Novel influenza A virus infections

2024 Case Definition

CSTE Position Statement Number: 24-ID-09

Background

When human infections with novel influenza A viruses that can be transmitted from person-to-person are detected more frequently, it 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 Description

In the absence of a more likely alternative diagnosis or cause, an acute illness is 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).
Two or more of the following: Headache, myalgia (muscle pain), arthralgia (joint pain), fatigue, rhinorrhea (runny nose) or nasal congestion, diarrhea (2 or more loose stools in a 24-hour period), vomiting.

Laboratory Criteria for Diagnosis

Confirmatory Laboratory Evidence:

Category 1 (novel virus detection)

Positive confirmatory molecular test result (e.g., reverse transcriptase polymerase chain reaction [rTPCR]) for novel influenza subtype.

OR

Genetic sequence indicative of novel influenza A strain.
Category 2 (viable virus)

Isolation of a novel influenza virus from a clinical specimen, which should not be performed outside of CDC.
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 on tests specifically designed to detect novel influenza, such as H5 or H7.
Category 2

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

Epidemiologic Linkage

Criteria for epidemiologic linkage:

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

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

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

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

Case Classification

Confirmed:

Meets clinical criteria AND confirmatory laboratory evidence category 1.

Meets confirmatory laboratory evidence category 2.

Meets confirmatory laboratory evidence category 3.

Probable:

Meets confirmatory laboratory evidence category

Meets clinical criteria AND presumptive laboratory evidence category 1.

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

Suspect:

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

Classification Table: Criteria for defining a case of novel influenza A infection.

Criterion	Confirmed		Probable			Suspect
Clinical Criteria
Acute illness	N			N	N	N
Absence of a more likely alternative diagnosis	N			N	N	N
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)	O			O	O	O
Two or more of the following: Headache Myalgia Arthralgia Fatigue Rhinorrhea or nasal congestion Diarrhea Vomiting	O			O	O	O
Laboratory Criteria
Positive confirmatory molecular test result (e.g., reverse transcriptase polymerase chain reaction [rT-PCR]) for novel influenza subtype	O		S
Genetic sequence indicative of novel influenza A strain	O		S
Isolation of a novel influenza virus from a clinical specimen*		S
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)		S
Presumptive positive for novel influenza on tests specifically designed to detect novel influenza, such as H5 or H7 ***				N
Virus testing results indicative of variant influenza, such as H1v or H3v, as determined in consultation with subject matter experts at CDC***					N
Testing results positive for influenza A and no evidence ruling out novel influenza A**						N
Epidemiological Link Criteria
Close contact with a confirmed human case of novel influenza A virus infection					O	O
Shared a common exposure (such as agricultural fair or live animal market) with a confirmed novel influenza A case					O	O
Direct or indirect contact (such as touching an animal, their environment, or their raw or unprocessed animal products) with animals with confirmed influenza A					O	O
Inadequate use or breach of PPE and exposed to novel influenza A virus in a laboratory					O	O

Notes:
S = This criterion alone is SUFFICIENT to classify a case.
N = All “N” criteria in the same column are NECESSARY to classify a case.
O = At least one of these “O” (ONE OR MORE) criteria in each category (categories=clinical evidence, laboratory
evidence, and epidemiologic evidence) in the same column—in conjunction with all “N” criteria in the same
column—is required to classify a case.
* Isolation of a novel virus should not be performed outside of CDC.
** Jurisdictions may choose to have another category, such as Persons Under Investigation (PUI), for all persons pending further investigation for novel influenza A.
*** See Appendix A.

Date Posted: January 9, 2025