Epidemiologic and economic burden of influenza in the outpatient setting: a prospective study in a subtropical area of china

Objectives

To understand the incidence of outpatient influenza cases in a subtropical area of China and the associated economic burden on patients'' families.

Methods

A hospital-based prospective study was conducted in Zhuhai City during 2008–2009. All outpatient influenza-like illness (ILI) cases were identified in 28 sentinel hospitals. A representative sample of throat swabs from ILI cases were collected for virus isolation using Madin-Darby canine kidney cells. The incidence of outpatient influenza cases in Zhuhai was estimated on the basis of the number of influenza patients detected by the sentinel sites. A telephone survey on the direct costs associated with illness was conducted as a follow-up.

Results

The incidence of influenza was estimated to be 4.1 per 1,000 population in 2008 and 19.2 per 1,000 population in 2009. Children aged <5 years were the most-affected population, suffering from influenza at the highest rates (34.3 per 1,000 population in 2008 and 95.3 per 1,000 population in 2009). A high incidence of 29.2–40.9 per 1000 population was also seen in young people aged 5–24 years in 2009. ILI activity and influenza virus isolations adopted a consistent seasonal pattern, with a summer peak in July 2008 and the longest epidemic period lasting from July–December 2009. The medical costs per episode of influenza among urban patients were higher than those for rural patients. A total of $1.1 million in direct economic losses were estimated to be associated with outpatient influenza during 2008–2009 in Zhuhai community.

Conclusions

Influenza attacks children aged <5 years in greater proportions than children in other age groups. Seasonal influenza 2008 and Pandemic influenza A (H1N1) 2009 had different epidemiological and etiological characteristics. Direct costs (mostly medical costs) impose an enormous burden on the patient family. Vaccination strategies for high-risk groups need to be further strengthened.     

The Burden of Influenza and RSV among Inpatients and Outpatients in Rural Western Kenya, 2009–2012

Background

In Kenya, detailed data on the age-specific burden of influenza and RSV are essential to inform use of limited vaccination and treatment resources.

Methods

We analyzed surveillance data from August 2009 to July 2012 for hospitalized severe acute respiratory illness (SARI) and outpatient influenza-like illness (ILI) at two health facilities in western Kenya to estimate the burden of influenza and respiratory syncytial virus (RSV). Incidence rates were estimated by dividing the number of cases with laboratory-confirmed virus infections by the mid-year population. Rates were adjusted for healthcare-seeking behavior, and to account for patients who met the SARI/ILI case definitions but were not tested.

Results

The average annual incidence of influenza-associated SARI hospitalization per 1,000 persons was 2.7 (95% CI 1.8–3.9) among children <5 years and 0.3 (95% CI 0.2–0.4) among persons ≥5 years; for RSV-associated SARI hospitalization, it was 5.2 (95% CI 4.0–6.8) among children <5 years and 0.1 (95% CI 0.0–0.2) among persons ≥5 years. The incidence of influenza-associated medically-attended ILI per 1,000 was 24.0 (95% CI 16.6–34.7) among children <5 years and 3.8 (95% CI 2.6–5.7) among persons ≥5 years. The incidence of RSV-associated medically-attended ILI was 24.6 (95% CI 17.0–35.4) among children <5 years and 0.8 (95% CI 0.3–1.9) among persons ≥5 years.

Conclusions

Influenza and RSV both exact an important burden in children. This highlights the possible value of influenza vaccines, and future RSV vaccines, for Kenyan children.     

School-Located Influenza Vaccination Reduces Community Risk for Influenza and Influenza-Like Illness Emergency Care Visits

Background

School-located influenza vaccination (SLIV) programs can substantially enhance the sub-optimal coverage achieved under existing delivery strategies. Randomized SLIV trials have shown these programs reduce laboratory-confirmed influenza among both vaccinated and unvaccinated children. This work explores the effectiveness of a SLIV program in reducing the community risk of influenza and influenza-like illness (ILI) associated emergency care visits.

Methods

For the 2011/12 and 2012/13 influenza seasons, we estimated age-group specific attack rates (AR) for ILI from routine surveillance and census data. Age-group specific SLIV program effectiveness was estimated as one minus the AR ratio for Alachua County versus two comparison regions: the 12 county region surrounding Alachua County, and all non-Alachua counties in Florida.

Results

Vaccination of ∼50% of 5–17 year-olds in Alachua reduced their risk of ILI-associated visits, compared to the rest of Florida, by 79% (95% confidence interval: 70, 85) in 2011/12 and 71% (63, 77) in 2012/13. The greatest indirect effectiveness was observed among 0–4 year-olds, reducing AR by 89% (84, 93) in 2011/12 and 84% (79, 88) in 2012/13. Among all non-school age residents, the estimated indirect effectiveness was 60% (54, 65) and 36% (31, 41) for 2011/12 and 2012/13. The overall effectiveness among all age-groups was 65% (61, 70) and 46% (42, 50) for 2011/12 and 2012/13.

Conclusion

Wider implementation of SLIV programs can significantly reduce the influenza-associated public health burden in communities.     

Impact of Influenza on Outpatient Visits,Hospitalizations, and Deaths by Using a Time Series Poisson Generalized Additive Model

Background

The disease burden associated with influenza in developing tropical and subtropical countries is poorly understood owing to the lack of a comprehensive disease surveillance system and information-exchange mechanisms. The impact of influenza on outpatient visits, hospital admissions, and deaths has not been fully demonstrated to date in south China.

Methods

A time series Poisson generalized additive model was used to quantitatively assess influenza-like illness (ILI) and influenza disease burden by using influenza surveillance data in Zhuhai City from 2007 to 2009, combined with the outpatient, inpatient, and respiratory disease mortality data of the same period.

Results

The influenza activity in Zhuhai City demonstrated a typical subtropical seasonal pattern; however, each influenza virus subtype showed a specific transmission variation. The weekly ILI case number and virus isolation rate had a very close positive correlation (r = 0.774, P < 0.0001). The impact of ILI and influenza on weekly outpatient visits was statistically significant (P < 0.05). We determined that 10.7% of outpatient visits were associated with ILI and 1.88% were associated with influenza. ILI also had a significant influence on the hospitalization rates (P < 0.05), but mainly in populations <25 years of age. No statistically significant effect of influenza on hospital admissions was found (P > 0.05). The impact of ILI on chronic obstructive pulmonary disease (COPD) was most significant (P < 0.05), with 33.1% of COPD-related deaths being attributable to ILI. The impact of influenza on the mortality rate requires further evaluation.

Conclusions

ILI is a feasible indicator of influenza activity. Both ILI and influenza have a large impact on outpatient visits. Although ILI affects the number of hospital admissions and deaths, we found no consistent influence of influenza, which requires further assessment.     

Monitoring influenza activity in the United States: a comparison of traditional surveillance systems with Google Flu Trends

Background

Google Flu Trends was developed to estimate US influenza-like illness (ILI) rates from internet searches; however ILI does not necessarily correlate with actual influenza virus infections.

Methods and Findings

Influenza activity data from 2003–04 through 2007–08 were obtained from three US surveillance systems: Google Flu Trends, CDC Outpatient ILI Surveillance Network (CDC ILI Surveillance), and US Influenza Virologic Surveillance System (CDC Virus Surveillance). Pearson''s correlation coefficients with 95% confidence intervals (95% CI) were calculated to compare surveillance data. An analysis was performed to investigate outlier observations and determine the extent to which they affected the correlations between surveillance data. Pearson''s correlation coefficient describing Google Flu Trends and CDC Virus Surveillance over the study period was 0.72 (95% CI: 0.64, 0.79). The correlation between CDC ILI Surveillance and CDC Virus Surveillance over the same period was 0.85 (95% CI: 0.81, 0.89). Most of the outlier observations in both comparisons were from the 2003–04 influenza season. Exclusion of the outlier observations did not substantially improve the correlation between Google Flu Trends and CDC Virus Surveillance (0.82; 95% CI: 0.76, 0.87) or CDC ILI Surveillance and CDC Virus Surveillance (0.86; 95%CI: 0.82, 0.90).

Conclusions

This analysis demonstrates that while Google Flu Trends is highly correlated with rates of ILI, it has a lower correlation with surveillance for laboratory-confirmed influenza. Most of the outlier observations occurred during the 2003–04 influenza season that was characterized by early and intense influenza activity, which potentially altered health care seeking behavior, physician testing practices, and internet search behavior.     

The Clinical and Etiological Characteristics of Influenza-Like Illness (ILI) in Outpatients in Shanghai,China, 2011 to 2013

Introduction

Clinical and etiological characteristics of influenza-like illness (ILI) in outpatients is poorly understood in the southern temperate region of China. We conducted laboratory-based surveillance of viral etiology for ILI outpatients in Shanghai from January 2011 to December 2013.

Materials and Methods

Clinical and epidemiological data from ILI outpatients, both children and adults, were collected. A total of 1970 nasopharyngeal swabs were collected and tested for 12 respiratory viruses using multiplex RT-PCR, and the data were analyzed anonymously.

Results

All 12 respiratory viruses were detected in the specimens. At least one virus was detected in 32.4% of 1970 specimens analyzed, with 1.1% showing co-infections. The most frequently detected agents were influenza A (11.7%), influenza B (9.6%), and rhinoviruses (3.1%).Other viruses were present at a frequency less than 3.0%. We observed a winter peak in the detection rate in ILI patients during 3 years of surveillance and a summer peak in 2012. HCoV, HADV, and HMPV were detected more frequently in children than in adults. Patients infected with influenza virus experienced higher temperatures, more coughs, running noses, headaches and fatigue than patients infected with other viruses and virus-free patients (p<0.001).

Conclusions

The spectrum, seasonality, age distribution and clinical associations of respiratory virus infections in children and adults with influenza-like illness were analyzed in this study for the first time. To a certain extent, the findings can provide baseline data for evaluating the burden of respiratory virus infection in children and adults in Shanghai. It will also provide clinicians with helpful information about the etiological patterns of outpatients presenting with complaints of acute respiratory syndrome, but further studies should be conducted, and longer-term laboratory-based surveillance would give a better picture of the etiology of ILI.     

Surveillance and Vaccine Effectiveness of an Influenza Epidemic Predominated by Vaccine-Mismatched Influenza B/Yamagata-Lineage Viruses in Taiwan, 2011?12 Season

Introduction

The 2011−12 trivalent influenza vaccine contains a strain of influenza B/Victoria-lineage viruses. Despite free provision of influenza vaccine among target populations, an epidemic predominated by influenza B/Yamagata-lineage viruses occurred during the 2011−12 season in Taiwan. We characterized this vaccine-mismatched epidemic and estimated influenza vaccine effectiveness (VE).

Methods

Influenza activity was monitored through sentinel viral surveillance, emergency department (ED) and outpatient influenza-like illness (ILI) syndromic surveillance, and case-based surveillance of influenza with complications and deaths. VE against laboratory-confirmed influenza was evaluated through a case-control study on ILI patients enrolled into sentinel viral surveillance. Logistic regression was used to estimate VE adjusted for confounding factors.

Results

During July 2011−June 2012, influenza B accounted for 2,382 (72.5%) of 3,285 influenza-positive respiratory specimens. Of 329 influenza B viral isolates with antigen characterization, 287 (87.2%) were B/Yamagata-lineage viruses. Proportions of ED and outpatient visits being ILI-related increased from November 2011 to January 2012. Of 1,704 confirmed cases of influenza with complications, including 154 (9.0%) deaths, influenza B accounted for 1,034 (60.7%) of the confirmed cases and 103 (66.9%) of the deaths. Reporting rates of confirmed influenza with complications and deaths were 73.5 and 6.6 per 1,000,000, respectively, highest among those aged ≥65 years, 50−64 years, 3−6 years, and 0−2 years. Adjusted VE was −31% (95% CI: −80, 4) against all influenza, 54% (95% CI: 3, 78) against influenza A, and −66% (95% CI: −132, −18) against influenza B.

Conclusions

This influenza epidemic in Taiwan was predominated by B/Yamagata-lineage viruses unprotected by the 2011−12 trivalent vaccine. The morbidity and mortality of this vaccine-mismatched epidemic warrants careful consideration of introducing a quadrivalent influenza vaccine that includes strains of both B lineages.     

Synchrony of clinical and laboratory surveillance for influenza in Hong Kong

Background

Consultation rates of influenza-like illness (ILI) in an outpatient setting have been regarded as a good indicator of influenza virus activity in the community. As ILI-like symptoms may be caused by etiologies other than influenza, and influenza virus activity in the tropics and subtropics is less predictable than in temperate regions, the correlation between of ILI and influenza virus activity in tropical and subtropical regions is less well defined.

Methodology and Principal Findings

In this study, we used wavelet analysis to investigate the relationship between seasonality of influenza virus activity and consultation rates of ILI reported separately by General Out-patient Clinics (GOPC) and General Practitioners (GP). During the periods 1998–2000 and 2002–2003, influenza virus activity exhibited both annual and semiannual cycles, with one peak in the winter and another in late spring or early summer. But during 2001 and 2004–2006, only annual cycles could be clearly identified. ILI consultation rates in both GOPC and GP settings share a similar non-stationary seasonal pattern. We found high coherence between ILI in GOPC and influenza virus activity for the annual cycle, but this was only significant (p<0.05) during the periods 1998–1999 and 2002–2006. For the semiannual cycle high coherence (p<0.05) was also found significant during the period 1998–1999 and year 2003 when two peaks of influenza were evident. Similarly, ILI in GP setting is also associated with influenza virus activity for both the annual and semiannual cycles. On average, oscillation of ILI in GP and of ILI in GOPC preceded influenza virus isolation by approximately four and two weeks, respectively.

Conclusions

Our findings suggest that consultation rates of ILI precede the oscillations of laboratory surveillance by at least two weeks and can be used as a predictor for influenza epidemics in Hong Kong. The validity of our model for other tropical regions needs to be explored.     

Household Transmission of Influenza A(H1N1)pdm09 in the Pandemic and Post-Pandemic Seasons

Background

The transmission of influenza viruses occurs person to person and is facilitated by contacts within enclosed environments such as households. The aim of this study was to evaluate secondary attack rates and factors associated with household transmission of laboratory-confirmed influenza A(H1N1)pdm09 in the pandemic and post-pandemic seasons.

Methods

During the 2009–2010 and 2010–2011 influenza seasons, 76 sentinel physicians in Navarra, Spain, took nasopharyngeal and pharyngeal swabs from patients diagnosed with influenza-like illness. A trained nurse telephoned households of those patients who were laboratory-confirmed for influenza A(H1N1)pdm09 to ask about the symptoms, risk factors and vaccination status of each household member.

Results

In the 405 households with a patient laboratory-confirmed for influenza A(H1N1)pdm09, 977 susceptible contacts were identified; 16% of them (95% CI 14–19%) presented influenza-like illness and were considered as secondary cases. The secondary attack rate was 14% in 2009–2010 and 19% in the 2010–2011 season (p = 0.049), an increase that mainly affected persons with major chronic conditions. In the multivariate logistic regression analysis, the risk of being a secondary case was higher in the 2010–2011 season than in the 2009–2010 season (adjusted odds ratio: 1.72; 95% CI 1.17–2.54), and in children under 5 years, with a decreasing risk in older contacts. Influenza vaccination was associated with lesser incidence of influenza-like illness near to statistical significance (adjusted odds ratio: 0.29; 95% CI 0.08–1.03).

Conclusion

The secondary attack rate in households was higher in the second season than in the first pandemic season. Children had a greater risk of infection. Preventive measures should be maintained in the second pandemic season, especially in high-risk persons.     

Influenza A (H1N1) in Victoria, Australia: a community case series and analysis of household transmission

Background

We characterise the clinical features and household transmission of pandemic influenza A (pH1N1) in community cases from Victoria, Australia in 2009.

Methods

Questionnaires were used to collect information on epidemiological characteristics, illness features and co-morbidities of cases identified in the 2009 Victorian Influenza Sentinel Surveillance program.

Results

The median age of 132 index cases was 21 years, of whom 54 (41%) were under 18 years old and 28 (21%) had medical co-morbidities. The median symptom duration was significantly shorter for children who received antivirals than in those who did not (p = 0.03). Assumed influenza transmission was observed in 63 (51%) households. Influenza-like illness (ILI) developed in 115 of 351 household contacts, a crude secondary attack rate of 33%. Increased ILI rates were seen in households with larger numbers of children but not larger numbers of adults. Multivariate analysis indicated contacts of cases with cough and diarrhoea, and contacts in quarantined households were significantly more likely to develop influenza-like symptoms.

Conclusion

Most cases of pH1N1 in our study were mild with similar clinical characteristics to seasonal influenza. Illness and case features relating to virus excretion, age and household quarantine may have influenced secondary ILI rates within households.     

Influenza surveillance among outpatients and inpatients in Morocco, 1996-2009

Background

There is limited information about the epidemiology of influenza in Africa. We describe the epidemiology and seasonality of influenza in Morocco from 1996 to 2009 with particular emphasis on the 2007–2008 and 2008–2009 influenza seasons. Successes and challenges of the enhanced surveillance system introduced in 2007 are also discussed.

Methods

Virologic sentinel surveillance for influenza virus was initiated in Morocco in 1996 using a network of private practitioners that collected oro-pharyngeal and naso-pharyngeal swabs from outpatients presenting with influenza-like-illness (ILI). The surveillance network expanded over the years to include inpatients presenting with severe acute respiratory illness (SARI) at hospitals and syndromic surveillance for ILI and acute respiratory infection (ARI). Respiratory samples and structured questionnaires were collected from eligible patients, and samples were tested by immunofluorescence assays and by viral isolation for influenza viruses.

Results

We obtained a total of 6465 respiratory specimens during 1996 to 2009, of which, 3102 were collected during 2007–2009. Of those, 2249 (72%) were from patients with ILI, and 853 (27%) were from patients with SARI. Among the 3,102 patients, 98 (3%) had laboratory-confirmed influenza, of whom, 85 (87%) had ILI and 13 (13%) had SARI. Among ILI patients, the highest proportion of laboratory-confirmed influenza occurred in children less than 5 years of age (3/169; 2% during 2007–2008 and 23/271; 9% during 2008–2009) and patients 25–59 years of age (8/440; 2% during 2007–2009 and 21/483; 4% during 2008–2009). All SARI patients with influenza were less than 14 years of age. During all surveillance years, influenza virus circulation was seasonal with peak circulation during the winter months of October through April.

Conclusion

Influenza results in both mild and severe respiratory infections in Morocco, and accounted for a large proportion of all hospitalizations for severe respiratory illness among children 5 years of age and younger.     

Demonstrating the Use of High-Volume Electronic Medical Claims Data to Monitor Local and Regional Influenza Activity in the US

Introduction

Fine-grained influenza surveillance data are lacking in the US, hampering our ability to monitor disease spread at a local scale. Here we evaluate the performances of high-volume electronic medical claims data to assess local and regional influenza activity.

Material and Methods

We used electronic medical claims data compiled by IMS Health in 480 US locations to create weekly regional influenza-like-illness (ILI) time series during 2003–2010. IMS Health captured 62% of US outpatient visits in 2009. We studied the performances of IMS-ILI indicators against reference influenza surveillance datasets, including CDC-ILI outpatient and laboratory-confirmed influenza data. We estimated correlation in weekly incidences, peak timing and seasonal intensity across datasets, stratified by 10 regions and four age groups (<5, 5–29, 30–59, and 60+ years). To test IMS-Health performances at the city level, we compared IMS-ILI indicators to syndromic surveillance data for New York City. We also used control data on laboratory-confirmed Respiratory Syncytial Virus (RSV) activity to test the specificity of IMS-ILI for influenza surveillance.

Results

Regional IMS-ILI indicators were highly synchronous with CDC''s reference influenza surveillance data (Pearson correlation coefficients rho≥0.89; range across regions, 0.80–0.97, P<0.001). Seasonal intensity estimates were weakly correlated across datasets in all age data (rho≤0.52), moderately correlated among adults (rho≥0.64) and uncorrelated among school-age children. IMS-ILI indicators were more correlated with reference influenza data than control RSV indicators (rho = 0.93 with influenza v. rho = 0.33 with RSV, P<0.05). City-level IMS-ILI indicators were highly consistent with reference syndromic data (rho≥0.86).

Conclusion

Medical claims-based ILI indicators accurately capture weekly fluctuations in influenza activity in all US regions during inter-pandemic and pandemic seasons, and can be broken down by age groups and fine geographical areas. Medical claims data provide more reliable and fine-grained indicators of influenza activity than other high-volume electronic algorithms and should be used to augment existing influenza surveillance systems.     

Evaluation of Two Influenza Surveillance Systems in South Africa

Background

The World Health Organisation recommends outpatient influenza-like illness (ILI) and inpatient severe acute respiratory illness (SARI) surveillance. We evaluated two influenza surveillance systems in South Africa: one for ILI and another for SARI.

Methodology

The Viral Watch (VW) programme has collected virological influenza surveillance data voluntarily from patients with ILI since 1984 in private and public clinics in all 9 South African provinces. The SARI surveillance programme has collected epidemiological and virological influenza surveillance data since 2009 in public hospitals in 4 provinces by dedicated personnel. We compared nine surveillance system attributes from 2009–2012.

Results

We analysed data from 18,293 SARI patients and 9,104 ILI patients. The annual proportion of samples testing positive for influenza was higher for VW (mean 41%) than SARI (mean 8%) and generally exceeded the seasonal threshold from May to September (VW: weeks 21–40; SARI: weeks 23–39). Data quality was a major strength of SARI (most data completion measures >90%; adherence to definitions: 88–89%) and a relative weakness of the VW programme (62% of forms complete, with limited epidemiologic data collected; adherence to definitions: 65–82%). Timeliness was a relative strength of both systems (e.g. both collected >93% of all respiratory specimens within 7 days of symptom onset). ILI surveillance was more nationally representative, financially sustainable and expandable than the SARI system. Though the SARI programme is not nationally representative, the high quality and detail of SARI data collection sheds light on the local burden and epidemiology of severe influenza-associated disease.

Conclusions

To best monitor influenza in South Africa, we propose that both ILI and SARI should be under surveillance. Improving ILI surveillance will require better quality and more systematic data collection, and SARI surveillance should be expanded to be more nationally representative, even if this requires scaling back on information gathered.     

Field effectiveness of pandemic and 2009-2010 seasonal vaccines against 2009-2010 A(H1N1) influenza: estimations from surveillance data in France

Background

In this study, we assess how effective pandemic and trivalent 2009-2010 seasonal vaccines were in preventing influenza-like illness (ILI) during the 2009 A(H1N1) pandemic in France. We also compare vaccine effectiveness against ILI versus laboratory-confirmed pandemic A(H1N1) influenza, and assess the possible bias caused by using non-specific endpoints and observational data.

Methodology and Principal Findings

We estimated vaccine effectiveness by using the following formula: VE  =  (PPV-PCV)/(PPV(1-PCV)) × 100%, where PPV is the proportion vaccinated in the population and PCV the proportion of vaccinated influenza cases. People were considered vaccinated three weeks after receiving a dose of vaccine. ILI and pandemic A(H1N1) laboratory-confirmed cases were obtained from two surveillance networks of general practitioners. During the epidemic, 99.7% of influenza isolates were pandemic A(H1N1). Pandemic and seasonal vaccine uptakes in the population were obtained from the National Health Insurance database and by telephonic surveys, respectively. Effectiveness estimates were adjusted by age and week. The presence of residual biases was explored by calculating vaccine effectiveness after the influenza period. The effectiveness of pandemic vaccines in preventing ILI was 52% (95% confidence interval: 30–69) during the pandemic and 33% (4–55) after. It was 86% (56–98) against confirmed influenza. The effectiveness of seasonal vaccines against ILI was 61% (56–66) during the pandemic and 19% (−10–41) after. It was 60% (41–74) against confirmed influenza.

Conclusions

The effectiveness of pandemic vaccines in preventing confirmed pandemic A(H1N1) influenza on the field was high, consistently with published findings. It was significantly lower against ILI. This is unsurprising since not all ILI cases are caused by influenza. Trivalent 2009-2010 seasonal vaccines had a statistically significant effectiveness in preventing ILI and confirmed pandemic influenza, but were not better in preventing confirmed pandemic influenza than in preventing ILI. This lack of difference might be indicative of selection bias.     

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.     

Elementary School-Based Influenza Vaccination: Evaluating Impact on Respiratory Illness Absenteeism and Laboratory-Confirmed Influenza

Background

Studies of influenza vaccine effectiveness in schools have assessed all-cause absenteeism rather than laboratory-confirmed influenza. We conducted an observational pilot study to identify absences due to respiratory illness and laboratory-confirmed influenza in schools with and without school-based vaccination.

Methods

A local public health agency initiated school-based influenza vaccination in two Wisconsin elementary schools during October 2010 (exposed schools); two nearby schools served as a comparison group (non-exposed schools). Absences due to fever or cough illness were monitored for 12 weeks. During the 4 weeks of peak influenza activity, parents of absent children with fever/cough illness were contacted and offered influenza testing.

Results

Parental consent for sharing absenteeism data was obtained for 937 (57%) of 1,640 students. Fifty-two percent and 28%, respectively, of all students in exposed and non-exposed schools were vaccinated. Absences due to fever or cough illness were significantly lower in the exposed schools during seven of 12 surveillance weeks. Twenty-seven percent of students at exposed schools and 39% at unexposed schools had one or more days of absence due to fever/cough illness (p<0.0001). There was no significant difference in the proportion of students absent for other reasons (p = 0.23). During the 4 week period of influenza testing, respiratory samples were obtained for 68 (42%) of 163 episodes of absence due to fever or cough illness. Influenza was detected in 6 students; 3 attended exposed schools.

Conclusions

Detection of laboratory-confirmed influenza in schools was challenging due to multiple consent requirements, difficulty obtaining samples from absent children, and a mild influenza season. School-based influenza vaccination was associated with reduced absenteeism due to fever or cough illness, but not absenteeism for other reasons. Although nonspecific, absence due to fever or cough illness may be a useful surrogate endpoint in school-based studies if identification of laboratory confirmed influenza is not feasible.     

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.     

Estimating the Influenza Vaccine Effectiveness against Medically Attended Influenza in Clinical Settings: A Hospital-Based Case-Control Study with a Rapid Diagnostic Test in Japan

Background

Influenza vaccine effectiveness (VE) studies are usually conducted by specialized agencies and require time and resources. The objective of this study was to estimate the influenza VE against medically attended influenza using a test-negative case-control design with rapid influenza diagnostic tests (RIDT) in a clinical setting.

Methods

A prospective study was conducted at a community hospital in Nagasaki, western Japan during the 2010/11 influenza season. All outpatients aged 15 years and older with influenza-like illnesses (ILI) who had undergone RIDT were enrolled. A test-negative case-control design was applied to estimate the VEs: the cases were ILI patients with positive RIDT results and the controls were ILI patients with negative RIDT results. Information on patient characteristics, including vaccination histories, was collected using questionnaires and medical records.

Results

Between December 2010 and April 2011, 526 ILI patients were tested with RIDT, and 476 were eligible for the analysis. The overall VE estimate against medically attended influenza was 47.6%, after adjusting for the patients'' age groups, presence of chronic conditions, month of visit, and smoking and alcohol use. The seasonal influenza vaccine reduced the risk of medically attended influenza by 60.9% for patients less than 50 years of age, but a significant reduction was not observed for patients 50 years of age and older. A sensitivity analysis provided similar figures.

Conclusion

The test-negative case-control study using RIDT provided moderate influenza VE consistent with other reports. Utilizing the commonly used RIDT to estimate VE provides rapid assessment of VE; however, it may require validation with more specific endpoint.     

Etiology and clinical characteristics of influenza-like illness (ILI) in outpatients in Beijing, June 2010 to May 2011

Background

Since May 2009, exposure of the population of Beijing, China to pH1N1 has resulted in an increase in respiratory illnesses. Limited information is available on the etiology and clinical characteristics of the influenza-like illness (ILI) that ensued in adults following the pH1N1 pandemic.

Methods

Clinical and epidemiological data of ILI in adults was collected. A total of 279 throat swabs were tested for twelve respiratory viruses using multiplex RT-PCR. Clinical characteristics of influenza A in outpatients versus test-negative patients were compared using Pearson''s χ2 and the Mann-Whitney U test. 190 swabs were tested for pH1N1 by virus isolation. Consultation rates for ILI were compared between 2009 and 2010.

Results

One or two virus were detected in 29% of the samples. Influenza A virus (FLU-A) accounted for 22.9% (64/279). Other viruses were present at a frequency less than 3.0%. Cough was significantly associated with Influenza A virus infection (χ2, p<0.001). The positive rate of FLU-A was consistent with changes in the ILI rate during the same period and there was a significant reduction in the incidence of ILI in 2010 when compared to 2009. During the 2010–2011 influenza season, the incidence peaked in January 2011 in Beijing and north China.

Conclusions

Exposure to pH1N1 had no impact on typical influenza seasonal peaks, although FLU-A remained the predominant virus for 2010 in Beijing. Symptomatically, cough was associated with FLU-A infection. The positive rate of influenza virus was consistent with changes in the ILI rate during the same period and there was a significant reduction in the incidence of ILI in 2010 when compared to that of 2009.