Highly pathogenic avian influenza (HPAI) A(H5N1) virus strains have infected poultry or wild birds in more than 60 countries since 2003.
Globally, from May 1997 to 12 December 2024, 974 cases of human HPAI A(H5N1) infection were reported from 25 countries. This includes 18 cases and six deaths in Hong Kong during May through December 1997, and two cases and one death in Hong Kong in February 2003.[35]Chan PK. Outbreak of avian influenza A(H5N1) virus infection in Hong Kong in 1997. Clin Infect Dis. 2002 May 1;34(suppl 2):S58-64.
https://academic.oup.com/cid/article/34/Supplement_2/S58/459477?login=false
http://www.ncbi.nlm.nih.gov/pubmed/11938498?tool=bestpractice.com
[36]Peiris JS, Yu WC, Leung CW, et al. Re-emergence of fatal human influenza A subtype H5N1 disease. Lancet. 2004 Feb 21;363(9409):617-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112424
http://www.ncbi.nlm.nih.gov/pubmed/14987888?tool=bestpractice.com
[37]World Health Organization. Cumulative number of confirmed human cases for avian influenza A(H5N1) reported to WHO, 2003-2024, 12 December 2024. Dec 2024 [internet publication].
https://www.who.int/publications/m/item/cumulative-number-of-confirmed-human-cases-for-avian-influenza-a(h5n1)-reported-to-who--2003-2024--20-december-2024
From November 2003 to 12 December 2024, 49% of reported HPAI A(H5N1) cases were fatal.[37]World Health Organization. Cumulative number of confirmed human cases for avian influenza A(H5N1) reported to WHO, 2003-2024, 12 December 2024. Dec 2024 [internet publication].
https://www.who.int/publications/m/item/cumulative-number-of-confirmed-human-cases-for-avian-influenza-a(h5n1)-reported-to-who--2003-2024--20-december-2024
Since a large outbreak of cases was reported in Egypt during 2015 (136 cases), few sporadic human cases have been reported worldwide until the ongoing 2024-2025 outbreak in the US.
US outbreak 2024-2025
Since March 2024, sporadic human infections have been reported in the US associated with exposure to poultry or dairy cattle as part of ongoing multistate outbreaks among poultry and dairy cattle. As of 31 January 2025, 67 human cases and one death have been reported as part of this outbreak.[22]Centers for Disease Control and Prevention. H5 bird flu: current situation. Feb 2025 [internet publication].
https://www.cdc.gov/bird-flu/situation-summary/index.html
April 2024: one HPAI A(H5N1) human case was reported in Texas. The person developed conjunctivitis (eye redness) as their only symptom, and they had exposure to dairy cattle presumed to be infected with HPAI A(H5N1) virus.[43]World Health Organization. Disease outbreak news: avian influenza A(H5N1) - United States of America. Apr 2024 [internet publication].
https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON512
[44]Centers for Disease Control and Prevention. Highly pathogenic avian influenza A (H5N1) virus infection reported in a person in the U.S. Apr 2024 [internet publication].
https://www.cdc.gov/media/releases/2024/p0401-avian-flu.html
May 2024: a second human case was reported in a dairy worker in Michigan. Similar to the case in Texas, the person worked on a dairy farm where H5N1 virus had been identified in cows, and only reported eye symptoms.[45]Centers for Disease Control and Prevention. CDC reports second human case of H5 bird flu tied to dairy cow outbreak. May 2024 [internet publication].
https://www.cdc.gov/media/releases/2024/s0522-human-case-h5.html
May 2024: a third human case was reported in a dairy worker in Michigan with exposure to infected cows. This was the first case in the US to report more typical upper respiratory tract symptoms including cough and eye discomfort with watery discharge.[46]Centers for Disease Control and Prevention. CDC confirms second human H5 bird flu case in Michigan; third case tied to dairy outbreak. May 2024 [internet publication].
https://www.cdc.gov/media/releases/2024/p0530-h5-human-case-michigan.html
July 2024: a fourth human case was reported in a dairy worker in Colorado with exposure to infected cows. The person reported eye symptoms only.[47]Centers for Disease Control and Prevention. CDC reports fourth human case of H5 bird flu tied to dairy cow outbreak. Jul 2024 [internet publication].
https://www.cdc.gov/media/releases/2024/p-0703-4th-human-case-h5.html
July 2024: a further nine confirmed cases of human infection associated with exposure to poultry at two facilities were reported in Colorado. All cases were in farm workers involved in the depopulation of poultry at a facility experiencing a H5N1 outbreak. The workers reported mild illness with conjunctivitis as the most common symptom.[48]Drehoff CC, White EB, Frutos AM, et al. Cluster of influenza A(H5) cases associated with poultry exposure at two facilities - Colorado, July 2024. MMWR Morb Mortal Wkly Rep. 2024 Aug 29;73(34):734-9.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11361414
http://www.ncbi.nlm.nih.gov/pubmed/39207932?tool=bestpractice.com
September 2024: a human case was reported in Missouri, and was the first case without a known occupational exposure to sick or infected animals. The case was identified through the state’s seasonal influenza surveillance system. No ongoing transmission has been reported.[49]Centers for Disease Control and Prevention. CDC confirms human H5 bird flu case in Missouri. Sep 2024 [internet publication].
https://www.cdc.gov/media/releases/2024/s0906-birdflu-case-missouri.html
October 2024: three human cases were reported in people with occupational exposure to infected dairy cows in California. All cases experienced only mild symptoms (including conjunctivitis).[50]Centers for Disease Control and Prevention. CDC confirms new human cases of H5 bird flu in California. Oct 2024 [internet publication].
https://www.cdc.gov/media/releases/2024/s1003-birdflu-case-california.html
[51]Centers for Disease Control and Prevention. CDC confirms 3rd human case of H5 bird flu in California. Oct 2024 [internet publication].
https://www.cdc.gov/media/releases/2024/s1009-human-case-bird-flu.html
Several cases have been reported in California since these initial three cases (38 in total), including the first case in a child.[38]Centers for Disease Control and Prevention. CDC confirms H5N1 bird flu infection in a child in California. Nov 2024 [internet publication].
https://www.cdc.gov/media/releases/2024/p1122-h5n1-bird-flu.html
December 2024: the first case of severe infection in the US was reported in Louisiana. The patient had exposure to sick and dead birds in backyard flocks. The virus was identified as belonging to the D1.1 genotype currently detected in poultry and wild birds in the US. The patient died in early January 2025, and was the first person in the US to die as a result of H5 virus infection.[39]Centers for Disease Control and Prevention. CDC confirms first severe case of H5N1 bird flu in the United States. Dec 2024 [internet publication].
https://www.cdc.gov/media/releases/2024/m1218-h5n1-flu.html
[40]Centers for Disease Control and Prevention. First H5 bird flu death reported in United States. Jan 2025 [internet publication].
https://www.cdc.gov/media/releases/2025/m0106-h5-birdflu-death.html
Cases have also been reported in Iowa, Oregon, Washington, and Wisconsin in 2024.[22]Centers for Disease Control and Prevention. H5 bird flu: current situation. Feb 2025 [internet publication].
https://www.cdc.gov/bird-flu/situation-summary/index.html
Prior to this, the first human case of infection ever reported in the US was in 2022 in Colorado, and was associated with direct exposure to infected poultry during a culling process.
Cases outside of the US: January 2023 to January 2025
January 2025: one HPAI A(H5N1) case was reported in the West Midlands region in the UK. The case acquired the infection on a farm after close prolonged contact with a large number of infected birds. The infection was detected during routine surveillance.[42]UK Health Security Agency. Human case of avian flu detected in England. Jan 2025 [internet publication].
https://www.gov.uk/government/news/human-case-of-avian-flu-detected-in-england
November 2024: one HPAI A(H5N1) case was reported in a 13-year-old girl in British Columbia, Canada. The case was detected through enhanced hospital-based influenza surveillance, and the patient had no travel history. The source of infection is currently unknown. The patient had a history of mild asthma and elevated body mass index, and was hospitalized due to worsening respiratory symptoms and hemodynamic instability, which progressed to acute respiratory distress syndrome (ARDS). Genomic sequencing revealed the virus belonged to the 2.3.4.4b clade (D1.1. genotype), the virus currently detected in bird outbreaks in Canada and the US.[52]Jassem AN, Roberts A, Tyson J, et al. Critical illness in an adolescent with influenza A(H5N1) virus infection. N Engl J Med. 2024 Dec 31 [Epub ahead of print].
https://www.nejm.org/doi/full/10.1056/NEJMc2415890
http://www.ncbi.nlm.nih.gov/pubmed/39740022?tool=bestpractice.com
November 2024: one HPAI A(H5N1) case was reported in a 18-year-old boy in Vietnam. The patient resided in an area where a H5N1 outbreak in poultry and waterfowl had been reported, with the patient reporting exposure to sick and dead poultry. The patient was diagnosed with severe pneumonia, hospitalized, and treated with antiviral therapy, and has since recovered.[53]World Health Organization. Influenza at the human-animal interface summary and assessment, 12 December 2024: 2 November to 12 December 2024. Dec 2024 [internet publication].
https://www.who.int/publications/m/item/influenza-at-the-human-animal-interface-summary-and-assessment--12-december-2024
September 2024: one HPAI A(H5N1) case was reported in a 15-year-old child in Cambodia. The patient was admitted to the hospital after presenting with fever, cough, sore throat, and difficulty breathing. The patient was treated with oseltamivir, but died 3 days later. The patient was exposed to potentially infected chickens in the days prior to the onset of illness.[54]World Health Organization. Disease outbreak news: avian influenza A(H5N1) - Cambodia. Sep 2024 [internet publication].
https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON533
May 2024: one HPAI A(H5N1) case was reported in Victoria, Australia. The case occurred in a child who acquired the infection in India. The child was unwell in March 2024 and experienced severe infection, but has since made a full recovery. The source of exposure to the virus in this case is currently unknown. No further cases have been connected to this case. This is the first human case of infection reported in Australia.[55]World Health Organization. Disease outbreak news: avian influenza A (H5N1) - Australia. Jun 2024 [internet publication].
https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON519
March 2024: one HPAI A(H5N1) case was reported in a 21-year-old man in Khanh Hoa Province, Vietnam. He developed fever and cough before being admitted to the hospital with persistent abdominal pain and diarrhea. He then developed severe pneumonia, sepsis, and acute respiratory distress syndrome, and died 12 days after initial symptom onset. The man went bird hunting in February 2024 and did not have contact with dead or sick poultry since then. No evidence of human-to-human transmission was identified.[56]World Health Organization. Disease outbreak news: avian influenza A(H5N1) - Viet Nam. Apr 2024 [internet publication].
https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON511
February 2024: two HPAI A(H5N1) cases were reported in epidemiologically-unrelated people in different provinces in Cambodia. A 3-year-old child exposed to dead backyard poultry was hospitalized with mild uncomplicated upper respiratory tract illness, and a 69-year-old patient who raised domestic poultry and fighting roosters was hospitalized with difficulty breathing. Both patients recovered, and no evidence of human-to-human transmission was identified.[57]World Health Organization. Disease outbreak news: avian influenza A (H5N1) - Cambodia. Feb 2024 [internet publication].
https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON501
November 2023: two HPAI A(H5N1) cases were reported in people living in different households in the same rural village in Cambodia. After exposure to sick or dead backyard poultry, a young girl experienced mild uncomplicated upper respiratory tract illness and survived, and a previously healthy young woman developed severe pneumonia and died. No evidence of human-to-human transmission was identified.[58]World Health Oragnization. Disease outbreak news: avian influenza A (H5N1) - Cambodia. Nov 2023 [internet publication].
https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON495
October 2023: two HPAI A(H5N1) cases were reported in epidemiologically-unrelated people in different provinces in Cambodia. A young child and a middle-aged adult both died of severe pneumonia after close exposure to sick and dead poultry in rural villages. No evidence of human-to-human transmission was identified.[20]Centers for Disease Control and Prevention. Technical report: June 2024 highly pathogenic avian influenza A(H5N1) viruses. Jun 2024 [internet publication].
https://www.cdc.gov/bird-flu/php/technical-report/h5n1-06052024.html
May 2023: two HPAI A(H5N1) cases were identified in poultry farm workers in the UK. Both cases were asymptomatic and were detected through a surveillance study of asymptomatic workers exposed to infected poultry. Both people have since tested negative, and work to determine whether these are false positives (rather than mucosal contamination of the nose with virus particles) is ongoing. No evidence of human-to-human transmission was identified.[59]World Health Organization. Disease outbreak news: avian influenza A H5N1 - United Kingdom of Great Britain and Northern Ireland. May 2023 [internet publication].
https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON468
March 2023: the first case of HPAI A(H5N1) virus infection in Chile was identified in a middle-aged man who developed severe pneumonia and respiratory failure. The man lived in an area where H5N1 virus was detected in wild birds and sea lions in northern Chile, but the source of his infection was unknown.[60]World Health Organization. Disease outbreak news: human infection caused by avian Influenza A (H5N1) - Chile. Apr 2023 [internet publication].
https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON461
[61]Castillo A, Fasce R, Parra B, et al. The first case of human infection with H5N1 avian Influenza A virus in Chile. J Travel Med. 2023 Sep 5;30(5):taad083.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10481412
http://www.ncbi.nlm.nih.gov/pubmed/37310882?tool=bestpractice.com
[62]Centers for Disease Control and Prevention. Human infection with highly pathogenic avian influenza A(H5N1) virus in Chile. Mar 2023 [internet publication].
https://www.cdc.gov/bird-flu/spotlights/chile-first-case-h5n1-addendum.html
February 2023: two HPAI A(H5N1) cases were reported in family members, an 11-year-old girl and her father, in a rural Cambodian village after exposure to sick and dead infected poultry. The girl died of respiratory failure while her father only experienced mild upper respiratory tract illness. No evidence of human-to-human transmission was identified.[63]World Health Organization. Disease outbreak news: avian influenza A (H5N1) - Cambodia. Feb 2023 [internet publication].
https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON445
January 2023: one HPAI A(H5N1) case was reported in a 9-year-old girl who was admitted to the hospital on December 30, 2022 for respiratory illness after exposure to sick and dead backyard poultry in a rural area of Ecuador. She was transferred to an intensive care unit of a pediatric hospital for septic shock and pneumonia, and survived. This was the first human case of HPAI A(H5N1) virus infection ever reported in South America.[64]World Health Organization. Disease outbreak news: human infection caused by avian influenza A(H5) - Ecuador. Jan 2023 [internet publication].
https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON434
[65]Bruno A, Alfaro-Núñez A, de Mora D, et al. First case of human infection with highly pathogenic H5 avian Influenza A virus in South America: A new zoonotic pandemic threat for 2023? J Travel Med. 2023 Sep 5;30(5):taad032.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10481407
http://www.ncbi.nlm.nih.gov/pubmed/36881656?tool=bestpractice.com
Current situation reports are available from the World Health Organization (WHO), the Centers for Disease Control and Prevention (CDC), and the UK Health Security Agency:
Prior to the current 2024-2025 outbreak in the US, most human HPAI A(H5N1) cases were reported among previously healthy children and young adults. The median age of patients was approximately 20 years, with an age range for all patients from under 1 year to 81 years.[66]World Health Organization. Update: WHO-confirmed human cases of avian influenza A (H5N1) infection, November 2003-May 2008. Wkly Epidemiol Rec. 2008 Nov 14;83(46):415-20.
http://www.ncbi.nlm.nih.gov/pubmed/19009716?tool=bestpractice.com
The ratio of male-to-female cases was about equal; however, there was a higher case-fatality proportion in females, which may be due to many different epidemiologic factors, such as delay in accessing healthcare, case age, and physician testing patterns.[26]World Health Organization. Update on human cases of highly pathogenic avian influenza A(H5N1) virus infection, 2010. Wkly Epidemiol Rec. 2011 Apr 22;86(17):161-6.
https://www.who.int/publications/i/item/who-wer-8617-161-166
http://www.ncbi.nlm.nih.gov/pubmed/21516633?tool=bestpractice.com
From 2003-2010, patients under 20 years of age had a significantly lower risk of dying than those ages over 20 years (case-fatality proportions: 52% vs. 66%).[26]World Health Organization. Update on human cases of highly pathogenic avian influenza A(H5N1) virus infection, 2010. Wkly Epidemiol Rec. 2011 Apr 22;86(17):161-6.
https://www.who.int/publications/i/item/who-wer-8617-161-166
http://www.ncbi.nlm.nih.gov/pubmed/21516633?tool=bestpractice.com
Mortality is associated with delayed recognition of disease and hospitalization after symptom onset.[26]World Health Organization. Update on human cases of highly pathogenic avian influenza A(H5N1) virus infection, 2010. Wkly Epidemiol Rec. 2011 Apr 22;86(17):161-6.
https://www.who.int/publications/i/item/who-wer-8617-161-166
http://www.ncbi.nlm.nih.gov/pubmed/21516633?tool=bestpractice.com
One study reported that the presence of rhinorrhea appeared to indicate a better prognosis for children with HPAI A(H5N1).[32]Oner AF, Dogan N, Gasimov V, et al. H5N1 avian influenza in children. Clin Infect Dis. 2012 Jul;55(1):26-32.
https://academic.oup.com/cid/article/55/1/26/317646/H5N1-Avian-Influenza-in-Children
http://www.ncbi.nlm.nih.gov/pubmed/22423125?tool=bestpractice.com
While rare, asymptomatic infection with HPAI A(H5N1) virus confirmed virologically and serologically has been reported, detections of A(H5N1) viral RNA in asymptomatic individuals exposed to infected poultry are more common.[57]World Health Organization. Disease outbreak news: avian influenza A (H5N1) - Cambodia. Feb 2024 [internet publication].
https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON501
[67]Le MQ, Horby P, Fox A, et al. Subclinical avian influenza A(H5N1) virus infection in human, Vietnam. Emerg Infect Dis. 2013 Oct;19(10):1674-7.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3810763
http://www.ncbi.nlm.nih.gov/pubmed/24047510?tool=bestpractice.com
[68]Capelastegui F, Smith J, Kumbang J, et al. Pilot of asymptomatic swabbing of humans following exposures to confirmed avian influenza A(H5) in avian species in England, 2021/2022. Influenza Other Respir Viruses. 2023 Aug;17(8):e13187.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10447230
http://www.ncbi.nlm.nih.gov/pubmed/37638093?tool=bestpractice.com
[69]Aznar E, Casas I, González Praetorius A, et al. Influenza A(H5N1) detection in two asymptomatic poultry farm workers in Spain, September to October 2022: suspected environmental contamination. Euro Surveill. 2023 Feb;28(8):2300107.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9951258
http://www.ncbi.nlm.nih.gov/pubmed/36820643?tool=bestpractice.com
[70]Oliver I, Roberts J, Brown CS, et al. A case of avian influenza A(H5N1) in England, January 2022. Euro Surveill. 2022 Feb;27(5):2200061.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8815099
http://www.ncbi.nlm.nih.gov/pubmed/35115075?tool=bestpractice.com
Most likely, this represents transient detection of viral RNA, and not evidence of HPAI A(H5N1) virus infection.[20]Centers for Disease Control and Prevention. Technical report: June 2024 highly pathogenic avian influenza A(H5N1) viruses. Jun 2024 [internet publication].
https://www.cdc.gov/bird-flu/php/technical-report/h5n1-06052024.html
[69]Aznar E, Casas I, González Praetorius A, et al. Influenza A(H5N1) detection in two asymptomatic poultry farm workers in Spain, September to October 2022: suspected environmental contamination. Euro Surveill. 2023 Feb;28(8):2300107.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9951258
http://www.ncbi.nlm.nih.gov/pubmed/36820643?tool=bestpractice.com
One systematic review and meta-analysis of human seroprevalence of H5N1 in China detected an overall seroprevalence of 2.45%. A higher seroprevalence of 7.32% was detected in central China.[71]Qi Y, Ni HB, Chen X, et al. Seroprevalence of highly pathogenic avian influenza (H5N1) virus infection among humans in mainland China: a systematic review and meta-analysis. Transbound Emerg Dis. 2020 Sep;67(5):1861-71.
http://www.ncbi.nlm.nih.gov/pubmed/32259345?tool=bestpractice.com
One cohort study of human infections with HPAI A(H5N1) virus in households raising backyard poultry in Egypt found a very low seroprevalence of antibodies to H5N1 virus (0.4% at baseline and 0.2% at follow-up).[72]Gomaa MR, El Rifay AS, Abu Zeid D, et al. Incidence and seroprevalence of avian influenza in a cohort of backyard poultry growers, Egypt, Aug 2015-Mar 2019. Emerg Infect Dis. 2020 Sep;26(9):2129-36.
https://www.doi.org/10.3201/eid2609.200266
http://www.ncbi.nlm.nih.gov/pubmed/32818403?tool=bestpractice.com