Influenza, Avian

Paul G. Auwaerter, M.D.

PATHOGENS

  • Avian influenza A viruses are classified as highly or low pathogenic based on their pathogenicity in poultry; this classification does not predict the severity of human infection.
  • Highly pathogenic avian influenza (HPAI):
    • Influenza (H5N1), avian, was first detected in Chinese geese in 1996.
    • Occasional human pathogen since 1997
      • Since 2003, the WHO has reported 1,002 laboratory-confirmed human A(H5N1) infections in 25 countries through August 7, 2026, including 479 deaths (~48% reported case-fatality proportion).
        • Case ascertainment has favored clinically apparent disease, particularly in earlier outbreaks.
      • H5 avian influenza infection in a man from Colorado (CDC, April 2022) with direct poultry exposure; extensive avian influenza among poultry flocks and wild birds in N. America in 2021-2022.
      • Since 2020, HPAI A(H5N1) clade 2.3.4.4b viruses have caused significant mortality among wild birds and poultry, affecting countries in Africa, Asia, and Europe. By 2021, it had spread to North America and then, in 2022, to Central and South America.
        • It also affects a wide variety of mammals, including both terrestrial and marine species.
  • U.S. (2022–2026): CDC reports 71 human A(H5) cases since February 2024, including 2 deaths.
    • An additional poultry-associated A(H5) infection occurred in Colorado in 2022.
    • Most recent U.S. infections have followed exposure to infected dairy cattle or poultry and have been mild, frequently presenting with conjunctivitis.
    • Three cases had no identified exposure. No person-to-person spread has been identified.
    • The current risk to the U.S. general public is considered low. The CDC continues human surveillance and case reporting, while the USDA reports detections and outbreaks in animals.
    • Human infections with avian influenza viruses are reported by the CDC as novel influenza A virus infections, which include all non-seasonal animal-origin influenza A viruses detected in humans.
  • Low pathogenic avian influenza (LPAI):
    • Human infections with avian influenza viruses classified as LPAI in poultry are uncommon but can range from mild to severe.
  • WHO publishes regularly updated global assessments of influenza viruses at the human–animal interface.

CLINICAL

  • Epidemiology:
    • Currently circulating A(H5N1) viruses have not demonstrated sustained human-to-human transmission.
      • WHO/FAO/WOAH assess the global risk to the general population as low and the risk to occupationally or frequently exposed persons as low to moderate, depending on local epidemiology and protective measures.
      • Human infections usually result from direct or indirect exposure to infected birds, poultry, dairy cattle, or other animals, or to contaminated environments or animal products.
        • Workers at increased risk include poultry and dairy/livestock workers, live-bird-market and processing workers, disease-control/depopulation personnel, veterinarians, wildlife personnel, and others handling infected animals or contaminated animal products.
    • HPAI A(H5N1) has circulated in U.S. dairy cattle since 2024, creating an important new occupational exposure setting.
      • Animal-health control measures include enhanced surveillance and biosecurity, movement controls, depopulation of affected flocks when indicated, and vaccination strategies in some countries.
    • A(H7N9) caused five major waves of human disease in China beginning in 2013, usually after poultry exposure, with high rates of severe pneumonia and death.
      • Human cases fell sharply following the introduction of H5/H7 poultry vaccination in China in 2017.
      • Sustained human-to-human transmission has not occurred.
  • Clinical:
    • Clinical manifestations range from isolated conjunctivitis or mild upper respiratory illness to severe viral pneumonia, respiratory failure/ARDS.
      • Complications include encephalopathy, multiorgan failure, and death.
      • Gastrointestinal symptoms may occur.
      • Recent U.S. occupational cases have most often been mild, with conjunctivitis prominent.
    • Initial U.S. A(H5N1) case series, March–October 2024 (n=46)[1]
      • Among 46 patients
        • Exposures:
          • 20 infected poultry
          • 25 infected or presumably infected dairy cows
          • 1 no identified exposure
        • Clinical presentations
          • 42 (93%) conjunctivitis, highly characteristic
            • 15 (33%) conjunctivitis only.
          • 22 (49%) fever
          • 16 (36%) had respiratory symptoms
        • Most (87%) received oseltamivir ~2 days after symptom onset.
        • No additional cases were found among the total of 97 household contacts of case patients.

DIAGNOSIS

  • For suspected cases, contact the local/state public health department ASAP; see Interim Guidance on Testing from CDC.
    • Molecular:
      • H5- or H7-specific RT-PCR (can be performed on refrigerated or frozen specimens).
        • Molecular testing for novel influenza A, including subtype-specific RT-PCR, is coordinated through public health laboratories.
          • Obtain respiratory specimens; in patients with conjunctivitis, also obtain a conjunctival swab.
          • Lower respiratory specimens should be obtained in severe lower respiratory disease when possible.
    • Viral culture:
      • Laboratories should not attempt to isolate novel influenza A viruses using viral culture.
      • Presumptive novel A specimens should be forwarded through public health laboratory systems to the CDC for confirmatory testing and additional characterization.

TREATMENT

Antivirals

  • In the U.S., follow the current CDC Interim Guidance for individuals exposed to birds or other animals regarding evaluation, treatment, and post-exposure prophylaxis for suspected novel influenza A infection.
  • Preferred: Most H5N1 viruses remain susceptible to neuraminidase inhibitors, although resistance can occur.
    • Oseltamivir 75mg PO twice daily; active in vitro vs. nearly all H5N1 strains tested.
      • Duration: 5 days for uncomplicated outpatient infection.
        • Hospitalized/severe infection should receive oseltamivir promptly.
        • Longer treatment (e.g., 10 days) may be considered for prolonged or severe illness, particularly with persistent lower-respiratory viral replication.
        • The benefit is greatest with early treatment, but treatment should not be withheld solely because more than 48 hours have elapsed.
  • Alternatives:
    • Peramivir
      • Consider when oral or enteric oseltamivir cannot be tolerated or absorbed.
      • If used for hospitalized novel influenza A, CDC recommends once-daily dosing for at least 5 days.
        • Do not use the single-dose regimen used for uncomplicated seasonal influenza.
      • Evidence is limited.
    • Zanamivir
      • Not recommended for severe/hospitalized novel influenza A; limited human experience with H5N1.
    • Others:
      • Amantadine and rimantadine: A(H5N1) viruses are often resistant to amantadine and rimantadine; adamantanes are not recommended.
      • Baloxavir has in vitro activity and animal data.
        • In hospitalized patients, particularly those with prolonged infection or immunocompromise, a combination of oseltamivir and baloxavir may be considered on a case-by-case basis, despite the absence of human H5N1 efficacy data.
  • Bacterial coinfection/superinfection:
    • Evaluate and treat when clinically suspected, following current community- or hospital-acquired pneumonia guidance and local susceptibility data. Important post-influenza pathogens include S. pneumoniae, S. aureus (including MRSA), and group A streptococci.
    • Routine antibacterial therapy is not indicated in the absence of suspected bacterial coinfection.
  • Steroids:
    • Systemic corticosteroids are not routinely recommended as adjunctive therapy for severe influenza unless there is another clinical indication.
  • Antiviral resistance can emerge during therapy, particularly in prolonged infection or in immunocompromised patients; consult local public health authorities and the CDC if resistance is suspected.

Prevention: General Measures

  • Avoid exposure to potential avian influenza A when possible (infected or potentially infected poultry or birds, contaminated surfaces, bird feces, infected humans, dairy cattle or other animals).
    • Exposed persons should monitor for illness during exposure and for 10 days after the last exposure, including fever/feverishness, respiratory symptoms, conjunctivitis/eye irritation, headache, myalgias, and diarrhea or vomiting.
      • Fever may be absent.
    • CDC guidance for post-exposure prophylaxis (PEP) is risk-based.
      • PEP is not routinely necessary when recommended PPE was used without breach. It should be considered promptly after high-risk unprotected exposure.
        • Antivirals: asymptomatic
          • Oseltamivir 75mg PO twice daily
            • Not once daily as in seasonal influenza.
            • Initiate as soon as possible, ideally within 48 hours after the first exposure.
            • Duration: 5 days after the last time-limited exposure.
              • Consider 10 days for ongoing high-risk exposure.
  • Hospital infection control:
    • Standard, contact, and airborne precautions, along with eye protection, are recommended for suspected or confirmed novel influenza A infection.
    • Use an airborne-infection isolation room when available.
    • Exposed healthcare personnel who develop symptoms: do not report to work; contact occupational/public health services, test promptly, and initiate empiric oseltamivir when novel influenza is suspected.
  • Vaccines:
    • No commercially available human H5N1 vaccine in the United States.
  • Pandemic preparedness:
    • WHO recommends risk-informed, context-specific planning for pandemic influenza medical countermeasure stockpiles rather than a fixed, population-based antiviral target.

Prevention: Travelers to Regions with Avian Influenza Activity

  • Travelers should remain up to date with seasonal influenza vaccination.
    • The seasonal vaccine does not specifically protect against H5N1 but reduces seasonal influenza and may reduce the rare possibility of simultaneous seasonal and avian influenza infection and viral reassortment.
  • CDC recommendations for travel to countries with outbreaks of avian influenza A:
    • Avoid contact with live poultry markets, poultry farms, or dairy herds that are infected.
    • Avoid
      • Raw or undercooked poultry, eggs, and beef; cook animal products to recommended safe internal temperatures.
      • Raw/unpasteurized milk and dairy products; consume pasteurized dairy products.
    • Practice good hand hygiene.
    • Seek medical evaluation and report the exposure if respiratory symptoms, conjunctivitis, fever, or other compatible illness develop within 10 days after the last relevant animal exposure.

Selected Drug Comments

Drug

Recommendation

Amantadine

Not recommended; novel avian influenza A viruses are frequently resistant to adamantanes.

Baloxavir

Active in vitro against many novel influenza A viruses; no established human efficacy data for H5N1. Combination therapy with oseltamivir may be considered on a case-by-case basis in selected hospitalized/immunocompromised patients.

Rimantadine

Not recommended; novel avian influenza A viruses are frequently resistant to adamantanes.

Oseltamivir

Preferred antiviral for suspected or confirmed H5N1. Start as soon as possible without awaiting confirmatory testing. Treatment remains recommended when presentation is more than 48 hours after symptom onset, particularly in hospitalized patients or those with severe disease.

Peramivir

Not routinely recommended. Useful mainly when enteric oseltamivir cannot be absorbed or tolerated. If used for hospitalized novel influenza, give daily for a minimum of 5 days per the CDC.

Zanamivir

Inhaled zanamivir is not recommended for severe/hospitalized novel influenza due to insufficient clinical data; avoid in patients with underlying airway disease due to the risk of bronchospasm. IV zanamivir (Dectova) is authorized in the EU for complicated or potentially life-threatening influenza when other antivirals are unsuitable or resistance is suspected; its role in H5N1 should be individualized with expert consultation.

OTHER INFORMATION

  • The current public health risk is considered low by the CDC and WHO/FAO/WOAH, although it is higher among persons with frequent or unprotected animal exposure.
  • Historically reported H5N1 cases have had a high case-fatality proportion (~48% since 2003), whereas most recent North American clade 2.3.4.4b infections have been mild; differences in surveillance and case ascertainment are substantial.
  • Sustained human-to-human transmission has not been documented.

Basis for recommendation

  1. Garg S, Reinhart K, Couture A, et al. Highly Pathogenic Avian Influenza A(H5N1) Virus Infections in Humans. N Engl J Med. 2025;392(9):843-854.  [PMID:39740051]

    Comment: U.S. series of 46 A(H5N1) infections detected March–October 2024, primarily following dairy-cattle or poultry exposure. Illness was mild, conjunctivitis was prominent, and no secondary infections were identified among 97 household contacts. Illustrates the distinctly mild ocular/upper-respiratory phenotype of many recent North American clade 2.3.4.4b infections compared with historical Asian H5N1 disease.

  2. CDC. Information on Avian Influenza: https://www.cdc.gov/flu/avianflu/index.htm (accessed 9/4/2026)

    Comment: A helpful site updates information on bird flu, most notably H5N1. Current diagnosis, treatment, and prophylaxis recommendations are taken from this source and from information on low-pathogenic avian influenza A infections (H6, H9, and H10), which are listed.

  3. CDC. Interim Guidance on the Use of Antiviral Medications for Treatment of Human Infections with Novel Influenza A Viruses Associated with Severe Human Disease.[last updated 7/3/2025, accessed 9/4/2026].

    Comment:
    Primary CDC guidance for treatment of suspected, probable, or confirmed human infection with novel influenza A viruses associated with severe disease. Recommends prompt oseltamivir; treatment should not be delayed while awaiting confirmation. Addresses prolonged therapy in severe disease, alternatives when enteric oseltamivir cannot be used, antiviral resistance, and selected use of combination therapy.


References

  1. Gupta N, Smielewska A, Felix Drexler J, et al. Avian Influenza in Humans: Virology, Transmission, and Clinical Priorities. QJM. 2026.  [PMID:42213088]

    Comment: Clinician-oriented review of human avian influenza, including virology, changing animal-to-human exposure patterns, global epidemiology, clinical manifestations, diagnosis, treatment, prevention, mammalian adaptation, and One Health considerations.

  2. Blais-Savoie J, Halajian E, Nirmalarajah K, et al. Examining the Threat of H5N1 Highly Pathogenic Avian Influenza to Human Health. Chest. 2026;169(4):947-957.  [PMID:41197866]

    Comment: H5N1-focused narrative review covering clade 2.3.4.4b evolution and mammalian spread, the U.S. dairy-cattle epizootic, human epidemiology and clinical manifestations, diagnosis, treatment, and pandemic risk. Particularly useful for contrasting recent conjunctivitis/mild respiratory presentations with historical severe H5N1 disease. Rating: Important.

  3. Wang X, Jiang H, Wu P, et al. Epidemiology of avian influenza A H7N9 virus in human beings across five epidemics in mainland China, 2013-17: an epidemiological study of laboratory-confirmed case series. Lancet Infect Dis. 2017;17(8):822-832.  [PMID:28583578]

    Comment: Epidemiologic analysis of 1,220 laboratory-confirmed A(H7N9) infections across the first five epidemics in mainland China. The fifth epidemic began earlier and spread more widely; the proportion of middle-aged adults increased, residence shifted toward semi-urban/rural populations, and severity among hospitalized patients remained similar across waves.

  4. Liem NT, Tung CV, Hien ND, et al. Clinical features of human influenza A (H5N1) infection in Vietnam: 2004-2006. Clin Infect Dis. 2009;48(12):1639-46.  [PMID:19435433]

    Comment: Observations in 67 cases in Vietnam. Findings included bilateral infiltrates on chest X-ray (72%), leukopenia (73%), and elevated transaminases (69%). The case-fatality proportion was 39% and was higher for young persons (< 16 years) compared to older persons (0.001). Oseltamivir showed a survival benefit.
    Rating: Important

  5. Beigel JH, Farrar J, Han AM, et al. Avian influenza A (H5N1) infection in humans. N Engl J Med. 2005;353(13):1374-85.  [PMID:16192482]

    Comment: Classic review of early Asian H5N1 experience, highlighting poultry exposure, severe viral pneumonia/ARDS, high case fatality, and limited human-to-human transmission. Antiviral experience was limited, and treatment was often initiated late. Useful historical contrast with North American clade 2.3.4.4b infections.

  6. CDC. A(H5) Bird Flu: Current Situation. [last updated 3/6/26, accessed 9/4/2026].

    Comment: Living CDC source for current U.S. A(H5) epidemiology. CDC currently reports 71 human cases since February 2024, including 2 deaths, with no known person-to-person spread; the current public health risk is assessed as low. Animal detections are now reported by USDA, while CDC continues human case reporting and surveillance.
    This page, A(H5) Bird Flu Surveillance and Human Monitoring, is updated more frequently (last updated 8/7/2026).
    Current CDC U.S. surveillance page. Through August 1, 2026, at least 33,200 exposed persons had been monitored, and 1,340 had been tested for novel influenza A since February 2022; from September 28, 2025, through August 1, 2026, at least 4,900 were monitored, and 156 were tested. CDC surveillance showed no indicators of unusual human influenza activity.

  7. WHO. Clinical practice guidelines for influenza. Geneva: World Health Organization; 2024. ISBN 978-92-4-009775-9.

    Comment: Current WHO clinical guideline covering seasonal, pandemic, and novel influenza A viruses associated with severe disease. For severe influenza, it conditionally recommends oseltamivir and recommends against routine peramivir, zanamivir, and systemic corticosteroids; it also addresses antiviral prophylaxis after zoonotic influenza exposure. CDC-specific guidance should remain the primary source for U.S. H5N1 treatment and PEP regimens.



  8. WHO. Clinical practice guidelines for influenza. Geneva: World Health Organization; 2024. ISBN 978-92-4-009775-9.

    Comment: Current WHO clinical guideline covering seasonal, pandemic, and novel influenza A viruses associated with severe disease. For severe influenza, it conditionally recommends oseltamivir and recommends against routine peramivir, zanamivir, and systemic corticosteroids; it also addresses antiviral prophylaxis after zoonotic influenza exposure. CDC-specific guidance should remain the primary source for U.S. H5N1 treatment and PEP regimens.



  9. CDC. Clinical Guidance for Evaluating Patients and Treatment and Post-exposure Prophylaxis (PEP) of Influenza A(H5N1) Virus Infection.[last revised 7/7/2025, accessed 9/4/2026].

    Comment: Primary CDC guidance for antiviral PEP following animal exposure to novel influenza A viruses. Recommends risk-based use of oseltamivir at treatment-frequency dosing (twice daily), initiated as soon as possible; duration is 5 days after the last discrete exposure or 10 days when exposure is ongoing. PEP is not routinely recommended when appropriate PPE was used without breach.


  10. FAO/WHO/WOAH. Updated joint public health assessment of recent high-pathogenicity avian influenza A(H5) virus events in animals and people. May 18, 2026, accessed Sept. 8. 2026.

    Comment: Joint contemporary global risk assessment. Assesses the overall global public health risk from HPAI A(H5) viruses as low and the risk for occupationally or frequently exposed persons as low to moderate depending on local epidemiology and mitigation measures; continued sporadic zoonotic infections are expected.


  11. WHO. Influenza at the human-animal interface: summary and assessment, 7 August 2026.

    Comment: WHO’s regularly updated global surveillance summary for zoonotic influenza viruses, including current human detections and cumulative A(H5N1) surveillance. Useful living source for global epidemiology and changes in influenza viruses at the human-animal interface.



Last updated: September 12, 2026