Efficacy of inactivated trivalent influenza vaccine in rural India: a 3-year cluster-randomised controlled trial.

BACKGROUND: Paediatric vaccination against influenza can result in indirect protection, by reducing transmission to their unvaccinated contacts. We investigated whether influenza vaccination of children would protect them and their household members in a resource-limited setting. METHODS: We did a cluster-randomised, blinded, controlled study in three villages in India. Clusters were defined as households (ie, dwellings that shared a courtyard), and children aged 6 months to 10 years were eligible for vaccination as and when they became age-eligible throughout the study. Households were randomly assigned (1:1) by a computer-based system to intramuscular trivalent inactivated influenza vaccine (IIV3) or a control of inactivated poliovirus vaccine (IPV) in the beginning of the study; vaccination occurred once a year for 3 years. The primary efficacy outcome was laboratory-confirmed influenza in a vaccinated child with febrile acute respiratory illness, analysed in the modified intention-to-treat population (ie, children who received at least one dose of vaccine, were under surveillance, and had not an influenza infection within 15 days of last vaccine dose). The secondary outcome for indirect effectiveness (surveillance study) was febrile acute respiratory illness in an unvaccinated household member of a vaccine study participant. Data from each year (year 1: November, 2009, to October, 2010; year 2: October, 2010, to October, 2011; and year 3: October, 2011, to May, 2012) were analysed separately. Safety was analysed among all participants who were vaccinated with at least one dose of the vaccine. This trial is registered with ClinicalTrials.gov, number NCT00934245. FINDINGS: Between Nov 1, 2009, to May 1, 2012, we enrolled 3208 households, of which 1959 had vaccine-eligible children. 1010 households were assigned to IIV3 and 949 households were assigned to IPV. In 3 years, we vaccinated 4345 children (2132 with IIV3 and 2213 with IPV) from 1868 households (968 with IIV3 and 900 with IPV) with 10 813 unvaccinated household contacts. In year 1, influenza virus was detected in 151 (10%) of 1572 IIV3 recipients and 206 (13%) of 1633 of IPV recipients (total IIV3 vaccine efficacy 25·6% [95% CI 6·8-40·6]; p=0·010). In year 2, 105 (6%) of 1705 IIV3 recipients and 182 (10%) of 1814 IPV recipients had influenza (vaccine efficacy 41·0% [24·1-54·1]; p<0·0001). In year 3, 20 (1%) of 1670 IIV3 recipients and 81 (5%) of 1786 IPV recipients had influenza (vaccine efficacy 74·2% [57·8-84·3]; p<0·0001). In year 1, total vaccine efficacy against influenza A(H1N1)pdm09 was 14·5% (-20·4 to 39·3). In year 2, total vaccine efficacy against influenza A(H3N2) was 64·5% (48·5-75·5). Total vaccine efficacy against influenza B was 32·5% (11·3-48·6) in year 1, 4·9% (-38·9 to 34·9) in year 2, and 76·5% (59·4-86·4) in year 3. Indirect vaccine effectiveness was statistically significant only in year 3 (38·1% [7·4-58·6], p=0·0197) when influenza was detected in 39 (1%) of 4323 IIV3-allocated and 60 (1%) of 4121 IPV-allocated household unvaccinated individuals. In the IIV3 group, 225 (12%) of 1632 children in year 1, 375 (22%) of 1718 in year 2, and 209 (12%) of 1673 in year 3 had an adverse reaction (compared with 216 [13%] of 1730, 380 [21%] of 1825, and 235 [13%] of 1796, respectively, in the IPV group). The most common reactions in both groups were fever and tenderness at site. No vaccine-related deaths occurred in either group. INTERPRETATION: IIV3 provided variable direct and indirect protection against influenza infection. Indirect protection was significant during the year of highest direct protection and should be considered when quantifying the effect of vaccination programmes. FUNDING: US Centers for Disease Control and Prevention.

The Sierra Leone Trial to Introduce a Vaccine Against Ebola: An Evaluation of rVSV∆G-ZEBOV-GP Vaccine Tolerability and Safety During the West Africa Ebola Outbreak.

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Rates and risk factors associated with hospitalization for pneumonia with ICU admission among adults.

BACKGROUND: Pneumonia poses a significant burden to the U.S. health-care system. However, there are few data focusing on severe pneumonia, particularly cases of pneumonia associated with specialized care in intensive care units (ICU). METHODS: We used administrative and electronic medical record data from six integrated health care systems to estimate rates of pneumonia hospitalizations with ICU admissions among adults during 2006 through 2010. Pneumonia hospitalization was defined as either a primary discharge diagnosis of pneumonia or a primary discharge diagnosis of sepsis or respiratory failure with a secondary diagnosis of pneumonia in administrative data. ICU admissions were collected from internal electronic medical records from each system. Comorbidities were identified by ICD-9-CM codes coded during the current pneumonia hospitalization, as well as during medical visits that occurred during the year prior to the date of admission. RESULTS: We identified 119,537 adult hospitalizations meeting our definition for pneumonia. Approximately 19% of adult pneumonia hospitalizations had an ICU admission. The rate of pneumonia hospitalizations requiring ICU admission during the study period was 76 per 100,000 population/year; rates increased for each age-group with the highest rates among adults aged ≥85 years. Having a co-morbidity approximately doubled the risk of ICU admission in all age-groups. CONCLUSIONS: Our study indicates a significant burden of pneumonia hospitalizations with an ICU admission among adults in our cohort during 2006 through 2010, especially older age-groups and persons with underlying medical conditions. These findings reinforce current strategies aimed to prevent pneumonia among adults.

School-Based Influenza Vaccination: Health and Economic Impact of Maine's 2009 Influenza Vaccination Program.

OBJECTIVE: To estimate the societal economic and health impacts of Maine's school-based influenza vaccination (SIV) program during the 2009 A(H1N1) influenza pandemic. DATA SOURCES: Primary and secondary data covering the 2008-09 and 2009-10 influenza seasons. STUDY DESIGN: We estimated weekly monovalent influenza vaccine uptake in Maine and 15 other states, using difference-in-difference-in-differences analysis to assess the program's impact on immunization among six age groups. We also developed a health and economic Markov microsimulation model and conducted Monte Carlo sensitivity analysis. DATA COLLECTION: We used national survey data to estimate the impact of the SIV program on vaccine coverage. We used primary data and published studies to develop the microsimulation model. PRINCIPAL FINDINGS: The program was associated with higher immunization among children and lower immunization among adults aged 18-49 years and 65 and older. The program prevented 4,600 influenza infections and generated $4.9 million in net economic benefits. Cost savings from lower adult vaccination accounted for 54 percent of the economic gain. Economic benefits were positive in 98 percent of Monte Carlo simulations. CONCLUSIONS: SIV may be a cost-beneficial approach to increase immunization during pandemics, but programs should be designed to prevent lower immunization among nontargeted groups.

Influenza Vaccine Effectiveness Against Pediatric Deaths: 2010-2014.

BACKGROUND AND OBJECTIVES: Surveillance for laboratory-confirmed influenza-associated pediatric deaths since 2004 has shown that most deaths occur in unvaccinated children. We assessed whether influenza vaccination reduced the risk of influenza-associated death in children and adolescents. METHODS: We conducted a case-cohort analysis comparing vaccination uptake among laboratory-confirmed influenza-associated pediatric deaths with estimated vaccination coverage among pediatric cohorts in the United States. Case vaccination and high-risk status were determined by case investigation. Influenza vaccination coverage estimates were obtained from national survey data or a national insurance claims database. We estimated odds ratios from logistic regression comparing odds of vaccination among cases with odds of vaccination in comparison cohorts. We used Bayesian methods to compute 95% credible intervals (CIs) for vaccine effectiveness (VE), calculated as (1 - odds ratio) × 100. RESULTS: From July 2010 through June 2014, 358 laboratory-confirmed influenza-associated pediatric deaths were reported among children aged 6 months through 17 years. Vaccination status was determined for 291 deaths; 75 (26%) received vaccine before illness onset. Average vaccination coverage in survey cohorts was 48%. Overall VE against death was 65% (95% CI, 54% to 74%). Among 153 deaths in children with underlying high-risk medical conditions, 47 (31%) were vaccinated. VE among children with high-risk conditions was 51% (95% CI, 31% to 67%), compared with 65% (95% CI, 47% to 78%) among children without high-risk conditions. CONCLUSIONS: Influenza vaccination was associated with reduced risk of laboratory-confirmed influenza-associated pediatric death. Increasing influenza vaccination could prevent influenza-associated deaths among children and adolescents.

Estimating Direct and Indirect Protective Effect of Influenza Vaccination in the United States.

With influenza vaccination rates in the United States recently exceeding 45% of the population, it is important to understand the impact that vaccination is having on influenza transmission. In this study, we used a Bayesian modeling approach, combined with a simple dynamical model of influenza transmission, to estimate this impact. The combined framework synthesized evidence from a range of data sources relating to influenza transmission and vaccination in the United States. We found that, for seasonal epidemics, the number of infections averted ranged from 9.6 million in the 2006-2007 season (95% credible interval (CI): 8.7, 10.9) to 37.2 million (95% CI: 34.1, 39.6) in the 2012-2013 season. Expressed in relative terms, the proportion averted ranged from 20.8% (95% CI: 16.8, 24.3) of potential infections in the 2011-2012 season to 47.5% (95% CI: 43.7, 50.8) in the 2008-2009 season. The percentage averted was only 1.04% (95% CI: 0.15, 3.2) for the 2009 H1N1 pandemic, owing to the late timing of the vaccination program in relation to the pandemic in the Northern hemisphere. In the future, further vaccination coverage, as well as improved influenza vaccines (especially those offering better protection in the elderly), could have an even stronger effect on annual influenza epidemics.

Hospitalizations within 14days of vaccination among pediatric recipients of the live attenuated influenza vaccine, United States 2010-2012.

BACKGROUND: Live attenuated influenza vaccine (LAIV) is safe in healthy children ⩾2years. The original clinical trials excluded individuals with underlying conditions; however, post-marketing data suggest LAIV may be safe for these populations. METHODS: We analyzed MarketScan Commercial Claims Databases from 2010 to 2012 to describe hospitalizations within 14days of vaccination among LAIV recipients. We evaluated LAIV recipients aged 2-18years and defined underlying conditions by presence of inpatient or outpatient ICD-9 code during the previous calendar year. We excluded asthma and immunocompromising conditions. We defined risk windows as 1-7days and 8-14days after vaccination; the control period was 12-4days prior to and 15-23days after vaccination. We conducted a self-controlled case series analysis using a conditional Poisson regression model to estimate incidence-rate ratios (IRR). RESULTS: 1,216,123 children aged 2-18years received LAIV from 2010 to 2012. 634 children met our inclusion criteria and were hospitalized during the observation period (12days prior to vaccination to 23days after vaccination). Of those hospitalized, 72 (11.4%) had non-asthma, non-immunocompromising underlying conditions. Children with non-asthma, non-immunocompromising underlying conditions had an all-cause hospitalization IRR of 1.1 (95% CI 0.6-2.0, p=0.83) in the 1-7day risk period and 0.9 (95% CI 0.4-1.7, p=0.67) in the 8-14day risk period. Children with no underlying conditions had an all-cause hospitalization IRR of 0.9 (0.8-1.2, p=0.60) in the 1-7day risk period and 1.1 (95% CI 0.9-1.3, p=0.53) in the 8-14day risk period. There were no differences in all-cause hospitalization risk in individuals with non-asthma, non-immunocompromising underlying conditions compared to those without underlying conditions in the 1-7day (p=0.88) or 8-14day (p=0.24) risk period. CONCLUSIONS: We found no evidence of differences in post-LAIV hospitalization risk among children with non-asthma, non-immunocompromising underlying conditions compared to healthy children.

Seasonal Influenza Vaccination of Children Induces Humoral and Cell-Mediated Immunity Beyond the Current Season: Cross-reactivity With Past and Future Strains.

BACKGROUND: Influenza viruses gradually accumulate point mutations, reducing the effectiveness of prior immune protection. METHODS: Children aged 9-14 years received 2010-2011 trivalent inactivated influenza vaccine (TIV). Vaccination history, hemagglutination-inhibition (HI) titers, and cell-mediated immune responses were assessed to investigate the cross-reactivity with past and future influenza virus strains. RESULTS: 2010-2011 TIV induced significant T-cell responses and HI titers of ≥160, with a fold-rise of ≥4 and titers of ≥100 maintained for >7 months in the majority of children. Pre-existing memory B cells in these children differentiated quickly to antibody-secreting cells to the new vaccine antigens. Children vaccinated in the previous year maintained high HI titers well into 2010, demonstrating elevated HI titers against A/Perth/16/2009, the future (in 2010-2011) H3N2 component. Prior vaccination enhanced CD8+ T-cell responses to A/Perth/16/2009. Children vaccinated with the prior 2009-2010 seasonal vaccine also demonstrated higher preexisting levels of interferon γ-secreting CD4+CD69+ T cells to 2009 pandemic influenza A(H1N1). Children previously vaccinated with 2009-2010 seasonal influenza vaccine also showed greater expansion of tumor necrosis factor α-secreting CD8+CD69+ T cells to 2009 pandemic influenza A(H1N1) upon vaccination in the 2010-2011 season than those who were not previously vaccinated. CONCLUSIONS: Seasonal influenza viruses continuously drift, which allows them to circumvent protective immunity, but conserved epitopes provide immunological cross-reactivity in children through either vaccination directly or through prime/boost in the prior influenza season.

A randomized, double-blind, placebo-controlled trial evaluating the safety of early oseltamivir treatment among children 0-9 years of age hospitalized with influenza in El Salvador and Panama.

BACKGROUND: Oseltamivir reduces symptom duration among children with uncomplicated influenza, but few data exist on treatment efficacy and tolerability among hospitalized children, particularly among infants aged <1 year. We evaluated tolerability and efficacy of oseltamivir treatment of children aged 0-9 years hospitalized with influenza. METHODS: We conducted a double-blind, randomized, placebo-controlled trial at tertiary care hospitals in El Salvador and Panama. Primary outcomes were length of hospitalization and increased work of breathing. Children were eligible if hospitalized <7 days after symptom onset with cough or sore throat plus tachypnea. Children were randomized 1:1 to receive oseltamivir or placebo; had swabs collected at enrollment for influenza RT-PCR testing; were assessed at enrollment and every 12 h for work of breathing; and were followed for adverse events through 7 days after discharge. Analyses were intention-to-treat. RESULTS: Overall, 683 children were randomized (oseltamivir, n = 341, placebo n = 342). Fifty-three percent were aged <1 year and 30 had influenza (oseltamivir, n = 19; placebo, n = 11). The study was terminated early after enrollment of 21% of the sample size due to lower than anticipated participant accrual. Using Kaplan-Meier analysis, there was no significant difference in median length of hospitalization (3 days, IQR 2-4 vs. 5 days, IQR 3-7, p = 0.22) and increased work of breathing (36 h, IQR 24-72 vs. 96 h, IQR 13-108, p = 0.14) between oseltamivir versus placebo recipients. There was no difference in adverse events between groups. CONCLUSION: Oseltamivir treatment was well tolerated among hospitalized children, including among infants aged <1 year.

Benefit of Early Initiation of Influenza Antiviral Treatment to Pregnant Women Hospitalized With Laboratory-Confirmed Influenza.

BACKGROUND: We describe the impact of early initiation of influenza antiviral treatment among pregnant women hospitalized with laboratory-confirmed influenza during the 2010-2014 influenza seasons. METHODS: Severe influenza was defined as illness with ≥1 of the following: intensive care unit admission, need for mechanical ventilation, respiratory failure, pulmonary embolism, sepsis, or death. Within severity stratum, we used parametric survival analysis to compare length of stay by timing of antiviral treatment, adjusting for underlying conditions, influenza vaccination, and pregnancy trimester. RESULTS: Among 865 pregnant women, the median age was 27 years (interquartile range [IQR], 23-31 years). Most (68%) were healthy, and 85% received antiviral treatment. Sixty-three women (7%) had severe influenza, and 4 died. Severity was associated with preterm delivery and fetal loss. Women with severe influenza were less likely to be vaccinated than those without severe influenza (14% vs 26%; P = .03). Among women treated with antivirals ≤2 days versus those treated >2 days from illness onset, the median length of stay was 2.2 days (interquartile range [IQR], 0.9-5.8 days; n = 8) versus 7.8 days (IQR, 3.0-20.6 days; n = 7), respectively, for severe influenza (P = .03) and 2.4 days (IQR, 2.3-2.5 days; n = 153) versus 3.1 days (IQR, 2.8-3.5 days; n = 62), respectively, for nonsevere influenza (P < .01). CONCLUSIONS: Early initiation of influenza antiviral treatment to pregnant women hospitalized with influenza may reduce the length of stay, especially among those with severe influenza. Influenza during pregnancy is associated with maternal and infant morbidity, and annual influenza vaccination is warranted.

Preexisting Immunity, More Than Aging, Influences Influenza Vaccine Responses.

Background. Influenza disproportionately impacts older adults while current vaccines have reduced effectiveness in the older population. Methods. We conducted a comprehensive evaluation of cellular and humoral immune responses of adults aged 50 years and older to the 2008-2009 seasonal trivalent inactivated influenza vaccine and assessed factors influencing vaccine response. Results. Vaccination increased hemagglutination inhibition and neutralizing antibody; however, 66.3% of subjects did not reach hemagglutination inhibition titers ≥ 40 for H1N1, compared with 22.5% for H3N2. Increasing age had a minor negative impact on antibody responses, whereas prevaccination titers were the best predictors of postvaccination antibody levels. Preexisting memory B cells declined with age, especially for H3N2. However, older adults still demonstrated a significant increase in antigen-specific IgG(+) and IgA(+) memory B cells postvaccination. Despite reduced frequency of preexisting memory B cells associated with advanced age, fold-rise in memory B cell frequency in subjects 60+ was comparable to subjects age 50-59. Conclusions. Older adults mounted statistically significant humoral and cell-mediated immune responses, but many failed to reach hemagglutination inhibition titers ≥40, especially for H1N1. Although age had a modest negative effect on vaccine responses, prevaccination titers were the best predictor of postvaccination antibody levels, irrespective of age.

Investigation of an Outbreak of Variant Influenza A(H3N2) Virus Infection Associated With an Agricultural Fair-Ohio, August 2012.

BACKGROUND: In 2012, one third of cases in a multistate outbreak of variant influenza A(H3N2) virus ([H3N2]v) infection occurred in Ohio. We conducted an investigation of (H3N2)v cases associated with agricultural Fair A in Ohio. METHODS: We surveyed Fair A swine exhibitors and their household members. Confirmed cases had influenza-like illness (ILI) and a positive laboratory test for (H3N2)v, and probable cases had ILI. We calculated attack rates. We determined risk factors for infection, using multivariable log-binomial regression. RESULTS: We identified 20 confirmed and 94 probable cases associated with Fair A. Among 114 cases, the median age was 10 years, there were no hospitalizations or deaths, and 82% had swine exposure. In the exhibitor household cohort of 359 persons (83 households), we identified 6 confirmed cases (2%) and 40 probable cases (11%). An age of <10 years was a significant risk factor (P < .01) for illness. One instance of likely human-to-human transmission was identified. CONCLUSIONS: In this (H3N2)v outbreak, no evidence of sustained human-to-human (H3N2)v transmission was found. Our risk factor analysis contributed to the development of the recommendation that people at increased risk of influenza-associated complications, including children aged <5 years, avoid swine barns at fairs during the 2012 fair season.

Relationship between Guillain-Barré syndrome, influenza-related hospitalizations, and influenza vaccine coverage.

Some studies reported an increased risk of Guillain-Barré syndrome (GBS) within six weeks of influenza vaccination. It has also been suggested that this finding could have been confounded by influenza illnesses. We explored the complex relationship between influenza illness, influenza vaccination, and GBS, from an ecologic perspective using nationally representative data. We also studied seasonal patterns for GBS hospitalizations. Monthly hospitalization data (2000-2009) for GBS, and pneumonia and influenza (P&I) in the Nationwide Inpatient Sample were included. Seasonal influenza vaccination coverage for 2004-2005 through the 2008-2009 influenza seasons (August-May) was estimated from the National Health Interview Survey data. GBS seasonality was determined using Poisson regression. GBS and P&I temporal clusters were identified using scan statistics. The association between P&I and GBS hospitalizations in the same month (concurrent) or in the following month (lagged) were determined using negative binomial regression. Vaccine coverage increased over the years (from 19.7% during 2004-2005 to 35.5% during 2008-2009 season) but GBS hospitalization did not follow a similar pattern. Overall, a significant correlation between monthly P&I and GBS hospitalizations was observed (Spearman's correlation coefficient=0.7016, p<0.0001). A significant (p=0.001) cluster of P&I hospitalizations during December 2004-March 2005 overlapped a significant (p=0.001) cluster of GBS hospitalizations during January 2005-February 2005. After accounting for effects of monthly vaccine coverage and age, P&I hospitalization was significantly associated (p<0.0001) with GBS hospitalization in the concurrent month but not with GBS hospitalization in the following month. Monthly vaccine coverage was not associated with GBS hospitalization in adjusted models (both concurrent and lagged). GBS hospitalizations demonstrated a seasonal pattern with winter months having higher rates compared to the month of June. P&I hospitalization rates were significantly correlated with hospitalization rates for GBS. Vaccine coverage did not significantly affect the rates of GBS hospitalization at the population level.

Estimated influenza illnesses and hospitalizations averted by vaccination--United States, 2013-14 influenza season.

The Advisory Committee on Immunization Practices recommends annual influenza vaccination for all persons aged ≥6 months to reduce morbidity and mortality caused by influenza in the United States. CDC previously developed a model to estimate that annual influenza vaccination resulted in 1.1-6.6 million fewer cases and 7,700-79,000 fewer hospitalizations per season during the 2005-2013 influenza seasons. For the 2013-14 influenza season, using updated estimates of vaccination coverage, vaccine effectiveness, and influenza hospitalizations, CDC estimates that influenza vaccination prevented approximately 7.2 million illnesses, 3.1 million medically attended illnesses, and 90,000 hospitalizations associated with influenza. Similar to prior seasons, fewer than half of persons aged ≥6 months are estimated to have been vaccinated. If influenza vaccination levels had reached the Healthy People 2020 target of 70%, an estimated additional 5.9 million illnesses, 2.3 million medically attended illnesses, and 42,000 hospitalizations associated with influenza might have been averted. For the nation to more fully benefit from influenza vaccines, more effort is needed to reach the Healthy People 2020 target.

Child, household, and caregiver characteristics associated with hospitalization for influenza among children 6-59 months of age: an emerging infections program study.

BACKGROUND: Young children are at increased risk of severe outcomes from influenza illness, including hospitalization. We conducted a case-control study to identify risk factors for influenza-associated hospitalizations among children in US Emerging Infections Program sites. METHODS: Cases were children 6-59 months of age hospitalized for laboratory-confirmed influenza infections during 2005-2008. Age- and zip-code-matched controls were enrolled. Data on child, caregiver and household characteristics were collected from parents and medical records. Conditional logistic regression was used to identify independent risk factors for hospitalization. RESULTS: We enrolled 290 (64%) of 454 eligible cases and 1089 (49%) of 2204 eligible controls. Risk for influenza hospitalization increased with maternal age <26 years [odds ratio (OR): 1.8, 95% confidence interval (CI): 1.1-2.9]; household income below the poverty threshold (OR: 2.2, 95% CI: 1.4-3.6); smoking by >50% of household members (OR: 2.9, 95% CI: 1.4-6.6); lack of household influenza vaccination (OR: 1.8, 95% CI: 1.2-2.5) and presence of chronic illnesses, including hematologic/oncologic (OR: 11.8, 95% CI: 4.5-31.0), pulmonary (OR: 2.9, 95% CI: 1.9-4.4) and neurologic (OR: 3.8, 95% CI: 1.6-9.2) conditions. Full influenza immunization decreased the risk among children 6-23 months of age (OR: 0.5, 95% CI: 0.3-0.9) but not among those 24-59 months of age (OR: 1.5, 95% CI: 0.8-3.0; P value for difference = 0.01). CONCLUSIONS: Chronic illnesses, young maternal age, poverty, household smoking and lack of household influenza vaccination increased the risk of influenza hospitalization. These characteristics may help providers to identify young children who are at greatest risk for severe outcomes from influenza illness.

Influenza Illness and Hospitalizations Averted by Influenza Vaccination in the United States, 2005-2011.

CONTEXT: The goal of influenza vaccination programs is to reduce influenza-associated disease outcomes. Therefore, estimating the reduced burden of influenza as a result of vaccination over time and by age group would allow for a clear understanding of the value of influenza vaccines in the US, and of areas where improvements could lead to greatest benefits. OBJECTIVE: To estimate the direct effect of influenza vaccination in the US in terms of averted number of cases, medically-attended cases, and hospitalizations over six recent influenza seasons. DESIGN: Using existing surveillance data, we present a method for assessing the impact of influenza vaccination where impact is defined as either the number of averted outcomes or as the prevented disease fraction (the number of cases estimated to have been averted relative to the number of cases that would have occurred in the absence of vaccination). RESULTS: We estimated that during our 6-year study period, the number of influenza illnesses averted by vaccination ranged from a low of approximately 1.1 million (95% confidence interval (CI) 0.6-1.7 million) during the 2006-2007 season to a high of 5 million (CI 2.9-8.6 million) during the 2010-2011 season while the number of averted hospitalizations ranged from a low of 7,700 (CI 3,700-14,100) in 2009-2010 to a high of 40,400 (CI 20,800-73,000) in 2010-2011. Prevented fractions varied across age groups and over time. The highest prevented fraction in the study period was observed in 2010-2011, reflecting the post-pandemic expansion of vaccination coverage. CONCLUSIONS: Influenza vaccination programs in the US produce a substantial health benefit in terms of averted cases, clinic visits and hospitalizations. Our results underscore the potential for additional disease prevention through increased vaccination coverage, particularly among nonelderly adults, and increased vaccine effectiveness, particularly among the elderly.

Inactivated influenza vaccines for prevention of community-acquired pneumonia: the limits of using nonspecific outcomes in vaccine effectiveness studies.

BACKGROUND: One to 4 million cases of community-acquired pneumonia (CAP) occur annually in the United States, resulting in 600,000 hospitalizations and 45,000 deaths. Influenza infection facilitates secondary bacterial infections, and influenza vaccination may prevent CAP directly by preventing influenza pneumonia or indirectly by preventing secondary bacterial CAP. METHODS: We investigated how influenza vaccination could affect incidence of CAP using deterministic probability and stochastic simulation models. The models included likely influential factors, including vaccine effectiveness (VE) against influenza, rates of influenza in the unvaccinated, vaccination coverage, and the relative risk (RR) of pneumonia, given influenza infection. To estimate effectiveness of influenza vaccine against CAP, we assumed mean VE against influenza of 55% and vaccine coverage of 38%. RESULTS: Given our baseline parameters, influenza vaccine had a mean effectiveness against CAP of 7% (95% confidence interval = 0-25%). Effectiveness of influenza vaccine against CAP increased as its effectiveness against influenza increased, as RR of pneumonia after influenza infection increased, and as rates of influenza among unvaccinated persons increased. CONCLUSIONS: No matter how effective vaccine may be in preventing influenza infection, it is only modestly effective at preventing CAP. Because of the large annual burden of CAP, a vaccine that is only moderately effective in preventing influenza infection has the potential to prevent a substantial number of CAP cases. This modeling approach may be useful for planning influenza vaccine-probe studies and evaluating the effectiveness of other interventions targeted against infections that manifest in nonspecific outcomes.

Association between Guillain-Barré syndrome and influenza A (H1N1) 2009 monovalent inactivated vaccines in the USA: a meta-analysis.

BACKGROUND: The influenza A (H1N1) 2009 monovalent vaccination programme was the largest mass vaccination initiative in recent US history. Commensurate with the size and scope of the vaccination programme, a project to monitor vaccine adverse events was undertaken, the most comprehensive safety surveillance agenda in the USA to date. The adverse event monitoring project identified an increased risk of Guillain-Barré syndrome after vaccination; however, some individual variability in results was noted. Guillain-Barré syndrome is a rare but serious health disorder in which a person's own immune system damages their nerve cells, causing muscle weakness, sometimes paralysis, and infrequently death. We did a meta-analysis of data from the adverse event monitoring project to ascertain whether influenza A (H1N1) 2009 monovalent inactivated vaccines used in the USA increased the risk of Guillain-Barré syndrome. METHODS: Data were obtained from six adverse event monitoring systems. About 23 million vaccinated people were included in the analysis. The primary analysis entailed calculation of incidence rate ratios and attributable risks of excess cases of Guillain-Barré syndrome per million vaccinations. We used a self-controlled risk-interval design. FINDINGS: Influenza A (H1N1) 2009 monovalent inactivated vaccines were associated with a small increased risk of Guillain-Barré syndrome (incidence rate ratio 2·35, 95% CI 1·42-4·01, p=0·0003). This finding translated to about 1·6 excess cases of Guillain-Barré syndrome per million people vaccinated. INTERPRETATION: The modest risk of Guillain-Barré syndrome attributed to vaccination is consistent with previous estimates of the disorder after seasonal influenza vaccination. A risk of this small magnitude would be difficult to capture during routine seasonal influenza vaccine programmes, which have extensive, but comparatively less, safety monitoring. In view of the morbidity and mortality caused by 2009 H1N1 influenza and the effectiveness of the vaccine, clinicians, policy makers, and those eligible for vaccination should be assured that the benefits of inactivated pandemic vaccines greatly outweigh the risks. FUNDING: US Federal Government.

Effectiveness of 1 dose of influenza A (H1N1) 2009 monovalent vaccines in preventing reverse-transcription polymerase chain reaction-confirmed H1N1 infection among school-aged children in maine.

BACKGROUND: In late October 2009, school-located pandemic vaccination was initiated in Maine before or concurrent with 2009 pandemic influenza A (H1N1) virus (pH1N1) peak activity. METHODS: A case-control evaluation of 2009 H1N1 vaccine effectiveness was conducted in schools in Cumberland County, Maine. A case was a child who had an acute respiratory illness during 2 November-18 December 2009, and who tested positive for pH1N1 by real-time reverse-transcription polymerase chain reaction (rRT-PCR). For each case, ≥ 4 event time-matched controls were sampled among classmates present in school during the study period who did not have an influenza-like illness. Vaccine effectiveness was calculated as (1 - adjusted odds ratio [aOR])100%; aOR was estimated by using weighted logistic regression. RESULTS: After adjusting for a diagnosis of asthma, 1 dose of 2009 H1N1 vaccine provided 69% protection (95% confidence interval (CI), 13-89) against rRT-PCR-confirmed H1N1 infection. Vaccine effectiveness estimates for live attenuated and inactivated vaccine were 81% (95% CI, -37 to 97), and 58% (95% CI: -39 to 87), respectively. CONCLUSIONS: One dose of monovalent pandemic vaccine provided substantial protection against pH1N1 infection among school-aged children.

Factors associated with bowel resection among infants with intussusception in the United States.

BACKGROUND: Intussusception is the most common cause of infant bowel obstruction. Because delays in diagnosis can lead to severe outcomes, differentiating milder cases from those with potentially serious outcomes is important. OBJECTIVE: The objective of this study was to identify factors associated with bowel resection among intussusception cases using data from a large nationwide study, which investigated the association between intussusception and Rotashield. METHODS: We examined characteristics of 376 intussusception cases not associated with Rotashield use. Cases were confirmed by a radiologic procedure, surgery, or autopsy. Clinical characteristics of infants with and without bowel resection were compared. RESULTS: During the week before hospitalization, 93% of the 376 infants with intussusception had vomiting, 72% reported bloody stool, 63% had hemoccult positive stool, 51% had diarrhea, 43% reported fever, and 14% had documented fever. Surgery was performed on 209 cases (56%). Of these 209 cases, 33% (67/209) required bowel resection. Documented fever on admission significantly increased the risk of bowel resection (odds ratio, adjusted for race and sex, 2.7; 95% confidence interval, 1.2-6.0). Among infants with intussusception, the presence of a reported symptom for at least 2 days before hospital admission was also an independent predictor of bowel resection (adjusted odds ratio, 2.7; 95% confidence interval, 1.5-4.8). CONCLUSIONS: Bowel resection appears to be more likely among intussusception patients with documented fever and symptoms for at least 2 days. However, because resection also occurred among those without fever or prolonged symptoms, severe disease must also be considered in absence of these symptoms.