Mark G. Thompson

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.

Influenza Vaccine Effectiveness in the Community and the Household

BACKGROUND There is a recognized need to determine influenza vaccine effectiveness on an annual basis and a long history of studying respiratory illnesses in households. METHODS We recruited 328 households with 1441 members, including 839 children, and followed them during the 2010-2011 influenza season. Specimens were collected from subjects with reported acute respiratory illnesses and tested by real-time reverse transcriptase polymerase chain reaction. Receipt of influenza vaccine was defined based on documented evidence of vaccination in medical records or an immunization registry. The effectiveness of 2010-2011 influenza vaccination in preventing laboratory-confirmed influenza was estimated using Cox proportional hazards models adjusted for age and presence of high-risk condition, and stratified by prior season (2009-2010) vaccination status. RESULTS Influenza was identified in 78 (24%) households and 125 (9%) individuals; the infection risk was 8.5% in the vaccinated and 8.9% in the unvaccinated (P = .83). Adjusted vaccine effectiveness in preventing community-acquired influenza was 31% (95% confidence interval [CI], -7% to 55%). In vaccinated subjects with no evidence of prior season vaccination, significant protection (62% [95% CI, 17%-82%]) against community-acquired influenza was demonstrated. Substantially lower effectiveness was noted among subjects who were vaccinated in both the current and prior season. There was no evidence that vaccination prevented household transmission once influenza was introduced; adults were at particular risk despite vaccination. CONCLUSIONS Vaccine effectiveness estimates were lower than those demonstrated in other observational studies carried out during the same season. The unexpected findings of lower effectiveness with repeated vaccination and no protection given household exposure require further study.

Effectiveness of Seasonal Trivalent Influenza Vaccine for Preventing Influenza Virus Illness Among Pregnant Women: A Population-Based Case-Control Study During the 2010–2011 and 2011–2012 Influenza Seasons

BACKGROUND Although vaccination with trivalent inactivated influenza vaccine (TIV) is recommended for all pregnant women, no vaccine effectiveness (VE) studies of TIV in pregnant women have assessed laboratory-confirmed influenza outcomes. METHODS We conducted a case-control study over 2 influenza seasons (2010-2011 and 2011-2012) among Kaiser Permanente health plan members in 2 metropolitan areas in California and Oregon. We compared the proportion vaccinated among 100 influenza cases (confirmed by reverse transcription polymerase chain reaction) with the proportions vaccinated among 192 controls with acute respiratory illness (ARI) who tested negative for influenza and 200 controls without ARI (matched by season, site, and trimester). RESULTS Among influenza cases, 42% were vaccinated during the study season compared to 58% and 63% vaccinated among influenza-negative controls and matched ARI-negative controls, respectively. The adjusted VE of the current season vaccine against influenza A and B was 44% (95% confidence interval [CI], 5%-67%) using the influenza-negative controls and 53% (95% CI, 24%-72%) using the ARI-negative controls. Receipt of the prior seasons vaccine, however, had an effect similar to receipt of the current seasons vaccine. As such, vaccination in either or both seasons had statistically similar adjusted VE using influenza-negative controls (VE point estimates range = 51%-76%) and ARI-negative controls (48%-76%). CONCLUSIONS Influenza vaccination reduced the risk of ARI associated with laboratory-confirmed influenza among pregnant women by about one-half, similar to VE observed among all adults during these seasons.

Effectiveness of influenza vaccine against life-threatening RT-PCR-confirmed influenza illness in US children, 2010-2012

BACKGROUND No studies have examined the effectiveness of influenza vaccine against intensive care unit (ICU) admission associated with influenza virus infection among children. METHODS In 2010-2011 and 2011-2012, children aged 6 months to 17 years admitted to 21 US pediatric intensive care units (PICUs) with acute severe respiratory illness and testing positive for influenza were enrolled as cases; children who tested negative were PICU controls. Community controls were children without an influenza-related hospitalization, matched to cases by comorbidities and geographic region. Vaccine effectiveness was estimated with logistic regression models. RESULTS We analyzed data from 44 cases, 172 PICU controls, and 93 community controls. Eighteen percent of cases, 31% of PICU controls, and 51% of community controls were fully vaccinated. Compared to unvaccinated children, children who were fully vaccinated were 74% (95% CI, 19% to 91%) or 82% (95% CI, 23% to 96%) less likely to be admitted to a PICU for influenza compared to PICU controls or community controls, respectively. Receipt of 1 dose of vaccine among children for whom 2 doses were recommended was not protective. CONCLUSIONS During the 2010-2011 and 2011-2012 US influenza seasons, influenza vaccination was associated with a three-quarters reduction in the risk of life-threatening influenza illness in children.

Effectiveness of Influenza Vaccine for Preventing Laboratory-Confirmed Influenza Hospitalizations in Adults, 2011–2012 Influenza Season

During the 2011-2012 influenza season, we enrolled hospitalized adults with acute respiratory illness and tested each for influenza using reverse transcription polymerase chain reaction. Influenza vaccination was verified in 35% (6/17) of adults with influenza-associated hospitalizations compared to 64% (97/152) of test-negative controls; adjusted vaccine effectiveness was 71.4% (95% confidence interval, 17.1%-94.9%).

Seasonal Effectiveness of Live Attenuated and Inactivated Influenza Vaccine

BACKGROUND: Few observational studies have evaluated the relative effectiveness of live attenuated (LAIV) and inactivated (IIV) influenza vaccines against medically attended laboratory-confirmed influenza. METHODS: We analyzed US Influenza Vaccine Effectiveness Network data from participants aged 2 to 17 years during 4 seasons (2010–2011 through 2013–2014) to compare relative effectiveness of LAIV and IIV against influenza-associated illness. Vaccine receipt was confirmed via provider/electronic medical records or immunization registry. We calculated the ratio (odds) of influenza-positive to influenza-negative participants among those age-appropriately vaccinated with either LAIV or IIV for the corresponding season. We examined relative effectiveness of LAIV and IIV by using adjusted odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression. RESULTS: Of 6819 participants aged 2 to 17 years, 2703 were age-appropriately vaccinated with LAIV (n = 637) or IIV (n = 2066). Odds of influenza were similar for LAIV and IIV recipients during 3 seasons (2010–2011 through 2012–2013). In 2013–2014, odds of influenza were significantly higher among LAIV recipients compared with IIV recipients 2 to 8 years old (OR 5.36; 95% CI, 2.37 to 12.13). Participants vaccinated with LAIV or IIV had similar odds of illness associated with influenza A/H3N2 or B. LAIV recipients had greater odds of illness due to influenza A/H1N1pdm09 in 2010–2011 and 2013–2014. CONCLUSIONS: We observed lower effectiveness of LAIV compared with IIV against influenza A/H1N1pdm09 but not A(H3N2) or B among children and adolescents, suggesting poor performance related to the LAIV A/H1N1pdm09 viral construct.

Frequency of Acute Respiratory Illnesses and Circulation of Respiratory Viruses in Households With Children Over 3 Surveillance Seasons

Abstract Background. The household has traditionally been the site for studying acute respiratory illnesses (ARIs). Most studies were conducted many years ago, and more broadly sensitive laboratory methods to determine ARI etiology are now available. Methods. We recruited and followed households with children over 3 annual surveillance periods and collected respiratory tract specimens from subjects with reported ARI. Virus etiology was determined by real-time reverse-transcription polymerase chain reaction (RT-PCR) analysis. Results. Individuals in larger households (defined as households with >4 members) and those in households with children aged <5 years had significantly higher ARI frequencies than others. ARI frequency generally declined with increasing age. Virus etiology was most likely to be determined in young children, who were also most likely to have virus coinfection. Overall, 16% of ARIs with 1 virus identified had ≥1 coinfecting virus. Rhinoviruses and coronaviruses were the most frequently identified agents of ARI in all age categories. Influenza virus and adenovirus were less frequently identified but were most likely to cause ARI that required medical attention. Conclusions. Longitudinal studies in families remain a valuable way to study respiratory infections. RT-PCR has increased the sensitivity of virus detection, including coinfecting viruses, and expanded our ability to detect viruses now known to cause ARI.

Influenza transmission in a cohort of households with children: 2010-2011.

Background Households play a major role in community spread of influenza and are potential targets for mitigation strategies. Methods We enrolled and followed 328 households with children during the 2010-2011 influenza season; this season was characterized by circulation of influenza A (H3N2), A (H1N1)pdm09 and type B viruses. Specimens were collected from subjects with acute respiratory illnesses and tested for influenza in real-time reverse transcriptase polymerase chain reaction (RT-PCR) assays. Influenza cases were classified as community-acquired or household-acquired, and transmission parameters estimated. Results Influenza was introduced to 78 (24%) households and transmission to exposed household members was documented in 23 households. Transmission was more likely in younger households (mean age <22 years) and those not reporting home humidification, but was not associated with household vaccination coverage. The secondary infection risk (overall 9.7%) was highest among young children (<9 years) and varied substantially by influenza type/subtype with the highest risk for influenza A (H3N2). The serial interval (overall 3.2 days) also varied by influenza type and was longest for influenza B. Duration of symptomatic illness was shorter in children compared with adults, and did not differ by influenza vaccination status. Discussion Prospective study of households with children over a single influenza season identified differences in household transmission by influenza type/subtype, subject age, and home humidification, suggesting possible targets for interventions to reduce transmission.

Safety of influenza vaccination during pregnancy: A review of subsequent maternal obstetric events and findings from two recent cohort studies

Pregnant women and their infants are vulnerable to severe disease and secondary complications from influenza infection. For this reason, annual influenza vaccination is recommended for all pregnant women in the United States. Women frequently cite concerns about vaccine safety as a barrier to vaccination. This review describes the safety of inactivated influenza vaccination during pregnancy with a focus on maternal obstetric events, including hypertensive disorders, gestational diabetes, and chorioamnionitis. Included in the review are new findings from two studies which examined the safety of seasonal inactivated influenza vaccination during pregnancy. The first study enrolled 641 pregnant women during the 2010-2011 season and prospectively followed them until delivery or pregnancy termination. The second study enrolled 1616 pregnant women during the 2010-2011 influenza season, and followed the women and their infants for six months after delivery. No associations between inactivated influenza vaccination and gestational diabetes, gestational hypertension, preeclampsia/eclampsia, or chorioamnionitis were observed in either cohort. When considered as a whole, these studies should further reassure women and clinicians that influenza vaccination during pregnancy is safe for mothers.