Source of SARS-CoV-2 infection: results from a series of 584,846 cases in France from October 2020 to August 2022.

BACKGROUND: We aimed to study the source of infection for recently SARS-CoV-2-infected individuals from October 2020 to August 2022 in France. METHODS: Participants from the nationwide ComCor case-control study who reported recent SARS-CoV-2 infection were asked to document the source and circumstances of their infection through an online questionnaire. Multivariable logistic regression was used to identify the factors associated with not identifying any source of infection. RESULTS: Among 584,846 adults with a recent SARS-CoV-2 infection in France, 46.9% identified the source of infection and an additional 22.6% suspected an event during which they might have become infected. Known and suspected sources of infection were household members (30.8%), extended family (15.6%), work colleagues (15.0%), friends (11.0%), and possibly multiple/other sources (27.6%). When the source of infection was known, was not a household member, and involved a unique contact (n = 69,788), characteristics associated with transmission events were indoors settings (91.6%), prolonged (> 15 min) encounters (50.5%), symptomatic source case (64.9%), and neither the source of infection nor the participant wearing a mask (82.2%). Male gender, older age, lower education, living alone, using public transportation, attending places of public recreation (bars, restaurants, nightclubs), public gatherings, and cultural events, and practicing indoor sports were all independently associated with not knowing the source of infection. CONCLUSION: Two-thirds of infections were attributed to interactions with close relatives, friends, or work colleagues. Extra-household indoor encounters without masks were commonly reported and represented avoidable circumstances of infection. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT04607941.

Encephalitis in HIV-negative immunodeficient patients: a prospective multicentre study, France, 2016 to 2019.

BackgroundData on infectious encephalitis in immunodeficient (ID) individuals are scarce. This population may present with atypical clinical symptoms, be infected by uncommon pathogens and develop poor outcomes.AimWe aimed to describe the epidemiology of infectious encephalitis among HIV-negative ID patients.MethodsPatients from the ENCEIF (Etude Nationale de Cohorte des Encéphalites Infectieuses en France) prospective cohort meeting criteria for infectious encephalitis between January 2016 and December 2019 were included. We compared clinical presentation, magnetic resonance imaging (MRI) results, biological results, infection causes and outcome of ID patients with immunocompetent (IC) patients using Pearson's chi-squared test and Student's t-test. We carried out logistic regression to assess the role of immunodeficiency as risk factor for poor outcome.ResultsID patients (n = 58) were older (mean 72 vs 59 years), had higher prevalence of diabetes (26% vs 12%), pre-existing neurological disorders (12% vs 5%) and higher case-fatality rate (23.6% vs 5.6%) compared to IC patients (n = 436). Varicella zoster virus was the primary cause of encephalitis in ID patients (this aetiology was more frequent in ID (25.9%) than in IC patients (11.5%)), with herpes simplex virus second (22.4% in ID patients vs 27.3% in IC patients). Immunodeficiency was an independent risk factor for death or major sequelae (odds ratio: 3.41, 95%CI: 1.70-6.85).ConclusionsVaricella zoster virus is the most frequent cause of infectious encephalitis in ID patients. Immunodeficiency is a major risk factor for poor outcome. ID encephalitis patients should benefit from stringent investigation of cause and early empiric treatment.

Mpox in children and adolescents and contact follow-up in school settings in greater Paris, France, May 2022 to July 2023.

BackgroundDuring the 2022 mpox outbreak in Europe, primarily affecting men who have sex with men, a limited number of cases among children and adolescents were identified. Paediatric cases from outbreaks in endemic countries have been associated with a higher likelihood of severe illness. Detailed clinical case descriptions and interventions in school settings before 2022 are limited.AimTo describe clinical characteristics of mpox cases among children (< 15 years) and adolescents (15-17 years) in the greater Paris area in France, and infection control measures in schools.MethodsWe describe all notified laboratory-confirmed and non-laboratory-confirmed cases among children and adolescents identified from May 2022 to July 2023, including demographic and clinical characterisation and infection control measures in school settings, i.e. contact tracing, contact vaccination, secondary attack rate and post-exposure vaccination uptake.ResultsNineteen cases were notified (13 children, 6 adolescents). Four adolescent cases reported sexual contact before symptom onset. Ten child cases were secondary cases of adult patients; three cases were cryptic, with vesicles on hands, arms and/or legs and one case additionally presented with genitoanal lesions. Five cases attended school during their infectious period, with 160 at-risk contacts identified, and one secondary case. Five at-risk contacts were vaccinated following exposure.ConclusionCases among children and adolescents are infrequent but require a careful approach to identify the source of infection and ensure infection control measures. We advocate a 'contact warning' strategy vs 'contact tracing' in order to prevent alarm and stigma. Low post-exposure vaccination rates are expected.

Infectious encephalitis in elderly patients: a prospective multicentre observational study in France 2016-2019.

PURPOSE: Data on encephalitis in elderly patients are scarce. We aimed to describe the characteristics, aetiologies, management, and outcome of encephalitis in patients older than 65 years. METHODS: We performed an ancillary study of ENCEIF, a prospective cohort that enrolled all cases of encephalitis managed in 46 clinical sites in France during years 2016-2019. Cases were categorized in three age groups: (1) 18-64; (2) 65-79; (3) ≥ 80 years. RESULTS: Of the 494 adults with encephalitis enrolled, 258 (52%) were ≥ 65 years, including 74 (15%) ≥ 80 years. Patients ≥ 65 years were more likely to present with coma, impaired consciousness, confusion, aphasia, and rash, but less likely to present with fever, and headache (P < 0.05 for each). Median cerebrospinal fluid (CSF) white cells count was 61/mm3[13-220] in 65-79 years, 62 [17-180] in ≥ 80 years, vs. 114 [34-302] in < 65 years (P = 0.01). The proportion of cases due to Listeria monocytogenes and VZV increased after 65 years (P < 0.001), while the proportion of tick-borne encephalitis and Mycobacterium tuberculosis decreased with age (P < 0.05 for each). In-hospital mortality was 6/234 (3%) in < 65 years, 18/183 (10%) in 65-79 years, and 13/73 (18%) in ≥ 80 years (P < 0.001). Age ≥ 80 years, coma on admission, CSF protein ≥ 0.8 g/L and viral encephalitis were independently predictive of 6 month mortality. CONCLUSION: Elderly patients represent > 50% of adults with encephalitis in France, with higher proportion of L. monocytogenes and VZV encephalitis, increased risk of death, and sequels. The empirical treatment currently recommended, aciclovir and amoxicillin, is appropriate for this age group.

Reduction of SARS-CoV-2 intra-household child-to-parent transmission associated with ventilation: results from a case-control study.

PURPOSE: Our objective was to describe circumstances of SARS-CoV-2 household transmission and to identify factors associated with a lower risk of transmission in a nationwide case-control study in France. METHODS: In a descriptive analysis, we analysed cases reporting transmission from someone in the household (source case). Index cases could invite a non-infected household member to participate as a related control. In such situations, we compared the exposures of the index case and related control to the source case by conditional logistic regression matched for household, restricted to households in which the source case was a child, and the index case and related control were the infected child's parents. RESULTS: From October 27, 2020 to May 16, 2022, we included 104 373 cases for the descriptive analysis with a documented infection from another household member. The source case was mostly the index case's child (46.9%) or partner (45.7%). In total, 1026 index cases invited a related control to participate in the study. In the case-control analysis, we included 611 parental pairs of cases and controls exposed to the same infected child. COVID-19 vaccination with 3 + doses versus no vaccination (OR 0.1, 95%CI: 0.04-0.4), isolation from the source case (OR 0.6, 95%CI: 0.4-0.97) and the ventilation of indoor areas (OR 0.6, 95%CI: 0.4-0.9) were associated with lower risk of infection. CONCLUSION: Household transmission was common during the SARS-CoV-2 pandemic in France. Mitigation strategies, including isolation and ventilation, decreased the risk of secondary transmission within the household. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT04607941.

SARS-CoV-2 self-test uptake and factors associated with self-testing during Omicron BA.1 and BA.2 waves in France, January to May 2022.

BackgroundFollowing the SARS-CoV-2 Omicron variant spread, the use of unsupervised antigenic rapid diagnostic tests (self-tests) increased.AimThis study aimed to measure self-test uptake and factors associated with self-testing.MethodsIn this cross-sectional study from 20 January to 2 May 2022, the case series from a case-control study on factors associated with SARS-CoV-2 infection were used to analyse self-testing habits in France. A multivariable quasi-Poisson regression was used to explore the variables associated with self-testing among symptomatic cases who were not contacts of another infected individual. The control series from the same study was used as a proxy for the self-test background rate in the non-infected population of France.ResultsDuring the study period, 179,165 cases who tested positive through supervised tests were recruited. Of these, 64.7% had performed a self-test in the 3 days preceding this supervised test, of which 79,038 (68.2%) were positive. The most frequently reported reason for self-testing was the presence of symptoms (64.6%). Among symptomatic cases who were not aware of being contacts of another case, self-testing was positively associated with being female, higher education, household size, being a teacher and negatively associated with older age, not French by birth, healthcare-related work and immunosuppression. Among the control series, 12% self-tested during the 8 days preceding questionnaire filling, with temporal heterogeneity.ConclusionThe analysis showed high self-test uptake in France with some inequalities which must be addressed through education and facilitated access (cost and availability) for making it a more efficient epidemic control tool.

Mpox outbreak in France: epidemiological characteristics and sexual behaviour of cases aged 15 years or older, 2022.

BackgroundLocally-acquired mpox cases were rarely reported outside Africa until May 2022, when locally-acquired-mpox cases occurred in various European countries.AimWe describe the mpox epidemic in France, including demographic and behavioural changes among a subset of cases, during its course.MethodsData were retrieved from the enhanced national surveillance system until 30 September 2022. Laboratory-confirmed cases tested positive for monkeypox virus or orthopoxviruses by PCR; non-laboratory-confirmed cases had clinical symptoms and an epidemiological link to a laboratory-confirmed case. A subset of ≥ 15-year-old male cases, notified until 1 August, was interviewed for epidemiological, clinical and sexual behaviour information. Association of symptom-onset month with quantitative outcomes was evaluated by t- or Wilcoxon tests, and with binary outcomes, by Pearson's chi-squared or Fisher exact tests.ResultsA total of 4,856 mpox cases were notified, mostly in Île-de-France region (62%; 3,025/4,855). Cases aged ≥ 15 years were predominantly male (97%; 4,668/4,812), with 37 years (range: 15-81) as mean age. Between May and July, among the subset interviewed, mpox cases increased in regions other than Île-de-France, and mean age rose from 35 (range: 21-64) to 38 years (range: 16-75; p = 0.007). Proportions of cases attending men-who-have-sex-with-men (MSM) meeting venues declined from 60% (55/91) to 46% (164/359; p = 0.012); median number of sexual partners decreased from four (interquartile range (IQR): 1-10) to two (IQR: 1-4; p < 0.001).ConclusionChanges in cases' characteristics during the epidemic, could reflect virus spread from people who were more to less behaviourally vulnerable to mpox between May and July, or MSM reducing numbers of sexual partners as recommended.

Estimated incubation period distributions of mpox using cases from two international European festivals and outbreaks in a club in Berlin, May to June 2022.

BackgroundSince May 2022, an mpox outbreak affecting primarily men who have sex with men (MSM) has occurred in numerous non-endemic countries worldwide. As MSM frequently reported multiple sexual encounters in this outbreak, reliably determining the time of infection is difficult; consequently, estimation of the incubation period is challenging.AimWe aimed to provide valid and precise estimates of the incubation period distribution of mpox by using cases associated with early outbreak settings where infection likely occurred.MethodsColleagues in European countries were invited to provide information on exposure intervals and date of symptom onset for mpox cases who attended a fetish festival in Antwerp, Belgium, a gay pride festival in Gran Canaria, Spain or a particular club in Berlin, Germany, where early mpox outbreaks occurred. Cases of these outbreaks were pooled; doubly censored models using the log-normal, Weibull and Gamma distributions were fitted to estimate the incubation period distribution.ResultsWe included data on 122 laboratory-confirmed cases from 10 European countries. Depending on the distribution used, the median incubation period ranged between 8 and 9 days, with 5th and 95th percentiles ranging from 2 to 3 and from 20 to 23 days, respectively. The shortest interval that included 50% of incubation periods spanned 8 days (4-11 days).ConclusionCurrent public health management of close contacts should consider that in approximately 5% of cases, the incubation period exceeds the commonly used monitoring period of 21 days.

Early chains of transmission of COVID-19 in France, January to March 2020.

IntroductionSARS-CoV-2, the virus that causes COVID-19, has spread rapidly worldwide. In January 2020, a surveillance system was implemented in France for early detection of cases and their contacts to help limit secondary transmissions.AimTo use contact-tracing data collected during the initial phase of the COVID-19 pandemic to better characterise SARS-CoV-2 transmission.MethodsWe analysed data collected during contact tracing and retrospective epidemiological investigations in France from 24 January to 30 March 2020. We assessed the secondary clinical attack rate and characterised the risk of a contact becoming a case. We described chains of transmission and estimated key parameters of spread.ResultsDuring the study period, 6,082 contacts of 735 confirmed cases were traced. The overall secondary clinical attack rate was 4.1% (95% confidence interval (CI): 3.6-4.6), increasing with age of index case and contact. Compared with co-workers/friends, family contacts were at higher risk of becoming cases (adjusted odds ratio (AOR): 2.1, 95% CI: 1.4-3.0) and nosocomial contacts were at lower risk (AOR: 0.3, 95% CI: 0.1-0.7). Of 328 infector/infectee pairs, 49% were family members. The distribution of secondary cases was highly over-dispersed: 80% of secondary cases were caused by 10% of cases. The mean serial interval was 5.1 days (interquartile range (IQR): 2-8 days) in contact tracing pairs, where late transmission events may be censored, and 6.8 (3-8) days in pairs investigated retrospectively.ConclusionThis study increases knowledge of SARS-CoV-2 transmission, including the importance of superspreading events during the onset of the pandemic.

Impact of the Omicron variant on SARS-CoV-2 reinfections in France, March 2021 to February 2022.

Since the first reports in summer 2020, SARS-CoV-2 reinfections have raised concerns about the immunogenicity of the virus, which will affect SARS-CoV-2 epidemiology and possibly the burden of COVID-19 on our societies in the future. This study provides data on the frequency and characteristics of possible reinfections, using the French national COVID-19 testing database. The Omicron variant had a large impact on the frequency of possible reinfections in France, which represented 3.8% of all confirmed COVID-19 cases since December 2021.

A Prospective Cohort Study to Identify Clinical, Biological, and Imaging Features That Predict the Etiology of Acute Encephalitis.

BACKGROUND: New diagnostic tools have been developed to improve the diagnosis of infectious encephalitis. Using a prospective cohort of encephalitis patients, our objective was to identify possible clusters of patients with similar patterns among encephalitis of unknown cause (EUC) and to describe to what extent a patient's initial presentation may be predictive of encephalitis etiology, particularly herpes simplex virus (HSV) and varicella-zoster virus (VZV). METHODS: The National Cohort of Infectious Encephalitis in France is an ongoing prospective cohort study implemented in France in 2016. Patients who present with documented or suspected acute infectious encephalitis were included. Focusing on the variables that describe the initial presentation, we performed a factor analysis of mixed data (FAMD) to investigate a pattern of association between the initial presentation of a patient and the etiologic pathogen. RESULTS: As of 1 August 2018, data from 349 patients were analyzed. The most frequent pathogens were HSV (25%), VZV (11%), tick-borne encephalitis virus (6%), Listeria (5%), influenza virus (3%), and EUC (34%). Using the FAMD, it was not possible to identify a specific pattern related to the group of EUC. Age, temporal or hemorrhagic lesions, and cerebral spinal fluid lymphocytosis were significantly associated with HSV/VZV encephalitis. CONCLUSIONS: No initial clinical/imaging/biology pattern was identified at admission among EUC, despite the improvement in diagnostic tools. In this context, the recommendation for a universal, early, probabilistic, initial treatment against HSV and VZV is still relevant, regardless of the initial clinical presentation of the encephalitis.

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.

Prevention of human rabies: a challenge for the European Union and the European Economic Area.

Rabies is enzootic in over one hundred countries worldwide. In the European Union/European Economic Area (EU/EEA), the vast majority of human rabies cases are travellers bitten by dogs in rabies-enzootic countries, mostly in Asia and Africa. Thus, EU/EEA travellers visiting rabies enzootic countries should be aware of the risk of being infected with the rabies virus when having physical contact with mammals. They should consider pre-exposure vaccination following criteria recommended by the World Health Organization and if unvaccinated, immediately seek medical attention in case of bites or scratches from mammals. As the majority of the EU/EEA countries are free from rabies in mammals, elimination of the disease (no enzootic circulation of the virus and low number of imported cases) has been achieved by 2020. However, illegal import of potentially infected animals, mainly dogs, poses a risk to public health and might threaten the elimination goal. Additionally, newly recognised bat lyssaviruses represent a potential emerging threat as the rabies vaccine may not confer protective immunity. To support preparedness activities in EU/EEA countries, guidance for the assessment and the management of the public health risk related to rabies but also other lyssaviruses, should be developed.

First cases of coronavirus disease 2019 (COVID-19) in France: surveillance, investigations and control measures, January 2020.

A novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) causing a cluster of respiratory infections (coronavirus disease 2019, COVID-19) in Wuhan, China, was identified on 7 January 2020. The epidemic quickly disseminated from Wuhan and as at 12 February 2020, 45,179 cases have been confirmed in 25 countries, including 1,116 deaths. Strengthened surveillance was implemented in France on 10 January 2020 in order to identify imported cases early and prevent secondary transmission. Three categories of risk exposure and follow-up procedure were defined for contacts. Three cases of COVID-19 were confirmed on 24 January, the first cases in Europe. Contact tracing was immediately initiated. Five contacts were evaluated as at low risk of exposure and 18 at moderate/high risk. As at 12 February 2020, two cases have been discharged and the third one remains symptomatic with a persistent cough, and no secondary transmission has been identified. Effective collaboration between all parties involved in the surveillance and response to emerging threats is required to detect imported cases early and to implement adequate control measures.

First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020.

In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters' index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases.

Tick-Borne Encephalitis in Auvergne-Rhône-Alpes Region, France, 2017-2018.

Three autochthonous cases of tick-borne encephalitis (TBE) acquired in rural areas of France where Lyme borreliosis, but not TBE, is endemic highlight the emergence of TBE in new areas. For patients with neurologic involvement who have been in regions where Ixodes ticks circulate, clinicians should test for TBE virus and other tickborne viruses.

Herpes simplex virus encephalitis update.

PURPOSE OF REVIEW: HSV is the most frequently identified cause of infectious encephalitis, in Western countries. This article is an update on the topic based on a review of recent studies from 2017 to 2018. RECENT FINDINGS: Acyclovir is still the first line treatment, and no new drugs are currently available for clinical use. The major considerations for HSV encephalitis are as follows: point one, clinical evaluation remains the most important factor, as though CSF HSV PCR has a good sensitivity, in a small proportion of patients the initial testing might be negative. MRI brain is the first line imaging test, and mesial temporal lobe involvement and other typical findings are important for diagnosis; point 2, there should be emphasis on sequela, short-term, and long-term outcomes, and not just case fatality rated in future studies and clinical management. Auto-immune encephalitis can be triggered by HSV, and should be considered in patients who are not responding to treatment; point 3, future studies should be on better management of sequela, and better treatment regimens including those targeting the immune response. SUMMARY: Autoimmune encephalitis is a clearly identified complication of HSV encephalitis. Inflammatory mechanisms are linked to the clinical presentation as well as severity and poor outcome. Initial corticosteroid therapy has to be evaluated in order to prevent complications.

Paediatric haemolytic uraemic syndrome related to Shiga toxin-producing Escherichia coli, an overview of 10 years of surveillance in France, 2007 to 2016.

IntroductionHaemolytic uraemic syndrome (HUS) related to Shiga toxin-producing Escherichia coli (STEC) is the leading cause of acute renal failure in young children. In France, HUS surveillance in children aged < 15 years was implemented starting from 1996.AimWe present the results of this surveillance between 2007 and 2016.MethodsA voluntary nationwide network of 32 paediatric departments notifies cases. Two national reference centres perform microbiological STEC confirmation.ResultsOver the study period, the paediatric HUS incidence rate (IR) was 1.0 per 100,000 children-years, with a median of 116 cases/year. In 2011, IR peaked at 1.3 per 100,000 children-years, and decreased to 1.0 per 100,000 children-years in 2016. STEC O157 associated HUS peaked at 37 cases in 2011 and decreased to seven cases in 2016. Cases of STEC O26-associated HUS have increased since 2010 and STEC O80 associated HUS has emerged since 2012, with 28 and 18 cases respectively reported in 2016. Four STEC-HUS food-borne outbreaks were detected (three STEC O157 linked to ground beef and raw-milk cheese and one STEC O104 linked to fenugreek sprouts). In addition, two outbreaks related to person-to-person transmission occurred in distinct kindergartens (STEC O111 and O26).ConclusionsNo major changes in HUS IRs were observed over the study period of 10 years. However, changes in the STEC serogroups over time and the outbreaks detected argue for continuing epidemiological and microbiological surveillance.

Outbreak of Shiga toxin-producing Escherichia coli (STEC) O26 paediatric haemolytic uraemic syndrome (HUS) cases associated with the consumption of soft raw cow's milk cheeses, France, March to May 2019.

We report an outbreak of Shiga toxin-producing Escherichia coli (STEC) associated paediatric haemolytic uraemic syndrome linked to the consumption of raw cow's milk soft cheeses. From 25 March to 27 May 2019, 16 outbreak cases infected with STEC O26 (median age: 22 months) were identified. Interviews and trace-back investigations using loyalty cards identified the consumption of raw milk cheeses from a single producer. Trace-forward investigations revealed that these cheeses were internationally distributed.