Regional excess mortality in France during COVID-19 pandemic: the first three epidemic periods (March 2020-June 2021).

BACKGROUND: This study aimed to describe the mortality excess during the three first epidemic periods of COVID-19 in all regions of France. METHODS: Two complementary approaches were implemented. First, we described the number of death of patients infected with or diagnosed with COVID-19 in health care (HC) and medico-social (MS) institutions. Then, we estimated general all-cause mortality excess (all ages) by comparing the mortality observed with the expected mortality. We used a daily number of death model according to a negative binomial distribution, as a function of the long-term trend in mortality (penalized spline function of time) and its seasonal variation (cyclic spline function). The model provided expected mortality during epidemic periods with a 95% credibility interval. Each region defined three epidemic periods, including the overseas territories. RESULTS: The two approaches were consistent in the most affected regions but there are major regional disparities that vary according to the epidemic period. There is an east-west gradient in the relative excess of deaths from all-causes during each epidemic period. The deaths observed in HC and MS institutions alone do not explain the excess (or deficit) of mortality in each region and epidemic period. CONCLUSION: An analysis by age group according to the two approaches and a comparison of death specific causes could provide a better understanding of these differences. Electronic death registration system (mortality by medical causes) would allow a rapid mortality related estimation to an emerging pathology like Coronavirus Disease-2019 (COVID-19) but is still insufficient for real-time medical causes of death monitoring.

Sexual transmission of Zika virus in an entirely asymptomatic couple returning from a Zika epidemic area, France, April 2016.

The current Zika virus outbreak and its potential severe health consequences, especially congenital fetal syndrome, have led to increased concern about sexual transmission, especially in pregnant women and women of reproductive age. Here we report a case of Zika virus sexual transmission, likely male-to-female, in a totally asymptomatic couple.

A major impact of the influenza seasonal epidemic on intensive care units, Réunion, April to August 2016.

The 2016 seasonal influenza in Réunion in the southern hemisphere, was dominated by influenza A(H1N1)pdm09 (possibly genogroup 6B.1). An estimated 100,500 patients with acute respiratory infection (ARI) consulted a physician (cumulative attack rate 11.9%). Sixty-six laboratory-confirmed cases (65.7/100,000 ARI consultations) were hospitalised in an intensive care unit, the highest number since 2009. Impact on intensive care units was major. Correlation between severe cases was 0.83 between Réunion and France and good for 2009 to 2015.

Intensive care unit surveillance of influenza infection in France: the 2009/10 pandemic and the three subsequent seasons.

During the 2009/10 pandemic, a national surveillance system for severe influenza cases was set up in France. We present results from the system's first four years. All severe influenza cases admitted to intensive care units (ICU) were reported to the Institut de Veille Sanitaire using a standardised form: data on demographics, immunisation and virological status, risk factors, severity (e.g. acute respiratory distress syndrome (ARDS) onset, mechanical ventilation, extracorporeal life support) and outcome. Multivariate analysis was performed to identify factors associated with ARDS and death. The number of confirmed influenza cases varied from 1,210 in 2009/10 to 321 in 2011/12. Most ICU patients were infected with A(H1N1)pdm09, except during the 2011/12 winter season when A(H3N2)-related infections predominated. Patients' characteristics varied according to the predominant strain. Based on multivariate analysis, risk factors associated with death were age ≥ 65 years, patients with any of the usual recommended indications for vaccination and clinical severity. ARDS occurred more frequently in patients who were middle-aged (36-55 years), pregnant, obese, or infected with A(H1N1)pdm09. Female sex and influenza vaccination were protective. These data confirm the persistent virulence of A(H1N1)pdm09 after the pandemic and the heterogeneity of influenza seasons, and reinforce the need for surveillance of severe influenza cases.

Comparing the age and sex trajectories of SARS-CoV-2 morbidity and mortality with other respiratory pathogens.

Comparing age and sex differences in SARS-CoV-2 hospitalization and mortality with MERS-CoV, seasonal coronaviruses, influenza and other health outcomes opens the way to generating hypotheses as to underlying mechanisms driving disease risk. Using 60-year-olds as a reference age group, we find that relative rates of hospitalization and mortality associated with the emergent coronaviruses are lower during childhood and start to increase earlier (around puberty) as compared with influenza and seasonal coronaviruses. The changing distribution of disease risk by age for emerging pathogens appears to broadly track the gradual deterioration of the immune system (immunosenescence), which starts around puberty. By contrast, differences in severe disease risk by age from endemic pathogens are more decoupled from the immune ageing process. Intriguingly, age-specific sex differences in hospitalizations are largely similar across endemic and emerging infections. We discuss potential mechanisms that may be associated with these patterns.

Characteristics of hospitalizations with an influenza diagnosis, France, 2012-2013 to 2016-2017 influenza seasons.

BACKGROUND: Estimating the global burden of influenza hospitalizations is required to allocate resources and assess interventions that aim to prevent severe influenza. In France, the current routine influenza surveillance system does not fully measure the burden of severe influenza cases. The objective was to describe the characteristics and severity of influenza hospitalizations by age-group and by season between 2012 and 2017. METHODS: All hospitalizations with a diagnosis of influenza in metropolitan France between July 2012 and June 2017 were extracted from the French national hospital discharge database (PMSI). For each season, the total number of influenza hospitalizations, admissions to intensive care units (ICU), proportion of deaths, lengths of stay, and distribution in diagnosis-related groups were described by age-group. RESULTS: Over the five seasons, 91 255 hospitalizations with a diagnosis of influenza were identified. The average influenza hospitalization rate varied from 13/100 000 in 2013-2014 to 46/100 000 in 2016-2017. A high rate was observed in elderlies during the 2014-2015 and 2016-2017 seasons, dominated by A(H3N2) virus. The youngest were impacted in 2015-2016, dominated by B/Victoria virus. The proportion of influenza hospitalizations with ICU admission was 10%, and was higher in age-group 40-79 years. The proportion of deaths and length of stay increased with age. CONCLUSIONS: The description of influenza hospitalizations recorded in the PMSI give key information on the burden of severe influenza in France. Analyses of these data annually is valuable in order to document the severity of influenza hospitalizations by age-group and according to the circulating influenza viruses.

Dengue 1 virus and dengue hemorrhagic fever, French Polynesia, 2001.

An epidemic of dengue 1 virus (DENV-1) occurred in French Polynesia in 2001, 4 years after a DENV-2 epidemic that ended in 1997. Surveillance data from hospitalized case-patients showed that case-patients with dengue hemorrhagic fever (DHF) exhibited a bimodal age distribution with 1 peak among infants 6-10 months of age and a second peak at 4-11 years of age. The relative risk of DHF developing in children born before rather than after the DENV-2 epidemic was 186 (95% confidence interval 26-1,324). Among children born toward the end of the DENV-2 epidemic, a strong temporal association was found between the month of birth and the risk of being hospitalized for DHF. This study documents epidemic pathogenicity associated with the sequence of DENV-2 infection followed by DENV-1 infection.

Determinants of Fatal Outcome in Patients Admitted to Intensive Care Units With Influenza, European Union 2009-2017.

BACKGROUND: Morbidity, severity, and mortality associated with annual influenza epidemics are of public health concern. We analyzed surveillance data on hospitalized laboratory-confirmed influenza cases admitted to intensive care units to identify common determinants for fatal outcome and inform and target public health prevention strategies, including risk communication. METHODS: We performed a descriptive analysis and used Poisson regression models with robust variance to estimate the association of age, sex, virus (sub)type, and underlying medical condition with fatal outcome using European Union data from 2009 to 2017. RESULTS: Of 13 368 cases included in the basic dataset, 2806 (21%) were fatal. Age ≥40 years and infection with influenza A virus were associated with fatal outcome. Of 5886 cases with known underlying medical conditions and virus A subtype included in a more detailed analysis, 1349 (23%) were fatal. Influenza virus A(H1N1)pdm09 or A(H3N2) infection, age ≥60 years, cancer, human immunodeficiency virus infection and/or other immune deficiency, and heart, kidney, and liver disease were associated with fatal outcome; the risk of death was lower for patients with chronic lung disease and for pregnant women. CONCLUSIONS: This study re-emphasises the importance of preventing influenza in the elderly and tailoring strategies to risk groups with underlying medical conditions.

[Evaluation of the efficacy of the Toxoplasma gondii screening program among pregnant women in Nunavik, 1994-2003]. / Evaluation du Programme de dépistage de la toxoplasmose chez les femmes enceintes du Nunavik, 1994-2003.

OBJECTIVES: (1) To evaluate the efficacy of the Toxoplasma gondii screening program among Nunavik pregnant women in identifying seroconversions during pregnancy and performing an appropriate follow-up of the seroconverted women and their child; and (2) to evaluate the consequences of congenital Toxoplasma gondii infection. PARTICIPANTS: Women of child-bearing age and their children born between January 1994 and September 2003. SETTING: Nunavik. INTERVENTION: Potential cases of infection during pregnancy and of congenital toxoplasmosis were identified on the basis of serologic and hospitalization data. A medical chart revision was then performed. Descriptive statistics regarding the medical follow-up and treatment of suspected cases were compiled. OUTCOMES: 31 women who gave birth to 32 children were identified as potential cases. According to the medical charts, 19 women had a potential infection during pregnancy, the others were deemed to have been infected before conception. One woman had a definite infection. This woman and most of the 18 other potentially infected women and their children were treated appropriately. Because of missing data, it was impossible to determine with certainty the final status of two children. A diagnosis of congenital infection was rejected among the other children. CONCLUSION: Women with suspected infection and their children were generally well managed by the health care system. No clinical effect of congenital toxoplasmosis was noted during the studied period.

A portrait of the geographic dissemination of the Clostridium difficile North American pulsed-field type 1 strain and the epidemiology of C. difficile-associated disease in Québec.

BACKGROUND: An increase in the incidence and severity of Clostridium difficile-associated disease in Québec and the United States has been associated with a hypervirulent strain referred to as North American pulsed-field type 1 (NAP1)/027. METHODS: In 2005, a prospective study was conducted in 88 Québec hospitals, and 478 consecutive nosocomial isolates of C. difficile were obtained. The isolates were subjected to pulsed-field gel electrophoresis (PFGE) typing, antimicrobial susceptibility testing, and detection of binary toxin genes and tcdC gene deletion. Data on patient age and occurrence of complications were collected. RESULTS: PFGE typing of 478 isolates of C. difficile yielded 61 PFGE profiles. Pulsovars A (57%), B (10%), and B1 (8%) were predominant. The PFGE profile of pulsovar A was identical to that of strain NAP1. It showed 67% relatedness with 15 other PFGE patterns, among which 11 had both binary toxin genes and a partial tcdC deletion but different antibiotic susceptibility profiles. Pulsovars B and B1 were identical to strain NAP2/ribotype 001. In hospitals showing a predominant clonal A or B-B1 PFGE pattern, incidence of C. difficile-associated disease was 2 and 1.3 times higher, respectively, than in hospitals without any predominant clonal PFGE pattern. Severe disease was twice as frequent among patients with strains possessing binary toxin genes and tcdC deletion than among patients with strains lacking these virulence factors. CONCLUSIONS: This study helped to quantify the impact of strain NAP1 on the incidence and severity of C. difficile-associated disease in Québec in 2005. The identification of the geographic dissemination of this predominant strain may help to focus regional infection-control efforts.

Outbreak of Skin Infections Due to Panton-Valentine Leukocidin-Positive Methicillin-Susceptible Staphylococcus aureus in a French Prison in 2010-2011.

Background. An outbreak of PVL-positive MSSA skin and soft tissue-infections (SSTIs) was suspected in May 2010 when recurrent SSTI was diagnosed in an inmate of a large prison in Nantes, France. Methods and findings. Retrospective and prospective investigations were performed. Microbiological characterisation was by DNA microarray testing (S. aureus genotyping - Identibac, Alere). We identified 14 inmates meeting our clinical and microbiological case definition for PVL-MSSA SSTI between March 2010 and April 2011. The SSTIs developed in tattooed areas in 4 patients and in areas shaved daily with a mechanical razor in 4 other patients. All case isolates exhibited a similar SmaI pulsed-field gel electrophoresis pattern. Microarray analysis showed that all 14 isolates harboured genes encoding PVL and enterotoxins (A, H, K, and Q) and belonged to clonal complex 1 (CC1). Individual and collective hygiene measures, education delivered to inmates and prison employees, and antibiotic treatment of SSTIs were successful in controlling the outbreak. No new cases were identified after April 2011. Routine screening for PVL-positive MSSA carriage was not feasible. Conclusions. Our data suggest that tattooing and shaving with mechanical razors may constitute risk factors for SSTIs among previously colonised inmates and contribute to the PVL-MSSA outbreak in the prison. Allowing inmates access to professional tattooists and to the hygiene and safety conditions available to people in the community would help to prevent tattoo-related infections.

Development of a safety culture: initial measurements at six hospitals in France.

A cross-sectional and descriptive survey of a safety culture (SC) was conducted in 20 clinical units in France. A self-administered questionnaire measuring 12 dimensions of safety culture was given to healthcare professionals. The overall response rate was 65%. The poorly developed dimensions of safety culture that were identified were nonpunitive response to error, staffing, management support for patient safety, handoffs, and transitions.

Epidemiological patterns and hospital characteristics associated with increased incidence of Clostridium difficile infection in Quebec, Canada, 1998-2006.

OBJECTIVE: To explore epidemiological patterns of the incidence of Clostridium difficile infection (CDI) and hospital characteristics associated with increased incidence during nonepidemic and epidemic years. DESIGN: Retrospective and prospective ecological study. SETTING: Eighty-three acute care hospitals participating in CDI surveillance in the province of Quebec, Canada. METHODS: A Serfling-type regression model applied to data obtained from an administrative database (1998-2006) and prospective Quebec CDI surveillance (2004-2006) was used to calculate expected CDI baseline incidence and to detect incidence exceeding the defined epidemic threshold at the provincial and hospital level. Multivariable Poisson regression was used to determine hospital characteristics associated with increased incidence during nonepidemic (1998-2001) and epidemic (2003-2005) periods. RESULTS: During the study period (1998-2006), 4,525,847 discharges, including 45,508 with a CDI in any diagnosis field, were reported by 83 hospitals. During 1998-2001, the average Quebec incidence of CDI was 10,304 cases in 1,775,822 discharges (5.8 cases per 1,000 discharges) and presented a pattern of seasonality, with similar patterns at the hospital level for some hospitals. The Quebec epidemic started in October-November 2002 and peaked in March 2004 at 845 cases in 40,852 discharges (20.7 cases per 1,000 discharges). In multivariable analysis, higher incidence was associated with location in Montreal and surrounding regions, greater hospital size, larger proportion of hospitalized elderly patients, longer length of stay, and greater proportion of comorbidities in patients, whereas teaching profile was associated with decreased incidence during both nonepidemic and epidemic periods. The effect of geographical location on incidence was greater during the epidemic. CONCLUSION: Baseline incidence from nonepidemic years and hospital characteristics associated with CDI incidence should be taken into account when estimating the efficacy of interventions.

Temporal trends and epidemiological aspects of ciguatera in French Polynesia: a 10-year analysis.

OBJECTIVES: The purpose of this study was to report the temporal trends of the incidence of ciguatera poisoning from 1992 to 2001 in French Polynesia. METHODS: This retrospective study analysed 7842 cases of ciguatera disease recorded over a period of 10 years. RESULTS: The annual incidence varied from 26.3 to 41.9 per 10,000 person-years. An analysis of cases grouped by archipelago revealed differences in incidences (P < 0.0001) with the most remote archipelagos having the highest incidences. A detailed analysis on a sub-sample of recorded cases for which clinical information was available (n = 1824) confirmed the neurological and gastrointestinal nature of this seafood poisoning. CONCLUSION: The incidence of ciguatera poisoning appeared relatively stable during the 10 years of the study period. However, the gradient of remoteness observed suggests an adaptation of management of ciguatera disease to each archipelago.

Introduction of SARS in France, March-April, 2003.

We describe severe acute respiratory syndrome (SARS) in France. Patients meeting the World Health Organization definition of a suspected case underwent a clinical, radiologic, and biologic assessment at the closest university-affiliated infectious disease ward. Suspected cases were immediately reported to the Institut de Veille Sanitaire. Probable case-patients were isolated, their contacts quarantined at home, and were followed for 10 days after exposure. Five probable cases occurred from March through April 2003; four were confirmed as SARS coronavirus by reverse transcription-polymerase chain reaction, serologic testing, or both. The index case-patient (patient A), who had worked in the French hospital of Hanoi, Vietnam, was the most probable source of transmission for the three other confirmed cases; two had been exposed to patient A while on the Hanoi-Paris flight of March 22-23. Timely detection, isolation of probable case-patients, and quarantine of their contacts appear to have been effective in preventing the secondary spread of SARS in France.