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Effectiveness of seasonal influenza vaccination in community-dwelling elderly people: an individual participant data meta-analysis of test-negative design case-control studies.
Lancet Respir Med. 2017 03; 5(3):200-211.LR

Abstract

BACKGROUND

Several aggregate data meta-analyses have provided estimates of the effectiveness of influenza vaccination in community-dwelling elderly people. However, these studies ignored the effects of patient-level confounders such as sex, age, and chronic diseases that could bias effectiveness estimates. We aimed to assess the confounder-adjusted effectiveness of influenza vaccines on laboratory-confirmed influenza among elderly people by conducting a global individual participant data meta-analysis.

METHODS

In this individual participant data meta-analysis, we considered studies included in a previously conducted aggregate data meta-analysis that included test-negative design case-control studies published up to July 13, 2014. We contacted all authors of the included studies on Dec 1, 2014, to request individual participant data. Patients were excluded if their unique identifier was missing, their vaccination status was unknown, their outcome status was unknown, or they had had suspected influenza infection more than once in the same influenza season. Cases were patients with influenza-like illness symptoms who tested positive for at least one of A H1N1, A H1N1 pdm09, A H3N2, or B viruses; controls were patients with influenza-like illness symptoms who tested negative for these virus types or subtypes. Influenza vaccine effectiveness against overall and subtype-specific laboratory-confirmed influenza were the primary and secondary outcomes. We used a generalised linear mixed model to calculate adjusted vaccine effectiveness according to vaccine match to the circulating strains of influenza virus and intensity of the virus activity (epidemic or non-epidemic). Vaccine effectiveness was defined as the relative reduction in risk of laboratory-confirmed influenza in vaccinated patients compared with unvaccinated patients. We did subgroup analyses to estimate vaccine effectiveness according to hemisphere, age category, and health status.

FINDINGS

We received 23 of the 53 datasets included in the aggregate data meta-analysis. Furthermore, six additional datasets were provided by data collaborators, which resulted in individual participant data for a total of 5210 participants. A total of 4975 patients had the required data for analysis. Of these, 3146 (63%) were controls and 1829 (37%) were cases. Influenza vaccination was significantly effective during epidemic seasons irrespective of vaccine match status (matched adjusted vaccine effectiveness 44·38%, 95% CI 22·63-60·01; mismatched adjusted vaccine effectiveness 20·00%, 95% CI 3·46-33·68; analyses in the imputed dataset). Seasonal influenza vaccination did not show significant effectiveness during non-epidemic seasons. We found substantial variation in vaccine effectiveness across virus types and subtypes, with the highest estimate for A H1N1 pdm09 (53·19%, 10·25-75·58) and the lowest estimate for B virus types (-1·52%, -39·58 to 26·16). Although we observed no significant differences between subgroups in each category (hemisphere, age, and health status), influenza vaccination showed a protective effect among elderly people with cardiovascular disease, lung disease, or aged 75 years and younger.

INTERPRETATION

Influenza vaccination is moderately effective against laboratory-confirmed influenza in elderly people during epidemic seasons. More research is needed to investigate factors affecting vaccine protection (eg, brand-specific or type-specific vaccine effectiveness and repeated annual vaccination) in elderly people.

FUNDING

University Medical Center Groningen.

Authors+Show Affiliations

Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; Unit of Pharmacoepidemiology & Pharmacoeconomics (PE2), Department of Pharmacy, University of Groningen, Groningen, Netherlands; British Columbia Centre for Disease Control, Vancouver, BC, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada. Electronic address: maryam.darvishian@bccdc.ca.Eindhoven University of Technology, Eindhoven, Netherlands.Institute of Environmental Science and Research, Wallaceville, New Zealand.Instituto de Salud Pública, Navarra Institute for Health Research (IdiSNA), Pamplona, Spain; CIBER Epidemiología y Salud Pública, Spain.Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.Unit for Vaccination Programs, Department of Monitoring and Evaluation, Public Health Agency of Sweden, Solna, Sweden.Lithuanian University of Health Sciences, Kaunas, Lithuania.Taiwan Centers for Disease Control, Taipei, Taiwan.Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.Instituto de Salud Pública, Navarra Institute for Health Research (IdiSNA), Pamplona, Spain; CIBER Epidemiología y Salud Pública, Spain.National Institute for Communicable Diseases of the National Health Laboratory Services, Johannesburg, South Africa.Division of Public Health Surveillance and Response, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Japan.Department of General Practice and Primary Care, University of Auckland, New Zealand.Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; Unit of Pharmacoepidemiology & Pharmacoeconomics (PE2), Department of Pharmacy, University of Groningen, Groningen, Netherlands.

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28189522

Citation

Darvishian, Maryam, et al. "Effectiveness of Seasonal Influenza Vaccination in Community-dwelling Elderly People: an Individual Participant Data Meta-analysis of Test-negative Design Case-control Studies." The Lancet. Respiratory Medicine, vol. 5, no. 3, 2017, pp. 200-211.
Darvishian M, van den Heuvel ER, Bissielo A, et al. Effectiveness of seasonal influenza vaccination in community-dwelling elderly people: an individual participant data meta-analysis of test-negative design case-control studies. Lancet Respir Med. 2017;5(3):200-211.
Darvishian, M., van den Heuvel, E. R., Bissielo, A., Castilla, J., Cohen, C., Englund, H., Gefenaite, G., Huang, W. T., la Bastide-van Gemert, S., Martinez-Baz, I., McAnerney, J. M., Ntshoe, G. M., Suzuki, M., Turner, N., & Hak, E. (2017). Effectiveness of seasonal influenza vaccination in community-dwelling elderly people: an individual participant data meta-analysis of test-negative design case-control studies. The Lancet. Respiratory Medicine, 5(3), 200-211. https://doi.org/10.1016/S2213-2600(17)30043-7
Darvishian M, et al. Effectiveness of Seasonal Influenza Vaccination in Community-dwelling Elderly People: an Individual Participant Data Meta-analysis of Test-negative Design Case-control Studies. Lancet Respir Med. 2017;5(3):200-211. PubMed PMID: 28189522.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effectiveness of seasonal influenza vaccination in community-dwelling elderly people: an individual participant data meta-analysis of test-negative design case-control studies. AU - Darvishian,Maryam, AU - van den Heuvel,Edwin R, AU - Bissielo,Ange, AU - Castilla,Jesus, AU - Cohen,Cheryl, AU - Englund,Helene, AU - Gefenaite,Giedre, AU - Huang,Wan-Ting, AU - la Bastide-van Gemert,Sacha, AU - Martinez-Baz,Iván, AU - McAnerney,Johanna M, AU - Ntshoe,Genevie M, AU - Suzuki,Motoi, AU - Turner,Nikki, AU - Hak,Eelko, Y1 - 2017/02/09/ PY - 2016/09/19/received PY - 2016/11/21/revised PY - 2016/11/29/accepted PY - 2017/2/13/pubmed PY - 2017/12/8/medline PY - 2017/2/13/entrez SP - 200 EP - 211 JF - The Lancet. Respiratory medicine JO - Lancet Respir Med VL - 5 IS - 3 N2 - BACKGROUND: Several aggregate data meta-analyses have provided estimates of the effectiveness of influenza vaccination in community-dwelling elderly people. However, these studies ignored the effects of patient-level confounders such as sex, age, and chronic diseases that could bias effectiveness estimates. We aimed to assess the confounder-adjusted effectiveness of influenza vaccines on laboratory-confirmed influenza among elderly people by conducting a global individual participant data meta-analysis. METHODS: In this individual participant data meta-analysis, we considered studies included in a previously conducted aggregate data meta-analysis that included test-negative design case-control studies published up to July 13, 2014. We contacted all authors of the included studies on Dec 1, 2014, to request individual participant data. Patients were excluded if their unique identifier was missing, their vaccination status was unknown, their outcome status was unknown, or they had had suspected influenza infection more than once in the same influenza season. Cases were patients with influenza-like illness symptoms who tested positive for at least one of A H1N1, A H1N1 pdm09, A H3N2, or B viruses; controls were patients with influenza-like illness symptoms who tested negative for these virus types or subtypes. Influenza vaccine effectiveness against overall and subtype-specific laboratory-confirmed influenza were the primary and secondary outcomes. We used a generalised linear mixed model to calculate adjusted vaccine effectiveness according to vaccine match to the circulating strains of influenza virus and intensity of the virus activity (epidemic or non-epidemic). Vaccine effectiveness was defined as the relative reduction in risk of laboratory-confirmed influenza in vaccinated patients compared with unvaccinated patients. We did subgroup analyses to estimate vaccine effectiveness according to hemisphere, age category, and health status. FINDINGS: We received 23 of the 53 datasets included in the aggregate data meta-analysis. Furthermore, six additional datasets were provided by data collaborators, which resulted in individual participant data for a total of 5210 participants. A total of 4975 patients had the required data for analysis. Of these, 3146 (63%) were controls and 1829 (37%) were cases. Influenza vaccination was significantly effective during epidemic seasons irrespective of vaccine match status (matched adjusted vaccine effectiveness 44·38%, 95% CI 22·63-60·01; mismatched adjusted vaccine effectiveness 20·00%, 95% CI 3·46-33·68; analyses in the imputed dataset). Seasonal influenza vaccination did not show significant effectiveness during non-epidemic seasons. We found substantial variation in vaccine effectiveness across virus types and subtypes, with the highest estimate for A H1N1 pdm09 (53·19%, 10·25-75·58) and the lowest estimate for B virus types (-1·52%, -39·58 to 26·16). Although we observed no significant differences between subgroups in each category (hemisphere, age, and health status), influenza vaccination showed a protective effect among elderly people with cardiovascular disease, lung disease, or aged 75 years and younger. INTERPRETATION: Influenza vaccination is moderately effective against laboratory-confirmed influenza in elderly people during epidemic seasons. More research is needed to investigate factors affecting vaccine protection (eg, brand-specific or type-specific vaccine effectiveness and repeated annual vaccination) in elderly people. FUNDING: University Medical Center Groningen. SN - 2213-2619 UR - https://www.unboundmedicine.com/medline/citation/28189522/Effectiveness_of_seasonal_influenza_vaccination_in_community_dwelling_elderly_people:_an_individual_participant_data_meta_analysis_of_test_negative_design_case_control_studies_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-2600(17)30043-7 DB - PRIME DP - Unbound Medicine ER -