A multidisciplinary and structured investigation of three suspected clusters of transverse upper limb reduction defects in France.

INTRODUCTION: Between 2019-2021, facing public concern, a scientific expert committee (SEC) reanalysed suspected clusters of transverse upper limb reduction defects (TULRD) in three administrative areas in France, where initial investigations had not identified any risk exposure. We share here the national approach we developed for managing suspicious clusters of the same group of congenital anomalies occurring in several areas. METHODS: The SEC analysed the medical records of TURLD suspected cases and performed spatiotemporal analyses on confirmed cases. If the cluster was statistically significant and included at least three cases, the SEC reviewed exposures obtained from questionnaires, environmental databases, and a survey among farmers living near to cases' homes concerning their plant product use. RESULTS: After case re-ascertainment, no statistically significant cluster was observed in the first administrative areas. In the second area, a cluster of four children born in two nearby towns over two years was confirmed, but as with the initial investigations, no exposure to a known risk factor explaining the number of cases in excess was identified. In the third area, a cluster including just two cases born the same year in the same town was confirmed. DISCUSSION: Our experience highlights that in the event of suspicious clusters occurring in different areas of a country, a coordinated and standardised approach should be preferred.

The state of integrated disease surveillance globally: synthesis report of a mixed methods study.

OBJECTIVES: Disease surveillance is an essential public health function needed to prevent, detect, monitor and respond to health threats. Integrated disease surveillance (IDS) enhances its utility and has been advocated for decades by the World Health Organization. This study sought to examine the state of IDS implementation worldwide. STUDY DESIGN: The study used a concurrent mixed methods approach consisting of a systematic scoping review of the literature on IDS, a survey of International Association of National Public Health Institutes (IANPHI) members and qualitative deep dive case studies in seven countries. METHODS: This report collates, analyses and synthesises the findings from the three components. The scoping review consisted of a review of summarised evidence on IDS. Eight reviews and five primary studies were included. The cross-sectional survey was conducted of 110 IANPHI members representing ninety-five countries. Qualitative case studies were conducted in Malawi, Mozambique, Uganda, Pakistan, Canada, Sweden, and England, which involved thirty-four focus group discussions and forty-eight key informant interviews. RESULTS: In the different countries, IDS is conceptualised differently and there are differing levels of maturity of IDS functions. Although the role of National Public Health Institutes has not been well defined in the IDS, they play a significant role in IDS in many countries. Fragmentation between sectors and resourcing (human and financial) issues were common. Good governance measures such as appropriate legislative and regulatory frameworks and roles and responsibilities for IDS were often unclear. The COVID-19 pandemic has strengthened some surveillance systems, often through leveraging existing respiratory surveillance systems. In some instances, improvements were seen only for COVID-19 related data but these changes were not sustained. Evaluation of IDS was also reported to be weak. CONCLUSIONS: Integration should be driven by a clear purpose and contextualised. Political commitment, clear governance, and resourcing are needed. Technology and the establishment of technical communities of practice may help. However, the complexity and cost of integration should not be under-estimated, and further economic and impact evaluations of IDS are needed.

Seroprevalence for Borrelia burgdorferi sensu lato and tick-borne encephalitis virus antibodies and associated risk factors among forestry workers in northern France, 2019 to 2020.

BackgroundLyme borreliosis (LB) is the most common tick-borne disease (TBD) in France. Forestry workers are at high risk of TBD because of frequent exposure to tick bites.AimWe aimed to estimate the seroprevalence of Borrelia burgdorferi sensu lato and tick-borne encephalitis virus (TBEV) antibodies among forestry workers in northern France. We compared seroprevalence by geographical area and assessed factors associated with seropositivity.MethodsBetween 2019 and 2020, we conducted a randomised cross-sectional seroprevalence survey. Borrelia burgdorferi sl seropositivity was defined as positive ELISA and positive or equivocal result in western blot. Seropositivity for TBEV was defined as positive result from two ELISA tests, confirmed by serum neutralisation. We calculated weighted seroprevalence and adjusted prevalence ratios to determine association between potential risk factors and seropositivity.ResultsA total of 1,778 forestry workers participated. Seroprevalence for B. burgdorferi sl was 15.5% (95% confidence interval (CI): 13.9-17.3), 3.5 times higher in the eastern regions than in the western and increased with seniority and with weekly time in a forest environment. Seroprevalence was 2.5 times higher in forestry workers reporting a tick bite during past years and reporting usually not removing ticks rapidly. Seroprevalence for TBEV was 0.14% (95% CI: 0.05-0.42).ConclusionWe assessed for the first time seroprevalence of B. burgdorferi sl and TBEV antibodies among forestry workers in northern France. These results will be used, together with data on LB and tick-borne encephalitis (TBE) incidence and on exposure to tick-bites, to target prevention programmes.

Estimating chikungunya virus transmission parameters and vector control effectiveness highlights key factors to mitigate arboviral disease outbreaks.

BACKGROUND: Viruses transmitted by Aedes mosquitoes have greatly expanded their geographic range in recent decades. They are considered emerging public health threats throughout the world, including Europe. Therefore, public health authorities must be prepared by quantifying the potential magnitude of virus transmission and the effectiveness of interventions. METHODOLOGY: We developed a mathematical model with a vector-host structure for chikungunya virus transmission and estimated model parameters from epidemiological data of the two main autochthonous chikungunya virus transmission events that occurred in Southern France, in Montpellier (2014) and in Le Cannet-des-Maures (2017). We then performed simulations of the model using these estimates to forecast the magnitude of the foci of transmission as a function of the response delay and the moment of virus introduction. CONCLUSIONS: The results of the different simulations underline the relative importance of each variable and can be useful to stakeholders when designing context-based intervention strategies. The findings emphasize the importance of, and advocate for early detection of imported cases and timely biological confirmation of autochthonous cases to ensure timely vector control measures, supporting the implementation and the maintenance of sustainable surveillance systems.

SARS-CoV-2 transmission across age groups in France and implications for control.

The shielding of older individuals has been proposed to limit COVID-19 hospitalizations while relaxing general social distancing in the absence of vaccines. Evaluating such approaches requires a deep understanding of transmission dynamics across ages. Here, we use detailed age-specific case and hospitalization data to model the rebound in the French epidemic in summer 2020, characterize age-specific transmission dynamics and critically evaluate different age-targeted intervention measures in the absence of vaccines. We find that while the rebound started in young adults, it reached individuals aged ≥80 y.o. after 4 weeks, despite substantial contact reductions, indicating substantial transmission flows across ages. We derive the contribution of each age group to transmission. While shielding older individuals reduces mortality, it is insufficient to allow major relaxations of social distancing. When the epidemic remains manageable (R close to 1), targeting those most contributing to transmission is better than shielding at-risk individuals. Pandemic control requires an effort from all age groups.

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.

Increased awareness and knowledge of Lyme Borreliosis and tick bite prevention among the general population in France: 2016 and 2019 health barometer survey.

BACKGROUND: Lyme borreliosis (LB) is the most frequent tick-borne disease in France. In the absence of a vaccine, LB prevention mainly relies on reducing tick bites. In 2016, the French Ministry of Health launched a national plan against tick-borne infections, including a prevention component. To evaluate the impact of this prevention strategy, we assessed knowledge and practices of tick bite prevention using the 2016 and 2019 national surveys on health attitudes and beliefs known as the French Health Barometer. METHODS: The Health Barometer is a repeated nationwide phone survey conducted annually on a random sample aged 18 to 75 years living in mainland France. In 2016 and 2019, participants were asked, among others, about their exposure to ticks, their behavior and practices regarding tick bites, and their knowledge about LB and its prevention. RESULTS: In 2019, 30% of the population reported a lifetime tick bite and 6% in the last year, an increase from 25% and 4%, respectively, in 2016 (p < 0.001). In 2019, 25% of the population felt exposed to tick bites compared to 23% in 2016 (p < 0.001). The proportion of participants who had heard about LB and who considered themselves well informed respectively increased from 66% and 29% in 2016 to 79% and 41% in 2019, (p < 0.001). In 2019 compared to 2016, a greater part of the French population applied protective measures against tick bites, particularly wearing protective clothing (74% vs 66%, p < 0.001) and regular tick checks and prompt tick removal after exposure (54% vs 47%, p < 0.001). CONCLUSIONS: A substantial proportion of French residents are exposed to tick bites and apply protective measures. Our findings indicate a trend toward an increased knowledge and awareness of tick bites and LB between 2016 and 2019 in France. Our results can be used to target future information campaigns to specific age groups or at-risk areas in addition to the general population. However, we need to further study the barriers to the use of preventive measures.

Evidence of early circulation of SARS-CoV-2 in France: findings from the population-based "CONSTANCES" cohort.

Using serum samples routinely collected in 9144 adults from a French general population-based cohort, we identified 353 participants with a positive anti-SARS-CoV-2 IgG test, among whom 13 were sampled between November 2019 and January 2020 and were confirmed by neutralizing antibodies testing. Investigations in 11 of these participants revealed experience of symptoms possibly related to a SARS-CoV-2 infection or situations at risk of potential SARS-CoV-2 exposure. This suggests early circulation of SARS-CoV-2 in Europe.

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.

From importation to autochthonous transmission: Drivers of chikungunya and dengue emergence in a temperate area.

BACKGROUND: The global spread of Aedes albopictus has exposed new geographical areas to the risk of dengue and chikungunya virus transmission. Several autochthonous transmission events have occurred in recent decades in Southern Europe and many indicators suggest that it will become more frequent in this region in the future. Environmental, socioeconomic and climatic factors are generally considered to trigger the emergence of these viruses. Accordingly, a greater knowledge of the determinants of this emergence in a European context is necessary to develop adapted surveillance and control strategies, and public health interventions. METHODOLOGY/PRINCIPAL FINDINGS: Using French surveillance data collected from between 2010 and 2018 in areas of Southern France where Ae. albopictus is already established, we assessed factors associated with the autochthonous transmission of dengue and chikungunya. Cases leading to autochthonous transmission were compared with those without subsequent transmission using binomial regression. We identified a long reporting delay (≥ 21 days) of imported cases to local health authorities as the main driver for autochthonous transmission of dengue and chikungunya in Southern France. The presence of wooded areas around the cases' place of residence and the accumulation of heat during the season also increased the risk of autochthonous arbovirus transmission. CONCLUSIONS: Our findings could inform policy-makers when developing strategies to the emerging threats of dengue and chikungunya in Southern Europe and can be extrapolated in this area to other viruses such as Zika and yellow fever, which share the same vector. Furthermore, our results allow a more accurate characterization of the environments most at risk, and highlight the importance of implementing surveillance systems which ensure the timely reporting and of imported cases and swift interventions.

Extension of French vaccination mandates: from the recommendation of the Steering Committee of the Citizen Consultation on Vaccination to the law.

On 4 December 2017, French parliamentarians passed a law extending the vaccination mandates for children up to 2 years of age from three vaccinations (against diphtheria, tetanus and poliomyelitis) to 11 by adding vaccinations against pertussis, Haemophilus influenza b (Hib), hepatitis B, pneumococcal diseases, meningococcal C diseases, measles, mumps and rubella. This vote follows a recommendation made by the Steering Committee of the Citizen Consultation on Vaccination that took place in 2016. The law applies to all children born after 1 January 2018. Parents who do not fulfil the mandate will not be fined but non-vaccinated children will not be admitted to any collective child services such as nurseries or schools. No exemption other than for medical reasons will be considered. Here we describe the historical background of this evolution and its main epidemiological, sociological and policy drivers. They mainly refer to insufficient vaccine coverage, persistence of a preventable burden for some diseases and growing vaccine hesitancy in the French population. We also discuss some of the challenges and conditions of success.

Association between maternal prepregnancy obesity and breastfeeding duration: Data from a nationwide prospective birth cohort.

Association of maternal obesity with shorter breastfeeding duration may involve different factors and might be modified by parity. In a national birth cohort, we aimed to estimate the association between prepregnancy body mass index (pBMI) and breastfeeding duration after adjustment for sociodemographic, pregnancy, and other characteristics and assess the effect modification of parity in such associations. In 2012, 3,368 mother-infant dyads were randomly included at birth in the French Epifane cohort. Breastfeeding information was collected in maternity wards and by phone interview at 1, 4, 8, and 12 months postpartum. Poisson regression analyses estimated the association of pBMI with the number of days of "any breastfeeding" (ABF) and "exclusive breastfeeding" (EBF) in unadjusted and adjusted models. Interactions between parity and pBMI were tested. Obesity before pregnancy was independently associated with shorter ABF duration (incidence rate ratio [IRR] = 0.86, 95%CI [0.74, 0.99]) compared to normal-weight status. Parity showed an effect modification only with EBF duration. Among primiparae, no association was found for obesity, but overweight was significantly associated with shorter EBF duration independently of all covariates (IRR = 0.74 [0.58, 0.95]). Among multiparas, obesity was associated with shorter EBF duration after controlling for sociodemographic factors (IRR = 0.71 [0.53, 0.95]). This association was no longer statistically significant after controlling for other covariates. Obesity appears to be a strong risk factor in shorter ABF duration. Furthermore, parity is a key factor in the relationship of pBMI to shorter EBF duration. Overweight primiparous and obese multiparous women need additional support to prolong breastfeeding duration.

Estimated Annual Numbers of Foodborne Pathogen-Associated Illnesses, Hospitalizations, and Deaths, France, 2008-2013.

Estimates of the annual numbers of foodborne illnesses and associated hospitalizations and deaths are needed to set priorities for surveillance, prevention, and control strategies. The objective of this study was to determine such estimates for 2008-2013 in France. We considered 15 major foodborne pathogens (10 bacteria, 3 viruses, and 2 parasites) and estimated that each year, the pathogens accounted for 1.28-2.23 million illnesses, 16,500-20,800 hospitalizations, and 250 deaths. Campylobacter spp., nontyphoidal Salmonella spp., and norovirus accounted for >70% of all foodborne pathogen-associated illnesses and hospitalizations; nontyphoidal Salmonella spp. and Listeria monocytogenes were the main causes of foodborne pathogen-associated deaths; and hepatitis E virus appeared to be a previously unrecognized foodborne pathogen causing ≈68,000 illnesses in France every year. The substantial annual numbers of foodborne illnesses and associated hospitalizations and deaths in France highlight the need for food-safety policymakers to prioritize foodborne disease prevention and control strategies.

Sociodemographic factors and pregnancy outcomes associated with prepregnancy obesity: effect modification of parity in the nationwide Epifane birth-cohort.

BACKGROUND: In light of the adverse outcomes for mothers and offspring related to maternal obesity, identification of subgroups of women at risk of prepregnancy obesity and its related-adverse issues is crucial for optimizing antenatal care. We aimed to identify sociodemographic factors and maternal and neonatal outcomes associated with prepregnancy obesity, and we tested the effect modification of parity on these associations. METHODS: In 2012, 3368 mothers who had delivered in 136 randomly selected maternity wards were included just after birth in the French birth cohort, Epifane. Maternal height and weight before and at the last month of pregnancy were self-reported. Maternal and neonatal outcomes were collected in medical records. Prepregnancy Body Mass Index (pBMI) was classified into underweight (<18.5), normal (18.5-24.9), overweight (25.0-29.9) and obesity (≥30.0). Since we found statistically significant interactions with parity, the multinomial logistic regression model estimating associations of pBMI class with sociodemographic characteristics and pregnancy outcomes was stratified on parity (1335 primiparous and 1814 multiparous). RESULTS: Before pregnancy, 7.6% of women were underweight, 64.2% were of normal weight, 18.0% were overweight and 10.2% were obese. Among the primiparous, maternal age of 25-29 years (OR = 2.09 [1.13-3.87]; vs. 30-34 years), high school level (OR = 2.22 [1.33-3.73]; vs. university level), gestational diabetes (OR = 2.80 [1.56-5.01]) and hypertensive complications (OR = 3.80 [1.83-7.89]) were independently associated with prepregnancy obesity. Among the multiparous, primary (OR = 6.30 [2.40-16.57]), junior high (OR = 2.89 [1.81-4.64]) and high school (OR = 1.86 [1.18-2.93]) education levels (vs. university level), no attendance at antenatal classes (OR = 1.77 [1.16-2.72]), excess gestational weight gain (OR = 1.82 [1.20-2.76]), gestational diabetes (OR =5.16 [3.15-8.46]), hypertensive complications (OR = 8.13 [3.97-16.64]), caesarean delivery (OR = 1.80 [1.18-2.77]) and infant birth weight ≥ 4 kg (OR = 1.70 [1.03-2.80]; vs. birth weight between 2.5 kg and 4 kg) were independently associated with prepregnancy obesity. CONCLUSION: Obesity before pregnancy is associated with a set of sociodemographic characteristics and adverse pregnancy outcomes that differ across parity groups. Such findings are useful for targeted health policies aimed at attaining healthy prepregnancy weight and organizing perinatal care.

Continuum of hepatitis C care in France: A 20-year cohort study.

BACKGROUND: Hepatitis C virus (HCV)-infected patients require a specific continuum of care (CoC) from HCV screening to treatment. We assessed CoC of HCV-infected patients in a longitudinal study. METHODS: We established a cohort of subjects undergoing HCV screening (high alanine aminotransferase levels or risk factors) during preventive consultations at a French regional medical center from 1993 to 2013. Patients were considered to be HCV-infected if HCV RNA was detected in their serum. CoC was assessed as described by Viner et al. (Hepatology 2015): Stage 1, HCV screening; Stage 2, HCV RNA testing; Stage 3, continuing care; Stage 4, antiviral treatment. Cox multivariate analysis was performed to identify factors favoring CoC, defined as at least one course of antiviral treatment. RESULTS: In total, 12,993 HCV tests were performed and 478 outpatients were found to be HCV-seropositive. We included 417 seropositive patients, after excluding false positives and patients lost to follow-up. The baseline characteristics of the patients were: sex ratio (M/F) 1.4; mean age 38.5 years; intravenous drug use (IDU) in 55%; and 28% in unstable social situations, estimated by the EPICES deprivation score. Antiviral treatment was initiated for 179 (42.9%) of the 379 (90.9%) patients attending specialist consultations. CoC was associated with screening after 1997 (HR 2.0, 95%CI 1.4-2.9), age > 45 years (HR 1.5, 95%CI 1.02-2.3), patient acceptance of care (HR 9.3, 95%CI 5.4-16.10), specialist motivation for treatment (HR 10.9, 95%CI 7.4-16.0), and absence of cancer (HR 6.7, 95%CI 1.6-27.9). Other comorbid conditions, such as depression and IDU, were not associated with CoC. CONCLUSIONS: Our 20-year cohort study reveals the real-life continuum of care for HCV-infected patients in France. The number of patients involved in HCV care after positive testing was substantial due to the organization of healthcare in France. An improved CoC along with new direct-acting antivirals should help to decrease chronic HCV infection.

[Horizon scanning in preparation for future health threats: a pilot exercise conducted by the French Institute for Public Health Surveillance in 2014]. / La veille prospective, une démarche de préparation aux futures menaces de la santé publique : exercice mené à l'Institut de veille sanitaire en 2014.

Background: Health surveillance is a reactive process, with no real hindsight for dealing with signals and alerts. It may fail to detect more radical changes with a major medium-term or long-term impact on public health. To increase proactivity, the French Institute for Public Health Surveillance has opted for a prospective monitoring approach.Methods: Several steps were necessary: 1) Identification of public health determinants. 2) Identification of key variables based on a combination of determinants. Variables were classified into three groups (health event trigger factors, dissemination factors and response factors) and were submitted to future development assumptions. 3) Identification, in each of the three groups, of micro-scenarios derived from variable trends. 4) Identification of macro-scenarios, each built from the three micro-scenarios for each of the three groups. 5) Identification of issues for the future of public health.Results: The exercise identified 22 key variables, 17 micro-scenarios and 5 macro-scenarios. The topics retained relate to issues on social and territorial health inequalities, health burden, individual and collective responsibilities in terms of health, ethical aspects, emerging phenomena, 'Big data', data mining, new health technologies, interlocking of analysis scales.Conclusions: The approach presented here guides the programming of activities of a health safety agency, particularly for monitoring and surveillance. By describing possible future scenarios, health surveillance can help decision-makers to influence the context towards one or more favourable futures.

Predicting Dengue Fever Outbreaks in French Guiana Using Climate Indicators.

BACKGROUND: Dengue fever epidemic dynamics are driven by complex interactions between hosts, vectors and viruses. Associations between climate and dengue have been studied around the world, but the results have shown that the impact of the climate can vary widely from one study site to another. In French Guiana, climate-based models are not available to assist in developing an early warning system. This study aims to evaluate the potential of using oceanic and atmospheric conditions to help predict dengue fever outbreaks in French Guiana. METHODOLOGY/PRINCIPAL FINDINGS: Lagged correlations and composite analyses were performed to identify the climatic conditions that characterized a typical epidemic year and to define the best indices for predicting dengue fever outbreaks during the period 1991-2013. A logistic regression was then performed to build a forecast model. We demonstrate that a model based on summer Equatorial Pacific Ocean sea surface temperatures and Azores High sea-level pressure had predictive value and was able to predict 80% of the outbreaks while incorrectly predicting only 15% of the non-epidemic years. Predictions for 2014-2015 were consistent with the observed non-epidemic conditions, and an outbreak in early 2016 was predicted. CONCLUSIONS/SIGNIFICANCE: These findings indicate that outbreak resurgence can be modeled using a simple combination of climate indicators. This might be useful for anticipating public health actions to mitigate the effects of major outbreaks, particularly in areas where resources are limited and medical infrastructures are generally insufficient.