance approach aimed at detecting novel (nonseasonal) influenza. This approach involves cultivating trust not only among numerous entities but with people seeking care for symptoms of concern, including conjunctivitis.
Second, the mutations evident in the Canadian case highlight the urgent need for vigilant surveillance of emerging mutations and assessment of the threat of human-to-human transmission. The One Health paradigm is foundational to this outbreak, yet to date, genomic sequencing data that have been collected from animals frequently lack critical metadata. Without information pertaining to where and when isolates were collected, the data cannot be linked phylogenetically to other reported sequences, which limits insight into how the virus is spreading. Such data would also provide opportunity for early detection of mutations that might portend avidity for human respiratory epithelium, which may require as little as one mutation.4
Third, we must continue to pursue development and testing of medical countermeasures. Fortunately, current vaccine candidates neutralize the circulating strains in vitro, and these strains so far are susceptible to antiviral agents. Studies have shown the safety and immunogenicity of A(H5N1) vaccines and the need for a two-dose prime–boost approach and use with adjuvants.5 Work is ongoing to complete candidate vaccines for cli/www/us/ca/palo-alto/vrx/rs79/opinions/ideas/pharma/ortho/04_flu/h5/2024/2024_Ison
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Bird flu slightly on the rise
"Bird flu infections are rare in people. Sixty-one human cases have been confirmed in the US this year, according to the US Centers for Disease Control and Prevention, and all but three have been in people who work on poultry or dairy farms.
As the name suggests, avian influenza viruses prefer to infect birds. They break into cells by latching onto sugars that stick up from their surfaces called sialic acids. H5N1, the bird flu virus behind the ongoing outbreak in the US, has really only demonstrated an affinity for the types of sialic acid receptors that are most plentiful in the respiratory tracts of birds.
But flu viruses can also mutate quickly, and since 2022, H5N1 has been infecting a growing variety of mammals, including dairy cattle.
The United States’ first severe case was announced this week in a person in Louisiana who remains hospitalized in critical condition. The CDC said Wednesday the person was exposed to sick and dead birds on their property, not from commercial poultry.
No one who has gotten H5N1 in the US is known to have given the infection to anyone else. For that reason, the CDC estimates that the current risk to the public is low, but there are certain occupations and situations that can increase a person’s risk of catching bird flu.
The two groups of people who are most at risk are farm workers who work with cows or poultry and people who keep backyard flocks, said Dr. Michael Osterholm, who directs the Center for Infectious Disease Research and Policy at the University of Minnesota."
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