Effectiveness of the 2023 Southern Hemisphere Influenza Vaccine against Outpatient Influenza-Like Illness: A Multi-Country Test-Negative Design Study

Background Routine monitoring of seasonal influenza vaccine effectiveness (VE) across multiple countries is essential to understand the performance of seasonal vaccine programs. Methods Using a test-negative study design, we estimated the effectiveness of the 2023 Southern Hemisphere formulation of the seasonal influenza vaccine in preventing outpatient medically attended influenza-like illness (ILI) in Australia, South Africa, and Thailand. Sentinel surveillance systems identified patients presenting with ILI who were tested by RT-PCR for influenza. VE was estimated as one minus the odds ratio comparing the vaccination status of test-positive cases and test-negative non-cases. Models adjusted for country, patients’ age group, sex, underlying medical conditions, and calendar week of symptom onset. We assessed duration of protection by modeling the effect of the interval between vaccination and symptom onset on influenza status. Results 2,469 ILI outpatients were identified, including 966 (39%) test-positive cases and 1,503 (61%) test-negative non-cases; 78% (n=750/966) of viruses detected were influenza A; 8% (n=72/966) of test-positive cases and 29% (n=439/1,503) of test-negative non-cases had received an influenza vaccine. Pooled VE was 68% (95%CI: 57%, 76%) against ILI with any influenza virus, 62% (95%CI: 39%, 76%) against influenza A(H1N1)pdm09, 60% (95%CI: 38%, 75%) against influenza A(H3N2), and 76% (95%CI: 59%, 86%) against influenza B. VE point estimates declined from 82% to 43% when the time from vaccination increased from 14 days to 150 days. Conclusions The 2023 Southern Hemisphere formulation of seasonal influenza vaccines offered protection against ILI in three countries, underscoring the public health benefits of seasonal influenza vaccination programs.