Avian influenza is caused by strains of influenza virus A that normally infect only wild birds and domestic poultry. Infections due to some of these strains have been detected in humans. Human-to-human transmission is limited, most cases are acquired from animals, typically poultry.
Most subtypes of avian influenza that have caused human infections are H5, H7, and H9 viruses. Most cases of avian influenza in humans have been caused by Asian strains H5N1 and H7N9, but other types have also caused some human infections. Avian influenza infections are often asymptomatic in wild birds but may cause highly lethal illness in domestic poultry. Marine mammals can also become infected with avian influenza strains (eg, H10N7 in harbor seals), with subsequent human infection reported.
Humans can become infected with avian influenza viruses through inhalation of or direct contact with secretions (saliva, mucous, or feces) from infected birds. It is likely that avian influenza viruses of any antigenic specificity can cause influenza in humans whenever the virus acquires mutations, enabling it to attach to human-specific receptor sites in the respiratory tract. Because all influenza viruses are capable of rapid genetic change, avian strains could possibly acquire the ability to spread more easily from person-to-person via direct mutation or via reassortment of genome subunits with human strains during replication in a human, animal or, avian host. If these strains acquire the ability to spread efficiently from person to person, an influenza pandemic could result.
All cases of human infection with an influenza A subtype other than H1 or H3 should be reported to a government health authority.
The first human cases of H5N1 were discovered in Hong Kong in 1997 (1); of the 18 people affected, many patients had severe respiratory symptoms, and the mortality rate was 33% (2). Spread to humans was contained by culling domestic bird populations. However, in 2003 and 2004, H5N1 infections in humans reappeared, and occasional cases continue to be reported, primarily in Asia and the Middle East. Two cases of H5N1 have been reported in humans in the United States. One case was in Colorado in 2022 likely due to contact with infected poultry. The second case was in a dairy farm worker in Texas in 2024. H5N1 was reported among dairy cattle in several states in 2024. The Centers for Disease Control and Prevention (CDC), Food and Drug Administration, and the United States Department of Agriculture (USDA) continue to monitor the situation (see CDC: Information on Bird Flu and H5N1 Bird Flu: Current Situation Summary; also see USDA: Highly Pathogenic Avian Influenza (HPAI) Detections in Livestock).
Since 2014, over 50 human infections with H5N6 have been documented; all occurred in Western Pacific Region, mostly in mainland China (3).
In February 2021, the first human infections with H5N8 were reported in 7 poultry workers in Russia; all cases were reported to be mild or asymptomatic. No human-to-human transmission was observed, and the risk to the general public is considered to be very low (4).
In early 2013, an extensive outbreak of H7N9 avian influenza in humans occurred in several provinces of southeastern China. About one third of cases were fatal, but significant illness typically occurred only in older adults. Sustained human-to-human transmission did not occur, although there is some evidence of limited human-to-human transmission. Human infection appeared to result from direct exposure to infected birds in live (wet) poultry markets, where birds are purchased for subsequent consumption at home. Seasonal outbreaks typically correspond with increased poultry traffic and handling for Chinese New Year celebrations.
China's sixth wave of H7N9 avian influenza in humans peaked in 2016–2017 with nearly 800 cases, and only sporadic cases have been reported since that time. Worldwide, over 1500 human cases and at least 615 deaths have been reported to the World Health Organization since 2013 (3). Some cases of Asian H7N9 avian influenza have been reported outside of mainland China, but most occurred in people who had traveled to mainland China before becoming ill.
Human infection with other avian influenza strains have occurred sporadically, including H7N3 in Canada, H7N7 in the Netherlands, and H7N4 and H9N2 mainly in China and most recently in Vietnam (see CDC: Vietnam Reports First Human Infection with Avian Influenza H9N2 Virus).
Surveillance data indicate that many avian influenza infections may cause mild respiratory symptoms or even be subclinical. However, severe pneumonia with high case fatality rates has been reported in H5N1, H5N6 and H7N9 clusters.
General references
1. Bender C, Hall H, Huang J, Klimov A, Cox N, Hay A, Gregory V, Cameron K, Lim W, Subbarao K: Characterization of the surface proteins of influenza A (H5N1) viruses isolated from humans in 1997-1998. Virology. 1999 Feb 1;254(1):115-23. doi: 10.1006/viro.1998.9529. PMID: 9927579.
Chan PK: Outbreak of avian influenza A(H5N1) virus infection in Hong Kong in 1997. Clin Infect Dis. 2002;34 Suppl 2:S58-S64. doi:10.1086/338820
3. World Health Organization: Avian Influenza Weekly Update Number 937. Accessed April 2024.
4. World Health Organization: Avian influenza A(H5N8) infects humans in Russian Federation. Accessed April 2024.
Symptoms and Signs of Avian Influenza
Manifestations of avian influenza are the same as those of seasonal influenza; however, disease severity and case fatality rate tend to be higher, although with wide variation depending on the viral strain.
Diagnosis of Avian Influenza
History and physical examination
Reverse transcriptase–polymerase chain reaction (RT-PCR)
An appropriate clinical syndrome in a patient exposed to a person known to be infected or exposed to birds in an area with an ongoing avian influenza outbreak should prompt consideration of this infection. History of exposure to birds, dairy cows, or infected people should prompt testing for influenza A.
Testing is done with RT–PCR using a nasal or throat swab. Patients with lower respiratory tract illness can have samples taken from sputum, endotracheal aspirate, or bronchoalveolar lavage fluid. Culture of the organism should not be attempted because special precautions are required for these highly pathogenic viruses.
Suspected and confirmed cases should be reported to the appropriate government health authority (Centers for Disease Control and Prevention [CDC] in the United States).
Treatment of Avian Influenza
Oseltamivir or zanamivir (neuraminidase inhibitors)
Baloxavir marboxil (endonuclease inhibitor)
Treatment with oseltamivir or zanamivir at usual doses is indicated (see CDC: Prevention and Antiviral Treatment of Bird Flu Viruses in People).
The H7N9 and H5N1 viruses are resistant to the earlier antiviral medications amantadine and rimantadine; resistance or reduced susceptibility to oseltamivir has also been reported.
The antiviral medication baloxavir marboxil is a polymerase acidic endonuclease inhibitor that is indicated for treatment of patients ≥ 12 years of age with acute uncomplicated influenza who have been symptomatic for ≤ 48 hours.
Prevention of Avian Influenza
People should avoid contact with sick or dead animals, especially wild and domesticated birds, poultry, and cattle. Raw or undercooked food products, such as unpasteurized milk and dairy products, should also be avoided. In the United States, initial testing of commercial milk samples has shown no live, infectious virus, suggesting that pasteurization is effective in inactivating avian influenza virus (see US Food and Drug Administration: Updates on Highly Pathogenic Avian Influenza (HPAI)). Dairies are required to send only milk from healthy animals into processing for human consumption, and pasteurization is required for milk sold in stores.
Spread is contained by identifying and destroying infected flocks of domestic birds.
China has active poultry vaccination campaigns for H5 and H7 influenza viruses to help prevent the spread from wild to domestic birds, which are more likely to come in contact with and spread the virus to humans.
In the United States, a vaccine for humans against H5N1 avian influenza is available for distribution if deemed necessary by public health authorities. The standard vaccine for influenza does not prevent avian influenza.
Key Points
Avian influenza affects mainly birds, but several strains of avian influenza virus have caused severe respiratory illness and death in humans.
Human infection is typically acquired from infected birds although human-to-human transmission has occurred.
These viruses should not be cultured because they are highly pathogenic and special precautions are required.
Treat with oseltamivir or zanamivir at usual doses or with baloxavir marboxil.
