The first human case of an infection due to the highly pathogenic avian influenza A(H5N1) virus occurred in Hong Kong in 1997. Since November 2003, more than 900 human cases have been reported globally in 24 countries, with a cumulative case fatality of approximately 50%, as of November 1, 2024. Currently, circulating clade 2.3.4.4b influenza A(H5N1) viruses in the United States started showing a resurgence in the year 2021.
Since January 2022, there have been 11 cases of the clade 2.3.4.4b influenza A(H5N1) reported from 5 countries, excluding all human cases from the United States. Of the 11 cases, 7 were reported to be asymptomatic, while 4 were symptomatic with severe or critical symptoms (1 death). Prior to 2024, only 1 human case of influenza A(H5N1) infection had been reported in the U.S.: in 2022, a poultry worker in Colorado experienced fatigue as the only symptom.
The viruses were mostly highly pathogenic avian influenza A(H5N1), which has infected various numbers of dairy cows across the United States, with sporadic human cases reported. Researchers have summarized the characteristics of human influenza A(H5N1) cases in the United States from March through October 2024. For this concern, a recent study was published in the New England Journal of Medicine (NEJM).
Individuals were observed for 10 days following their last exposure to animals suspected or known to be infected with influenza A(H5N1) viruses. Samples were taken from individuals who were symptomatic. All cases with acute respiratory illness and other symptoms of influenza A(H5N1) were referred for nasopharyngeal swabs, combined nasal-oropharyngeal swabs, or both for those who have eye-related symptoms in addition to other symptoms; from those, sample collection is also advised conjunctival swab. It entailed active symptom monitoring and subsequent molecular detection of influenza A(H5N1) virus by the Centers for Disease Control and Prevention (CDC) Human Influenza Virus Real-Time RT-PCR (reverse-transcriptase-polymerase-chain-reaction) Diagnostic Panel Influenza A(H5) Subtyping assay from an exposed person to infected animals.
In this evaluation, a person exposed to infected poultry or infected or supposedly infected dairy cows (hereafter referred to as cows) would be considered exposed to the influenza A(H5N1) virus. Testing presumptively positive specimens were sent to the state or local public health laboratory and subsequently routed to the CDC for confirmation of results through real-time RT-PCR and genetic sequencing. Here, cases of influenza A(H5N1) were confirmed by the CDC during the period between 28 March and 31 October 2024 are reported.
Among 46 case-patients, 20 had exposures to infected poultry, 25 had associated exposures with infected or probable infected dairy cows, and 1 patient had no known exposure. The last one was already admitted because of non-respiratory symptoms; influenza A(H5N1) virus infection was recognized through routine surveillance. The 45 patients with removed identified animal exposure had a median age of 34 years. All the above patients manifested mild influenza A(H5N1) symptoms during the development of the disease; none was admitted to the hospitals and no death was recorded.
A total of 42 patients (93%) suffered conjunctivitis, 22 had a fever (49%), 16 respiratory symptoms (36%), and 15 (33%) only had conjunctivitis. The median duration of illness in these 16 patients was 4 days (range, 1 to 8) during which information was available. Most patients (87%) received oseltamivir, with a median time since the onset of symptoms was 2 days to start oseltamivir. Among the 97 householders who happened to be in contact with infected patients who had animal exposure, no secondary case developed. Workers having contact with infected animals commonly use gloves (71%), eye protection (60%), and face masks (47%) as personal protective equipment during exposure.
There are several limitations to this study. To the extent, that on-farm monitoring varied from farm to farm as well as with jurisdiction, ascertainment bias led to some cases going undetected or underreported. Some data in the case-report forms were missing or incomplete, meaning the case data were often collected before symptom resolution short a period that probably skewed some of the results. The exposure data could not ascertain which exact behaviors were associated with an increased risk of infection. Exposure to both infected cows and raw milk correlates highly, making it difficult to separate the relative contributions of each factor. Additionally, no human-to-human transmission was identified among close contacts of case patients, limiting the ability to test for transmission risk.
Up to now, the cases reported with regard to influenza A(H5N1) viruses have usually resulted in mild illness, the majority being conjunctivitis of short duration, primarily in adults in the United States exposed to infected animals; most of them were under prompt antiviral treatment. No evidence has been found towards influenza A(H5N1) human-to-human transmission. PPE use among occupationally exposed persons was suboptimal, which suggests additional measures are required to reduce exposure risk.
Reference: Garg S, Reinhart K, Couture A, et al. Highly pathogenic avian influenza A(H5N1) virus infections in humans. Published December 31, 2024. Copyright © 2024.
