What is the relevancy of a surveillance of mumps without a systematic laboratory confirmation in highly immunized populations? Epidemiology of suspected and biologically confirmed mumps cases seen in general practice in France between 2014 and 2020.

BACKGROUND: In France, mumps surveillance is conducted in primary care by the Sentinelles network, the National Reference Centre for Measles, Mumps and Rubella and Santé publique France. AIM: The objective of this study was to estimate the incidence of suspected mumps in general practice, the proportion of laboratory confirmed cases and the factors associated with a virological confirmation. METHODS: General practitioners (GPs) participating in the Sentinelles network should report all patients with suspected mumps according to a clinical definition in case of parotitis and a serological definition in case of clinical expression without parotitis. All suspected mumps cases reported between January 2014 and December 2020 were included. A sample of these cases were tested by real time reverse transcriptase polymerase chain reaction (RT-PCR) for mumps biological confirmation. RESULTS: A total of 252 individuals with suspected mumps were included in the study. The average annual incidence rate of suspected mumps in general practice in France between 2014 and 2020 was estimated at 11 cases per 100,000 population [CI95%: 6-17]. A mumps confirmation RT-PCR test was performed on 146 cases amongst which 17 (11.5 %) were positive. Age (between 20 and 29 years old), the presence of a clinical complication and an exposure to a suspected mumps case within the 21 days prior the current episode were associated with a mumps biological confirmation. CONCLUSION: If these results confirm the circulation of mumps virus in France, they highlight the limits of a surveillance without a systematic laboratory confirmation in highly immunized populations.

Two-dose measles vaccine effectiveness remains high over time: A French observational study, 2017-2019.

BACKGROUND: From 2008 to 2019, France has experienced a resurgence of measles epidemics. Surveillance data have shown that the proportion of cases vaccinated with two doses of measles-containing vaccine (MCV) increased with age, raising concerns about the duration of vaccine protection. Our objectives were to investigate age-stratified vaccine effectiveness (VE) for the second dose of MCV (MCV2) and to quantify protection levels over time. METHODS: We analyzed data on measles cases aged 2-31 years, reported via mandatory notification to the French measles surveillance system from October 2017 to September 2019. We estimated an age-stratified VE for MCV2 using the screening method, which compares the vaccination status of cases with that of the general population. We improved this method by accounting for natural immunity, exploring four scenarios with four possible levels of natural immunity in the population. In addition, we quantified the decay rate of protection over time, by fitting an exponential decay model among individuals vaccinated in early life. RESULTS: In the baseline analysis (absence of natural immunity), VE estimates were high in all age groups and decreased with age, from 99.6 % (95 % confidence interval: 99.3-99.8) in 2-5 years old to 91.4 % (85.1-95.0) in 26-31 years old. Accounting for natural immunity increased VE in the older age group to 93.2-99.2 % depending on the scenario. We estimated that VE was slowly decreasing over time, with an exponential decay rate of 0.0022/year (0.0017-0.0028), leading to VE of 96.7 % (96.0-97.4) 16 years after MCV2 vaccination. This decline was most compatible with scenario 2, a scenario of 4.4 % naturally immunized, non-vaccinated individuals in the 26-31 years old. CONCLUSION: Our study confirms the continued high effectiveness of two doses of MCV with only slight degradation, decades after immunization. These findings support the importance of achieving a very high vaccination coverage with 2 doses of MCV.

Correction to "Hyper inflammatory syndrome following COVID-19 mRNA vaccine in children: A national post-authorization pharmacovigilance study".

[This corrects the article DOI: 10.1016/j.lanepe.2022.100393.].

Hyper inflammatory syndrome following COVID-19 mRNA vaccine in children: A national post-authorization pharmacovigilance study.

Background: Multisystem inflammatory syndrome in children (MIS-C) is the most severe clinical entity associated with pediatric SARS-CoV-2 infection with a putative role of the spike protein into the immune system activation. Whether COVID-19 mRNA vaccine can induce this complication in children is unknown. We aimed to assess the risk of hyper-inflammatory syndrome following COVID-19 mRNA vaccine in children. Methods: We conducted a post-authorization national population-based surveillance using the French enhanced pharmacovigilance surveillance system for COVID-19 vaccines. All cases of suspected hyper-inflammatory syndrome following COVID-19 mRNA vaccine in 12-17-year-old children between June 15th, 2021 and January 1st, 2022, were reported. Cases were reviewed according to WHO criteria for MIS-C. The reporting rate of this syndrome was compared to the MIS-C rate per 1,000,000 12-17-year-old children infected by SARS-CoV-2. Findings: Up to January 2022, 8,113,058 COVID-19 mRNA vaccine doses were administered to 4,079,234 12-17-year-old children. Among them, 12 presented a hyper-inflammatory syndrome with multisystemic involvement. Main clinical features included male predominance (10/12, 83%), cardiac involvement (10/12, 83%), digestive symptoms (10/12, 83%), coagulopathy (7/12, 58%), cytolytic hepatitis (6/12, 50%), and shock (5/12, 42%). 4/12 (33%) required intensive care unit transfer, and 3/12 (25%) hemodynamic support. All cases recovered. In eight cases, no evidence of previous SARS-CoV-2 infection was found. The reporting rate was 1.5 (95%CI [0.8; 2.6]) per 1,000,000 doses injected, i.e. 2.9 (95%CI [1.5; 5.1]) per 1,000,000 12-17-year-old vaccinated children. As a comparison, 113 MIS-C (95%CI [95; 135]) occurred per 1,000,000 12-17-year-old children infected by SARS-CoV-2. Interpretation: Very few cases of hyper-inflammatory syndrome with multi-organ involvement occurred following COVID-19 mRNA vaccine in 12-17-year-old children. The low reporting rate of this syndrome, compared to the rate of post-SARS-CoV-2 MIS-C in the same age-group, largely supports the vaccination in a context of an important circulation of SARS-CoV-2. Funding: ESPID Fellowship Award; Grandir-Fonds de Solidarité Pour L'enfance.

[Vaccination, a public health tool]. / La vaccination, un outil de santé publique.

Vaccination remains a major public health tool, the only one that has enabled the eradication of an infectious disease, smallpox. In this fight, biotechnological innovations point to considerable progress in the development of new vaccines. However, whatever technical progress is made, the impact of a vaccination program will depend on its performance and on the support of the population.

Educational Setting and SARS-CoV-2 Transmission Among Children With Multisystem Inflammatory Syndrome: A French National Surveillance System.

Background: Multisystem inflammatory syndrome in children (MIS-C) is the most severe form associated with SARS-CoV-2 infection in children. To reduce the spread of SARS-CoV-2 at the population level, educational setting closure have been implemented in many countries. However, the direct benefit of school closure on the MIS-C burden remains to be explored. We aimed to assess the role of educational settings in SARS-CoV-2 transmission among children with MIS-C. Methods: We conducted a French national prospective surveillance of MIS-C, coordinated by Public Health France, from April 2020 to March 2021. During this period, we included all children with MIS-C fulfilling the WHO definition who were reported to Public Health France. For each child, we traced the source of SARS-CoV-2 transmission. The main outcome was the proportion of children with MIS-C, with educational setting-related SARS-CoV-2 infection, during the period of school opening. Results: We included 142 children fulfilling WHO criteria for MIS-C: 104 (70%) cases occurred during school opening periods. In total, 62/104 children (60%, 95%CI [50; 69]) had been contaminated by a household contact and 5/104 in educational settings (5%, 95%CI [2; 11]). Among children with MIS-C occurring during school closure periods, the proportion of household transmission remained similar (66%, 25/38). Conclusion: Children with MIS-C were mainly infected by SARS-CoV-2 within their family environment, and the educational setting played a marginal role in this transmission. This suggests that mitigating school attendance may not reduce substantially the burden of MIS-C.

Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains unknown. Objective: To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C. Design, Setting, and Participants: Retrospective cohort study drawn from a national surveillance system with propensity score-matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021. Exposures: IVIG and methylprednisolone vs IVIG alone. Main Outcomes and Measures: The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1. Results: Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females [52%]; median age, 8.6 years [interquartile range, 4.7 to 12.1]). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, -0.28 [95% CI, -0.48 to -0.08]; odds ratio [OR], 0.25 [95% CI, 0.09 to 0.70]; P = .008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, -0.22 [95% CI, -0.40 to -0.04]; OR, 0.19 [95% CI, 0.06 to 0.61]; P = .004), hemodynamic support (absolute risk difference, -0.17 [95% CI, -0.34 to -0.004]; OR, 0.21 [95% CI, 0.06 to 0.76]), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, -0.18 [95% CI, -0.35 to -0.01]; OR, 0.20 [95% CI, 0.06 to 0.66]), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, -2.4 [95% CI, -4.0 to -0.7]). Conclusions and Relevance: Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design.

Prolonged Maternal Shedding and Maternal-fetal Transmission of Measles Virus.

Prolonged measles virus detection in maternal saliva and blood was evidenced in 6 pregnant women. Maternal-fetal transmission was evidenced in 2 of 4 infants who were asymptomatic at birth, 21-24 weeks after maternal infection. Whereas peripartum congenital measles is severe, asymptomatic measles virus vertical transmission can occur earlier in pregnancy.

Targeted vaccination campaigns of teenagers after two clusters of B invasive meningococcal disease in Brittany, France, 2017.

BACKGROUND: In December 2016, three cases of serogroup B invasive meningococcal disease, including two children from the same middle school (11 to 15 years old pupils), occurred in the department (administrative district) Côtes-d'Armor (Brittany, France). They were infected by a rare strain (B:P1.7-2,4:F5-9:cc162), covered by the 4CMenB vaccine (Bexsero®). Four months later, two cases due to the same strain occurred in a high school in the same area (15 to 19 years old students). In accordance with French recommendations, vaccination was proposed to students of both schools and to all individuals aged 11-19 years living or studying in the hyperendemic area. We describe these vaccination campaigns, from the alert to the impact evaluation. METHODS: The target population included 8884 people: 579 in the middle school, 2007 in the high school and 6298 in the community. In both schools, vaccination sessions were organized directly on site. In the community, teenagers were vaccinated by general practitioners. The vaccination campaign took place from May to October 2017. An active pharmacovigilance follow-up was set up to document adverse effects of the vaccine. RESULTS: Considering the whole target population, the vaccination coverage was estimated at 43% for 1 dose and 34% for 2 doses. Higher vaccination coverage was observed in the schools (79% in the middle school and 42% in the high school for 2 doses) than in the community (27% for 2 doses). The reported adverse effects were consistent with the safety profile of the vaccine and no severe adverse effect was reported. CONCLUSIONS: This vaccination campaign was the third one implemented with Bexsero® in France and constitutes a reproducible approach for future targeted vaccination campaigns. No additional cases of the same strain have occurred since the end of the campaigns in the area.

Risk Assessment and Virological Monitoring Following an Accidental Exposure to Concentrated Sabin Poliovirus Type 3 in France, November 2018.

The safe and secure containment of infectious poliovirus (PV) in facilities where live PV are handled is the condition to achieve and maintain poliomyelitis eradication. Despite precautions to minimize the risk of release of PV from such facilities to the environment, breaches of containment have already been documented. Here, we report the management of an incident that occurred on 30 November 2018 in a French vaccine manufacturing plant. Five adequately vaccinated operators were exposed to a Sabin poliovirus type 3 (PV3) spill. A microbiological risk assessment was conducted and the operators were monitored for PV shedding. On day 5 after exposure, Sabin PV3 was detected only in the stool sample of the most exposed worker. Shedding of Sabin PV3 (as detected by viral culture) was restricted to a very short period (less than 15 days). Monitoring of this incident was an opportunity to assess the relevance of our national response plan. We concluded that the measures undertaken and reported here were appropriate and proportional.

SARS-CoV-2-related paediatric inflammatory multisystem syndrome, an epidemiological study, France, 1 March to 17 May 2020.

End of April 2020, French clinicians observed an increase in cases presenting with paediatric inflammatory multisystem syndrome (PIMS). Nationwide surveillance was set up and demonstrated temporospatial association with the coronavirus disease (COVID-19) epidemic for 156 reported cases as at 17 May: 108 were classified as confirmed (n = 79), probable (n = 16) or possible (n = 13) post-COVID-19 PIMS cases. A continuum of clinical features from Kawasaki-like disease to myocarditis was observed, requiring intensive care in 67% of cases.

Severe Acute Flaccid Myelitis Associated With Enterovirus in Children: Two Phenotypes for Two Evolution Profiles?

Acute flaccid myelitis (AFM) is an acute paralysis syndrome defined by a specific inflammation of the anterior horn cells of the spinal cord. From 2014, worrying waves of life-threatening AFM consecutive to enterovirus infection (EV-D68 and EV-A71) have been reported. We describe 10 children displaying an AFM with an EV infection, the treatments performed and the 1 to 3-years follow-up. Two groups of patients were distinguished: 6 children ("polio-like group") had severe motor disability whereas 4 other children ("brainstem group") displayed severe brainstem weakness requiring ventilation support. Electrodiagnostic studies (n = 8) support the presence of a motor neuronopathy associated to myelitis. The best prognosis factor seems to be the motor recovery after the first 4 weeks of the disease.

Assessment of the impact of the extension of vaccination mandates on vaccine coverage after 1 year, France, 2019.

One year after the extension of the childhood vaccination mandates to the 11 routine vaccinations for children under 2 years old, we estimated vaccination coverage through vaccine reimbursement data. Coverage for children born in 2018 has notably increased. Moreover, vaccine coverage for children and for vaccines not concerned by the law have also shown an increasing trend, supporting a positive impact of the ongoing communication strategy on vaccination, beyond the extension of vaccination mandates.

Measles outbreak linked to insufficient vaccination coverage in Nouvelle-Aquitaine Region, France, October 2017 to July 2018.

On 30 October 2017, an outbreak of measles started in the Nouvelle-Aquitaine (NA) region in France among Bordeaux University students before spreading to other regions. Until 1 July 2018, 1,101 cases were reported in NA, including 98 complications and two deaths. Cases were related to clusters (e.g. students, healthcare workers) in 16%; 81% of cases were not vaccinated against measles as recommended. Vaccination coverage above herd immunity threshold remains the main preventative outbreak measure.

Clonal replacement and expansion among invasive meningococcal isolates of serogroup W in France.

BACKGROUND: Neisseria meningitidis group W (NmW) belonging to the clonal complex ST-11 (NmW/cc11) spread in Europe and in France in 2000 and declined thereafter. In France, invasive meningococcal disease (IMD) due to NmW increased again in 2012 and thereafter since 2015. Several sub-lineages of NmW/cc11 are circulating worldwide with successive epidemic waves. We aimed to describe recent epidemiological trends of NmW in France and to explore the microbiological and epidemiological characteristics associated with different NmW/cc11 sub-lineages. METHODS: The epidemiology of NmW was described based on data collected through mandatory notification of IMD and strain typing data for culture-confirmed and PCR-confirmed cases for the period 2000-2016. All culture-confirmed cases due to NmW from the period 2010-2016 were characterised by whole genome sequencing (WGS). A detailed epidemiological analysis was performed for culture-confirmed cases on the basis of WGS data. FINDINGS: During the period 2010-2016, genotyping was obtained for 148 cases including all the 132 culture-confirmed cases, among which 127 were matched with epidemiological data, and 16 PCR-confirmed cases (out of a total of 47 PCR-confirmed cases). An increase in IMD was observed in 2012 and was linked to isolates belonging to the "Anglo-French-Hajj" sub-lineage. These isolates have decreased significantly since 2013 and have been replaced by NmW/cc11 isolates related to the "South American - UK" sub-lineage which caused a marked increase in the number of cases of NmW in 2016. In this sub-lineage, the "original UK strain" was first detected in 2012 and increased thereafter, followed by the recently described "UK 2013-strain". Isolates related to the "South American-UK" sub-lineage represented 45% of all NmW cultured isolates from the whole period 2010-2016 but were the most frequent isolates in 2016, representing 76% of the total NmW typed isolates and 94% of the typed NmW/cc11 isolates. A changing pattern in the epidemiology of NmW has been observed in 2015-2016 in relation to the spread of the "UK 2013-strain" with a sharp increase in the number of cases among persons aged 15 years and over and a high case fatality rate (CFR). Among cases due to the "UK 2013-strain", 94% of cases were aged 15 years and over and the CFR was 28%. INTERPRETATION: Our data suggest a recent clonal replacement among NmW/cc11 isolates with the expansion of the "South American-UK" sub-lineage in France and particularly the "UK 2013-strain" which was predominant in 2015 and 2016. A shift in the age-distribution of IMD due to NmW to older ages and the high CFR are consistent with the expansion of a new virulent clone in a naive population. These data may have an impact on tailoring vaccination strategies against NmW.

Complete Genome Sequence of a Wild-Type Measles Virus Isolated during a 2016 Winter Outbreak in a Refugee Settlement in Calais, France.

Measles outbreaks are regularly reported in European countries despite efforts to improve vaccination coverage. In January 2016, an outbreak occurred in a refugee settlement in Calais, France. We report here the complete genome sequence of a wild-type measles virus isolated from a health care worker (MVi/Calais. FRA/01.16) infected during this outbreak.

Severe paediatric conditions linked with EV-A71 and EV-D68, France, May to October 2016.

We report 59 cases of severe paediatric conditions linked with enterovirus (EV)-A71 and EV-D68 in France between May and October 2016. Fifty-two children had severe neurological symptoms. EV sequence-based typing for 42 cases revealed EV-A71 in 21 (18 subgenotype C1, detected for the first time in France) and EV-D68 in eight. Clinicians should be encouraged to obtain stool and respiratory specimens from patients presenting with severe neurological disorders for EV detection and characterisation.

Epidemiological and clinical characteristics of patients infected with enterovirus D68, France, July to December 2014.

In 2014, the United States (US) experienced a nationwide outbreak of enterovirus D68 (EV-D68) infection with 1,152 cases reported mainly in hospitalised children with severe asthma or bronchiolitis. Following the US alert, 11 laboratories of the French enterovirus (EV) surveillance network participated in an EV-D68 survey. A total of 6,229 respiratory samples, collected from 1 July to 31 December 2014, were screened for EV-D68 resulting in 212 EV-D68-positive samples. These 212 samples corresponded to 200 EV-D68 cases. The overall EV-D68 positivity rates among respiratory samples were of 5% (184/3,645) and 1.1% (28/2,584) in hospitalised children and adults respectively. The maximum weekly EV-D68 positivity rates were of 16.1% for children (n = 24/149; week 43) and 2.6% for adults (n = 3/115; week 42). Of 173 children with EV-D68 infection alone, the main symptoms were asthma (n = 83; 48.0%) and bronchiolitis (n = 37; 21.4%). One child developed acute flaccid paralysis (AFP) following EV-D68-associated pneumonia. Although there was no significant increase in severe respiratory tract infections reported to the French public health authorities, 10.7% (19/177) of the EV-D68 infected children and 14.3% (3/21) of the EV-D68 infected adults were hospitalised in intensive care units. Phylogenetic analysis of the viral protein 1 (VP1) sequences of 179 EV-D68 cases, revealed that 117 sequences (65.4%), including that of the case of AFP, belonged to the B2 variant of clade B viruses. Continuous surveillance of EV-D68 infections is warranted and could benefit from existing influenza-like illness and EV surveillance networks.