About the influenza epidemic of 2024/2025

The influenza epidemic of the 2024/2025 respiratory season lasted from week 3 of 2025 through week 11 of 2025. The epidemic lasted nine weeks. This is based on data from all available surveillance sources (in Dutch) for influenza virus.

The number of people visiting the general practitioner (GP) with influenza-like illness (ILI) was above the threshold for increased activity (53 per 100,000 people) only during the first seven weeks of the influenza epidemic (week 3 to 9 of 2025). However, specimens from these patients and other surveillance sources showed that there was still increased circulation of influenza virus up to and including week 11. Influenza virus type A was most common this season. Influenza virus type B was found relatively little during the whole season, but the proportion of type B increased slightly at the end of the influenza season.

Mainly influenza virus type A

In the laboratory, testing is performed to determine the subtype or genetic lineage of the influenza viruses found. Of the specimens taken from people with an influenza-like illness who visited the GP, 20% had influenza virus subtype A(H3N2), 16% had subtype A(H1N1)pdm09, and 9% had type B of the Victoria lineage. Two of the A(H3N2) viruses were so-called reassortant  viruses. In this case, it was a mix of the human A(H3N2) virus and A(H1N1)pdm09 virus. These viruses are likely related to an outbreak of respiratory infections at a school. Among Infectieradar participants with respiratory complaints (acute respiratory infection) who sent in a specimen to RIVM, 3% tested positive for influenza virus subtype A(H3N2), 3% for A(H1N1)pdm09, and 1% for type B of the Victoria lineage (see figure 2 on the syndromic surveillance page). Of the influenza specimens received by the National Influenza Center (Erasmus MC and RIVM) from diagnostic laboratories, a total of 1,479 viruses were subtyped. Of these, 36% were influenza virus type A(H1N1)pdm09, 29% were influenza virus type A(H3N2), and 35% were influenza virus type B of the Victoria lineage.

In all age groups, influenza virus A subtypes were found. B/Victoria was found most often in age groups under 50 years old. Worldwide, influenza virus type B of the Yamagata lineage has not been detected since the start of the COVID-19 pandemic in March 2020 (Caini, Meijer et al.).  In October 2024, a small amount of genetic material of influenza virus type B of the Yamagata lineage was found in a patient with influenza-like illness who was sampled by a sentinel GP. Since the patient had not been vaccinated against influenza, vaccination had not yet started in the practice, and the patient had not had contact with people vaccinated with the live attenuated influenza vaccine, there is no indication of contamination of the specimen with the vaccine virus. Because of the low amount of virus in the specimen, the virus could not be cultured or sequenced. Therefore, infection with B/Yamagata virus could not be definitively proven. This finding has been reported and discussed with the WHO and ECDC. During the 2024/2025 respiratory season, the possible presence of B/Yamagata viruses in the Netherlands was closely monitored, but there were no further detections. 

Reduced sensitivity to antiviral drugs

All the influenza viruses found through surveillance that have been sequenced are analysed for known genetic changes (mutations that lead to amino acid changes) that cause reduced sensitivity to antiviral drugs. The effects of these genetic changes on the phenotypic properties of the virus are also examined, together with wildtype influenza viruses for comparison. These tests assess the level of sensitivity of the viruses to the antivirals oseltamivir, zanamivir, and baloxavir marboxil. In the Netherlands, antivirals are infrequently used for treatment, only for people with a very high risk of becoming seriously ill from influenza. Among most of the tested A(H1N1)pdm09 and all A(H3N2) and B/Victoria viruses, no reduced sensitivity was found for oseltamivir, zanamivir, or baloxavir marboxil.

In the 2023/2024 season, a variant of A(H1N1)pdm09 was found with two amino acid changes, NA-I223V and NA-S247N, which caused a slight reduction inhibition by oseltamivir. This variant was not found in the 2024/2025 season. However, A(H1N1)pdm09 viruses with only the NA-S247N change were found. These had a higher half-maximal inhibition by oseltamivir, but not enough to be considered reduced inhibition. Three A(H1N1)pdm09 viruses had a NA-H275Y change, which causes a strong reduction in the inhibition by oseltamivir. In addition, one A(H3N2) virus was found with the NA-S331R change. This change was previously linked to reduced sensitivity to both oseltamivir and zanamivir. However, laboratory tests showed that this virus was still normal sensitive to both antivirals. One B/Victoria virus with the NA-M464T change showed a slight reduction in the inhibition by zanamivir. No viruses were found with amino acid changes that cause reduced sensitivity to baloxavir marboxil.

The NA-H275Y mutants can be considered resistant to oseltamivir and therefore cannot be treated with oseltamivir therapy. For the other mutants found, this is less clear, as there is little or no data on the treatment of patients infected with these mutant viruses. However, these mutants are less well inhibited by oseltamivir, which could make the treatment less effective.

Comparison of virus and vaccine

For the influenza A(H1N1)pdm09 viruses and influenza B viruses of the Victoria lineage, the vaccine composition for 2024/2025 matched well with the variants of these influenza viruses that circulated during the respiratory season in the Netherlands. Based on information available by the end of February 2025 for these viruses, no update of the vaccine for the 2025/2026 season was proposed by the WHO. Several influenza virus type A(H3N2) variants circulated worldwide at the same time, including the variant with a double amino acid change in the hemagglutinin protein (HA-N158K + K189R), which was at first mainly found in the Netherlands. This and some other A(H3N2) variants are less well recognized by the immune system of people who received the influenza vaccine in the autumn of 2024 or who have had influenza before. As a result, these people were probably less well protected against particularly the A(H3N2) (HA-N158K + K189R) variant. In week 50 of 2024, this variant was seen for the first time in the Netherlands. Its proportion increased each week to a maximum of 25% of A(H3N2) viruses that were sequenced. Because most A(H3N2) virus variants in circulation are well recognized by the A(H3N2) vaccine strain of the Southern Hemisphere vaccine for 2025, this vaccine strain has also been recommended for the 2025/2026 Northern Hemisphere vaccine. The National Influenza Center will closely monitor which viruses are circulating outside the Netherlands and at the start of the 2025/2026 season.

The vaccine strains used in the Netherlands for the 2024/2025 season belonged to the 5a.2a.1 (subclade D.1) for A(H1N1)pdm09, 2a.3a.1 for A(H3N2), and V1A.3a.2 clade for B/Victoria. Most of the characterized influenza A(H1N1)pdm09 viruses belonged to clade 5a.2a (subclade C.1.9.3), followed by clade 5a.2a.1 (subclade D.3). All characterized influenza A(H3N2) viruses belonged to clade 2a.3a.1, with the vast majority in subclade J.2. The characterized influenza B (Victoria lineage) viruses all belonged to clade V1A.3a.2. Most were in subclade C.5.1, followed by subclade C.5.7 and then C.5.6. In laboratory tests for similarity with the vaccine viruses, most subclades of the viruses were similar to the vaccine viruses. As mentioned earlier, some of the A(H3N2) viruses had a double amino acid change in the hemagglutinin protein (HA-N158K + K189R), making them antigenic quite different from the vaccine virus.

Effectiveness of the influenza vaccine

In the 2024/2025 respiratory season, the vaccine effectiveness of the influenza vaccine in Europe against influenza A(H1N1)pdm09 infections was 30% (95% confidence interval: 7% to 47%), and against influenza type A(H3N2) infections 29% (95% confidence interval: -22% to 60%). Against influenza type B of the Victoria lineage, the vaccine effectiveness was 61% (95% confidence interval: 38% to 76%) (Rose, Lucaccioni et al.). These interim estimates, from the European VEBIS study, were made during the winter season. RIVM, together with Nivel and other European countries, provided data for this study. The estimates are calculated for influenza virus infections in people of all ages who visited the GP with an influenza-like illness and had a throat/nose specimen taken. The final vaccine effectiveness based on data from the entire winter season will be published later.

Table 1: Overview of influenza epidemics in the past 10 respiratory seasons