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

Annette K Regan; Radhika Gharpure; Monique Chilver; Nigel Stocks; Siobhan St George; Sibongile Walaza; Anne von Gottberg; Nicole Wolter; Cheryl Cohen; Aaron M Samuels; Kriengkrai Prasert; Prabda Praphasiri; William W Davis; Chakrarat Pittayawonganon; Sheena G Sullivan; Eduardo Azziz-Baumgartner

doi:10.1093/ofid/ofaf560

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

Open Forum Infect Dis. 2025 Sep 17;12(10):ofaf560. doi: 10.1093/ofid/ofaf560. eCollection 2025 Oct.

Authors

Annette K Regan^{1

2

3}, Radhika Gharpure⁴, Monique Chilver⁵, Nigel Stocks⁵, Siobhan St George⁶, Sibongile Walaza^{7

8}, Anne von Gottberg^{7

9}, Nicole Wolter^{7

9}, Cheryl Cohen^{7

8}, Aaron M Samuels^{4

10}, Kriengkrai Prasert^{11

12}, Prabda Praphasiri^{12

13}, William W Davis¹³, Chakrarat Pittayawonganon¹⁴, Sheena G Sullivan^{2

5

15}, Eduardo Azziz-Baumgartner⁴

Affiliations

¹ Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, California, USA.
² Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, California, USA.
³ School of Nursing and Health Professions, University of San Francisco, San Francisco, California, USA.
⁴ Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
⁵ The Discipline of General Practice, The University of Adelaide, Adelaide, South Australia, Australia.
⁶ Public Health and Surveillance Branch, Interim Australian Centre for Disease Control, Australian Government Department of Health, Disability and Ageing, Canberra, Australian Capital Territory, Australia.
⁷ Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
⁸ School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁹ School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
¹⁰ Influenza Program, Centers for Disease Control and Prevention, Pretoria, South Africa.
¹¹ Nakhon Phanom Provincial Hospital, Nai Mueang, Mueang Nakhon Phanom District, Nakhon Phanom, Thailand.
¹² Faculty of Public Health, Kasetsart University, Chalermprakiat Sakon Nakhon Province Campus, Mueang Sakon Nakhon District, Sakon Nakhon, Thailand.
¹³ Influenza Program, Thailand Ministry of Public Health-U.S. Centers for Disease Control and Prevention Collaboration, Muang, Nonthaburi, Thailand.
¹⁴ Institute of Preventive Medicine, Department of Disease Control, Ministry of Public Health, Muang, Nonthaburi, Thailand.
¹⁵ School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia.

Abstract

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 the duration of protection by modeling the effect of the interval between vaccination and symptom onset on influenza status.

Results: About 2469 ILI outpatients were identified, including 966 (39%) test-positive cases and 1503 (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 = 439/1503) 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.

Keywords: influenza vaccine; pooled analysis; surveillance; test-negative design; vaccine effectiveness.