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1. Impact of vaccination against severe COVID-19 in the French population aged 50 years and above: a retrospective population-based study

Author

Laetitia Tan-Lhernould, Cynthia Tamandjou, Guilhem Deschamps, Johnny Platon, Cécile Sommen, Fanny Chereau, Isabelle Parent du Châtelet, Simon Cauchemez, Sophie Vaux, and Juliette Paireau

Subjects
COVID-19, Vaccination, Impact, Mortality, Hospitalization, Burden, Medicine
Abstract

Abstract Background Given the widespread implementation of COVID-19 vaccination to mitigate the pandemic from the end of 2020, it is important to retrospectively evaluate its impact, in particular by quantifying the number of severe outcomes prevented through vaccination. Methods We estimated the number of hospitalizations, intensive care unit (ICU) admissions and deaths directly averted by vaccination in France, in people aged ≥ 50 years, from December 2020 to March 2022, based on (1) the number of observed events, (2) vaccination coverage, and (3) vaccine effectiveness. We accounted for the effect of primary vaccination and the first booster dose, the circulating variants, the age groups, and the waning of vaccine-induced protection over time. Results An estimated 480,150 (95% CI: 260,072–582,516) hospitalizations, 132,156 (50,409–157,767) ICU admissions and 125,376 (53,792–152,037) deaths were directly averted by vaccination in people aged ≥ 50 years, which corresponds to a reduction of 63.2% (48.2–67.6), 68.7% (45.6–72.4) and 62.7% (41.9–67.1) respectively, compared to what would have been expected without vaccination over the study period. An estimated 5852 (2285–6853) deaths were directly averted among the 50–59 years old, 16,837 (6568–19,473) among the 60–69 years old, 32,136 (13,651–36,758) among the 70–79 years old and 70,551 (31,288–88,953) among the ≥ 80 years old. Conclusions The vaccination campaign in France considerably reduced COVID-19 morbidity and mortality, as well as stress on the healthcare system.

Published
2023
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2. Impact of non-pharmaceutical interventions, weather, vaccination, and variants on COVID-19 transmission across departments in France

Author

Juliette Paireau, Marie-Laure Charpignon, Sophie Larrieu, Clémentine Calba, Nathanaël Hozé, Pierre-Yves Boëlle, Rodolphe Thiebaut, Mélanie Prague, and Simon Cauchemez

Subjects
COVID-19, Non-pharmaceutical interventions, Vaccination, Weather, Reproduction number, Regression model, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Multiple factors shape the temporal dynamics of the COVID-19 pandemic. Quantifying their relative contributions is key to guide future control strategies. Our objective was to disentangle the individual effects of non-pharmaceutical interventions (NPIs), weather, vaccination, and variants of concern (VOC) on local SARS-CoV-2 transmission. Methods We developed a log-linear model for the weekly reproduction number (R) of hospital admissions in 92 French metropolitan departments. We leveraged (i) the homogeneity in data collection and NPI definitions across departments, (ii) the spatial heterogeneity in the timing of NPIs, and (iii) an extensive observation period (14 months) covering different weather conditions, VOC proportions, and vaccine coverage levels. Findings Three lockdowns reduced R by 72.7% (95% CI 71.3–74.1), 70.4% (69.2–71.6) and 60.7% (56.4–64.5), respectively. Curfews implemented at 6/7 pm and 8/9 pm reduced R by 34.3% (27.9–40.2) and 18.9% (12.04–25.3), respectively. School closures reduced R by only 4.9% (2.0–7.8). We estimated that vaccination of the entire population would have reduced R by 71.7% (56.4–81.6), whereas the emergence of VOC (mainly Alpha during the study period) increased transmission by 44.6% (36.1–53.6) compared with the historical variant. Winter weather conditions (lower temperature and absolute humidity) increased R by 42.2% (37.3–47.3) compared to summer weather conditions. Additionally, we explored counterfactual scenarios (absence of VOC or vaccination) to assess their impact on hospital admissions. Interpretation Our study demonstrates the strong effectiveness of NPIs and vaccination and quantifies the role of weather while adjusting for other confounders. It highlights the importance of retrospective evaluation of interventions to inform future decision-making.

Published
2023
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3. Reconstructing Mayotte 2018–19 Rift Valley Fever outbreak in humans by combining serological and surveillance data

Author

Jonathan Bastard, Guillaume André Durand, Fanny Parenton, Youssouf Hassani, Laure Dommergues, Juliette Paireau, Nathanaël Hozé, Marc Ruello, Gilda Grard, Raphaëlle Métras, and Harold Noël

Subjects
Medicine
Abstract

Bastard et al. estimate the extent of zoonotic human infections during the 2018–2019 Rift Valley Fever outbreak in Mayotte, France, combining passive surveillance and serological data. Estimating the case reporting fraction shows that syndromic surveillance fails to capture most infections during the epidemic.

Published
2022
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4. Seroepidemiology of enterovirus A71 infection in prospective cohort studies of children in southern China, 2013-2018

Author

Juan Yang, Qiaohong Liao, Kaiwei Luo, Fengfeng Liu, Yonghong Zhou, Gang Zou, Wei Huang, Shuanbao Yu, Xianglin Wei, Jiaxin Zhou, Bingbing Dai, Qi Qiu, Ralf Altmeyer, Hongan Hu, Juliette Paireau, Li Luo, Lidong Gao, Birgit Nikolay, Shixiong Hu, Weijia Xing, Peng Wu, H. Rogier van Doorn, Peter W. Horby, Peter Simmonds, Gabriel M. Leung, Benjamin J. Cowling, Simon Cauchemez, and Hongjie Yu

Subjects
Science
Abstract

Hand, foot and mouth disease, caused by enterovirus A71 (EV-A71) infection, is common in children in China. Here, the authors estimate EV-A71 incidence and seroprevalence using data from two longitudinal cohorts and find that, despite high infection rates, a large proportion of children under 6 are susceptible.

Published
2022
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5. Adherence and sustainability of interventions informing optimal control against the COVID-19 pandemic

Author

Laura Di Domenico, Chiara E. Sabbatini, Pierre-Yves Boëlle, Chiara Poletto, Pascal Crépey, Juliette Paireau, Simon Cauchemez, François Beck, Harold Noel, Daniel Lévy-Bruhl, and Vittoria Colizza

Subjects
Medicine
Abstract

Di Domenico and Sabbatini et al. model the impact of lockdowns of varying duration and intensity on the control of COVID-19, using data from the third wave of the epidemic in the Paris region of France. The authors introduce a measure of policy-induced fatigue, the ‘distress index’, that helps to explain why shorter, more stringent restrictions might be more effective.

Published
2021
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6. SARS-CoV-2 transmission across age groups in France and implications for control

Author

Cécile Tran Kiem, Paolo Bosetti, Juliette Paireau, Pascal Crépey, Henrik Salje, Noémie Lefrancq, Arnaud Fontanet, Daniel Benamouzig, Pierre-Yves Boëlle, Jean-Claude Desenclos, Lulla Opatowski, and Simon Cauchemez

Subjects
Science
Abstract

In this study, Tran Kiem et al. examine the contribution of different age groups to COVID-19 transmission. Using data from the French epidemic in summer 2020, they report that while individuals aged 80 years and older are more at risk, pandemic control in the absence of vaccines required measures targeted at all age groups.

Published
2021
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7. Monitoring the reproductive number of COVID-19 in France: Comparative estimates from three datasets.

Author

Christophe Bonaldi, Anne Fouillet, Cécile Sommen, Daniel Lévy-Bruhl, and Juliette Paireau

Subjects
Medicine, Science
Abstract

BackgroundThe effective reproduction number (Rt) quantifies the average number of secondary cases caused by one person with an infectious disease. Near-real-time monitoring of Rt during an outbreak is a major indicator used to monitor changes in disease transmission and assess the effectiveness of interventions. The estimation of Rt usually requires the identification of infected cases in the population, which can prove challenging with the available data, especially when asymptomatic people or with mild symptoms are not usually screened. The purpose of this study was to perform sensitivity analysis of Rt estimates for COVID-19 surveillance in France based on three data sources with different sensitivities and specificities for identifying infected cases.MethodsWe applied a statistical method developed by Cori et al. to estimate Rt using (1) confirmed cases identified from positive virological tests in the population, (2) suspected cases recorded by a national network of emergency departments, and (3) COVID-19 hospital admissions recorded by a national administrative system to manage hospital organization.ResultsRt estimates in France from May 27, 2020, to August 12, 2022, showed similar temporal trends regardless of the dataset. Estimates based on the daily number of confirmed cases provided an earlier signal than the two other sources, with an average lag of 3 and 6 days for estimates based on emergency department visits and hospital admissions, respectively.ConclusionThe COVID-19 experience confirmed that monitoring temporal changes in Rt was a key indicator to help the public health authorities control the outbreak in real time. However, gaining access to data on all infected people in the population in order to estimate Rt is not straightforward in practice. As this analysis has shown, the opportunity to use more readily available data to estimate Rt trends, provided that it is highly correlated with the spread of infection, provides a practical solution for monitoring the COVID-19 pandemic and indeed any other epidemic.

Published
2023
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8. Modelling the end of a Zero-COVID strategy using nirmatrelvir/ritonavir, vaccination and NPIs in Wallis and FutunaResearch in context

Author

Antoine Brault, Cécile Tran-Kiem, Clément Couteaux, Valérie Olié, Juliette Paireau, Yazdan Yazdanpanah, Jade Ghosn, Guillaume Martin-Blondel, Paolo Bosetti, and Simon Cauchemez

Subjects
COVID-19, SARS-CoV-2, Treatment, Antiviral, Nirmatrelvir/ritonavir, Paxlovid, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: Ending Zero-COVID is challenging, particularly when vaccine coverage is low. Considering Wallis and Futuna, a French Zero-COVID territory affected by reluctance to vaccination, low immunity and high levels of comorbidities, we investigate how targeted use of nirmatrelvir/ritonavir (brand name Paxlovid) can complement vaccination and non-pharmaceutical interventions (NPIs), and mitigate the epidemic rebound expected when Zero-COVID ends. Methods: We developed a discrete age-stratified compartmental model describing SARS-CoV-2 spread and healthcare impact once Wallis and Futuna reopens. It accounts for comorbidity risk groups (CRG), vaccine coverage (2 doses, 3 doses), the effectiveness of vaccines (recent or old injection), treatments and NPIs. In our baseline scenario, cases aged 65+ in intermediate/high CRG and 40+ in high CRG are eligible for treatment. Findings: The epidemic is expected to start 13–20 days after reopening with a doubling time of 1.6-3.7 days. For medium transmission intensity (R0 = 5), 134 (115–156) hospital admissions are expected within 3 months, with no pharmaceutical measures. In our baseline scenario, admissions are reduced by 11%–21% if 50% of the target group receive treatment, with maximum impact when combined with NPIs and vaccination. The number of hospitalisations averted (HA) per patient treated (PT) is maximum when 65+ in high CRG are targeted (0.124 HA/PT), quickly followed by 65+ in intermediate/high CRG (0.097 HA/PT), and any 65+ (0.093 HA/PT). Expanding the target group increases both PT and HA, but marginal gains diminish. Interpretation: Modelling suggests that test and treat may contribute to the mitigation of epidemic rebounds at the end of Zero-COVID, particularly in populations with low immunity and high levels of comorbidities. Funding: RECOVER, VEO, AXA, Groupama, SpF, IBEID, INCEPTION, EMERGEN.

Published
2023
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9. Analytical framework to evaluate and optimize the use of imperfect diagnostics to inform outbreak response: Application to the 2017 plague epidemic in Madagascar.

Author

Quirine Ten Bosch, Voahangy Andrianaivoarimanana, Beza Ramasindrazana, Guillain Mikaty, Rado J L Rakotonanahary, Birgit Nikolay, Soloandry Rahajandraibe, Maxence Feher, Quentin Grassin, Juliette Paireau, Soanandrasana Rahelinirina, Rindra Randremanana, Feno Rakotoarimanana, Marie Melocco, Voahangy Rasolofo, Javier Pizarro-Cerdá, Anne-Sophie Le Guern, Eric Bertherat, Maherisoa Ratsitorahina, André Spiegel, Laurence Baril, Minoarisoa Rajerison, and Simon Cauchemez

Subjects
Biology (General), QH301-705.5
Abstract

During outbreaks, the lack of diagnostic "gold standard" can mask the true burden of infection in the population and hamper the allocation of resources required for control. Here, we present an analytical framework to evaluate and optimize the use of diagnostics when multiple yet imperfect diagnostic tests are available. We apply it to laboratory results of 2,136 samples, analyzed with 3 diagnostic tests (based on up to 7 diagnostic outcomes), collected during the 2017 pneumonic (PP) and bubonic plague (BP) outbreak in Madagascar, which was unprecedented both in the number of notified cases, clinical presentation, and spatial distribution. The extent of these outbreaks has however remained unclear due to nonoptimal assays. Using latent class methods, we estimate that 7% to 15% of notified cases were Yersinia pestis-infected. Overreporting was highest during the peak of the outbreak and lowest in the rural settings endemic to Y. pestis. Molecular biology methods offered the best compromise between sensitivity and specificity. The specificity of the rapid diagnostic test was relatively low (PP: 82%, BP: 85%), particularly for use in contexts with large quantities of misclassified cases. Comparison with data from a subsequent seasonal Y. pestis outbreak in 2018 reveal better test performance (BP: specificity 99%, sensitivity: 91%), indicating that factors related to the response to a large, explosive outbreak may well have affected test performance. We used our framework to optimize the case classification and derive consolidated epidemic trends. Our approach may help reduce uncertainties in other outbreaks where diagnostics are imperfect.

Published
2022
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10. Cold and dry winter conditions are associated with greater SARS-CoV-2 transmission at regional level in western countries during the first epidemic wave

Author

Jordi Landier, Juliette Paireau, Stanislas Rebaudet, Eva Legendre, Laurent Lehot, Arnaud Fontanet, Simon Cauchemez, and Jean Gaudart

Subjects
Medicine, Science
Abstract

Abstract Higher transmissibility of SARS-CoV-2 in cold and dry weather conditions has been hypothesized since the onset of the COVID-19 pandemic but the level of epidemiological evidence remains low. During the first wave of the pandemic, Spain, Italy, France, Portugal, Canada and USA presented an early spread, a heavy COVID-19 burden, and low initial public health response until lockdowns. In a context when testing was limited, we calculated the basic reproduction number (R0) in 63 regions from the growth in regional death counts. After adjusting for population density, early spread of the epidemic, and age structure, temperature and humidity were negatively associated with SARS-CoV-2 transmissibility. A reduction of mean absolute humidity by 1 g/m3 was associated with a 0.15-unit increase of R0. Below 10 °C, a temperature reduction of 1 °C was associated with a 0.16-unit increase of R0. Our results confirm a dependency of SARS-CoV-2 transmissibility to weather conditions in the absence of control measures during the first wave. The transition from summer to winter, corresponding to drop in temperature associated with an overall decrease in absolute humidity, likely contributed to the intensification of the second wave in north-west hemisphere countries. Non-pharmaceutical interventions must be adjusted to account for increased transmissibility in winter conditions.

Published
2021
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11. Evaluating the impact of curfews and other measures on SARS-CoV-2 transmission in French Guiana

Author

Alessio Andronico, Cécile Tran Kiem, Juliette Paireau, Tiphanie Succo, Paolo Bosetti, Noémie Lefrancq, Mathieu Nacher, Félix Djossou, Alice Sanna, Claude Flamand, Henrik Salje, Cyril Rousseau, and Simon Cauchemez

Subjects
Science
Abstract

Identifying effective combinations of control measures in different populations is important for SARS-CoV-2 control. Here, the authors show that in French Guiana, which has a relatively young population, curfews and localised lockdowns appeared to contribute to reducing transmission.

Published
2021
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12. Comparing the age and sex trajectories of SARS-CoV-2 morbidity and mortality with other respiratory pathogens

Author

C. Jessica E. Metcalf, Juliette Paireau, Megan O'Driscoll, Mathilde Pivette, Bruno Hubert, Isabelle Pontais, Sema Nickbakhsh, Derek A. T. Cummings, Simon Cauchemez, and Henrik Salje

Subjects
comparing, age, sex, trajectories, SARS, CoV-2, Science
Abstract

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.

Published
2022
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13. Impact of SARS-CoV-2 Delta variant on incubation, transmission settings and vaccine effectiveness: Results from a nationwide case-control study in France

Author

Rebecca Grant, Tiffany Charmet, Laura Schaeffer, Simon Galmiche, Yoann Madec, Cassandre Von Platen, Olivia Chény, Faïza Omar, Christophe David, Alexandra Rogoff, Juliette Paireau, Simon Cauchemez, Fabrice Carrat, Alexandra Septfons, Daniel Levy-Bruhl, Alexandra Mailles, and Arnaud Fontanet

Subjects
Public aspects of medicine, RA1-1270
Abstract

Summary: Background: We aimed to assess the settings and activities associated with SARS-CoV-2 infection in the context of B.1.617.2 (Delta) variant circulation in France, as well as the protection against symptomatic Delta infection. Methods: In this nationwide case-control study, cases were SARS-CoV-2 infected adults recruited between 23 May and 13 August 2021. Controls were non-infected adults from a national representative panel matched to cases by age, sex, region, population density and calendar week. Participants completed an online questionnaire and multivariable logistic regression analysis was used to determine the association between acute SARS-CoV-2 infection and recent activity-related exposures, past history of SARS-CoV-2 infection, and COVID-19 vaccination. Findings: We did not find any differences in the settings and activities associated with Delta versus non-Delta infections and grouped them for subsequent analyses. In multivariable analysis involving 12634 cases (8644 Delta and 3990 non-Delta) and 5560 controls, we found individuals under 40 years and attending bars (aOR:1.9; 95%CI:1.6-2.2) or parties (aOR:3.4; 95%CI:2.8-4.2) to be at increased risk of infection. In those aged 40 years and older, having children attend daycare (aOR:1.9; 95%CI:1.1-3.3), kindergarten (aOR:1.6; 95%CI:1.2-2.1), primary school (aOR:1.4; 95%CI:1.2-1.6) or middle school (aOR:1.3; 95%CI:1.2-1.6) were associated with increased risk of infection. We found strong protection against symptomatic Delta infection for those with prior infection whether it was recent (2-6 months) (95%; 95%CI:90-97) or associated with one dose (85%; 95%CI:78-90) or two doses of mRNA vaccine (96%; 95%CI:87-99). For those without past infection, protection was lower with two doses of mRNA vaccine (67%; 95%CI:63-71). Interpretation: In line with other observational studies, we find reduced vaccine effectiveness against symptomatic Delta infections. The settings and activities at increased risk of infection indicate where efforts to reinforce individual and public health measures need to be concentrated.

Published
2022
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14. Exposures associated with SARS-CoV-2 infection in France: A nationwide online case-control study

Author

Simon Galmiche, Tiffany Charmet, Laura Schaeffer, Juliette Paireau, Rebecca Grant, Olivia Chény, Cassandre Von Platen, Alexandra Maurizot, Carole Blanc, Annika Dinis, Sophie Martin, Faïza Omar, Christophe David, Alexandra Septfons, Simon Cauchemez, Fabrice Carrat, Alexandra Mailles, Daniel Levy-Bruhl, and Arnaud Fontanet

Subjects
Public aspects of medicine, RA1-1270
Abstract

Summary: Background: We aimed to assess the role of different setting and activities in acquiring SARS-CoV-2 infection. Methods: In this nationwide case-control study, cases were SARS-CoV-2 infected adults recruited between 27 October and 30 November 2020. Controls were individuals from the Ipsos market research database matched to cases by age, sex, region, population density and time period. Participants completed an online questionnaire on recent activity-related exposures. Findings: Among 3426 cases and 1713 controls, in multivariable analysis, we found an increased risk of infection associated with any additional person living in the household (adjusted-OR: 1•16; 95%CI: 1•11-1•21); having children attending day-care (aOR: 1•31; 95%CI: 1•02-1•62), kindergarten (aOR: 1•27; 95%CI: 1•09-1•45), middle school (aOR: 1•30; 95%CI: 1•15-1•47), or high school (aOR: 1•18; 95%CI: 1•05-1•34); with attending professional (aOR: 1•15; 95%CI: 1•04-1•26) or private gatherings (aOR: 1•57; 95%CI: 1•45-1•71); and with having frequented bars and restaurants (aOR: 1•95; 95%CI: 1•76-2•15), or having practiced indoor sports activities (aOR: 1•36; 95%CI: 1•15-1•62). We found no increase in risk associated with frequenting shops, cultural or religious gatherings, or with transportation, except for carpooling (aOR: 1•47; 95%CI: 1•28-1•69). Teleworking was associated with decreased risk of infection (aOR: 0•65; 95%CI: 0•56-0•75). Interpretation: Places and activities during which infection prevention and control measures may be difficult to fully enforce were those with increased risk of infection. Children attending day-care, kindergarten, middle and high schools, but not primary schools, were potential sources of infection for the household. Funding: Institut Pasteur, Research & Action Emerging Infectious Diseases (REACTing), Fondation de France (Alliance” Tous unis contre le virus”).

Published
2021
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15. Evolution of outcomes for patients hospitalised during the first 9 months of the SARS-CoV-2 pandemic in France: A retrospective national surveillance data analysis

Author

Noémie Lefrancq, Juliette Paireau, Nathanaël Hozé, Noémie Courtejoie, Yazdan Yazdanpanah, Lila Bouadma, Pierre-Yves Boëlle, Fanny Chereau, Henrik Salje, and Simon Cauchemez

Subjects
Public aspects of medicine, RA1-1270
Abstract

Background: As SARS-CoV-2 continues to spread, a thorough characterisation of healthcare needs and patient outcomes, and how they have changed over time, is essential to inform planning. Methods: We developed a probabilistic framework to analyse detailed patient trajectories from 198,846 hospitalisations in France during the first nine months of the pandemic. Our model accounts for the varying age- and sex- distribution of patients, and explore changes in outcome probabilities as well as length of stay. Findings: We found that there were marked changes in the age and sex of hospitalisations over the study period. In particular, the proportion of hospitalised individuals that were >80y varied between 27% and 48% over the course of the epidemic, and was lowest during the inter-peak period. The probability of hospitalised patients entering ICU dropped from 0·25 (0·24–0·26) to 0·13 (0·12–0·14) over the four first months as case numbers fell, before rising to 0·19 (0·19–0·20) during the second wave. The probability of death followed a similar trajectory, falling from 0·25 (0·24–0·26) to 0·10 (0·09–0·11) after the first wave before increasing again during the second wave to 0·19 (0·18–0·19). Overall, we find both the probability of death and the probability of entering ICU were significantly correlated with COVID-19 ICU occupancy. Interpretation: There are large scale trends in patients outcomes by age, sex and over time. These need to be considered in ongoing healthcare planning efforts. Funding: INCEPTION.

Published
2021
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16. Monitoring the proportion of the population infected by SARS-CoV-2 using age-stratified hospitalisation and serological data: a modelling study

Author

Nathanaël Hozé, PhD, Juliette Paireau, PhD, Nathanaël Lapidus, MD, Cécile Tran Kiem, MSc, Henrik Salje, PhD, Gianluca Severi, PhD, Mathilde Touvier, PhD, Marie Zins, ProfMD, Xavier de Lamballerie, ProfMD, Daniel Lévy-Bruhl, MPH, Fabrice Carrat, ProfMD, and Simon Cauchemez, PhD

Subjects
Public aspects of medicine, RA1-1270
Abstract

Summary: Background: Regional monitoring of the proportion of the population who have been infected by SARS-CoV-2 is important to guide local management of the epidemic, but is difficult in the absence of regular nationwide serosurveys. We aimed to estimate in near real time the proportion of adults who have been infected by SARS-CoV-2. Methods: In this modelling study, we developed a method to reconstruct the proportion of adults who have been infected by SARS-CoV-2 and the proportion of infections being detected, using the joint analysis of age-stratified seroprevalence, hospitalisation, and case data, with deconvolution methods. We developed our method on a dataset consisting of seroprevalence estimates from 9782 participants (aged ≥20 years) in the two worst affected regions of France in May, 2020, and applied our approach to the 13 French metropolitan regions over the period March, 2020, to January, 2021. We validated our method externally using data from a national seroprevalence study done between May and June, 2020. Findings: We estimate that 5·7% (95% CI 5·1–6·4) of adults in metropolitan France had been infected with SARS-CoV-2 by May 11, 2020. This proportion remained stable until August, 2020, and increased to 14·9% (13·2–16·9) by Jan 15, 2021. With 26·5% (23·4–29·8) of adult residents having been infected in Île-de-France (Paris region) compared with 5·1% (4·5–5·8) in Brittany by January, 2021, regional variations remained large (coefficient of variation [CV] 0·50) although less so than in May, 2020 (CV 0·74). The proportion infected was twice as high (20·4%, 15·6–26·3) in 20–49-year-olds than in individuals aged 50 years or older (9·7%, 6·9–14·1). 40·2% (34·3–46·3) of infections in adults were detected in June to August, 2020, compared with 49·3% (42·9–55·9) in November, 2020, to January, 2021. Our regional estimates of seroprevalence were strongly correlated with the external validation dataset (coefficient of correlation 0·89). Interpretation: Our simple approach to estimate the proportion of adults that have been infected with SARS-CoV-2 can help to characterise the burden of SARS-CoV-2 infection, epidemic dynamics, and the performance of surveillance in different regions. Funding: EU RECOVER, Agence Nationale de la Recherche, Fondation pour la Recherche Médicale, Institut National de la Santé et de la Recherche Médicale (Inserm).

Published
2021
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17. Hypoglycemic Toxins and Enteroviruses as Causes of Outbreaks of Acute Encephalitis-Like Syndrome in Children, Bac Giang Province, Northern Vietnam

Author

Nga Thi Phan, Meriadeg Ar Gouilh, Juliette Paireau, Loan Phuong, Justine Cheval, Nghia Duy Ngu, Charles Hébert, Tuan Hai Nguyen, Olivier Lortholary, Laura Tondeur, Jean-Claude Manuguerra, Robert Barouki, Johannes Sander, Nils Janzen, Hien Tran Nguyen, Paul T. Brey, Arnaud Fontanet, and Marc Eloit

Subjects
hypoglycemic toxins, enteroviruses, viruses, meningitis/encephalitis, encephalitis, acute encephalitis syndrome, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

We investigated the cause of seasonal outbreaks of pediatric acute encephalitis-like syndrome associated with litchi harvests (May–July) in northern Vietnam since 2008. Nineteen cerebrospinal fluid samples were positive for human enterovirus B, and 8 blood samples were positive for hypoglycemic toxins present in litchi fruits. Patients who were positive for hypoglycemic toxins had shorter median times between disease onset and admission, more reports of seizures, more reports of hypoglycemia (glucose level

Published
2018
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18. Towards understanding the epidemiology of Neisseria meningitidis in the African meningitis belt: a multi-disciplinary overview

Author

Lydiane Agier, Nadège Martiny, Oumy Thiongane, Judith E. Mueller, Juliette Paireau, Eleanor R. Watkins, Tom J. Irving, Thibaut Koutangni, and Hélène Broutin

Subjects
Bacterial meningitis, Disease control, Research priorities, African belt, Infectious and parasitic diseases, RC109-216
Abstract

Objectives: Neisseria meningitidis is the major cause of seasonal meningitis epidemics in the African meningitis belt. In the changing context of a reduction in incidence of serogroup A and an increase in incidence of serogroups W and C and of Streptococcus pneumoniae, a better understanding of the determinants driving the disease transmission dynamics remains crucial to improving bacterial meningitis control. Methods: The literature was searched to provide a multi-disciplinary overview of the determinants of meningitis transmission dynamics in the African meningitis belt. Results: Seasonal hyperendemicity is likely predominantly caused by increased invasion rates, sporadic localized epidemics by increased transmission rates, and larger pluri-annual epidemic waves by changing population immunity. Carriage likely involves competition for colonization and cross-immunity. The duration of immunity likely depends on the acquisition type. Major risk factors include dust and low humidity, and presumably human contact rates and co-infections; social studies highlighted environmental and dietary factors, with supernatural explanations. Conclusions: Efforts should focus on implementing multi-country, longitudinal seroprevalence and epidemiological studies, validating immune markers of protection, and improving surveillance, including more systematic molecular characterizations of the bacteria. Integrating climate and social factors into disease control strategies represents a high priority for optimizing the public health response and anticipating the geographic evolution of the African meningitis belt.

Published
2017
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19. Response Strategies against Meningitis Epidemics after Elimination of Serogroup A Meningococci, Niger

Author

Halima Boubacar Maïnassara, Juliette Paireau, Issa Idi, Jean-Paul Moulia Pelat, Odile Ouwe Missi Oukem-Boyer, Arnaud Fontanet, and Judith E. Mueller

Subjects
Meningitis, epidemics, Niger, surveillance, bacteria, vaccines, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

To inform epidemic response strategies for the African meningitis belt after a meningococcal serogroup A conjugate vaccine was introduced in 2010, we compared the effectiveness and efficiency of meningitis surveillance and vaccine response strategies at district and health area levels using various thresholds of weekly incidence rates. We analyzed reports of suspected cases from 3 regions in Niger during 2002–2012 (154,392 health area weeks), simulating elimination of serogroup A meningitis by excluding health area years with identification of such cases. Effectiveness was highest for health area surveillance and district vaccination (58–366 cases; thresholds 7–20 cases/100,000 doses), whereas efficiency was optimized with health area vaccination (5.6–7.7 cases/100,000 doses). District-level intervention prevented

Published
2015
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20. Timeliness of Yellow Fever Surveillance, Central African Republic

Author

Antoine Rachas, Emmanuel Nakouné, Julie Bouscaillou, Juliette Paireau, Benjamin Selekon, Dominique Senekian, Arnaud Fontanet, and Mirdad Kazanji

Subjects
yellow fever, viruses, epidemiology, public health, surveillance, Central African Republic, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

During January 2007–July 2012, a total of 3,220 suspected yellow fever cases were reported in the Central African Republic; 55 were confirmed and 11 case-patients died. Mean delay between onset of jaundice and case confirmation was 16.6 days. Delay between disease onset and blood collection could be reduced by increasing awareness of the population.

Published
2014
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21. Litchi–associated Acute Encephalitis in Children, Northern Vietnam, 2004–2009

Author

Juliette Paireau, Nguyen Hai Tuan, Rémi Lefrançois, Matthew R. Buckwalter, Ngu Duy Nghia, Nguyen Tran Hien, Olivier Lortholary, Sylvain Poirée, Jean-Claude Manuguerra, Antoine Gessain, Matthew L. Albert, Paul T. Brey, Phan Thi Nga, and Arnaud Fontanet

Subjects
Encephalitis, epidemics, disease outbreaks, epidemiology, risk factors, litchi, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

Since the end of the 1990s, unexplained outbreaks of acute encephalitis in children coinciding with litchi harvesting (May–July) have been documented in the Bac Giang Province in northern Vietnam. A retrospective ecologic analysis of data for 2004–2009 involving environmental, agronomic, and climatic factors was conducted to investigate the suspected association between the outbreaks and litchi harvesting. The clinical, biological, and immunologic characteristics of the patients suggested a viral etiology. The ecologic study revealed an independent association between litchi plantation surface proportion and acute encephalitis incidence: Incidence rate ratios were 1.52 (95% CI 0.90–2.57), 2.94 (95% CI 1.88–4.60), and 2.76 (95% CI 1.76–4.32) for second, third, and fourth quartiles, respectively, compared with the lowest quartile. This ecologic study confirmed the suspected association between incidence of acute encephalitis and litchi plantations and should be followed by other studies to identify the causative agent for this syndrome.

Published
2012
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22. Serogroup-Specific Characteristics of Localized Meningococcal Meningitis Epidemics in Niger 2002-2012 and 2015: Analysis of Health Center Level Surveillance Data.

Author

Halima Boubacar Maïnassara, Juliette Paireau, Issa Idi, Jean-François Jusot, Jean-Paul Moulia Pelat, Odile Ouwe Missi Oukem-Boyer, Arnaud Fontanet, and Judith E Mueller

Subjects
Medicine, Science
Abstract

To compare dynamics of localized meningitis epidemics (LE) by meningococcal (Nm) serogroup, we analyzed a surveillance database of suspected and laboratory-confirmed Nm cases from 373 health areas (HA) of three regions in Niger during 2002-2012 and one region concerned by NmC epidemics during 2015. We defined LE as HA weekly incidence rates of ≥20 suspected cases per 100,000 during ≥2 weeks and assigned the predominant serogroup based on polymerase chain reaction testing of cerebrospinal fluid. Among the 175 LE, median peak weekly incidence rate in LE due to NmA, W, X and C were 54, 39, 109 and 46 per 100,000, respectively. These differences impacted ability of the epidemic to be detected at the district level. While this analysis is limited by the small number of LE due to NmX (N = 4) and NmW (N = 5), further research should explore whether strategies for prevention and response to meningitis epidemics need to be adapted according to predominant meningococcal serogroups.

Published
2016
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23. Spatio-temporal factors associated with meningococcal meningitis annual incidence at the health centre level in Niger, 2004-2010.

Author

Juliette Paireau, Halima B Maïnassara, Jean-François Jusot, Jean-Marc Collard, Issa Idi, Jean-Paul Moulia-Pelat, Judith E Mueller, and Arnaud Fontanet

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

BACKGROUND:Epidemics of meningococcal meningitis (MM) recurrently strike the African Meningitis Belt. This study aimed at investigating factors, still poorly understood, that influence annual incidence of MM serogroup A, the main etiologic agent over 2004-2010, at a fine spatial scale in Niger. METHODOLOGY/PRINCIPAL FINDINGS:To take into account data dependencies over space and time and control for unobserved confounding factors, we developed an explanatory Bayesian hierarchical model over 2004-2010 at the health centre catchment area (HCCA) level. The multivariate model revealed that both climatic and non-climatic factors were important for explaining spatio-temporal variations in incidence: mean relative humidity during November-June over the study region (posterior mean Incidence Rate Ratio (IRR) = 0.656, 95% Credible Interval (CI) 0.405-0.949) and occurrence of early rains in March in a HCCA (IRR = 0.353, 95% CI 0.239-0.502) were protective factors; a higher risk was associated with the percentage of neighbouring HCCAs having at least one MM A case during the same year (IRR = 2.365, 95% CI 2.078-2.695), the presence of a road crossing the HCCA (IRR = 1.743, 95% CI 1.173-2.474) and the occurrence of cases before 31 December in a HCCA (IRR = 6.801, 95% CI 4.004-10.910). At the study region level, higher annual incidence correlated with greater geographic spread and, to a lesser extent, with higher intensity of localized outbreaks. CONCLUSIONS:Based on these findings, we hypothesize that spatio-temporal variability of MM A incidence between years and HCCAs result from variations in the intensity or duration of the dry season climatic effects on disease risk, and is further impacted by factors of spatial contacts, representing facilitated pathogen transmission. Additional unexplained factors may contribute to the observed incidence patterns and should be further investigated.

Published
2014
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24. Analysing spatio-temporal clustering of meningococcal meningitis outbreaks in Niger reveals opportunities for improved disease control.

Author

Juliette Paireau, Florian Girond, Jean-Marc Collard, Halima B Maïnassara, and Jean-François Jusot

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

BackgroundMeningococcal meningitis is a major health problem in the "African Meningitis Belt" where recurrent epidemics occur during the hot, dry season. In Niger, a central country belonging to the Meningitis Belt, reported meningitis cases varied between 1,000 and 13,000 from 2003 to 2009, with a case-fatality rate of 5-15%.Methodology/principal findingsIn order to gain insight in the epidemiology of meningococcal meningitis in Niger and to improve control strategies, the emergence of the epidemics and their diffusion patterns at a fine spatial scale have been investigated. A statistical analysis of the spatio-temporal distribution of confirmed meningococcal meningitis cases was performed between 2002 and 2009, based on health centre catchment areas (HCCAs) as spatial units. Anselin's local Moran's I test for spatial autocorrelation and Kulldorff's spatial scan statistic were used to identify spatial and spatio-temporal clusters of cases. Spatial clusters were detected every year and most frequently occurred within nine southern districts. Clusters most often encompassed few HCCAs within a district, without expanding to the entire district. Besides, strong intra-district heterogeneity and inter-annual variability in the spatio-temporal epidemic patterns were observed. To further investigate the benefit of using a finer spatial scale for surveillance and disease control, we compared timeliness of epidemic detection at the HCCA level versus district level and showed that a decision based on threshold estimated at the HCCA level may lead to earlier detection of outbreaks.Conclusions/significanceOur findings provide an evidence-based approach to improve control of meningitis in sub-Saharan Africa. First, they can assist public health authorities in Niger to better adjust allocation of resources (antibiotics, rapid diagnostic tests and medical staff). Then, this spatio-temporal analysis showed that surveillance at a finer spatial scale (HCCA) would be more efficient for public health response: outbreaks would be detected earlier and reactive vaccination would be better targeted.

Published
2012
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26. Vaccine effectiveness and duration of protection of COVID-19 mRNA vaccines against Delta and Omicron BA.1 symptomatic and severe COVID-19 outcomes in adults aged 50 years and over in France

Author

Cynthia Raissa Tamandjou Tchuem, Vincent Auvigne, Sophie Vaux, Charline Montagnat, Juliette Paireau, Stéphanie Monnier Besnard, Amélie Gabet, Nabil Benhajkassen, Yann Le Strat, Isabelle Parent Du Chatelet, and Daniel Levy-Bruhl

Subjects
Infectious Diseases, General Veterinary, General Immunology and Microbiology, Public Health, Environmental and Occupational Health, Molecular Medicine
Published
2023
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27. Retrieving the global distribution of the threshold of wind erosion from satellite data and implementing it into the Geophysical Fluid Dynamics Laboratory land–atmosphere model (GFDL AM4.0/LM4.0)

Author

Bing Pu, Paul Ginoux, Huan Guo, N. Christina Hsu, John Kimball, Beatrice Marticorena, Sergey Malyshev, Vaishali Naik, Norman T. O’Neill, Carlos Pérez García‐Pando, Juliette Paireau, Joseph M. Prospero, Elena Shevliakova, and Ming Zhao

Subjects
Geosciences (General)
Abstract

Dust emission is initiated when surface wind velocities exceed the threshold of wind erosion. Many dust models used constant threshold values globally. Here we use satellite products to characterize the frequency of dust events and land surface properties. By matching this frequency derived from Moderate Resolution Imaging Spectroradiometer (MODIS) Deep Blue aerosol products with surface winds, we are able to retrieve a climatological monthly global distribution of the wind erosion threshold (V(threshold)) over dry and sparsely vegetated surfaces. This monthly two-dimensional threshold velocity is then implemented into the Geophysical Fluid Dynamics Laboratory coupled land–atmosphere model (AM4.0/LM4.0). It is found that the climatology of dust optical depth (DOD) and total aerosol optical depth, surface PM10 dust concentrations, and the seasonal cycle of DOD are better captured over the “dust belt” (i.e., northern Africa and the Middle East) by simulations with the new wind erosion threshold than those using the default globally constant threshold. The most significant improvement is the frequency distribution of dust events, which is generally ignored in model evaluation. By using monthly rather than annual mean V(threshold), all comparisons with observations are further improved. The monthly global threshold of wind erosion can be retrieved under different spatial resolutions to match the resolution of dust models and thus can help improve the simulations of dust climatology and seasonal cycles as well as dust forecasting.

Published
2021
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29. Modelling the end of a Zero-COVID strategy using nirmatrelvir/ritonavir, vaccination and NPIs in Wallis and Futuna

Author

Antoine Brault, Cécile Tran-Kiem, Clément Couteaux, Valérie Olié, Juliette Paireau, Yazdan Yazdanpanah, Jade Ghosn, Guillaume Martin-Blondel, Paolo Bosetti, Simon Cauchemez, Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Collège Doctoral, Sorbonne Université (SU), Agence de Santé des îles Wallis & Futuna, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), Duchange, Nathalie, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Toulouse [Toulouse], and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
NPIs, SARS-CoV-2, Nirmatrelvir/ritonavir, Health Policy, Public Health, Environmental and Occupational Health, Paxlovid, Obstetrics and Gynecology, COVID-19, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Zero-COVID, Treatment, Psychiatry and Mental health, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Pediatrics, Perinatology and Child Health, Internal Medicine, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, Geriatrics and Gerontology, Antiviral, Vaccine
Abstract

International audience; Ending Zero-COVID is challenging, particularly when vaccine coverage is low. Considering Wallis and Futuna, a French Zero-COVID territory affected by reluctance to vaccination, low immunity and high levels of comorbidities, we investigate how targeted use of nirmatrelvir/ritonavir (brand name Paxlovid) can complement vaccination and non-pharmaceutical interventions (NPIs) and mitigate the epidemic rebound expected when Zero-COVID ends.We developed a discrete age-stratified compartmental model describing SARS-CoV-2 spread and healthcare impact once Wallis and Futuna reopens. It accounts for comorbidity risk groups (CRG), vaccine coverage (2 doses, 3 doses), the effectiveness of vaccines (recent or old injection), treatments and NPIs. In our baseline scenario, cases aged 65+ in intermediate/high CRG and 40+ in high CRG are eligible for treatment.FindingsThe epidemic is expected to start 13-20 days after reopening with a doubling time of 1·6-3·7 days. For medium transmission intensity (R0=5), 134 (115-156) hospital admissions are expected within 3 months, with no pharmaceutical measures. In our baseline scenario, admissions are reduced by 11%-21% if 50% of the target group receive treatment, with maximum impact when combined with NPIs and vaccination. The number of hospitalisations averted (HA) per patient treated (PT) is maximum when 65+ in high CRG are targeted (0·124 HA/PT), quickly followed by 65+ in intermediate/high CRG (0·097 HA/PT), and any 65+ (0·093 HA/PT). Expanding the target group increases both PT and HA, but marginal gains diminish.Modelling suggests that test and treat may contribute to the mitigation of epidemic rebounds at the end of Zero-COVID, particularly in populations with low immunity and high levels of comorbidities.

Published
2022
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30. Association between the COVID-19 pandemic and pertussis derived from multiple nationwide data sources, France, 2013 to 2020

Author

Soraya Matczak, Corinne Levy, Camille Fortas, Jérémie F Cohen, Stéphane Béchet, Fatima Aït El Belghiti, Sophie Guillot, Sabine Trombert-Paolantoni, Véronique Jacomo, Yann Savitch, Juliette Paireau, Sylvain Brisse, Nicole Guiso, Daniel Lévy-Bruhl, Robert Cohen, Julie Toubiana, Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV), Groupe de Pathologie Infectieuse Pédiatrique [Paris] (GPIP), Société Française de Pédiatrie (SFP), Centre de Recherche Clinique [Créteil] (CRC), Centre Hospitalier Intercommunal de Créteil (CHIC), Association Française de Pédiatrie Ambulatoire (AFPA), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre national de Référence de la Coqueluche et autres Bordetelloses - National Reference Center for Whooping Cough and other Bordetella infections (CNR), Institut Pasteur [Paris] (IP), Laboratoire CERBA [Saint Ouen l'Aumône], Eurofins Biomnis, Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)

Subjects
Epidemiology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Whooping Cough, Virology, Communicable Disease Control, Public Health, Environmental and Occupational Health, COVID-19, Humans, Information Storage and Retrieval, France, Child, Pandemics
Abstract

Background Interventions to mitigate the COVID-19 pandemic may impact other respiratory diseases. Aims We aimed to study the course of pertussis in France over an 8-year period including the beginning of the COVID-19 pandemic and its association with COVID-19 mitigation strategies, using multiple nationwide data sources and regression models. Methods We analysed the number of French pertussis cases between 2013 and 2020, using PCR test results from nationwide outpatient laboratories (Source 1) and a network of the paediatric wards from 41 hospitals (Source 2). We also used reports of a national primary care paediatric network (Source 3). We conducted a quasi-experimental interrupted time series analysis, relying on negative binomial regression models. The models accounted for seasonality, long-term cycles and secular trend, and included a binary variable for the first national lockdown (start 16 March 2020). Results We identified 19,039 pertussis cases from these data sources. Pertussis cases decreased significantly following the implementation of mitigation measures, with adjusted incidence rate ratios of 0.10 (95% CI: 0.04–0.26) and 0.22 (95% CI: 0.07–0.66) for Source 1 and Source 2, respectively. The association was confirmed in Source 3 with a median of, respectively, one (IQR: 0–2) and 0 cases (IQR: 0–0) per month before and after lockdown (p = 0.0048). Conclusions The strong reduction in outpatient and hospitalised pertussis cases suggests an impact of COVID-19 mitigation measures on pertussis epidemiology. Pertussis vaccination recommendations should be followed carefully, and disease monitoring should be continued to detect any resurgence after relaxation of mitigation measures.

Published
2022
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31. An ensemble model based on early predictors to forecast COVID-19 health care demand in France

Author

Juliette Paireau, Alessio Andronico, Nathanaël Hozé, Maylis Layan, Pascal Crépey, Alix Roumagnac, Marc Lavielle, Pierre-Yves Boëlle, Simon Cauchemez, Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Direction des maladies infectieuses - Infectious Diseases Division [Saint-Maurice], Santé publique France - French National Public Health Agency [Saint-Maurice, France], Centre de Recherches sur l'Action Politique en Europe (ARENES), Université de Rennes (UR)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), Recherche sur les services et le management en santé (RSMS), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Predict Services [Castelnau-le-Lez], Modélisation en pharmacologie de population (XPOP), Centre de Mathématiques Appliquées - Ecole Polytechnique (CMAP), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institut Polytechnique de Paris (IP Paris), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), We acknowledge financial support from the Investissement d’Avenir program, the Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases program (grant ANR-10-LABX-62- IBEID), Santé publique France, the INCEPTION project (PIA/ANR16-CONV-0005), the European Union’s Horizon 2020 research and innovation program under grants 101003589(RECOVER) and 874735 (VEO), AXA, Groupama, and EMERGEN, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), European Project: 874735,H2020-SC1-2019-Single-Stage-RTD,VEO(2020), Lassailly-Bondaz, Anne, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, Rapid European COVID-19 Emergency Response research - RECOVER - - H2020-SC1-PHE-CORONAVIRUS-20202020-02-14 - 2022-02-13 - 101003589 - VALID, and Versatile Emerging infectious disease Observatory - VEO - - H2020-SC1-2019-Single-Stage-RTD2020-01-01 - 2024-12-31 - 874735 - VALID

Subjects
MESH: Health Services Needs and Demand, Health Services Needs and Demand, MESH: Pandemics, Multidisciplinary, MESH: Humans, MESH: Delivery of Health Care, COVID-19, forecasting, MESH: Retrospective Studies, MESH: France, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Humans, MESH: COVID-19, ensemble model, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Delivery of Health Care, Pandemics, Retrospective Studies
Abstract

Short-term forecasting of the COVID-19 pandemic is required to facilitate the planning of COVID-19 health care demand in hospitals. Here, we evaluate the performance of 12 individual models and 19 predictors to anticipate French COVID-19-related health care needs from September 7, 2020, to March 6, 2021. We then build an ensemble model by combining the individual forecasts and retrospectively test this model from March 7, 2021, to July 6, 2021. We find that the inclusion of early predictors (epidemiological, mobility, and meteorological predictors) can halve the rms error for 14-d–ahead forecasts, with epidemiological and mobility predictors contributing the most to the improvement. On average, the ensemble model is the best or second-best model, depending on the evaluation metric. Our approach facilitates the comparison and benchmarking of competing models through their integration in a coherent analytical framework, ensuring that avenues for future improvements can be identified.

Published
2022
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32. Early chains of transmission of COVID-19 in France, January to March 2020

Author

Juliette Paireau, Alexandra Mailles, Catherine Eisenhauer, Franck de Laval, François Delon, Paolo Bosetti, Henrik Salje, Valérie Pontiès, Simon Cauchemez, Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'épidémiologie et de santé publique des armées [Marseille] (CESPA), Service de Santé des Armées, Institut des sciences de la santé publique [Marseille] (ISSPAM), University of Cambridge [UK] (CAM), Santé publique France, Haut-de-France [Lille, France], This work was supported by the LabEx Integrative Biology of Emerging Infectious Diseases (IBEID) (Grant Number ANR-10-LABX-62-IBEID), Santé Publique France, project Theracov, the INCEPTION project (PIA/ANR-16-CONV-0005), the European Union’s Horizon 2020 research and innovation program under grants 101003589 (RECOVER) and 874735 (VEO), and the National Research Agency (ANR) through the ANR-Flash call for COVID-19 (Grant ANR-20-COVI-0018)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-20-COVI-0018,TheraCoV,Dynamique virale au niveau individuel et populationnel : implications pour l'optimisation des stratégies antivirales(2020), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), European Project: 874735,H2020-SC1-2019-Single-Stage-RTD,VEO(2020), PAIREAU, Juliette, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, Dynamique virale au niveau individuel et populationnel : implications pour l'optimisation des stratégies antivirales - - TheraCoV2020 - ANR-20-COVI-0018 - COVID-19 - VALID, Rapid European COVID-19 Emergency Response research - RECOVER - - H2020-SC1-PHE-CORONAVIRUS-20202020-02-14 - 2022-02-13 - 101003589 - VALID, and Versatile Emerging infectious disease Observatory - VEO - - H2020-SC1-2019-Single-Stage-RTD2020-01-01 - 2024-12-31 - 874735 - VALID

Subjects
MESH: Pandemics, MESH: Humans, SARS-CoV-2, Epidemiology, transmission, Public Health, Environmental and Occupational Health, COVID-19, MESH: Retrospective Studies, contact tracing, secondary clinical attack rate, MESH: Contact Tracing, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Virology, Humans, MESH: COVID-19, superspreading, MESH: SARS-CoV-2, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, cluster, Pandemics, Retrospective Studies
Abstract

Introduction SARS-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. Aim To use contact-tracing data collected during the initial phase of the COVID-19 pandemic to better characterise SARS-CoV-2 transmission. Methods We 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. Results During 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. Conclusion This study increases knowledge of SARS-CoV-2 transmission, including the importance of superspreading events during the onset of the pandemic.

Published
2022
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33. Impact of booster vaccination on the control of COVID-19 Delta wave in the context of waning immunity: application to France in the winter 2021/22

Author

Paolo Bosetti, Cécile Tran Kiem, Alessio Andronico, Juliette Paireau, Daniel Levy-Bruhl, Lise Alter, Arnaud Fontanet, Simon Cauchemez, Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Collège Doctoral, Sorbonne Université (SU), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Haute Autorité de Santé [Saint-Denis La Plaine] (HAS), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Université Paris Cité (UPCité)-Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Pasteur-Cnam Risques infectieux et émergents (PACRI), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité), We acknowledge financial support from the Investissement d’Avenir program, the Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases program (grant ANR-10-LABX-62-IBEID), HAS, Santé Publique France, the EMERGEN project (ANRS0151), the INCEPTION project (PIA/ANR-16-CONV-0005), the European Union’s Horizon 2020 research and innovation program under grant 101003589 (RECOVER) and 874735 (VEO), AXA and Groupama., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), European Project: 874735,H2020-SC1-2019-Single-Stage-RTD,VEO(2020), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), European Project: 874735,VEO, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Université Paris Cité (UPC)-Pasteur-Cnam Risques infectieux et émergents (PACRI), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Paris Cité (UPC)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM), and HESAM Université (HESAM)-HESAM Université (HESAM)-Université Paris Cité (UPC)

Subjects
0303 health sciences, COVID-19 Vaccines, SARS-CoV-2, Epidemiology, Vaccination, Immunization, Secondary, Public Health, Environmental and Occupational Health, COVID-19, 3. Good health, modelling, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Seasons, 030212 general & internal medicine, Rapid Communication, 030304 developmental biology
Abstract

Europe has experienced a large COVID-19 wave caused by the Delta variant in winter 2021/22. Using mathematical models applied to Metropolitan France, we find that boosters administered to ≥ 65, ≥ 50 or ≥ 18 year-olds may reduce the hospitalisation peak by 25%, 36% and 43% respectively, with a delay of 5 months between second and third dose. A 10% reduction in transmission rates might further reduce it by 41%, indicating that even small increases in protective behaviours may be critical to mitigate the wave.

Published
2022
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34. Evaluating and optimizing the use of diagnostics during epidemics: Application to the 2017 plague outbreak in Madagascar

Author

Quirine Bosch, Voahangy Andrianaivoarimanana, Beza Ramasindrazana, Guillain Mikaty, Rado JL Rakotonanahary, Birgit Nikolay, Soloandry Rahajandraibe, Maxence Feher, Quentin Grassin, Juliette Paireau, Soanandrasana Rahelinirina, Rindra Randremanana, Feno Rakotoarimanana, Marie Melocco, Voahangy Rasolofo, Javier Pizarro-Cerda, Anne-Sophie Le Guern, Eric Bertherat, Maherisoa Ratsitorahina, Andre Spiegel, Laurence Baril, Minoarisoa Rajerison, and Simon Cauchemez

Abstract

During outbreaks, the lack of diagnostic “gold standard” can mask the true burden of infection in the population and hamper the allocation of resources required for control. Here, we present an analytical framework to evaluate and optimize the use of diagnostics when multiple yet imperfect diagnostic tests are available. We apply it to laboratory results of 2,136 samples, analyzed with three diagnostic tests (based on up to seven diagnostic outcomes), collected during the 2017 pneumonic (PP) and bubonic plague (BP) outbreak in Madagascar, which was unprecedented both in the number of notified cases, clinical presentation, and spatial distribution. The extent of this outbreaks has however remained unclear due to non-optimal assays. Using latent class methods, we estimate that 7%-15% of notified cases were Yersinia pestis-infected. Overreporting was highest during the peak of the outbreak and lowest in the rural settings endemic to Yersinia pestis. Molecular biology methods offered the best compromise between sensitivity and specificity. The specificity of the rapid diagnostic test was relatively low (PP: 82%, BP: 85%), particularly for use in contexts with large quantities of misclassified cases. Comparison with data from a subsequent seasonal Yersinia pestis outbreak in 2018 reveal better test performance (BP: specificity 99%, sensitivity: 91%), indicating that factors related to the response to a large, explosive outbreak may well have affected test performance. We used our framework to optimize the case classification and derive consolidated epidemic trends. Our approach may help reduce uncertainties in other outbreaks where diagnostics are imperfect.

Published
2021
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35. The epidemiology of hepatitis delta virus infection in Cameroon

Author

Juliette Paireau, Mathurin Cyrille Tejiokem, Jacques Pépin, Richard Njouom, Arnaud Fontanet, Guillaume Lachenal, Simon Cauchemez, Gaëtan Texier, Camille Besombes, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Médialab (Sciences Po) (Médialab), Sciences Po (Sciences Po), Université de Sherbrooke (UdeS), This study was funded by the Agence Nationale de Recherche sur le Sida et les Hépatites Virales (grant ANRS 12289) and got support from the INCEPTION project (PIA/ANR-16-CONV-0005)., ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and médialab (Sciences Po) (médialab)

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, HBsAg, Adolescent, viruses, Hepatitis C virus, medicine.disease_cause, Virus, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Epidemiology, Prevalence, medicine, Humans, Cameroon, Geography, Medical, Hepatitis B virus, Family Characteristics, biology, Transmission (medicine), business.industry, Gastroenterology, virus diseases, biochemical phenomena, metabolism, and nutrition, Middle Aged, medicine.disease, [SDE.ES]Environmental Sciences/Environmental and Society, Hepatitis D, Virology, 3. Good health, 030104 developmental biology, biology.protein, Female, 030211 gastroenterology & hepatology, Hepatitis Delta Virus, Antibody, business
Abstract

ObjectiveTo investigate the distribution and risk factors of hepatitis delta virus (HDV) infection in Cameroon.DesignWe tested for hepatitis B virus (HBV) surface antigen (HBsAg) and anti-HDV antibody 14 150 samples collected during a survey whose participants were representative of the Cameroonian adult population. The samples had already been tested for hepatitis C virus and HIV antibodies.ResultsOverall, 1621/14 150 (weighted prevalence=11.9%) participants were HBsAg positive, among whom 224/1621 (10.6%) were anti-HDV positive. In 2011, the estimated numbers of HBsAg positive and HDV seropositives were 1 160 799 and 122 910 in the 15–49 years age group, respectively. There were substantial regional variations in prevalence of chronic HBV infection, but even more so for HDV (from 1% to 54%). In multivariable analysis, HDV seropositivity was independently associated with living with an HDV-seropositive person (OR=8.80; 95% CI: 3.23 to 24.0), being HIV infected (OR=2.82; 95% CI: 1.32 to 6.02) and living in the South (latitude ConclusionWe found evidence for effective intra-household transmission of HDV in Cameroon. We also identified large differences in prevalence between regions, with cases concentrated in forested areas close to the Equator, as described in other tropical areas. The reasons underlying these geographical variations in HDV prevalence deserve further investigation.

Published
2020
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36. Association between the COVID-19 pandemic and pertussis in France using multiple nationwide data sources

Author

Jérémie F. Cohen, Fatima Aït El Belghiti, Juliette Paireau, Camille Fortas, Yann Savitch, Sylvain Brisse, Soraya Matczak, Julie Toubiana, Stéphane Béchet, Nicole Guiso, Robert M. Cohen, Sophie Guillot, Daniel Levy Bruhl, Sabine Trombert, Véronique Jacomo, and Corinne Levy

Subjects
medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Pcr test, Environmental health, Epidemiology, Pandemic, medicine, Psychological intervention, Pertussis vaccination, Disease, Disease monitoring, business
Abstract

BackgroundInterventions to mitigate coronavirus disease 19 (COVID-19) pandemic may impact other respiratory diseases such as pertussis. We aimed to study the course of pertussis in France over an 8-year period and its association with COVID-19 mitigation strategies, using multiple nationwide data sources.MethodsWe analyzed the number of French pertussis cases between 2013 and 2020, using the PCR test results from nationwide outpatient laboratories (Source 1) and the pediatric network of 41 hospitals (Source 2), and using the reports of an office-based pediatric national network (Source 3). We conducted a quasi-experimental interrupted time-series analysis, relying on negative binomial regression models. The models accounted for seasonality, long-term cycles, and secular trend, and included a binary variable for the first national lockdown (ordered on March 16, 2021).ResultsWe identified 19,039 cases of pertussis from the three data sources during the study period. There was a significant decrease of pertussis cases following the implementation of mitigation measures, with adjusted incidence rate ratios of 0.102 (95% CI 0.040-0.256) and 0.216 (95% CI 0.071-0.656) for Source 1 and Source 2, respectively. The association was confirmed in Source 3 (median of 1 [IQR 0-2] vs. 0 [IQR 0-0] pertussis cases per month before and after lockdown, respectively, p=0.0048).ConclusionThe drastic reduction of outpatient and hospitalized cases of pertussis strongly suggests an impact of COVID-19 mitigation measures and their consequences on pertussis epidemiology. Pertussis vaccination recommendations should be carefully followed, and disease monitoring should be continued to detect any resurgence after relaxation of mitigation measures.FundingThere was no specific funding for the study.

Published
2021
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37. Benefits and risks associated with different uses of the COVID-19 vaccine Vaxzevria: a modelling study, France, May to September 2021

Author

Lise Alter, Daniel Lévy-Bruhl, Cécile Tran Kiem, Pierre-Yves Boëlle, Paolo Bosetti, Simon Cauchemez, Juliette Paireau, Alessio Andronico, Arnaud Fontanet, Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Collège Doctoral, Sorbonne Université (SU), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Haute Autorité de Santé [Saint-Denis La Plaine] (HAS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), We acknowledge financial support from the Investissement d’Avenir programme, the Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases programme (grant ANR-10-LABX-62-IBEID), and the European Union’s Horizon 2020 research and innovation programme under grants 101003589 (RECOVER) and 874735 (VEO), AXA, Groupama, INCEPTION project (PIA/ANR-16-CONV-0005)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), European Project: 874735,H2020-SC1-2019-Single-Stage-RTD,VEO(2020), Gestionnaire, HAL Sorbonne Université 5, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, Rapid European COVID-19 Emergency Response research - RECOVER - - H2020-SC1-PHE-CORONAVIRUS-20202020-02-14 - 2022-02-13 - 101003589 - VALID, Versatile Emerging infectious disease Observatory - VEO - - H2020-SC1-2019-Single-Stage-RTD2020-01-01 - 2024-12-31 - 874735 - VALID, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Collège doctoral [Sorbonne universités], Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and European Project: 874735,VEO

Subjects
2019-20 coronavirus outbreak, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Epidemiology, Vaxzevria, 030204 cardiovascular system & hematology, Risk Assessment, Young Adult, 03 medical and health sciences, 0302 clinical medicine, vaccine, Virology, Environmental health, Humans, Medicine, benefit-risk balance, 030212 general & internal medicine, Young adult, Adverse effect, thrombosis, SARS-CoV-2, business.industry, Public Health, Environmental and Occupational Health, COVID-19, AstraZeneca, 3. Good health, Metropolitan France, Vaccination, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Risk of death, business, Risk assessment, Rapid Communication
Abstract

International audience; Thrombosis with thrombocytopenia (TTS) has been identified as a rare adverse event following COVID-19 vaccination with Vaxzevria. We modelled the benefits and risks of Vaxzevria distribution from May to September 2021 in metropolitan France where other vaccines are available, considering French hospitalisation data and European data on TTS. Across different scenarios, benefits of Vaxzevria distribution in people 55 years and older exceeded the risk of death from COVID-19. In young adults, risks were at least of similar magnitude as benefits.

Published
2021
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38. Exposures associated with SARS-CoV-2 infection in France: A nationwide online case-control study

Author

Cassandre Von Platen, Simon Galmiche, Alexandra Maurizot, Sophie Martin, Faïza Omar, Laura Schaeffer, Olivia Chény, Juliette Paireau, Annika Dinis, Alexandra Septfons, Rebecca Grant, Fabrice Carrat, Carole Blanc, Simon Cauchemez, Arnaud Fontanet, Alexandra Mailles, Christophe David, Tiffany Charmet, Daniel Lévy-Bruhl, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Sorbonne Université (SU), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris], Caisse Nationale d'Assurance Maladie des Travailleurs salariés (CNAMTS), Ministère de l'économie et des finances, Ipsos, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur, Research & Action Emerging Infectious Diseases (REACTing), Fondation de France (Alliance' Tous unis contre le virus')., We would like to thank the AC transmission group of REACTing (Research & Action Emerging Infectious Diseases) for helpful discussions about the study design, Xavier Duval and Sarah Tubiana for pilot testing the questionnaire, and Nathalie Bajos and Dominique Costagliola for their critical review of an earlier version of the manuscript., Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), and Limouzin, Cécile

Subjects
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], 030231 tropical medicine, Computer-assisted web interviewing, 03 medical and health sciences, 0302 clinical medicine, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], Environmental health, Internal Medicine, Medicine, Infection control, 030212 general & internal medicine, Sports activity, [MATH.MATH-ST] Mathematics [math]/Statistics [math.ST], business.industry, Health Policy, Risk of infection, Case-control study, 3. Good health, [SDV] Life Sciences [q-bio], Increased risk, Oncology, Public aspects of medicine, RA1-1270, business, Research Paper
Abstract

Summary: Background: We aimed to assess the role of different setting and activities in acquiring SARS-CoV-2 infection. Methods: In this nationwide case-control study, cases were SARS-CoV-2 infected adults recruited between 27 October and 30 November 2020. Controls were individuals from the Ipsos market research database matched to cases by age, sex, region, population density and time period. Participants completed an online questionnaire on recent activity-related exposures. Findings: Among 3426 cases and 1713 controls, in multivariable analysis, we found an increased risk of infection associated with any additional person living in the household (adjusted-OR: 1•16; 95%CI: 1•11-1•21); having children attending day-care (aOR: 1•31; 95%CI: 1•02-1•62), kindergarten (aOR: 1•27; 95%CI: 1•09-1•45), middle school (aOR: 1•30; 95%CI: 1•15-1•47), or high school (aOR: 1•18; 95%CI: 1•05-1•34); with attending professional (aOR: 1•15; 95%CI: 1•04-1•26) or private gatherings (aOR: 1•57; 95%CI: 1•45-1•71); and with having frequented bars and restaurants (aOR: 1•95; 95%CI: 1•76-2•15), or having practiced indoor sports activities (aOR: 1•36; 95%CI: 1•15-1•62). We found no increase in risk associated with frequenting shops, cultural or religious gatherings, or with transportation, except for carpooling (aOR: 1•47; 95%CI: 1•28-1•69). Teleworking was associated with decreased risk of infection (aOR: 0•65; 95%CI: 0•56-0•75). Interpretation: Places and activities during which infection prevention and control measures may be difficult to fully enforce were those with increased risk of infection. Children attending day-care, kindergarten, middle and high schools, but not primary schools, were potential sources of infection for the household. Funding: Institut Pasteur, Research & Action Emerging Infectious Diseases (REACTing), Fondation de France (Alliance” Tous unis contre le virus”).

Published
2021
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39. Do not neglect SARS-CoV-2 hospitalization and fatality risks in the middle-aged adult population

Author

Xavier de Lamballerie, Daniel Lévy-Bruhl, Mathilde Touvier, Simon Cauchemez, Juliette Paireau, Gianluca Severi, Fabrice Carrat, Nathanael Lapidus, Marie Zins, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Paris (UP), Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Paris (UP), The SAPRIS-SERO study was supported by Agence Nationale de la Recherche, #ANR-10-COHO-06, Fondation pour la Recherche Médicale (#20RR052-00), Inserm (Institut National de la Santé et de la Recherche Médicale), #C20-26., The SAPRIS-SERO study group Sofiane Kab, Adeline Renuy, Stephane Le-Got, Celine Ribet, Emmanuel Wiernik, Marcel Goldberg, Marie Zins (Constances cohort). Fanny Artaud, Pascale Gerbouin-Rérolle, Mélody Enguix, Camille Laplanche, Roselyn Gomes-Rima, Lyan Hoang, Emmanuelle Correia, Alpha Amadou Barry, Nadège Senina, Gianluca Severi (E3N-E4 N cohort). Fabien Szabo de Edelenyi, Nathalie Druesne-Pecollo, Younes Esseddik, Serge Hercberg, Mathilde Touvier (NutriNet-Santé cohort). Marie-Aline Charles, Pierre-Yves Ancel, Valérie Benhammou, Anass Ritmi, Laetitia Marchand, Cecile Zaros, Elodie Lordmi, Adriana Candea, Sophie de Visme, Thierry Simeon, Xavier Thierry, Bertrand Geay, Marie-Noelle Dufourg, Karen Milcent (Epipage2 and Elfe child cohorts). Clovis Lusivika-Nzinga, Gregory Pannetier, Nathanael Lapidus, Frédéric Chau, Isabelle Goderel, Céline Dorival, Jérôme Nicol, Fabrice Carrat (IPLESP–methodology and coordinating data center). Cindy Lai, Hélène Esperou, Sandrine Couffin-Cadiergues (Inserm). Jean-Marie Gagliolo (Institut de Santé Publique). Hélène Blanché, Jean-Marc Sébaoun, Jean-Christophe Beaudoin, Laetitia Gressin, Valérie Morel, Ouissam Ouili, Jean-François Deleuze (Fondation Jean-Dausset, CEPH-Biobank). Stéphane Priet, Paola Mariela Saba Villarroel, Toscane Fourié, Souand Mohamed Ali, Abdenour Amroun, Morgan Seston, Nazli Ayhan, Boris Pastorino, Xavier de Lamballerie (Unité des Virus Émergents)., ANR-10-COHO-0006,E4N,Etude Epidémiologique des Enfants de femmes de l'Education Nationale(2010), HAL-SU, Gestionnaire, Cohortes - Etude Epidémiologique des Enfants de femmes de l'Education Nationale - - E4N2010 - ANR-10-COHO-0006 - COHO - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Firenze = University of Florence (UniFI), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris Cité (UPCité), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité)

Subjects
Male, Adult, Age-Specific Death Rate, Short Communication, media_common.quotation_subject, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Population, Risk Assessment, Neglect, Young Adult, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pandemic, Humans, Medicine, 030212 general & internal medicine, Young adult, education, Aged, 030304 developmental biology, media_common, Aged, 80 and over, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, education.field_of_study, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, business.industry, SARS-CoV-2, Incidence (epidemiology), COVID-19, Middle Aged, 3. Good health, Hospitalization, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Relative risk, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Age Specific Death Rate, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business, Risk assessment, Demography
Abstract

Highlights • During the first wave of the pandemic in France, the estimated overall infection hospitalization ratio (IHR, probability of hospitalization in infected adults) was 2.7%. • At that time, the estimated overall infection fatality ratio (IFR, probability of death in infected adults) was 0.49%. • Both IHR and IFR were higher in men. • IHR approximately doubled every 10 years while IFR doubled every 5 years. • IFR should not be neglected, even in young and middle-aged adults (0.042% in individuals aged 40-50 years)., Objectives This study aimed at estimating the SARS-CoV-2 infection hospitalization (IHR) and infection fatality ratios (IFR) in France. Patients and methods A serosurvey was conducted in 9782 subjects from the two French regions with the highest incidence of COVID-19 during the first wave of the pandemic and coupled with surveillance data. Results IHR and IFR were 2.7% and 0.49% overall. Both were higher in men and increased exponentially with age. The relative risks of hospitalization and death were 2.1 (95% CI: 1.9-2.3) and 3.8 (2.4-4.2) per 10-year increase, meaning that IHR and IFR approximately doubled every 10 and 5 years, respectively. They were dramatically high in the very elderly (80-90 years: IHR: 26%, IFR: 9.2%), and also substantial in younger adults (40-50 years: IHR: 0.98%, IFR: 0.042%). Conclusions These findings support the need for comprehensive preventive measures to help reduce the spread of the virus, even in young or middle-aged adults.

Published
2021
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40. Adherence and sustainability of interventions informing optimal control against COVID-19 pandemic

Author

Vittoria Colizza, Juliette Paireau, Harold Noel, Simon Cauchemez, Laura Di Domenico, François Beck, Daniel Lévy-Bruhl, Pascal Crépey, Pierre-Yves Boëlle, Chiara Poletto, and Chiara E. Sabbatini

Subjects
Distress, Coronavirus disease 2019 (COVID-19), High intensity, Social distance, Sustainability, Development economics, Pandemic, Psychological intervention, Duration (project management), Psychology
Abstract

After one year of stop-and-go COVID-19 mitigation, some European countries still experience sustained viral circulation due to the B.1.1.7 variant. As the prospect of phasing out this stage through vaccination draws closer, it is critical to balance the efficacy of long-lasting interventions and their impact on the quality of life. Focusing on the current situation in France, we show that moderate interventions require a much longer time to achieve the same result as high intensity lockdowns, with the additional risk of deteriorating control as adherence wanes. Integrating intensity and duration of social distancing in a data-driven “distress” index, we show that shorter strict lockdowns are largely more performant than longer moderate lockdowns, for similar intermediate distress and infringement on individual freedom. Our study shows that favoring milder interventions over more stringent short approaches on the basis of perceived acceptability could be detrimental in the long term, especially with waning adherence.

Published
2021
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41. Effect of change in vaccine schedule on pertussis epidemiology in France: a modelling and serological study

Author

Julie Toubiana, Muhamed-Kheir Taha, Soraya Matczak, Daniel Lévy-Bruhl, Simon Cauchemez, Juliette Paireau, Henrik Salje, Sophie Guillot, Sylvain Brisse, Véronique Jacomo, Fatima Aït El Belghiti, and Sabine Trombert-Paolantoni

Subjects
Pertussis Vaccine, Schedule, Pediatrics, medicine.medical_specialty, Booster (rocketry), business.industry, Whooping Cough, Immunization, Secondary, Bayes Theorem, Diphtheria-Tetanus-acellular Pertussis Vaccines, Antibodies, Bacterial, Serology, Clinical trial, Vaccination, Infectious Diseases, Pertussis Toxin, Immunity, Relative risk, Epidemiology, medicine, Humans, business, Child
Abstract

Summary Background In April–May, 2013, France modified its pertussis vaccination schedule, which uses the acellular pertussis vaccine, from three primary doses at 2, 3, and 4 months of age and a first booster at 16–18 months of age (former schedule) to two primary doses at 2 and 4 months of age and a first booster at 11 months of age (new schedule). We aimed to assess the subsequent effect of the vaccine schedule change on pertussis epidemiology in France. Methods In this modelling study, using data collected between Jan 1, 2012, and Dec 31, 2019, from French national surveillance sources, we analysed the PCR test results of nasopharyngeal swabs collected from symptomatic outpatients aged 2–20 years with suspected pertussis. We developed a negative binomial regression model for the number of confirmed pertussis cases by year and age to assess the relative risks of pertussis depending on vaccine schedule. The linear predictor included the year, the age group, the population size, and a proxy of waning immunity. We tested different models in which waning immunity could vary with vaccine schedule and type of primary vaccine. The models were fitted to the 2012–18 data via Bayesian Markov chain Monte Carlo sampling, and the 2019 data were left out for external model validation. We also compared the anti-pertussis toxin (PT) antibody concentrations in leftover sera from children not tested for pertussis or recent respiratory tract infection aged 2–5 years born before and after the vaccine schedule change. Findings We collected data on 7493 confirmed cases of pertussis. The model that best fitted the 2012–18 epidemiological data supported a faster waning of immunity following vaccination with the new vaccine schedule. 3 years after vaccination, the risk of developing pertussis was 1·7 (95% CI 1·4–2·0) times higher for children vaccinated according to the new schedule than those vaccinated according to the former schedule. The model correctly predicted the age distribution of cases in 2019. Geometric mean concentrations (GMC) of anti-PT IgG were 50% lower in children aged 2 years vaccinated with the new schedule (GMC=5·85 IU/mL [95% CI 4·08–8·39]) than in children of the same age vaccinated with the former schedule (GMC=11·62 IU/mL [95% CI 9·05–14·92]; p=0·0016), and 43% lower in children aged 3 years vaccinated with the new schedule (GMC=3·88 IU/mL [95% CI 2·82–5·34]) than those with the former schedule (GMC=6·80 IU/mL [95% CI 4·77–9·70]; p=0·026). Interpretation A shorter-lived protection induced by the new vaccine schedule recommended in France since 2013 is associated with an increase of pertussis cases in children aged 2–5 years. If similar findings are observed in other countries and clinical trials, these findings should be considered in future pertussis vaccination policies. Funding INCEPTION, Labex-IBEID, Institut Pasteur, and Sante Publique France.

Published
2021

42. Colder and drier winter conditions are associated with greater SARS-CoV-2 transmission: a regional study of the first epidemic wave in north-west hemisphere countries

Author

Eva Legendre, Jordi Landier, Stanislas Rebaudet, Arnaud Fontanet, Laurent Le Hot, Simon Cauchemez, Juliette Paireau, and Jean Gaudart

Subjects
Geography, Transmission (mechanics), law, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pandemic, Humidity, Context (language use), Population density, Basic reproduction number, Transmissibility (vibration), Demography, law.invention
Abstract

Higher transmissibility of SARS-CoV-2 in cold and dry weather conditions has been hypothesized since the onset of the COVID-19 pandemic but the level of epidemiological evidence remains low.During the first wave of the pandemic, Spain, Italy, France, Portugal, Canada and USA presented an early spread, a heavy COVID-19 burden, and low initial public health response until lockdowns. In a context when testing was limited, we calculated the basic reproduction number (R0) in 63 regions from the growth in regional death counts. After adjusting for population density, early spread of the epidemic, and age structure, temperature and humidity were negatively associated to SARS-CoV-2 transmissibility. A reduction of mean absolute humidity by 1g/m3 was associated with a 0.15-unit increase of R0. Below 10°C, a temperature reduction of 1°C was associated with a 0.16-unit increase of R0.Our results confirm a dependency of SARS-CoV-2 transmissibility to weather conditions in the absence of control measures during the first wave. The transition from summer-to winter-like conditions likely contributed to the intensification of the second wave in north-west hemisphere countries. Adjustments of the levels of social mobility restrictions need to account for increased SARS-CoV-2 transmissibility in winter conditions.

Published
2021
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43. Monitoring the proportion infected by SARS-CoV-2 from age-stratified hospitalisation and serological data

Author

Daniel Lévy-Bruhl, Mathilde Touvier, Marie Zins, Juliette Paireau, Henrik Salje, Cécile Tran Kiem, Gianluca Severi, Fabrice Carrat, Xavier de Lamballerie, Nathanaël Hozé, Simon Cauchemez, and Nathanael Lapidus

Subjects
Metropolitan France, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Seroprevalence, Medicine, Joint analysis, business, Demography, Serology
Abstract

BackgroundRegional monitoring of the proportion infected by SARS-CoV-2 is important to guide local management of the epidemic, but is difficult in the absence of regular nationwide serosurveys.MethodsWe developed a method to reconstruct in real-time the proportion infected by SARS-CoV-2 and the proportion of infections being detected from the joint analysis of age-stratified seroprevalence, hospitalisation and case data. We applied our approach to the 13 French metropolitan regions.FindingsWe estimate that 5.7% [5.1%-6.4%] of adults in metropolitan France had been infected by SARS-CoV-2 by May 2020. This proportion remained stable until August and increased to 12.6% [11.2%-14.3%] by the end of November. With 23.8% [21.2%-26.8%] infected in the Paris region compared to 4.0% [3.5% - 4.6%] in Brittany, regional variations remained large (Coefficient of Variation CV: 0.53) although less so than in May (CV: 0.74). The proportion infected was twice higher (17.6% [13.4%-22.7%]) in 20-49 y.o. than in 50+ y.o (8.0% [5.7% - 11.5%]). Forty percent [33.7% - 45.4%] of infections in adults were detected in June-August compared to 55.7% [48.7% - 63.1%] in September-November. Our method correctly predicted seroprevalence in 11 regions in which only hospitalisation data were used.InterpretationIn the absence of contemporary serosurvey, our real-time monitoring indicates that the proportion infected by SARS-CoV-2 may be above 20% in some French regions.FundingEU RECOVER, ANR, Fondation pour la Recherche Médicale, Inserm.

Published
2021
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44. Comparing the age and sex trajectories of SARS-CoV-2 morbidity with other respiratory pathogens points to potential immune mechanisms

Author

Bruno Hubert, Simon Cauchemez, C. Jessica E. Metcalf, Juliette Paireau, Megan O'Driscoll, Henrik Salje, Isabelle Pontais, Mathilde Pivette, and Derek A. T. Cummings

Subjects
Adult life, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, Medicine, Immunosenescence, Age and sex, business, Health outcomes, Acquired immune system, Immune mechanisms, Respiratory pathogens
Abstract

Comparing age and sex differences in SARS-CoV-2 hospitalization and mortality with influenza and other health outcomes opens the way to generating hypotheses as to the underlying mechanisms, building on the extraordinary advances in immunology and physiology that have occurred over the last year. Notable departures in health outcomes starting around puberty suggest that burdens associated with influenza and other causes are reduced relative to the two emergent coronaviruses over much of adult life. Two possible hypotheses could explain this: protective adaptive immunity for influenza and other infections, or greater sensitivity to immunosenescence in the coronaviruses. Comparison of sex differences suggest an important role for adaptive immunity; but immunosenescence might also be relevant, if males experience faster immunosenescence. Involvement of the renin-angiotensin-system in SARS-CoV-2 infection might drive high sensitivity to disruptions of homeostasis. Overall, these results highlight the long tail of vulnerability in the age profile relevant to the emergent coronaviruses, which more transmissible variants have the potential to uncover at the younger end of the scale, and aging populations will expose at the other end of the scale.

Published
2021
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45. Monitoring the Proportion Infected by SARS-CoV-2 from Age-Stratified Hospitalisation and Serological Data

Author

Juliette Paireau, Mathilde Touvier, Gianluca Severi, Fabrice Carrat, Nathanael Lapidus, Marie Zins, Henrik Salje, Daniel Lévy-Bruhl, Simon Cauchemez, Nathanaël Hozé, Xavier de Lamballerie, and Cécile Tran Kiem

Subjects
Competing interests, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Medicine, Seroprevalence, Joint analysis, business, Serology, Demography
Abstract

Background: Regional monitoring of the proportion infected by SARS-CoV-2 is important to guide local management of the epidemic, but is difficult in the absence of regular nationwide serosurveys. Methods: We developed a method to reconstruct in real-time the proportion infected by SARS-CoV-2 and the proportion of infections being detected from the joint analysis of age-stratified seroprevalence, hospitalisation and case data. We applied our approach to the 13 French metropolitan regions. Findings: We estimate that 5.7% [5.1%-6.4%] of adults in metropolitan France had been infected by SARS-CoV-2 by May 2020. This proportion remained stable until August and increased to 12.6% [11.2%-14.3%] by the end of November. With 23.8% [21.2%-26.8%] infected in the Paris region compared to 4.0% [3.5% - 4.6%] in Brittany, regional variations remained large (Coefficient of Variation CV: 0.53) although less so than in May (CV: 0.74). The proportion infected was twice higher (17.6% [13.4%-22.7%]) in 20-49 y.o. than in 50+ y.o (8.0% [5.7% - 11.5%]). Forty percent [33.7% - 45.4%] of infections in adults were detected in June-August compared to 55.7% [48.7% - 63.1%] in September-November. Our method correctly predicted seroprevalence in 11 regions in which only hospitalisation data were used. Interpretation: In the absence of contemporary serosurvey, our real-time monitoring indicates that the proportion infected by SARS-CoV-2 may be above 20% in some French regions. Funding Statement: EU RECOVER, ANR, Fondation pour la Recherche Medicale, Inserm. Declaration of Interests: Prof Fabrice Carrat reports personal fees from Imaxio and Sanofi, outside the submitted work. The other authors declare no competing interests.

Published
2021
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46. Impact of Vaccine Schedule Change on Pertussis Epidemiology in France: A Modelling and Serological Study

Author

Henrik Salje, Sophie Guillot, Daniel Lévy-Bruhl, Julie Toubiana, Sylvain Brisse, Muhamed-Kheir Taha, Soraya Matczak, Sabine Trombert-Paolantoni, Fatima Aït El Belghiti, Véronique Jacomo, Simon Cauchemez, Juliette Paireau, Direction des maladies infectieuses - Infectious Diseases Division [Saint-Maurice], Santé publique France - French National Public Health Agency [Saint-Maurice, France], Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre national de Référence de la Coqueluche et autres Bordetelloses - National Reference Center for Whooping Cough and other Bordetella infections (CNR), Infections respiratoires et vaccination [Saint-Maurice], Département de Pédiatrie et maladies infectieuses [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire CERBA [Saint Ouen l'Aumône], Eurofins Biomnis, Infections Bactériennes Invasives - Invasive Bacterial Infections, Centre National de Référence des Méningocoques et Haemophilus influenzae - National Reference Center Meningococci and Haemophilus influenzae (CNR), University of Cambridge [UK] (CAM), This project was funded by the INCEPTION interdisciplinary project at Institut Pasteur, Understanding whooping cough resurgence in Europe by combining genomic, epidemiological, and sociological approaches (French Government Investissements d'Avenir grant ANR-16-CONV-0005). This work also received financial support from the French Government's Investissement d'Avenir programme, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases (grant n_ANR-10-LABX-62-IBEID). Institutional support was provided by an Institut Pasteur and Santé publique France grant to SB. SM was supported by a PhD grant from Fondation pour la Recherche Médicale. We thank Martin Chalumeau (CRESS, INSERM, Paris, France), for his contributions to the serological study., ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), and Institut Pasteur [Paris]-Université Paris Cité (UPC)

Subjects
medicine.medical_specialty, Booster dose, medicine.disease, Institutional review board, Helsinki declaration, [STAT]Statistics [stat], Vaccination, Schedule (workplace), Informed consent, Family medicine, Epidemiology, medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Whooping cough
Abstract

Background: In 2013, France modified its pertussis vaccination schedule to remove one dose at 3 months of age and change the age of the booster dose from 16 to 11 months. We aimed to assess the subsequent impact on pertussis epidemiology in France. Methods: We analysed the PCR test results of nasopharyngeal swabs (N=7493) collected from symptomatic outpatients aged 2-20 years old between 2012 and 2019 in France. We developed a Poisson regression model in which the number of positive cases by year and age depended on the year, age group, population size of each age group and a proxy of waning immunity that could vary with vaccine schedule. We also compared the anti-pertussis toxin (PT) antibody levels of 315 children born before and after the vaccine schedule change. Findings: The model that best fitted the 2012-2018 epidemiological data supported a faster waning of immunity following vaccination with the new vaccine schedule. Four years after vaccination, the risk of developing pertussis was 2.1 (95% CI, 1.7-2.2) times higher for children vaccinated according to the new schedule than those vaccinated according to the previous schedule. The model correctly predicted the age distribution of cases in 2019. Anti-PT IgG levels were significantly lower in children born after implementation of the new schedule, compared to children born before. Interpretation: A shorter-lived protection induced by the 2/4+11 vaccine schedule recommended in France since 2013 is associated with an increase of pertussis cases in 2-5-year olds. Funding Statement: This project was funded by the INCEPTION interdisciplinary project at Institut Pasteur, “Understanding whooping cough resurgence in Europe by combining genomic, epidemiological and sociological approaches” (French Government Investissements d’Avenir grant ANR-16-CONV-0005). This work received financial support from the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant n_ANR-10-LABX-62-IBEID). Institutional support was provided by Institut Pasteur and Sante publique France. Declaration of Interests: None to declare. Ethics Approval Statement: The data collection received approval by French supervisory ethics authority (CNIL, n°1474593), and was approved by the local Institutional Review board (N° 2020 1028160733). All data processing and storage comply with the General Data Protection Regulation (GDPR) and ethical standards of the National Research Committee. This study was conducted in accordance with the Helsinki Declaration, with informed consent obtained from each patient’s guardians.

Published
2021
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47. Early chains of transmission of COVID-19 in France

Author

Alexandra Mailles, Paolo Bosetti, Henrik Salje, Catherine Eisenhauer, Juliette Paireau, Franck de Laval, Valerie Ponties, François Delon, and Simon Cauchemez

Subjects
medicine.medical_specialty, business.industry, Attack rate, Odds ratio, law.invention, Transmission (mechanics), law, Epidemiology, medicine, media_common.cataloged_instance, European union, business, Index case, Contact tracing, Demography, media_common, Serial interval
Abstract

IntroductionSARS-CoV-2, which causes COVID-19, has spread rapidly across the world. A dedicated surveillance system was implemented in France in January 2020 to improve early detection of cases and their contacts and limit secondary transmission. Our objective was to use contact-tracing data collected during this initial phase of the epidemic to better characterize 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 characterized the risk of a contact becoming a case. We described chains of transmission and estimated key parameters of spread.ResultsOver the study period, 6,082 contacts of 735 confirmed cases were traced. The overall secondary clinical attack rate was 4.1% (95%CI 3.6-4.6) and increased with age of the index case and of the contact. Family contacts were at higher risk of becoming cases (adjusted odds ratio 2.1 (95%CI 1.4-3.0)) while nosocomial contacts were at lower risk (adjusted odds ratio 0.3 (95%CI 0.1-0.7)), compared to coworkers/friends. We identified 328 infector/infectee pairs, 49% of which were family members. The distribution of secondary cases was highly over-dispersed with 80% of secondary cases being caused by 10% of cases. The mean serial interval was 5.1 days (interquartile range 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 contributes to improving our knowledge of SARS-CoV-2 transmission, such as the importance of superspreading events. Contact-tracing data are challenging to collect but are key to better understand emerging pathogens.Funding statementThis work was supported by the LabEx “Integrative Biology of Emerging Infectious Diseases (IBEID)” (Grant Number ANR-10-LABX-62-IBEID), Santé Publique France, the INCEPTION project (PIA/ANR-16-CONV-0005), and the European Union’s Horizon 2020 research and innovation program under grants 101003589 (RECOVER) and 874735 (VEO).

Published
2020
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48. Ready for a BASE jump? Do not neglect SARS-CoV-2 hospitalization and fatality risks in the middle-aged adult population

Author

Daniel Lévy-Bruhl, Xavier de Lamballerie, Mathilde Touvier, Nathanael Lapidus, Gianluca Severi, Fabrice Carrat, Juliette Paireau, Simon Cauchemez, and Marie Zins

Subjects
education.field_of_study, 2019-20 coronavirus outbreak, Surveillance data, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), media_common.quotation_subject, Population, Neglect, Medicine, Seroprevalence, Middle-aged adult, business, education, Demography, media_common
Abstract

Seroprevalence results coupled with surveillance data were used to estimate the SARS-CoV-2 infection hospitalization (IHR) and infection fatality ratios (IFR) in France. IHR and IFR were dramatically high in the very elderly (80-90 years: IHR: 30%, IFR: 11%), but also substantial in middle-aged adults (40-50 years: IHR: 1.2%, IFR: 0.05%).

Published
2020
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49. Evaluating the impact of curfews and other measures on SARS-CoV-2 transmission in French Guiana

Author

Noémie Lefrancq, Alessio Andronico, Alice Sanna, Mathieu Nacher, Cyril Rousseau, Henrik Salje, Cécile Tran Kiem, Félix Djossou, Simon Cauchemez, Claude Flamand, Tiphanie Succo, Paolo Bosetti, and Juliette Paireau

Subjects
0303 health sciences, education.field_of_study, business.industry, Population, Psychological intervention, Context (language use), 3. Good health, law.invention, Metropolitan France, 03 medical and health sciences, 0302 clinical medicine, Geography, Transmission (mechanics), law, Environmental health, Health care, 030212 general & internal medicine, Economic impact analysis, business, education, Basic reproduction number, 030304 developmental biology
Abstract

While general lockdowns have proven effective to control SARS-CoV-2 epidemics, they come with enormous costs for society. It is therefore essential to identify control strategies with lower social and economic impact. Here, we report and evaluate the control strategy implemented during a large SARS-CoV-2 epidemic in June-July 2020 in French Guiana that relied on curfews, targeted lockdowns and other measures. We find that the combination of these interventions reduced the basic reproduction number of SARS-CoV-2 from 1.7 to 1.1, which was sufficient to avoid saturation of hospitals. We estimate that thanks to the young demographics across the territory, the risk of hospitalisation following infection was 0.3 times that of metropolitan France and that about 20% of the population was infected by July. Our model projections are consistent with a recent seroprevalence study. The study showcases how mathematical modeling can be used to support healthcare planning and decision making in a context of high uncertainty.

Published
2020
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50. Lockdown impact on COVID-19 epidemics in regions across metropolitan France

Author

Patrick Rolland, Simon Cauchemez, Juliette Paireau, Cécile Tran Kiem, Arnaud Fontanet, Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Collège Doctoral, Sorbonne Université (SU), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), We acknowledge financial support from the Investissement d'Avenir programme, the Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases programme (grant ANR-10-LABX-62-IBEID), the INCEPTION project (PIA/ANR-16-CONV-0005), and the European Union's Horizon 2020 research and innovation programme under grant 101003589 (RECOVER)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Collège doctoral [Sorbonne universités], and Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)

Subjects
MESH: Social Isolation, MESH: Pandemics, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), MESH: Coronavirus Infections, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, 030204 cardiovascular system & hematology, Betacoronavirus, MESH: Communicable Disease Control, 03 medical and health sciences, 0302 clinical medicine, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], Pandemic, Correspondence, Humans, MESH: COVID-19, MESH: SARS-CoV-2, 030212 general & internal medicine, Socioeconomics, Pandemics, ComputingMilieux_MISCELLANEOUS, MESH: Humans, SARS-CoV-2, COVID-19, General Medicine, Metropolitan area, 3. Good health, MESH: France, Metropolitan France, Geography, Social Isolation, MESH: Pneumonia, Viral, Communicable Disease Control, MESH: Betacoronavirus, France, Coronavirus Infections
Abstract

Lockdowns have been used by most European countries in response to the COVID-19 pandemic. In France, a national lockdown was implemented on March 17, 2020. Some have questioned the need for a nationwide implementation given that most hospital admissions were concentrated in two of 13 regions; others have even questioned the impact of the lockdown on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread, arguing that the natural epidemic peak was about to be reached. Here we discuss the impact of lockdown on COVID-19 epidemics in regions across metropolitan France.

Published
2020
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