Respiratory Viruses

Novel Influenza A Viruses

Novel (also referred to as variant) influenza viruses are any Influenza A infection from an Influenza A virus that is different from currently circulating human seasonal influenza (H1 and H3 viruses). Novel viruses include those that are sub-typed as nonhuman in origin as well as those that are not able to be sub-typed using standard laboratory methods and reagents.

Human infections with novel influenza A viruses include influenza A virus sub-types different from currently circulating human H1 and H3 influenza viruses.

Novel Influenza Sub-Types

Novel influenza includes, but are not limited to:

Human influenza virus sub-types

• H2

• H5

• H7

• H9

Non-Human species influenza viruses, or from genetic reassortment between human and animal viruses

• H1

• H3

Novel Influenza Nomenclature

Human infections with an influenza virus that normally circulates in another species (swine or avian) and not in humans are called variant viruses. They are denoted by using the letter "v" at the end of the sub-type. 

Swine Influenza A(H1N2)v - March 2024

On March 29th, a human infection with a novel influenza A virus was reported by the Pennsylvania Department of Health. The patient was infected with an influenza A(H1N2) variant (A(H1N2)v) virus. The patient is < 18 years of age, sought healthcare during the week ending March 9, 2024 (week 10), was hospitalized, and has since recovered. An investigation by local public health officials found that the patient had swine contact prior to their illness onset. Additional investigation identified mild illness in two of the patient’s close contacts who also had contact with swine, that began prior to the patient’s onset of symptoms. No person-to-person transmission of A(H1N2)v virus associated with this patient has been identified. The investigation is ongoing. This is the first human infection with a variant influenza A virus reported in the United States in 2024.

Swine Influenza A(H1N2)v - August 2023

On 4 August 2023, the United States IHR National Focal Point informed PAHO/WHO of a human infection with a novel influenza A(H1N2) variant virus identified in the State of Michigan and confirmed by the US CDC.  

According to the report, the case is under 18 years old, with no comorbidities, resident in the State of Michigan, who developed respiratory illness on 29 July 2023. The case presented with fever, cough, sore throat, muscle aches, headache, shortness of breath, diarrhea, nausea, dizziness, and lethargy. On 29 July, the case sought medical care at an emergency department, and an upper respiratory tract specimen was collected on 30 July. The specimen tested positive for influenza A virus on the same day. On 1 August, the patient received influenza antiviral treatment (Oseltamivir).

On 31 July, the specimen was tested at the Michigan Department of Health and Human Services (MDHHS), and RT-PCR results were positive for influenza A virus but lacked reactivity with diagnostic tests for contemporary human influenza viruses representing either (H1) pdm09 or (H3) subtypes. The specimen was then sent to the US CDC for further testing and received on 2 August. On the same day, RT-PCR analysis of the specimen indicated an influenza A(H1N2) variant (v) virus. The virus was isolated and subsequent analysis including genetic sequencing is underway.

The case was not hospitalized. Investigation by local public health officials identified swine exposure by the patient at an agricultural fair, that took place between 23 and 29 July, within 10 days prior to illness onset. Additional investigation did not identify respiratory illness in any of the patient’s close contacts or household contacts. No additional cases were identified related to this agriculture fair. No person-to-person transmission of influenza A(H1N2)v virus associated with this case has been identified. No additional cases of human infection with A(H1N2)v virus have been identified as of 10 August 2023.

This is the first influenza A(H1N2)v virus infection identified in the United States this year. Since 2005, there have been 512 influenza A variant virus infections (all subtypes), including 37 (human infections with influenza A (H1N2)v viruses reported in the United States.

Avian Influenza A(H5N1)v - May 2022

On 29 April 2022, the National IHR Focal Point of the United States of America notified WHO of a laboratory confirmed human case of avian influenza A(H5), in a male from Colorado State.

The case developed fatigue on 20 April, during participation in slaughtering poultry from 18 to 22 April, at a commercial poultry facility in Colorado where influenza A (H5N1) virus had been confirmed in the poultry.

Upon request of the organization providing personnel for culling of poultry at this facility, a respiratory sample was collected from the case on 20 April. The sample was received by the Colorado Department of Public Health and Environment Laboratory Services on 22 April and testing was completed on 25 April. Influenza A virus was detected by reverse transcriptase- polymerase chain reaction (RT-PCR). The sample was sent to the Influenza division of the United States Centers for Disease Control and Prevention (CDC) for further confirmation. Influenza A(H5) virus was confirmed by RT-PCR on 27 April and subtype N1 was subsequently confirmed by sequence analysis. 

On 26 April 2022, the patient was isolated and treated with antivirals. The patient did not report symptoms other than fatigue, was not hospitalized and has since recovered.

This is the first human case of influenza A (H5N1) virus reported in the United States of America.  

Swine Influenza A(H3N2)v  -- February 2021

On 13 January, 2021, a child under 18 years of age in Wisconsin developed respiratory disease. A respiratory specimen was collected on 14 January. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) testing conducted at the Wisconsin State Laboratory of Hygiene indicated a presumptive positive influenza A(H3N2) variant virus infection. The specimen was forwarded to the Influenza Division of the Centers for Disease Control and Prevention (CDC) on 21 January for further testing. On 22 January, CDC confirmed an influenza A (H3N2)v virus infection using RT-PCR and genome sequence analysis. Investigation into the source of the infection has been completed and revealed that the child lives on a farm with swine present. Sampling of the swine on the property for influenza virus has not yet been conducted but is planned. Five family members of the patient reported respiratory illness during the investigation and were tested for influenza; all tested negative. The patient was prescribed antiviral treatment and was not hospitalized and has made a full recovery. No human to human transmission has been identified associated with this investigation.

Sequencing of the virus by CDC revealed it is similar to A (H3N2) viruses circulating in swine in the mid-western United States during 2019-2020. Viruses related to this A (H3N2)v virus were previously circulating as human seasonal A (H3N2) viruses until around 2010-2011 when they entered the USA swine population. Thus, past vaccination or infection with human seasonal A (H3N2) virus is likely to offer some protection in humans.

This is the first influenza A (H3N2)v virus identified in the United States in 2021. Since 2005, a total of 485 influenza variant virus human infections caused by all subtypes including 437 human infections with A (H3N2)v, including this one, have been reported in the United States.

Surveillance for Novel Influenza A Viruses

In 2007, human infection with a novel influenza A virus became a nationally notifiable condition. Novel influenza A virus infections include all human infections with influenza A viruses that are different from currently circulating human seasonal influenza H1 and H3 viruses. These viruses include those that are subtyped as nonhuman in origin and those that cannot be subtyped with standard laboratory methods and reagents. Rapid detection and reporting of human infections with novel influenza A viruses – viruses against which there is often little to no pre-existing immunity – is important to facilitate prompt awareness and characterization of influenza A viruses with pandemic potential and accelerate the implementation of public health responses to limit the transmission and impact of these viruses.

Newly reported cases of human infections with novel influenza A viruses in the United States are reported in FluView and additional information, including case counts by geographic location, virus subtype, and calendar year, are available on FluView Interactive.

Since 2005, HPAI A(H5N1) viruses have undergone extensive genetic diversification including the formation of hundreds of genotypes following reassortment with other avian influenza A viruses. Clade 2.3.4.4b HPAI A(H5N1) viruses emerged in 2020 and were introduced into North America in late 2021 and have spread to Central and South America, resulting in wild bird infections (in terrestrial, seabird, shorebird, and migratory species) and poultry outbreaks in many countries.

Globally, this 2.3.4.4b clade of HPAI A(H5N1) viruses has become widespread causing record numbers of bird outbreaks in wild, backyard, village, and farm birds. Over 17,000 animal outbreaks of HPAI A(H5N1) viruses were reported by 80 member countries to the World Organisation for Animal Health since January 2022.

A small number of sporadic human cases of A(H5N1) have been identified since 2022, despite the panzootic of highly pathogenic avian influenza (HPAI) A(H5N1) viruses in wild birds and poultry. Nearly all reported human cases since 2022 were associated with poultry exposures, and no cases of mammal-to-human or human-to-human transmission of HPAI A(H5N1) virus have been identified. In a few cases, the source of exposure to HPAI A(H5N1) virus was unknown.

To date, HPAI A(H5N1) viruses currently circulating in birds and poultry, with spillover to mammals, and those that have caused human infections do not have the ability to easily bind to receptors that predominate in the human upper respiratory tract. Therefore, the current risk to the public from HPAI A(H5N1) viruses remains low.

However, because of the potential for influenza viruses to rapidly evolve and the wide global prevalence of HPAI A(H5N1) viruses in wild birds and poultry outbreaks, continued sporadic human infections are anticipated. Continued comprehensive surveillance of these viruses in wild birds, poultry, mammals, and people worldwide, and frequent reassessments are critical to determine the public health risk, along with ongoing preparedness efforts.

Avian Influenza Infections in Humans, 2022-2024