14th Meeting of #WHO #Expert Working Group of the Global #Influenza #Surveillance and Response System (GISRS) for Surveillance of #Antiviral Susceptibility (March 20 '26)
Weekly epidemiological record
20 MARCH 2026, 101th YEAR, No 12, 2026, 101, 53–56
Executive Summary
The WHO Expert Working Group on Surveillance of Influenza Antiviral Susceptibility (AVWG) supports the WHO GISRS by providing practical guidance for monitoring antiviral susceptibility of seasonal and emerging influenza viruses through global surveillance efforts.
The 14th WHO-AVWG meeting was held in virtual format on 10-12 June 2025.
Update on susceptibility of seasonal influenza viruses to approved antiviral agents
From approximately May 2024 to May 2025, five WHO Collaborating Centres (CCs) and two National Influenza Centres (NICs) reported co-circulation of influenza A(H1N1) pdm09, A(H3N2), and B/Victoria viruses.
A(H1N1)pdm09 dominated in Eastern Asia{1}. Elevated frequency of influenza neuraminidase (NA) inhibitor (NAI) reduced inhibition/ highly reduced inhibition (RI/HRI) was identified among A(H1N1)pdm09 viruses, largely conferred by the NA-H275Y substitution.
Reporting frequency was 3.8% in China, lower (≤1%) in other reporting regions, but still measurable and were in some cases a result of prior antiviral use or specific local outbreaks (e.g., a hospital in Iceland with a NA-H275Y+S247N cluster, a primary school classroom outbreak in Japan{2}. The NA-S247N substitution (≤3.3%) was also noted by three centres, but these viruses exhibited normal inhibition (NI) by NAIs when available isolates were tested.
Incidence of RI/HRI or NA-associated markers were less frequently reported for A(H3N2) and B/Victoria viruses than A(H1N1)pdm09 viruses.
Markers and incidence of reduced susceptibility to baloxavir was detected at low frequencies of 0.07 to 2.2%, where the latter value represented a small sample set of only 2 of 89 viruses in Japan.
Reduced susceptibility or amino acid markers indicative of reduced susceptibility were observed only in influenza A viruses and not influenza B.
Update on susceptibility of zoonotic and animal influenza viruses to approved antiviral agents
From approximately May 2024 to May 2025, global surveillance data from WHO CCs, NICs, and associated partners including WHO Essential Regulatory Laboratories and the OFFLU (WOAH/FAO Network of Expertise on Animal Influenza) network reported that most zoonotic and avian influenza viruses, particularly circulating A(H5N1/x) HA clade 2.3.4.4b and 2.3.2.1a/e viruses, were broadly susceptible to NAIs and baloxavir.
A(H5N1) 2.3.4.4b virus oseltamivir inhibitory concentrations remain elevated vs. seasonal N1 viruses.
Small and isolated incidence of NAI associated RI/HRI or markers included: NA-D199G mediated oseltamivir/zanamivir RI detected in A(H5N1) 2.3.4.4b poultry in the Russian Federation (February 2024, reported June 2025), NA-N295S in poultry in India A(H5N1) 2.3.2.1a isolates, and 8 poultry farms in British Columbia, Canada exhibiting A(H5N1) 2.3.4.4b with NA-H275Y.
Only two viruses with reduced baloxavir susceptibility were identified, 1 human virus with PA-I38M (California, USA) and 1 environmental virus isolate with PA-V100I (China, Hong Kong Special Administrative Region).
Beyond A(H5N1/x), nearly 30 avian influenza subtypes including A(H9N2), A(H7N2), A(H7N7), and A(H7N9), and A(H10N7) were analysed across surveillance sites in the Bangladesh, Egypt, the Netherlands and the United States of America (USA).
They generally lacked NA or PA genotypic markers of reduced drug susceptibility and when available for phenotypic testing, were susceptible to both NAIs and baloxavir.
A(H7N2) and A(H7N7) viruses from the Netherlands displayed oseltamivir RI compared to human seasonal references, but this may be due to foldchange comparison to a mismatched NA subtype.
Swine-origin variant viruses (A(H1N1)v, A(H1N2)v, A(H3N2)v) tested across the USA and Europe were largely free of genotypic or phenotypic indicators of reduced susceptibility/inhibition to NAIs or baloxavir.
Some viruses (the Netherlands) showed slightly higher NAI median inhibitory concentrations to historical or human seasonal baselines, but all remained below NAI RI thresholds.
Update of protocols and guidance for GISRS laboratories
Both genotypic and phenotypic assays may be used as tools to monitor susceptibility of influenza viruses to NAIs and baloxavir.
The WHO-AVWG routinely reviews and updates influenza NA and PA amino acid substitutions associated with reduced susceptibility to NAIs and baloxavir; updated tables for the previous reporting period were included on the WHO website{3–5}.
The US CDC continues to update and ship reference virus panels that can be used for NAI and baloxavir susceptibility testing, available via the International Reagent Resource{6}
Further guidance on baloxavir and other PA inhibitor testing included the Influenza Replication Inhibition Neuraminidase-based Assay (IRINA), published by the Centers for Disease Control and Prevention, USA{7} and included on the WHO website{8}.
The WHO AVWG continues to develop algorithms for NICs to aid in influenza response planning (zoonotic, pandemic, and antiviral resistance-specific events), guidance to aid in decisions making for testing strategies (genotypic vs. phenotypic), and guidance for consideration of baloxavir and PA inhibitor specific amino acid substitutions associated with reduced drug susceptibility{9}.
Additionally, the WHO-AVWG has worked with GISAID to continue to refine and implement modifications to existing tools to facilitate identification of NA and PA substitutions upon sequence submission.
Outbreak and pandemic preparedness with clinicians’ perspectives
Two physicians, Profs. Prof. David Hui and Bin Cao, were invited to present recently updated WHO guidance on clinical practice guidelines for influenza{10}.
Significant updates and discussion surrounded inclusion of baloxavir, which was conditionally recommended for non-severe disease high-risk patients and post-virus exposure prophylaxis (PEP) including influenza viruses associated with high mortality.
Conditional recommendation against any NAI or baloxavir intervention remains for non-severe disease low-risk patients or seasonal virus PEP.
Data was presented on multiple PA inhibitors rapidly moving through late-stage clinical trials in China which may have implications on expanded usage of this newer class of influenza drugs.
Review of External Quality Assessment Programme (EQAP) panels
EQAP was initiated in 2007 to monitor the quality of GISRS, NICs, other national influenza reference laboratories’ capacity for influenza diagnosis and detection.
An optional antiviral phenotypic NAI panel was introduced in 2013, and genotypic baloxavir susceptibility was introduced in 2020.
Results for the 2024 Global EQAP panel were reported during the 14th WHO-AVWG meeting.
Of the 194 participating laboratories, 26.3% participated in NAI susceptibility testing.
Results and subsequent discussion from this year’s panel were used by members of WHO-AVWG to assess the training needs of NICs.
Way forward
The 2020–2023 Annual Global Update on the Susceptibility of Influenza Viruses (Global AVS) manuscript was published{11} and drafting of a 2023–2025 publication is underway. The next WHO-AVWG meeting will be held in June 2026.
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{1} World Health Organization. Influenza Transmission Zones. 2026. https://cdn.who.int/media/docs/ default-source/influenza/influenzaupdates/2025_09_24_influenza-transmission-zones. pdf?sfvrsn=22361408_3&download=true.
{2} Takashita E, Shimizu K, Usuku S, Senda R, Okubo I, Morita H, et al. An outbreak of influenza A(H1N1) pdm09 antigenic variants exhibiting cross-resistance to oseltamivir and peramivir in an elementary school in Japan, September 2024. Euro Surveill. 2024;29(50).
{3} World Health Organization. Summary of neuraminidase (NA) amino acid substitutions assessed for their effects on inhibition by neuraminidase inhibitors (NAIs). 2025. https://cdn.who.int/media/docs/default-source/ influenza/laboratory---network/quality-assurance/human-nai-marker-table_ for-publication_final_20240918.pdf.
{4} World Health Organization. Summary of neuraminidase (NA) amino acid substitutions assessed for their effects on inhibition by NA inhibitors (NAIs) among avian influenza viruses of Group 1 (N1, N4, N5, N8 subtypes) and Group 2 (N2, N3, N6, N7, N9 subtypes) NAs. 2025. https://cdn.who.int/media/ docs/default-source/influenza/avwg/avian-nai-marker-whotable__10-10-2025.pdf?sfvrsn=bc0d1e9a_10
{5} World Health Organization. Summary of polymerase acidic protein (PA) amino acid substitutions assessed for their effects on PA inhibitor (PAI) baloxavir susceptibility. 2025. https://cdn.who.int/media/docs/default-source/influenza/ laboratory---network/quality-assurance/antiviral-susceptibility-influenza/ pa-marker-who-table_28-11-2025_updated.pdf?sfvrsn=5307d6fe_4.
{6} International Reagent Resource. 2026. https://www. internationalreagentresource.org/.
{7} Patel MC, Flanigan D, Feng C, Chesnokov A, Nguyen HT, Elal AA, et al. An optimized cell-based assay to assess influenza virus replication by measuring neuraminidase activity and its applications for virological surveillance. Antiviral Res. 2022;208:105457.
{8} World Health Organization. Baloxavir Susceptibility Assessment using Influenza Replication Inhibition Neuraminidase-based Assay (IRINA). https:// cdn.who.int/media/docs/default-source/influenza/avwg/cdc-phenotypic-lp492rev01d---baloxavir-susceptibility-assessment-using-irina.pdf?
{9} Patel MC, Nguyen HT, Mishin VP, Pascua PNQ, Champion C, Lopez-Esteva M, et al. Antiviral susceptibility monitoring: testing algorithm, methods, and f indings for influenza season, 2023-2024. Antiviral Res. 2025;244:106299.
{10} World Health Organization. Clinical practice guidelines for influenza 2024. https://www.who.int/publications/i/item/9789240097759.
{11} Hussain S, Meijer A, Govorkova EA, Dapat C, Gubareva LV, Barr I, et al. Global update on the susceptibilities of influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2020-2023. Antiviral Res. 2025:106217.
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