Investigations
1st investigations to order
FBC 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 dyspnoea or suspected pneumonia.
Result
may show hypoxia
sputum Gram stain
Test
Primary bacterial pneumonia and potential bacterial co-infection should be evaluated. Few co-infections have been reported in highly pathogenic avian influenza (HPAI) A(H5N1) patients, except with ventilator-associated pneumonia.
Result
visualisation of infecting organisms if bacterial pneumonia or potential bacterial co-infection
sputum and blood bacterial culture
Test
Primary bacterial pneumonia and potential bacterial co-infection should be evaluated.
Result
growth of infecting organism if bacterial pneumonia or potential bacterial co-infection
real-time reverse transcription polymerase chain reaction (rtRT-PCR)
Test
Recommended for diagnosis of highly pathogenic avian influenza (HPAI) A(H5N1) virus infection.[122][123] If influenza A is positive, then subtyping should be performed for seasonal influenza A(H1) and A(H3) viruses. If influenza A testing is positive but A(H1) and A(H3) are negative, then testing for A(H5) should be performed at a specialised public health laboratory.[124]
Perform testing on people who meet epidemiological criteria and either clinical or public health response criteria.[119]
Testing of asymptomatic people is not routinely recommended, but may be considered 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).[41]
Infection prevention and control precautions are recommended when collecting specimens. Preferred specimens in non-intubated patients are upper respiratory tract specimens (e.g., oropharyngeal swab, nasopharyngeal swab, nasal aspirate or wash). Two swabs may be combined into one vial (e.g., one nasal or nasopharyngeal swab and one oropharyngeal swab). Ideally both a nasopharyngeal swab, and a combined nasal swab and oropharyngeal swab should be collected and tested separately.[122][126]
Preferred specimens in intubated patients or patients with severe lower respiratory tract illness are lower respiratory tract specimens (e.g., endotracheal aspirate, bronchoalveolar lavage fluid). Multiple respiratory specimens should be collected from different sites on at least two consecutive days for hospitalised patients.[122][126]
A conjunctival swab (with a nasopharyngeal swab) and/or nasal swab combined with an oropharyngeal swab should be collected if the person has conjunctivitis (with or without respiratory symptoms).[41][122]
Swabs with a synthetic tip (e.g., Dacron®, polyester) and an aluminum or plastic shaft should be used. Obtain specimens as soon as possible, ideally within 7 days of symptom onset.[122][126]
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 hospitalised 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.[121]
Result
positive for H5-specific viral RNA
Investigations 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 WHO H5 reference laboratories and WHO collaborating influenza centres.
Viral culture is important for virological surveillance, antigenic monitoring for vaccine strain selection, and assessment and analyses of viral characteristics such as genetic re-assortment, receptor binding affinity, and antiviral susceptibility.
Clinical specimens testing positive for highly pathogenic avian influenza (HPAI) A(H5N1) viral RNA by RT-PCR should be cultured by a WHO H5 Reference Laboratory or WHO collaborating influenza centre laboratory.[126]
Result
positive for H5N1 virus
Use of this content is subject to our disclaimer