Incidence and severity of pertussis hospitalisations in infants aged less than 1 year in 37 hospitals of six EU/EEA countries, results of PERTINENT sentinel pilot surveillance system, December 2015 to December 2018.

IntroductionPERTINENT is a pilot active surveillance system of infants hospitalised with pertussis in six European Union/European Economic Area countries (37 hospitals, seven sites).AimThis observational study aimed to estimate annual pertussis incidence per site from 2016 to 2018 and respective trends between 2017 and 2018. Pertussis cases were described, including their severity.MethodsWe developed a generic protocol and laboratory guidelines to harmonise practices across sites. Cases were hospitalised infants testing positive for Bordetella pertussis by PCR or culture. Sites collected demographic, clinical, laboratory data, vaccination status, and risk/protective factors. We estimated sites' annual incidences by dividing case numbers by the catchment populations.ResultsFrom December 2015 to December 2018, we identified 469 cases (247 males; 53%). The median age, birthweight and gestational age were 2.5 months (range: 0-11.6; interquartile range (IQR): 2.5), 3,280 g (range: 700-4,925; IQR: 720) and 39 weeks (range: 25-42; IQR: 2), respectively. Thirty cases (6%) had atypical presentation either with cough or cyanosis only or with absence of pertussis-like symptoms. Of 330 cases with information, 83 (25%) were admitted to intensive care units including five deceased infants too young to be vaccinated. Incidence rate ratios between 2018 and 2017 were 1.43 in Czech Republic (p = 0.468), 0.25 in Catalonia (p = 0.002), 0.71 in France (p = 0.034), 0.14 in Ireland (p = 0.002), 0.63 in Italy (p = 0.053), 0.21 in Navarra (p = 0.148) and zero in Norway.ConclusionsIncidence appeared to decrease between 2017 and 2018 in all but one site. Enhanced surveillance of hospitalised pertussis in Europe is essential to monitor pertussis epidemiology and disease burden.

Low 2016/17 season vaccine effectiveness against hospitalised influenza A(H3N2) among elderly: awareness warranted for 2017/18 season.

In a multicentre European hospital study we measured influenza vaccine effectiveness (IVE) against A(H3N2) in 2016/17. Adjusted IVE was 17% (95% confidence interval (CI): 1 to 31) overall; 25% (95% CI: 2 to 43) among 65-79-year-olds and 13% (95% CI: -15 to 30) among those ≥ 80 years. As the A(H3N2) vaccine component has not changed for 2017/18, physicians and public health experts should be aware that IVE could be low where A(H3N2) viruses predominate.

Vaccine effectiveness in preventing laboratory-confirmed influenza in primary care patients in a season of co-circulation of influenza A(H1N1)pdm09, B and drifted A(H3N2), I-MOVE Multicentre Case-Control Study, Europe 2014/15.

Influenza A(H3N2), A(H1N1)pdm09 and B viruses co-circulated in Europe in 2014/15. We undertook a multicentre case-control study in eight European countries to measure 2014/15 influenza vaccine effectiveness (VE) against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. General practitioners swabbed all or a systematic sample of ILI patients. We compared the odds of vaccination of ILI influenza positive patients to negative patients. We calculated adjusted VE by influenza type/subtype, and age group. Among 6,579 ILI patients included, 1,828 were A(H3N2), 539 A(H1N1)pdm09 and 1,038 B. VE against A(H3N2) was 14.4% (95% confidence interval (CI): -6.3 to 31.0) overall, 20.7% (95%CI: -22.3 to 48.5), 10.9% (95%CI -30.8 to 39.3) and 15.8% (95% CI: -20.2 to 41.0) among those aged 0-14, 15-59 and  ≥60 years, respectively. VE against A(H1N1)pdm09 was 54.2% (95%CI: 31.2 to 69.6) overall, 73.1% (95%CI: 39.6 to 88.1), 59.7% (95%CI: 10.9 to 81.8), and 22.4% (95%CI: -44.4 to 58.4) among those aged 0-14, 15-59 and  ≥60 years respectively. VE against B was 48.0% (95%CI: 28.9 to 61.9) overall, 62.1% (95%CI: 14.9 to 83.1), 41.4% (95%CI: 6.2 to 63.4) and 50.4% (95%CI: 14.6 to 71.2) among those aged 0-14, 15-59 and ≥60 years respectively. VE against A(H1N1)pdm09 and B was moderate. The low VE against A(H3N2) is consistent with the reported mismatch between circulating and vaccine strains.

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.

Effectiveness of pertussis vaccination in pregnancy to prevent hospitalisation in infants aged <2 months and effectiveness of both primary vaccination and mother's vaccination in pregnancy in infants aged 2-11 months.

BACKGROUND: PERTINENT is an active hospital-based surveillance system for pertussis in infants. In 2019, four of the six participating European countries recommended pertussis vaccination in pregnancy. Among infants aged <2 months, we measured the vaccine effectiveness (VE) in pregnancy; among infants aged 2-11 months, VE of vaccination in pregnancy and of primary vaccination (PV). METHODS: From December 2015 to 2019, we included all infants aged <1 year presenting with pertussis-like symptoms. Using a test-negative-design, cases were infants testing positive for Bordetella pertussis by PCR or culture. Controls were those testing negative for all Bordetella species. Vaccinated mothers were those who received vaccine in pregnancy. Vaccinated infants were those who received ≥1 dose of PV > 14 days before symptom onset. We excluded infants with unknown maternal or PV status or with mothers vaccinated ≤14 days before delivery. We calculated pooled VE as 100 * (1-odds ratio of vaccination) adjusted for study site, onset date in quarters and infants' age group. RESULTS: Of 829 infants presenting with pertussis-like symptoms, 336 (41%) were too young for PV. For the VE in pregnancy analysis, we included 75 cases and 201 controls. Vaccination in pregnancy was recorded for 9 cases (12%) and 92 controls (46%), adjusted VE was between 75% [95%CI: 35-91%] and 88% [95%CI: 57-96%]. Of 493 infants eligible for PV, we included 123 cases and 253 controls. Thirty-one cases and 98 controls recorded both PV with ≥ 1 dose and vaccination in pregnancy, adjusted VE was between 74% [95%CI: 33-90] and 95% [95%CI: 69-99]; 27 cases and 53 controls recorded PV only, adjusted VE was between 68% [95%CI: 27-86] and 94% [95%CI: 59-99]. CONCLUSION: Our findings suggest that vaccination in pregnancy reduces pertussis incidence in infants too young for PV. In infants aged 2-11 months, PV only and both PV and vaccination in pregnancy provide significant protection against severe pertussis.

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.

Vaccine effectiveness against influenza A(H3N2) and B among laboratory-confirmed, hospitalised older adults, Europe, 2017-18: A season of B lineage mismatched to the trivalent vaccine.

BACKGROUND: Influenza A(H3N2), A(H1N1)pdm09 and B viruses co-circulated in Europe in 2017-18, predominated by influenza B. WHO-recommended, trivalent vaccine components were lineage-mismatched for B. The I-MOVE hospital network measured 2017-18 seasonal influenza vaccine effectiveness (IVE) against influenza A(H3N2) and B among hospitalised patients (≥65 years) in Europe. METHODS: Following the same generic protocol for test-negative design, hospital teams in nine countries swabbed patients ≥65 years with recent onset (≤7 days) severe acute respiratory infection (SARI), collecting information on demographics, vaccination status and underlying conditions. Cases were RT-PCR positive for influenza A(H3N2) or B; controls: negative for any influenza. "Vaccinated" patients had SARI onset >14 days after vaccination. We measured pooled IVE against influenza, adjusted for study site, age, sex, onset date and chronic conditions. RESULTS: We included 3483 patients: 376 influenza A(H3N2) and 928 B cases, and 2028 controls. Most (>99%) vaccinated patients received the B lineage-mismatched trivalent vaccine. IVE against influenza A(H3N2) was 24% (95% CI: 2 to 40); 35% (95% CI: 6 to 55) in 65- to 79-year-olds and 14% (95% CI: -22 to 39) in ≥80-year-olds. Against influenza B, IVE was 30% (95% CI: 16 to 41); 37% (95% CI: 19 to 51) in 65- to 79-year-olds and 19% (95% CI: -7 to 38) in ≥80-year-olds. CONCLUSIONS: IVE against influenza B was similar to A(H3N2) in hospitalised older adults, despite trivalent vaccine and circulating B lineage mismatch, suggesting some cross-protection. IVE was lower in those ≥80 than 65-79 years. We reinforce the importance of influenza vaccination in older adults as, even with a poorly matched vaccine, it still protects one in three to four of this population from severe influenza.

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.

2015/16 I-MOVE/I-MOVE+ multicentre case-control study in Europe: Moderate vaccine effectiveness estimates against influenza A(H1N1)pdm09 and low estimates against lineage-mismatched influenza B among children.

BACKGROUND: During the 2015/16 influenza season in Europe, the cocirculating influenza viruses were A(H1N1)pdm09 and B/Victoria, which was antigenically distinct from the B/Yamagata component in the trivalent influenza vaccine. METHODS: We used the test-negative design in a multicentre case-control study in twelve European countries to measure 2015/16 influenza vaccine effectiveness (VE) against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza. General practitioners swabbed a systematic sample of consulting ILI patients and a random sample of influenza-positive swabs was sequenced. We calculated adjusted VE against influenza A(H1N1)pdm09, A(H1N1)pdm09 genetic group 6B.1 and influenza B overall and by age group. RESULTS: We included 11 430 ILI patients, of which 2272 were influenza A(H1N1)pdm09 and 2901 were influenza B cases. Overall VE against influenza A(H1N1)pdm09 was 32.9% (95% CI: 15.5-46.7). Among those aged 0-14, 15-64 and ≥65 years, VE against A(H1N1)pdm09 was 31.9% (95% CI: -32.3 to 65.0), 41.4% (95% CI: 20.5-56.7) and 13.2% (95% CI: -38.0 to 45.3), respectively. Overall VE against influenza A(H1N1)pdm09 genetic group 6B.1 was 32.8% (95% CI: -4.1 to 56.7). Among those aged 0-14, 15-64 and ≥65 years, VE against influenza B was -47.6% (95% CI: -124.9 to 3.1), 27.3% (95% CI: -4.6 to 49.4) and 9.3% (95% CI: -44.1 to 42.9), respectively. CONCLUSIONS: Vaccine effectiveness (VE) against influenza A(H1N1)pdm09 and its genetic group 6B.1 was moderate in children and adults, and low among individuals ≥65 years. Vaccine effectiveness (VE) against influenza B was low and heterogeneous among age groups. More information on effects of previous vaccination and previous infection is needed to understand the VE results against influenza B in the context of a mismatched vaccine.

Effectiveness of influenza vaccines in preventing severe influenza illness among adults: A systematic review and meta-analysis of test-negative design case-control studies.

OBJECTIVES: Summary evidence of influenza vaccine effectiveness (IVE) against hospitalized influenza is lacking. We conducted a meta-analysis of studies reporting IVE against laboratory-confirmed hospitalized influenza among adults. METHODS: We searched Pubmed (January 2009 to November 2016) for studies that used test-negative design (TND) to enrol patients hospitalized with influenza-associated conditions. Two independent authors selected relevant articles. We calculated pooled IVE against any and (sub)type specific influenza among all adults, and stratified by age group (18-64 and 65 years and above) using random-effects models. RESULTS: We identified 3411 publications and 30 met our inclusion criteria. Between 2010-11 and 2014-15, the pooled seasonal IVE was 41% (95%CI:34;48) for any influenza (51% (95%CI:44;58) among people aged 18-64y and 37% (95%CI:30;44) among ≥65 years). IVE was 48% (95%CI:37;59),37% (95%CI:24;50) and 38% (95%CI:23;53) against influenza A(H1N1)pdm09, A(H3N2) and B, respectively. Among persons aged ≥65 year, IVE against A(H3N2) was 43% (95%CI:33;53) in seasons when circulating and vaccine strains were antigenically similar and 14% (95%CI:-3;30) when A(H3N2) variant viruses predominated. CONCLUSIONS: Influenza vaccines provided moderate protection against influenza-associated hospitalizations among adults. They seemed to provide low protection among elderly in seasons where vaccine and circulating A(H3N2) strains were antigenically variant.

Repeated seasonal influenza vaccination among elderly in Europe: Effects on laboratory confirmed hospitalised influenza.

In Europe, annual influenza vaccination is recommended to elderly. From 2011 to 2014 and in 2015-16, we conducted a multicentre test negative case control study in hospitals of 11 European countries to measure influenza vaccine effectiveness (IVE) against laboratory confirmed hospitalised influenza among people aged ≥65years. We pooled four seasons data to measure IVE by past exposures to influenza vaccination. We swabbed patients admitted for clinical conditions related to influenza with onset of severe acute respiratory infection ≤7days before admission. Cases were patients RT-PCR positive for influenza virus and controls those negative for any influenza virus. We documented seasonal vaccination status for the current season and the two previous seasons. We recruited 5295 patients over the four seasons, including 465A(H1N1)pdm09, 642A(H3N2), 278 B case-patients and 3910 controls. Among patients unvaccinated in both previous two seasons, current seasonal IVE (pooled across seasons) was 30% (95%CI: -35 to 64), 8% (95%CI: -94 to 56) and 33% (95%CI: -43 to 68) against influenza A(H1N1)pdm09, A(H3N2) and B respectively. Among patients vaccinated in both previous seasons, current seasonal IVE (pooled across seasons) was -1% (95%CI: -80 to 43), 37% (95%CI: 7-57) and 43% (95%CI: 1-68) against influenza A(H1N1)pdm09, A(H3N2) and B respectively. Our results suggest that, regardless of patients' recent vaccination history, current seasonal vaccine conferred some protection to vaccinated patients against hospitalisation with influenza A(H3N2) and B. Vaccination of patients already vaccinated in both the past two seasons did not seem to be effective against A(H1N1)pdm09. To better understand the effect of repeated vaccination, engaging in large cohort studies documenting exposures to vaccine and natural infection is needed.

Four years into the Indian ocean field epidemiology training programme.

INTRODUCTION: Following the 2005-6 chikungunya outbreak, a project to strengthen regional Public Health preparedness in the Indian Ocean was implemented. It includes the Comoros, Madagascar, Mauritius, Reunion (France) and Seychelles. A Field Epidemiology Training Programme (FETP-OI) was started in 2011 to develop a pool of well-trained intervention epidemiologists. METHODS: The FETP-OI consists of two years of supervised, learning-by-doing, on-the-job training at national sites involved in disease surveillance and response. It includes work placements at the Madagascar Pasteur Institute and the French regional epidemiology unit in Reunion and up to three training courses per year. Training objectives include epidemiological surveillance, outbreak investigations, research studies, scientific communication and transfer of competencies. RESULTS: In four years, two cohorts of in total 15 fellows originating from four countries followed the FETP-OI. They led 42 surveillance projects (71% routine management, 14% evaluations, 12% setup, 3% other) and investigated 36 outbreak alerts, 58% of them in Madagascar; most investigations (72%) concerned foodborne pathogens, plague or malaria. Fellows performed 18 studies (44% descriptive analyses, 22% disease risk factors, and 34% on other subjects), and presented results during regional and international conferences through 26 oral and 15 poster presentations. Four articles were published in regional Public Health bulletins and several scientific manuscripts are in process. CONCLUSION: The FETP-OI has created a regional force of intervention consisting of field epidemiologists and trained supervisors using the same technical language and epidemiological methods. The third cohort is now ongoing. Technically and financially sustainable FETP-OI projects help addressing public health priorities of the Indian Ocean.

A large outbreak of hepatitis E among a displaced population in Darfur, Sudan, 2004: the role of water treatment methods.

BACKGROUND: The conflict in Darfur, Sudan, was responsible for the displacement of 1.8 million civilians. We investigated a large outbreak of hepatitis E virus (HEV) infection in Mornay camp (78,800 inhabitants) in western Darfur. METHODS: To describe the outbreak, we used clinical and demographic information from cases recorded at the camp between 26 July and 31 December 2004. We conducted a case-cohort study and a retrospective cohort study to identify risk factors for clinical and asymptomatic hepatitis E, respectively. We collected stool and serum samples from animals and performed a bacteriological analysis of water samples. Human samples were tested for immunoglobulin G and immunoglobulin M antibody to HEV (for serum samples) and for amplification of the HEV genome (for serum and stool samples). RESULTS: In 6 months, 2621 hepatitis E cases were recorded (attack rate, 3.3%), with a case-fatality rate of 1.7% (45 deaths, 19 of which involved were pregnant women). Risk factors for clinical HEV infection included age of 15-45 years (odds ratio, 2.13; 95% confidence interval, 1.02-4.46) and drinking chlorinated surface water (odds ratio, 2.49; 95% confidence interval, 1.22-5.08). Both factors were also suggestive of increased risk for asymptomatic HEV infection, although this was not found to be statistically significant. HEV RNA was positively identified in serum samples obtained from 2 donkeys. No bacteria were identified from any sample of chlorinated water tested. CONCLUSIONS: Current recommendations to ensure a safe water supply may have been insufficient to inactivate HEV and control this epidemic. This research highlights the need to evaluate current water treatment methods and to identify alternative solutions adapted to complex emergencies.

The European Programme for Intervention Epidemiology Training.

The European Programme for Intervention Epidemiology Training (EPIET) provides practical experience in infectious disease epidemiology. EPIET aims to create a network of professionals throughout Europe trained to use a standard approach in intervention ep

Vaccine effects and impact of vaccination programmes in post-licensure studies.

Once a vaccine is licensed and introduced in the population, post-licensure studies are required to measure vaccine effectiveness and impact of vaccination programmes on the population at large. However, confusion still prevails around these concepts, making it difficult to discern which effects are measured in such studies and how their findings should be interpreted. We review from the public health evaluation perspective the effects of vaccine-related exposures, describe the methods used to measure them and their assumptions. We distinguish effects due to exposure to individual vaccination from those due to exposure to a vaccination programme, as the latter depends on vaccine coverage, other population factors and includes indirect effects as well. Vaccine (direct) effectiveness is estimated by comparing vaccinated and unvaccinated individuals exposed to the same vaccination programme. The impact of a vaccination programme, defined here as the population prevented fraction when exposure is the programme, is measured by comparing populations with and without a vaccination programme, most commonly the same population before and after vaccination. These designs are based on a number of assumptions for valid inference. In particular, they assume that vaccinees and non-vaccinees do not differ in terms of susceptibility and exposure to the disease or in ascertainment of vaccination and disease status. In pre and post-vaccination design, the population is assumed to have similar baseline transmission, case detection and reporting, risk factors and medical practices in both periods. These principles are frequently violated in post-licensure studies. Potential confounding and biases must be minimized in study design and analyses, or taken into account during result interpretation. It is also essential to define which exposure is evaluated (individual vaccination or vaccination programme) and which effect is measured. This may help decision-makers clarify which type of study is needed and how to interpret the results.

2011-12 seasonal influenza vaccines effectiveness against confirmed A(H3N2) influenza hospitalisation: pooled analysis from a European network of hospitals. A pilot study.

BACKGROUND: Influenza vaccination strategies aim at protecting high-risk population from severe outcomes. Estimating the effectiveness of seasonal vaccines against influenza related hospitalisation is important to guide these strategies. Large sample size is needed to have precise estimate of influenza vaccine effectiveness (IVE) against severe outcomes. We assessed the feasibility of measuring seasonal IVE against hospitalisation with laboratory confirmed influenza through a network of 21 hospitals in the European Union. METHODS: We conducted a multicentre study in France (seven hospitals), Italy (one hospital), and Navarra (four hospitals) and Valencia (nine hospitals) regions in Spain. All ≥18 years hospitalised patients presenting an influenza-like illness within seven days were swabbed. Cases were patients RT-PCR positive for influenza A (H3N2); controls were patients negative for any influenza virus. Using logistic regression with study site as a fixed effect we calculated IVE adjusted for potential confounders. We restricted the analyses to those swabbed within four days. RESULTS: We included, 375 A(H3N2) cases and 770 controls. The overall adjusted IVE was 24.9% (95%CI-1.8;44.6). Among the target group for vaccination (N = 1058) the adjusted IVE was 28.8% (95%CI:2.8;47.9); it was respectively 36.8% (95%CI:-48.8; 73.1), 42.6% (95%CI:-16.5;71.7), 17.8%(95%CI:-40.8; 52.1) and 37.5% (95%CI:-22.8;68.2) in the age groups 18-64, 65-74, 75-84 and more than 84 years. DISCUSSION: Estimation of IVE based on the pooling of data obtained through a European network of hospitals was feasible. Our results suggest a low IVE against hospitalised confirmed influenza in 2011-12. The low IVE may be explained by a poor immune response in the high-risk population, imperfect match between vaccine and circulating strain or waning immunity due to a late season. Increased sample size within this network would allow more precise estimates and stratification of the IVE by time since vaccination and vaccine types or brands.

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.

Study designs for timely estimation of influenza vaccine effectiveness using European sentinel practitioner networks.

European sentinel practitioner influenza surveillance networks represent a simple and feasible framework to conduct observational studies providing rapid and repeated influenza vaccine effectiveness estimates. The minimum requirements for those studies should be to correctly ascertain vaccination status, to include laboratory-confirmed influenza as outcome and to collect variables to control for confounding. Various study designs are possible including the screening method, computerised cohort and case control studies using various control groups. Selecting the study design is a compromise between methodological constraints, availability and ease of access to data sources and resources available. Results from practitioner-based studies complement other pieces of evidence (e.g. immunogenicity studies, vaccine efficacy, surveillance data) to assess the effect of influenza vaccination in the population.