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Background: Within the ECDC-VEBIS project, we prospectively monitored vaccine effectiveness (VE) against COVID-19 hospitalisation and COVID-19-related death, using electronic health registries (EHR), between October 2021 and November 2022, in community-dwelling residents aged 65–79 and ≥80-years in six European countries. Methods: EHR linkage was used to construct population cohorts in Belgium, Denmark, Luxembourg, Navarre (Spain), Norway and Portugal. Using a common protocol, for each outcome (hospitalisation and death), VE was estimated monthly over eight-week follow-up periods, allowing one month-lag for data consolidation. Cox proportional-hazards regression models were used to estimate adjusted hazard ratios (aHR) and VE=(1 – aHR) x100. Site-specific estimates were pooled using random-effects meta-analysis. Results: For ≥80-years, VE against COVID-19 hospitalisation decreased from 66.9% (95%CI: 60.1; 72.6) to 36.1% (95%CI: -27.3; 67.9) for the primary vaccination and from 95.6% (95%CI: 88.0; 98.4) to 67.7% (95%CI: 45.9; 80.8) for the first booster. Similar trends were observed for 65-79-years. The second booster VE against hospitalisation ranged between 82.0% (95%CI: 75.9; 87.0) and 83.9% (95%CI: 77.7; 88.4) for the ≥80-years and between 39.3% (95%CI: -3.9; 64.5) and 80.6% (95%CI: 67.2; 88.5) for 65-79-years. The first booster VE against COVID-19-related death declined over time for both age groups, while the second booster VE against death remained above 80% for the ≥80-years. Conclusions: Successive vaccine boosters played a relevant role in maintaining protection against COVID-19 hospitalisation and death, in the context of decreasing VE over time. Multi-country data from EHR facilitate robust near-real-time monitoring of VE in the EU/EEA and supports public health decision-making.

Background The World Health Organization European Action Plan 2020 targets for the elimination of viral hepatitis are that > 75% of eligible individuals with chronic hepatitis B (HBV) or hepatitis C (HCV) are treated, of whom > 90% achieve viral suppression. Aim To report the results from a pilot sentinel surveillance to monitor chronic HBV and HCV treatment uptake and outcomes in 2019. Methods We undertook retrospective enhanced data collection on patients with a confirmed chronic HBV or HCV infection presenting at one of seven clinics in three countries (Croatia, Romania and Spain) for the first time between 1 January 2019 and 30 June 2019. Clinical records were reviewed from date of first attendance to 31 December 2019 and data on sociodemographics, clinical history, laboratory results, treatment and treatment outcomes were collected. Treatment eligibility, uptake and case outcome were assessed. Results Of 229 individuals with chronic HBV infection, treatment status was reported for 203 (89%). Of the 80 individuals reported as eligible for treatment, 51% (41/80) were treated of whom 89% (33/37) had achieved viral suppression. Of 240 individuals with chronic HCV infection, treatment status was reported for 231 (96%). Of 231 eligible individuals, 77% (179/231) were treated, the majority of whom had received direct acting antivirals (99%, 174/176) and had achieved sustained virological response (98%, 165/169). Conclusion Treatment targets for global elimination were missed for HBV but not for HCV. A wider European implementation of sentinel surveillance with a representative sample of sites could help monitor progress towards achieving hepatitis control targets.

Background The secondary attack rate (SAR) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was estimated, and the risk factors for infection among members of households with a coronavirus disease 2019 (COVID-19) index case were identified to inform preventive measures. Methods Between 3 August and 19 December 2020, a household transmission study was implemented based on a standardized World Health Organization protocol. Laboratory-confirmed cases of SARS-CoV-2 infection were recruited through the federal COVID-19 database. Trained contact tracers interviewed index cases and household members to collect information on demographic, clinical and behavioural factors. Contacts were followed up for 28 days to identify secondary infections. SAR was estimated and odds ratios (OR) were calculated for risk factors for transmission. Results In total, 383 households and 793 contacts were included in this study. The overall SAR was 17% [95% confidence interval (CI) 14–21]. Contacts had higher risk for infection if the primary case had both cough and runny nose (OR 4.31, 95% CI 1.60–11.63), if the contact was aged 18–49 years (OR 4.67, 95% CI 1.83–11.93), if the contact kissed the primary case (OR 3.16, 95% CI 1.19–8.43), or if the contact shared a meal with the primary case (OR 3.10, 95% CI 1.17–8.27). Conclusions These results add to the global literature by providing evidence from a middle-income setting. Standard preventive measures in households with positive cases remain critical to reduce transmission.

BACKGROUND: The declaration of Coronavirus disease 2019 (COVID-19) as a Public Health Emergency of International Concern (PHEIC) on 30 January 2020 required rapid implementation of early investigations to inform appropriate national and global public health actions. METHODS: The suite of existing pandemic preparedness generic epidemiological early investigation protocols was rapidly adapted for COVID-19, branded the 'UNITY studies' and promoted globally for the implementation of standardized and quality studies. Ten protocols were developed investigating household (HH) transmission, the first few cases (FFX), population seroprevalence (SEROPREV), health facilities transmission (n = 2), vaccine effectiveness (n = 2), pregnancy outcomes and transmission, school transmission, and surface contamination. Implementation was supported by WHO and its partners globally, with emphasis to support building surveillance and research capacities in low- and middle-income countries (LMIC). RESULTS: WHO generic protocols were rapidly developed and published on the WHO website, 5/10 protocols within the first 3 months of the response. As of 30 June 2021, 172 investigations were implemented by 97 countries, of which 62 (64%) were LMIC. The majority of countries implemented population seroprevalence (71 countries) and first few cases/household transmission (37 countries) studies. CONCLUSION: The widespread adoption of UNITY protocols across all WHO regions indicates that they addressed subnational and national needs to support local public health decision-making to prevent and control the pandemic.

Background: In 2021–22, influenza A viruses dominated in Europe. The I-MOVE primary care network conducted a multicentre test-negative study to measure influenza vaccine effectiveness (VE). Methods: Primary care practitioners collected information on patients presenting with acute respiratory infection. Cases were influenza A(H3N2) or A(H1N1)pdm09 RT-PCR positive and controls were influenza virus negative. We calculated VE using logistic regression, adjusting for study site, age, sex, onset date, and presence of chronic conditions. Results: Between week 40 2021 and week 20 2022, we included over 11,000 patients of whom 253 and 1595 were positive for influenza A(H1N1)pdm09 and A(H3N2), respectively. Overall VE against influenza A(H1N1)pdm09 was 75% (95%CI: 43–89) and 81% (95%CI: 44–93) among those aged 15–64 years. Overall VE against influenza A(H3N2) was 29% (95%CI: 12–42) and 25% (95%CI: -41–61), 33% (95%CI: 14–49) and 26% (95% CI: -22 to 55) among those aged 0–14, 15–64 and over 65 years, respectively. The A(H3N2) VE among the influenza vaccination target group was 20% (95%CI: -6–39). All 53 sequenced A(H1N1)pdm09 viruses belonged to clade 6B.1A.5a.1. Among 410 sequenced influenza A(H3N2) viruses, all but 8 belonged to clade 3C.2a1b.2a.2. Discussion: Despite antigenic mismatch between vaccine and circulating strains for influenza A(H3N2) and A(H1N1)pdm09, 2021–22 VE estimates against circulating influenza A(H1N1)pdm09 were the highest within the I-MOVE network since the 2009 influenza pandemic. VE against A(H3N2) was lower than A(H1N1)pdm09, but at least one in five individuals vaccinated against influenza were protected against presentation to primary care with laboratory-confirmed influenza.

IntroductionCritical questions remain about COVID-19 vaccine effectiveness (VE) in real-world settings, particularly in middle-income countries. We describe a study protocol to evaluate COVID-19 VE in preventing laboratory-confirmed SARS-CoV-2 infection in health workers (HWs) in Albania, an upper-middle-income country.Methods and analysisIn this 12-month prospective cohort study, we enrolled HWs at three hospitals in Albania. HWs are vaccinated through the routine COVID-19 vaccine campaign. Participants completed a baseline survey about demographics, clinical comorbidities, and infection risk behaviours. Baseline serology samples were also collected and tested against the SARS-CoV-2 spike protein, and respiratory swabs were collected and tested for SARS-CoV-2 by RT-PCR. Participants complete weekly symptom questionnaires and symptomatic participants have a respiratory swab collected, which is tested for SARS-CoV-2. At 3, 6, 9 months and 12 months of the study, serology will be collected and tested for antibodies against the SARS-CoV-2 nucleocapsid protein and spike protein. VE will be estimated using a piecewise proportional hazards model (VE=1−HR).Baseline dataFrom February to May 2021, 1504 HWs were enrolled. The median age was 44 (range: 22–71) and 78% were female. At enrolment, 72% of participants were seropositive for SARS-CoV-2. 56% of participants were vaccinated with one dose, of whom 98% received their first shot within 4 days of enrolment. All HWs received the Pfizer BNT162b2 mRNA COVID-19 vaccine.Ethics and disseminationThe study protocol and procedures were reviewed and approved by the WHO Ethical Review Board, reference number CERC.0097A, and the Albanian Institute of Public Health Ethical Review Board, reference number 156. All participants have provided written informed consent to participate in this study. The primary results of this study will be published in a peer-reviewed journal at the time of completion.Trial registration numberNCT04811391.

IntroductionEstimating COVID-19 cumulative incidence in Africa remains problematic due to challenges in contact tracing, routine surveillance systems and laboratory testing capacities and strategies. We undertook a meta-analysis of population-based seroprevalence studies to estimate SARS-CoV-2 seroprevalence in Africa to inform evidence-based decision making on Public Health and Social Measures (PHSM) and vaccine strategy.MethodsWe searched for seroprevalence studies conducted in Africa published 01-01-2020 to 30-12-2021 in Medline, Embase, Web of Science, and Europe PMC (preprints), grey literature, media releases and early results from WHO Unity studies. All studies were screened, extracted, assessed for risk of bias and evaluated for alignment with the WHO Unity protocol for seroepidemiological investigations. We conducted descriptive analyses of seroprevalence and meta-analysed seroprevalence differences by demographic groups, place and time. We estimated the extent of undetected infections by comparing seroprevalence and cumulative incidence of confirmed cases reported to WHO. PROSPERO: CRD42020183634.ResultsWe identified 54 full texts or early results, reporting 151 distinct seroprevalence studies in Africa Of these, 95 (63%) were low/moderate risk of bias studies. SARS-CoV-2 seroprevalence rose from 3.0% [95% CI: 1.0-9.2%] in Q2 2020 to 65.1% [95% CI: 56.3-73.0%] in Q3 2021. The ratios of seroprevalence from infection to cumulative incidence of confirmed cases was large (overall: 97:1, ranging from 10:1 to 958:1) and steady over time. Seroprevalence was highly heterogeneous both within countries - urban vs. rural (lower seroprevalence for rural geographic areas), children vs. adults (children aged 0-9 years had the lowest seroprevalence) - and between countries and African sub-regions (Middle, Western and Eastern Africa associated with higher seroprevalence).ConclusionWe report high seroprevalence in Africa suggesting greater population exposure to SARS-CoV-2 and protection against COVID-19 disease than indicated by surveillance data. As seroprevalence was heterogeneous, targeted PHSM and vaccination strategies need to be tailored to local epidemiological situations.

IntroductionEstimating COVID-19 cumulative incidence in Africa remains problematic due to challenges in contact tracing, routine surveillance systems and laboratory testing capacities and strategies. We undertook a meta-analysis of population-based seroprevalence studies to estimate SARS-CoV-2 seroprevalence in Africa to inform evidence-based decision making on public health and social measures (PHSM) and vaccine strategy.MethodsWe searched for seroprevalence studies conducted in Africa published 1 January 2020–30 December 2021 in Medline, Embase, Web of Science and Europe PMC (preprints), grey literature, media releases and early results from WHO Unity studies. All studies were screened, extracted, assessed for risk of bias and evaluated for alignment with the WHO Unity seroprevalence protocol. We conducted descriptive analyses of seroprevalence and meta-analysed seroprevalence differences by demographic groups, place and time. We estimated the extent of undetected infections by comparing seroprevalence and cumulative incidence of confirmed cases reported to WHO.PROSPERO: CRD42020183634.ResultsWe identified 56 full texts or early results, reporting 153 distinct seroprevalence studies in Africa. Of these, 97 (63%) were low/moderate risk of bias studies. SARS-CoV-2 seroprevalence rose from 3.0% (95% CI 1.0% to 9.2%) in April–June 2020 to 65.1% (95% CI 56.3% to 73.0%) in July–September 2021. The ratios of seroprevalence from infection to cumulative incidence of confirmed cases was large (overall: 100:1, ranging from 18:1 to 954:1) and steady over time. Seroprevalence was highly heterogeneous both within countries—urban versus rural (lower seroprevalence for rural geographic areas), children versus adults (children aged 0–9 years had the lowest seroprevalence)—and between countries and African subregions.ConclusionWe report high seroprevalence in Africa suggesting greater population exposure to SARS-CoV-2 and potential protection against COVID-19 severe disease than indicated by surveillance data. As seroprevalence was heterogeneous, targeted PHSM and vaccination strategies need to be tailored to local epidemiological situations.

Household transmission investigations (HHTI) contribute timely epidemiologic knowledge in response to emerging pathogens. HHTIs conducted in the context of the COVID-19 pandemic in 2020-21 reported variable methodological approaches, producing epidemiological estimates that vary in meaning, precision, and accuracy. Since specific tools to assist with the optimal design and critical appraisal of HHTIs are not available, the aggregation and pooling of HHTI to inform policy and interventions may be challenging. In this manuscript, we discuss key aspects of the HHTI design, we provide recommendations for the reporting of these studies, and propose an appraisal tool that contributes to the optimal design and critical appraisal of HHTI studies. The appraisal tool consists of 12 questions that explore 10 aspects of HHTIs and can be answered ‘yes’, ‘no’ or ‘unclear’. The manuscript seeks to fill a gap in the epidemiologic literature and contribute to standardise HHTI approaches across settings, to achieve richer and more informative datasets. The manuscript also calls for a periodic revision of HHTI protocols and critical appraisal tools

IntroductionIn July and August 2021, the SARS-CoV-2 Delta variant dominated in Europe. We measured COVID-19 vaccine effectiveness (VE) against symptomatic infection, using a multicentre test-negative study at primary care/community level in Europe.MethodsPatients presenting with COVID-19/ARI symptoms at primary care/community level in 10 countries were tested for SARS-CoV-2. We measured complete primary course overall VE among those aged 30–44, 45–59, 60–74 and ≥75 years, and among those 30–59 and ≥60 years by vaccine brand and by time since vaccination.ResultsOverall VE was 74% (95%CI: 69–79), 76% (95%CI: 71–80), 63% (95%CI: 48–75), 63% (95%CI: 16–83) among those aged 30–44, 45–59, 60–74 and ≥75 years, respectively. VE among those aged 30–59 years was 78% (95%CI: 75–81), 66% (95%CI: 58–73), 91% (95%CI: 87–94) and 52% (95%CI: 40–61), for Comirnaty, Vaxzevria, Spikevax and COVID-19 Vaccine Janssen, respectively. VE among those aged ≥60 years was 67% (95%CI: 52–77), 65% (95%CI: 48–76), 83% (95%CI: 64–92) for Comirnaty, Vaxzevria and Spikevax, respectively. Comirnaty VE among those aged 30–59 years was 87% (95%CI: 83–89) and 65% (95%CI: 56–71%) at 14–29 days and ≥90 days between vaccination and onset of symptoms, respectively.ConclusionsVE against the symptomatic SARS-CoV-2 Delta variant infection varied among brands, ranging from 52–91%. While some waning of the vaccine effect may be present (sample size limited this analysis to only Comirnaty), protection was 65% ≥90 days between vaccination and onset.

BackgroundOur understanding of the global scale of SARS-CoV-2 infection remains incomplete: routine surveillance data underestimates infection and cannot infer on population immunity, there is a predominance of asymptomatic infections, and uneven access to diagnostics. We meta-analyzed SARS-CoV-2 seroprevalence studies, standardized to those described in WHO’s Unity protocol for general population seroepidemiological studies, two years into the pandemic, to estimate the extent of population infection and remaining susceptibility.Methods and FindingsWe conducted a systematic review and meta-analysis, searching MEDLINE, Embase, Web of Science, preprints, and grey literature for SARS-CoV-2 seroprevalence published between 2020-01-01 and 2022-05-20. The review protocol is registered with PROSPERO, (CRD42020183634). We included general population cross-sectional and cohort studies meeting an assay quality threshold (90% sensitivity, 97% specificity; exceptions for humanitarian settings). We excluded studies with an unclear or closed population sample frame. Eligible studies - those aligned with the WHO Unity protocol - were extracted and critically appraised in duplicate, with Risk of Bias evaluated using a modified Joanna Briggs Institute checklist. We meta-analyzed seroprevalence by country and month, pooling to estimate regional and global seroprevalence over time; compared seroprevalence from infection to confirmed cases to estimate under-ascertainment; meta-analyzed differences in seroprevalence between demographic subgroups such as age and sex; and identified national factors associated with seroprevalence using meta-regression. The main limitations of our methodology include that some estimates were driven by certain countries or populations being over-represented. We identified 513 full texts reporting 965 distinct seroprevalence studies (41% LMIC) sampling 5,346,069 participants between January 2020 and April 2022, including 459 low/moderate risk of bias studies with national/sub-national scope in further analysis. By September 2021, global SARS-CoV-2 seroprevalence from infection or vaccination was 59.2%, 95% CI [56.1-62.2%]. Overall seroprevalence rose steeply in 2021 due to infection in some regions (e.g., 26.6% [24.6-28.8] to 86.7% [84.6-88.5%] in Africa in December 2021) and vaccination and infection in others (e.g., 9.6% [8.3-11.0%] to 95.9% [92.6-97.8%] in Europe high-income countries in December 2021). After the emergence of Omicron, infection-induced seroprevalence rose to 47.9% [41.0-54.9%] in EUR HIC and 33.7% [31.6-36.0%] in AMR HIC in March 2022. In 2021 Quarter Three (July to September), median seroprevalence to cumulative incidence ratios ranged from around 2:1 in the Americas and Europe HICs to over 100:1 in Africa (LMICs). Children 0-9 years and adults 60+ were at lower risk of seropositivity than adults 20-29 (pp=0.005, respectively). In a multivariable model using pre-vaccination data, stringent public health and social measures were associated with lower seroprevalence (p=0.02).ConclusionsIn this study, we observed that global seroprevalence has risen considerably over time and with regional variation, however around 40 % of the global population remains susceptible to SARS-CoV-2 infection. Our estimates of infections based on seroprevalence far exceed reported COVID-19 cases. Quality and standardized seroprevalence studies are essential to inform COVID-19 response, particularly in resource-limited regions.

Purpose The purpose of this study was to characterize the nasopharyngeal microbiota of infants with possible and confirmed pertussis compared to healthy controls. Methods This prospective study included all infants Results Twelve confirmed cases, 21 possible cases and 9 healthy controls were included. Confirmed whooping cough was primarily driven by detection of Bordetella with no other major changes on nasopharyngeal microbiota. Possible cases had limited abundance or absence of Bordetella and a distinctive microbiota with lower bacterial richness and diversity and higher rates of viral co-infection than both confirmed cases and healthy controls. Bordetella reads determined by 16S rRNA gene sequencing were found in all 12 confirmed cases (100%), 3 out of the 21 possible cases (14.3%) but in any healthy control. Conclusion This study supports the usefulness of 16S rRNA gene sequencing for improved sensitivity on pertussis diagnosis compared to real-time PCR and to understand other microbial changes occurring in the nasopharynx in children

Phase 3 randomized-controlled trials have provided promising results of COVID-19 vaccine efficacy, ranging from 50 to 95% against symptomatic disease as the primary endpoints, resulting in emergency use authorization/listing for several vaccines. However, given the short duration of follow-up during the clinical trials, strict eligibility criteria, emerging variants of concern, and the changing epidemiology of the pandemic, many questions still remain unanswered regarding vaccine performance. Post-introduction vaccine effectiveness evaluations can help us to understand the vaccine's effect on reducing infection and disease when used in real-world conditions. They can also address important questions that were either not studied or were incompletely studied in the trials and that will inform evolving vaccine policy, including assessment of the duration of effectiveness; effectiveness in key subpopulations, such as the very old or immunocompromised; against severe disease and death due to COVID-19; against emerging SARS-CoV-2 variants of concern; and with different vaccination schedules, such as number of doses and varying dosing intervals. WHO convened an expert panel to develop interim best practice guidance for COVID-19 vaccine effectiveness evaluations. We present a summary of the interim guidance, including discussion of different study designs, priority outcomes to evaluate, potential biases, existing surveillance platforms that can be used, and recommendations for reporting results.

Well‐designed population‐based seroepidemiologic studies can be used to refine estimates of infection severity and transmission, and are therefore an important component of epidemic surveillance. However, the interpretation of the results of seroepidemiologic studies for SARS‐CoV‐2 has been hampered to date principally by heterogeneity in the quality of the reporting of the results of the study and a lack of standardized methods and reporting. We provide here the ROSES‐S: Reporting of Seroepidemiologic studies—SARS‐CoV‐2. This is an updated checklist of 22 items that should be included in the reporting of all SARS‐CoV‐2 seroepidemiologic studies, irrespective of study design.

The I‐MOVE‐COVID‐19 network has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement no 101003673. Background : Claims of influenza vaccination increasing COVID-19 risk are circulating. Within the I-MOVE-COVID-19 primary care multicentre study, we measured the association between 2019-20 influenza vaccination and COVID-19. Methods : We conducted a multicentre test-negative case-control study at primary care level, in study sites in five European countries, from March to August 2020. Patients presenting with acute respiratory infection were swabbed, with demographic, 2019-20 influenza vaccination and clinical information documented. Using logistic regression, we measured the adjusted odds ratio (aOR), adjusting for study site and age, sex, calendar time, presence of chronic conditions. The main analysis included patients swabbed ≤7 days after onset from the three countries with

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. 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. 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. 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. This study received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 634446. The I‐MOVE study team is very grateful to all patients, hospital teams, laboratory teams and regional epidemiologists who have contributed to the studies. Sí

Background To increase the acceptability of influenza vaccine, it is important to quantify the overall benefits of the vaccination programme. Aim To assess the impact of influenza vaccination in Portugal, Spain and the Netherlands, we estimated the number of medically attended influenza-confirmed cases (MAICC) in primary care averted in the seasons 2015/16 to 2017/18 among those ≥ 65 years. Methods We used an ecological approach to estimate vaccination impact. We compared the number of observed MAICC (n) to the estimated number that would have occurred without the vaccination programme (N). To estimate N, we used: (i) MAICC estimated from influenza surveillance systems, (ii) vaccine coverage, (iii) pooled (sub)type-specific influenza vaccine effectiveness estimates for seasons 2015/16 to 2017/18, weighted by the proportion of virus circulation in each season and country. We estimated the number of MAICC averted (NAE) and the prevented fraction (PF) by the vaccination programme. Results The annual average of NAE in the population ≥ 65 years was 33, 58 and 204 MAICC per 100,000 in Portugal, Spain and the Netherlands, respectively. On average, influenza vaccination prevented 10.7%, 10.9% and 14.2% of potential influenza MAICC each season in these countries. The lowest PF was in 2016/17 (4.9–6.1%) with an NAE ranging from 24 to 69 per 100,000. Conclusions Our results suggest that influenza vaccination programmes reduced a substantial number of MAICC. Together with studies on hospitalisations and deaths averted by influenza vaccination programmes, this will contribute to the evaluation of the impact of vaccination strategies and strengthen public health communication.

The start of the cholera epidemic in Haiti quickly highlighted the necessity of the implementation of an Alert and Response (A&R) System to complement the existing national surveillance system. The national system had been able to detect and confirm the outbreak etiology but required external support to monitor the spread of cholera and coordinate response, because much of the information produced was insufficiently timely for real-time monitoring and directing of a rapid, targeted response. The A&R System was designed by the Pan American Health Organization/World Health Organization in collaboration with the Haiti Ministry of Health, and it was based on a network of partners, including any institution, structure, or individual that could identify, verify, and respond to alerts. The defined objectives were to (1) save lives through early detection and treatment of cases and (2) control the spread through early intervention at the community level. The operational structure could be broken down into three principle categories: (1) alert (early warning), (2) verification and assessment of the information, and (3) efficient and timely response in coordination with partners to avoid duplication. Information generated by the A&R System was analyzed and interpreted, and the qualitative information was critical in qualifying the epidemic and defining vulnerable areas, particularly because the national surveillance system reported incomplete data for more than one department. The A&R System detected a number of alerts unrelated to cholera and facilitated rapid access to that information. The sensitivity of the system and its ability to react quickly was shown in May of 2011, when an abnormal increase in alerts coming from several communes in the Sud-Est Department in epidemiological weeks (EWs) 17 and 18 were noted and disseminated network-wide and response activities were implemented. The national cholera surveillance system did not register the increase until EWs 21 and 22, and the information did not become available until EWs 23 and 24, when the peak of cases had already been reached. Although many of the partners reporting alerts during the peak of the cholera epidemic have since left Haiti, the A&R System has continued to function as an Early Warning (EWARN) System, and it continues to be developed with recent activities, such as the distribution of cell phones to enhance alert communication.

Influenza vaccines are currently the best method available to prevent seasonal influenza infection. In most European countries one dose (or two doses for children) of seasonal vaccine is given from September to December to the elderly and other target groups for vaccination. In Europe, influenza seasons can last until mid-May (1), and it is expected that vaccination conveys protection on the individual for the duration of the season. In 13/15 reviewed studies on the length of vaccine-induced protection among the elderly, using anti-haemagglutination antibody titres as a proxy for seroprotection levels, seroprotection rates lasted at least >4 months after vaccination (2). However in the 2011-12 influenza season various studies in Europe reported a decrease in influenza vaccine effectiveness (VE) against A(H3N2) over time within the season (3–5). In the United States, a decrease in VE against A(H3N2) with time since vaccination was suggested in the 2007-8 influenza season (6). The observed decrease of VE over time can be explained by viral change (notably antigenic drift) occurring in the season. Drift in B viruses may be slower than in A viruses (7), and A(H3N2) viruses undergo antigenic drift more frequently than A(H1N1)pdm09 viruses (8). The decrease of VE over time can also be explained by a waning of the immunity conferred by the vaccine independently from viral changes. If vaccine-induced protection wanes more rapidly during the season, then depending on the start and duration of the influenza season, the decline of VE may cause increases in overall incidence, hospitalisations and deaths. Changes to vaccination strategies (timing and boosters) may be needed. As anti-haemagglutination antibody titres are not well defined as a correlate of protection (9,10), vaccine efficacy (as measured in trials) or vaccine effectiveness observational studies may be one way to measure vaccine-induced protection. These studies require a large sample size to model VE by time since vaccination and currently, most of the seasonal observational studies lack the precision required to provide evidence for waning immunity. In this study we pooled data across five post-pandemic seasons (2010/11-2014/15) from the I-MOVE (Influenza - Monitoring Vaccine Effectiveness) multicentre case control studies (1,3,11,12), to obtain a greater sample size to study the effects of time since vaccination on influenza type/subtype-specific VE. We measure influenza type/subtype-specific VE by time since vaccination for the overall season, but also in the early influenza phase; under the hypothesis that virological changes are fewer in the early season, but waning of the vaccine effect should be present regardless of time within the influenza phase.

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. Sí

In April-May 2004, the World Health Organization (WHO) implemented, with local authorities, United Nations (UN) agencies and non-governmental organisations (NGOs), an early warning system (EWS) in Darfur, West Sudan, for internally displaced persons (IDPs). The number of consultations and deaths per week for 12 health events is recorded for two age groups (less than five years and five years and above). Thresholds are used to detect potential outbreaks. Ten weeks after the introduction of the system, NGOs were covering 54 camps, and 924,281 people (IDPs and the host population). Of these 54 camps, 41 (76%) were reporting regularly under the EWS. Between 22 May and 30 July, 179,795 consultations were reported: 18.7% for acute respiratory infections; 15% for malaria; 8.4% for bloody diarrhoea; and 1% for severe acute malnutrition. The EWS is useful for detecting outbreaks and monitoring the number of consultations required to trigger actions, but not for estimating mortality.

In the fifth season of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE), we undertook a multicentre case-control study (MCCS) in seven European Union (EU) Member States to measure 2012/13 influenza vaccine effectiveness against medically attended influenza-like illness (ILI) laboratory confirmed as influenza. The season was characterised by substantial co-circulation of influenza B, A(H1N1)pdm09 and A(H3N2) viruses. Practitioners systematically selected ILI patients to swab ≤7 days of symptom onset. We compared influenza-positive by type/subtype to influenza-negative patients among those who met the EU ILI case definition. We conducted a complete case analysis using logistic regression with study as fixed effect and calculated adjusted vaccine effectiveness (AVE), controlling for potential confounders (age, sex, symptom onset week and presence of chronic conditions). We calculated AVE by type/subtype. Study sites sent 7,954 ILI/acute respiratory infection records for analysis. After applying exclusion criteria, we included 4,627 ILI patients in the analysis of VE against influenza B (1,937 cases), 3,516 for A(H1N1)pdm09 (1,068 cases) and 3,340 for influenza A(H3N2) (730 cases). AVE was 49.3% (95% confidence interval (CI): 32.4 to 62.0) against influenza B, 50.4% (95% CI: 28.4 to 65.6) against A(H1N1)pdm09 and 42.2% (95% CI: 14.9 to 60.7) against A(H3N2). Our results suggest an overall low to moderate AVE against influenza B, A(H1N1)pdm09 and A(H3N2), between 42 and 50%. In this season with many co-circulating viruses, the high sample size enabled stratified AVE by type/subtype. The low estimates indicate seasonal influenza vaccines should be improved to achieve acceptable protection levels. .

This article is the second of a series of three, which compare vaccination programmes, immunisation schedules, vaccine coverage, and the epidemiological impact of vaccination for diphtheria, pertussis, measles, mumps, and rubella in eight countries (Denma

Objective To discuss challenges and opportunities in the introduction of an automated approach for time series analysis (TSA) regarding epidemiological methodology for generation of hypotheses, steps to be performed and interpretation of outputs. Introduction ECDC long term strategies for surveillance include analysis of trends of communicable disease of public health importance for European Union countries to guide public health actions. The European Surveillance System (TESSy) holds data on 49 communicable diseases reported by 30 countries for at least the past five years. To simplify time related analysis using surveillance data, ECDC launched a project to enable descriptive and routine TSA without the need for complex programming. Methods Protocols for TESSy data were developed specifying hypotheses to be tested, types and format of variables needed for TSA for several diseases, including VTEC, and legionellosis. Stata scripts were developed to comply with the basic steps of TSA, including data aggregation, data checking, data description, analysis of trends and seasonality, residual analysis, simple modelling and long-term forecasting. TSA steps were presented as successive tabs in a TSA dialogue box in Stata. Before using the Stata TSA dialogue box, experts were offered a two-day training, and provided with an in-depth manual supporting use and interpretation of TSA outputs using the Stata TSA dialogue box. Results For VTEC, it was possible to identify a small increase in the trend and a seasonal pattern in surveillance data with an estimate of the start of the increased risk for infection in the beginning of the summer season [1]. For legionellosis, an increasing trend in the number of reported cases was observed in 2010 [2]. Feedback from the training showed that using the Stata TSA dialogue box enables a quick exploratory analysis even by non-Stata users who could focus on interpretation of results, rather than the programme writing. However, we emphasise that statistical knowledge of TSA as well as rigorous preparation of the datasets (including data quality checks) and generation of hypotheses, are essential to ensure appropriate analysis and meaningful interpretation of the results. Conclusions Using the Stata TSA dialogue box saves time when performing rapid exploratory TSA of epidemiological data, avoiding the need for complex programming which is still needed for sophisticated TSA. Results of exploratory TSA analysis can trigger new hypothesis, for more advanced and sophisticated TSA. The introduction of a new technology (Stata TSA dialogue box) does not replace multi-disciplinary approach, knowledge and application of a methodological approach to TSA to produce meaningful results that can inform public health decision making. Further testing and training will be performed to enhance simplicity before appropriate dissemination of the Stata TSA dialogue box for a wider use.

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. (C) 2013 Elsevier Ltd. All rights reserved.

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. The authors have no support or funding to report. Sí

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.

Within I-MOVE (European programme to monitor seasonal and pandemic influenza vaccine effectiveness (IVE)) five countries conducted IVE pilot case-control studies in 2008-9. One hundred and sixty sentinel general practitioners (GP) swabbed all elderly consulting for influenza-like illness (ILI). Influenza confirmed cases were compared to influenza negative controls. We conducted a pooled analysis to obtain a summary IVE in the age group of ≥65 years. We measured IVE in each study and assessed heterogeneity between studies qualitatively and using the I2 index. We used a one-stage pooled model with study as a fixed effect. We adjusted estimates for age-group, sex, chronic diseases, smoking, functional status, previous influenza vaccinations and previous hospitalisations. The pooled analysis included 138 cases and 189 test-negative controls. There was no statistical heterogeneity (I2=0) between studies but ILI case definition, previous hospitalisations and functional status were slightly different. The adjusted IVE was 59.1% (95% CI: 15.3-80.3%). IVE was 65.4% (95% CI: 15.6-85.8%) in the 65-74, 59.6% (95% CI: -72.6 -90.6%) in the age group of ≥75 and 56.4% (95% CI: -0.2-81.3%) for A(H3). Pooled analysis is feasible among European studies. The variables definitions need further standardisation. Larger sample sizes are needed to achieve greater precision for subgroup analysis. For 2009-10, I-MOVE will extend the study to obtain early IVE estimates in groups targeted for pandemic H1N1 influenza vaccination.

In April-May 2004, the World Health Organization (WHO) implemented, with local authorities, United Nations (UN) agencies and non-governmental organisations (NGOs), an early warning system (EWS) in Darfur, West Sudan, for internally displaced persons (IDPs). The number of consultations and deaths per week for 12 health events is recorded for two age groups (less than five years and five years and above). Thresholds are used to detect potential outbreaks. Ten weeks after the introduction of the system, NGOs were covering 54 camps, and 924,281 people (IDPs and the host population). Of these 54 camps, 41 (76%) were reporting regularly under the EWS. Between 22 May and 30 July, 179,795 consultations were reported: 18.7% for acute respiratory infections; 15% for malaria; 8.4% for bloody diarrhoea; and 1% for severe acute malnutrition. The EWS is useful for detecting outbreaks and monitoring the number of consultations required to trigger actions, but not for estimating mortality.

Cet article est le dernier d’une série de trois articles portant sur la comparaison, dans huit pays (Danemark, Angleterre et Pays de Galles, Finlande, France, Allemagne, Italie, Suède et Pays-Bas), des programmes vaccinaux et de l’impact épidémiologique d

The aim of the European Sero-Epidemiology Network (ESEN) is to coordinate and harmonise the serological surveillance of immunity to vaccine preventable diseases in eight countries in Europe (Denmark, England, France, Germany, Italy, the Netherlands, Finla

Aims. To describe syringe exchange programme attendees and their injection practices. Design. Cross-sectional study (one week in 1998). Data were collected through a standardized questionnaire. Setting. 60/74 syringe exchange programmes (SEPs) in France. Participants. Clients requesting syringes in 60 SEPs. Measurements. Self-reports of drug use, injecting behaviour, sexual behaviour, serological status (HIV, HBV, HCV). Prevalence of unsafe injecting practices in the previous month such as: syringe sharing; and sharing other injection paraphernalia. Findings. 1004 questionnaires were collected (response rate: 50%). The mean age of respondents was 30 years, and 70% were males. Among individuals tested, HIV reported prevalence was 19.2%, HCV 58.4% and HBV 20. 8%. The mean duration of drug use was 11 years. Eighty-five percent were polydrug users and buprenorphine high-dosage was the substance most used (73%). In the previous month, 45% of the participants had re-used a syringe, 93% injected at least daily (mean 3.6 injections per day), 18% shared a syringe and 71% shared injection paraphernalia. In multivariate analyses, unsafe injecting practices were associated with heroin and cocaine use and with living in a couple. The cluster analysis identified five categories of IDUs: users of buprenorphine-HD (45% of the responders), morphine-sulphate (17%), benzodiazepines and other legal drugs (13%), methadone associated with other legal drugs (13%) and crack-cocaine (13%). The buprenorphine-HD group had better social status and safer injection practices. Conclusions. In France, despite an increase in the accessibility to syringes and substitution treatments, unsafe injecting practices persist among SEP attenders. Interventions should stress the importance of using sterile material for each injection, even with a steady sex partner.

The recent war in Iraq presents significant challenges for the surveillance and control of communicable diseases. In early April 2003, the World Health Organization (WHO) sent a team of public health experts to Kuwait and a base was established in the southern Iraqi governorate of Basrah on May 3. We present the lessons learned from the communicable disease surveillance and control program implemented in the Basrah governorate in Iraq (population of 1.9 million) in April and May 2003, and we report communicable disease surveillance data through June 2003. Following the war, communicable disease control programs were disrupted, access to safe water was reduced, and public health facilities were looted. Rapid health assessments were carried out in health centers and hospitals to identify priorities for action. A Health Sector Coordination Group was organized with local and international health partners, and an early warning surveillance system for communicable disease was set up. In the first week of May 2003, physicians in hospitals in Basrah suspected cholera cases and WHO formed a cholera control committee. As of June 29, 2003, Iraqi hospital laboratories have confirmed 94 cases of cholera from 7 of the 8 districts of the Basrah governorate. To prevent the transmission of major communicable diseases, restoring basic public health and water/sanitation services is currently a top priority in Iraq. Lack of security continues to be a barrier for effective public health surveillance and response in Iraq.

Within the Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) project we conducted a multicentre case–control study in eight European Union (EU) Member States to estimate the 2011/12 influenza vaccine effectiveness against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza A(H3) among the vaccination target groups. Practitioners systematically selected ILI / acute respiratory infection patients to swab within seven days of symptom onset. We restricted the study population to those meeting the EU ILI case definition and compared influenza A(H3) positive to influenza laboratory-negative patients. We used logistic regression with study site as fixed effect and calculated adjusted influenza vaccine effectiveness (IVE), controlling for potential confounders (age group, sex, month of symptom onset, chronic diseases and related hospitalisations, number of practitioner visits in the previous year). Adjusted IVE was 25% (95% confidence intervals (CI): -6 to 47) among all ages (n=1,014), 63% (95% CI: 26 to 82) in adults aged between 15 and 59 years and 15% (95% CI: -33 to 46) among those aged 60 years and above. Adjusted IVE was 38% (95%CI: -8 to 65) in the early influenza season (up to week 6 of 2012) and -1% (95% CI: -60 to 37) in the late phase. The results suggested a low adjusted IVE in 2011/12. The lower IVE in the late season could be due to virus changes through the season or waning immunity. Virological surveillance should be enhanced to quantify change over time and understand its relation with duration of immunological protection. Seasonal influenza vaccines should be improved to achieve acceptable levels of protection. ECDC

Introduction PERTINENT is a pilot active surveillance system of infants hospitalised with pertussis in six European Union/European Economic Area countries (37 hospitals, seven sites). Aim This 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. Methods We 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. Results From 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. Conclusions Incidence 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.

Between September 2017 and February 2018, influenza A(H1N1)pdm09, A(H3N2) and B viruses (mainly B/Yamagata, not included in 2017/18 trivalent vaccines) co-circulated in Europe. Interim results from five European studies indicate that, in all age groups, 2017/18 influenza vaccine effectiveness was 25 to 52% against any influenza, 55 to 68% against influenza A(H1N1)pdm09, -42 to 7% against influenza A(H3N2) and 36 to 54% against influenza B. 2017/18 influenza vaccine should be promoted where influenza still circulates. Funding: The five studies have received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 634446 to conduct the study in individuals aged 65 years or more. ECDC has contributed to fund some study sites of the EU-PC study under the Framework contract No ECDC/2014/026 for the individuals aged less than 65 years. All study teams are very grateful to all patients, general practitioners, paediatricians, hospital teams, laboratory teams, regional epidemiologists who have contributed to the studies. We acknowledge the authors, originating and submitting laboratories of the sequences from GISAID’s EpiFlu Database used for this study. All submitters of data may be contacted directly via the GISAID website www.gisaid.org Sí