History and exam
Key diagnostic factors
common
cough
Can be dry or productive. Blood-tinged sputum has been described but is not common.
influenza-like illness
Some nonspecific symptoms consistent with influenza-like illness have been reported (including rhinorrhea, headache, sore throat, myalgia, and fatigue).
conjunctivitis
Nonspecific symptoms consistent with influenza-like illness, including conjunctivitis, have been reported.
Conjunctivitis is part of the current US case definition, and has been the only symptom in some of the cases linked to the dairy cattle outbreak in the US in 2024-2025.[45][44]
There is limited evidence describing the clinical characteristics of patients with conjunctivitis caused by influenza A(H5).[127]
dyspnea
Ranges from mild to severe.
fever
Usually temperature >100.4°F (38°C) occurs early in the course of illness and often persists, especially with severe illness.
rales, rhonchi
Auscultatory finding described in patients with highly pathogenic avian influenza (HPAI) A(H5N1) virus infection.
wheeze
Auscultatory finding described in patients with highly pathogenic avian influenza (HPAI) A(H5N1) virus infection.
decreased breath sounds
Auscultatory finding described in patients with highly pathogenic avian influenza (HPAI) A(H5N1) virus infection.
tachypnea
Usually develops within 5 days of illness onset in patients with severe disease.
Other diagnostic factors
uncommon
abdominal pain, vomiting, diarrhea
Several nonspecific primary gastrointestinal symptoms have been reported in children and adults with highly pathogenic avian influenza (HPAI) A(H5N1) virus infection.
altered mental status
Nonspecific neurologic symptoms have been reported.
seizures
Nonspecific neurologic symptoms have been reported.
Risk factors
strong
close contact with infected birds or poultry
Direct contact (touching) or close (within ≤3 feet [≤1 meter]) exposure with sick or dead poultry or other birds suspected or confirmed to have highly pathogenic avian influenza (HPAI) A(H5N1) virus infection is a risk factor for infection.[26][75][76][77]
Most people with HPAI A(H5N1) virus infection had direct or close unprotected exposure with infected sick or dead poultry before illness onset, but exposure appears to rarely result in HPAI A(H5N1) virus infection. Every year, many people are exposed to HPAI A(H5N1) virus but only a very small proportion become infected.
close contact with infected animals or mammals
Animal species other than birds can be infected by influenza A viruses, including pigs, cows, wild terrestrial and marine mammals, horses, dogs, cats, and bats.[74]
Transmission from animals or mammals to humans may be possible, but it is thought to be rare. The first instance of likely mammal-to-human transmission was reported in Texas, US, in April 2024.[3] The person developed conjunctivitis as their only symptom after exposure to dairy cattle presumed to be infected with highly pathogenic avian influenza (HPAI) A(H5N1) virus.[43][44] Other cases of transmission from dairy cattle have been reported in the US since then.
recent travel to a country with H5N1 virus outbreaks
A recent history of travel to a country with outbreaks of highly pathogenic avian influenza (HPAI) A(H5N1) virus in birds (or other animals) should prompt consideration of HPAI A(H5N1) virus infection in the differential diagnosis of a patient presenting with fever and respiratory symptoms, especially if there is a history of exposure to sick or dead poultry or wild birds, or visiting live poultry markets. For example, a traveler who had returned to Canada after visiting China presented with fever, pleuritic chest pain, and abdominal pain, and progressed to lower respiratory tract disease with meningoencephalitis and died of HPAI H5N1 virus infection.[29]
environmental exposure to H5N1 virus
Direct contact (touching) with surfaces contaminated with poultry feces and visiting a live poultry market in highly pathogenic avian influenza (HPAI) A(H5N1) virus-endemic countries are risk factors for infection.[78][79][80] Inhalation of aerosolized material (e.g., feces) containing infectious virus is a likely route of transmission from poultry to humans. Consumption of uncooked poultry or dairy cattle products also may be a potential risk factor.[107]
Exposure to pond water in regions where HPAI A(H5N1) virus has been widespread among birds has also been suggested as a possible risk factor.[81]
weak
close contact with infected humans
Unprotected close contact with a symptomatic human case of highly pathogenic avian influenza (HPAI) A(H5N1) virus infection may be a risk factor. Risk is defined as prolonged direct or close unprotected contact (within 3-6 feet [1-2 meters]) with ill people suspected or confirmed to have HPAI H5N1 virus infection. However, human-to-human transmission remains rare, and there is no evidence of ongoing human-to-human transmission of HPAI H5N1 virus.[83][84][85][86][87]
The risk is highest among related family members, usually in caregivers of an ill, genetically related family member.[85] Although limited, nonsustained human-to-human transmission among genetically related family members has typically occurred in households before a sick patient was hospitalized, and this has also been reported in hospitals.[1][2]
Nosocomial transmission of HPAI A(H5N1) virus from a patient to a healthcare worker has been reported.[1][2][88] However, serologic surveys of healthcare personnel using no or inadequate personal protective equipment while caring for patients with confirmed HPAI A(H5N1) virus infection have demonstrated a very low risk of transmission.[108][109][110]
laboratory work with H5N1 virus
Highly pathogenic avian influenza (HPAI) A(H5N1) virus transmission to laboratory workers using proper techniques and personal protective equipment in appropriate biosafety precautions has not been documented. A small serosurvey of laboratory workers exposed to HPAI A(H5N1) virus with incomplete personal protective equipment use and adherence to biosafety precautions demonstrated no serologic evidence of prior HPAI A(H5N1) virus infection.[111]
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