COVID-19 hotspots through clusters analysis in France (may-October 2020): where should we track the virus to mitigate the spread?

BACKGROUND: In France, the lifting of the lockdown implemented to control the COVID-19 first wave in 2020 was followed by a reinforced contact-tracing (CT) strategy for the early detection of cases and transmission chains. We developed a reporting system of clusters defined as at least three COVID-19 cases, within seven days and belonging to the same community or having participated in the same gathering, whether they know each other or not. The aim of this study was to describe the typology and criticality of clusters reported between the two lockdowns in France to guide future action prioritisation. METHODS: In this study we describe the typology and criticality of COVID-19 clusters between the two lockdowns implemented in France (between May and end of October 2020). Clusters were registered in a national database named "MONIC" (MONItoring des Clusters), established in May 2020. This surveillance system identified the most affected communities in a timely manner. A level of criticality was defined for each cluster to take into consideration the risk of spreading within and outside the community of occurrence, and the health impact within the community. We compared the level of criticality according to the type of community in which the cluster occurred using Pearson's chi-square tests. RESULTS: A total of 7236 clusters were reported over the study period, particularly in occupational environment (25.1%, n = 1813), elderly care structures (21.9%, n = 1586), and educational establishments (15.9%, n = 1154). We show a shift over time of the most affected communities in terms of number of clusters. Clusters reported in occupational environment and the personal sphere had increased during summer while clusters reported in educational environment increased after the start of the school year. This trend mirrors change of transmission pattern overtime according to social contacts. Among all reported clusters, 43.1% had a high level of criticality with significant differences between communities (p < 0.0001). A majority of clusters had a high level of criticality in elderly care structures (82.2%), in disability care centres (56.6%), and health care facilities (51.7%). CONCLUSION: These results highlight the importance of targeting public health action based on timely sustained investigations, testing capacity and targeted awareness campaigns. The emergence of new SARS-CoV-2 variants strengthen these public health recommendations and the need for rapid and prioritise vaccination campaigns.

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.

Early assessment of the impact of mitigation measures to control COVID-19 in 22 French metropolitan areas, October to November 2020.

In France, measures including curfew and lockdown were implemented to control the COVID-19 pandemic second wave in 2020. This study descriptively assesses their possible effects, also relative to their timing. A considerable decrease in incidence of COVID-19 cases and hospital admissions was observed 7 to 10 days after mitigation measures were put in place, occurring earlier in metropolitan areas which had implemented these first. This temporal coincidence suggests the measures' positive impact, consistent with international experiences.

Waning immunity against mumps in vaccinated young adults, France 2013.

In 2013, 15 clusters of mumps were notified in France; 72% (82/114) of the cases had been vaccinated twice with measles-mumps-rubella vaccine. To determine whether the risk of mumps increased with time since the last vaccination, we conducted a case-control study among clusters in universities and military barracks. A confirmed case had an inflammation of a salivary gland plus laboratory confirmation in 2013. A probable case presented with inflammation of a salivary gland in 2013 either lasting for > 2 days or with epidemiological link to a confirmed case. Controls had no mumps symptoms and attended the same university course, student party or military barracks. We collected clinical and vaccination data via web questionnaire and medical records. We calculated adjusted odds ratios (aOR) using logistic regression. 59% (50/85) of cases and 62% (199/321) of controls had been vaccinated twice. The odds of mumps increased for twice-vaccinated individuals by 10% for every year that had passed since the second dose (aOR 1.10; 95% confidence interval (CI): 1.02-1.19; p = 0.02). Mumps immunity waned with increasing time since vaccination. Our findings contributed to the French High Council of Public Health's decision to recommend a third MMR dose during outbreaks for individuals whose second dose dates > 10 years.

Outbreak of Escherichia coli O104:H4 haemolytic uraemic syndrome in France: outcome with eculizumab.

BACKGROUND: An outbreak of haemolytic uraemic syndrome (HUS) due to Shiga toxin-secreting Escherichia coli (STEC) O104:H4 from contaminated fenugreek sprouts occurred in June 2011 near Bordeaux, France. In the context of this outbreak, all patients were treated with the monoclonal anti-C5 antibody, eculizumab. METHODS: The diagnosis of HUS was made based on haemolytic anaemia, low platelet count and acute kidney injury. Data were obtained from initial gastrointestinal symptoms to the end of follow-up 10 weeks after the start of eculizumab. RESULTS: Among 24 cases of STEC gastroenteritis, HUS developed in nine patients (eight adults and one child), 6 (median; range 3-12) days after digestive symptoms begun. The median (range) highest or lowest biological values were platelet count 26 (range 14-93) G/L; haemoglobin 6.6 (range 5-10.7) g/dL; LDH 1520 (range 510-2568) IU/L; creatinine 152 (range 48-797) µmol/L. All patients had extra-renal complications (liver 9, pancreas 5, brain 3 and heart 3). Two patients were dialysed, and one was ventilated. After failure of plasma exchange to increase platelets in the first three patients, eculizumab was administered in all nine patients, 0-4 days after HUS diagnosis (median 1 day). One patient with very severe neurological HUS received immunoadsorption. Outcome was favourable in all patients, with rapid normalization of haemoglobin, platelets, LDH levels, renal function and neurological improvement. There were no deaths and no serious adverse events related to eculizumab. CONCLUSIONS: Early treatment of O104:H4 STEC-HUS by eculizumab was associated with a rapid and efficient recovery. Controlled prospective evaluation of eculizumab in STEC-HUS is warranted.

Compensation of pleural mesothelioma in France: data from the French National Mesothelioma Surveillance Programme.

BACKGROUND: The aim of this study was to determine the rates of compensation awarded to patients presenting with pleural mesothelioma and factors linked to such compensation in France. METHODS: The study population consisted of 2,407 patients presenting with pleural mesothelioma, recorded by the National Mesothelioma Surveillance Programme between January 1, 1999 and December 31, 2009. Analysis of claims for recognition as "occupational disease" (OD) and claims for compensation by the Compensation Fund for Asbestos Victims (FIVA) were analyzed. RESULTS: Approximately 30% of subjects presenting with pleural mesothelioma, affiliated to the General National Health Insurance fund, neither sought recognition as an OD nor claimed for FIVA compensation. Gender, age at diagnosis, type of health insurance, and socio-professional category influence the likelihood of patients presenting with mesothelioma seeking compensation for this disease. CONCLUSIONS: Results show an under-compensation of pleural mesothelioma as OD and by the FIVA in France.

Outbreak of Shiga toxin-producing Escherichia coli O104:H4 associated with organic fenugreek sprouts, France, June 2011.

BACKGROUND: On 22 June 2011, 8 patients with hemolytic uremic syndrome (HUS) or bloody diarrhea were reported in France. All 8 were attendees of a community center event on 8 June near Bordeaux. Three Escherichia coli cases were confirmed by isolation of Shiga toxin-producing E. coli O104:H4 stx2 aggR producing a cefotaximase (CTX-M) ß-lactamase (STEC O104:H4); the same rare serotype caused the outbreak in Germany in May-July 2011. An investigation was initiated to describe the outbreak, identify the vehicle for infection, and guide control measures. METHODS: We conducted a retrospective cohort study among all adults attending the event, including food handlers. A standardized questionnaire was administered to participants. A case was an attendee who developed HUS or diarrhea between 8 and 24 June. Cases were confirmed by isolation of STEC O104:H4 or O104 serology. Relative risks (RRs) and 95% confidence intervals (CIs) by exposure were calculated using a Poisson regression model. RESULTS: Twenty-four cases were identified (14% attack rate). Of these, 18 (75%) were women, 22 (92%) were adults, 7 (29%) developed HUS, 5 (21%) developed bloody diarrhea, and 12 (50%) developed diarrhea. Ten (42%) cases were confirmed. Fenugreek was the only sprout type with an independent association to illness (RR, 5.1; 95% CI, 2.3-11.1) in multivariable analysis. CONCLUSIONS: This investigation identified a point-source STEC O104:H4 outbreak associated with consumption of fenugreek sprouts. Comparison of results from French and German STEC O104:H4 outbreak investigations enabled identification of a common food vehicle, fenugreek sprouts, and resulted in implementation of Europe-wide control measures in July 2011.

Temporal patterns of occupational asbestos exposure and risk of pleural mesothelioma.

Asbestos is the primary cause of pleural mesothelioma (PM). The objective of this study was to elucidate the importance of different temporal patterns of occupational asbestos exposure on the risk of PM using case-control data in male subjects. Cases were selected from a French case-control study conducted in 1987-1993 and the French National Mesothelioma Surveillance Program in 1998-2006. Population controls were frequency matched to cases by year of birth. Occupational asbestos exposure was evaluated with a job-exposure matrix. The dose-response relationships were estimated using restricted cubic spline functions in logistic regression models. A total of 2,466 ever-asbestos-exposed males (1,041 cases and 1,425 controls) were used. After adjustment for intensity and total duration of occupational asbestos exposure, the risk of PM was lower for subjects first exposed after the age of 20 yrs and continued to increase until 30 yrs after cessation of exposure. The effect of total duration of exposure decreased when age at first exposure and time since last exposure increased. These results, based on a large population-based case-control study, underline the need to take into account the temporal pattern of exposure on risk assessment.

Choice of rating method for assessing occupational asbestos exposure: study for compensation purposes in France.

BACKGROUND: In the course of setting up the National Mesothelioma Surveillance Program (PNSM), established in France in 1998, the question arose as to the most suitable method of assessing occupational exposure. The aim of this study was to define the most suitable rating method for assessing occupational asbestos exposure in order to assess medico-social care. METHOD: The study included 100 subjects-50 cases of mesothelioma and 50 controls-randomly selected and representing 457 jobs held. Job asbestos exposure was assessed by a six-expert panel using two methods: "by job" rating, where all the jobs in were assessed regardless of the subjects; and "by subject" rating, where all the jobs of a subject were assessed at the same time. Consensus was obtained and subjects' exposure was calculated for each rating. Then, two internal experts assessed job asbestos exposure with the "by subject" rating. Kappa coefficients were used to measure agreement between the ratings. RESULTS: Agreement between "by job" and "by subject" ratings was very good for subject probability of exposure (kappa = 0.84) and cumulative exposure index (kappa = 0.80). Agreement between the six-expert panel and the two internal experts was good for subject exposure (kappa for probability = 0.71; kappa for cumulative exposure index= 0.68). CONCLUSION: This study shows that the two rating systems have good or very good agreement. These results validate the routine use in the PNSM of the "by subject" rating, with the advantage of being convenient and quick to provide feedback on occupational asbestos exposure to mesothelioma cases for compensation.

Attributable risk in men in two French case-control studies on mesothelioma and asbestos.

Pleural mesothelioma is a primary tumor of the pleura that is mainly due to asbestos exposure. To study the relationship between mesothelioma and occupational asbestos exposure in France, two case-control studies (A and B) were conducted. A substantial difference in the attributable risk in the population (AR(p)) was observed among men: 44.5% (95% CI: [32.6-56.4]) in study A and 83.2% (95% CI: [76.8-89.6]) in study B. As different exposure assessment expert methods were used, the main objective of this work was to re-estimate the AR(p) men in two case-control studies according to a common standardized exposure assessment by using a Job Exposure Matrix (JEM) and to assess the role of subjects' selection. The initial observed AR(p) difference was maintained: 36.3% (95% CI: [24.3-50.3]) in study A and 69.7% (95% CI: [51.7-83.2]) in study B. Further investigations highlighted the potential selection bias introduced in both studies, especially among controls. The AR(p) could be underestimated in study A and overestimated in study B. After weighting subjects according to distribution of socio-economic status in the general population for controls and according to distribution of socio-economic status of cases registered by the French National Mesothelioma Surveillance Program, re-estimated AR(p) values were 52.4% in study A and 70.2% in study B. These results provide additional information to describe the relationship between pleural mesothelioma and occupational asbestos exposure, but also confirm the importance of subjects' recruitment in case control studies, particularly control selection.

Possible effect of environmental exposure to asbestos on geographical variation in mesothelioma rates.

BACKGROUND: In population-based mesothelioma studies in industrialised countries, the incidence of mesothelioma without any identified asbestos exposure (IAE) is usually higher among women, while male incidence is mainly attributed to IAE. Through a comparison of the spatial distribution of male and female rates, and IAE and no IAE incidence, this study investigated whether mesotheliomas without IAE are in fact induced by non-recognised asbestos exposure, mostly from environmental sources. METHODS: We calculated mesothelioma mortality (SMR) and incidence (SIR) ratios by district in France, pooling 30 and 10 years of data, respectively. Using correlation coefficients, we compared geographical patterns of male and female mesothelioma ratios, and IAE and no IAE mesothelioma ratios. RESULTS: The raw numbers of male and female mesothelioma cases were equivalent. Mesothelioma SMR (0.76) and SIR (0.80) geographical correlations between men and women were strongly positive. SIR correlation between occupationally IAE and no IAE cases was also positive (0.69). Correlation between occupationally IAE and no IAE cases was positive among women but not among men. CONCLUSIONS: Data analyses of mesothelioma mortality and incidence showed that female cases occur in the same geographical areas as male cases. Female mesotheliomas with no IAE occur in the same geographical areas as exposed cases, suggesting asbestos has a major influence on female mesothelioma, likely through environmental exposure.

Occupations and industries in France at high risk for pleural mesothelioma: A population-based case-control study (1998-2002).

BACKGROUND: Occupational exposure to asbestos, widely used in various industries for decades, is the most important risk factor for pleural mesothelioma. We report here the ranking of occupations and industries in France at high risk for this cancer among men and women. METHODS: A population-based case-control study, conducted from 1998 to 2002, included 462 cases (80.3% men) and 897 controls. Data were collected in face-to-face interviews with a standardized questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each occupation and industry; subjects never employed in each category were the reference. RESULTS: For men, risks were high for several occupations and industries. Besides the expected high risks for non-metallic mineral product makers and manufacturing asbestos products, occupations such as plumbers (OR = 5.57, 95% CI: 2.90-10.69), sheet-metal workers, welders, metal molders, coremakers, and cabinetmakers were also at high risk. Elevated risks were found in the industries of shipbuilding (OR = 9.13, 95% CI: 5.20-16.06) and construction, but also in the manufacturing of metal products, chemicals, and railroad and aircraft equipment. The results for women showed increased but not significant risks in several occupational activities. CONCLUSIONS: This report provides new insight into the epidemiology of mesothelioma, confirming risks for occupational activities reported earlier and pointing out risks in activities never previously reported. It offers guidance to authorities for the compensation of asbestos victims and for prevention in at-risk activities still involving asbestos-containing products.

Lymphohistiocytoid variant of malignant mesothelioma of the pleura: a series of 22 cases.

The lymphohistiocytoid variant of diffuse malignant mesothelioma is rare with very few cases described in the literature. It is characterized by mesothelial cells with a histiocytelike appearance and an associated dense lymphoid infiltrate. We studied clinicopathologic features and immunohistochemical patterns of a series of 22 cases. The histiocytelike cells had a mesothelial immunophenotype: AE1/AE3 (100%), calretinin (100%), CK5/6 (46%), and EMA (52%). The prominent lymphoid component showed a cytotoxic T-cell immunophenotype. Prognosis was similar to that of a large series of epithelioid diffuse malignant mesotheliomas. Formely, it was classified within the sarcomatoid type. We suggest that it should be reclassified as an epithelioid variant because of its similar behavioural characteristics. There was no evidence of Epstein-Barr virus-related infection.

Portuguese man-of-war (Physalia physalis) envenomation on the Aquitaine Coast of France: an emerging health risk.

CONTEXT: The Portuguese man-o-war is a cnidaria classically found in tropical waters. It can cause serious and even life-threatening envenomation in swimmers, surfers and seafarers. Presence of the Atlantic species Physalia physalis has long been reported in European coastal waters but was always an exceptional event. OBJECTIVE: To describe the experience of the Bordeaux Poison centre about Physalia stings since the first collective episode reported in 2008. METHODS: Clinical retrospective description of cases series of Physalia envenomations reported to the local poison centre from 2008 to 2011 inclusive. RESULTS: In the summer of 2008, multiple-case incident involving 40 victims were recorded on the same day on one beach in the Southern French Atlantic coast. The following year in 2009, no envenomation cases were reported in the same area, but in the next 2 years, numerous man-of-war envenomations occurred along the Aquitaine coast, that is, 154 cases in 2010 and 885 in 2011. Portuguese man-o-war stings led to severe manifestations with 15-20% of patients suffering of general symptoms that were sometimes severe enough to be considered as potentially life-threatening (8% of patients in 2011, most frequent signs: muscle pain and cramps with fasciculations, confusion and drowsiness, fainting, respiratory distress). No deaths due to Portuguese man-o-war envenomation were reported over the 4-year study period. CONCLUSION: The results suggest that national multidisciplinary summer surveillance program in the Aquitaine coast is required in order to provide alerts to the public, to better identify patients at risk for developing severe clinical symptoms, and hopefully to improve quality of health care.