Highly pathogenic avian influenza (HPAI) H5N1 virus strains have infected poultry or wild birds in more than 50 countries since 2003. Sixteen countries have reported detection of cases of human HPAI H5N1 virus infection since 2003. Between 2003 and 2018, 860 cases were reported, with 454 deaths (a case fatality rate of 53%).[26]World Health Organization. Cumulative number of confirmed human cases of avian influenza A(H5N1) reported to WHO. 2018 [internet publication].
http://www.who.int/influenza/human_animal_interface/H5N1_cumulative_table_archives/en/
WHO: cumulative number of confirmed human cases of avian influenza A(H5N1) reported to WHO
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In 2019, only one human case was reported to the World Health Organization.[27]World Health Organization. Information on avian influenza A (H5N1) identified in human in Nepal. May 2019 [internet publication].
https://www.who.int/nepal/news/detail/01-05-2019-information-on-avian-influenza-a-(h5n1)-identified-in-human-in-nepal
In October 2020, the Lao People’s Democratic Republic reported a case of human infection in a one-year-old female.[28]World Health Organization. Avian Influenza A(H5N1)- Lao People's Democratic Republic. Nov 2020 [internet publication].
https://www.who.int/csr/don/17-november-2020-ah5n1-lao/en/
Most human HPAI H5N1 cases have been among previously healthy children and young adults. The median age of patients is approximately 20 years, with an age range for all patients from under 1 year to 81 years.[29]World Health Organization. Update: WHO-confirmed human cases of avian influenza A (H5N1) infection, November 2003-May 2008. Wkly Epidemiol Rec. 2008;83:415-420.
http://www.who.int/wer/2008/wer8346.pdf
http://www.ncbi.nlm.nih.gov/pubmed/19009716?tool=bestpractice.com
The ratio of male to female cases is about equal; however, there is a higher case-fatality proportion in females, which may be due to many different epidemiological factors, such as delay in accessing healthcare, case age, and physician testing patterns.[18]World Health Organization. Update on human cases of highly pathogenic avian influenza A(H5N1) virus infection, 2010. Wkly Epidemiol Rec. 2011;86:161-166.
http://www.who.int/wer/2011/wer8617.pdf
http://www.ncbi.nlm.nih.gov/pubmed/21516633?tool=bestpractice.com
From 2003 to 2010, patients under 20 years of age had a significantly lower risk of dying than those aged over 20 years (case-fatality proportions: 52% vs. 66%).[18]World Health Organization. Update on human cases of highly pathogenic avian influenza A(H5N1) virus infection, 2010. Wkly Epidemiol Rec. 2011;86:161-166.
http://www.who.int/wer/2011/wer8617.pdf
http://www.ncbi.nlm.nih.gov/pubmed/21516633?tool=bestpractice.com
Mortality is associated with delayed recognition of disease and hospitalisation after symptom onset.[18]World Health Organization. Update on human cases of highly pathogenic avian influenza A(H5N1) virus infection, 2010. Wkly Epidemiol Rec. 2011;86:161-166.
http://www.who.int/wer/2011/wer8617.pdf
http://www.ncbi.nlm.nih.gov/pubmed/21516633?tool=bestpractice.com
One study reported that the presence of rhinorrhoea appeared to indicate a better prognosis for children with HPAI H5N1.[24]Oner AF, Dogan N, Gasimov V, et al. H5N1 avian influenza in children. Clin Infect Dis. 2012;55:26-32.
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
In January 2014, Canada reported identifying a human case of HPAI H5N1 in a person who travelled from China to Canada, where the patient was hospitalised and died.[30]Centers for Disease Control and Prevention. Highly pathogenic Asian avian influenza A (H5N1) virus. May 2018 [internet publication].
https://www.cdc.gov/flu/avianflu/h5n1-virus.htm
While there is no indication that the infection was acquired within North America, this case highlights that clinicians should remain vigilant for influenza virus infections, including HPAI H5N1 and other novel influenza A viruses, in critically ill patients. Also in 2014, the United Nations Food and Agriculture Organization (FAO) reported that there were at least 6 countries with endemic HPAI H5N1 virus circulation among poultry populations: Bangladesh, the People’s Republic of China, Egypt, India, Indonesia, and Vietnam, with sporadic poultry outbreaks in other countries.[31]Food and Agriculture Organization of the United Nations. Update on the continuous spread and expansion of H5N1 highly pathogenic avian influenza: clade 2.3.2.1 in Asia (2010-2012). January 2014 [internet publication].
http://www.fao.org/3/a-i3610e.pdf
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.[32]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 Apr 7 [Epub ahead of print].
http://www.ncbi.nlm.nih.gov/pubmed/32259345?tool=bestpractice.com
A cohort study of human avian influenza virus infections in households raising backyard poultry in Egypt found a very low prevalence of H5N1 (0.4% at baseline and 0.2% at follow up).[33]Gomaa MR, El Rifay AS, Abu Zeid D, et al. Incidence and seroprevalence of avian influenza in a cohort of backyard poultry growers, Egypt, August 2015-March 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
Asian lineage HPAI H5N1 virus strains have not been detected in domestic poultry in North or South America to date, though antigenically distinct HPAI H5N1 viruses not associated with human infection have been identified in birds in the US.[34]Centers for Disease Control and Prevention. Highly pathogenic avian influenza A (H5N1) in birds and other animals. Jan 2015 [internet publication].
https://www.cdc.gov/flu/avianflu/h5n1-animals.htm