Avian influenza (AI) is a viral infection that affects primarily domestic poultry and pet, zoo, and wild birds. In domestic poultry, AI viruses are typically of low pathogenicity (LPAI), causing subclinical infections, respiratory disease, or decreased egg production. A few AI viruses, however, are highly pathogenic (HPAI), causing severe systemic disease with multiple organ failure and high mortality rates. The form of the disease resulting from HPAI viruses has historically been called fowl plague or fowl pest.
Etiology of Avian Influenza
Avian influenza viruses are type A orthomyxoviruses (Alphainfluenzavirus or Influenzavirus A) characterized by antigenically homologous nucleoprotein and matrix internal proteins, which are identified by serologic testing such as agar gel immunodiffusion (AGID) or ELISA. AI viruses are further divided into 16 hemagglutinin (H1–H16) and 9 neuraminidase (N1–N9) subtypes.
Epidemiology of Avian Influenza
Low-pathogenicity avian influenza (LPAI) viruses are distributed worldwide and are recovered frequently from clinically normal shorebirds (Charadriiformes) and migrating waterfowl (Anseriformes). Occasionally, LPAI viruses are recovered from pet birds and ratites. The viruses may be present in village or backyard poultry flocks and in other birds sold through live poultry markets. In the US and Europe, most commercially raised poultry is free of AI viruses. H9N2 LPAI is common in commercial and live poultry market birds in Asia, the Middle East, and North Africa; however, any subtype of LPAI viruses can cause sporadic infections.
Highly pathogenic avian influenza (HPAI) viruses arise from the mutation of some H5 and H7 LPAI viruses. Stamping-out programs have been successfully used to quickly eliminate HPAI viruses; however, some resource-limited areas may use vaccines and management strategies with the aim of control rather than elimination.
The incubation period of AI viruses is highly variable, ranging from a few days in individual birds to 2 weeks in a flock. The World Organisation for Animal Health recognizes 14 days as the incubation period for control programs.
The morbidity and mortality rates of LPAI viral infections are usually low, unless the infection is accompanied by secondary bacterial or viral infections or aggravated by environmental stressors. Even in the absence of secondary pathogens, HPAI viruses cause severe, systemic disease with high mortality rates in chickens, turkeys, and other gallinaceous poultry; mortality rates can be as high as 100% in a few days.
AI viruses are transmitted between individual birds by ingestion or inhalation. Spread between farms results from breaches in biosecurity practices, principally by the movement of infected poultry or contaminated feces and respiratory secretions on fomites such as equipment or clothing. Airborne dissemination between farms may be important over limited distances.
In limited cases, the Eurasian H5-strain HPAI virus has been transmitted by wild birds, and this limited transmission has been associated since 2005 with five transcontinental movements, with more frequent transmission from wild birds to poultry since 2020. Dispersion by wild birds has not been typical of other HPAI viruses. Other HPAI strains and all LPAI strains have minimal potential to infect dogs and cats.
Sporadic natural and experimental infections due to Eurasian H5 HPAI viruses have been reported in cats and dogs, as well as in wild mammals such as red foxes. Such experimental infections occurred after aerosol or respiratory exposure, ingestion of infected chickens or wild birds, or close contact exposure. Potentially, domestic pets could serve as a transmission vector between farms; however, the ability of other AI viruses, including other HPAI strains, to infect pets is unknown. Laboratory mammals have been experimentally infected with Eurasian H5 HPAI viruses, including pigs, ferrets, rats, rabbits, guinea pigs, mice, mink, and nonhuman primates. Cases of Eurasian H5N1 HPAI have been reported also in farmed mink, wild sea lions, wild sea otters, and harbor seals.
In certain geographic areas, dogs and cats may be commonly infected by specific influenza A viruses that are adapted to each specific species (H3N8 and H3N2 in dogs [see Canine Influenza Canine Influenza (Flu) Canine influenza is spread by dog-to-dog by aerosolization of two strains of the canine influenza virus (H3N8 and H3N2), as well as by contaminated objects and fomites. Most infections are mild... read more ]; H7N2 in cats).
Avian influenza viruses exhibit host adaptation to birds. AI infections have occurred in humans, usually as isolated, rare, individual cases. Most human cases have originated from infection with Eurasian H5 HPAI viruses (A/Goose/Guangdong lineage) and H7N9 LPAI and HPAI viruses (Eurasian lineage). From 2003 to February 2023, the total number of human cases of the Eurasian lineage of H5N1 HPAI infection, mostly in Asia and Africa, was 873, of which 458 were fatal.
The primary risk factor for AI infection in humans has been direct contact with live or dead infected poultry; however, a few cases have resulted from consumption of uncooked poultry products, defeathering of infected wild swans, or close contact with other human cases. The Eurasian H5N6 HPAI virus has caused 84 laboratory-confirmed cases of infection in humans in China and Laos. Respiratory infection has been the most frequent clinical sign in human H5 cases. This virus has limited human-to-human transmission.
For the H7N9 LPAI and HPAI, the total number of human cases in China between 2013 and February 2023 was 1,568, of which 616 were fatal. Most cases had exposure risk to live poultry markets. Conjunctivitis was the most common sign in human cases of H7N7 HPAI virus infection in the Netherlands during 2003, with 89 confirmed cases and 1 death. Other HPAI viruses and all LPAI viruses have produced infections in humans either rarely or not at all.
Clinical Findings of Avian Influenza
Clinical signs, severity of disease, and mortality rates of avian influenza vary, depending on the AI virus strain and the host species.
Most AI viruses (subtypes H1–H16) are LPAI viruses. However, some of the H5 and H7 AI viruses are HPAI viruses and highly lethal for chickens, turkeys, and related gallinaceous domestic poultry.
In most wild birds, AI viral infections are subclinical. The H5 HPAI viruses of Eurasian lineage are an exception. These Eurasian viruses have been associated with death in wild and domestic waterfowl and other species of wild and domestic birds, in some situations causing major die-offs in wild birds such as common cranes (Israel), turkey and black vultures (US), and various pelican species.
Low-Pathogenicity Avian Influenza Viruses
Infection with LPAI viruses typically produces respiratory signs such as sneezing, coughing, ocular and nasal discharge, and swollen infraorbital sinuses in poultry. Sinusitis is common in domestic ducks, quail, and turkeys (see Mycoplasma gallisepticum Infection in Poultry Mycoplasma gallisepticum Infection in Poultry Mycoplasma gallisepticum causes respiratory infections in chickens, turkeys, and other avian species. Morbidity is typically high and mortality low in affected flocks, and signs are generally... read more ). Lesions in the respiratory tract typically include congestion and inflammation of the trachea and lungs.
In layers and breeders, signs of avian influenza may include decreased egg production or infertility, ova rupture (evidenced by yolk in the abdominal cavity) or involution, or mucosal edema and inflammatory exudates in the lumen of the oviduct. Rarely, layer and breeder chickens may have acute renal failure and visceral urate deposition (visceral gout).
Highly Pathogenic Avian Influenza Viruses
In peracute cases, clinical signs or gross lesions of avian influenza may be lacking before death. In acute cases, however, lesions may include cyanosis and edema of the head, comb, wattle, and snood (turkey); ischemic necrosis of the comb, wattles, or snood; edema and red discoloration of the shanks and feet due to subcutaneous ecchymotic hemorrhages; petechial hemorrhages on visceral organs and in muscles; and blood-tinged oral and nasal discharges. In severely affected birds, greenish diarrhea is common.
Birds that survive peracute AI infection may develop CNS involvement evident as torticollis, opisthotonos, incoordination, paralysis, and drooping wings. Microscopic lesions are highly variable in both location and severity, and they may consist of edema, hemorrhage, and necrosis in parenchymal cells of multiple visceral organs, the skin, and the CNS.
Diagnosis of Avian Influenza
Detection of AI viral RNA
Detection of AI-specific antibodies
AI virus isolation
Clinical signs alone are not diagnostic for avian influenza.
LPAI and HPAI viruses can be readily isolated from oropharyngeal and cloacal swabs and, in the case of HPAI viruses, from many internal organs. AI viruses grow well in the allantoic sac of 9- to 11-day-old embryonating chicken eggs, and they agglutinate RBCs. Such hemagglutination is not inhibited by antisera for Newcastle disease virus or other paramyxoviruses.
Identification of AI viruses is based on the following:
Influenza A matrix or nucleoprotein antigens, demonstrated by AGID or other suitable immunoassays
Viral RNA, demonstrated by influenza A–specific reverse-transcription PCR assay
Reaction with antibodies specific for AI virus
AI viruses are further classified into hemagglutinin (H1–H16) and neuraminidase (N1–N9) subtypes on the basis of the hemagglutinin inhibition and neuraminidase inhibition tests, respectively, which are performed at a national or international reference laboratory, or by genetic analysis of sequence data.
Laboratory Tests for Avian Influenza Antibodies
AI infections in birds that have recovered from the disease can be confirmed by serologic testing for influenza virus A (AGID or ELISA) and further classified by hemagglutinin and neuraminidase subtype on the basis of hemagglutinin inhibition and neuraminidase inhibition tests, respectively.
LPAI must be differentiated from other respiratory diseases or causes of decreased egg production, including the following:
Acute to subacute viral diseases such as infectious bronchitis Infectious Bronchitis in Poultry Infectious bronchitis is an acute, highly contagious upper respiratory tract disease in chickens. In addition to respiratory signs, decreased egg production and egg quality are common, and nephritis... read more , infectious laryngotracheitis Infectious Laryngotracheitis in Poultry Infectious laryngotracheitis (ILT) is an economically important respiratory disease of poultry. This highly contagious disease is caused by Gallid alpha herpesvirus type 1 (GaHV-1), commonly... read more , low virulent Newcastle disease Newcastle Disease in Poultry Newcastle disease is a severe, systemic, and fatal viral disease of poultry due to virulent strains of avian paramyxovirus type 1. Clinical signs in unvaccinated birds include sudden death,... read more , and infections by other paramyxoviruses Other Avian Paramyxovirus Infections Avian paramyxoviruses types 2–22 are predominantly harbored in wild bird populations. Infections of poultry with these viruses are mostly inapparent. Occasionally, types 2, 3, 6, and 7 have... read more
Bacterial diseases such as mycoplasmosis Mycoplasmosis in Poultry Mycoplasmas are bacteria that lack a cell wall, are small in size, and have the smallest genome among all independently replicating forms of life .Because of their small genome and the lack... read more , infectious coryza Infectious Coryza in Chickens Infectious coryza is an acute respiratory disease of chickens caused by the bacterium Avibacterium paragallinarum. Clinical signs include decreased activity, nasal discharge, sneezing... read more , ornithobacteriosis, turkey coryza, and the respiratory form of fowl cholera Fowl Cholera Fowl cholera is a contagious, bacterial disease of birds caused by Pasteurella multocida. Acutely, it causes elevated mortality. Chronically, it causes lameness, swollen wattles (in chickens)... read more
HPAI must be differentiated from other causes of high mortality rates, such as virulent Newcastle disease, the peracute septicemic form of fowl cholera, heat exhaustion, and severe water deprivation.
Treatment of Avian Influenza
Antimicrobials against secondary pathogens
Treating LPAI-affected flocks with broad-spectrum antimicrobials to control secondary pathogens and increasing house temperatures may decrease morbidity and mortality rates. Treatment with antiviral compounds is not approved or recommended.
Prevention of Avian Influenza
Exclusion biosecurity strategies to prevent the introduction of avian influenza into poultry are the best preventive measure. Suspected outbreaks should be reported to appropriate regulatory authorities.
Antigenically matched and properly administered vaccines can prevent AI infections, clinical signs, and death. If birds become infected, vaccines greatly decrease virus replication and shedding from the respiratory and GI tracts. Specific protection is achieved through autogenous virus vaccines and through vaccines prepared from the AI virus of the same hemagglutinin subtype. Antibodies against the homologous viral neuraminidase antigens may provide partial protection. Only inactivated whole AI virus, DNA of H5 hemagglutinin, RNA particle (defective eastern equine encephalitis virus) with H5 hemagglutinin insert, recombinant fowlpox-AI-H5, and recombinant herpesvirus-turkey-AI-H5 (rHVT-AI-H5) vaccines are licensed in the US.
Vaccination against AI viruses is highly regulated and restricted in many countries. In the US, the use of any licensed AI vaccine for H1–H4, H6, and H8–H16 hemagglutinin subtypes requires approval by the state veterinarian for the state in question. In addition, the use of H5 and H7 AI vaccines in the US requires declaration of an emergency and approval by the secretary of agriculture.
Avian influenza viruses are detected seasonally in subclinically affected migratory waterfowl and shorebirds.
Two clinical types of avian influenza occur in poultry: a low-pathogenicity form (LPAI), as subclinical infections, respiratory disease, or decreased egg production; and a highly pathogenic form (HPAI), as severe systemic disease with multiple organ failure and high mortality rates.
Diagnosis is by detection of viral RNA or avian influenza–specific antibodies, or by virus isolation.
Prevention is by exclusion biosecurity strategies and vaccination; however, vaccination is highly regulated and restricted in many countries.
Zoonotic infections are rare but have been reported in humans without clinical signs or accompanied by conjunctivitis, respiratory disease, or multiple organ failure and death.
For More Information
USDA Animal and Plant Health Inspection Service: Avian Influenza
World Organisation for Animal Health: Avian Influenza
Also see pet health content regarding avian influenza in pet birds Avian Influenza (Bird Flu) In pet birds, diseases of the respiratory tract are very common. They can be caused by bacteria, viruses, fungi, or parasites. It is critical to recognize and treat these diseases in the early... read more .