The potential effect of temporary immunity as a result of bias associated with healthy users and social determinants on observations of influenza vaccine effectiveness; could unmeasured confounding explain observed links between seasonal influenza vaccine and pandemic H1N1 infection?

BMC Public Health

Laura C Rosella¹  Natasha S Crowcroft² 

[1] Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada;Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

关键词: Epidemiology;    Confounding;    Influenza vaccination;    Influenza;   

Others  :  1163517
DOI  :  10.1186/1471-2458-12-458

 received in 2012-01-14, accepted in 2012-06-15,  发布年份 2012

【 摘 要 】

Background

Five observational studies from Canada found an association between seasonal influenza vaccine receipt and increased risk of pandemic influenza H1N1 2009 infection. This association remains unexplained. Although uncontrolled confounding has been suggested as a possible explanation, the nature of such confounding has not been identified. Observational studies of influenza vaccination can be affected by confounding due to healthy users and the influence of social determinants on health. The purpose of this study was to investigate the influence that these two potential confounders may have in combination with temporary immunity, using stratified tables. The hypothesis is that respiratory virus infections may activate a temporary immunity that provides short-term non-specific protection against influenza and that the relationship with being a healthy user or having a social determinant may result in confounding.

Methods

We simulated the effect of confounding on vaccine effectiveness assuming that this could result from both social determinants and healthy user effects as they both influence the risk of seasonal influenza and non-influenza respiratory virus infections as well as the likelihood of being vaccinated. We then examined what impact this may have had on measurement of seasonal influenza vaccine effectiveness against pandemic influenza.

Results

In this simulation, failure to adjust for healthy users and social determinants would result in an erroneously increased risk of pandemic influenza infection associated with seasonal influenza vaccination. The effect sizes were not however large.

Conclusions

We found that unmeasured healthy user effects and social determinants could result in an apparent association between seasonal influenza vaccine and pandemic influenza infection by virtue of being related to temporary immunity. Adjustment for social determinants of health and the healthy user effects are required in order to improve the quality of observational studies of influenza vaccine effectiveness.

【 授权许可】

   
2012 Crowcroft and Rosella; licensee BioMed Central Ltd.

【 图 表 】

Figure 1 .

Figure 2 .

【 参考文献 】

• [1]Skowronski DM, De Serres G, Crowcroft NS, Janjua NZ, Boulianne N, Hottes TS, et al.: Association between the 2008-09 seasonal influenza vaccine and pandemic H1N1 illness during Spring-Summer 2009: four observational studies from Canada. PLoS Med 2010, 7(4):e1000258.
• [2]Janjua NZ, Skowronski DM, Hottes TS, et al.: Seasonal Influenza Vaccine and Increased Risk of Pandemic A/H1N1-Related Illness: First Detection of the Association in British Columbia, Canada. Clin Infect Dis 2010, 51(9):1017-1027.
• [3]Baxter R, Lee J, Fireman B: Evidence of Bias in Studies of Influenza Vaccine Effectiveness in Elderly Patients. J Infect Dis 2010, 201(2):186-189.
• [4]Hak E, Verheij TJM, Grobbee DE, Nichol KL, Hoes AW: Confounding by indication in non-experimental evaluation of vaccine effectiveness: the example of prevention of influenza complications. J Epidemiol Community Health 2002, 56(12):951-955.
• [5]Rosella LC, Groenwold RHH, Crowcroft NS: Assessing the impact of confounding (measured and unmeasured) in a case control study to examine the increased risk of pandemic A/H1N1 associated with receipt of the 2008-9 seasonal influenza vaccine. Vaccine
• [6]Kelly H, Barry S, Laurie K, Mercer G: Seasonal influenza vaccination and the risk of infection with pandemic influenza: a possible illustration of non-specific temporary immunity following infection. Euro Surveill 2010., 15(47) pii: 19722
• [7]Skowronski DM, Janjua NZ, De Serres G, Hottes TS, Dickinson JA, Crowcroft N, Kwindt TL, Tang P, Charest H, Fonseca K, Gubbay JB, Bastien N, Li Y, Petric M: Effectiveness of AS03 adjuvanted pandemic H1N1 vaccine: case-control evaluation based on sentinel surveillance system in Canada, autumn 2009. BMJ 2011, 342:c7297.
• [8]Damiani G, Federico B, Visca M, Agostini F, Ricciardi W: The impact of socioeconomic level on influenza vaccination among Italian adults and elderly: A cross-sectional study. Prev Med 2007, 45(5):373-379.
• [9]Uddin M, Cherkowski GC, Liu G, Zhang J, Monto AS, Aiello AE: Demographic and socioeconomic determinants of influenza vaccination disparities among university students. J Epidemiol Community Health 2010, 64(9):808-813.
• [10]Pawlinska-Chmara R, Wronka I: Assessment of the effect of socioeconomic factors on the prevalence of respiratory disorders in children. J Physiol Pharmacol 2007, 58:523-529.
• [11]Ontario Health Quality Council press release on Chronic Disease in Ontario: Ontario Health Quality Council press release on Chronic Disease in Ontario. 2011. http://www.ohqc.ca/pdfs/final_press_release_march_26th_english.pdf webcite Accessed 29th September
• [12]Statistics Canada: Table 105-0501 - Health indicator profile, annual estimates, by age group and sex, Canada, provinces, territories, health regions and peer groups, occasional. CANSIM (database) [accessed:September 22, 2011]. 2011. http://www5.statcan.gc.ca/cansim/a01?lang=eng webcite.
• [13]Xing Z, Cardona CJ: Preexisting immunity to pandemic (H1N1) 2009 [letter]. Emerg Infect Dis [serial on the Internet]. 2009. http://wwwnc.cdc.gov/eid/article/15/11/09-0685.htm webcite.
• [14]Fleiss JL: Statistical Methods for rates and proportions. 2nd edition. New York: Wiley; 1981.
• [15]Groenwold RHH, Hoes AW, Nichol KL, Hak E: Quantifying the potential role of unmeasured confounders: the example of influenza vaccination. Int J Epidemiol 2008, 37(6):1422-1429.
• [16]Mercer GN, Barry SI, Kelly H: Modelling the effect of seasonal influenza vaccination on the risk of pandemic influenza infection. BMC Public Health 2011, 11(Suppl 1):S11.
• [17]Steenland K, Greenland S: Monte Carlo sensitivity analysis and Bayesian analysis of smoking as an unmeasured confounder in a study of silica and lung cancer. Am J Epidemiol 2004, 160(4):384-392.