Interim Guidance for Clinicians on Human Infections with Variant Influenza Viruses

Background

Influenza A viruses circulating in swine that have infected humans are referred to as "variant" influenza viruses and denoted with a letter "v". Human infections with influenza A(H1N1)v, A(H1N2)v, and A(H3N2)v viruses have been detected in the United States.

Most commonly, human infections with variant influenza viruses occur in people with exposure to infected swine (e.g., children exposed to swine at an agricultural fair, people who raise swine, or workers in the swine industry). The vast majority of variant influenza A virus infections do not result in subsequent person-to-person spread; however, rare cases of limited spread of variant influenza viruses from person-to-person have occurred. Each variant influenza A virus infection that is identified should be fully investigated to determine (i) the source of exposure and infection; (ii) to prevent and control additional infections of animals and people, and (iii) importantly to assess whether such viruses are spreading from person-to-person.

Clinical presentation and risk groups

Clinical characteristics of human infections with variant influenza A viruses generally have been similar to signs and symptoms of uncomplicated seasonal influenza, including fever, cough, pharyngitis, rhinorrhea, myalgia, and headache. Vomiting and diarrhea also have been reported in some infections in children. Milder clinical illness is possible, including lack of fever, and conjunctivitis has been reported. The duration of illness appears to be similar to uncomplicated seasonal influenza, approximately 3 to 5 days. While assumed to be similar to seasonal influenza A virus infection, the duration of viral replication and possible infectiousness of variant influenza A virus infection has not been well studied.

Most variant influenza A virus infections have resulted in mild illness. Although uncommon, severe and fatal illness resulting from variant influenza A virus infection has been reported. Exacerbation of underlying conditions (e.g., asthma) has occurred. The same people at increased risk for complications of seasonal influenza are also likely at higher risk for serious complications, including death from variant influenza virus infection; these people include children younger than 5 years, pregnant people, people 65 years and older, those who are immunocompromised, and people with chronic pulmonary, cardiac, metabolic, hematologic, renal, hepatic, neurological or neurodevelopmental conditions, as well as those with other co-morbidities, including extreme obesity (BMI ≥ 40).

Clinical diagnosis

Variant influenza A virus infection cannot be distinguished by clinical features from seasonal influenza virus infection, or from infection with other respiratory viruses that can cause influenza-like illness (fever and either cough or sore throat). Therefore, the key to suspecting variant influenza A virus infection in an ill patient is to elicit an epidemiological link to swine exposure in the week prior to illness onset.

Exposure can be defined as follows:

• Contact with swine or bodily fluids (e.g., saliva, blood, urine, mucous, feces) from swine. This can happen when showing swine, raising swine, feeding swine, or cleaning swine waste.
• Contact with areas where swine live or objects or surfaces that have been contaminated with germs from swine (e.g., visiting a swine farm or walking through a swine barn), especially if swine were known to be ill; or
• Close contact (within 2 meters or approximately 6 feet) with an ill person who had recent swine exposure or is known to be infected with a variant influenza A virus.

For any ill person with an exposure as defined above, respiratory specimens should be collected for influenza testing. Clinicians should obtain a nasopharyngeal swab or aspirate (or a combined nasal swab and throat swab), place the swab or aspirate (or combined specimen) into viral transport media, and contact their state or local health department to arrange transport and request timely influenza diagnostic testing at a state public health laboratory. Only CDC and state public health laboratories can confirm variant influenza virus A infections. If influenza testing is also going to be done at the hospital or clinic, the specimen should be split or two specimens should be taken so that one can be immediately sent to the health department for influenza testing.

Infection Control – Patient Care

Limited, non-sustained human-to-human transmission of some variant influenza A viruses has been reported. While limited data are available, the risk of human-to-human transmission is thought to be low. However, it is assumed that variant influenza A viruses may be transmitted from person-to-person. Therefore, in health care settings, infection control recommendations are the same as for seasonal influenza, including standard and droplet (i.e., health care provider wears a facemask) precautions. For aerosol-generating procedures, a fit-tested N95 respirator or equivalent should be used. Prevention Strategies for Seasonal Influenza in Healthcare Settings and Infection Control in Health Care Facilities.

Infection Control – Specimen Collection

Health care personnel who collect respiratory specimens from ill persons for influenza testing should follow standard and droplet precautions, as recommended for patient care.

Lab diagnosis and test interpretation

Hospital and Clinical Laboratories

Most antigen detection tests, such as commercially available rapid influenza diagnostic tests (RIDTs) and immunofluorescence assays [e.g., direct fluorescent antibody staining (DFA)] are likely to detect variant influenza A viruses in respiratory specimens as indicated by a positive result for influenza A. However, antigen detection tests cannot distinguish between seasonal influenza A, variant influenza A, or other novel influenza A viruses. Some RIDTs may not detect variant influenza A viruses in respiratory specimens (i.e., they may provide a false negative result). While some variant influenza A virus infections have tested positive by RIDTs, some variant influenza A virus infections confirmed by RT-PCR assays have tested negative by RIDTs.

There are a variety of commercial molecular assays, including RT-PCR assays, that can detect influenza viruses in respiratory specimens. Molecular influenza assays have higher sensitivity to detect influenza A viruses than RIDTs. Detection of variant viruses in respiratory specimens by molecular influenza assays will yield a positive result for influenza A. However, commercially available molecular assays cannot differentiate variant influenza A viruses from seasonal influenza A, variant influenza A, or other novel influenza A viruses, and the sensitivity and specificity of molecular assays to detect variant influenza A viruses are not known. Some academic medical center laboratories may use non-commercially available molecular assays for influenza ("home brews"); the sensitivity and specificity of home brew molecular assays to detect variant influenza A viruses are not known.

Confirmation of variant influenza A virus infection requires testing for variant influenza viruses in respiratory specimens at state public health laboratories and confirmation at CDC.

Clinician reporting

Clinicians should notify the local public health department of any suspected variant influenza A virus infections as soon as possible. The health department can arrange for appropriate testing of clinical specimens at the state public health laboratory.

Clinical management

Clinical management of variant influenza A virus infection is similar to management of seasonal influenza virus infections. Patients with mild uncomplicated variant influenza A virus infection can be managed on an outpatient basis, with close monitoring for clinical progression and development of complications. Early initiation of antiviral treatment with a neuraminidase inhibitor (oseltamivir, zanamivir, peramivir) or baloxavir is recommended for any outpatients at higher risk of severe illness with suspected or confirmed variant influenza A virus infection. Management of mild to moderate complications such as non-severe exacerbation of underlying co-morbidities may be managed on an outpatient basis. For patients with severe and progressive disease who do not require hospital admission, prompt oseltamivir treatment is recommended. However, hospitalization may be required for some patients with severe complications. For hospitalized patients with suspected or confirmed variant influenza A virus infection, antiviral treatment with oseltamivir should be started as soon as possible for previously untreated patients. If secondary invasive bacterial infection is suspected, appropriate empiric antibiotic therapy should be started promptly. Additional clinical management includes supportive care of complications (e.g., supplemental oxygen for hypoxia; mechanical ventilation for respiratory failure; vasopressors for shock; renal replacement therapy for acute kidney injury).

Antiviral Treatment

Variant influenza A viruses tested to date are susceptible to the neuraminidase inhibitor drugs oseltamivir, peramivir and zanamivir, and the cap-dependent endonuclease inhibitor baloxavir. These drugs can be prescribed to treat variant influenza A virus infections. However, most variant influenza A viruses are resistant to the antiviral drugs amantadine and rimantadine; therefore, amantadine and rimantadine should not be prescribed.

• Oral oseltamivir, inhaled zanamivir, intravenous peramivir, or oral baloxavir are recommended for treatment of variant influenza A virus infections.
• While early initiation of antiviral treatment (within 48 hours of illness onset) provides the greatest clinical benefit, antiviral treatment may still be effective when administered later in patients with moderate and severe illness.
• Antiviral treatment with oral oseltamivir, inhaled zanamivir, intravenous peramivir, or oral baloxavir is recommended for outpatients with suspected influenza or confirmed influenza, including variant influenza A virus infection, if they are in a group considered to be at higher risk for serious complications from influenza.
• Antiviral treatment also can be considered for any previously healthy, symptomatic outpatient not at higher risk for serious complications who has suspected or confirmed variant influenza A virus infection on the basis of clinical judgment, if treatment can be initiated within 48 hours of illness onset.
• For people suspected of having variant influenza A virus infection and who are hospitalized, have severe or progressive illness, or are in a higher-risk group, empiric antiviral treatment should be started as soon as possible, without waiting for the results of influenza testing.
• For hospitalized patients and patients with severe or complicated illness, treatment with oral or enterically administered oseltamivir is recommended. Inhaled zanamivir and oral baloxavir are not recommended because of the lack of data for use in patients with severe influenza disease to date. There also are insufficient data regarding efficacy of intravenous peramivir for hospitalized influenza patients.

Antiviral treatment recommendations for variant influenza A virus infection are based upon those for seasonal influenza.

Antiviral Chemoprophylaxis

Antiviral chemoprophylaxis (before or after swine exposure) is not routinely recommended, but can be considered in limited instances (see IDSA Influenza Clinical Practice Guidelines) for people who are at higher risk for influenza complications. If such higher-risk people become ill, they should seek medical care as soon as possible and early antiviral treatment should be started if influenza, including variant influenza A virus infection, is suspected.

In most instances, variant influenza A viruses have not spread easily from person to person. Recommendations for seasonal influenza at Influenza Antiviral Medications: Summary for Clinicians.

Over-the-Counter Medications

Clinicians should remind parents that aspirin or aspirin-containing products should not be given to children with influenza-like illness, including persons who are suspected of having variant influenza A virus infection, because of the risk of Reye syndrome with influenza virus infection.

Caring for a sick family member

Ill people with suspected or confirmed variant influenza A virus infections who do not require hospitalization should be isolated at home away from other family members as much as possible. Household members who are at increased risk for serious influenza complications should avoid coming within 2 meters (or approximately 6 feet) of ill people. When caring for someone who is sick, both the caretaker and the person who is sick should wear a facemask when in close contact, if possible. Close contact with someone who is sick, even when that person is wearing a facemask, should be minimizedd to the extent possible. More information is available at Caring for Someone Sick | CDC.

Vaccination

No vaccine specifically targeted against variant influenza A viruses is available at this time. Seasonal influenza vaccines are not intended (or designed) to provide protection against infection with variant influenza A viruses.

Seasonal influenza A and B viruses circulate during the fall and winter months. Therefore, annual seasonal influenza vaccination is recommended for all people aged 6 months and older each fall to prevent seasonal influenza. For more information: Recommendations of the Advisory Committee on Immunization Practices (ACIP).

Prevention

People who are at higher risk for serious influenza complications, including young children, are not routinely recommended for antiviral chemoprophylaxis. These people should avoid exposure to swine and to ill people with swine exposure. If exposure to swine cannot be avoided, people at higher risk for serious influenza complications should consider wearing appropriate personal protective equipment. Guidance for people who work with or raise swine is available at Variant Flu Information for People with Exposure to Pigs.