Iván Martínez-Baz

Influenza Vaccine Effectiveness in Preventing Outpatient, Inpatient, and Severe Cases of Laboratory-Confirmed Influenza

BACKGROUND In most seasons, the influenza vaccine is effective in preventing influenza, but it is not clear whether it is equally effective in preventing mild and severe cases. We designed a case-control study to compare the effectiveness of the influenza vaccine in preventing outpatient, inpatient, and severe or fatal cases of laboratory-confirmed influenza. METHODS Hospitalized patients (n = 691) with laboratory-confirmed influenza in the 2010-2011 season recruited in 29 Spanish hospitals were individually matched by age, admission/visit date, and province with an outpatient with laboratory-confirmed influenza and an outpatient control. Severe cases were considered those patients admitted to intensive care units or who died in the hospital (n = 177). We compared the influenza vaccine status of controls and outpatient cases, inpatient cases, and severe cases using conditional logistic regression adjusted for potential confounding factors. Severe and nonsevere inpatient influenza cases were compared using unconditional logistic regression. Vaccine effectiveness was (1 - odds ratio) × 100. RESULTS Vaccine effectiveness was 75% (adjusted odds ratio [AOR], 0.25; 95% confidence interval [CI], .16-.39) in preventing influenza outpatient cases, 60% (AOR, 0.40; 95% CI, .25-.63) in preventing influenza-associated hospitalizations, and 89% (AOR, 0.11; 95% CI, .04-.37) in preventing severe cases. In inpatients, influenza vaccination was associated with a lower risk of severe influenza (AOR, 0.42; 95% CI, .22-.80). CONCLUSIONS Influenza vaccination prevented influenza cases and hospitalizations and was associated with a better prognosis in inpatients with influenza. The combined effect of these 2 mechanisms would explain the high effectiveness of the vaccine in preventing severe cases due to influenza.

Vaccine effectiveness in preventing influenza hospitalizations in Navarre, Spain, 2010-2011: cohort and case-control study.

We evaluated the 2010-2011 seasonal influenza vaccine effectiveness in preventing hospitalizations. Using healthcare databases we defined the target population for vaccination in Navarre, Spain, consisting of 217,320 people with major chronic conditions or aged 60 years and older. All hospitalized patients with influenza-like illness (ILI) were swabbed for influenza testing. A total of 269 patients with ILI were hospitalized and 61 of them were found positive for influenza virus: 58 for A(H1N1)2009 and 3 for B virus. The incidence rates of hospitalization with laboratory-confirmed influenza were compared by vaccination status. In the Cox regression model adjusted for sex, age, children in the household, urban/rural residence, comorbidity, pandemic vaccination, pneumococcal vaccination, outpatient visits and hospitalization in the previous year, the seasonal vaccine effectiveness was 58% (95% CI: 16-79%). The nested test-negative case-control analysis gave an adjusted estimate of 59% (95% CI: 4-83%). These results suggest a moderate effect of the 2010-2011 seasonal influenza vaccine in preventing hospitalization in a risk population. The close estimates obtained in the cohort and the test-negative case-control analyses suggest good control of biases.

Impact of universal two-dose vaccination on varicella epidemiology in Navarre, Spain, 2006 to 2012

In 2007 in Navarre, Spain, universal varicella vaccination with two doses of Varivax was introduced in the childhood immunisation schedule for children aged 15 months and three years. This study describes changes in the epidemiology of varicella in the period 2006 to 2012 and evaluates vaccination effectiveness using epidemiological surveillance data. The incidence of varicella in children aged 0 to 14 years decreased by 98.1%, from 50.1 cases per 1,000 inhabitants in 2006, to 1.0 per 1,000 in 2012. Children aged one to eight years were the vaccinated cohorts, and their incidence of varicella decreased by 98.5% (p<0.0001). In unvaccinated age groups, important reductions were also achieved between 2006 and 2012: 90.5% (p<0.0001) in infants under one year of age, and 89.4% (p<0.0001) in children aged nine years. In the period 2006 to 2012, the hospital admissions rate for varicella or its complications decreased by 89.0%, and in 2012, there was only one admission of a newborn with neonatal varicella. Vaccine effectiveness for at least one dose was 96.8% (95% confidence interval: 96.3-97.2%). Universal vaccination with two doses has reduced varicella circulation to minimum levels within five years and has proved highly effective.

Effectiveness of the trivalent influenza vaccine in Navarre, Spain, 2010-2011: a population-based test-negative case-control study.

BackgroundSome studies have evaluated vaccine effectiveness in preventing outpatient influenza while others have analysed its effectiveness in preventing hospitalizations. This study evaluates the effectiveness of the trivalent influenza vaccine in preventing outpatient illness and hospitalizations from laboratory-confirmed influenza in the 2010–2011 season.MethodsWe conducted a nested case–control study in the population covered by the general practitioner sentinel network for influenza surveillance in Navarre, Spain. Patients with influenza-like illness in hospitals and primary health care were swabbed for influenza testing. Influenza vaccination status and other covariates were obtained from health care databases. Using logistic regression, the vaccination status of laboratory-confirmed influenza cases was compared with that of test-negative controls, adjusting for age, sex, comorbidity, outpatient visits in the previous 12 months, health care setting, time between symptom onset and swabbing, period and A(H1N1)pdm09 vaccination. Effectiveness was calculated as (1-odds ratio)x100.ResultsThe 303 confirmed influenza cases (88% for A(H1N1)pdm09 influenza) were compared with the 286 influenza test-negative controls. The percentage of persons vaccinated against influenza was 4.3% and 15.7%, respectively (p<0.001). The adjusted estimate of effectiveness was 67% (95% CI: 24%, 86%) for all patients and 64% (95% CI: 8%, 86%) in those with an indication for vaccination (persons age 60 or older or with major chronic conditions). Having received both the 2010–2011 seasonal influenza vaccine and the 2009–2010 pandemic influenza vaccine provided 87% protection (95% CI: 30%, 98%) as compared to those not vaccinated.ConclusionThe 2010–2011 seasonal influenza vaccine had a moderate protective effect in preventing laboratory-confirmed influenza.

Factors associated with continued adherence to influenza vaccination in the elderly.

OBJECTIVE We aimed to analyze the factors influencing continued adherence to influenza vaccination in elderly persons vaccinated in the preceding season. METHODS Using a population-based vaccination registry, we evaluated the proportion of persons vaccinated against influenza in Navarre, Spain, in the 2010-11 season among non-institutionalized persons aged 65 years or over who had been vaccinated in the 2009-10 season. Logistic regression was used to analyze the influence of sociodemographic, clinical and health care factors. RESULTS Of the 64,245 persons vaccinated against influenza in the 2009-10 season, 87% were vaccinated in the 2010-11 season. Continued adherence to vaccination increased with the number of physician visits per year. It was lower in women, in the 65-69 and ≥ 95 year age-groups, in those hospitalized or diagnosed with any major chronic condition in the previous year, and in persons with hematological cancer or dementia. Health districts and physicians with higher coverage in the previous season continued to have higher adherence in the following season. CONCLUSIONS People vaccinated against influenza in one season tend to be vaccinated in the following one. Sociodemographic, clinical and health care factors have a moderate effect on the continuity of vaccination, with the most important factor being the treating physician.

Vaccine effectiveness in preventing laboratory-confirmed influenza in Navarre, Spain: 2013/14 mid-season analysis.

We estimate mid-2013/14 season vaccine effectiveness (VE) of the influenza trivalent vaccine in Navarre, Spain. Influenza-like illness cases attended in hospital (n=431) and primary healthcare (n=344) were included. The overall adjusted VE in preventing laboratory-confirmed influenza was 24% (95% CI: -14 to 50). The VE was 40% (95% CI: -12 to 68) against influenza A(H1)pdm09 and 13% (95% CI: -36 to 45) against influenza A(H3). These results suggest a moderate preventive effect against influenza A(H1)pdm09 and low protection against influenza A(H3).

Trends in influenza vaccine coverage among primary healthcare workers in Spain, 2008-2011.

OBJECTIVE To evaluate trends in seasonal influenza vaccination coverage in primary healthcare workers (PHCWs) in Spain between 2008 and 2011. METHODS We made an anonymous web survey of PHCWs in 2012. Information on attitudes towards and knowledge of influenza vaccine, and immunization in previous seasons was collected. Self-reported vaccination coverage and factors related to vaccination continuity were analysed. RESULTS Of 5433 workers contacted, 2625 (48.3%) responded to the survey: 47.0% were general practitioners, 10.3% paediatricians and 42.7% nurses. Their reported vaccination rates from seasons 2008-2009 to 2011-2012 decreased over time: 58.4%, 57.4%, 53.2% and 49.3% (linear trend, p < 0.001). Among workers vaccinated in any previous season, 70.2% were vaccinated again in 2011-2012, compared with 5.2% among those not previously vaccinated (p < 0.001). Continuity of vaccination increased with age and with the worker or cohabitant having a major chronic condition. Vaccination was higher in workers who recognized vaccination as effective and those worried about being infected or infecting patients. CONCLUSION Influenza vaccination coverage in PHCWs has declined, especially after the pandemic. Intensive interventions are needed to change this trend. Knowledge of vaccination should be reinforced by stressing the effectiveness of the vaccine and the risks of influenza for workers and patients.

Effectiveness of seasonal influenza vaccination in community-dwelling elderly people: an individual participant data meta-analysis of test-negative design case-control studies

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.

Effectiveness of subunit influenza vaccination in the 2014-2015 season and residual effect of split vaccination in previous seasons.

BACKGROUND In Navarra, Spain, subunit vaccine was first used in the 2014-2015 season, whereas trivalent split-virion influenza vaccines had been used in previous seasons. We estimate the effectiveness of the subunit vaccine in the current season and split vaccine in the two previous seasons against laboratory-confirmed influenza in the 2014-2015 season. METHODS Patients with influenza-like illness hospitalized or attended by sentinel general practitioners were swabbed for influenza testing. The previous and current vaccine status of laboratory-confirmed cases was compared to test-negative controls. RESULTS Among 1213 patients tested, 619 (51%) were confirmed for influenza virus: 52% influenza A(H3N2), 46% influenza B, and 2% A(H1N1)pdm09. The overall effectiveness for subunit vaccination in the current season was 19% (95% confidence interval [CI]: -13 to 42), 2% (95%CI: -47 to 35) against influenza A(H3N2) and 32% (95%CI: -4 to 56) against influenza B. The effectiveness against any influenza was 67% (95%CI: 17-87) for 2012-2013 and 2013-2014 vaccination only, 42% (95%CI: -31 to 74) for 2014-2015 vaccination only, and 38% (95%CI: 8-58) for vaccination in the 2012-2013, 2013-2014 and 2014-2015 seasons. The same estimates against influenza A(H3N2) were 47% (95%CI: -60 to 82), -54% (95%CI: -274 to 37) and 28% (95%CI: -17 to 56), and against influenza B were 82% (95%CI: 19-96), 93% (95%CI: 45-99) and 43% (95%CI: 5-66), respectively. CONCLUSION These results suggest a considerable residual protection of split vaccination in previous seasons, low overall effectiveness of current season subunit vaccination, and possible interference between current subunit and previous split vaccines.

Effect of Repeated Vaccination With the Same Vaccine Component Against 2009 Pandemic Influenza A(H1N1) Virus

Background The 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) vaccine component has remained unchanged from 2009. We estimate the effectiveness of current and prior inactivated influenza A(H1N1)pdm09 vaccination from influenza seasons 2010-2011 to 2015-2016. Methods Patients attended with influenza-like illness were tested for influenza. Four periods with continued A(H1N1)pdm09 circulation were included in a test-negative design. Results We enrolled 1278 cases and 2343 controls. As compared to individuals never vaccinated against influenza A(H1N1)pdm09, the highest effectiveness (66%; 95% confidence interval, 49%-78%) was observed in those vaccinated in the current season who had received 1-2 prior doses. The effectiveness was not statistically lower in individuals vaccinated in the current season only (52%) or in those without current vaccination and >2 prior doses (47%). However, the protection was lower in individuals vaccinated in the current season after >2 prior doses (38%; P = .009) or those currently unvaccinated with 1-2 prior doses (10%; P < .001). Current-season vaccination improved the effect in individuals with 1-2 prior doses and did not modify significantly the risk of influenza in individuals with >2 prior doses. Conclusion Current vaccination or several prior doses were needed for high protection. Despite the decreasing effect of repeated vaccination, current-season vaccination was not inferior to no current-season vaccination.