Tests
1st tests to order
CBC with differential
Test
Described in most patients in small case series.
Result
leukopenia, lymphopenia, thrombocytopenia
LFTs
Test
Described in most patients in small case series.
Result
elevated aspartate aminotransferase/alanine aminotransferase
chest x-ray
Test
A chest x-ray alone cannot exclude viral or bacterial pneumonia.
Result
may be normal; may show infiltrates consistent with pneumonia in severe cases
pulse oximetry
Test
Indicated in patients with dyspnea or suspected pneumonia.
Result
may show hypoxia
sputum Gram stain
Test
Primary bacterial pneumonia and potential bacterial coinfection should be evaluated. Few coinfections have been reported in highly pathogenic avian influenza (HPAI) A(H5N1) patients, except with ventilator-associated pneumonia.
Result
visualization of infecting organisms if bacterial pneumonia or potential bacterial coinfection
sputum and blood bacterial culture
Test
Primary bacterial pneumonia and potential bacterial coinfection should be evaluated.
Result
growth of infecting organism if bacterial pneumonia or potential bacterial coinfection
real-time reverse transcription polymerase chain reaction (rtRT-PCR)
Test
Recommended for diagnosis of highly pathogenic avian influenza (HPAI) A(H5N1) virus infection.[111][124]
Perform testing on people with signs or symptoms of acute respiratory illness or conjunctivitis who have a relevant exposure history and who meet the suspected case definition.[111] For case definitions, see Criteria.
Testing of asymptomatic people is not routinely recommended, but may be considered on a case-by-case basis as part of public health investigations (e.g., workers with a high risk of exposure to infected animals who do not report wearing the recommended personal protective equipment, close contacts of a confirmed case).[111][121]
Infection prevention and control precautions are recommended when collecting specimens. Obtain specimens as soon as possible, ideally within 7 days of symptom onset.[123]
Preferred specimens are a nasopharyngeal swab, and a nasal swab combined with an oropharyngeal swab (two swabs collected separately and combined into one transport vial). In patients with conjunctivitis (with or without respiratory symptoms), a conjunctival swab and nasopharyngeal swab should be collected and tested separately, when possible. However, conjunctival swabs may be tested without a respiratory sample if a paired respiratory sample is not available. If these specimens cannot be collected, a single nasal swab or oropharyngeal swab is considered acceptable.[123]
Patients with severe respiratory disease should also have lower respiratory tract specimens (e.g., endotracheal aspirate or bronchoalveolar fluid from intubated patients, or induced sputum) collected, in addition to upper respiratory tract specimens, if possible. These specimens have a higher yield for detecting HPAI A(H5N1) virus.[123]
Multiple respiratory specimens should be collected from different sites on at least two consecutive days for severely ill patients, because testing single specimens may miss detection of HPAI A(H5N1) virus.[123]
Swabs with a synthetic tip (e.g., Dacron®, polyester) and an aluminum or plastic shaft should be used.[123]
Specific A(H5) testing may not be available in some clinical settings. Many regional public health laboratories, most national laboratories, and some private laboratories can perform this test. It takes approximately 4 hours to produce preliminary results, but transport time and testing logistics may delay testing results.
In the context of the current outbreak in the US, as of 16 January 2025, the Centers for Disease Control and Prevention (CDC) recommends routinely testing all patients with suspected influenza and to expedite the subtyping of influenza A-positive specimens from hospitalized patients, particularly those in the intensive care unit. Subtyping should be performed as soon as possible following admission, ideally within 24 hours. The goal of this approach is to prevent delays in identifying infections.[122]
All influenza A positive specimens that are not able to be subtyped should be sent to a National Influenza Centre, if originally tested elsewhere, and then to a World Health Organization (WHO) Global Influenza Surveillance and Response System (GISRS) for further analysis.[121]
Result
positive for H5-specific viral RNA
Tests to consider
viral culture
Test
Virus culture will not produce timely results for clinical management and must be performed in a biosafety level 3-enhanced laboratory. Viral culture can be performed at World Health Organization (WHO) H5 reference laboratories and WHO collaborating influenza centers.
Viral culture is important for virologic surveillance, antigenic monitoring for vaccine strain selection, and assessment and analyses of viral characteristics such as genetic reassortment, receptor binding affinity, and antiviral susceptibility.
Result
positive for H5N1 virus
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