New research shows that flu vaccines provide strong protection for children but underscores the need for improved efficacy against specific subtypes like H3N2.

Rapid communication: Effectiveness of influenza vaccines in children aged 6 to 59 months: a test-negative case–control study at primary care and hospital level, Spain 2023/24. Image Credit: Billion Photos / Shutterstock

A Spanish study investigating the effectiveness of influenza vaccination in children finds that the vaccine is highly effective in preventing influenza infection and related hospitalization.

The study is published in the journal Eurosurveillance.

Background

Global estimates indicate that influenza infections affect 109 million infants aged 0 to 59 months yearly. Both younger and older age groups are highly susceptible to developing severe influenza infections.

In Spain, children under five and older adults aged 65 years or above have the highest rates of influenza-related hospitalization. Regarding virus transmission, evidence indicates that children play a key role in the community circulation of the virus and in the amplification of influenza epidemics.

For the first time at the national level, influenza vaccination has been recommended for all children aged 6 to 59 months during the 2023-2024 season.

In this study, scientists estimated the effectiveness of influenza vaccination against acute respiratory infection in children attending primary care or against severe acute respiratory infections in hospitalized children.

Study Design

The study analyzed data collected from the Surveillance System of Acute Respiratory Infections in Spain (SiVIRA), which monitors acute respiratory infections at the primary care level and severe acute respiratory infections at the hospital level.

This test-negative case-control study analyzed SiVIRA data from 12 regions and 27 hospitals in Spain. Children who tested positive for the influenza virus were regarded as cases, and test-negative children were regarded as controls.

Important Observations

The study population included a total of 244 cases and 1,120 controls in primary care and 48 cases and 254 controls in hospitals.

The influenza vaccination coverage was significantly higher among controls compared to that among cases in primary care.

In both primary care and hospitals, influenza A (H1N1) pdm09 was the dominant subtype, followed by the influenza A (H3N2) subtype. Influenza B had very low circulation, reducing the ability to estimate vaccine effectiveness for this virus.

Effectiveness of Influenza Vaccination

The effectiveness of influenza vaccination was estimated by virus type, subtype, or clade. Potential confounding factors, including sex, age, epidemiological week, presence of chronic conditions, and region or hospital for acute or severe respiratory infections, were adjusted in the analysis.

The effectiveness of influenza vaccination was estimated to be 70% against any influenza infection among children with acute respiratory infections in primary care.

The vaccine efficacy against the influenza A H1N1 pdm09 subtype and the clade 5a.2a was 77% and 96%, respectively. However, no significant protective efficacy was observed against the influenza A H3N2 subtype or other clades, which could be attributed to the limited number of cases and the extremely wide confidence interval (the range of probable values of a given parameter).

The effectiveness of influenza vaccination was estimated to be 77% against any influenza infection among hospitalized children with severe acute respiratory infections.

The study was unable to accurately estimate vaccine efficacy by subtype or clade among hospitalized children because of an insufficient sample size, particularly for H3N2, which led to imprecise estimates.

A sensitivity analysis was conducted including controls positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or respiratory syncytial virus (RSV). This changed the vaccine efficacy to 68% against any influenza infection, 76% against the influenza A H1N1 pdm09 subtype, and 2% against the influenza A H3N2 subtype in primary care.

In hospitals, the vaccine efficacy changed to 76%, 78%, and 19% against any influenza infection, influenza A H1N1 pdm09 subtype, and influenza A H3N2 subtype, respectively.

In this analysis, the low efficacy against H3N2 remained, further emphasizing the challenges in drawing firm conclusions for this subtype due to the small sample size.

Another set of sensitivity analyses was conducted by categorizing unknown vaccination status as unvaccinated. This changed the vaccine efficacy in hospitals to 86% and 76% against any influenza infection and influenza A H1N1 pdm09 subtype, respectively. The vaccine efficacy against influenza A H3N2 subtype became negative (-7%).

This negative result highlights the difficulties in interpreting vaccine effectiveness when dealing with small sample sizes and low circulation of specific subtypes, like H3N2. 

In the second sensitivity analysis, no change in vaccine efficacy was observed in primary care settings.

Study Significance

The study finds that influenza vaccination is highly effective in preventing influenza infection and related hospitalization among children aged 6 to 59 months.

However, the study acknowledges the limitations in the precision of its findings, particularly regarding the influenza A H3N2 subtype and the influenza B virus, which had very low circulation. The study finds a relatively lower vaccine efficacy against the clade 5a.2a.1. Existing evidence indicates that a mutation in the 2023-2024 clade 5a.2a.1 vaccine high-growth reassortant may be responsible for reduced vaccine efficacy.

This mutation has been found to affect only the high-growth reassortant used for egg-based vaccines. This indicates that comparing vaccine efficacy between different vaccine brands against the same clade could provide more information.

Considering the study observations, scientists highlight the need for continuous efforts to increase influenza vaccine coverage in future seasons among children belonging to this age group.