Modélisation de la transmission du virus de l’Hépatite C en milieu hospitalier : De l’évaluation au contrôle, application au contexte égyptien

The hepatitis C virus (HCV) is a blood-borne pathogen. The majority infections caused by this virus (50-80%) becomes chronic, and it is at the origin of multiple complications such as cirrhosis and liver cancer. Egypt is historically associated with the highest prevalence of chronic HCV infection worldwide. In order to reduce this burden, the Egyptian government implemented a nationwide mass testing and treatment campaign in 2018. Hospitals are likely playing a role in the transmission of the virus, particularly if infectious control measures are sub-optimal. In this context, the main objective of this thesis was to study the intra-hospital transmission of HCV and to propose tools to reduce its spread.First, we explored existing measures of association between HCV infections and a number of hospital procedures in order to obtain estimations, through a meta-analysis of the risk of infection associated with each of these procedures. We were able to show that the majority of invasive procedures were associated with an increased risk of HCV infection. In particular, the risk was higher for transplants and wound care, and lower for endoscopy and dental procedures.We then studied the iatrogenic risk of HCV acquisition using data collected in 2017 in the Ain Shams Hospital in Cairo. A risk assessment model was proposed, and profiles of at-risk patients and departments within the hospital were determined. In particular, we were able to differentiate 4 patient trajectories within the hospital, and the risk of infection appeared to be greater for patients hospitalized in the internal medicine department than for those hospitalized in the surgery department. A risk score based on the data collected upon admission was then proposed, and numerical simulation of simple interventions was used to determine the relative effectiveness of implementing them for all patients versus those in the highest-risk departments.Finally, we proposed a dynamic individual-based model of the transmission of blood-borne pathogens within a hospital, implemented using data previously collected in the Ain Shams Hospital, Cairo. We were then able to simulate the number of new infections linked to the reuse of contaminated equipment within a hospital over the course of a year in the context of HCV in Egypt, but were also able to extend this work by studying the hospital spread of hepatitis B virus (HBV) in Ethiopia. These analyses were accompanied by the simulation of interventions that aimed at reducing the number of new infections in these hospitals.This work highlighted that there still seems to be an increased risk of HCV transmission through various invasive procedures. On the other hand, it improved our understanding of HCV transmission in hospitals, particularly in the Egyptian context. The mathematical tools proposed in this project have a wide range of applications and could be used to control the spread of blood-borne pathogens in a wide variety of contexts.Le virus de l’hépatite C (VHC) est un pathogène transmis par le sang. La majorité des infections qu’il cause (50 à 80%) devient chronique et il est à l’origine de multiples complications comme les cirrhoses ou les cancers hépatiques. L’Egypte est pays historiquement associé à la plus importante prévalence d’infections chroniques au VHC dans le monde. Afin de réduire ce fardeau, le gouvernement égyptien a mis en place dès 2018 une campagne de test et de traitement de masse à l’échelle nationale. Le rôle des hôpitaux dans la dynamique de transmission du VHC est encore imparfaitement compris, notamment lorsque les mesures de contrôle infectieux ne sont pas optimales. Dans ce contexte, l’objectif principal de cette thèse était d’étudier la transmission intra-hospitalière du VHC et de proposer des outils afin de réduire sa propagation.Dans un premier temps, nous avons exploré les mesures d’associations existantes entre les infections au VHC et un certain nombre de procédures hospitalières afin d’obtenir des estimations, au travers d’une méta-analyse, des risques d’infection pour chacune des procédures. Nous avons pu montrer que la majorité des procédures invasives étaient associées à un risque accru d’infection au VHC. En particulier celui-ci était plus important pour les transplantations et le soin aux plaies et moindre pour les endoscopies et les procédures dentaires.Par la suite, nous avons étudié le risque iatrogène d’acquisition du VHC à partir de données récoltées en 2017 dans l’hôpital Ain Shams du Caire. Un modèle d’évaluation du risque pour les patients a été proposé et des profils de patients et de services à risque ont pu être déterminés au sein de l’hopital. En particulier, nous avons pu distinguer 4 trajectoires types de patients au sein de l’hopital et le risque d’infection semblait plus important pour les patients hospitalisés dans le département de médecine interne que pour ceux hospitalisés dans le département de chirurgie. Un score de risque basé sur les données récoltées à l’admission a ensuite pu être proposé et la simulation numérique d’interventions simples a permis de déterminer l’efficacité relative de leur mise en place auprès de tous les patients par rapport à une mise en place dans les services les plus à risque.Pour finir, nous avons proposé un modèle dynamique individu-centré de la transmission de pathogènes transmissibles par le sang au sein d’un hopital et l’avons en particulier alimenté avec les données récoltées précédemment dans l’Hopital Ain Shams. Ainsi, nous avons pu simuler sur une année le nombre de nouvelles infections liées à la réutilisation de matériel contaminé au sein d’un hopital dans le contexte du VHC en Egypte, mais avons aussi pu l’étendre avec l’étude de la propagation hospitalière du virus de l’hépatite B (VHB) en Ethiopie. Ces analyses ont été complétée par la simulation d’interventions visant à réduire le nombre de nouvelles infections aux sein de ces hôpitaux.Ce travail a mis en avant l’existence d’un risque accru de transmission du VHC par différentes procédures invasives. D’autre part, il a permis d’améliorer la compréhension de la transmission du VHC en milieu hospitalier, en particulier dans le contexte Egyptien. Les outils mathématiques qui y sont proposés permettent une multiplicité d’applications, et ceux-ci pourraient servir dans le cadre du contrôle de la diffusion de pathogènes transmissibles par le sang dans de nombreux contextes

Ecole et immigration

Payet Jean-Paul, Van Zanten Agnès. Ecole et immigration. In: Revue française de pédagogie, volume 117, 1996. L'école et la question de l'immigration. pp. 5-6

Note de synthèse

Payet Jean-Paul, Henriot-Van Zanten Agnès. Note de synthèse. In: Revue française de pédagogie, volume 117, 1996. L'école et la question de l'immigration. pp. 87-149

Modeling the impact of urban and hospital eco-exposomes on antibiotic-resistance dynamics in wastewaters

International audienceThe emergence and selection of antibiotic resistance is a major public health problem worldwide. The presence of antibiotic-resistant bacteria (ARBs) in natural and anthropogenic environments threatens the sustainability of efforts to reduce resistance in human and animal populations. Here, we use mathematical modeling of the selective effect of antibiotics and contaminants on the dynamics of bacterial resistance in water to analyze longitudinal spatio-temporal data collected in hospital and urban wastewater between 2012 and 2015. Samples were collected monthly during the study period at four different sites in Haute-Savoie, France: hospital and urban wastewater, before and after water treatment plants. Three different categories of exposure variables were collected simultaneously: 1) heavy metals, 2) antibiotics and 3) surfactants for a total of 13 drugs/molecules; in parallel to the normalized abundance of 88 individual genes and mobile genetic elements, mostly conferring resistance to antibiotics. A simple hypothesis-driven model describing weekly antibiotic resistance gene (ARG) dynamics was proposed to fit the available data, assuming that normalized gene abundance is proportional to antibiotic resistant bacteria (ARB) populations in water. The detected compounds were found to influence the dynamics of 17 genes found at multiple sites. While mercury and vancomycin were associated with increased ARG and affected the dynamics of 10 and 12 identified genes respectively, surfactants antagonistically affected the dynamics of three genes. The models proposed here make it possible to analyze the relationship between the persistence of resistance genes in the aquatic environment and specific compounds associated with human activities from longitudinal data. Our analysis of French data over 2012–2015 identified mercury and vancomycin as co-selectors for some ARGs

Meta‐analysis: Risk of hepatitis C virus infection associated with hospital‐based invasive procedures

International audienceBackgroundHealthcare settings, where invasive procedures are frequently performed, may play an important role in the transmission dynamics of blood-borne pathogens when compliance with infection control precautions is suboptimal.AimsTo understand and quantify the role of hospital-based invasive procedures on hepatitis C virus (HCV) transmission.MethodsWe conducted a systematic review and meta-analysis to identify recent studies reporting association measures of HCV infection risk that are linked to iatrogenic procedures. Based on expert opinion, invasive procedures were categorised into 10 groups for which pooled measures were calculated. Finally, the relationship between pooled measures and the country-level HCV prevalence or the Healthcare Access and Quality (HAQ) index was assessed by meta-regression.ResultsWe included 71 studies in the analysis. The most frequently evaluated procedures were blood transfusion (66 measures) and surgery (43 measures). The pooled odds ratio (OR) of HCV infection varied widely, ranging from 1.46 (95% confidence interval: 1.14–1.88) for dental procedures to 3.22 (1.7–6.11) for transplantation. The OR for blood transfusion was higher for transfusions performed before 1998 (3.77, 2.42–5.88) than for those without a specified/recent date (2.20, 1.77–2.75). In procedure-specific analyses, the HCV infection risk was significantly negatively associated with the HAQ for endoscopy and positively associated with HCV prevalence for endoscopy and surgery.ConclusionsVarious invasive procedures were significantly associated with HCV infection. Our results provide a ranking of procedures in terms of HCV risk that may be used for prioritisation of infection control interventions, especially in high HCV prevalence settings

Meta‐analysis: Risk of hepatitis C virus infection associated with hospital‐based invasive procedures

International audienceBackgroundHealthcare settings, where invasive procedures are frequently performed, may play an important role in the transmission dynamics of blood-borne pathogens when compliance with infection control precautions is suboptimal.AimsTo understand and quantify the role of hospital-based invasive procedures on hepatitis C virus (HCV) transmission.MethodsWe conducted a systematic review and meta-analysis to identify recent studies reporting association measures of HCV infection risk that are linked to iatrogenic procedures. Based on expert opinion, invasive procedures were categorised into 10 groups for which pooled measures were calculated. Finally, the relationship between pooled measures and the country-level HCV prevalence or the Healthcare Access and Quality (HAQ) index was assessed by meta-regression.ResultsWe included 71 studies in the analysis. The most frequently evaluated procedures were blood transfusion (66 measures) and surgery (43 measures). The pooled odds ratio (OR) of HCV infection varied widely, ranging from 1.46 (95% confidence interval: 1.14–1.88) for dental procedures to 3.22 (1.7–6.11) for transplantation. The OR for blood transfusion was higher for transfusions performed before 1998 (3.77, 2.42–5.88) than for those without a specified/recent date (2.20, 1.77–2.75). In procedure-specific analyses, the HCV infection risk was significantly negatively associated with the HAQ for endoscopy and positively associated with HCV prevalence for endoscopy and surgery.ConclusionsVarious invasive procedures were significantly associated with HCV infection. Our results provide a ranking of procedures in terms of HCV risk that may be used for prioritisation of infection control interventions, especially in high HCV prevalence settings

A modeling study on the impact of COVID-19 pandemic responses on the community transmission of antibiotic-resistant bacteria

Abstract Non-pharmaceutical COVID-19 interventions have dramatically modified the transmission dynamics of pathogens other than SARS-CoV-2. In many countries, reports have shown that implementation of population-wide lockdowns led to substantial reductions in invasive bacterial disease caused by respiratory bacteria such as Streptococcus pneumoniae . By contrast, most European countries reported increased antibiotic resistance among S. pneumoniae isolates from 2019 to 2020. To disentangle impacts of the COVID-19 pandemic responses on bacterial epidemiology in the community setting, we propose a mathematical model formalizing simultaneous transmission of SARS-CoV-2 and antibiotic-sensitive and -resistant strains of S. pneumoniae . The impacts of population-wide lockdowns, isolation of COVID-19 cases, changes in antibiotic consumption due to altered healthcare-seeking behavior and prophylactic use in the early pandemic were explored across six pandemic scenarios. Our model was able to reproduce the observed trends, showing how lockdowns substantially reduce invasive pneumococcal disease incidence, while surges in prophylactic antibiotic prescribing favor disease caused by resistant strains. Surges in COVID-19 cases were associated with increased antibiotic resistance rates across all pandemic scenarios. Introducing synergistic within-host SARS-CoV-2-pneumococcus interactions further exacerbates increasing incidence of resistant disease. When data availability is limited, mathematical modeling can help improve our understanding of the complex interactions between COVID-19 and antibiotic resistance

Exploring factors shaping antibiotic resistance patterns in Streptococcus pneumoniae during the 2020 COVID-19 pandemic

Non-pharmaceutical interventions implemented to block SARS-CoV-2 transmission in early 2020 led to global reductions in the incidence of invasive pneumococcal disease (IPD). By contrast, most European countries reported an increase in antibiotic resistance among invasive Streptococcus pneumoniae isolates from 2019 to 2020, while an increasing number of studies reported stable pneumococcal carriage prevalence over the same period. To disentangle the impacts of the COVID-19 pandemic on pneumococcal epidemiology in the community setting, we propose a mathematical model formalizing simultaneous transmission of SARS-CoV-2 and antibiotic-sensitive and -resistant strains of S. pneumoniae. To test hypotheses underlying these trends five mechanisms were built into the model and examined: (1) a population-wide reduction of antibiotic prescriptions in the community, (2) lockdown effect on pneumococcal transmission, (3) a reduced risk of developing an IPD due to the absence of common respiratory viruses, (4) community azithromycin use in COVID-19 infected individuals, (5) and a longer carriage duration of antibiotic-resistant pneumococcal strains. Among 31 possible pandemic scenarios involving mechanisms individually or in combination, model simulations surprisingly identified only two scenarios that reproduced the reported trends in the general population. They included factors (1), (3), and (4). These scenarios replicated a nearly 50% reduction in annual IPD, and an increase in antibiotic resistance from 20% to 22%, all while maintaining a relatively stable pneumococcal carriage. Exploring further, higher SARS-CoV-2 R0 values and synergistic within-host virus-bacteria interaction mechanisms could have additionally contributed to the observed antibiotic resistance increase. Our work demonstrates the utility of the mathematical modeling approach in unraveling the complex effects of the COVID-19 pandemic responses on AMR dynamics