Reopening schools in the context of increasing COVID-19 community transmission: The French experience.

BACKGROUND AND OBJECTIVES: The role of schools in the spread of SARS-CoV-2 infections in the community is still controversial. The objective of our study was to describe the epidemiology of SARS-CoV-2 infections in different pediatric age groups during the first 2 months of the fall back-to-school period, in the context of increasing viral transmission in France. METHODS: Weekly epidemiological data provided by Santé Publique France and the Ministry of National Education were analyzed according to the age groups defined by the different school levels. Weeks (W) 34-42 were considered for analysis. RESULTS: The PCR positivity rate and incidence rate increased in all age groups during the study period, in an age-dependent manner. At W42, with adults being considered as reference, the risk ratio for a positive PCR test was 0.46 [95% CI: 0.44-0.49] and 0.69 [0.68-0.70] for children aged 0-5 years and 6-17 years, respectively. Similarly, the incidence rate ratio was 0.09 [0.08-0.09], 0.31 [0.30-0.32], 0.64 [0.63-0.66], and 1.07 [1.05-1.10] for children aged 0-5 years, 6-10 years, 11-14 years, and 15-17 years, respectively. Children and adolescents accounted for 1.9% of the newly hospitalized patients between W34 and W42, and for 1.3% of new intensive care admissions. No death was observed. Among infected children and adolescents, the percentage of asymptomatic individuals was 57% at W34 and 48% at W42. The number of schools closed remained low, less than 1% throughout the study period. The number of confirmed cases among school staff was consistent with the data measured in the general population. CONCLUSION: In the context of increasing viral transmission in the population, the spread among children and adolescents remained lower than that observed among adults, despite keeping schools open. However, the impact was age-dependent, with data in high schools close to those observed in adults.

Comparison of whole-cell versus acellular pertussis vaccine effectiveness in school clusters of pertussis, France, 2013.

OBJECTIVES AND METHOD: We conducted a prospective study in 2013 to compare the whole-cell versus acellular pertussis vaccines effectiveness and duration of protection, following the occurrence of pertussis clusters. RESULTS: During seven school outbreaks, we identified 102 clinical pertussis cases, including 10 cases biologically confirmed by Bordetella pertussis specific PCR, among a cohort of 305 children in 2nd to 6th grade. The risk of pertussis when vaccinated with an acellular vaccine alone was 1.6 (RR=1.6; 95% CI=1.1-2.5) times higher than when vaccinated with a whole-cell vaccine or using a combined schedule. CONCLUSIONS: The limited duration of protection conferred by the acellular vaccine reinforces the 2013 introduction of the pertussis booster at six years old.

Are vaccinated measles cases protected against severe disease?

OBJECTIVES: We aimed to estimate vaccine effectiveness against severe measles based on the number of vaccine doses administered and the time since last vaccination. PATIENTS AND METHODS: We included measles cases aged at least 2 years and born since 1980 who were notified in France between 2006 and mid-2019. We considered two severity levels (moderate, severe) and calculated adjusted relative risks (aRR) using multinomial logistic regression. RESULTS: We included 10,399 cases. The risk of severe measles in two-dose vaccine recipients was 71% (aRR = 0.29 [95%CI 0.12-0.72]) and 83% (aRR = 0.17 [95%CI 0.04-0.70]) lower than in unvaccinated cases, if the time since last dose was less or more than 15 years, respectively. The risk of moderate disease followed a similar pattern. CONCLUSIONS: Two-dose measles vaccination provided long-term protection against severe cases, even after vaccine failures. These findings underscore the need for compliance to the recommended measles vaccination schedule to prevent severe cases.

Cluster of serogroup W invasive meningococcal disease in a university campus.

INTRODUCTION: In France, the expansion of an hypervirulent strain causing serogroup W invasive meningococcal disease (MenW) has been observed since 2015/16. We describe a cluster of three MenW cases, causing two deaths, at the end of 2016 in a university campus, and the vaccination campaign which was consequently organized. METHODS: Epidemiological and microbiological analyses led a multidisciplinary expertise group to recommend the organization of a mass vaccination campaign using ACWY vaccine targeting more than 30,000 students and staff in the university campus. Individual data on vaccination was collected using the lists of students and staff registered at the university to estimate vaccine coverage. RESULTS: Three MenW cases occurred within a 2-month period among students in different academic courses. All three isolates were identical and belonged to the "UK-2013 strain" phylogenetic branch. The attack rate was 10.8/100,000 students. The vaccination campaign was organized only 15 days after the third case occurred. In total, 13,198 persons were vaccinated. Vaccine coverage was estimated at 41% for students of the university and 35% for university staff. CONCLUSION: Timely notification of cases to health authorities was essential for the detection of the cluster and the rapid implementation of the vaccination campaign. No further cases occurred in the campus in the year following the vaccination campaign. This episode is the second cluster of MenW caused by the "UK-2013 strain" in a university since 2016.

Measles and rubella seroprevalence in a population of young adult blood donors, France 2013.

As part of the evaluation of the French plan for the elimination of measles and rubella, we conducted a seroprevalence survey in 2013, aimed at updating seroprevalence data for people 18-32 years old. A secondary objective was to estimate measles incidence in this population during the 2009-2011 outbreak, and thus estimate the exhaustiveness of measles mandatory reporting. We used a cross-sectional survey design, targeting blood donors 18-32 years old, living in France since 2009, who came to give blood in a blood collecting site. We included 4647 people in metropolitan France, 806 people in Réunion Island and 496 in the French Caribbean. A further 3942 individuals were interviewed in the south-east region of metropolitan France to estimate the exhaustiveness of measles mandatory reporting. One of the main findings of this survey is that the proportion of people 18-32 years old susceptible to both measles and rubella infections remained high in France in 2013, 9.2% and 5.4%, respectively, in metropolitan France, even after the promotion campaigns about vaccination catch-up during and following the major measles epidemic in 2009-2011. Applying our results to French census data would suggest that around 1 million people aged 18-32 years old are currently susceptible to measles in France, despite this age group being one of the vaccination targets of the national measles elimination plan. Another important finding is that only an estimated 45% of the true number of cases in this age group was actually notified, despite notification being mandatory.

Characteristics and changes in invasive meningococcal disease epidemiology in France, 2006-2015.

OBJECTIVES: This work aimed to describe the epidemiology of invasive meningococcal disease (IMD) in France, 2006-2015, including group- and genotype-specific disease burden, incidence trends before and after introduction of meningococcal C conjugate vaccines (MCCV) in 2010, and factors influencing the case fatality rate. METHODS: Mandatory notification data on incidence and IMD case characteristics were used. Genotyping of invasive strains and whole genome sequencing were performed by the French National Reference Center. Vaccination coverage was estimated from the National Health Insurance Information System's reimbursement data. RESULTS: The decrease in annual IMD incidence rates (per 100,000 inhabitants) from 1.23 in 2006 to 0.78 in 2016 was mainly related to the decrease in group B IMD. Group C incidence decreased from 0.29 in 2006 to 0.13 in 2010 but increased thereafter in age groups not targeted by MCCV. From 2010 onwards, MCCV coverage gradually increased but remained below 25% in 15-19 year-olds in 2015. Age, clinical presentation and, to a lesser extent, clonal complex 11 were the most significant factors determining mortality. CONCLUSIONS: The limited impact of vaccination on group C IMD incidence may be explained by the emergence of a new epidemic cycle in 2011 and the low vaccination coverage rates among adolescents and young adults.

Socioeconomic inequalities to accessing vaccination against human papillomavirus in France: Results of the Health, Health Care and Insurance Survey, 2012.

BACKGROUND: In France, human papillomavirus (HPV) vaccination coverage among adolescents and young women is low and decreasing. We analysed data from the 2012 Health, Health Care and Insurance Survey with the aim of identifying factors associated with this vaccination. We also compared the socioeconomic profile of unvaccinated young women to that of women who do not undergo cervical cancer screening (CCS). METHODS: Data were collected through interviews and self-administered questionnaires completed by a randomised sample of Health insurance beneficiaries. Two analyses were performed using Poisson regression: one to investigate the determinants of CCS uptake in women aged 25-65 years old (n=4508), the other to investigate the determinants of HPV vaccination in young women aged 16-24 years old (n=899). A sub-analysis was performed in 685 "daughter-mother" couples from the same household in order to analyse the association between participation to CCS in mothers and HPV vaccination in daughters. RESULTS: Factors significantly associated both to a lower CCS uptake and to an insufficient HPV vaccination were the lack of a complementary private health insurance (P=0.023 and P=0.037, respectively) and living in a family with a low household income (P<0.001 and P=0.005, respectively). A low education level was associated to a lower CCS uptake (P<0.001). The absence of CCS uptake in the last three years in mothers was associated to a lower level of HPV vaccination in their daughter (P=0.014). CONCLUSION: Women who do not undergo CCS and HPV unvaccinated young women tend to be of modest socioeconomic status. Unvaccinated young females tend to have mothers who do not undergo CCS and are therefore at risk of benefiting from none of the two cervical cancer preventive measures. The current implementation strategy concerning HPV vaccination in France may therefore increase inequalities regarding cervical cancer prevention.

Seroprevalence of cytomegalovirus infection in France in 2010.

Cytomegalovirus (CMV) infection remains the leading cause of congenital virus infection in developed countries. Measuring the national prevalence of this infection, especially among women of childbearing age, is of great value to estimate the risk of congenital CMV infection, as well as to identify risk groups that should be targeted for behavioural interventions and/or vaccination once a CMV vaccine finally becomes available. In order to fulfil these objectives, a seroprevalence survey was conducted in 2010, using a nationally representative, population-based sample of 2536 people aged between 15 and 49 years, living in metropolitan France and attending private microbiological laboratories for blood testing. All blood samples were analysed in the same laboratory and screened for CMV-specific IgG using an enzyme-linked immunoassay technique (Elisa PKS Medac Enzyme immunoassay). The overall point estimate of CMV infection seroprevalence for individuals aged 15-49 years was 41.9%. The estimates were higher in women than in men (respectively 45.6% and 39.3%), and people born in a non-Western country were more likely to be CMV seropositive than those born in France or in another Western country (93.7% vs. 37.7%). Our results showed that a substantial percentage of women of childbearing age in France are CMV seronegative and therefore at risk of primary CMV infection during pregnancy. Educational measures and future vaccine are key issues to prevent infection in pregnant women and congenital CMV disease.

[Vaccination coverage and socioeconomic determinants of BCG vaccination in children before 3 months: Results of the Elfe cohort study, 2011]. / Couverture vaccinale et déterminants socioéconomiques de la vaccination BCG chez l'enfant avant 3 mois : résultats de la cohorte Elfe, 2011.

BACKGROUND: In 2007, French authorities changed mandatory BCG vaccination for all children into a strong recommendation to vaccinate only children considered at high risk of tuberculosis. Vaccination coverage (VC) data are insufficient in France. We estimated VC at approximately two months of age and identified socioeconomic factors associated with BCG vaccination. METHODS: The Elfe study (Étude Longitudinale Française depuis l'Enfance) included a random sample of about 18 000 children born in 2011 selected at birth from 320 maternity wards from mainland France. Information was collected through questionnaires and telephone interviews conducted approximately two months after delivery. Because BCG recommendations are different in the Paris region (Île-de-France [IDF]) and outside this region, VC was estimated separately in these two regions. We estimated VC for different levels of tuberculosis risk, approached by the geographical origin of the parents. Poisson regression was performed to analyze the association between socioeconomic factors and BCG vaccination status, and results expressed by prevalence ratios (PR). RESULTS: CV was higher in IDF (59.5%) compared to at-risk children outside IDF (46.7%) (p<0.001). VC in children with two parents from a tuberculosis highly endemic country was 80.5% in IDF and 60.4% outside IDF. In the multivariable model, having one or two parents from a tuberculosis highly endemic country (PR around 1.40) or consulting a private pediatrician (PR around 1.15) or a maternal and child health (MCH) center (PR around 1.40) after leaving the maternity ward were associated with a higher VC, whereas a university educational level in mothers was associated with a lower VC (PR=0.80). CONCLUSION: In France, BCG vaccination in infants is performed early after discharge from the maternity ward. A first consultation with a pediatrician or in a MCH center is associated with better vaccination coverage. Children at higher risk are probably well identified by physicians and better vaccinated.

Use of health care reimbursement data to estimate vaccination coverage in France: Example of hepatitis B, meningitis C, and human papillomavirus vaccination.

BACKGROUND: Sources of data used in France to routinely monitor vaccination coverage, such as the Child Health Certificates and school surveys, allow reliable estimations, but data are not made available with long delays. To rapidly identify recent changes, we have explored the feasibility and relevance of using vaccine reimbursement data. METHODS: We used the Permanent Sample of Beneficiaries, a representative sample of the National Health Insurance Information System, which contains data on health spending reimbursement of the vast majority of the population. We first validated this new source by comparing measles vaccine coverage between Child Health Certificates and the Permanent Sample of Beneficiaries. We present herein the results on hepatitis B, meningococcal C, and human papillomavirus vaccination (HPV) coverage. RESULTS: Measles vaccine coverage estimated with the Permanent Sample of Beneficiaries (91.4%) is very close to the estimation obtained through Child Health Certificates (90.6%). For children born in 2011, hepatitis B vaccination coverage at 24 months of age was 88.7% for one dose and meningococcal vaccination coverage was 56.4% for one dose in December 2013. Of girls born in 1997, 20.1% had received the full HPV vaccination series on their 16th birthday. CONCLUSION: This novel routine vaccination coverage monitoring tool provides regularly updated reactive and reliable vaccination coverage estimates in children.

[Vaccination coverage against hepatitis B in first-grade children, Paris, 2002-2008]. / Couverture vaccinale contre l'hépatite B des enfants scolarisés à Paris en classe préparatoire entre 2002 et 2008.

INTRODUCTION: The French controversy over the possible risks of vaccination against hepatitis B seems to have resulted in a slowdown or delay in vaccination of target populations since the mid-1990s. This article reports the results of the analysis of vaccination coverage against hepatitis B of first-grade children in Paris between 2002 and 2008. METHODOLOGY: Retrospective and descriptive study of vaccination status against hepatitis B for children born between 1997 and 2002 and attending first grade in a Paris school between 2002 and 2008, using anonymous data from the prevention service of the city of Paris. RESULTS: The analysis included 108,114 children whose Health Book (carnet de santé) included sociodemographic data and the presence of at least one diphtheria-tetanus-polio vaccination. Among these targeted children, 66,597 (61.6%) had started a vaccination against hepatitis B, 61,190 (56.6%) were considered "vaccinated" (at least three doses), and 47,489 (43.9%) "adequately vaccinated" (at least three doses respecting the prescribed intervals between injections). The sociodemographic factors associated with hepatitis B coverage were as follows: Paris arrondissement where the child attended school, year, and country of birth. CONCLUSION: Nearly 40% of the children in this cohort had not been vaccinated against hepatitis B before beginning first grade. They have now become adolescents aged 12-17 years. Current data indicate that only one-third of them have benefited from the catch-up campaign. This finding reinforces the need for vigilance on the vaccination status of adolescents against hepatitis B.

Impact of the BCG vaccination policy on tuberculous meningitis in children under 6 years in metropolitan France between 2000 and 2011.

In France, Bacillus Calmette­Guérin (BCG) vaccination by multipuncture device was withdrawn in 2006. In 2007, universal mandatory BCG vaccination was replaced by vaccination of high-risk children. To evaluate the impact of these changes on tuberculous meningitis (TBM) epidemiology, data on culture-positive and culture-negative (or unknown microbiological result) TBM in ≤5 years olds were collected from 2000­2011. Ten culture-positive and 17 culture-negative TBM cases were identified, with an annual incidence rate ranging from 0.16 to 0.66 cases per 10 million inhabitants. The average annual numbers of TBM cases were 2.7 and 1.8 from 2000­2005 and 2006­2011, respectively. In Ile-de-France where all children are considered at risk, the overall incidence rates were 1.14 and 0.29 per million for the two periods. In other regions where only at-risk children are vaccinated since 2007, rates were 0.30 and 0.47, respectively. None of these differences were significant. Annual incidence rates for each one year age group cohort were comparable before and after changes. Childhood TBM remains rare in France. No increase in incidence was observed after changes in BCG vaccination strategy. Ongoing surveillance should be maintained, as a slight increase in TBM in the coming years remains possible, in the context of suboptimal vaccination coverage of high-risk children.

Characteristics and practices of National Immunisation Technical Advisory Groups in Europe and potential for collaboration, April 2014.

In many countries, national vaccination recommendations are developed by independent expert committees, so-called national immunisation technical advisory groups (NITAG). Since the evaluation of vaccines is complex and resource-demanding, collaboration between NITAGs that evaluate the same vaccines could be beneficial. We conducted a cross-sectional survey among 30 European countries in February 2014, to explore basic characteristics and current practices of European NITAGs and identify potential modes and barriers for collaboration. Of 28 responding countries, 26 reported to have a NITAG or an equivalent expert group. Of these, 20 apply a systematic approach in the vaccine decision-making process, e.g. by considering criteria such as country-specific disease epidemiology, vaccine efficacy/effectiveness/safety, health economics, programme implementation/logistics or country-specific values/preferences. However, applied frameworks and extent of evidence review differ widely. The use of systematic reviews is required for 15 of 26 NITAGs, while results from transmission modelling and health economic evaluations are routinely considered by 18 and 20 of 26 NITAGs, respectively. Twenty-five countries saw potential for NITAG-collaboration, but most often named structural concerns, e.g. different NITAG structures or countries' healthcare systems. Our survey gathered information that can serve as an inventory on European NITAGs, allowing further exploration of options and structures for NITAG collaboration.

Impact of the pneumococcal conjugate vaccines on invasive pneumococcal disease in France, 2001-2012.

CONTEXT AND AIMS: Vaccination with the 7-valent pneumococcal conjugate vaccine (PCV7) was recommended in France in 2003 for children <2 years. The 13-valent conjugate vaccine (PCV13) replaced PCV7 in 2010. We assessed the impact of PCVs vaccination on the incidence of invasive pneumococcal diseases (IPD) in French children (0-15 years) and adults (>15 years). METHODS: IPD rates were calculated using cases reported from 2001 to 2012 to Epibac, a laboratory network. The distribution of serotypes was assessed from invasive isolates serotyped at the National reference Centre for Pneumococci. IPD incidence rates were compared between the pre-PCV7 (2001-2002), late PCV7 (2008-2009) and post PCV13 (2012) periods. RESULTS: The PCVs coverage increased from 56% in the 2004 birth-cohort to 94% in the 2008 and following birth-cohorts. Following PCV7 introduction, IPD incidence decreased by 19% between 2001-2002 and 2008-2009 in children <2 years, but increased in children aged 2-15 years and adults, despite a sharp decline in PCV7-IPD in all age-groups. After PCV13 introduction, IPD incidence decreased by 34% in children <5 years, by 50% in those aged 5-15 years and 15% in adults from 2008-2009 to 2012. The incidence of PCV13-Non PCV7-IPD decreased by 74% in children <5 years and by 60% in those aged 5-15 years. CONCLUSIONS: Vaccination with PCV13 was rapidly followed by a decrease in the incidence of all-type IPD in children, in relation with a sharp decrease in the incidence of PCV13-Non PCV7-IPD. Moreover, all-type IPD decreased after PCV13 introduction in older non-vaccinated age-groups, with a shift in the distribution of serotypes. Considering the whole 2001-2012 period, the vaccination with PCV7 and PCV13 resulted in a decline in the incidence of IPD in children up to the age of 5 but not in older children and adults.

Validity of self-reported vaccination status among French healthcare students.

Data on validity of self-reported vaccinations are scarce. This study, performed on healthcare students in Paris (France), aimed to evaluate this validity for occupational vaccinations. The validity of self-reported vaccination status was compared with written information. A total of 432 students were enrolled. Sensitivity rates for BCG, hepatitis B and measles were over 74%. For diphtheria-tetanus-polio and pertussis, sensitivity was below 50%. Specificity was between 70 and 95% for dTP-pertussis, and below 35% for all others. Overall, the validity of self-reported information was low, meaning that checking medical records remains the preferable strategy for assessing immunization status.

Assessment of the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic in the Middle East and risk of international spread using a novel maximum likelihood analysis approach.

The emergence of the novel Middle East (ME) respiratory syndrome coronavirus (MERS-CoV) has raised global public health concerns regarding the current situation and its future evolution. Here we propose an integrative maximum likelihood analysis of both cluster data in the ME and importations in a set of European countries to assess the transmission scenario and incidence of sporadic infections. Our approach is based on a spatial-transmission model integrating mobility data worldwide and allows for variations in the zoonotic/environmental transmission and under-ascertainment. Maximum likelihood estimates for the ME, considering outbreak data up to 31 August 2013, indicate the occurrence of a subcritical epidemic with a reproductive number R of 0.50 (95% confidence interval (CI): 0.30-0.77) associated with a daily rate of sporadic introductions psp of 0.28 (95% CI: 0.12-0.85). Infections in the ME appear to be mainly dominated by zoonotic/environmental transmissions, with possible under-ascertainment (ratio of estimated to observed (0.116) sporadic cases equal to 2.41, 95% CI: 1.03-7.32). No time evolution of the situation emerges. Analyses of flight passenger data from ME countries indicate areas at high risk of importation. While dismissing an immediate threat for global health security, this analysis provides a baseline scenario for future reference and updates, suggests reinforced surveillance to limit under-ascertainment, and calls for alertness in high importation risk areas worldwide.

Impact of free on-site vaccine and/or healthcare workers training on hepatitis B vaccination acceptability in high-risk subjects: a pre-post cluster randomized study.

Despite recommendations for adults at high-risk of hepatitis B virus (HBV) infection, HBV vaccine uptake remains low in this population. A pre-post randomized cluster study was conducted to evaluate the impact of on-site free HBV vaccine availability and/or healthcare worker training on HBV vaccination acceptability in high-risk adults consulting in 12 free and anonymous HIV and hepatitis B/C testing centres (FATC). The FATC were randomly allocated into three groups receiving a different intervention: training on HBV epidemiology, risk factors and vaccination (Group A), free vaccination in the FATC (Group B), both interventions (Group C). The main outcomes were the increase in HBV vaccination acceptability (receipt of at least one dose of vaccine) and vaccine coverage (receipt of at least two doses of vaccine) after intervention. Respectively, 872 and 809 HBV-seronegative adults at high-risk for HBV infection were included in the pre- and post-intervention assessments. HBV vaccination acceptability increased from 14.0% to 75.6% (p <0.001) in Group B and from 17.1% to 85.8% (p <0.001) in Group C and HBV vaccine coverage increased from 9.4% to 48.8% (p <0.001) in Group B and from 11.2% to 41.0% (p <0.001) in Group C. The association of training and free on-site vaccine availability was more effective than free on-site vaccine availability alone to increase vaccination acceptability (ratio 1.14; from 1.02 to 1.26; p 0.017). No effect of training alone was observed. These results support the policy of making HBV vaccine available in health structures attended by high-risk individuals. Updating healthcare workers' knowledge on HBV virus and its prevention brings an additional benefit to vaccination acceptability.