Methodological issues of retrospective surveys for measuring mortality of highly clustered diseases: case study of the 2014-16 Ebola outbreak in Bo District, Sierra Leone.

BACKGROUND: There is a lack of empirical data on design effects (DEFF) for mortality rate for highly clustered data such as with Ebola virus disease (EVD), along with a lack of documentation of methodological limitations and operational utility of mortality estimated from cluster-sampled studies when the DEFF is high. OBJECTIVES: The objectives of this paper are to report EVD mortality rate and DEFF estimates, and discuss the methodological limitations of cluster surveys when data are highly clustered such as during an EVD outbreak. METHODS: We analysed the outputs of two independent population-based surveys conducted at the end of the 2014-2016 EVD outbreak in Bo District, Sierra Leone, in urban and rural areas. In each area, 35 clusters of 14 households were selected with probability proportional to population size. We collected information on morbidity, mortality and changes in household composition during the recall period (May 2014 to April 2015). Rates were calculated for all-cause, all-age, under-5 and EVD-specific mortality, respectively, by areas and overall. Crude and adjusted mortality rates were estimated using Poisson regression, accounting for the surveys sample weights and the clustered design. RESULTS: Overall 980 households and 6,522 individuals participated in both surveys. A total of 64 deaths were reported, of which 20 were attributed to EVD. The crude and EVD-specific mortality rates were 0.35/10,000 person-days (95%CI: 0.23-0.52) and 0.12/10,000 person-days (95%CI: 0.05-0.32), respectively. The DEFF for EVD mortality was 5.53, and for non-EVD mortality, it was 1.53. DEFF for EVD-specific mortality was 6.18 in the rural area and 0.58 in the urban area. DEFF for non-EVD-specific mortality was 1.87 in the rural area and 0.44 in the urban area. CONCLUSION: Our findings demonstrate a high degree of clustering; this contributed to imprecise mortality estimates, which have limited utility when assessing the impact of disease. We provide DEFF estimates that can inform future cluster surveys and discuss design improvements to mitigate the limitations of surveys for highly clustered data.

Main findings: For humanitarian organizations it is imperative to document the methodological limitations of cluster surveys and discuss the utility.Added knowledge: This paper adds new knowledge on cluster surveys for highly clustered data such us in Ebola virus disease.Global health impact of policy and action: We provided empirical estimates and discuss design improvements to inform future study.

Association of Nonpharmaceutical Interventions During the COVID-19 Pandemic With Invasive Pneumococcal Disease, Pneumococcal Carriage, and Respiratory Viral Infections Among Children in France.

Importance: An association between pneumococcal nasopharyngeal carriage and invasive pneumococcal disease (IPD) has been previously established. However, it is unclear whether the decrease in IPD incidence observed after implementation of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic was associated with concomitant changes in pneumococcal carriage and respiratory viral infections. Objective: To assess changes in IPD incidence after the implementation of NPIs during the COVID-19 pandemic and examine their temporal association with changes in pneumococcal carriage rate and respiratory viral infections (specifically respiratory syncytial virus [RSV] and influenza cases) among children in France. Design, Setting, and Participants: This cohort study used interrupted time series analysis of data from ambulatory and hospital-based national continuous surveillance systems of pneumococcal carriage, RSV and influenza-related diseases, and IPD between January 1, 2007, and March 31, 2021. Participants included 11 944 children younger than 15 years in France. Exposures: Implementation of NPIs during the COVID-19 pandemic. Main Outcomes and Measures: The estimated fraction of IPD change after implementation of NPIs and the association of this change with concomitant changes in pneumococcal carriage rate and RSV and influenza cases among children younger than 15 years. The estimated fraction of change was analyzed using a quasi-Poisson regression model. Results: During the study period, 5113 children (median [IQR] age, 1.0 [0.6-4.0] years; 2959 boys [57.9%]) had IPD, and 6831 healthy children (median [IQR] age, 1.5 [0.9-3.9] years; 3534 boys [51.7%]) received a swab test. Data on race and ethnicity were not collected. After NPI implementation, IPD incidence decreased by 63% (95% CI, -82% to -43%; P < .001) and was similar for non-13-valent pneumococcal conjugate vaccine serotypes with both high disease potential (-63%; 95% CI, -77% to -48%; P < .001) and low disease potential (-53%; 95% CI, -70% to -35%; P < .001). The overall pneumococcal carriage rate did not significantly change after NPI implementation (-12%; 95% CI, -37% to 12%; P = .32), nor did the carriage rate for non-PCV13 serotypes with high disease potential (-26%; 95% CI, -100% to 52%; P = .50) or low disease potential (-7%; 95% CI, -34% to 20%; P = .61). After NPI implementation, the estimated number of influenza cases decreased by 91% (95% CI, -74% to -97%; P < .001), and the estimated number of RSV cases decreased by 74% (95% CI, -55% to -85%; P < .001). Overall, the decrease in influenza and RSV cases accounted for 53% (95% CI, -28% to -78%; P < .001) and 40% (95% CI, -15% to -65%; P = .002) of the decrease in IPD incidence during the NPI period, respectively. The decrease in IPD incidence was not associated with pneumococcal carriage, with carriage accounting for only 4% (95% CI, -7% to 15%; P = .49) of the decrease. Conclusions and Relevance: In this cohort study of data from multiple national continuous surveillance systems, a decrease in pediatric IPD incidence occurred after the implementation of NPIs in France; this decrease was associated with a decrease in viral infection cases rather than pneumococcal carriage rate. The association between pneumococcal carriage and IPD was potentially modified by changes in the number of RSV and influenza cases, suggesting that interventions targeting respiratory viruses, such as immunoprophylaxis or vaccines for RSV and influenza, may be able to prevent a large proportion of pediatric IPD cases.

Effectiveness of 10 and 13-valent pneumococcal conjugate vaccines against invasive pneumococcal disease in European children: SpIDnet observational multicentre study.

BACKGROUND: Pneumococcal conjugate vaccines covering 10 (PCV10) and 13 (PCV13) serotypes have been introduced in the infant immunization schedule of most European countries in 2010-11. To provide additional real-life data, we measured the effectiveness of PCV10 and PCV13 against invasive pneumococcal disease (IPD) in children of 12 European sites (SpIDnet). METHODS: We compared the vaccination status of PCV10 and PCV13 serotype IPD (cases) to that of nonPCV13 serotype IPD (controls) reported in 2012-2018. We calculated pooled effectiveness as (1-vaccination odds ratio)*100, and measured effectiveness over time since booster dose. RESULTS: The PCV13 and PCV10 studies included 2522 IPD cases from ten sites and 486 cases from four sites, respectively. The effectiveness of ≥ 1 PCV13 dose was 84.2% (95 %CI: 79.0-88.1) against PCV13 serotypes (n = 2353) and decreased from 93.1% (87.8-96.1) < 12 months to 85.1% (72.0-92.1) ≥ 24 months after booster dose. PCV13 effectiveness of ≥ 1 dose was 84.7% (55.7-94.7) against fatal PCV13 IPD, 64.5% (43.7-77.6), 83.2% (73.7-89.3) and 85.1% (67.6-93.1) against top serotypes 3, 19A and 1, respectively, and 85.4% (62.3-94.4) against 6C. Serotype 3 and 19A effectiveness declined more rapidly. PCV10 effectiveness of ≥ 1 dose was 84.8% (69.4-92.5) against PCV10 serotypes (n = 370), 27.2% (-187.6 to 81.6) and 85.3% (35.2-96.7) against top serotypes 1 and 7F, 32.5% (-28.3 to 64.5) and -14.4% (-526.5 to 79.1) against vaccine-related serotypes 19A and 6C, respectively. CONCLUSIONS: PCV10 and PCV13 provide similar protection against IPD due to the respective vaccine serotype groups but serotype-specific effectiveness varies by serotype and vaccine. PCV13 provided individual protection against serotype 3 and vaccine-related serotype 6C IPD. PCV10 effectiveness was not significant against vaccine-related serotypes 19A and 6C. PCV13 effectiveness declined with time after booster vaccination. This multinational study enabled measuring serotype-specific vaccine effectiveness with a precision rarely possible at the national level. Such large networks are crucial for the post-licensure evaluation of vaccines.

Serotype Replacement after Introduction of 10-Valent and 13-Valent Pneumococcal Conjugate Vaccines in 10 Countries, Europe.

We evaluated invasive pneumococcal disease (IPD) during 8 years of infant pneumococcal conjugate vaccine (PCV) programs using 10-valent (PCV10) and 13-valent (PCV13) vaccines in 10 countries in Europe. IPD incidence declined during 2011-2014 but increased during 2015-2018 in all age groups. From the 7-valent PCV period to 2018, IPD incidence declined by 42% in children <5 years of age, 32% in persons 5-64 years of age, and 7% in persons >65 years of age; non-PCV13 serotype incidence increased by 111%, 63%, and 84%, respectively, for these groups. Trends were similar in countries using PCV13 or PCV10, despite different serotype distribution. In 2018, serotypes in the 15-valent and 20-valent PCVs represented one third of cases in children <5 years of age and two thirds of cases in persons >65 years of age. Non-PCV13 serotype increases reduced the overall effect of childhood PCV10/PCV13 programs on IPD. New vaccines providing broader serotype protection are needed.

Relationship between serotypes, disease characteristics and 30-day mortality in adults with invasive pneumococcal disease.

PURPOSE: Invasive pneumococcal disease (IPD) is responsible for substantial mortality and morbidity worldwide. We aimed to identify host and bacterial factors associated with 30-day mortality in 18-year-old patients hospitalized with IPD in France from 2013 to 2015. METHODS: This study analyzed data collected from consecutives IPD cases included in two parallel multi-center cohort studies: COMBAT study (280 patients with pneumococcal community-acquired bacterial meningitis) and SIIP study (491 patients with non-meningitis IPD). Factors associated with 30-day mortality were identified using logistic regression. RESULTS: Among the 771 enrolled patients (median age 66 years, IQR [52.0-79.7]), 592/767 (77.2%) had at least one chronic disease. Patients with meningitis were younger (60.2 vs 70.9 years; p < 0.001) and had fewer chronic diseases than those with non-meningitis IPD (73.3% vs 79.4%; p = 0.05). Non-vaccine serotypes were more frequent in meningitis patients than in those with other IPD (36.1% vs 23.1%; p < 0.001). The overall 30-day mortality was 16.7% and patients with concurrent meningitis and extra-cerebral IPD had the highest 30-day mortality rate (26.5%). On multivariate analyses, older age, history of malignant solid tumor, meningeal IPD and serotypes previously identified with high mortality potential were independently associated with 30-day mortality. Of the serotypes with high mortality potential, 80% were included in licensed (PCV13 or PPV23) vaccines. CONCLUSION: We observed an effect of both host factors and pneumococcal serotypes on 30-day mortality in IPD. This highlights the need for a focused strategy to vaccinate at-risk patients. CLINICAL TRIAL: ClinicalTrial. Gov identification number: NCT01730690.

Low vaccination coverage for human papillomavirus disease among young men who have sex with men, France, 2019.

BackgroundIn France, human papillomavirus (HPV) vaccination has been recommended in 2016 for men who have sex with men (MSM) up to age 26 years.AimWe aimed to estimate HPV vaccine coverage in 18-28 year-old MSM and identify uptake determinants.MethodsWe collected data on socio-demographic characteristics, sexual behaviour, sexually transmitted diseases (STI) screening and vaccination uptake using a voluntary cross-sectional online survey conducted in 2019 targeting MSM. We calculated coverage of at least one dose of HPV vaccine and prevalence ratios (PR) of determinants with 95% confidence intervals (CI) using Poisson regression.ResultsOf 9,469 respondents (age range: 18-28 years), 15% (95% CI: 14-16) reported being vaccinated for HPV. Coverage was significantly higher among MSM < 24 years (PR: 1.25; 95% CI: 1.13-1.39), with education level below university degree (PR: 1.12; 95% CI: 1.08-1.32), living in rural areas (PR: 1.21; 95% CI: 1.08-1.36), attending sex parties (PR: 1.12; 95% CI: 1.03-1.33), using HIV-related biomedical prevention methods (PR: 1.31; 95% CI: 1.12-1.54), with STI diagnosis (PR: 1.22; 95% CI: 1.08-1.38) and with hepatitis A or B vaccination (PR: 4.56; 95% CI: 3.63-5.81 vs PR: 3.35; 95% CI: 2.53-4.44).ConclusionsThe HPV vaccination uptake among MSM in France was not satisfactory. It was higher among MSM benefitting from other vaccinations and biomedical preventive methods against HIV, suggesting a synergistic effect of the national preventive sexual health recommendations for MSM. Further efforts to improve HPV vaccination coverage targeting MSM are warranted.

Impact of COVID-19 social distancing on viral infection in France: A delayed outbreak of RSV.

INTRODUCTION: COVID-19 pandemic and associated lockdown measures have deeply modified the natural course of seasonal viral infections, such as respiratory syncytial virus (RSV). METHODS: We analyzed French national data from three networks: emergency departments (ED) of French hospitals, general practitioners (GP), and hospital laboratories. We compared the number of ED or GP visits for bronchiolitis in children <2 years of age, and the percentage of RSV positive tests in the 2020 to 2021 season with those of the two previous seasons (2018-2019 and 2019-2020). We used time series of the previous 5 years to calculate epidemic thresholds. RESULTS: During the 2020-2021 season, the epidemic begun in February (Week 05) in the Ile de France (Paris and suburbs) region, 12 weeks later compared with the previous seasons and progressively spread across all the French metropolitan regions. The highest number of bronchiolitis cases in 2021 (Week 12) occurred 10-12 weeks after the previous seasonal peaks of previous seasons, but the number of cases remained lower than in the previous seasonal peaks. CONCLUSION: We identified a delayed RSV epidemic in the period that usually corresponds at the end of the epidemic season, raising concerns for the burden of RSV in the already strained healthcare systems during the COVID-19 pandemic.

Recommendations for respiratory syncytial virus surveillance at the national level.

Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory tract infections and hospitalisations among young children and is globally responsible for many deaths in young children, especially in infants aged <6 months. Furthermore, RSV is a common cause of severe respiratory disease and hospitalisation among older adults. The development of new candidate vaccines and monoclonal antibodies highlights the need for reliable surveillance of RSV. In the European Union (EU), no up-to-date general recommendations on RSV surveillance are currently available. Based on outcomes of a workshop with 29 European experts in the field of RSV virology, epidemiology and public health, we provide recommendations for developing a feasible and sustainable national surveillance strategy for RSV that will enable harmonisation and data comparison at the European level. We discuss three surveillance components: active sentinel community surveillance, active sentinel hospital surveillance and passive laboratory surveillance, using the EU acute respiratory infection and World Health Organization (WHO) extended severe acute respiratory infection case definitions. Furthermore, we recommend the use of quantitative reverse transcriptase PCR-based assays as the standard detection method for RSV and virus genetic characterisation, if possible, to monitor genetic evolution. These guidelines provide a basis for good quality, feasible and affordable surveillance of RSV. Harmonisation of surveillance standards at the European and global level will contribute to the wider availability of national level RSV surveillance data for regional and global analysis, and for estimation of RSV burden and the impact of future immunisation programmes.

Global Landscape Review of Serotype-Specific Invasive Pneumococcal Disease Surveillance among Countries Using PCV10/13: The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) Project.

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon.

Coronavirus Disease 2019 in French Residential Care Facilities: A Nationwide Study.

OBJECTIVES: The Coronavirus 2019 (COVID-19) pandemic caused a considerable mortality in long-term care facilities (LTCFs), including residential care setting and nursing homes. This study aimed to estimate COVID-19 incidence and mortality in residential care facilities and to compare them with those recorded in nursing homes. DESIGN: Nationwide observational study conducted by French health authorities. SETTINGS AND PARTICIPANTS: Since March 1, 2020, all LTCFs in France reported all COVID-19 cases and COVID-19-related deaths among their residents. METHODS: Possible cases were those with COVID-19-related symptoms without laboratory confirmation and confirmed cases those with a reverse transcriptase polymerase chain reaction test or serology positive for SARS-CoV-2. We included facilities with at least 1 confirmed case of COVID-19 and estimated the cumulative incidence of COVID-19 cases and mortality due to COVID-19 reported until June 30, 2020, using the maximum bed capacity as a denominator. RESULTS: Of the 2288 residential care facilities, 310 (14%) and, of the 7688 nursing homes, 3110 (40%) reported COVID-19 cases among residents (P < .001). The cumulative incidence of COVID-19 was significantly lower in residential care facilities as compared with nursing homes (1.10 vs 9.97 per 100 beds, P < .001). Mortality due to COVID-19 was also lower in residential care facilities compared with nursing homes (0.07 vs 1.29 per 100 beds, P < .001). Case fatality was lower in residential care facilities (6.49% vs 12.93%, P < .001). CONCLUSION AND IMPLICATIONS: French residential care facilities experienced a much lower burden from COVID-19 than nursing homes. Our findings may inform the implementation of better infection control practices in these settings.

Changes in Invasive Pneumococcal Disease Caused by Streptococcus pneumoniae Serotype 1 Following Introduction of PCV10 and PCV13: Findings from the PSERENADE Project.

Streptococcus pneumoniae serotype 1 (ST1) was an important cause of invasive pneumococcal disease (IPD) globally before the introduction of pneumococcal conjugate vaccines (PCVs) containing ST1 antigen. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project gathered ST1 IPD surveillance data from sites globally and aimed to estimate PCV10/13 impact on ST1 IPD incidence. We estimated ST1 IPD incidence rate ratios (IRRs) comparing the pre-PCV10/13 period to each post-PCV10/13 year by site using a Bayesian multi-level, mixed-effects Poisson regression and all-site IRRs using a linear mixed-effects regression (N = 45 sites). Following PCV10/13 introduction, the incidence rate (IR) of ST1 IPD declined among all ages. After six years of PCV10/13 use, the all-site IRR was 0.05 (95% credibility interval 0.04-0.06) for all ages, 0.05 (0.04-0.05) for <5 years of age, 0.08 (0.06-0.09) for 5-17 years, 0.06 (0.05-0.08) for 18-49 years, 0.06 (0.05-0.07) for 50-64 years, and 0.05 (0.04-0.06) for ≥65 years. PCV10/13 use in infant immunization programs was followed by a 95% reduction in ST1 IPD in all ages after approximately 6 years. Limited data availability from the highest ST1 disease burden countries using a 3+0 schedule constrains generalizability and data from these settings are needed.

Invasive pneumococcal disease incidence in children and adults in France during the pneumococcal conjugate vaccine era: an interrupted time-series analysis of data from a 17-year national prospective surveillance study.

BACKGROUND: The long-term benefits of pneumococcal conjugate vaccines (PCVs) remain unknown because of serotype replacement. We aimed to estimate the effect of PCV implementation on invasive pneumococcal disease incidence in France. METHODS: We did a quasi-experimental interrupted time-series analysis using data from a French national prospective surveillance system. We included all invasive pneumococcal disease cases in children and adults from more than 250 participating hospitals between Jan 1, 2001, and Dec 31, 2017. The primary outcome was incidence of invasive pneumococcal disease (meningitis and non-meningitis) over time, analysed by segmented regression with autoregressive error. Isolates were serotyped by latex agglutination with antiserum samples. FINDINGS: We included 75 903 patients with invasive pneumococcal disease, including 4302 (5·7%) children younger than 2 years and 37 534 (49·4%) adults aged 65 years or older. Before PCV7 implementation, the estimated monthly incidence of invasive pneumococcal disease was 0·78 cases per 100 000 inhabitants, which did not change significantly up to May, 2010. PCV13 implementation in 2010 was followed by a significant decrease in the incidence of invasive pneumococcal disease (-1·5% per month, 95% CI -2·2 to -0·8), reaching an estimated monthly incidence of 0·52 cases per 100 000 inhabitants in December, 2014. From January, 2015, the incidence rebounded (1·8% per month, 95% CI 1·0 to 2·6), reaching an estimated monthly incidence of 0·73 cases per 100 000 inhabitants in December, 2017. The estimated monthly incidence increased from 0·93 cases per 100 000 in December, 2014, to 1·73 cases per 100 000 in December, 2017, for children younger than 2 years, and from 1·54 cases per 100 000 in December, 2014, to 2·08 cases per 100 000 in December, 2017, for adults aged 65 years or older. The main non-PCV13 serotypes involved in the increase were 24F in young children and 12F, 22F, 9N, and 8 in adults aged 65 years or older. INTERPRETATION: PCV13 implementation led to a major reduction in the incidence of invasive pneumococcal disease. However, a rebound in cases among children and adults since 2015, driven by several emerging non-PCV13 serotypes, jeopardises the long-term PCV benefits. These findings, if confirmed in the coming years, should be considered in the development of next-generation PCVs and might guide policy makers in the selection of future pneumococcal vaccines. FUNDING: Foundation for Medical Research; Pfizer, BioMérieux, Sanofi for the Regional Observatory of Pneumococci.

Emergence of Kawasaki disease related to SARS-CoV-2 infection in an epicentre of the French COVID-19 epidemic: a time-series analysis.

BACKGROUND: Kawasaki disease is an acute febrile systemic childhood vasculitis, which is suspected to be triggered by respiratory viral infections. We aimed to examine whether the ongoing COVID-19 epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with an increase in the incidence of Kawasaki disease. METHODS: We did a quasi-experimental interrupted time series analysis over the past 15 years in a tertiary paediatric centre in the Paris region, a French epicentre of the COVID-19 outbreak. The main outcome was the number of Kawasaki disease cases over time, estimated by quasi-Poisson regression. In the same centre, we recorded the number of hospital admissions from the emergency department (2005-2020) and the results of nasopharyngeal multiplex PCR to identify respiratory pathogens (2017-2020). These data were compared with daily hospital admissions due to confirmed COVID-19 in the same region, recorded by Public Health France. FINDINGS: Between Dec 1, 2005, and May 20, 2020, we included 230 patients with Kawasaki disease. The median number of Kawasaki disease hospitalisations estimated by the quasi-Poisson model was 1·2 per month (IQR 1·1-1·3). In April, 2020, we identified a rapid increase of Kawasaki disease that was related to SARS-CoV-2 (six cases per month; 497% increase [95% CI 72-1082]; p=0·0011), starting 2 weeks after the peak of the COVID-19 epidemic. SARS-CoV-2 was the only virus circulating intensely during this period, and was found in eight (80%) of ten patients with Kawasaki disease since April 15 (SARS-CoV-2-positive PCR or serology). A second peak of hospital admissions due to Kawasaki disease was observed in December, 2009 (six cases per month; 365% increase ([31-719]; p=0.0053), concomitant with the influenza A H1N1 pandemic. INTERPRETATION: Our study further suggests that viral respiratory infections, including SAR-CoV-2, could be triggers for Kawasaki disease and indicates the potential timing of an increase in incidence of the disease in COVID-19 epidemics. Health-care providers should be prepared to manage an influx of patients with severe Kawasaki disease, particularly in countries where the peak of COVID-19 has recently been reached. FUNDING: French National Research Agency.

High impact of COVID-19 in long-term care facilities, suggestion for monitoring in the EU/EEA, May 2020.

Residents in long-term care facilities (LTCF) are a vulnerable population group. Coronavirus disease (COVID-19)-related deaths in LTCF residents represent 30-60% of all COVID-19 deaths in many European countries. This situation demands that countries implement local and national testing, infection prevention and control, and monitoring programmes for COVID-19 in LTCF in order to identify clusters early, decrease the spread within and between facilities and reduce the size and severity of outbreaks.

Clinical and epidemiological performance of WHO Ebola case definitions: a systematic review and meta-analysis.

BACKGROUND: Ebola virus disease case definition is a crucial surveillance tool to detect suspected cases for referral and as a screening tool for clinicians to support admission and laboratory testing decisions at Ebola health facilities. We aimed to assess the performance of the WHO Ebola virus disease case definitions and other screening scores. METHODS: In this systematic review and meta-analysis, we searched PubMed, Scopus, Embase, and Web of Science for studies published in English between June 13, 1978, and Jan 14, 2020. We included studies that estimated the sensitivity and specificity of WHO Ebola virus disease case definitions, clinical and epidemiological characteristics (symptoms at admission and contact history), and predictive risk scores against the reference standard (laboratory-confirmed Ebola virus disease). Summary estimates of sensitivity and specificity were calculated using bivariate and hierarchical summary receiver operating characteristic (when four or more studies provided data) or random-effects meta-analysis (fewer than four studies provided data). FINDINGS: We identified 2493 publications, of which 14 studies from four countries (Sierra Leone, Guinea, Liberia, and Angola) were included in the analysis. 12 021 people with suspected disease were included, of whom 4874 were confirmed as positive for Ebola virus infection. Six studies explored the performance of WHO case definitions in non-paediatric populations, and in all of these studies, suspected and probable cases were combined and could not be disaggregated for analysis. The pooled sensitivity of the WHO Ebola virus disease case definitions from these studies was 81·5% (95% CI 74·1-87·2) and pooled specificity was 35·7% (28·5-43·6). History of contact or epidemiological link was a key predictor for the WHO case definitions (seven studies) and for risk scores (six studies). The most sensitive symptom was intense fatigue (79·0% [95% CI 74·4-83·0]), assessed in seven studies, and the least sensitive symptom was pain behind the eyes (1·0% [0·0-7·0]), assessed in three studies. The performance of fever as a symptom varied depending on the cutoff used to define fever. INTERPRETATION: WHO Ebola virus disease case definitions perform suboptimally to identify cases at both community level and during triage at Ebola health facilities. Inclusion of intense fatigue as a key symptom and contact history could improve the performance of case definitions, but implementation of these changes will require effective collaboration with, and trust of, affected communities. FUNDING: Médecins sans Frontières.

Cluster of Coronavirus Disease 2019 (COVID-19) in the French Alps, February 2020.

BACKGROUND: On 7 February 2020, French Health authorities were informed of a confirmed case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an Englishman infected in Singapore who had recently stayed in a chalet in the French Alps. We conducted an investigation to identify secondary cases and interrupt transmission. METHODS: We defined as a confirmed case a person linked to the chalet with a positive reverse-transcription polymerase chain reaction sample for SARS-CoV-2. RESULTS: The index case stayed 4 days in the chalet with 10 English tourists and a family of 5 French residents; SARS-CoV-2 was detected in 5 individuals in France, 6 in England (including the index case), and 1 in Spain (overall attack rate in the chalet: 75%). One pediatric case, with picornavirus and influenza A coinfection, visited 3 different schools while symptomatic. One case was asymptomatic, with similar viral load as that of a symptomatic case. Seven days after the first cases were diagnosed, 1 tertiary case was detected in a symptomatic patient with from the chalet a positive endotracheal aspirate; all previous and concurrent nasopharyngeal specimens were negative. Additionally, 172 contacts were monitored; all contacts tested for SARS-CoV-2 (N = 73) were negative. CONCLUSIONS: The occurrence in this cluster of 1 asymptomatic case with similar viral load as a symptomatic patient suggests transmission potential of asymptomatic individuals. The fact that an infected child did not transmit the disease despite close interactions within schools suggests potential different transmission dynamics in children. Finally, the dissociation between upper and lower respiratory tract results underscores the need for close monitoring of the clinical evolution of suspected cases of coronavirus disease 2019.

Outbreak of pneumococcal pneumonia among shipyard workers in Marseille, France, January to February 2020.

We report the third outbreak of pneumococcal pneumonia within one year among workers in European shipyards. During January and February 2020, 37 cases of pneumonia were identified in a shipyard in Marseille, south-eastern France. Outbreak control measures were implemented, including a mass vaccination campaign with 23-valent pneumococcal polysaccharide vaccine targeting all shipyard workers. Given the high mobility of shipyard workers, coordinated responses between European public health institutes are necessary to avoid further outbreaks.

Maternal health after Ebola: unmet needs and barriers to healthcare in rural Sierra Leone.

Sierra Leone has the world's highest estimated maternal mortality. Following the 2014-16 Ebola outbreak, we described health outcomes and health-seeking behaviour amongst pregnant women to inform health policy. In October 2016-January 2017, we conducted a sequential mixed-methods study in urban and rural areas of Tonkolili District comprising: household survey targeting women who had given birth since onset of the Ebola outbreak; structured interviews at rural sites investigating maternal deaths and reporting; and in-depth interviews (IDIs) targeting mothers, community leaders and health workers. We selected 30 clusters in each area: by random GPS points (urban) and by random village selection stratified by population size (rural). We collected data on health-seeking behaviours, barriers to healthcare, childbirth and outcomes using structured questionnaires. IDIs exploring topics identified through the survey were conducted with a purposive sample and analysed thematically. We surveyed 608 women and conducted 29 structured and 72 IDIs. Barriers, including costs of healthcare and physical inaccessibility of healthcare facilities, delayed or prevented 90% [95% confidence interval (CI): 80-95] (rural) vs 59% (95% CI: 48-68) (urban) pregnant women from receiving healthcare. Despite a general preference for biomedical care, 48% of rural and 31% of urban women gave birth outside of a health facility; of those, just 4% and 34%, respectively received skilled assistance. Women expressed mistrust of healthcare workers (HCWs) primarily due to payment demanded for 'free' healthcare. HCWs described lack of pay and poor conditions precluding provision of quality care. Twenty percent of women reported labour complications. Twenty-eight percent of villages had materials to record maternal deaths. Pregnant women faced important barriers to care, particularly in rural areas, leading to high preventable mortality and morbidity. Women wanted to access healthcare, but services available were often costly, unreachable and poor quality. We recommend urgent interventions, including health promotion, free healthcare access and strengthening rural services to address barriers to maternal healthcare.

Factors Associated With Severe Nonmeningitis Invasive Pneumococcal Disease in Adults in France.

BACKGROUND: In France, pneumococcal vaccination in adults is recommended for risk groups (chronic conditions/immunosuppression). We conducted a study on invasive pneumococcal disease (IPD) in adults to identify factors associated with disease severity and death. METHODS: We included IPD cases, excluding meningitis, from 25 acute care hospitals in 6 regions. We defined severe cases as those with shock or severe sepsis or intensive care unit admission/mechanical ventilation. We included deaths occurring within 30 days of hospitalization. Infectious disease specialists collected clinical/microbiological data on cases. RESULTS: During 2014-2017, 908 nonmeningitis IPD cases were diagnosed; 48% were severe, 84% had comorbidities, 21% died. Ninety percent of cases with comorbidities who previously sought health care were not vaccinated against pneumococcus. Compared with previously healthy cases, the risk of severe IPD increased from 20% (adjusted risk ratio [aRR], 1.2; 95% confidence interval [CI], 1.0-1.4) in cases with 1-2 chronic diseases to 30% (aRR, 1.3; 95% CI, 1.0-7.0) in those with >2 chronic diseases. Among risk groups, 13-valent pneumococcal conjugate vaccine (PCV13) serotypes and 23-valent pneumococcal polysaccharide vaccine (PPSV23) nonPCV13 serotypes were more likely to induce severe IPD compared with nonvaccine serotypes (aRR, 1.5; 95% CI, 1.3-1.9; aRR, 1.3; 95% CI, 1.0-1.5, respectively). CONCLUSIONS: We observed a cumulative effect of concurrent comorbidities on severe IPD. Vaccine serotypes were more likely to induce severe IPD among risk groups. The missed opportunities for vaccination underscore the need to enhance vaccination in risk groups.