The Temporal Trend of Influenza-Associated Morbidity and the Impact of Early Appearance of Antigenic Drifted Strains in a Southeast Asian Country

Abstract

Globally, influenza infection is a major cause of morbidity and mortality in the elderly, who are suggested to be the major target group for trivalent influenza vaccine (TIV) vaccination by World Health Organization. In spite of an increasing trend in vaccine coverage rates in many countries, the effect of vaccination among the elderly in reducing hospitalization and mortality remains controversial. In this study, we conducted a historical cohort study to evaluate the temporal pattern of influenza-associated morbidity among persons older than 64 years over a decade. The temporal patterns of influenza-associated morbidity rates among the elderly older than 64 years indicated that Taiwan's elderly P&I outpatient visits have been decreasing since the beginning of the 1999–2000 influenza season; however, hospitalization has been increasing despite significant increases in vaccine coverage. The propensity score logistic regression model was implemented to evaluate the source of bias and it was found that the TIV-receiving group had a higher propensity score than the non-receiving group (P<0.0001). In order to investigate the major factors affecting the temporal pattern of influenza-associated morbidity, we then used the propensity score as a summary confounder in a multivariate Poisson regression model based on the trimmed data. Our final models suggested that the factors affected the temporal pattern of morbidity differently. The variables including co-morbidity, vaccination rate, influenza virus type A and B isolation rate were associated with increased outpatient visits and hospitalization (p<0.05). In contrast, variables including high propensity score, increased 1°C in temperature, matching vaccine strains of type A/H1N1 and type B were associated with decreased outpatient visits and hospitalization (p<0.05). Finally, we assessed the impact of early appearance of antigenic-drifted strains and concluded that an excess influenza-associated morbidity substantial trends toward higher P&I hospitalization, but not outpatient visits, during the influenza season with early appearance of antigenic-drifted strains.

<p>A Population-Based Propensity Score-Matched Study to Assess the Impact of Repeated Vaccination on Vaccine Effectiveness for Influenza-Associated Hospitalization Among the Elderly</p>

“…Our previous study suggested that the TIV-receiving group had a higher propensity score of being vaccinated than the non-receiving group. 11 To assess the true effect of revaccination on the influenza-associated hospitalization with minimum interference from unmeasured confounding factors, we then performed propensity score matching on both vaccination and non-vaccination groups. A total of 38,815 and 40,934 subjects were selected in the propensity score-matched non-vaccination groups in the 2007 and 2008 influenza seasons, respectively.…”

“…To cope with a large number of potential confounders, we performed matching to create comparable cohorts with or without trivalent influenza vaccine (TIV) vaccination in the current influenza season based on individual propensity score obtained from the propensity score logistic regression model, as described previously. 11 In brief, potential confounding variables incorporated in the model included both demographic and clinical confounders. The demographicconfounders included age, gender, geographic region of residence, urbanization level of residenceand individual socioeconomic status.…”

“…For each year, we acquired the records of those aged 65 or older from the NHIRD, and the process was repeated by year from 1999 to 2012, as previously described. 11 Instead of using calendar year, annual influenza year was marked as the period beginning on 1 September and concluding on 31 August of the following year. Since the FIVP requires that all the elderly older than 64 years use an insurance card to receive vaccination, vaccination rate data among the elderly were obtained from three different codings of outpatient visit prescriptions from the complete NHI claims database in Taiwan during the period 1999-2012.…”

“…The results are consistent with the vaccination rate data compiled from local health bureaus by Centers for Disease Control, Taiwan (Taiwan-CDC) without subject selection bias, as previously described. 11 All personal identification numbers in the NHIRD were encrypted as scrambled numbers before data processing, for confidentiality and compliance with regulations on personal privacy in Taiwan.…”

“…9,10 Therefore, an excess influenza-associated morbidity, with a substantial trend toward higher rates of hospitalization due to pneumonia and influenza (P&I), was reported during the influenza season with early appearance of antigenically drifted strains. 11 Although repeated immunization has been advised to ensure compliance with the antigenic drift of the viruses and the decrease in antibody level with time, 12,13 several studies have suggested that VE may be influenced by prior season vaccination, owing to the observation of impaired vaccine seroresponse to influenza HA antigens among repeated vaccine recipients. [14][15][16][17][18][19] Field vaccination efficacy trial studies are difficult to perform because of the poor predictability of influenza outbreaks, and require large numbers of participants to observe significant reductions in mortality or severe morbidity.…”