Influenza continues to be a constant threat and an enormous public health problem, and vaccination is the most effective preventive measure. In 2012, the World Health Organization (WHO) recommended giving children aged 6–59 months priority group status for vaccination against influenza. Since 2005, the Advisory Committee on Vaccines and Immunizations (CAV) of the Asociación Española de Pediatría (AEP, Spanish Association of Paediatrics) publishes annual recommendations for vaccination against influenza in children and adolescents, judging that in children aged more than 6 months who do not belong to any established risk groups, vaccination is advisable to grant the child individual protection and to contribute to the protection of the family and the community, and has recommended routine vaccination of children aged 6–59 months from the 2021–2022 season. In December 2022, the Interterritorial Council of the National Health System of Spain (known as CISNS) included routine vaccination against influenza for all children aged 6–59 months in its unified immunization schedule for the lifespan for 2023, a measure that was implemented by all the autonomous communities in Spain in 2023–2024, although three of them (Andalusia, Galicia and the Region of Murcia) had already started implementing it in the previous season.

Priority is given to vaccination against influenza of individuals older than 6 months who belong to any risk group for severe influenza, including pregnant women, household contacts of individuals at risk and health care workers. Unfortunately, the vaccination coverages achieved in these groups and in healthy children included in seasonal campaigns have been low, generally falling short of established objectives. Health care authorities, health care professionals, scientific societies and patient associations need to get involved more actively to succeed in increasing them.

In this article, we present the recommendations of the CAV-AEP for vaccination against influenza in the 2024−2025 season (summarised in Table 1), and discuss other related aspects, such as the effectiveness and safety of these vaccines in the paediatric population.

Every year, there are approximately 1000 million cases of seasonal flu, including 3–5 million severe cases and 290 000–650 000 deaths.1 The proportion of the paediatric population affected during the annual influenza outbreaks ranges between 30% and 40%, with nearly 1 million severe cases in children under 5 years worldwide and 99% of flu-related deaths occurring in developing countries.

Each season, children aged less than 15 years, especially those age less than 5 years, are the age group with the highest incidence of influenza. In Spain, the disease activity data for the 2023–2024 season (through week 15 of 2024) reported by the acute respiratory tract infection surveillance system (SIVIRA)2 show that the incidence at the primary care level peaked on week 52/2023, a very high and intense peak compared to previous seasons, while the value below the threshold that marks the end of the season occurred in week 06/2024. By age group, once again the highest incidence occurred in infants aged less than 1 year, followed by children aged 1–4 years and children and adolescents aged 5–14 years. As regards hospital admission due to influenza, following the group aged more than 65 years, infants aged less than 1 year were the group with the highest hospitalization rate. In Europe, in the 2023–2024 season influenza activity also started around mid-November, peaking in the second or third week of December and gradually decreasing until the early weeks of January. The main circulating strain was A(H1N1)pdm09, followed by a lower proportion of A(H3N2) and a few isolated cases of B/Victoria.3

Every year, the WHO issues recommendations regarding the composition of the seasonal influenza vaccines for each hemisphere to aim at achieving an adequate match between the components of the vaccines and the viruses expected to be circulating during the season based on epidemiological surveillance data and the characterization of the circulating viruses in the previous season. For the first time in years, the WHO4 has recommended the use of trivalent vaccines for the upcoming season excluding the B/Yamagata lineage on account of the lack of detection of viruses of this lineage since 2020 (Table 2).

In Spain, seven vaccine formulations will be distributed for the upcoming season, of which 5 (4 inactivated and 1 live attenuated) are authorised for use in children and adolescents (Table 3). The attenuated vaccine, following the recommendation of the WHO, will have a trivalent composition excluding the Yamagata lineage. The inactivated vaccines will continue to be quadrivalent.

Of the 4 inactivated vaccines, 3 are manufactured using fertilised chicken eggs in a regulated process, allowing the viruses to replicate in the eggs prior to inactivation, and the remaining one is a cell culture-based vaccine manufactured by inoculating virus into cultured mammalian cells and allowing them to replicate, after which the viral antigen is purified. In theory, the cell culture method could offer better results compared to the egg-based method, as adaptive mutations may affect viral synthesis in the latter, although the current evidence5 is not consistent enough due to the lack of comparative clinical studies spanning several seasons.

The intranasal live attenuated vaccine is developed using embryonated chicken eggs. It has the capacity to simulate natural infection and thus induce a humoral and cell-mediated immune response that also involves mucosal immunity.

The vaccine effectiveness (VE) of influenza vaccines varies widely based on the vaccinated population, the vaccine used, the viruses circulating in the season and the match with the viruses contained in the vaccines, among other factors,7 and whether the outcomes considered include efficacy against confirmed influenza, emergency department visits, hospital admission or prevented deaths.

When it comes to VE in the paediatric population, a recent review estimated it ranged between 25.6% and 78.8%.8 A Cochrane review of 41 studies and more than 200 000 individuals, most aged more than 2 years, concluded that universal vaccination of individuals aged 3–16 years reduced the risk of influenza infection, both with attenuated vaccines (relative risk [RR], 0.22; 95% confidence interval [CI], 0.11−0.41) and with inactivated vaccines (RR, 0.36; 95% CI, 0.28−0.48).9 Another systematic review found a VE for prevention of any type influenza-related hospitalization of 57.48% (95% CI, 49.46–65.49), with a higher VE against H1N1 (74.07%; 95% CI, 54.85–93.30) compared to influenza B (50.87%; 95% CI, 41.75–59.98), and a moderate VE against H3N2 (40.77%; 95% CI, 25.65–55.89). The VE was highest in children under 5 years (61.71%; 95% CI, 49.29–74.12) and children aged 6–17 years (54.37%; 95% CI, 35.14–73.60).10

An interim report of data for 10 European countries, including Spain, showed that the 2023–2024 VE against influenza A for all ages was 51% (95% CI, 41–59) in primary care settings, with a VE of 71% (95% CI, 55–82) in the group aged 0–17 years that was even greater against A(H1N1)pdm09 (85%; 95% CI, 71–93). When it came to preventing hospitalization, the overall VE was 38% (95% CI, 27–48), with no figures given for the group aged less than 18 years.11

In the United States, interim estimates for the 2023–2024 season showed a VE in the group aged 6 months to 17 years of 52%–67%, of 46%–59% for influenza A and of 64%–89% for influenza B.12

Influenza vaccines have a high safety profile with an overall favourable risk-benefit ratio.

With inactivated vaccines, local reactions are the most frequent type of adverse event (redness and tenderness), and the most common systemic adverse events are fever, myalgia and fatigue, with a frequency that ranges between 5% and 20%. These events are usually mild and do not require medical care.13

When it comes to the attenuated vaccine, many clinical trials and postmarketing surveillance studies support its good safety profile. The most frequent adverse reactions are nasal congestion and fever. In a prospective observational study,14 the adverse events observed most frequently were lower respiratory tract infection and wheezing, although there was not an increase in hospital admissions compared to the unvaccinated group.

A history of anaphylactic reaction to any vaccine component, with the exception of egg,15 or to a previous dose of influenza vaccine is considered an absolute contraindication for the influenza vaccine.

The intranasal influenza vaccine is also contraindicated in16:

• •

  Immunocompromised individuals, with the exception of children with stable HIV infection receiving antiretroviral therapy and with adequate immune function.

• •

  Household contacts of severely immunocompromised individuals. If they receive this vaccine, contact needs to be avoided for 1–2 weeks following vaccination.

• •

  Children aged 2–17 years currently taking aspirin or other treatment containing acetylsalicylic acid due to the association with Reye syndrome.

• •

  Pregnant women, due to the lack of safety data.

The attenuated vaccine must be used with caution in individuals with severe asthma or active wheezing, as these conditions were not studied during clinical trials.17 The Centers for Disease Control and Prevention (CDC) of the United States consider it contraindicated in children aged 2–4 years with asthma or who have had a wheezing episode in the past 12 months, while they recommend precaution in children aged 5 or more years with asthma.18 When this vaccine has been used in children with asthma aged 5–17 years, there have been no significant differences in the frequency of asthma symptoms or changes in pulmonary function tests in the 14 days following vaccination.19

There is no evidence in children that vaccination against influenza is a risk factor for Guillain-Barré syndrome (GBS). In addition, it is estimated that the risk of developing GBS after an influenza infection is greater than the risk associated with vaccination.20,21 Although it is not a contraindication but a precaution,18 the CDC recommends against administering additional doses to healthy children who developed GBS within 6 weeks of receiving the influenza vaccine. However, vaccination in subsequent seasons should still be considered in children with underlying diseases, in whom its benefits of vaccination exceed the hypothetical risk.16

Caution must be exerted in children who developed immune thrombocytopaenic purpura in the week following receipt of the inactivated influenza vaccine. Given the risk of recurrence, the appropriateness of vaccination should be determined on a case-by-case basis.16

The intranasal vaccine can be administered at the same time as other parenteral or oral attenuated vaccines or as apart as desired.

The CAV-AEP recommends vaccination against influenza in the following groups (Table 5):

• 1

  Children aged 6–59 months (routine vaccination).

• 2

  Children and adolescents aged 5–18 years, based on individual indicationsa.

• 3

  Individuals at risk of complicated influenza due to their age or risk factors.

• 4

  Individuals who could transmit influenza to groups at risk of complicated disease, including household contacts of infants aged less than 6 months.

• 5

  Other cases. In general, essential workers and individuals exposed to influenza at work.

The intranasal vaccine offers the advantages of greater acceptability,40 easy administration, superior effectiveness compared to inactivated vaccines and a low reactogenicity, so, from age 2 years, the minimum age from which it can be administered according to the summary of product characteristics, it is the vaccine recommended for preferential use by the CAV-AEP.

The development of these recommendations (analysis of the published data, debate, consensus and publication) has not been supported by any funding source outside of the logistic support provided by the AEP.

Javier Álvalrez Aldeán has collaborated in educational activities funded by AstraZeneca, GlaxoSmithKline, MSD, Pfizer, Sanofi and Seqirus; as a researcher in clinical trials for GlaxoSmithKline and Sanofi, and as a consultant in AstraZeneca, GlaxoSmithKline, MSD, Pfizer and Sanofi advisory boards.

Francisco José Álvarez García has collaborated in educational activities funded by Alter, AstraZeneca, GlaxoSmithKline, MSD, Pfizer and Sanofi, and as a consultant in GlaxoSmithKline, MSD, Pfizer and Sanofi advisory boards.

María Garcés-Sánchez has collaborated in educational activities funded by Astra, GlaxoSmithKline, MSD, Pfizer and Sanofi, as a researcher in clinical trials for GlaxoSmithKline, Janssen, MSD, Pfizer and Sanofi, and as a consultant in GlaxoSmithKline, Novartis and Pfizer advisory boards.

Elisa Garrote Llanos has received funding to attend domestic educational activities and has participated in educational activities funded by GlaxoSmithKline, MSD, Pfizer and Sanofi, as a researcher in studies for GlaxoSmithKline and MSD, and as a consultant in GlaxoSmithKline advisory boards.

Antonio Iofrío de Arce has collaborated in educational activities funded by AstraZeneca and GlaxoSmithKline, MSD and Pfizer, and as a consultant in GlaxoSmithKline and Pfizer advisory boards. He has received financial support from GlaxoSmithKline, MSD and Pfizer to attend domestic educational activities.

Marisa Luisa Navarro Gómez has collaborated in educational activities funded by Gilead, GlaxoSmithKline, Janssen, MSD, Pfizer and ViiV, as a consultant in Abbott, AstraZeneca, Novartis and ViiV advisory boards and in clinical trials funded by GlaxoSmithKline, Pfizer, Roche and Sanofi.

Valentín Pineda Solas has received funding from MSD, Pfizer and Sanofi to attend domestic and international educational activities, has collaborated in educational activities funded by AstraZeneca, GlaxoSmithKline, MSD, Pfizer and Sanofi, and as a consultant in GlaxoSmithKline, Pfizer and Sanofi advisory boards.

Irene Rivero Calle has collaborated in educational activities funded by GlaxoSmithKline, MSD, Pfizer and Sanofi, as a researcher in vaccine clinical trials for Abbott, AstraZeneca, Enanta, Gilead, GlaxoSmithKline, HIPRA, Janssen, Medimmune, Merck, Moderna, MSD, Novavax, Pfizer, Reviral, Roche, Sanofi and Seqirus, and as a consultant in GlaxoSmithKline, MSD, Pfizer and Sanofi advisory boards.

Jesús Ruiz-Contreras has collaborated in educational activities funded by GlaxoSmithKline, MSD, Pfizer and Sanofi, and as a researcher in clinical trials for GlaxoSmithKline and Pfizer.

Ignacio Salamanca de la Cueva has collaborated in educational activities funded by GlaxoSmithKline, MSD, Moderna, Novavax, Pfizer, Sanofi Pasteur and Seqirus, as a researcher in vaccine clinical trials for Ablynx, Abbott, Almirall, Allergan, AstraZeneca, Biomedal, GlaxoSmithKline, Janssen, Lilly, Medimmune, Merck, MSD, Moderna, Nestlé, Novavax, Novartis, Nutricia, Pfizer, Roche, Regeneron, Sanofi Pasteur, Seqirus and Wyeth, and as a consultant in AstraZeneca, GSK, MSD, Moderna, Novavax, Pfizer and Sanofi Pasteur advisory boards.

Pepe Serrano Marchuet has collaborated in educational activities funded by AstraZeneca, GlaxoSmithKline and MSD, as a researcher in clinical trials for Sanofi, and as a consultant in GlaxoSmithKline and Sanofi advisory boards. He has received funding from GlaxoSmithKline, MSD and Pfizer to attend domestic and international educational activities. He has also received grants with the support of GlaxoSmithKline.