Testing and diagnosis of avian influenza

ECDC jointly with EFSA, the European Agency for Safety and Health at Work (EU-OSHA) and the EURL published a document that provides guidance on ‘Testing and detection of zoonotic influenza virus infections in humans in the EU/EEA, and occupational safety and health measures for those exposed at work’. The document describes the different exposed groups at risk and raises awareness about the possibility of atypical presentations in humans similar to what has been recently observed in other mammals with severe infection of the brain, i.e. encephalitis or meningoencephalitis. 

People in the EU presenting with severe acute respiratory infections (SARI) or influenza-like infections (ILI) and a history of exposure to dead or sick poultry, wild birds or other mammals likely infected with A(H5N1) avian influenza viruses will require careful investigation, management and infection control. Neurological symptoms have also been observed in mammals infected with avian influenza viruses. If transmission to humans occur, other non-respiratory symptoms might possibly also occur.

Clinicians should consider testing severely ill patients for influenza, who present with respiratory and also other symptoms (e.g. neurological). Appropriate samples for influenza tests should be rapidly taken and processed from patients with relevant exposure history within 10–14 days preceding the symptom onset. If positive specimens cannot be subtyped, they should be shared with the national reference laboratory of the respective country (National Influenza Centres – NICs).  

With routine diagnostic laboratory assays for seasonal influenza viruses, human infection with A(H5Nx) viruses should be positive for influenza A virus, and negative for influenza B, A(H1), A(H1)pdm09 and A(H3) viruses. Such non-seasonal influenza type A virus isolates, or clinical samples that cannot be subtyped, should be sent to the respective NIC. If they are confirmed positive for H5 virus, the samples should be sent further along to a WHO Collaborating Centre for Reference and Research on Influenza (WHO-CCRRI).

The confirmation of a productive avian influenza infection in a person (symptomatic or asymptomatic) with a positive PCR should include repeated testing to exclude a false-positive signal. True positives should be subjected to subsequent virus sequencing to produce full-length genomes for further analysis and virus cultivation. Specimens should be shared with reference laboratories and WHO-CCRRIs for virus characterisation as outlined in the ECDC guidance document ‘Testing and detection of zoonotic influenza virus infections in humans in the EU/EEA, and occupationally safety and health measures for those exposed at work’.

Serological investigations are also needed to identify seroconversion for case ascertainment. However, for some virus positivity findings, it might be challenging to confirm or rule out a true infection. More work needs to be performed globally to develop criteria on how to categorise such inconclusive results.

Reference viruses and sera against reference viruses need to be developed, constantly updated, and provided to countries to investigate transmission events and confirm infections serologically. This is also needed to support risk assessments and conduct larger studies in population groups (such as poultry workers, cullers, slaughterhouse workers) at high risk of exposure to avian influenza viruses or to potentially infected birds.