#USA, Weekly #US #Influenza #Surveillance #Report: Key Updates for Week 13, ending April 4, 2026 (#CDC, summary)

 

(...)

Key Points

-- Seasonal influenza activity continues to decrease in most areas of the country. 

- Influenza A activity is low across all HHS regions while the amount of and trends in influenza B activity vary by region.

-- Influenza A(H3N2) viruses are the most frequently reported influenza viruses overall this season.

-- Among 2,166 influenza A(H3N2) viruses collected since September 28, 2025, that underwent additional genetic characterization at CDC, 92.8% belonged to subclade K.

-- The cumulative influenza-associated hospitalization rate overall in FluSurv-NET is the third highest since the 2010-2011 season. 

- Children younger than 18 years have the second highest cumulative hospitalization rate for that age group since the 2010-2011 season.

-- Twelve influenza-associated pediatric deaths occurring during the 2025-2026 season were reported to CDC this week, bringing the season total to 139 reported influenza-associated pediatric deaths.

-- Among children who were eligible for influenza vaccination and with known vaccination status, approximately 85% of reported pediatric deaths this season have occurred in children who were not fully vaccinated against influenza.

-- CDC's in-season severity assessment framework classified the season as moderate across all ages. 

- CDC also assesses severity by three age groups: pediatric (0-17 years), adult (18-64 years), and older adults (≥65 years). 

- At this point in the season, the pediatric age group is classified as having high severity, while both the adult and older adult age groups are classified as having moderate severity. 

- These assessments are conducted each week during the season, and the season's severity assessment can change if activity should increase again.

-- CDC estimates that there have been at least 31 million illnesses, 370,000 hospitalizations, and 23,000 deaths from flu so far this season.

-- Influenza (flu) vaccination has been shown to reduce the risk of flu and its potentially serious complications. 

- There is still time to get vaccinated against flu this season. 

- Approximately 135 million doses of influenza vaccine have been distributed in the United States this season.

-- There are prescription flu antiviral drugs that can treat flu illness; those should be started as early as possible and are especially important for patients at higher risk for flu-related complications.1

-- Influenza viruses are among several viruses contributing to respiratory disease activity. CDC provides updated, integrated information about COVID-19, flu, and respiratory syncytial virus (RSV) activity on a weekly basis.

-- No new avian influenza A(H5) infections were reported to CDC this week. To date, person-to-person transmission of influenza A(H5) viruses has not been identified in the United States.

(...)

Source: 

Link: https://www.cdc.gov/fluview/surveillance/2026-week-13.html

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#Oseltamivir aziridines are potent #influenza #neuraminidase #inhibitors and imaging agents

 

Significance

Influenza remains a major global health threat. We introduce oseltamivir-based aziridines that unite transition-state mimicry for tight binding with aziridine-enabled covalent capture of the catalytic tyrosine. This dual function yields potent, mechanism-based neuraminidase inhibition and enables activity-based quantification of active enzyme directly in complex samples. Across N1, N2, and influenza B enzymes, selected compounds show high potency against diverse viral neuraminidases and in live virus replication assays. By combining a clinically grounded scaffold with a reactivity handle, these molecules bridge therapeutic and diagnostic needs and offer a practical platform for neuraminidase imaging and antiviral development.

Abstract

Influenza neuraminidase (NA) is a critical target for seasonal and pandemic antivirals, including the strains of current concern. Current treatments, such as Zanamivir and Oseltamivir, are limited by noncovalent binding and emerging resistance. We hypothesized that Oseltamivir aziridines would unite transition-state mimicry for tight binding, with aziridine-enabled covalent capture of the catalytic tyrosine, thereby supporting both therapy and activity-based quantification. Here, we present oseltamivir-based aziridines, inspired by cyclophellitol chemistry, that act as covalent inhibitors and activity-based probes via an N-acylaziridine warhead. Free-energy calculations, and NMR observations, indicate a 4H5 half-chair preference consistent with the NA transition state, and selected analogues inhibit multiple NA subtypes with low nanomolar binding constants. Diverse evidence establishes covalency: time-dependent inactivation, inhibitor washout, intact-mass shifts, MS/MS identification of a tyrosine adduct, and QM/MM reaction profiles, while cryoEM of N1 aligns with the proposed binding mode, revealing an elimination product. The inhibitors demonstrate formidable activity against diverse viral neuraminidases, including H5N1, and further enable imaging and quantification of active NA. With their dual therapeutic and diagnostic potential, these first-in-class inhibitors indeed benefit from transition state mimicry and covalency, and thus offer a powerful platform for antiviral development and neuraminidase imaging, addressing urgent global health needs in influenza treatment and prevention.

Source: 

Link: https://www.pnas.org/doi/10.1073/pnas.2504045123

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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

http://www.who.int/wer 

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.

___

{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.

___

Source: 

Link: https://iris.who.int/server/api/core/bitstreams/1ea408da-cd90-438b-b80c-b00aaf4e7315/content

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Interim Estimates of 2025–26 Seasonal #Influenza #Vaccine #Effectiveness — #USA, September 2025–February 2026 (CDC MMWR)

 

Abstract

In the United States, annual influenza vaccination has been recommended for all persons aged ≥6 months, including during the 2025–26 season. Interim influenza vaccine effectiveness (VE) estimates were calculated for patients with acute respiratory illness–associated outpatient visits and hospitalizations from three U.S. respiratory virus VE networks during the 2025–26 influenza season, using a test-negative case-control design. Among children and adolescents aged <18 years, VE was 38%–41% against influenza outpatient visits and 41% against influenza-associated hospitalization. Among adults aged ≥18 years, VE was 22%–34% against influenza outpatient visits and 30% against influenza-associated hospitalization. Among children and adolescents, VE against influenza A ranged from 37% (against outpatient visits) to 42% (against hospitalization) across settings; among adults, VE against influenza A ranged from 30% (against hospitalization) to 34% (against outpatient visits) across settings. Among children and adolescents, VE against influenza A(H3N2)–associated outpatient visits was 35% and against influenza A(H3N2)–associated hospitalization was 38%. VE against influenza B outpatient visits ranged from 45%–71% among children and adolescents and was 63% among adults. Other estimates of VE were not statistically significant or were not reportable. Although interim influenza VE is lower during the 2025–26 influenza season than it was during recent influenza seasons, these findings demonstrate that influenza vaccination still provides protection against influenza. CDC recommends influenza vaccination; U.S. influenza vaccines remain available for persons aged ≥6 months.

Source: 

Link: http://dx.doi.org/10.15585/mmwr.mm7509a2

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Recommended #composition of #influenza virus #vaccines for use in the 2026 – 2027 northern hemisphere influenza season (#WHO, Feb. 27 '26)

 

February 2026 

WHO convenes technical consultations {1} in February and September each year to recommend viruses for inclusion in influenza vaccines {2} for the northern hemisphere (NH) and southern hemisphere (SH) influenza seasons, respectively. 

This recommendation relates to the influenza vaccines for use in the NH 2026-2027 influenza season. 

A recommendation will be made in September 2026 relating to vaccines that will be used for the SH 2027 influenza season. 

WHO guidance for choosing between the NH and SH formulations for countries in tropical and subtropical regions is available on the WHO Global Influenza Programme website {3}.  

National or regional authorities approve the composition and formulation of influenza vaccines used in each country. 

National public health authorities are responsible for making recommendations regarding the use of the vaccine. 

WHO has published recommendations on the prevention of influenza {4}.  

Seasonal influenza activity 

From September 2025 through January 2026, influenza activity was reported in all transmission zones. 

Overall influenza virus detections were higher compared to the same reporting period in 2024-2025 but peaked in December 2025 for this recent period compared to February 2025 for the previous period. 

During this reporting period, influenza A viruses predominated, although the proportion of virus detections varied among transmission zones. 

In Africa, influenza activity increased during the start of the reporting period, with a predominance of influenza A viruses in all transmission zones. 

In Eastern, Northern, and Western Africa, among subtyped influenza A viruses, A(H1N1)pdm09 viruses accounted for the majority of detections early in the reporting period while A(H3N2) viruses predominated later in the reporting period. 

Influenza detections peaked in November in Western Africa and December in Eastern and Northern Africa. 

In Middle Africa, influenza detections remained low throughout the reporting period with a slight predominance of A(H1N1)pdm09 viruses early in the reporting period. 

In Southern Africa, influenza detections remained low throughout the reporting period, with a predominance of influenza A viruses. 

In Northern and Middle Africa, there was low and sustained influenza B activity throughout the reporting period. 

In Asia, influenza activity increased during the start of the reporting period in South East and Western Asia, from October in Central and Eastern Asia, and from November in Southern Asia, with a predominance of influenza A viruses in all transmission zones. 

Most influenza detections were reported from Eastern Asia, where activity peaked in early December. 

In Southern Asia, influenza activity also peaked in December; in Central Asia influenza activity peaked in November, and in Western and South East Asia, influenza activity peaked in October. 

Among subtyped influenza A viruses, A(H3N2) viruses accounted for the majority of detections in all transmission zones; detections of A(H1N1)pdm09 and influenza B viruses remained low in most transmission zones throughout the reporting period, except in Eastern Asia where there was a substantial rise in influenza B viruses in recent weeks. 

In Europe, influenza activity increased from mid-September in Northern Europe, from October in South West Europe and from mid-November in Eastern Europe, with a predominance of influenza A viruses in all transmission zones. 

Influenza detections peaked in December in Northern and South West Europe but remained elevated through January. 

Influenza detections continued to increase through January in Eastern Europe. 

Among subtyped influenza A viruses, A(H3N2) viruses predominated. 

In South West Europe, detections of A(H1N1)pdm09 viruses slightly increased in mid-November. 

In Eastern and Northern Europe, detections of A(H1N1)pdm09 and influenza B viruses remained low throughout the reporting period.  

In the Americas, influenza activity increased from the start of the reporting period in Temperate and Tropical South America and from November in North America and Central America Caribbean. 

Influenza A viruses accounted for most detections, and influenza B virus detections remained low throughout the reporting period in all transmission zones, except in North America where there was a substantial rise in influenza B viruses in recent weeks. 

In North America, activity peaked in late December. 

Among subtyped influenza A viruses, there was a predominance of A(H3N2) viruses. 

In Central America Caribbean, influenza activity remained elevated through mid-January with A(H3N2) virus detections predominant from December. 

In Tropical South America, influenza activity peaked in early November and slowly declined until the end of the reporting period. 

Among subtyped influenza A viruses, A(H3N2) predominated through November then co-circulated at similar proportions to A(H1N1)pdm09 until the end of the reporting period. 

In Temperate South America, influenza activity peaked in mid-November and among subtyped influenza A viruses, A(H3N2) viruses predominated throughout the reporting period.  

In Oceania, influenza activity decreased until mid-October, increased in December and decreased since mid-December. A(H1N1)pdm09 and B viruses were detected at similar levels until mid-September and A(H3N2) virus detections predominated since then. 

Influenza A 

Globally, influenza A virus detections greatly outnumbered those of influenza B. 

Among subtyped influenza A viruses, A(H3N2) viruses predominated throughout the reporting period in most transmission zones. 

In Eastern, Northern, Western Africa, Central America Caribbean and Oceania, influenza A(H1N1)pdm09 virus detections predominated during the first part of the reporting period, and A(H3N2) virus detections predominated in the latter part of the reporting period. 

Influenza A(H1N1)pdm09 virus detections increased slightly towards the latter part of the reporting period in Eastern and South West Europe, Central America Caribbean and Tropical South America. 

The overall number of influenza detections was low in Middle and Southern Africa. 

Influenza B 

Globally, influenza B virus detections remained low throughout the reporting period. 

Increases in influenza B virus detections in January were reported in North America and Eastern Asia. 

All influenza B viruses where lineage was confirmed belonged to the B/Victoria lineage. 

(...)

Zoonotic influenza  

From 23 September 2025, sporadic zoonotic influenza infections were reported, in most cases, following exposure to infected birds, swine or contaminated environments. 

Single cases of A(H5N1) from Bangladesh, A(H5N2) from Mexico, and A(H5N5) from the United States of America were reported. 

Three A(H5N1) cases were reported from Cambodia. 

Fourteen cases of A(H9N2) and one case of A(H10N3) were reported from China. 

Single cases of A(H1N1)v and A(H1N2)v were reported from China, a case of A(H1N2)v from the United States of America, and a case of A(H3N2)v from Brazil. 

Genetic and antigenic characteristics of recent seasonal influenza viruses, human serology and antiviral susceptibility 

Influenza A(H1N1)pdm09 viruses  

Since September 2025, A(H1N1)pdm09 viruses circulated globally, but did not predominate in any region. 

The haemagglutinin (HA) genes of viruses that were genetically characterized belonged to the 5a.2a and 5a.2a.1 clades. 

Viruses from clade 5a.2a subclades C.1, C.1.9 and C.1.9.3 circulated in low numbers, with the largest proportion of detections in Africa {5}. 

Since September 2025, clade 5a.2a.1 subclades D.3.1 and D.3.1.1 viruses circulated globally. 

The D.3.1 subclade with substitutions T120A, I372V, I460T and V520A predominated in Western Pacific, Africa, South East Asia and several countries in the Americas. 

D.3.1.1 viruses characterized by R113K and more recently acquired substitutions A139D, E283K and K302E predominated in some countries in Europe, the Middle East and North America. 

The antigenic properties of A(H1N1)pdm09 viruses were assessed in haemagglutination inhibition (HI) assays with post-infection ferret antisera. 

HI results for viruses with collection dates since September 2025 showed that ferret antisera raised against cell culture-propagated A/Wisconsin/67/2022-like and eggpropagated A/Victoria/4897/2022-like viruses from the 5a.2a.1 clade recognized viruses in both 5a.2a and 5a.2a.1 clades well. 

However, post-infection ferret antisera raised against viruses from clade 5a.2a showed some reduction in recognition of the now predominating D.3.1 and D.3.1.1 subclade viruses. 

Post-infection ferret antisera raised against viruses from subclade D.3.1 (e.g., A/Missouri/11/2025) recognized recently circulating viruses from both 5a.2a and 5a.2a.1 clades well.  

Human serology studies used 15 serum panels from children, adults (18 to 64 years) and older adults (≥65 years) who had received egg-propagated inactivated (standard, high dose or adjuvanted), cell culture-propagated inactivated or recombinant trivalent or quadrivalent vaccines with NH 2025-2026 influenza vaccine formulations. 

-- NH 2025-2026 egg-based vaccines contained A/Victoria/4897/2022 (H1N1)pdm09like, 

-- A/Croatia/10136RV/2023 (H3N2)-like, 

-- B/Austria/1359417/2021-like (B/Victoria lineage) and, in quadrivalent vaccines, 

-- B/Phuket/3073/2013-like (B/Yamagata lineage) virus antigens. 

Cell culture-propagated and recombinant vaccines contained A/Wisconsin/67/2022 (H1N1)pdm09-like, A/District of Columbia/27/2023 (H3N2)-like and B/Austria/1359417/2021-like (B/Victoria lineage) virus antigens. 

Recent A(H1N1)pdm09 viruses with HA genes from clades 5a.2a (subclade C.1.9.3) and 5a.2a.1 (subclades D.3.1 and D.3.1.1) were analysed in HI assays using these human serum panels. 

When compared to the responses to cell culture-propagated A/Wisconsin/67/2022 (H1N1)pdm09-like vaccine reference viruses, post-vaccination geometric mean titres (GMTs) were significantly reduced for some recently circulating viruses from D.3.1 and D.3.1.1 subclades. 

Of 1 161 A(H1N1)pdm09 virus clinical samples and isolates examined by genetic and/or phenotypic analyses, 15 viruses showed evidence of reduced susceptibility to neuraminidase inhibitors (NAIs): seven had an H275Y neuraminidase (NA) substitution and eight had I223V and S247N substitutions. 

Of 1 331 A(H1N1)pdm09 viruses examined by genetic and/or phenotypic analyses, no viruses showed evidence of reduced susceptibility to the endonuclease inhibitor baloxavir marboxil. 

Influenza A(H3N2) viruses  

Phylogenetic analysis of the HA gene sequences of A(H3N2) viruses collected since September 2025 showed that the vast majority of viruses belonged to one of the J.2 subclades {6}, expressing HA N122D and K276E substitutions. 

HA genes have diversified with many subclades; J.2.2 (characterized by S124N), J.2.3 (characterized by N158K, K189R and S378N), J.2.4 (characterized by T135K [a potential loss of an N-glycosylation site] and K189R), and K (formerly designated as J.2.4.1; characterized by K2N, S144N [a potential addition of an N-glycosylation site], N158D, I160K, Q173R, T328A and S378N). 

During this reporting period, subclade K viruses were detected in all regions and predominated in many countries. 

There was still circulation of other J.2 subclades, notably J.2 or J.2.3 in South America, J.2.2 or J.2.4 in Africa and Asia.  

Post-infection ferret antisera raised against cell culture-propagated A/District of Columbia/27/2023-like and egg-propagated A/Croatia/10136RV/2023-like (clade 2a.3a.1, subclade J.2) viruses, representing the A(H3N2) component for the NH 2025-2026 influenza vaccines, showed poor recognition with recently circulating subclade J.2.3 (e.g., A/Netherlands/10685/2024), J.2.4 (e.g., A/Sydney/1359/2024) and K (e.g., A/Darwin/1415/2025) viruses. 

Ferret antisera raised against reference viruses from J.2.3 subclades showed good recognition of viruses expressing HA from J.2.3, but poor recognition of other subclades.  

Post-infection ferret antisera raised against cell culture-propagated A/Sydney/1359/2024-like and eggpropagated A/Singapore/GP20238/2024-like J.2.4 viruses, representing SH 2026 influenza vaccines, recognized most J.2.4 viruses and many subclade K viruses well. 

However, subclade K viruses and J.2.4 viruses with HA substitutions F79V, S144N (addition of a potential N-glycosylation site), N158D, I160K, T328A were better recognized by post-infection ferret antisera raised against cell culture-propagated A/Darwin/1415/2025-like and egg-propagated A/Darwin/1454/2025-like (subclade K) viruses. 

Human serology studies were conducted using the serum panels as described above by HI and virus neutralization (VN) assays with recent circulating A(H3N2) viruses with HA genes from subclades J.2, J.2.2, J.2.3, J.2.4, J.2.5 and K. 

When compared to titres against cell-propagated A/District of Columbia/27/2023-like vaccine reference viruses, post-vaccination HI GMTs or VN GMTs against many of the recent viruses in all subclades tested were significantly reduced in many serum panels.  

(...)

Of 4 458 influenza A(H3N2) viruses examined by genetic and/or phenotypic analyses, two viruses showed evidence of reduced susceptibility to NAIs; both had an NA E119V substitution. 

Of 4 828 A(H3N2) viruses examined by genetic and/or phenotypic analyses, nine viruses showed evidence of reduced susceptibility to the endonuclease inhibitor baloxavir marboxil: three had a PA I38T substitution, three had a PA I38I/T substitution, two had a PA I38I/M substitution and one had a PA E199E/G substitution.  

Influenza B viruses  

Since September 2025, influenza B viruses were detected in all WHO regions, and all those characterized belonged to the B/Victoria lineage. 

There have been no confirmed detections of circulating B/Yamagata lineage viruses after March 2020.  

All HA genes of B/Victoria lineage viruses characterized during this reporting period belonged to clade 3a.2 with HA substitutions A127T, P144L, and K203R. 

Viruses with clade 3a.2 HA genes have diversified further, forming several subclades (C.1-C.5)7. 

Viruses designated as C.5, C.5.1, C.5.6, C.5.6.1 and C.5.7, all of which had the HA substitution D197E, circulated at varying proportions in different regions. 

Viruses designated as C.3 have HA substitutions E128K, A154E and S208P. 

Subclade C.3.1 viruses shared additional mutations D197N (addition of a potential N-glycosylation site) and P208S. 

Recent C.3 viruses which had additional changes D197N (addition of a potential N-glycosylation site), S255P and I267V and C.3.1 viruses have been detected in increasing proportions in Eastern Asia and North America in recent weeks. 

Antigenic analysis showed that post-infection ferret antisera raised against B/Austria/1359417/2021-like viruses (3a.2), representing the vaccine viruses for the SH 2026 and NH 2025-2026 influenza seasons, recognized viruses within the C.5.1, C.5.6, C.5.6.1 and C.5.7 subclades well. 

C.3 and C.3.1 subclade viruses with the HA substitution D197N were recognized poorly. 

Post-infection ferret antisera raised against cell culture-propagated viruses from subclade C.3.1 (e.g., B/Pennsylvania/14/2025) recognized recently circulating viruses from C.3, C.3.1 and other 3a.2 subclades well. 

All available egg isolates for subclade C.3 and C.3.1 viruses acquired substitutions that remove the potential N-glycosylation site at HA 197 to 199. 

Post-infection ferret antisera raised against egg-propagated viruses from subclade C.3.1 (e.g., B/Tokyo/EIS13-175/2025, B/Tokyo/EIS13-011/2025, B/Perth/115/2025) showed reduced recognition of recently circulating viruses from C.3 and C.3.1 subclades compared to that of the cell equivalent.  

(...)

In human serology studies, recently circulating B/Victoria lineage viruses with HA genes from clade 3a.2 subclades C.3, C.3.1, C.5.1, C.5.6, C.5.6.1 and C.5.7 were tested using the serum panels described above. 

When compared to titres against egg- or cell culture-propagated B/Austria/1359417/2021-like vaccine reference virus, titres against most viruses with HA genes from C.5.1, C.5.6, C.5.6.1 and C.5.7 subclades were not significantly reduced; however, titres against viruses with HA genes from C.3 and C.3.1 were significantly reduced in most serum panels. Serology studies were not performed for B/Yamagata lineage viruses.  

Of 549 influenza B/Victoria lineage viruses examined by genetic and/or phenotypic analyses, two showed evidence of reduced or highly reduced susceptibility to NAIs, both with an NA M464T substitution. 

Of 760 B/Victoria lineage viruses examined by genetic and/or phenotypic analyses, no viruses showed evidence of reduced susceptibility to the endonuclease inhibitor baloxavir marboxil.  

Recommended composition of influenza virus vaccines for use in the 2026-2027 northern hemisphere influenza season  

Since September 2025, A(H1N1)pdm09 viruses circulated globally. The majority of viruses had HA genes belonging to the 5a.2a.1 clade which has further diversified into the D.3.1 and D.3.1.1 subclades. 

Postinfection ferret antisera raised against the northern hemisphere (NH) 2025-2026 A(H1N1)pdm09 vaccine viruses (cell culture-propagated A/Wisconsin/67/2022 and egg-propagated A/Victoria/4897/2022) and the southern hemisphere (SH) 2026 A(H1N1)pdm09 vaccine viruses A/Missouri/11/2025 recognized D.3.1 and D.3.1.1 viruses well. 

In human serology studies, post-vaccination geometric mean titres (GMTs) were significantly reduced for some recently circulating A(H1N1)pdm09 viruses when compared to the responses to cell culture-propagated A/Wisconsin/67/2022 A(H1N1)pdm09-like vaccine reference viruses. 

Since September 2025, A(H3N2) viruses circulated and predominated globally. 

The vast majority of A(H3N2) viruses collected had HA genes from subclades of J.2 and have continued to diversify with subclade K (previously designated as J.2.4.1) viruses predominating in most regions. 

Post-infection ferret antisera raised against NH 2025-2026 influenza season vaccine viruses (cell culture-propagated A/District of Columbia/27/2023 and egg-propagated A/Croatia/10136RV/2023) recognized some J.2 viruses well but showed poor recognition of viruses from subclades J.2.3, J.2.4 and K. 

Post-infection ferret antisera raised against subclade K viruses (cell culture-propagated A/Darwin/1415/2025 and egg-propagated A/Darwin/1454/2025) showed improved recognition of K viruses compared to post-infection antisera raised against NH 2025-2026 and SH 2026 A(H3N2) vaccine viruses. 

When compared to titres against cell culture-propagated A/District of Columbia/27/2023-like vaccine reference viruses, human post-vaccination haemagglutinin inhibition (HI) GMTs or virus neutralisation (VN) GMTs against many of the recent viruses in J.2.3, J.2.4 and K subclades were significantly reduced. 

Since September 2025, influenza B virus detections remained low globally, although some countries had increased detections in recent weeks. All circulating influenza B viruses characterized belonged to the B/Victoria lineage, and had HA genes belonging to clade 3a.2 with substitutions A127T, P144L and K203R. 

Post-infection ferret antisera raised against B/Austria/1359417/2021-like viruses (3a.2), representing the vaccine viruses for the SH 2026 and NH 2025-2026 influenza seasons, recognized viruses within the C.5.1, C.5.6, C.5.6.1 and C.5.7 subclades well. C.3 and C.3.1 subclade viruses with HA substitution D197N were recognized poorly. 

Post-infection ferret antisera raised against cell culture-propagated viruses from subclade C.3.1 (e.g., B/Pennsylvania/14/2025) recognized recently circulating viruses from C.3, C.3.1 and other 3a.2 subclades well. All available egg isolates for subclade C.3 and C.3.1 viruses (e.g., B/Tokyo/EIS13-175/2025) acquired egg-adaptive mutations that remove the potential N-glycosylation site at HA 197 to 199, leading to post-infection ferret antisera raised against egg-propagated viruses from subclade C.3.1 (e.g., B/Tokyo/EIS13-175/2025) showing reduced recognition of recently circulating viruses from C.3 and C.3.1 subclades compared to that of the cell equivalent. 

Human serology assays showed that post-vaccination titres against most recent B/Victoria lineage viruses with HA genes from subclades C.5.1, C.5.6, C.5.6.1 and C.5.7 were not significantly reduced when compared to titres against egg- or cell culturepropagated B/Austria/1359417/2021-like vaccine reference viruses. Titres against viruses with HA genes from subclade C.3 and C.3.1 were significantly reduced in most serum panels.  

For vaccines for use in the 2026-2027 northern hemisphere influenza season, WHO recommends the following:  

Egg-based vaccines  

• an A/Missouri/11/2025 (H1N1)pdm09-like virus;  

• an A/Darwin/1454/2025 (H3N2)-like virus; and  

• a B/Tokyo/EIS13-175/2025 (B/Victoria lineage)-like virus.  

Cell culture-, recombinant protein- or nucleic acid-based vaccines  

• an A/Missouri/11/2025 (H1N1)pdm09-like virus;  

• an A/Darwin/1415/2025 (H3N2)-like virus; and  

• a B/Pennsylvania/14/2025 (B/Victoria lineage)-like virus.  

Lists of prototype viruses for egg-, cell culture-, recombinant protein- and nucleic acid-based vaccines together with candidate vaccine viruses (CVVs) suitable for the development and production of human influenza vaccines are available on the WHO website {8}. 

A list of reagents for vaccine standardization, including those for this recommendation, can also be found on the WHO website.  

CVVs and reagents for use in the laboratory standardization of inactivated vaccines may be obtained from:  

• Therapeutic Goods Administration, P.O. Box 100, Woden, ACT, 2606, Australia (email: influenza.reagents@health.gov.au; website: http://www.tga.gov.au).  

• Medicines and Healthcare products Regulatory Agency (MHRA), Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, the United Kingdom of Great Britain and Northern Ireland  • (email: enquiries@mhra.gov.uk; website: http://www.nibsc.org/science_and_research/virology/influenza_resource_.aspx). 

• Division of Biological Standards and Quality Control, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, the United States of America (email: cbershippingrequests@fda.hhs.gov).  

• Research Centre for Influenza and Respiratory Viruses, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-Murayama, Tokyo 208-0011, Japan (email: flu-vaccine@nih.go.jp).  

Requests for reference viruses should be addressed to:  

• WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, Peter Doherty Institute, 792 Elizabeth Street, Melbourne, Victoria 3000, Australia (email: whoflu@influenzacentre.org; website: http://www.influenzacentre.org).  

• WHO Collaborating Centre for Reference and Research on Influenza, National Institute of Infectious Diseases, Japan Institute for Health Security 4-7-1 Gakuen, Musashi-Murayama, Tokyo 208-0011, Japan (email: whocc-flu@nih.go.jp).  

• Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road, Mail Stop H17-5, Atlanta, GA 30329, the United States of America (email: InfluenzaVirusSurvei@cdc.gov; website: http://www.cdc.gov/flu/).  

- WHO Collaborating Centre for Reference and Research on Influenza, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, the United Kingdom of Great Britain and Northern Ireland (Tel: +44 203 796 1520 or +44 203 796 2444, email: whocc@crick.ac.uk;  • website: http://www.crick.ac.uk/research/worldwideinfluenza-centre).  

• WHO Collaborating Centre for Reference and Research on Influenza, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Changping District, 102206, Beijing, China. (tel: +86 10 5890 0851; email: fluchina@ivdc.chinacdc.cn; website: https://ivdc.chinacdc.cn/cnic/en/).  

WHO provides weekly updates {9} of global influenza activity. Other information about influenza surveillance, risk assessment, preparedness and response can be found on the WHO Global Influenza Programme website {10}.  

Acknowledgements  

The WHO recommendation on vaccine composition is based on the year-round work of the WHO Global Influenza Surveillance and Response System (GISRS). We thank the National Influenza Centres (NICs) of GISRS, and non-GISRS laboratories including the World Organization for Animal Health (WOAH) and the Food and Agriculture Organization of the United Nations (FAO) Network of Expertise on Animal Influenza (OFFLU), who contributed information, clinical specimens, viruses and associated data; WHO Collaborating Centres of GISRS for their in-depth characterization and comprehensive analysis of viruses; University of Cambridge for performing antigenic cartography and phylogenetic analysis; WHO Essential Regulatory Laboratories of GISRS for their complementary virus analyses and contributions from a regulatory perspective; and laboratories involved in the production of high growth/yield reassortants as candidate vaccine viruses. We also acknowledge the GISAID Global Data Science Initiative for the EpiFluTM database and other sequence databases which were used to share gene sequences and associated information; modelling groups for virus fitness forecasting; and the Global Influenza Vaccine Effectiveness (GIVE) Collaboration for sharing estimates of influenza vaccine effectiveness on a confidential basis.  

(...)

___

{1} Recommendations for influenza vaccine composition: https://www.who.int/teams/global-influenza-programme/vaccines/who-recommendations 

{2} Description of the process of influenza vaccine virus selection and development: http://www.who.int/gb/pip/pdf_files/Fluvaccvirusselection.pdf 

{3} Vaccines in tropics and subtropics: https://www.who.int/teams/global-influenza-programme/vaccines/vaccine-in-tropics-and-subtropics 

{4} Vaccines against influenza WHO position paper – May 2022. Wkly Epidemiol Rec 2022; 97 (19): 185 - 208. Available at: https://iris.who.int/handle/10665/354264 

{5} Real-time tracking of influenza A(H1N1)pdm09 evolution: https://nextstrain.org/seasonal-flu/h1n1pdm/ha/2y?c=subclade 

{6} Real-time tracking of influenza A(H3N2) evolution: https://nextstrain.org/seasonal-flu/h3n2/ha/2y?c=subclade 

{7} Real-time tracking of influenza B/Victoria lineage evolution: https://nextstrain.org/seasonal-flu/vic/ha/2y?c=subclade 

{8} Candidate vaccine viruses: https://www.who.int/teams/global-influenza-programme/vaccines/who-recommendations/candidate-vaccine-viruses 

{9} Current respiratory virus update: https://www.who.int/teams/global-influenza-programme/surveillance-and-monitoring/influenza-updates 

{10} Global Influenza Programme: https://www.who.int/teams/global-influenza-programme 

___

Source: 

Link: https://www.who.int/publications/m/item/recommended-composition-of-influenza-virus-vaccines-for-use-in-the-2026-2027-northern-hemisphere-influenza-season

____

#Report on #influenza viruses received and tested by the #Melbourne #WHO CC for #Reference and Research on #Influenza during 2024

 

Abstract

As part of its role in the World Health Organization (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne received 12,180 human influenza-positive samples during 2024. Viruses were analysed for their antigenic, genetic, and antiviral susceptibility properties. Selected viruses were propagated in qualified cells or embryonated hens’ eggs for potential use in seasonal influenza virus vaccines. During 2024, influenza A(H1N1)pdm09 and A(H3N2) viruses predominated, accounting for 33% and 42%, respectively, of all viruses received, compared to 5% for influenza B/Victoria. Of note, one influenza A(H5N1) virus was also received in 2024. The majority of A(H1N1)pdm09 (98%), A(H3N2) (88%) and influenza B (100%) viruses analysed at the Centre were found to be antigenically and genetically similar to the respective WHO recommended vaccine strains for the Southern Hemisphere in 2024. Of 4,007 samples tested for susceptibility to the neuraminidase inhibitors oseltamivir and zanamivir, twelve A(H1N1)pdm09 viruses and one B/Victoria virus showed highly reduced inhibition against oseltamivir or zanamivir. Of 3,294 total samples sequenced for baloxavir susceptibility, 18 of the 1,825 A(H3N2) samples were identified with genetic evidence of reduced susceptibility to baloxavir marboxil in the PA gene.

Source: 

Link: https://ojs.cdi.cdc.gov.au/index.php/cdi/article/view/3449

____

#Haemagglutinin 162-164 #deletions enhance #influenza B/Victoria virus #fitness and #virulence in vivo

 

Abstract

Influenza B viruses cause substantial respiratory disease and seasonal outbreaks. Despite decades of circulation in humans, only the B/Victoria lineage persisted after the COVID-19 pandemic. Continual evolution has generated hemagglutinin deletion variants at residues 162-164 that drive successive epidemics, yet their functional consequences remain poorly understood. Using integrated phylodynamics and reverse genetics, we show that Clade V1A.1 viruses carrying a two-amino acid deletion exhibit enhanced replication and increased virulence compared with ancestral viruses lacking deletions. The recently prevailing Clade V1A.3, which harbors a three-amino acid deletion together with the K136E substitution, has completely displaced V1A.1 and causes more severe disease in mice. Both clades bound efficiently to alpha 2-3 and 2-6 sialylated glycans and exhibited broad tolerance to acidic pH and elevated temperatures. These findings reveal that specific combinations of HA deletions and substitutions confer pronounced fitness advantages to emerging variants, driving global selective sweeps, evolutionary success and long-term persistence of B/Victoria lineage, and posing challenges for vaccine efficacy and influenza control.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

National Institutes of Health, 75N93021C00016

Ministry of Health Singapore, CS-IRG/MOH-000374

Ministry of Health Singapore, OF-LCG/MOH-000505-05

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.01.08.698527v1

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#Influenza PA #Substitutions and Genetic Diversity of #H1N1pdm09, #H3N2, and B/Victoria Viruses in #Japan During the 2023–2024 Season

 

Abstract

We characterized influenza A(H1N1)pdm09, A(H3N2), and B/Victoria viruses circulating in Japan during 2023–2024, focusing on lineage placement relative to WHO-recommended vaccine strains and on baloxavir resistance (PA/I38T substitutions). We enrolled 210 outpatients with influenza-like illness across eight clinics in six prefectures (October 2023–September 2024). Of these, 209 had an analyzable pre-treatment respiratory specimen for RT-PCR; hemagglutinin (HA) and neuraminidase (NA) genes were sequenced by next-generation sequencing (NGS). PA/I38T substitutions that confer baloxavir resistance were assessed by cycling-probe RT-PCR, Sanger sequencing, and NGS. HA phylogenies were constructed with global datasets and WHO vaccine reference strains. Of 209 pre-treatment specimens, 181 were influenza-positive (A(H1N1)pdm09 44.2%, A(H3N2) 37.6%, B/Victoria 18.2%); 51 follow-up specimens were collected ≈4–5 days after baloxavir or neuraminidase inhibitor therapy. HA phylogeny placed A(H1N1)pdm09 in clades 5a.2a/5a.2a.1 with predominance of subclade D.2. A(H3N2) clustered exclusively in clade 2a.3a.1 (J lineage, mostly J.1), indicating a mismatch with the season’s A/Darwin/9/2021 vaccine component and supporting the subsequent J-lineage update. All B/Victoria genomes fell within V1A.3a.2 on a C.5 backbone (C.5.1 and C.5.7). No PA/I38T variant was detected in any pre-treatment specimen. Post-baloxavir, PA/I38T emerged in one A(H3N2) case (confirmed by all three methods) and in one B/Victoria case detected by NGS only (minority variant in a low-load sample). NA genes showed no substitutions associated with reduced susceptibility to laninamivir (e.g., E119A, G147E). During 2023–2024, A(H1N1)pdm09 and B/Victoria remained genetically aligned with their vaccine components, whereas A(H3N2) shifted to the J lineage, consistent with the 2024–2025 vaccine update. Although pre-treatment PA/I38T was absent, low-frequency on-therapy selection was observed, including a rare PA/I38T in influenza B/Victoria detected by NGS, suggesting the value of deep sequencing when viral loads are low. These integrated genomic–clinical data support vaccine strain realignment for H3N2 and continued monitoring of baloxavir resistance in outpatient care.

Source: 

Link: https://www.mdpi.com/1999-4915/18/1/13

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Seasonal #influenza - #Global #situation (#WHO, Dec. 10 '25, excerpts)

 

10 December 2025

Situation at a glance

Seasonal influenza (‘the flu’) is an acute respiratory infection caused by influenza viruses that circulate globally and year-round. 

It can cause illness ranging from mild to severe, sometimes resulting in hospitalization or death. 

Seasonal influenza activity has increased globally in recent months, with an increased proportion of seasonal influenza A(H3N2) viruses being detected. 

This rise coincides with the onset of winter in the northern hemisphere and an increase in acute respiratory infections caused by influenza and other respiratory viruses typically observed at this time of year. 

Although global activity remains within expected seasonal ranges, early increases and higher activity than typical at this time of year have been observed in some regions. 

Seasonal influenza viruses, including A(H3N2) viruses, continually evolve over time. 

Since August 2025, there has been a rapid increase of A(H3N2) J.2.4.1 alias K subclade viruses detected from several countries based on available genetic sequence data. 

These subclade K viruses have several changes from related A(H3N2) viruses. 

Current epidemiological data do not indicate an increase in disease severity, although this subclade marks a notable evolution in influenza A(H3N2) viruses. 

Early estimates suggest that the influenza vaccine continues to provide protection against hospital attendance in both children and adults, even though its effectiveness against clinical disease during the current season remains uncertain. 

Vaccines remain essential, especially for people at high risk of influenza complications and their care givers. 

Even if there are some genetic differences between the circulating influenza viruses and the strains included in the vaccines, the seasonal influenza vaccine may still provide protection against drifted viruses and the other virus strains included in the vaccine. 

Vaccination is still expected to protect against severe illness and remains one of the most effective public health measures. 

WHO continues to monitor global influenza activity and influenza viruses, supports countries in surveillance capacity and updates guidance as needed.

Description of the situation

Globally, influenza activity has increased since October 2025 with influenza A viruses predominant among the viruses detected globally.

In many northern hemisphere countries, acute respiratory infection levels increase at this time of year. 

These increases are typically caused by seasonal epidemics of respiratory pathogens such as influenza, respiratory syncytial virus (RSV) and other common respiratory viruses. 

The exact timing of the onset, the duration, magnitude and the severity of each epidemic might vary by location, influenced by multiple factors such as type of circulating viruses (including influenza and other respiratory pathogens), relative population immunity and environmental conditions.

In the northern hemisphere, some countries have reported early starts to the influenza season. 

In other countries, influenza activity is starting to increase, but has not yet reached the epidemic threshold.

In the southern hemisphere, some countries have had unusually long seasons compared to previous years, with virus activity remaining higher than usual in recent months.

Global influenza surveillance and monitoring is conducted through the Global Influenza Surveillance and Response System (GISRS), a WHO-coordinated network of over 160 institutions in 131 Member States. 

GISRS is tasked with conducting year-round surveillance and monitoring of influenza viruses and serving as the global alert mechanism for the emergence of novel influenza viruses and other respiratory pathogens with pandemic potential.

In the northern hemisphere temperate and sub-tropical countries, areas and territories, influenza activity was generally low from June to August 2025. 

Activity gradually increased in September and continued to increase through November 2025. Influenza A viruses, especially A(H3N2) viruses, predominated during this period (...).

In the southern hemisphere temperate and sub-tropical countries, areas and territories, influenza activity generally decreased from June 2025 and remained low through August. 

However, a slight increase has been observed since September. 

Influenza A(H1N1)pdm09 viruses predominated in June and July; however, A(H3N2) viruses have predominated since September (...).

In tropical areas, there has been sustained influenza activity from June through November. 

Influenza A(H1N1)pdm09 viruses predominated through July. Since then, the proportion of influenza A(H3N2) viruses among reported detections has increased and has become predominant since the end of September (...).

(...)

Genetic characteristics of recent seasonal influenza viruses

Influenza A(H1N1)pdm09 and influenza B/Victoria lineage viruses continue to circulate in all regions albeit at low levels.

Influenza A(H3N2) viruses

Based on genetic sequence data available in GISAID, a mixture of A(H3N2) haemagglutinin (HA) clades and subclades are currently circulating globally; however, there has been a recent and rapid rise in a particular  subclade of A(H3N2), J.2.4.1 (alias subclade K Nextclade/Nextstrain nomenclature). 

A(H3N2) subclade K viruses have genetically drifted from related J.2.4 viruses and have several amino acid changes in their HA in comparison. 

Detections of subclade K viruses are increasing in many parts of the world, with the exception, to date, of South America. 

Subclade K viruses were particularly evident from August 2025 in Australia and New Zealand and have now been detected in more than 34 countries over the last 6 months.

(...)

Overview of seasonal influenza by WHO Region

African region

Influenza detections in the WHO African Region overall increased in October with influenza A(H3N2) predominant. 

The timing and predominant virus varied by zone. 

In the western part of the region, influenza detections increased in September and October with A(H3N2) predominant since October. 

All seasonal subtypes have been detected continuously in the middle and eastern parts of the region. 

Influenza activity peaked in May 2025 in South Africa with almost exclusively A(H3N2) detections; in recent weeks influenza activity has increased slightly but remained low.

Eastern Mediterranean Region

While influenza activity in the WHO Eastern Mediterranean Region overall increased in October with A(H3N2) viruses predominant, there were variations by zone. 

In countries in the northern part of the region, influenza detections increased in October with influenza A(H1N1)pdm09 predominant and lesser proportions of influenza A(H3N2) and B virus detections reported. 

In the Arabian Peninsula, influenza detections also increased in October but with influenza A(H3N2) viruses predominant.

European Region

As of 21 November 2025, reported rates of influenza-like illness (ILI) and/or acute respiratory infection (ARI) in primary care were at baseline levels for most countries and areas of the WHO European Region. 

However, detections were increasing and regionally pooled test percent positivity in primary care sentinel surveillance rose above 10% in weeks 45 and 46 (ending on 15 November), marking the start of the 2025/26 influenza season for the European Region. 

This was approximately four weeks earlier than the median, but not out of the ordinary, with epidemiological trends similar to those observed in the 2022/23 influenza season.

Influenza activity was variable between countries, with those in the west of the Region generally seeing earlier increases of influenza indicators compared to others. 

Influenza admissions, detections, and percent positivity in hospital surveillance were also increasing from inter-seasonal levels, with a higher proportion aged 65 years or older. 

A majority of influenza detections from sentinel and non-sentinel primary care and hospital surveillance systems were A(H3N2) viruses.

Region of the Americas

During the 2025 southern hemisphere season in the Americas, influenza transmission exceeded the seasonal threshold in mid-March, remaining mostly at low to moderate levels. 

Circulation was driven by influenza A(H1N1)pdm09, reaching a peak positivity of 19%. 

Activity then declined to low levels until the end of August, when an increase in circulation was observed, associated with influenza A(H3N2) in Brazil and Chile. 

As of beginning of November, Chile remains at moderate levels of influenza A(H3N2) transmission, without evidence of increased severity or rises in outpatient consultations. 

As of 4 November 2025, subclade K had not been detected in South America.

In the northern hemisphere countries of the Americas, during week 45 of 2025, seasonal influenza circulation remained low, with influenza A(H1N1)pdm09 predominating in the Caribbean and Central America. 

In North America, influenza activity—although still low—was increasing, mainly driven by influenza A virus detections. 

While most detections in Mexico were influenza A(H1N1)pdm09, a predominance of influenza A(H3N2) has been observed in the United States and Canada, with growing detections of the A(H3N2) subclade K.

South-East Asia Region

Influenza detections in the South-East Asia Region started increasing from June,  peaked in August and since then  have generally remained low with some exceptions. 

During the 2025 till November, the proportion of Influenza A among all influenza viruses tested positive was 66% Influenza A(H3N2) was the predominant sub-type (43%) in transmission followed by A(H1N1)pdm09 (~20%). 

In Thailand, influenza detections of predominantly A(H3N2) increased in October and November. 

Influenza A(H3N2) detections also increased since July in Bangladesh and October in Sri Lanka. 

While the region has seen an increase in Influenza A(H3N2), 22 sequences of   subclade K have   been reported in GISAID from Nepal (1), India (4) and Thailand (17) as of 30 November.

Western Pacific Region

Since the beginning of October 2025, influenza seasonal activity has increased in the Western Pacific Region. 

In some countries, including Japan and the Republic of Korea, the onset of the typical seasonal influenza activity period started earlier than in previous years. 

As of 9 November 2025, influenza positivity ranged from 8% to 56% in the northern hemisphere countries. 

In southern hemisphere countries, influenza activity shows mixed trends; positivity has declined in Australia, remains high in New Zealand and is rapidly increasing in Fiji. 

The elevated influenza activity in New Zealand and Fiji is unusual for this time of the year.

The predominant circulating influenza subtype is influenza A(H3N2), marking a shift from A(H1N1)pdm09, which predominated during the 2024-2025 northern hemisphere winter season. 

The increases in influenza have predominantly been driven by the expansion of A(H3N2) subclade K, which represents 89% of sequences submitted to GISAID from the Western Pacific Region (as of 21 November 2025). 

Epidemiology

Seasonal influenza (the flu) is an acute respiratory infection caused by influenza viruses that circulate globally and year-round. In temperate regions, seasonal influenza typically peaks during the winter months, whereas in tropical areas, influenza viruses can circulate year-round with seasonality and intensity that varies across countries.  

There are four types of influenza viruses, types A, B, C and D. Influenza A and B viruses circulate and cause seasonal epidemics of disease:

Influenza A viruses are further classified into subtypes according to the combinations of the proteins on the surface of the virus. Currently circulating in humans are subtype A(H1N1) and A(H3N2) influenza viruses. Influenza B viruses are not classified into subtypes but can be broken down into lineages. Influenza type B viruses belong to either B/Yamagata or B/Victoria lineage.

Influenza spreads easily between people when they cough or sneeze. Influenza disease can cause illness ranging from mild to severe, sometimes resulting in hospitalization or death. While most individuals recover within a week without need for medical care, influenza can lead to serious complication including death, especially among high-risk groups such as young children, the elderly, pregnant women and those with underlying conditions. Health and care workers are at high risk of acquiring influenza virus infection due to increased exposure to the patients, and of further spreading particularly to vulnerable individuals.

Public health response

WHO is enhancing national, regional, and global capacities for influenza preparedness and response, including:

-- continuous global monitoring of influenza viruses and disease activity;

-- issuing seasonal influenza vaccine composition recommendations for both hemispheres;

-- providing technical guidance to Member States on vaccine selection and campaign timing;

-- supporting countries in developing prevention and control strategies;

-- enhancing diagnostic capabilities and laboratory networks;

-- monitoring vaccine effectiveness and susceptibility to approved antivirals;

-- supporting disease surveillance and outbreak response activities;

-- promoting increased vaccine coverage among high-risk groups;

-- facilitating research and development of new therapeutics and countermeasures; and

-- enhancing risk communication for the onset of the influenza season.

WHO risk assessment

Seasonal influenza activity has increased globally in recent months, and influenza A(H3N2) viruses are predominant. 

This rise coincides with the onset of winter in the northern hemisphere. 

Epidemics and outbreaks of seasonal influenza and other circulating respiratory viruses can place significant pressure on healthcare systems.  

Although global activity remains within expected seasonal ranges, early increases and higher activity than typical at this time of year have been observed in some regions. 

Seasonal influenza could place significant pressure on healthcare systems even in non-temperate countries. 

Genetically drifted influenza A(H3N2) viruses, known as subclade K viruses, have been detected in many countries. 

While data on how well the vaccine works against clinical disease this season are still limited, vaccination is still expected to protect against severe illness and remains one of the most effective public health measures. 

WHO advice

Surveillance

Due to the constantly evolving nature of influenza viruses, WHO continues to stress the importance of year-round global surveillance to detect and monitor virological, epidemiological and clinical changes associated with emerging or circulating influenza viruses that may affect human health and timely virus sharing for risk assessment.  Countries are encouraged to remain vigilant to the threat of influenza viruses and review any unusual epidemiological patterns.

WHO advises Member States to maintain surveillance for respiratory pathogens through an integrated approach, considering country context, priorities, resources and capacities. WHO has published guidance on integrated respiratory virus surveillance. WHO has also updated guidance on assessing influenza epidemic and pandemic severity, including the impact on healthcare facilities.

Clinical management and prophylaxis

Clinical care for seasonal influenza focuses on identifying illness severity, assessing risk of progression, and linking to definitive care. Most cases are mild and self-limiting, but severe disease, marked by respiratory distress, sepsis, acute respiratory distress syndrome or multi-organ failure, requires urgent supportive care and often hospitalization. Clinical management of influenza involves high-quality supportive care—oxygen therapy, monitoring, hydration and respiratory support—and is foundational to improving outcomes, especially in severe cases.

Diagnostic testing should support rapid decision-making: nucleic acid amplification test (NAAT) is conditionally recommended for confirmation of suspected disease in severely unwell patients, while either NAAT or digital immunoassay may be used for non-severe cases, depending on context and resource availability. Testing should be performed early with the aim of identifying people in need of treatment and linking them to care, including antivirals where indicated.

Patients at high risk of progressing to severe disease are likely to benefit from antiviral to reduce their chance of admission to hospital. High-risk groups include adults ≥65 years, those with immunocompromising conditions, chronic cardiovascular, neurological or respiratory disease; malignancy, pregnancy and diabetes further elevate risk. Individuals ≥85 years or those with multiple risk factors are considered extremely high risk and might be considered for antiviral prophylaxis if exposed to influenza.

Infection prevention and control measures in health-care settings

Seasonal influenza is known to cause health care-associated infection outbreaks, in particular in long-term care facilities. WHO advises the use of syndromic screening at all entry points to health-care settings and as part of daily inpatient assessment to ensure that patients with suspected or confirmed infections that are transmissible in health-care settings, including influenza, are identified as soon as possible and that appropriate transmission-based precautions are implemented. WHO advises the use of droplet precautions when caring for patients with suspected or confirmed influenza. This includes appropriate patient placement (isolation) of suspected or confirmed cases, and the use of a medical mask by all health and care workers and visitors when caring for patients with suspected or confirmed influenza.

Appropriate risk assessment for additional personal protective equipment (e.g. eye protection, filtering facepiece respirators, gown, gloves) should be performed by health and care workers when caring for patients with influenza. 

Increased risk of influenza transmission may occur instances where care activities or patient symptoms are likely to generate splashes or sprays of blood, body fluids, secretions and excretions onto mucosa of eyes, nose or mouth; or if in close contact with a patient with respiratory symptoms (e.g. coughing/sneezing) and sprays of secretions may reach the mucosa of eyes, nose or mouth directly, or indirectly via contaminated hands. When performing an aerosol-generating procedure on patients with suspected or confirmed influenza, patient placement in an airborne infection isolation room as well as airborne and contact precautions with eye protection are advised.

Vaccination

Vaccination is the best way to prevent influenza disease. Safe and effective vaccines have been used for more than 60 years. Influenza viruses are constantly changing, so the composition of the seasonal influenza vaccine is regularly updated to contain viruses that are more related to those circulating. WHO, through the Global Influenza Programme and GISRS, in collaboration with partners, continuously monitors influenza viruses and activity globally and recommends seasonal influenza vaccine compositions in February and September for the following northern and southern hemisphere influenza seasons, respectively.

WHO recommends annual vaccination for high-risk groups, including health and care workers. People should ideally get vaccinated just before the influenza season begins for the most effective coverage, although getting vaccinated at any time during the influenza season can still help prevent flu infections. While the effectiveness of the vaccine may vary across seasons and risk groups, it reduces disease severity and lowers the chance of complications and death. Vaccination is especially important for people at high risk of influenza complications and their caregivers.

Genetic changes or drift can occur in the circulating influenza viruses before or during the influenza season, including during the time between vaccine strain selection and the influenza season. Even if there are some genetic differences between the circulating influenza viruses and the strains that are included in the vaccines, the seasonal influenza vaccine may still provide protection against drifted viruses. Current vaccines include three influenza viruses: influenza A(H1N1)pdm09, influenza A(H3N2) and influenza B/Victoria lineage viruses. Therefore, circulation of a drifted virus does not always result in seasonal influenza vaccines being less effective in offering protection against influenza associated illness.

As of now, it remains unclear how the vaccine will protect against clinical disease during this current season. However, early vaccine effectiveness estimates show the current vaccine is 70 to 75% effective at preventing hospital attendance in children aged 2 to 17 years and 30 to 40% effective in adults.[1],[2]

Public health and social measures in the community

The implementation of appropriate and proportionate public health and social measures (PHSM) is an essential component in the overall response to seasonal influenza epidemics. 

Measures such as performing hand hygiene, respiratory hygiene and cough etiquette as well as voluntary self-isolation and mask wearing of individuals who are symptomatic or have tested positive for influenza viruses can reduce transmission of influenza viruses.  

Countries should consider developing a plan to scale up additional PHSM in the event of high or extraordinarily high epidemics.  

Risk communication and community engagement

Member States should consider to update and strengthen their risk communication and community engagement (RCCE) strategy integrating respiratory viruses. Enhanced risk communication and community engagement approach support empowerment of individuals to make informed decisions, countering misinformation, and community-led protection strategies.

Clear, regular, evidence-based, culturally acceptable and context adapted RCCE approaches are essential for building and maintaining trust with the concerned and affected populations to ensure adoption of interventions, practices and behaviours. For RCCE efforts to be successful, it is vital that national policies for RCCE incorporate community engagement and feedback mechanisms that acknowledge and address contextual challenges faced by different population groups, particularly those made most vulnerable. The integration of RCCE approaches to promote vaccination against influenza is also recommended.

WHO does not recommend any restriction on travel to or trade with the countries named in this report, based on the information available on the current event.  

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Source: 

Link: https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON586

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