Novel Influenza A Virus Infections
2024 Case Definition

Background

Human infections with novel influenza A viruses that can be transmitted from person to person may signal the beginning of an influenza pandemic. Rapid detection and reporting of human infections with novel influenza A viruses (viruses against which there is little to no pre-existing immunity) will facilitate prompt detection and characterization of influenza A viruses with pandemic potential and accelerate the implementation of effective public health responses.

Clinical Criteria

In the absence of a more likely alternative diagnosis or cause, an acute illness characterized by either:

• One or more of the following: Cough, sore throat, fever (measured or subjective), shortness of breath or difficulty breathing, conjunctivitis (red eye, discharge from eye),

OR

• Two or more of the following: Headache, myalgia, arthralgia, fatigue, rhinorrhea or nasal congestion, diarrhea, vomiting.

Laboratory Criteria

Confirmatory Laboratory Evidence:

Category 1 (novel influenza virus detection)

• Positive confirmatory molecular test result (e.g., reverse transcriptase polymerase chain reaction [rT-PCR]) for novel influenza A subtype,

OR

• Genetic sequence indicative of novel influenza A virus.

Category 2 (viable virus)

• Isolation of a novel influenza virus from a clinical specimen.*

Category 3 (evidence of infection)

• Significant IgG antibody rise to novel influenza A (i.e., at least a 4-fold rise in a quantitative titer or seroconversion) in paired acute and convalescent serum IgG in the absence of another explanation (such as vaccination).

Presumptive Laboratory Evidence:

Category 1

• Presumptive positive for novel influenza virus on tests specifically designed to detect novel influenza viruses, such as H5 or H7.**

Category 2

• Virus testing results indicative of variant influenza virus, such as H1v or H3v, as determined in consultation with subject matter experts at CDC.**

Note: The categorical labels used here to stratify laboratory evidence are intended to support the standardization of case classifications for public health surveillance. The categorical labels should not be used to interpret the utility or validity of any laboratory test methodology.

*Isolation of a novel virus should not be performed outside of CDC.

** See Appendix A (in the approved CSTE Position Statement).

Epidemiologic Linkage

• Close contact with a confirmed human case of novel influenza A virus infection,

OR

• Shared a common exposure (such as an agricultural fair or live animal market) with a confirmed novel influenza A case,

OR

• Direct or indirect contact (such as touching an animal, their environment, or their raw or unprocessed animal products) with animals with confirmed influenza A,

OR

• Inadequate use or breach of PPE and exposed to novel influenza A virus in a laboratory.

Criteria to Distinguish a New Case from an Existing Case

A person should be enumerated as a new case of a novel influenza A virus infection if:

• The virus is distinguishable from the individual’s previous novel influenza A virus infection,

OR

• The virus is indistinguishable from the individual’s previous novel influenza A virus infection, AND
  • The person has recovered fully or returned to baseline health,

OR

• • It has been >30 days since symptom onset date (if available) or first positive specimen collection date.

Note: For severely immunocompromised individuals, judgment should be used to determine if a repeat positive test is likely to result from long-term shedding and, therefore, not be enumerated as a new case. CDC defines severe immunocompromise as certain conditions, such as being on chemotherapy for cancer, untreated human immunodeficiency virus (HIV) infection with CD4 T lymphocyte count <200, combined primary immunodeficiency disorder, and receipt of prednisone >20mg/day for more than 14 days.

Suspect

• Meets clinical criteria AND epidemiologic linkage criteria AND laboratory testing results are positive for influenza A virus, but no laboratory evidence is available that would rule out novel influenza A.

Probable

• Meets confirmatory laboratory evidence category 1,

OR

• Meets clinical criteria AND presumptive laboratory evidence category 1,

OR

• Meets clinical criteria AND epidemiologic linkage criteria AND presumptive laboratory evidence category 2.

Note: A probable case classification should not undermine the diagnosis of novel influenza A under CLIA guidelines, and the patient should be provided the same care and investigation as a confirmed case.

Confirmed

• Meets clinical criteria AND confirmatory laboratory evidence category 1,

OR

• Meets confirmatory laboratory evidence category 2,

OR

• Meets confirmatory laboratory evidence category 3.

Jurisdictions may choose to have another case classification category, such as Persons Under Investigation (PUI), for all persons pending further investigation for novel influenza A.

• Novel Influenza A Virus Infections | 2014 Case Definition
• Novel Influenza A Virus Infections | 2013 Case Definition
• Novel Influenza A Virus Infections | 2010 Case Definition
• Novel Influenza A Virus Infections | 2007 Case Definition