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.

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.

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.

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.

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.

Disentangling a complex nationwide Salmonella Dublin outbreak associated with raw-milk cheese consumption, France, 2015 to 2016.

On 18 January 2016, the French National Reference Centre for Salmonella reported to Santé publique France an excess of Salmonella enterica serotype Dublin (S. Dublin) infections. We investigated to identify the source of infection and implement control measures. Whole genome sequencing (WGS) and multilocus variable-number tandem repeat analysis (MLVA) were performed to identify microbiological clusters and links among cases, animal and food sources. Clusters were defined as isolates with less than 15 single nucleotide polymorphisms determined by WGS and/or with identical MLVA pattern. We compared different clusters of cases with other cases (case-case study) and controls recruited from a web-based cohort (case-control study) in terms of food consumption. We interviewed 63/83 (76%) cases; 2,914 controls completed a questionnaire. Both studies' findings indicated that successive S. Dublin outbreaks from different sources had occurred between November 2015 and March 2016. In the case-control study, cases of distinct WGS clusters were more likely to have consumed Morbier (adjusted odds ratio (aOR): 14; 95% confidence interval (CI): 4.8-42) or Vacherin Mont d'Or (aOR: 27; 95% CI: 6.8-105), two bovine raw-milk cheeses. Based on these results, the Ministry of Agriculture launched a reinforced control plan for processing plants of raw-milk cheeses in the production region, to prevent future outbreaks.

Large outbreak of mumps virus genotype G among vaccinated students in Norway, 2015 to 2016.

From 6 September 2015-May 2016, a large mumps outbreak occurred among vaccinated students in Norway. A case was defined as a person presenting with a clinical mumps infection, notified between 1 September 2015 and 30 June 2016. Confirmed cases had positive laboratory confirmation and probable cases had an epidemiological link; PCR-positive specimens were genotyped. A total of 232 cases were notified (230 confirmed) with median age of 23 years (range 4-81) and 61% were male. Of 68 (30%) confirmed cases that were genotyped, 66 were genotype G and associated with the outbreak. Cases that had received two doses of the measles-mumps-rubella (MMR) vaccine had reduced risk of hospitalisation (adjusted relative risk (aRR): 0.14; 95%CI: 0.03-0.57), mumps-related orchitis (aRR: 0.21; 95% CI: 0.08-0.55) and severe outcome (aRR: 0.25; 95% CI: 0.10-0.62) compared with those unvaccinated. A third dose of the vaccine was offered to approximately 1,300 fully vaccinated close contacts and subsequently reported cases decreased. This large outbreak, occurring among predominately vaccinated students, suggests the current genotype A vaccine offers suboptimal protection against mumps genotype G. We recommend maintaining high vaccination coverage and offering the vaccine to all unvaccinated individuals.

Low measles vaccination coverage among medical residents in Marseille, France: reasons for non-vaccination, March 2013.

BACKGROUND: During 2008-12, France and Europe experienced large measles outbreaks, involving also healthcare workers (HCW). We aimed to estimate the vaccination coverage (VC) of measles among medical residents of the University of Aix/Marseille, in South-Eastern France. METHODS: In March 2013, we conducted a cross-sectional study among all medical residents of the Medical Faculty of Aix/Marseille. We used a self-administered questionnaire to collect information on self-reported VC and reasons for vaccination and non-vaccination. We compared proportions, using the chi-squared test and prevalence ratios (PRs) with 95% confidence intervals (95% CIs). RESULTS: Of 1152 eligible residents, 703 (61%) participated in the study and 95 (14%; 95% CI: 12-17%) reported having had measles in the past. Of all participants, 613 (93%; 95% CI: 91-95%) reported having been vaccinated against measles and 389 (76%; 95% CI: 73-80%) received two doses. Only 268 (38%) reported having visited an occupational health physician. Vaccinated individuals were more likely to report easy access to vaccination as the main motivation for measles vaccination, compared with unvaccinated residents (435; 71% and 21; 45%; P < 0.001, respectively). CONCLUSIONS: VC among the medical residents of the University of Aix/Marseille was well below the recommended 95% coverage for two doses of measles vaccination. The majority of the study participants had not visited an occupational health doctor. Lack of easy access seems to represent major barriers to measles vaccination. We recommend that the student union, occupational health services and hospitals co-operate and address these problems in order to improve VC in this group.

Injection of new psychoactive substance snow blow associated with recently acquired HIV infections among homeless people who inject drugs in Dublin, Ireland, 2015.

In February 2015, an outbreak of recently acquired HIV infections among people who inject drugs (PWID) was identified in Dublin, following similar outbreaks in Greece and Romania in 2011. We compared drug and risk behaviours among 15 HIV cases and 39 controls. Injecting a synthetic cathinone, snow blow, was associated with recent HIV infection (AOR: 49; p=0.003). Prevention and control efforts are underway among PWID in Dublin, but may also be needed elsewhere in Europe.

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.

Mapping environmental suitability for malaria transmission, Greece.

During 2009-2012, Greece experienced a resurgence of domestic malaria transmission. To help guide malaria response efforts, we used spatial modeling to characterize environmental signatures of areas suitable for transmission. Nonlinear discriminant analysis indicated that sea-level altitude and land-surface temperature parameters are predictive in this regard.

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.

Outbreak of West Nile virus infection in Greece, 2010.

During 2010, an outbreak of West Nile virus infection occurred in Greece. A total of 197 patients with neuroinvasive disease were reported, of whom 33 (17%) died. Advanced age and a history of heart disease were independently associated with death, emphasizing the need for prevention of this infection in persons with these risk factors.

Persistence of West Nile virus immunoglobulin M antibodies, Greece.

A major outbreak of West Nile virus (WNV) lineage 2 infections was observed in 2010 in Greece. In order to check the persistence of WNV IgM antibodies, a second serum sample taken 75-180 days after onset of the illness from 29 patients with WNV infection was tested. A third sample was obtained 181-270 days after onset of the illness from 8 of the 12 patients with IgM-positive second sample. Mixed effects linear regression analysis indicated that the approximate time at which IgM index became negative was 164 (95% confidence interval, 95% CI 99-236) days after the symptoms' onset. Persistence of IgM antibodies was observed in 12% of patients at 181-270 days of follow-up. A sharp decrease in the IgM levels was observed, mainly in patients who had high IgM index value in the acute phase. All patients were WNV IgG positive at the follow-up.

Development time of IgG antibodies to West Nile virus.

Following an outbreak of West Nile virus (WNV) infections in Greece during summer/autumn 2010, a study was conducted to investigate the patterns of WNV IgG reactivity in 255 patients with respect to the day of illness and the type of clinical syndrome. IgG antibodies were detectable after a mean of 8.1 ± 4.9 and 12.6 ± 11.3 days after onset of illness in neuroinvasive and non-neuroinvasive cases, respectively (p < 0.001), suggesting that a delay in the development of WNV IgG antibodies is seen in non-neuroinvasive cases.