Performance of influenza case definitions for influenza community surveillance: based on the French influenza surveillance network GROG, 2009-2014.

International case definitions recommended by the Centers for Disease Control and Prevention (CDC), the European Centre for Disease Prevention and Control (ECDC), and the World Health Organization (WHO) are commonly used for influenza surveillance. We evaluated clinical factors associated with the laboratory-confirmed diagnosis of influenza and the performance of these influenza case definitions by using a complete dataset of 14,994 patients with acute respiratory infection (ARI) from whom a specimen was collected between August 2009 and April 2014 by the Groupes Régionaux d'Observation de la Grippe (GROG), a French national influenza surveillance network. Cough and fever ≥ 39 °C most accurately predicted an influenza infection in all age groups. Several other symptoms were associated with an increased risk of influenza (headache, weakness, myalgia, coryza) or decreased risk (adenopathy, pharyngitis, shortness of breath, otitis/otalgia, bronchitis/ bronchiolitis), but not throughout all age groups. The WHO case definition for influenza-like illness (ILI) had the highest specificity with 21.4%, while the ECDC ILI case definition had the highest sensitivity with 96.1%. The diagnosis among children younger than 5 years remains challenging. The study compared the performance of clinical influenza definitions based on outpatient surveillance and will contribute to improving the comparability of data shared at international level.

I-MOVE multicentre case-control study 2010/11 to 2014/15: Is there within-season waning of influenza type/subtype vaccine effectiveness with increasing time since vaccination?

Since the 2008/9 influenza season, the I-MOVE multicentre case-control study measures influenza vaccine effectiveness (VE) against medically-attended influenza-like-illness (ILI) laboratory confirmed as influenza. In 2011/12, European studies reported a decline in VE against influenza A(H3N2) within the season. Using combined I-MOVE data from 2010/11 to 2014/15 we studied the effects of time since vaccination on influenza type/subtype-specific VE. We modelled influenza type/subtype-specific VE by time since vaccination using a restricted cubic spline, controlling for potential confounders (age, sex, time of onset, chronic conditions). Over 10,000 ILI cases were included in each analysis of influenza A(H3N2), A(H1N1)pdm09 and B; with 4,759, 3,152 and 3,617 influenza positive cases respectively. VE against influenza A(H3N2) reached 50.6% (95% CI: 30.0-65.1) 38 days after vaccination, declined to 0% (95% CI: -18.1-15.2) from 111 days onwards. At day 54 VE against influenza A(H1N1)pdm09 reached 55.3% (95% CI: 37.9-67.9) and remained between this value and 50.3% (95% CI: 34.8-62.1) until season end. VE against influenza B declined from 70.7% (95% CI: 51.3-82.4) 44 days after vaccination to 21.4% (95% CI: -57.4-60.8) at season end. To assess if vaccination campaign strategies need revising more evidence on VE by time since vaccination is urgently needed.

Ten influenza seasons in France: distribution and timing of influenza A and B circulation, 2003-2013.

BACKGROUND: Describing the circulation of influenza viruses and the characteristics of seasonal epidemics remains an essential tool to optimize the strategies of influenza prevention and control. Special attention has been recently paid to influenza B in the context of the availability of a quadrivalent vaccine, containing two influenza B strains. METHODS: We used data from a practitioners-based influenza surveillance network to describe the circulation of influenza viruses in France from 2003-2004 to 2012-2013. Nasopharyngeal swabs taken from acute respiratory infection (ARI) patients between October and April were tested for influenza. We reported the number of influenza cases by virus type (A, B), subtype (A(H1), A(H3)) and B lineage (Yamagata, Victoria) in each season and determined the frequency of influenza B vaccine mismatch. We estimated weekly incidence of influenza by extrapolating reported influenza cases to the French population. We compared the temporal characteristics of the epidemics caused by influenza A(H1), A(H3) and B. RESULTS: Overall, 49,919 ARI patients were tested, of which 16,287 (32.6 %) were positive for influenza. Type B virus caused 23.7 % of all influenza cases. Virus subtypes A(H1) and A(H3) caused 51.6 % and 48.4 % of influenza A cases, respectively. Viruses of the B-Yamagata and B-Victoria lineage caused 62.8 % and 37.2 % of influenza B cases, respectively. There was an influenza B vaccine mismatch in three of the five seasons where influenza B caused 10 % or more of all influenza cases. Influenza A(H3) had the highest average value of estimated weekly incidence during the study period. Influenza B peaked an average 3.8 weeks later than influenza A when both virus types were circulating. No differences in the duration of influenza A and B epidemics were observed. CONCLUSIONS: Influenza A(H3) was the most prevalent influenza type during the study period. Influenza B caused around one fourth of all influenza cases and tended to circulate later than influenza A. The frequency of influenza B vaccine mismatches was substantial. Timely data on the circulation of influenza viruses collected within influenza surveillance systems are essential to optimize influenza prevention and control strategies.

Prospective screening for significant liver fibrosis by fibrosis-4 in primary care patients without known liver disease.

BACKGROUND: Fibrosis-4 test (FIB-4) is one of the simplest, free of charge, noninvasive scoring tests. We aimed to prospectively measure the prevalence of liver fibrosis in adults with no previously known liver disease and who consulted a general practitioner by FIB-4 score; compare this test to an NAFLD Fibrosis Score (NFS) and Fibrometer (FM); explore the prevalence of risk factors (obesity, diabetes, alcohol, and hypertension) and reconsider a possible cause of liver disease in patients recognized as FIB-4-positive. METHODS: Over a 6-month period, 40 general practitioners (GPs) offered all their consecutive adult primary care patients with no previously known liver pathology and a liver fibrosis screening via a blood test of three scores. RESULTS: Among the consecutive 2121 patients included in the study, 39% had a BMI greater than 25 kg/m2, 13% had an alcohol consumption greater than 100 g/week, 10% had type 2 diabetes, and 29% had hypertension. The prevalence of significant liver fibrosis by FIB-4, according to age was 19.1% (95% confidence interval: 17.5-20.9%). By comparison, prevalence was 16.8% (15.0-18.5%) by the NFS and 8.2% (6.9-9.6%) by the FM. A significant relationship was observed between FIB-4 fibrosis risk stages and NFS and FM scores. GPs identified the cause of disease in 2/3 of FIB-4-positive cases, mainly nonalcoholic steatohepatitis. CONCLUSION: Liver fibrosis was suspected by FIB-4 score in 19.1% of patients with no previously known liver disease. The detection of significant fibrosis by the FIB-4 allowed the GP to suspect liver disease. The FIB-4 score that can be automatically generated should allow earlier recognition of liver disease in the general population.

Exploring the effect of previous inactivated influenza vaccination on seasonal influenza vaccine effectiveness against medically attended influenza: Results of the European I-MOVE multicentre test-negative case-control study, 2011/2012-2016/2017.

BACKGROUND: Results of previous influenza vaccination effects on current season influenza vaccine effectiveness (VE) are inconsistent. OBJECTIVES: To explore previous influenza vaccination effects on current season VE among population targeted for vaccination. METHODS: We used 2011/2012 to 2016/2017 I-MOVE primary care multicentre test-negative data. For each season, we compared current season adjusted VE (aVE) between individuals vaccinated and unvaccinated in previous season. Using unvaccinated in both seasons as a reference, we then compared aVE between vaccinated in both seasons, current only, and previous only. RESULTS: We included 941, 2645 and 959 influenza-like illness patients positive for influenza A(H1N1)pdm09, A(H3N2) and B, respectively, and 5532 controls. In 2011/2012, 2014/2015 and 2016/2017, A(H3N2) aVE point estimates among those vaccinated in previous season were -68%, -21% and -19%, respectively; among unvaccinated in previous season, these were 33%, 48% and 46%, respectively (aVE not computable for influenza A(H1N1)pdm09 and B). Compared to current season vaccination only, VE for both seasons' vaccination was (i) similar in two of four seasons for A(H3N2) (absolute difference [ad] 6% and 8%); (ii) lower in three of four seasons for influenza A(H1N1)pdm09 (ad 18%, 26% and 29%), in two seasons for influenza A(H3N2) (ad 27% and 39%) and in two of three seasons for influenza B (ad 26% and 37%); (iii) higher in one season for influenza A(H1N1)pdm09 (ad 20%) and influenza B (ad 24%). CONCLUSIONS: We did not identify any pattern of previous influenza vaccination effect. Prospective cohort studies documenting influenza infections, vaccinations and vaccine types are needed to understand previous influenza vaccinations' effects.

Does seasonal vaccination affect the clinical presentation of influenza among the elderly? A cross-sectional analysis in the outpatient setting in France, 2003-2014.

Vaccine-induced protection against influenza is not optimal, however it has been suggested that the vaccine may reduce the severity of symptoms among those who develop illness despite being vaccinated. We tested this hypothesis within a countrywide, sentinel general practitioners-based surveillance system in France. We included 2277 individuals aged 65years or older (of whom 1293 had been vaccinated against influenza, 56.8%) who consulted a general practitioner because of an acute respiratory infection (ARI) during 2003-2014. All patients were taken a nasopharyngeal swab, and information was collected on demographic characteristics and symptoms at disease onset. All specimens were tested for respiratory viruses and, if positive for influenza, the virus type and subtype were determined. We compared the average maximum temperature and the frequency of each symptom, between non-vaccinated and vaccinated influenza patients. We then used logistic regression models to calculate the odds of presenting with each symptom between vaccinated vs. non-vaccinated patients, adjusting by age group, virus (sub)type and season. Overall, 675 ARI patients (29.6%) tested positive for influenza. The A(H3) virus caused the majority of cases (55.1%), followed by influenza B (22.9%), A not-subtyped (11.7%), and A(H1) (10.3%) viruses. Compared to non-vaccinated influenza patients, those who had been vaccinated had a slightly reduced maximum temperature and presented less frequently with myalgia, shivering and headache. In stratified analyses, the observed effect was limited to patients infected with A(H3) or type B viruses. After adjusting by age group, virus (sub)type and season, the difference remained statistically significant only for headache, which was less frequent among vaccinated individuals (odds ratio 0.69, 95% confidence intervals 0.48-0.98). In conclusion, the vaccine was found to be modestly associated with less severe clinical presentation of influenza among the elderly. Our findings reinforce the need for influenza vaccines providing better protection.

Clinical Characteristics Are Similar across Type A and B Influenza Virus Infections.

BACKGROUND: Studies that aimed at comparing the clinical presentation of influenza patients across virus types and subtypes/lineages found divergent results, but this was never investigated using data collected over several years in a countrywide, primary care practitioners-based influenza surveillance system. METHODS: The IBVD (Influenza B in Vircases Database) study collected information on signs and symptoms at disease onset from laboratory-confirmed influenza patients of any age who consulted a sentinel practitioner in France. We compared the clinical presentation of influenza patients across age groups (0-4, 5-14, 15-64 and 65+ years), virus types (A, B) and subtypes/lineages (A(H3N2), pandemic A(H1N1), B Victoria, B Yamagata). RESULTS: Overall, 14,423 influenza cases (23.9% of which were influenza B) were included between 2003-2004 and 2012-2013. Influenza A and B accounted for over 50% of total influenza cases during eight and two seasons, respectively. There were minor differences in the distribution of signs and symptoms across influenza virus types and subtypes/lineages. Compared to patients aged 0-4 years, those aged 5-14 years were more likely to have been infected with type B viruses (OR 2.15, 95% CI 1.87-2.47) while those aged 15-64 years were less likely (OR 0.83, 95% CI 0.73-0.96). Males and influenza patients diagnosed during the epidemic period were less likely to be infected with type B viruses. CONCLUSIONS: Despite differences in age distribution, the clinical illness produced by the different influenza virus types and subtypes is indistinguishable among patients that consult a general practitioner for acute respiratory infections.

Use of neuraminidase inhibitors in primary health care during pandemic and seasonal influenza between 2009 and 2013.

BACKGROUND: In a context of controversy about influenza antiviral treatments, this study assessed primary health-care physicians' prescription of neuraminidase inhibitors (NIs) in France during pandemic and seasonal influenza between 2009 and 2013. METHODS: This observational study, using data recorded in three national databases, estimated the rate of NI prescription among influenza-like illness (ILI) patients seen in GP and paediatrician consultations, and determined factors associated with this prescription according to a multivariate analysis. NI delivery by pharmacists was also evaluated. RESULTS: Rates of NI prescription were estimated to be 61.1% among ILI patients with a severe influenza risk factor seen in GP consultation during the A(H1N1)pdm2009 pandemic versus an average rate of 25.9% during the three following seasonal influenza epidemics. Factors associated with NI prescription were a chronic disease in patients under 65 years (OR 14.85; 95% CI 13.00, 16.97) and in those aged 65 and older (OR 7.54; 5.86, 9.70), an age ≥65 years in patients without chronic disease (OR 1.35; 1.04, 1.74), a pregnancy (OR 10.63; 7.67, 15.76), obesity (OR 4.67; 3.50, 6.22) and a consultation during the pandemic A(H1N1)pdm2009 (OR 3.19; 2.93, 3.48). The number of antiviral treatments delivered by pharmacists during the A(H1N1)pdm2009 pandemic was 835 per 100,000 inhabitants, and an average of 275 per 100,000 inhabitants during the three following seasonal influenza epidemics. CONCLUSIONS: Although physicians seem to follow the recommended indications for NIs in primary health-care practice, this study confirms the low rate of NI prescription to ILI patients with a severe influenza risk factor, especially during seasonal epidemics.

Striking Similarities in the Presentation and Duration of Illness of Influenza A and B in the Community: A Study Based on Sentinel Surveillance Networks in France and Turkey, 2010-2012.

Influenza B represents a high proportion of influenza cases in some seasons (even over 50%). The Influenza B study in General Practice (IBGP) is a multicenter study providing information about the clinical, demographic and socio-economic characteristics of patients affected by lab-confirmed influenza A or B. Influenza B patients and age-matched influenza A patients were recruited within the sentinel surveillance networks of France and Turkey in 2010-11 and 2011-12 seasons. Data were collected for each patient at the swab test day, after 9±2 days and, if not recovered, after 28±5 days. It was related to patient's characteristics, symptoms at presentation, vaccination status, prescriptions of antibiotics and antivirals, duration of illness, follow-up consultations in general practice or emergency room. We performed descriptive analyses and developed a multiple regression model to investigate the effect of patients and disease characteristics on the duration of illness. Overall, 774 influenza cases were included in the study: 419 influenza B cases (209 in France and 210 in Turkey) and 355 influenza A cases (205 in France and 150 in Turkey). There were no differences between influenza A and B patients in terms of clinical presentation and number of consultations with a practitioner; however, the use of antivirals was higher among influenza B patients in both countries. The average (median) reported duration of illness in the age groups 0-14 years, 15-64 years and 65+ years was 7.4 (6), 8.7 (8) and 10.5 (9) days in France, and 6.3 (6), 8.2 (7) and 9.2 (6) days in Turkey; it increased with age but did not differ by virus type; increased duration of illness was associated with antibiotics prescription. In conclusion, our findings show that influenza B infection appears not to be milder disease than influenza A infection.

Field seasonal influenza vaccine effectiveness: evaluation of the screening method using different sources of data during the 2010/2011 French influenza season.

Thanks to the screening method, we estimated among target groups the 2010/2011 field vaccine effectiveness (FVE) against laboratory confirmed influenza cases seen in general practice. We also compared the values of FVE estimations obtained by using three sources of the population vaccination coverage (VC) based on three different methodologies: (1) administrative data from the main social security scheme (Caisse Nationale d'Assurance Maladie des Travailleurs Salariés--CNAMTS) covering about 85% of the French population, (2) a cross-sectional national telephone survey in the general population, and (3) a declarative survey in the population seen in a one-day general practitioner (GP) consultations. The FVE estimates among target groups were stratified by age (< 65 y old with reported chronic illness; ≥65 y old and overall). Using the VC of the CNAMTS, the FVE of the 2010/2011 seasonal trivalent vaccine against laboratory confirmed infection with any influenza virus was 59% (95% Confidence Interval, 17 to 81). It was 85% (17 to 99) and 50% (-16 to 80) for A(H1N1)pdm09 and B influenza infections, respectively. The values of FVE using the influenza VC obtained in a sample of the general population and of the population of GPs' patients were 73% (45 to 87) and 82% (63 to 92), respectively. We estimated a moderate influenza FVE in preventing confirmed influenza viruses in target groups by using the VC of the CNAMTS. We also observed that the screening method generates FVE values dependent on the choice of the source of VC and thus should be used cautiously.

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.