Maria E. Sundaram

Influenza Vaccine Effectiveness in the United States During 2012–2013: Variable Protection by Age and Virus Type

Background. During the 2012–2013 influenza season, there was cocirculation of influenza A(H3N2) and 2 influenza B lineage viruses in the United States. Methods. Patients with acute cough illness for ≤7 days were prospectively enrolled and had swab samples obtained at outpatient clinics in 5 states. Influenza vaccination dates were confirmed by medical records. The vaccine effectiveness (VE) was estimated as [100% × (1 − adjusted odds ratio)] for vaccination in cases versus test-negative controls. Results. Influenza was detected in 2307 of 6452 patients (36%); 1292 (56%) had influenza A(H3N2), 582 (25%) had influenza B/Yamagata, and 303 (13%) had influenza B/Victoria. VE was 49% (95% confidence interval [CI], 43%–55%) overall, 39% (95% CI, 29%–47%) against influenza A(H3N2), 66% (95% CI, 58%–73%) against influenza B/Yamagata (vaccine lineage), and 51% (95% CI, 36%–63%) against influenza B/Victoria. VE against influenza A(H3N2) was highest among persons aged 50–64 years (52%; 95% CI, 33%–65%) and persons aged 6 months–8 years (51%; 95% CI, 32%–64%) and lowest among persons aged ≥65 years (11%; 95% CI, −41% to 43%). In younger age groups, there was evidence of residual protection from receipt of the 2011–2012 vaccine 1 year earlier. Conclusions. The 2012–2013 vaccines were moderately effective in most age groups. Cross-lineage protection and residual effects from prior vaccination were observed and warrant further investigation.

Impact of Repeated Vaccination on Vaccine Effectiveness Against Influenza A(H3N2) and B During 8 Seasons

The effect of prior influenza vaccination history on vaccine effectiveness was assessed in a community cohort over 8 seasons. Current- and previous-season vaccination generated similar levels of protection; vaccine-induced protection was greatest for individuals with no recent vaccination history.

Waning vaccine protection against influenza A (H3N2) illness in children and older adults during a single season

BACKGROUND Recent studies have suggested that vaccine-induced protection against influenza may decline within one season. We reanalyzed data from a study of influenza vaccine effectiveness to determine if time since vaccination was an independent predictor of influenza A (H3N2). METHODS Patients with acute respiratory illness were actively recruited during the 2007-2008 season. Respiratory swabs were tested for influenza, and vaccination dates were determined by a validated immunization registry. The association between influenza RT-PCR result and vaccination interval (days) was examined using multivariable logistic regression, adjusting for calendar time, age and other confounders. RESULTS There were 629 vaccinated participants, including 177 influenza A (H3N2) cases and 452 test negative controls. The mean (SD) interval from vaccination to illness onset was 101.7 (25.9) days for influenza cases and 93.0 (29.9) days for controls. There was a significant association between vaccination interval and influenza result in the main effects model. The adjusted odds ratio (aOR) for influenza was 1.12 (CI 1.01, 1.26) for every 14 day increase in the vaccination interval. Age modified the association between vaccination interval and influenza (p=0.005 for interaction). Influenza was associated with increasing vaccination interval in young children and older adults, but not in adolescents or non-elderly adults. Similar results were found when calendar week of vaccine receipt was assessed as the primary exposure variable. CONCLUSIONS Identification of influenza A (H3N2) was associated with increasing time since vaccination among young children and older adults during a single influenza season.

Comparison of Interviewer-Administered and Automated Self-Administered 24-Hour Dietary Recalls in 3 Diverse Integrated Health Systems

Twenty-four-hour dietary recalls provide high-quality intake data but have been prohibitively expensive for large epidemiologic studies. This studys goal was to assess whether the web-based Automated Self-Administered 24-Hour Recall (ASA24) performs similarly enough to the standard interviewer-administered, Automated Multiple-Pass Method (AMPM) 24-hour dietary recall to be considered a viable alternative. In 2010-2011, 1,081 adults from 3 integrated health systems in Detroit, Michigan; Marshfield, Wisconsin; and Kaiser-Permanente Northern California participated in a field trial. A quota design ensured a diverse sample by sex, age, and race/ethnicity. Each participant was asked to complete 2 recalls and was randomly assigned to 1 of 4 protocols differing by type of recall and administration order. For energy, the mean intakes were 2,425 versus 2,374 kcal for men and 1,876 versus 1,906 kcal for women by AMPM and ASA24, respectively. Of 20 nutrients/food groups analyzed and controlling for false discovery rate, 87% were judged equivalent at the 20% bound. ASA24 was preferred over AMPM by 70% of the respondents. Attrition was lower in the ASA24/AMPM study group than in the AMPM/ASA24 group, and it was lower in the ASA24/ASA24 group than in the AMPM/AMPM group. ASA24 offers the potential to collect high-quality dietary intake information at low cost with less attrition.

Repeated annual influenza vaccination and vaccine effectiveness: review of evidence

ABSTRACT Introduction: Studies in the 1970s and 1980s signaled concern that repeated influenza vaccination could affect vaccine protection. The antigenic distance hypothesis provided a theoretical framework to explain variability in repeat vaccination effects based on antigenic similarity between successive vaccine components and the epidemic strain. Areas covered: A meta-analysis of vaccine effectiveness studies from 2010–11 through 2014–15 shows substantial heterogeneity in repeat vaccination effects within and between seasons and subtypes. When negative effects were observed, they were most pronounced for H3N2, especially in 2014–15 when vaccine components were unchanged and antigenically distinct from the epidemic strain. Studies of repeated vaccination across multiple seasons suggest that vaccine effectiveness may be influenced by more than one prior season. In immunogenicity studies, repeated vaccination blunts the hemagglutinin antibody response, particularly for H3N2. Expert commentary: Substantial heterogeneity in repeated vaccination effects is not surprising given the variation in study populations and seasons, and the variable effects of antigenic distance and immunological landscape in different age groups and populations. Caution is required in the interpretation of pooled results across multiple seasons, since this can mask important variation in repeat vaccination effects between seasons. Multi-season clinical studies are needed to understand repeat vaccination effects and guide recommendations.

Influenza Vaccination Is Not Associated With Detection of Noninfluenza Respiratory Viruses in Seasonal Studies of Influenza Vaccine Effectiveness

Influenza vaccination was not associated with detection of noninfluenza respiratory viruses in young children or older adults with acute respiratory illness. Use of influenza-negative controls did not generate a biased estimate of vaccine effectiveness due to an effect of vaccination on other respiratory virus infections.

Vitamin D and Influenza

Vitamin D has become increasingly recognized in the literature for its extra-skeletal roles, including an effect on inflammation and the immune response to infection. Our goal was to describe the role of vitamin D in the immune response and implications for the risk of influenza infection in humans. In this review, we first consider literature that provides molecular and genetic support to the idea that vitamin D is related to the adaptive and innate immune responses to influenza infection in vitro and in animal models. We then discuss observational studies and randomized controlled trials of vitamin D supplementation in humans. Finally, we consider some of the knowledge gaps surrounding vitamin D and immune response that must be filled.

Medically Attended Respiratory Syncytial Virus Infections in Adults Aged ≥50 Years: Clinical Characteristics and Outcomes

Respiratory syncytial virus (RSV) is a common cause of acute respiratory illness in adults aged ≥50 years. Patients with RSV were older and sought care later in the course of illness compared to those with influenza.

Vitamin D is not associated with serologic response to influenza vaccine in adults over 50 years old.

Vitamin D deficiency has been implicated in risk of respiratory illness. We determined whether serum vitamin D levels are related to influenza vaccine response measured by hemagglutination antibody inhibition (HAI) titer in adults aged ≥50 years old. The study was a prospective cohort study conducted over two influenza seasons (fall 2008-spring 2009 and fall 2009-spring 2010) in Marshfield, WI and Nashville, TN including 1103 community-dwelling adult volunteers ≥50 years of age. Pre-vaccination levels of serum vitamin D and HAI titer levels pre- and 21-28 days post-influenza vaccination were measured. Seroprotection was defined as HAI ≥40; seroconversion was defined as ≥4-fold rise in HAI titers from pre- to post-vaccination. More than 25% of participants were vitamin D deficient (<25ng/mL). Vitamin D measured as a continuous variable was not related to pre- or post-vaccination seroprotection or seroconversion for any vaccine strain in any year. Vitamin D deficiency was associated with a greater frequency of post-vaccination seroprotection for seasonal H1N1 in the first year of the study, but was not related to seroprotection or seroconversion for any other strain in either year. No consistent association was found between vitamin D levels or vitamin D deficiency and serologic response to influenza vaccination in older adults. Cell-mediated immune parameters should also be explored in order to further investigate possible relationships between micronutrient status and influenza vaccine response.

Seasonal Incidence of Medically Attended Respiratory Syncytial Virus Infection in a Community Cohort of Adults ≥50 Years Old

Background Diagnostic testing for respiratory syncytial virus (RSV) is not routinely performed in adults. We estimated medically attended RSV seasonal incidence in a community cohort of adults ≥50 years old during four influenza seasons (2006–07 through 2009–10). Methods Patients seeking care for acute respiratory illness (ARI) were prospectively enrolled and tested for RSV by multiplex RT-PCR. Results from enrolled patients were used to estimate projected cases among non-enrolled patients with ARI. The seasonal incidence of medically attended RSV was the sum of actual and projected cases divided by the community cohort denominator. Since each enrollment period did not include the entire RSV season, incidence estimates were adjusted to account for the statewide proportion of RSV occurring outside the study enrollment period. Results There were 16,088 to 17,694 adults in the cohort each season and 164 RSV cases in all 4 seasons. The overall seasonal incidence of medically attended RSV was 154 episodes (95% CI, 132–180) per 10,000 persons; the incidence was highest in 2007–08 (179) and lowest in 2006–07 (110). Among persons 50–59, 60–69, and ≥70 years old, RSV incidence was 124 (95% CI, 99–156), 147 (95% CI, 110–196), and 199 (95% CI, 153–258), respectively. Conclusions The incidence of medically attended RSV increased with age and was similar during four seasons.