Highly Pathogenic Avian Influenza A(H5N1) Viruses

Human cases of A(H5N1)

While HPAI A(H5N1) viruses are currently circulating widely in wild birds and poultry in many geographic regions, relatively few human cases of A(H5N1) have been reported in recent years [Figure 1]. From January 2022 through October 24, 2023, seventeen sporadic human cases of A(H5N1) were reported from eight countries, including eight cases of severe disease and four deaths, two cases of mild illness, and seven asymptomatic cases [Table 1].

One human case of A(H5N1) was reported in the United States in April 2022. The individual reported fatigue without other symptoms and a low level of A(H5N1) viral RNA was detected in a single upper respiratory tract specimen. It is possible that detection of A(H5N1) viral RNA resulted from deposition of non-infectious viral material in the upper respiratory tract of the individual and did not represent true infection, similar to the environmental contamination that was attributed to the two asymptomatic cases in poultry workers reported in Spain [17]. Transient environmental deposition may also explain the detection of A(H5N1) viral RNA in cases of A(H5N1) reported in asymptomatic poultry workers in the U.K. that were investigated as part of a surveillance study [18-20].

Nearly all reported cases reported since January 2022 had recent exposure to sick or dead poultry, and no cases of human-to-human HPAI A(H5N1) virus transmission were identified. Eight cases (four children, four adults) had severe disease, and four died. Twelve cases were associated with clade 2.3.4.4b HPAI A(H5N1) viruses, and four cases were associated with clade 2.3.2.1c HPAI A(H5N1) viruses; none of the HPAI A(H5N1) virus genetic sequences contained any known markers of reduced susceptibility to currently recommended FDA-approved influenza antiviral medications.

Since 1997, a total of 900 sporadic human A(H5N1) cases have been reported from 22 countries, caused by different HPAI A(H5N1) virus clades [21], with a cumulative case fatality proportion of greater than 50%. Human A(H5N1) cases peaked in 2006 (115 cases, 9 countries) and 2015 (145 cases, 4 countries) primarily due to a large epidemic in Egypt with 136 cases [Figure 1].

Nearly all reported human A(H5N1) cases had poultry exposures, such as to sick or dead poultry or visiting live poultry markets. Rare, limited, and non-sustained instances of human-to-human HPAI A(H5N1) virus transmission likely occurred in a small number of family members following prolonged, close unprotected exposure with a symptomatic case-patient during 2004-2007 in multiple countries [22-25].

Active monitoring of persons exposed to HPAI A(H5N1) virus in the United States

Of the more than 165 people showing symptoms who were tested for novel influenza A and seasonal influenza viruses along with other respiratory viruses, HPAI A(H5N1) virus genetic material was detected in a respiratory specimen from one person in Colorado who experienced fatigue without any other symptoms while participating in poultry culling activities. [See above section on “Human cases of A(H5N1).”]

U.S. influenza surveillance for human infections with novel influenza A viruses, including HPAI A(H5N1) virus

Human infection with a novel influenza A virus, including HPAI A(H5N1) virus, is a nationally notifiable condition (case definition: Novel Influenza A Virus Infections 2014 Case Definition | CDC)

Influenza testing is widely available in clinical laboratories and healthcare facilities. Assays in these settings would detect A(H5N1) virus infections as influenza A positive and a subset of assays would be able to also determine that they are not influenza A virus subtypes H1 or H3 that commonly circulate among humans. Specimens from persons possibly exposed to H5N1 virus or that test positive for an influenza A virus but negative for A(H1) and A(H3) subtypes should be forwarded to the appropriate state or local public health laboratory for further testing. Very few specimens have been submitted to CDC for H5 testing since January 2022.

• Seasonal influenza virus detection assays that can also detect novel influenza A viruses are used in 128 public health laboratories in all 50 U.S states.
• Specific diagnostic assays to detect current A(H5) viruses are available at 99 public health laboratories in all 50 states.

Per long-standing protocols, upon detection of a virus that tests positive for influenza A but is negative for human H1 or H3 genes the public health laboratory will rapidly contact CDC and ship the specimen to CDC.  Samples that are influenza A positive but negative for human H1 or H3 genes may also be tested for H5 by state public health laboratories and are rapidly sent to CDC for a diagnostic result.  An investigation of the case will be initiated, and a case report form submitted to CDC through the novel influenza A reporting module.