Investigations

1st investigations to order

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Described in majority of patients in case series.

Result

leukopenia or normal WBC; lymphopenia; thrombocytopenia

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Described in majority of patients in case series.

Result

elevated aspartate aminotransferase/alanine aminotransferase

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CXR alone cannot exclude or differentiate viral or bacterial pneumonia.

Lung infiltrates are commonly bilateral, diffuse (lower, middle, and upper zones can be affected), and show both central and peripheral distribution.[126]

Result

may be normal; may show infiltrates consistent with pneumonia in severe cases

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Indicated in patients with dyspnoea or suspected pneumonia.

Result

may show hypoxia

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Primary bacterial pneumonia and potential bacterial co-infection should be evaluated. Co-infections have been reported in Asian lineage A(H7N9) virus-infected patients, but mainly hospital-acquired bacterial infections and ventilator-associated pneumonia.

Result

visualisation of infecting organisms if bacterial pneumonia or potential bacterial co-infection

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Primary bacterial pneumonia and potential bacterial co-infection should be evaluated in severely ill patients.

Result

growth of infecting organism if bacterial pneumonia or potential bacterial co-infection

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This is the test of choice for diagnosis of Asian lineage A(H7N9)virus infection using H7-specific primers and probes to detect Asian lineage A(H7N9) viral RNA in respiratory clinical specimens.[127][128][129] Both real-time and conventional RT-PCR assays can be used to detect Asian lineage A(H7N9) virus RNA at national laboratories, highly specialised local public health laboratories, or some academic centre laboratories. RT-PCR for Asian lineage A(H7N9) virus is not available in most clinical settings. A(H7)-specific primers and probes should be updated regularly. RT-PCR for influenza A alone cannot differentiate between infection with seasonal influenza A and avian influenza A viruses, but failure to detect influenza A virus RNA reduces the likelihood of Asian lineage A(H7N9) virus infection. Concurrent assays for seasonal influenza A (H3N2 and H1N1pdm09) and influenza B viruses are recommended. All non-subtypable influenza A laboratory positive test results, particularly in clinically ill patients or those with risk factors for novel influenza virus infection, should undergo further testing with appropriate RT-PCR primers (or sequencing, if required) to identify the specific virus infection.

Testing of upper respiratory tract specimens (e.g., nasal swabs, throat swabs, nasopharyngeal swabs/aspirates), even with RT-PCR assays, may produce false-negative results due to differential virokinetics along the respiratory tract. In instances where Asian lineage A(H7N9) virus infection is strongly suspected, a lower respiratory tract sample (e.g., sputum, tracheal aspirate, bronchoalveolar lavage) should be considered if samples are available. Intubation, bronchoscopy, and thoracentesis should not be performed for the sole purpose of obtaining clinical specimens for A(H7N9) virus testing. Repeated testing is also advisable to minimise the effect of sampling error.

H7-positive results from national laboratories should be confirmed at World Health Organization (WHO) collaborating influenza centres. The WHO also accepts results of RT-PCR assays for novel influenza A viruses from some national influenza laboratories.[130]

It is important to note that commonly available rapid antigen tests are insensitive in detecting influenza virus infections, including A(H7N9) virus infections, and cannot specifically identify A(H7N9) virus.[131] Thus a negative rapid antigen test result cannot be used to rule out influenza virus infections. Commercially available molecular influenza assays available in clinics and hospitals have high sensitivity to detect influenza viruses, but cannot specifically identify A(H7N9) virus in respiratory tract specimens, or distinguish A(H7N9) virus from seasonal influenza A viruses.

Result

positive for H7-specific viral RNA

Investigations to consider

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Result
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Virus culture will not produce timely results for clinical management and must be performed in a biosafety level 3-enhanced (BSL 3+) laboratory. Viral culture can be performed at World Health Organization (WHO) avian influenza 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 reassortment, receptor binding affinity, and antiviral susceptibility.

Clinical specimens testing positive for A(H7N9) virus RNA by reverse transcription polymerase chain reaction may be cultured by a WHO avian influenza reference laboratory or WHO collaborating influenza centre laboratory.[130]

Result

positive for A(H7N9) virus

Emerging tests

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Result
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Serological testing to demonstrate Asian lineage A(H7N9) virus infection is not routinely available; due to the timelines involved, serological testing cannot inform clinical management and should not be considered for clinical diagnostic purposes.

It can be performed in only a few specialised laboratories, such as World Health Organization avian influenza reference laboratories. The microneutralisation assay is a highly sensitive and specific assay and specifically assesses the presence of specific, neutralising antibodies. The assay should be performed only in biosafety level 3 enhanced (BSL 3+) laboratories.[132]

Other serological assays include horse red blood cell haemagglutinin inhibition assay using live or betapropiolactone-inactivated A(H7N9) virus under appropriate biosafety conditions.[133]

Properly timed acute and convalescent sera can yield a retrospective diagnosis of Asian lineage A(H7N9) virus infection. A fourfold increase in A(H7N9) virus-specific antibody level after a 2- to 4-week period from the initial blood draw is diagnostic of A(H7N9) virus infection in a patient with clinically compatible illness.

Serological tests using standard influenza haemagglutination inhibition assays are non-specific for A(H7N9) virus and are not recommended.

Result

fourfold increase in A(H7N9) virus-specific antibody in convalescent serum when compared with acute serum

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