Investigations

1st investigations to order

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Described in most patients in small case series.

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leukopenia, lymphopenia, thrombocytopenia

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Described in most patients in small case series.

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elevated AST/ALT

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A chest x-ray alone cannot exclude viral or bacterial pneumonia.

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

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Indicated in patients with dyspnoea or suspected pneumonia.

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may show hypoxia

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Primary bacterial pneumonia and potential bacterial co-infection should be evaluated. Few co-infections have been reported in highly pathogenic avian influenza (HPAI) H5N1 patients, except with ventilator-associated pneumonia.

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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.

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

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Recommended clinical test for diagnosis of highly pathogenic avian influenza (HPAI) H5N1 virus infection using H5-specific primers and probes to detect HPAI H5N1 viral RNA in respiratory clinical specimens.[79][80] Both real-time and conventional RT-PCR assays can be used to detect HPAI H5N1 viral RNA at national laboratories, highly specialised local public health laboratories, or some academic centre laboratories. RT-PCR for HPAI H5N1 virus is not available in most clinical settings. H5-specific primers and probes should be updated regularly. RT-PCR for influenza A and B viruses can confirm a diagnosis of seasonal influenza.

H5-positive results from national laboratories should be confirmed at WHO H5 reference laboratories or World Health Organization (WHO) collaborating influenza centres. The WHO also accepts results of RT-PCR assays from some national influenza laboratories.[81][82]

Result

positive for H5-specific viral RNA

Investigations to consider

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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 reassortment, receptor binding affinity, and antiviral susceptibility.

Clinical specimens testing positive for highly pathogenic avian influenza (HPAI) H5N1 viral RNA by RT-PCR should be cultured by a WHO H5 Reference Laboratory or WHO collaborating influenza centre laboratory.

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positive for H5N1 virus

Emerging tests

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Serological testing for highly pathogenic avian influenza (HPAI) H5N1 virus antibodies is not routinely available, 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 WHO H5 reference laboratories, using live HPAI H5N1 virus in a microneutralisation assay under biosafety level 3-enhanced conditions.

Other serological assays include horse red blood cell haemagglutinin inhibition assay or assessment of HPAI H5N1-specific T-cell responses.[83] Properly timed acute and convalescent sera can yield a retrospective diagnosis of HPAI H5N1 virus infection. A fourfold increase in H5N1-specific antibody level after a 2- to 4-week period from the initial blood draw is diagnostic of HPAI H5N1 virus infection in a patient with clinically compatible illness.

Serological tests using standard influenza haemagglutination inhibition assays are non-specific for HPAI H5N1 virus and are not recommended.

Result

fourfold increase in H5N1-specific antibody

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