Estimates of pandemic influenza vaccine effectiveness in Europe, 2009-2010: results of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) multicentre case-control study

Background

A multicentre case-control study based on sentinel practitioner surveillance networks from seven European countries was undertaken to estimate the effectiveness of 2009–2010 pandemic and seasonal influenza vaccines against medically attended influenza-like illness (ILI) laboratory-confirmed as pandemic influenza A (H1N1) (pH1N1).

Methods and Findings

Sentinel practitioners swabbed ILI patients using systematic sampling. We included in the study patients meeting the European ILI case definition with onset of symptoms >14 days after the start of national pandemic vaccination campaigns. We compared pH1N1 cases to influenza laboratory-negative controls. A valid vaccination corresponded to >14 days between receiving a dose of vaccine and symptom onset. We estimated pooled vaccine effectiveness (VE) as 1 minus the odds ratio with the study site as a fixed effect. Using logistic regression, we adjusted VE for potential confounding factors (age group, sex, month of onset, chronic diseases and related hospitalizations, smoking history, seasonal influenza vaccinations, practitioner visits in previous year). We conducted a complete case analysis excluding individuals with missing values and a multiple multivariate imputation to estimate missing values. The multivariate imputation (n = 2902) adjusted pandemic VE (PIVE) estimates were 71.9% (95% confidence interval [CI] 45.6–85.5) overall; 78.4% (95% CI 54.4–89.8) in patients <65 years; and 72.9% (95% CI 39.8–87.8) in individuals without chronic disease. The complete case (n = 1,502) adjusted PIVE were 66.0% (95% CI 23.9–84.8), 71.3% (95% CI 29.1–88.4), and 70.2% (95% CI 19.4–89.0), respectively. The adjusted PIVE was 66.0% (95% CI −69.9 to 93.2) if vaccinated 8–14 days before ILI onset. The adjusted 2009–2010 seasonal influenza VE was 9.9% (95% CI −65.2 to 50.9).

Conclusions

Our results suggest good protection of the pandemic monovalent vaccine against medically attended pH1N1 and no effect of the 2009–2010 seasonal influenza vaccine. However, the late availability of the pandemic vaccine and subsequent limited coverage with this vaccine hampered our ability to study vaccine benefits during the outbreak period. Future studies should include estimation of the effectiveness of the new trivalent vaccine in the upcoming 2010–2011 season, when vaccination will occur before the influenza season starts. Please see later in the article for the Editors'' Summary     

Immune protection induced on day 10 following administration of the 2009 A/H1N1 pandemic influenza vaccine

Background

The 2009 swine-origin influenza virus (S-OIV) H1N1 pandemic has caused more than 18,000 deaths worldwide. Vaccines against the 2009 A/H1N1 influenza virus are useful for preventing infection and controlling the pandemic. The kinetics of the immune response following vaccination with the 2009 A/H1N1 influenza vaccine need further investigation.

Methodology/Principal Findings

58 volunteers were vaccinated with a 2009 A/H1N1 pandemic influenza monovalent split-virus vaccine (15 µg, single-dose). The sera were collected before Day 0 (pre-vaccination) and on Days 3, 5, 10, 14, 21, 30, 45 and 60 post vaccination. Specific antibody responses induced by the vaccination were analyzed using hemagglutination inhibition (HI) assay and enzyme-linked immunosorbent assay (ELISA). After administration of the 2009 A/H1N1 influenza vaccine, specific and protective antibody response with a major subtype of IgG was sufficiently developed as early as Day 10 (seroprotection rate: 93%). This specific antibody response could maintain for at least 60 days without significant reduction. Antibody response induced by the 2009 A/H1N1 influenza vaccine could not render protection against seasonal H1N1 influenza (seroconversion rate: 3% on Day 21). However, volunteers with higher pre-existing seasonal influenza antibody levels (pre-vaccination HI titer ≥1∶40, Group 1) more easily developed a strong antibody protection effect against the 2009 A/H1N1 influenza vaccine as compared with those showing lower pre-existing seasonal influenza antibody levels (pre-vaccination HI titer <1∶40, Group 2). The titer of the specific antibody against the 2009 A/H1N1 influenza was much higher in Group 1 (geometric mean titer: 146 on Day 21) than that in Group 2 (geometric mean titer: 70 on Day 21).

Conclusions/Significance

Recipients could gain sufficient protection as early as 10 days after vaccine administration. The protection could last at least 60 days. Individuals with a stronger pre-existing seasonal influenza antibody response may have a relatively higher potential for developing a stronger humoral immune response after vaccination with the 2009 A/H1N1 pandemic influenza vaccine.     

Seroprevalence of pandemic H1N1 antibody among health care workers in Hong Kong following receipt of monovalent 2009 H1N1 influenza vaccine

Background

Healthcare workers in many countries are recommended to receive influenza vaccine to protect themselves as well as patients. A monovalent H1N1 vaccine became available in Hong Kong in December 2009 and around 10% of local healthcare workers had received the vaccine by February 2010.

Methods

We conducted a cross-sectional study of the prevalence of antibody to pandemic (H1N1) 2009 among HCWs in Hong Kong in February–March 2010 following the first pandemic wave and the pH1N1 vaccination campaign. In this study we focus on the subset of healthcare workers who reported receipt of non-adjuvanted monovalent 2009 H1N1 vaccine (Panenza, Sanofi Pasteur). Sera collected from HCWs were tested for antibody against the pH1N1 virus by hemagglutination inhibition (HI) and viral neutralization (VN) assays.

Results

We enrolled 703 HCWs. Among 104 HCWs who reported receipt of pH1N1 vaccine, 54% (95% confidence interval (CI): 44%–63%) had antibody titer ≥1∶40 by HI and 42% (95% CI: 33%–52%) had antibody titer ≥1∶40 by VN. The proportion of HCWs with antibody titer ≥1∶40 by HI and VN significantly decreased with age, and the proportion with antibody titer ≥1∶40 by VN was marginally significantly lower among HCWs who reported prior receipt of 2007–08 seasonal influenza vaccine (odds ratio: 0.43; 95% CI: 0.19–1.00). After adjustment for age, the effect of prior seasonal vaccine receipt was not statistically significant.

Conclusions

Our findings suggest that monovalent H1N1 vaccine may have had suboptimal immunogenicity in HCWs in Hong Kong. Larger studies are required to confirm whether influenza vaccine maintains high efficacy and effectiveness in HCWs.     

Effectiveness of pandemic H1N1-2009 vaccination in reducing laboratory confirmed influenza infections among military recruits in tropical Singapore

Background

Limited information is available about pandemic H1N1-2009 influenza vaccine effectiveness in tropical communities. We studied the effectiveness of a pandemic H1N1 vaccination program in reducing influenza cases in Singapore.

Methods

A surveillance study was conducted among military personnel presenting with febrile respiratory illness from mid-2009 to mid-2010. Consenting individuals underwent nasal washes, which were tested with RT-PCR and subtyped. A vaccination program (inactivated monovalent Panvax H1N1-2009 vaccine) was carried out among recruits. A Bayesian hierarchical model was used to quantify relative risks in the pre- and post-vaccination periods. An autoregressive generalised linear model (GLM) was developed to minimise confounding.

Results

Of 2858 participants, 437(15.3%), 60(2.1%), and 273(9.6%) had pandemic H1N1, H3N2, and influenza B. The ratio of relative risks for pandemic H1N1 infection before and after vaccination for the recruit camp relative to other camps was 0.14(0.016,0.49); for H3N2, 0.44(0.035,1.8); and for influenza B, 18(0.77,89). Using the GLM for the recruit camp, post-vaccination weekly cases decreased by 54%(37%,67%, p<0.001) from that expected without vaccination; influenza B increased by 66 times(9–479 times, p<0.001); with no statistical difference for H3N2 (p = 0.54).

Conclusions

Pandemic vaccination reduced H1N1-2009 disease burden among military recruits. Routine seasonal influenza vaccination should be considered.     

Attitudes toward and uptake of H1N1 vaccine among health care workers during the 2009 H1N1 pandemic

Background

Though recommended by many and mandated by some, influenza vaccination rates among health care workers, even in pandemics, remain below optimal levels. The objective of this study was to assess vaccination uptake, attitudes, and distinguishing characteristics (including doctor-nurse differences) of health care workers who did and did not receive the pandemic H1N1 influenza vaccine in late 2009.

Methodology/Principal Findings

In early 2010 we mailed a self-administered survey to 800 physicians and 800 nurses currently licensed and practicing in Minnesota. 1,073 individuals responded (cooperation rate: 69%). 85% and 62% of Minnesota physicians and nurses, respectively, reported being vaccinated. Accurately estimating the risk of vaccine side effects (OR 2.0; 95% CI 1.5–2.7), agreeing with a professional obligation to be vaccinated (OR 10.1; 95% CI 7.1–14.2), an ethical obligation to follow public health authorities'' recommendations (OR 9.9; 95% CI 6.6–14.9), and laws mandating pandemic vaccination (OR 3.1; 95% CI 2.3–4.1) were all independently associated with receiving the H1N1 influenza vaccine.

Conclusions/Significance

While a majority of health care workers in one midwestern state reported receiving the pandemic H1N1 vaccine, physicians and nurses differed significantly in vaccination uptake. Several key attitudes and perceptions may influence health care workers'' decisions regarding vaccination. These data inform how states might optimally enlist health care workers'' support in achieving vaccination goals during a pandemic.     

Characterizing the epidemiology of the 2009 influenza A/H1N1 pandemic in Mexico

Background

Mexico''s local and national authorities initiated an intense public health response during the early stages of the 2009 A/H1N1 pandemic. In this study we analyzed the epidemiological patterns of the pandemic during April–December 2009 in Mexico and evaluated the impact of nonmedical interventions, school cycles, and demographic factors on influenza transmission.

Methods and Findings

We used influenza surveillance data compiled by the Mexican Institute for Social Security, representing 40% of the population, to study patterns in influenza-like illness (ILIs) hospitalizations, deaths, and case-fatality rate by pandemic wave and geographical region. We also estimated the reproduction number (R) on the basis of the growth rate of daily cases, and used a transmission model to evaluate the effectiveness of mitigation strategies initiated during the spring pandemic wave. A total of 117,626 ILI cases were identified during April–December 2009, of which 30.6% were tested for influenza, and 23.3% were positive for the influenza A/H1N1 pandemic virus. A three-wave pandemic profile was identified, with an initial wave in April–May (Mexico City area), a second wave in June–July (southeastern states), and a geographically widespread third wave in August–December. The median age of laboratory confirmed ILI cases was ∼18 years overall and increased to ∼31 years during autumn (p<0.0001). The case-fatality ratio among ILI cases was 1.2% overall, and highest (5.5%) among people over 60 years. The regional R estimates were 1.8–2.1, 1.6–1.9, and 1.2–1.3 for the spring, summer, and fall waves, respectively. We estimate that the 18-day period of mandatory school closures and other social distancing measures implemented in the greater Mexico City area was associated with a 29%–37% reduction in influenza transmission in spring 2009. In addition, an increase in R was observed in late May and early June in the southeast states, after mandatory school suspension resumed and before summer vacation started. State-specific fall pandemic waves began 2–5 weeks after school reopened for the fall term, coinciding with an age shift in influenza cases.

Conclusions

We documented three spatially heterogeneous waves of the 2009 A/H1N1 pandemic virus in Mexico, which were characterized by a relatively young age distribution of cases. Our study highlights the importance of school cycles on the transmission dynamics of this pandemic influenza strain and suggests that school closure and other mitigation measures could be useful to mitigate future influenza pandemics. Please see later in the article for the Editors'' Summary     

Intent to Receive Pandemic Influenza A (H1N1) Vaccine,Compliance with Social Distancing and Sources of Information in NC, 2009

Background

Public adherence to influenza vaccination recommendations has been low, particularly among younger adults and children under 2, despite the availability of safe and effective seasonal vaccine. Intention to receive 2009 pandemic influenza A (H1N1) vaccine has been estimated to be 50% in select populations. This report measures knowledge of and intention to receive pandemic vaccine in a population-based setting, including target groups for seasonal and H1N1 influenza.

Methodology and Principal Findings

On August 28–29, 2009, we conducted a population-based survey in 2 counties in North Carolina. The survey used the 30×7 two-stage cluster sampling methodology to identify 210 target households. Prevalence ratios (PR) and 95% confidence intervals (CI) were estimated. Knowledge of pandemic influenza A (H1N1) vaccine was high, with 165 (80%) aware that a vaccine was being prepared. A total of 133 (64%) respondents intended to receive pandemic vaccine, 134 (64%) intended to receive seasonal vaccine, and 109 (53%) intended to receive both. Reporting great concern about H1N1 infection (PR 1.55; 95%CI: 1.30, 1.85), receiving seasonal influenza vaccine in 2008–09 (PR 1.47; 95%CI: 1.18, 1.82), and intending to receive seasonal influenza vaccine in 2009–10 (PR 1.27; 95%CI: 1.14, 1.42) were associated with intention to receive pandemic vaccine. Not associated were knowledge of vaccine, employment, having children under age 18, gender, race/ethnicity and age. Reasons cited for not intending to get vaccinated include not being at risk for infection, concerns about vaccine side effects and belief that illness caused by pandemic H1N1 would be mild. Forty-five percent of households with children under 18 and 65% of working adults reported ability to comply with self-isolation at home for 7–10 days if recommended by authorities.

Conclusions and Significance

This is the first report of a population based rapid assessment used to assess knowledge and intent to receive pandemic vaccine in a community sample. Intention to receive pandemic and seasonal vaccines was higher than previously published reports. To reach persons not intending to receive pandemic vaccine, public health communications should focus on the perceived risk of infection and concerns about vaccine safety.     

Nationwide surveillance of influenza during the pandemic (2009-10) and post-pandemic (2010-11) periods in Taiwan

Introduction

Although WHO declared the world moving into the post-pandemic period on August 10, 2010, influenza A(H1N1) 2009 virus continued to circulate globally. Its impact was expected to continue during the 2010–11 influenza season. This study describes the nationwide surveillance findings of the pandemic and post-pandemic influenza periods in Taiwan and assesses the impact of influenza A(H1N1) 2009 during the post-pandemic period.

Methods

The Influenza Laboratory Surveillance Network consisted of 12 contract laboratories for collecting and testing samples with acute respiratory tract infections. Surveillance of emergency room visits and outpatient department visits for influenza-like illness (ILI) were conducted using the Real-Time Outbreak and Disease Surveillance system and the National Health Insurance program data, respectively. Hospitalized cases with severe complications and deaths were reported to the National Notifiable Disease Surveillance System.

Results

During the 2009–10 influenza season, pandemic A(H1N1) 2009 was the predominant circulating strain and caused 44 deaths. However, the 2010–11 influenza season began with A(H3N2) being the predominant circulating strain, changing to A(H1N1) 2009 in December 2010. Emergency room and outpatient department ILI surveillance displayed similar trends. By March 31, 2011, there were 1,751 cases of influenza with severe complications; 50.1% reported underlying diseases. Of the reported cases, 128 deaths were associated with influenza. Among these, 93 (72.6%) were influenza A(H1N1) 2009 and 30 (23.4%) A(H3N2). Compared to the pandemic period, during the immediate post-pandemic period, increased number of hospitalizations and deaths were observed, and the patients were consistently older.

Conclusions

Reemergence of influenza A(H1N1) 2009 during the 2010–11 influenza season had an intense activity with age distribution shift. To further mitigate the impact of future influenza epidemics, Taiwan must continue its multifaceted influenza surveillance systems, remain flexible with antiviral use policies, and revise the vaccine policies to include the population most at risk.     

I-MOVE multi-centre case control study 2010-11: overall and stratified estimates of influenza vaccine effectiveness in Europe

Background

In the third season of I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe), we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in eight European Union (EU) member states to estimate 2010/11 influenza vaccine effectiveness (VE) against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza.

Methods

Using systematic sampling, practitioners swabbed ILI/ARI patients within seven days of symptom onset. We compared influenza-positive to influenza laboratory-negative patients among those meeting the EU ILI case definition. A valid vaccination corresponded to > 14 days between receiving a dose of vaccine and symptom onset. We used multiple imputation with chained equations to estimate missing values. Using logistic regression with study as fixed effect we calculated influenza VE adjusting for potential confounders. We estimated influenza VE overall, by influenza type, age group and among the target group for vaccination.

Results

We included 2019 cases and 2391 controls in the analysis. Adjusted VE was 52% (95% CI 30-67) overall (N = 4410), 55% (95% CI 29-72) against A(H1N1) and 50% (95% CI 14-71) against influenza B. Adjusted VE against all influenza subtypes was 66% (95% CI 15-86), 41% (95% CI -3-66) and 60% (95% CI 17-81) among those aged 0-14, 15-59 and ≥60 respectively. Among target groups for vaccination (N = 1004), VE was 56% (95% CI 34-71) overall, 59% (95% CI 32-75) against A(H1N1) and 63% (95% CI 31-81) against influenza B.

Conclusions

Results suggest moderate protection from 2010-11 trivalent influenza vaccines against medically-attended ILI laboratory-confirmed as influenza across Europe. Adjusted and stratified influenza VE estimates are possible with the large sample size of this multi-centre case-control. I-MOVE shows how a network can provide precise summary VE measures across Europe.     

Determinants of non-vaccination against pandemic 2009 H1N1 influenza in pregnant women: a prospective cohort study

Background

In October 2009, the French government organized a national-wide, free of charge vaccination campaign against pandemic H1N1 influenza virus, especially targeting pregnant women, a high risk group for severe illness. The study objective was to evaluate pandemic flu vaccine uptake and factors associated with non-vaccination in a population of pregnant women.

Methodology/Principal Findings

In a prospective cohort conducted in 3 maternity hospitals in Paris, 882 pregnant women were randomly included between October 12, 2009 and February 3, 2010, with the aim to study characteristics of pandemic influenza during pregnancy. At inclusion, socio-demographic, medical, obstetrical factors and those associated with a higher risk of flu exposition and disease-spreading were systematically collected. Pandemic flu vaccine uptake was checked until delivery. 555 (62.9%) women did not get vaccinated. Determinants associated with non-vaccination in a multivariate logistic regression were: geographic origin (Sub-Saharan African origin, adjusted Odd Ratio aOR = 5.4[2.3–12.7], North African origin, aOR = 2.5[1.3–4.7] and Asian origin, aOR = 2.1[1.7–2.6] compared to French and European origin) and socio-professional categories (farmers, craftsmen and tradesmen, aOR = 2.3[2.0–2.6], intermediate professionals, aOR = 1.3[1.0–1.6], employees and manual workers, aOR = 2.5[1.4–4.4] compared to managers and intellectual professionals). The probability of not receiving pandemic flu vaccine was lower among women vaccinated against seasonal flu in the previous 5 years (aOR = 0.6[0.4–0.8]) and among those who stopped smoking before or early during pregnancy (aOR = 0.6[0.4–0.8]). Number of children less than 18 years old living at home, work in contact with children or in healthcare area, or professional contact with the public, were not associated with a higher vaccine uptake.

Conclusions/Significance

In this cohort of pregnant women, vaccine coverage against pandemic 2009 A/H1N1 flu was low, particularly in immigrant women and those having a low socio-economic status. To improve its effectiveness, future vaccination campaign for pregnant women should be more specifically tailored for these populations.     

Post-pandemic seroprevalence of pandemic influenza A (H1N1) 2009 infection (swine flu) among children <18 years in Germany

Background

We determined antibodies to the pandemic influenza A (H1N1) 2009 virus in children to assess: the incidence of (H1N1) 2009 infections in the 2009/2010 season in Germany, the proportion of subclinical infections and to compare titers in vaccinated and infected children.

Methodology/Principal Findings

Eight pediatric hospitals distributed over Germany prospectively provided sera from in- or outpatients aged 1 to 17 years from April 1^st to July 31^st 2010. Vaccination history, recall of infections and sociodemographic factors were ascertained. Antibody titers were measured with a sensitive and specific in-house hemagglutination inhibition test (HIT) and compared to age-matched sera collected during 6 months before the onset of the pandemic in Germany. We analyzed 1420 post-pandemic and 300 pre-pandemic sera. Among unvaccinated children aged 1–4 and 5–17 years the prevalence of HI titers (≥1∶10) was 27.1% (95% CI: 23.5–31.3) and 53.5% (95% CI: 50.9–56.2) compared to 1.7% and 5.5%, respectively, for pre-pandemic sera, accounting for a serologically determined incidence of influenza A (H1N1) 2009 during the season 2009/2010 of 25,4% (95% CI : 19.3–30.5) in children aged 1–4 years and 48.0% (95% CI: 42.6–52.0) in 5–17 year old children. Of children with HI titers ≥1∶10, 25.5% (95% CI: 22.5–28.8) reported no history of any infectious disease since June 2009. Among vaccinated children, 92% (95%-CI: 87.0–96.6) of the 5–17 year old but only 47.8% (95%-CI: 33.5–66.5) of the 1–4 year old children exhibited HI titers against influenza A virus (H1N1) 2009.

Conclusion

Serologically determined incidence of influenza A (H1N1) 2009 infections in children indicates high infection rates with older children (5–17 years) infected twice as often as younger children. In about a quarter of the children with HI titers after the season 2009/2010 subclinical infections must be assumed. Low HI titers in young children after vaccination with the AS03_B-adjuvanted split virion vaccine need further scrutiny.     

Predictors of the uptake of A (H1N1) influenza vaccine: findings from a population-based longitudinal study in Tokyo

Background

Overall pandemic A (H1N1) influenza vaccination rates remain low across all nations, including Japan. To increase the rates, it is important to understand the motives and barriers for the acceptance of the vaccine. We conducted this study to determine potential predictors of the uptake of A (H1N1) influenza vaccine in a cohort of Japanese general population.

Methodology/Principal Findings

By using self-administered questionnaires, this population-based longitudinal study was conducted from October 2009 to April 2010 among 428 adults aged 18–65 years randomly selected from each household residing in four wards and one city in Tokyo. Multiple logistic regression analyses were performed. Of total, 38.1% of participants received seasonal influenza vaccine during the preceding season, 57.0% had willingness to accept A (H1N1) influenza vaccine at baseline, and 12.1% had received A (H1N1) influenza vaccine by the time of follow-up. After adjustment for potential confounding variables, people who had been vaccinated were significantly more likely to be living with an underlying disease (p = 0.001), to perceive high susceptibility to influenza (p = 0.03), to have willingness to pay even if the vaccine costs ≥ US$44 (p = 0.04), to have received seasonal influenza vaccine during the preceding season (p<0.001), and to have willingness to accept A (H1N1) influenza vaccine at baseline (p<0.001) compared to those who had not been vaccinated.

Conclusions/Significance

While studies have reported high rates of willingness to receive A (H1N1) influenza vaccine, these rates may not transpire in the actual practices. The uptake of the vaccine may be determined by several potential factors such as perceived susceptibility to influenza and sensitivity to vaccination cost in general population.     

Effective Detection of the 2009 H1N1 Influenza Pandemic in U.S. Veterans Affairs Medical Centers Using a National Electronic Biosurveillance System

Background

The 2008–09 influenza season was the time in which the Department of Veterans Affairs (VA) utilized an electronic biosurveillance system for tracking and monitoring of influenza trends. The system, known as ESSENCE or Electronic Surveillance System for the Early Notification of Community-based Epidemics, was monitored for the influenza season as well as for a rise in influenza cases at the start of the H1N1 2009 influenza pandemic. We also describe trends noted in influenza-like illness (ILI) outpatient encounter data in VA medical centers during the 2008–09 influenza season, before and after the recognition of pandemic H1N1 2009 influenza virus.

Methodology/Principal Findings

We determined prevalence of ILI coded visits using VA''s ESSENCE for 2008–09 seasonal influenza (Sept. 28, 2008–April 25, 2009 corresponding to CDC 2008–2009 flu season weeks 40–16) and the early period of pandemic H1N1 2009 (April 26, 2009–July 31, 2009 corresponding to CDC 2008–2009 flu season weeks 17–30). Differences in diagnostic ICD-9-CM code frequencies were analyzed using Chi-square and odds ratios. There were 649,574 ILI encounters captured representing 633,893 patients. The prevalence of VA ILI visits mirrored the CDC''s Outpatient ILI Surveillance Network (ILINet) data with peaks in late December, early February, and late April/early May, mirroring the ILINet data; however, the peaks seen in the VA were smaller. Of 31 ILI codes, 6 decreased and 11 increased significantly during the early period of pandemic H1N1 2009. The ILI codes that significantly increased were more likely to be symptom codes. Although influenza with respiratory manifestation (487.1) was the most common code used among 150 confirmed pandemic H1N1 2009 cases, overall it significantly decreased since the start of the pandemic.

Conclusions/Significance

VA ESSENCE effectively detected and tracked changing ILI trends during pandemic H1N1 2009 and represents an important temporal alerting system for monitoring health events in VA facilities.     

Age distribution of cases of 2009 (H1N1) pandemic influenza in comparison with seasonal influenza

Introduction

Several aspects of the epidemiology of 2009 (H1N1) pandemic influenza have not been accurately determined. We sought to study whether the age distribution of cases differs in comparison with seasonal influenza.

Methods

We searched for official, publicly available data through the internet from different countries worldwide on the age distribution of cases of influenza during the 2009 (H1N1) pandemic influenza period and most recent seasonal influenza periods. Data had to be recorded through the same surveillance system for both compared periods.

Results

For 2009 pandemic influenza versus recent influenza seasons, in USA, visits for influenza-like illness to sentinel providers were more likely to involve the age groups of 5–24, 25–64 and 0–4 years compared with the reference group of >64 years [odds ratio (OR) (95% confidence interval (CI)): 2.43 (2.39–2.47), 1.66 (1.64–1.69), and 1.51 (1.48–1.54), respectively]. Pediatric deaths were less likely in the age groups of 2–4 and <2 years than the reference group of 5–17 years [OR (95% CI): 0.46 (0.25–0.85) and 0.49 (0.30–0.81), respectively]. In Australia, notifications for laboratory-confirmed influenza were more likely in the age groups of 10–19, 5–9, 20–44, 45–64 and 0–4 years than the reference group of >65 years [OR (95% CI): 7.19 (6.67–7.75), 5.33 (4.90–5.79), 5.04 (4.70–5.41), 3.12 (2.89–3.36) and 1.89 (1.75–2.05), respectively]. In New Zealand, consultations for influenza-like illness by sentinel providers were more likely in the age groups of <1, 1–4, 35–49, 5–19, 20–34 and 50–64 years than the reference group of >65 years [OR (95% CI): 2.38 (1.74–3.26), 1.99 (1.62–2.45), 1.57 (1.30–1.89), 1.57 (1.30–1.88), 1.40 (1.17–1.69) and 1.39 (1.14–1.70), respectively].

Conclusions

The greatest increase in influenza cases during 2009 (H1N1) pandemic influenza period, in comparison with most recent seasonal influenza periods, was seen for school-aged children, adolescents, and younger adults.     

Effectiveness of Seasonal Influenza Vaccines against Influenza-Associated Illnesses among US Military Personnel in 2010-11: A Case-Control Approach

Introduction

Following the 2009 influenza A/H1N1 (pH1N1) pandemic, both seasonal and pH1N1 viruses circulated in the US during the 2010–2011 influenza season; influenza vaccine effectiveness (VE) may vary between live attenuated (LAIV) and trivalent inactivated (TIV) vaccines as well as by virus subtype.

Materials and Methods

Vaccine type and virus subtype-specific VE were determined for US military active component personnel for the period of September 1, 2010 through April 30, 2011. Laboratory-confirmed influenza-related medical encounters were compared to matched individuals with a non-respiratory illness (healthy controls), and unmatched individuals who experienced a non-influenza respiratory illness (test-negative controls). Odds ratios (OR) and VE estimates were calculated overall, by vaccine type and influenza subtype.

Results

A total of 603 influenza cases were identified. Overall VE was relatively low and similar regardless of whether healthy controls (VE = 26%, 95% CI: −1 to 45) or test-negative controls (VE = 29%, 95% CI: −6 to 53) were used as comparison groups. Using test-negative controls, vaccine type-specific VE was found to be higher for TIV (53%, 95% CI: 25 to 71) than for LAIV (VE = −13%, 95% CI: −77 to 27). Influenza subtype-specific analyses revealed moderate protection against A/H3 (VE = 58%, 95% CI: 21 to 78), but not against A/H1 (VE = −38%, 95% CI: −211 to 39) or B (VE = 34%, 95% CI: −122 to 80).

Conclusion

Overall, a low level of protection against clinically-apparent, laboratory-confirmed, influenza was found for the 2010–11 seasonal influenza vaccines. TIV immunization was associated with higher protection than LAIV, however, no protection against A/H1 was noted, despite inclusion of a pandemic influenza strain as a vaccine component for two consecutive years. Vaccine virus mismatch or lower immunogenicity may have contributed to these findings and deserve further examination in controlled studies. Continued assessment of VE in military personnel is essential in order to better inform vaccination policy decisions.     

Response to 2009 pandemic influenza A (H1N1) vaccine in HIV-infected patients and the influence of prior seasonal influenza vaccination

Background

The immunogenicity of 2009 pandemic influenza A(H1N1) (pH1N1) vaccines and the effect of previous influenza vaccination is a matter of current interest and debate. We measured the immune response to pH1N1 vaccine in HIV-infected patients and in healthy controls. In addition we tested whether recent vaccination with seasonal trivalent inactivated vaccine (TIV) induced cross-reactive antibodies to pH1N1. (clinicaltrials.gov Identifier:{"type":"clinical-trial","attrs":{"text":"NCT01066169","term_id":"NCT01066169"}}NCT01066169)

Methods and Findings

In this single-center prospective cohort study MF59-adjuvanted pH1N1 vaccine (Focetria®, Novartis) was administered twice to 58 adult HIV-infected patients and 44 healthy controls in November 2009 (day 0 and day 21). Antibody responses were measured at baseline, day 21 and day 56 with hemagglutination-inhibition (HI) assay. The seroprotection rate (defined as HI titers ≥1∶40) for HIV-infected patients was 88% after the first and 91% after the second vaccination. These rates were comparable to those in healthy controls. Post-vaccination GMT, a sensitive marker of the immune competence of a group, was lower in HIV-infected patients. We found a high seroprotection rate at baseline (31%). Seroprotective titers at baseline were much more common in those who had received 2009–2010 seasonal TIV three weeks prior to the first dose of pH1N1 vaccine. Using stored serum samples of 51 HIV-infected participants we measured the pH1N1 specific response to 2009–2010 seasonal TIV. The seroprotection rate to pH1N1 increased from 22% to 49% after vaccination with 2009–2010 seasonal TIV. Seasonal TIV induced higher levels of antibodies to pH1N1 in older than in younger subjects.

Conclusion

In HIV-infected patients on combination antiretroviral therapy, with a median CD4+ T-lymphocyte count above 500 cells/mm³, one dose of MF59-adjuvanted pH1N1 vaccine induced a high seroprotection rate comparable to that in healthy controls. A second dose had a modest additional effect. Furthermore, seasonal TIV induced cross-reactive antibodies to pH1N1 and this effect was more pronounced in older subjects.     

The impact of pandemic influenza H1N1 on health-related quality of life: a prospective population-based study

Background

While the H1N1v influenza pandemic in 2009 was clinically mild, with a low case-fatality rate, the overall disease burden measured in quality-adjusted life years (QALY) lost has not been estimated. Such a measure would allow comparison with other diseases and assessment of the cost-effectiveness of pandemic control measures.

Methods and Findings

Cases of H1N1v confirmed by polymerase chain reaction (PCR) and PCR negative cases with similar influenza-like illness (ILI controls) in 7 regions of England were sent two questionnaires, one within a week of symptom onset and one two weeks later, requesting information on duration of illness, work loss and antiviral use together with EQ-5D questionnaires. Results were compared with those for seasonal influenza from a systematic literature review. A total QALY loss for the 2009 pandemic in England was calculated based on the estimated total clinical cases and reported deaths. A total of 655 questionnaires were sent and 296 (45%) returned. Symptoms and average illness duration were similar between confirmed cases and ILI controls (8.8 days and 8.7 days respectively). Days off work were greater for cases than ILI controls (7.3 and 4.9 days respectively, p = 0.003). The quality-adjusted life days lost was 2.92 for confirmed cases and 2.74 for ILI controls, with a reduction in QALY loss after prompt use of antivirals in confirmed cases. The overall QALY loss in the pandemic was estimated at 28,126 QALYs (22,267 discounted) of which 40% was due to deaths (24% with discounting).

Conclusion

Given the global public health significance of influenza, it is remarkable that no previous prospective study of the QALY loss of influenza using standardised and well validated methods has been performed. Although the QALY loss was minor for individual patients, the estimated total burden of influenza over the pandemic was substantial when compared to other infectious diseases.     

Cross-protection against lethal H5N1 challenge in ferrets with an adjuvanted pandemic influenza vaccine

Background

Unprecedented spread between birds and mammals of highly pathogenic avian influenza viruses (HPAI) of the H5N1 subtype has resulted in hundreds of human infections with a high fatality rate. This has highlighted the urgent need for the development of H5N1 vaccines that can be produced rapidly and in sufficient quantities. Potential pandemic inactivated vaccines will ideally induce substantial intra-subtypic cross-protection in humans to warrant the option of use, either prior to or just after the start of a pandemic outbreak. In the present study, we evaluated a split H5N1 A/H5N1/Vietnam/1194/04, clade 1 candidate vaccine, adjuvanted with a proprietary oil-in- water emulsion based Adjuvant System proven to be well-tolerated and highly immunogenic in the human (Leroux-Roels et al. (2007) The Lancet 370:580–589), for its ability to induce intra-subtypic cross-protection against clade 2 H5N1/A/Indonesia/5/05 challenge in ferrets.

Methodology and Principal Findings

All ferrets in control groups receiving non-adjuvanted vaccine or adjuvant alone failed to develop specific or cross-reactive neutralizing antibodies and all died or had to be euthanized within four days of virus challenge. Two doses of adjuvanted split H5N1 vaccine containing ≥1.7 µg HA induced neutralizing antibodies in the majority of ferrets to both clade 1 (17/23 (74%) responders) and clade 2 viruses (14/23 (61%) responders), and 96% (22/23) of vaccinees survived the lethal challenge. Furthermore lung virus loads and viral shedding in the upper respiratory tract were reduced in vaccinated animals relative to controls suggesting that vaccination might also confer a reduced risk of viral transmission.

Conclusion

These protection data in a stringent challenge model in association with an excellent clinical profile highlight the potential of this adjuvanted H5N1 candidate vaccine as an effective tool in pandemic preparedness.