Influenza vaccine protection and contact patterns among outpatients with influenza-like illness during the 2024–2025 season in China: a test-negative case-control study

Background: Continuous monitoring of both influenza vaccine protection and behavioural determinants of infection is important for understanding related risks. Evidence on influenza vaccine effectiveness (VE) in China during the 2024-2025 season, however, remains limited. We aimed to assess influenza VE among healthcare-seeking outpatients with influenza-like illness (ILI) and to examine the contact patterns associated with infection risk. Methods: We enrolled 928 outpatients with ILI from three sentinel hospitals in Ili Kazakh Autonomous Prefecture, China, between December 2024 and March 2025 in a test-negative case-control study. We confirmed influenza infection using reverse transcription-polymerase chain reaction and collected vaccination history and social contact frequency and duration through questionnaires. We estimated VE using logistic regression with covariate adjustment, and otherwise analysed social contact patterns and performed exploratory sequencing of six randomly selected influenza-positive samples. Results: Our full sample comprised 928 participants. We excluded 21 infants younger than 6 months from the VE analysis and included 907 participants, of whom 121 tested positive and 786 tested negative. The overall adjusted VE against medically attended influenza was 42.3% (95% credible interval = 11.1-62.5). In the analysis of social contacts for all 928 participants, test-positive children aged 0-10 years and adults aged 65 years or older reported more frequent and longer social contact than their test-negative counterparts. Exploratory sequencing of six samples suggested no major antigenic mismatch with the vaccine strains, but the very small number of sequenced samples limits the generalisability of this finding. Conclusions: Influenza vaccination provided moderate protection against medically attended influenza, while contact patterns were associated with infection risk among children and older adults. Combined vaccination and behavioural interventions warrant further evaluation, as the observational design of this study and its use of self-reporting data limit causal inference.