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.
Public health response
According to the International Health Regulations (IHR), human infection caused by a novel influenza A virus subtype is an event that has the potential for high public health impact. A novel influenza A virus is considered to have the potential to cause a pandemic if (1) the virus has demonstrated the capacity to infect and transmit efficiently among humans; and (2) differs from currently-circulating seasonal human influenza viruses such that the hemagglutinin (HA) gene (or protein) is not a mutated form of those, i.e. A/H1 or A/H3, circulating widely in the human population; and (3) the population has little to no immunity against it. Human infections with variant viruses tend to result in mild clinical illness, although some cases have been hospitalized with more severe disease. Nevertheless, human infections with these viruses need to be monitored closely.
CDC and Wisconsin State Authorities have taken the following monitoring, prevention and control measures
- Case management of the case and close contacts;
- Testing of close contacts;
- An epidemiological investigation was completed with no evidence of person-to-person transmission;
- Risk communication has been initiated for the public and healthcare workers;
- Strengthened surveillance in the community where the case resides;
- Laboratory samples were shared with the WHO Collaboration Centre
WHO risk assessment
Since 2005, there has been some limited, non-sustained human-to-human transmission of variant influenza viruses, but no ongoing community transmission has been identified. Current evidence suggests that these viruses have not acquired the ability of sustained transmission among humans, thus the likelihood is low.
Swine influenza viruses circulate in swine populations in many regions of the world. Depending on geographic location, the genetic characteristics of these viruses differ. When an influenza virus that normally circulates in swine (but not people) is detected in a person, it is called a “variant influenza virus”. Most human cases are the result of exposure to swine influenza viruses through contact with infected swine or contaminated environments. Because these viruses continue to be detected in swine populations around the world, further human cases can be expected.
Influenza viruses that infect pigs may be different from human influenza viruses. Thus, influenza vaccines against human influenza viruses are generally not expected to protect people from influenza viruses that normally circulate in pigs. In addition, pigs are susceptible to avian, human and swine influenza viruses; they may get infected with influenza viruses from different species at the same time. If this happens, it is possible for the genes of these viruses to mix and create a new virus. This type of major change in the influenza A viruses is known as antigenic shift. If this new virus causes illness in people and can be transmitted easily from person-to-person with no immunity, an influenza pandemic can occur.
The risk assessment will be reviewed as needed should further epidemiological or virological information become available.
All human infections caused by a novel influenza subtype are notifiable under the International Health Regulations (IHR) and State Parties to the IHR (2005) are required to immediately notify WHO of any laboratory-confirmed case of a recent human infection caused by an influenza A virus with the potential to cause a pandemic. Evidence of illness is not required for this report.
Due to the evolution influenza viruses, WHO continues to stress the importance of global surveillance to detect virologic, epidemiologic and clinical changes associated with circulating influenza viruses that may affect human (or animal) health with timely sharing of such viruses and related information for further characterization and risk assessment.
This case does not change the current WHO recommendations on public health measures and surveillance of seasonal influenza. All human infections caused by a novel influenza subtype are notifiable under the International Health Regulations (IHR) and State Parties to the IHR (2005) are required to immediately notify WHO of any laboratory-confirmed case of a recent human infection caused by an influenza A virus with the potential to cause a pandemic. Evidence of illness is not required for this report .
Travelers to countries with known outbreaks of animal influenza should avoid farms, contact with animals in live animal markets, entering areas where animals may be slaughtered, or contact with any surfaces that appear to be contaminated with animal feces. General hygiene measures, such as regular hand washing before and after touching animals and potentially contaminated environments and avoiding contact with sick animals, should be adhered to. WHO does not recommend any specific different measures for travellers. WHO does not advise special screening at points of entry regarding this event, nor does it recommend that any travel or trade restrictions be applied.
In the case of a confirmed or suspected human infection caused by a novel influenza virus with pandemic potential, including a variant virus, a thorough epidemiologic investigation (even while awaiting the confirmatory laboratory results) of history of exposure to animals, of travel, and contact tracing should be conducted. The epidemiologic investigation should include early identification of unusual respiratory events that could signal person-to-person transmission of the novel virus and clinical samples collected from the time and place that the case occurred should be tested and sent to a WHO Collaboration Center for further characterization.