Molecular epidemiology identifies the expansion of the DENV2 epidemic lineage from the French Caribbean Islands to French Guiana and mainland France, 2023 to 2024.

In 2023, dengue virus serotype 2 (DENV2) affected most French overseas territories. In the French Caribbean Islands, viral circulation continues with > 30,000 suspected infections by March 2024. Genome sequence analysis reveals that the epidemic lineage in the French Caribbean islands has also become established in French Guiana but not Réunion. It has moreover seeded autochthonous circulation events in mainland France. To guide prevention of further inter-territorial spread and DENV introduction in non-endemic settings, continued molecular surveillance and mosquito control are essential.

Prevalence and factors associated with a prescription of a Lyme borreliosis serology for erythema migrans diagnosis in general practice: a study from the French sentinel network, 2009-2020.

BACKGROUND: Serological testing of patients consulting for typical erythema migrans (EM) is not recommended in European recommendations for diagnosis of Lyme borreliosis (LB). Little is known on the level of adherence of French general practitioners to these recommendations. The objectives were to estimate the proportion of Lyme borreliosis serological test prescription in patients with erythema migrans seen in general practice consultations in France, and to study the factors associated with this prescription. METHODS: LB cases with an EM reported by the French general practitioners (GPs) of the Sentinelles network between January 2009 and December 2020 were included. To assess the associations with a prescription of a serological test, multilevel logistic regression models were used. RESULTS: Among the 1,831 EM cases included, a prescription for a LB serological test was requested in 24.0% of cases. This proportion decreased significantly over the study period, from 46.8% in 2009 to 15.8% in 2020. A LB serological prescription was associated with patients with no reported tick bite (Odds Ratio (OR): 1.95; 95% confidence interval [1.23-3.09]), multiple EM (OR: 3.82 [1.63-8.92]), EM of five centimeters or more (OR: 4.34 [2.33-8.08]), and GPs having diagnosed less than one EM case per year during the study period (OR: 5.28 [1.73-16.11]). CONCLUSIONS: Serological testing of patients consulting for EM is not recommended in European recommendations for diagnosis of Lyme borreliosis. Therefore, the significant decrease in the rate of LB serological test for EM over the study period is encouraging. The factors identified in this study can be used to improve messaging to GPs and patients. Further efforts are needed to continue to disseminate diagnostic recommendations for LB to GPs, especially those who rarely see patients with EM.

Emergence, spread and characterisation of the SARS-CoV-2 variant B.1.640 circulating in France, October 2021 to February 2022.

BackgroundSuccessive epidemic waves of COVID-19 illustrated the potential of SARS-CoV-2 variants to reshape the pandemic. Detecting and characterising emerging variants is essential to evaluate their public health impact and guide implementation of adapted control measures.AimTo describe the detection of emerging variant, B.1.640, in France through genomic surveillance and present investigations performed to inform public health decisions.MethodsIdentification and monitoring of SARS-CoV-2 variant B.1.640 was achieved through the French genomic surveillance system, producing 1,009 sequences. Additional investigation of 272 B.1.640-infected cases was performed between October 2021 and January 2022 using a standardised questionnaire and comparing with Omicron variant-infected cases.ResultsB.1.640 was identified in early October 2021 in a school cluster in Bretagne, later spreading throughout France. B.1.640 was detected at low levels at the end of SARS-CoV-2 Delta variant's dominance and progressively disappeared after the emergence of the Omicron (BA.1) variant. A high proportion of investigated B.1.640 cases were children aged under 14 (14%) and people over 60 (27%) years, because of large clusters in these age groups. B.1.640 cases reported previous SARS-CoV-2 infection (4%), anosmia (32%) and ageusia (34%), consistent with data on pre-Omicron SARS-CoV-2 variants. Eight percent of investigated B.1.640 cases were hospitalised, with an overrepresentation of individuals aged over 60 years and with risk factors.ConclusionEven though B.1.640 did not outcompete the Delta variant, its importation and continuous low-level spread raised concerns regarding its public health impact. The investigations informed public health decisions during the time that B.1.640 was circulating.

Severe hospital events following symptomatic infection with Sars-CoV-2 Omicron and Delta variants in France, December 2021-January 2022: A retrospective, population-based, matched cohort study.

Background: A rapid increase in incidence of the SARS-CoV-2 Omicron variant (sub-lineage BA.1) occurred in France in December 2021, while the Delta variant was prevailing since July 2021. We aimed to determine whether the risk of a severe hospital event following symptomatic SARS-CoV-2 infection differs for Omicron versus Delta. Methods: We conducted a retrospective cohort study to compare severe hospital events (admission to intensive care unit or death) between Omicron and Delta symptomatic cases matched according to week of virological diagnosis and age. The analysis was adjusted for age, sex, vaccination status, presence of comorbidities and region of residence, using Cox proportional hazards model. Findings: Between 06/12/2021-28/01/2022, 184 364 cases were included, of which 931 had a severe hospital event (822 Delta, 109 Omicron). The risk of severe event was lower among Omicron versus Delta cases; the difference in severity between the two variants decreased with age (adjusted Hazard Ratio (aHR)=0·13 95%CI: 0·08-0·20 among 40-64 years, aHR=0·50 95%CI: 0·26-0.98 among 80+ years). The risk of severe event increased with the presence of comorbidities (for very-high-risk comorbidity, aHR=4·15 95%CI: 2·86-6·01 among 40-64 years) and in males (aHR=2·28 95%CI: 1·82-2·85among 40-64 years) and was higher in unvaccinated compared to primo-vaccinated (aHR=7·29 95%CI: 5·58-9·54 among 40-64 years). A booster dose reduced the risk of severe hospital event in 80+ years infected with Omicron (aHR=0·29; 95%CI: 0·12-0·69). Interpretation: This study confirms the lower severity of Omicron compared to Delta. However, the difference in disease severity is less marked in the elderly. Further studies are needed to better understand the interactions between age and severity of variants. Funding: The study was performed as part of routine work at Public Health France.

Investigation of outbreak cases infected with the SARS-CoV-2 B.1.640 variant in a fully vaccinated elderly population, Normandy, France, November to December 2021.

Three confirmed infections with the SARS-CoV-2 B.1.640 variant under monitoring were reported in Normandy, north-western France in late November 2021. Investigations led to the identification of two events linked to the same cluster. A total of 75 confirmed and probable B.1.640 cases were reported. All had completed the primary vaccination series. Sixty-two cases were older than 65 years. Fifty-six cases had symptoms and four were hospitalised. This investigation provides preliminary results concerning a variant with limited information currently available.

Updated Mortality Analysis of SELTINE, the French Cohort of Nuclear Workers, 1968-2014.

Cohorts of nuclear workers are particularly relevant to study the health effects of protracted exposures to low doses at low dose-rates of ionizing radiation (IR). In France, a cohort of nuclear workers badge-monitored for external IR exposure has been followed-up for several decades. Its size and follow-up period have recently been extended. The present paper focuses on mortality from both cancer and non-cancer diseases in this cohort. The SELTINE cohort of nuclear workers employed by CEA, Orano, and EDF companies was followed-up for mortality from 1968 to 2014. Mortality in the cohort was compared to that in the French general population. Poisson regression methods were used to estimate excess relative rates of mortality per unit of cumulative dose of IR, adjusted for calendar year, age, company, duration of employment, and socioeconomic status. The cohort included 80,348 workers. At the end of the follow-up, the mean attained age was 63 years, and 15,695 deaths were observed. A strong healthy worker effect was observed overall. A significant excess of pleural cancer mortality was observed but not associated with IR dose. Death from solid cancers was positively but non-significantly associated with radiation. Death from leukaemia (excluding chronic lymphocytic leukaemia), dementia, and Alzheimer's disease were positively and significantly associated with IR dose. Estimated dose-risk relationships were consistent with those from other nuclear worker studies for all solid cancers and leukaemia but remained associated with large uncertainty. The association between IR dose and dementia mortality risk should be interpreted with caution and requires further investigation by other studies.

Bisphosphonate Use and Hospitalization for Hip Fractures in Women: An Observational Population-Based Study in France.

Bisphosphonates are widely used in the treatment of women at risk of osteoporotic hip fracture; however, the overall effectiveness of bisphosphonates in the prevention of osteoporotic fractures has not been studied in real life. To investigate whether the use of bisphosphonates in women aged 50 years and over is associated with a decrease in hospitalization for osteoporotic hip fractures, a historical prospective cohort study was conducted between 2009 and 2016 from a permanent representative sample consisting of 1/97 of the French health insurance beneficiaries. Bisphosphonate use was defined according to medication persistence and adherence regarding bisphosphonate dispensations. The primary outcome was the hospitalization rate for osteoporotic hip fracture. Among the 81,268 women included, 2005 were exposed to bisphosphonates. The median time of bisphosphonate exposure was 12 (IQR, 3-29) and 17 (IQR, 5-42) months for the persistence and adherence definitions, respectively. Exposure to bisphosphonates was not associated with a decrease in hospitalization for hip fracture: weighted HRadherence = 0.66 (95% CI, 0.33 to 1.33); HRpersistance = 0.77 (95% CI, 0.38 to 1.57). In real life, bisphosphonate use does not appear to reduce hospitalization for hip fractures, as to date, it is probably prescribed as primary prevention and for a duration too short to be effective.

A top 5 list for French general practice.

BACKGROUND: Medical overuse is an issue that has recently gained attention. The "Choosing Wisely" campaign invited each specialty in each country to create its own top five lists of care procedures with a negative benefit-risk balance to promote dialogue between patients and physicians. This study aims to create such a list for French general practice. METHODS: A panel of general practitioners (GPs) suggested care procedures that they felt ought to be prescribed less. Using the Delphi method, a short list of those suggestions was selected. Systematic literature reviews were performed for each item on the short list. The results were presented to the panel to assist with the final selection of the top five list. RESULTS: The panel included 40 GPs. The list includes: i/ antibiotics prescription for acute bronchitis, nasopharyngitis, otitis media with effusion, or uncomplicated influenza, ii/ systematic prostate specific antigen testing in men older than 50, iii/ prescription of cholinesterase inhibitors for mild cognitive impairment and for Alzheimer's disease and memantine for Alzheimer's disease, iv/ statins prescription in primary prevention of cardio-vascular risk in older patients, and v/ benzodiazepine or benzodiazepine-like agents prescription for generalised anxiety, insomnia, and for all indications in older patients. CONCLUSIONS: This study resulted in a French top five list in general practice using a panel of GPs. All the items selected have a negative risk-benefit balance and are frequently prescribed by French general practitioners. This list differs from other top five lists for general practice, reflecting the local medical culture.

Impact of considering non-occupational radiation exposure on the association between occupational dose and solid cancer among French nuclear workers.

OBJECTIVES: The French nuclear worker cohort allows for the assessment of cancer risk associated with occupational radiation exposure, but workers are also exposed to medical and environmental radiation which can be of the same order of magnitude. This study aims to examine the impact of non-occupational radiation exposures on the dose-risk analysis between occupational radiation exposure and cancer mortality. METHODS: The cohort included workers employed before 1995 for at least one year by CEA, AREVA NC or EDF and badge-monitored for external radiation exposure. Monitoring results were used to calculate occupational individual doses. Scenarios of work-related X-ray and environmental exposures were simulated. Poisson regression was used to quantify associations between occupational exposure and cancer mortality adjusting for non-occupational radiation exposure. RESULTS: The mean cumulative dose of external occupational radiation was 18.4 mSv among 59 004 workers. Depending on the hypotheses made, the mean cumulative work-related X-ray dose varied between 3.1 and 9.2 mSv and the mean cumulative environmental dose was around 130 mSv. The unadjusted excess relative rate of cancer per Sievert (ERR/Sv) was 0.34 (90% CI -0.44 to 1.24). Adjusting for environmental radiation exposure did not substantially modify this risk coefficient, but it was attenuated by medical exposure (ERR/Sv point estimate between 0.15 and 0.23). CONCLUSIONS: Occupational radiation risk estimates were lower when adjusted for work-related X-ray exposures. Environmental exposures had a very slight impact on the occupational exposure risk estimates. In any scenario of non-occupational exposure considered, a positive but insignificant excess cancer risk associated with occupational exposure was observed.

Consequences of combining siRNA-mediated DNA methyltransferase 1 depletion with 5-aza-2'-deoxycytidine in human leukemic KG1 cells.

5-azacytidine and 5-aza-2'-deoxycytidine are clinically used to treat patients with blood neoplasia. Their antileukemic property is mediated by the trapping and the subsequent degradation of a family of proteins, the DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) leading to DNA demethylation, tumor suppressor gene re-expression and DNA damage. Here we studied the respective role of each DNMT in the human leukemia KG1 cell line using a RNA interference approach. In addition we addressed the role of DNA damage formation in DNA demethylation by 5-aza-2'-deoxycytidine. Our data show that DNMT1 is the main DNMT involved in DNA methylation maintenance in KG1 cells and in mediating DNA damage formation upon exposure to 5-aza-2'-deoxycytidine. Moreover, KG1 cells express the DNMT1 protein at a level above the one required to ensure DNA methylation maintenance, and we identified a threshold for DNMT1 depletion that needs to be exceeded to achieve DNA demethylation. Most interestingly, by combining DNMT1 siRNA and treatment with low dose of 5-aza-2'-deoxycytidine, it is possible to uncouple DNA damage formation from DNA demethylation. This work strongly suggests that a direct pharmacological inhibition of DNMT1, unlike the use of 5-aza-2'-deoxycytidine, should lead to tumor suppressor gene hypomethylation and re-expression without inducing major DNA damage in leukemia.