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1. Appropriateness of small molecule agents for patients with IBD of childbearing age – a RAND/UCLA appropriateness panel

Author

Christian Selinger, Robyn Laube, Jimmy K. Limdi, Kate Headley, Alexandra Kent, Klaartje Kok, Aileen Fraser, Victoria Newman, Helen Ludlow, Fiona Rees, Nidhi Sagar, and Erin Walker

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background: Many women of childbearing age with inflammatory bowel disease (IBD) require advanced therapies. While biologics are largely low risk during pregnancy, the novel small molecules tofacitinib, filgotinib, upadacitinib and ozanimod (TFUO) have shown concerning teratogenic effects, and decreased fertility in animal studies. Therefore, their use in women of childbearing age needs careful consideration. Design: RAND/University of California Los Angeles (UCLA) Appropriateness Method (RAM). Objective: To evaluate the appropriateness of TFUO in women of childbearing age. Methods: We convened a panel of six gastroenterologists, two IBD nurses, one IBD pharmacist and three expert patients. Following a literature review, 13 statements were drafted and voted upon in 2 rounds. Results: All 13 statements were deemed appropriate. The panel concluded that women with IBD of childbearing age who wish to commence therapy with TFUO, need to use effective contraception and be counselled regarding the risk in unplanned pregnancies. For women using contraception while on Janus kinase inhibitor (JAKi) therapy, we suggest the preferred use of progesterone-only or non-hormonal long-acting contraception. TFUO are contraindicated during pregnancy and breast feeding. We recommend that women receiving TFUO cease therapy in time to establish clinical remission for at least 3 months prior to conception. Therapies other than TFUO should be considered as first-line therapy in women with IBD of childbearing age, except in select individual circumstances. TFUO may be appropriate for women of childbearing age after failure of, intolerance or contraindications to one biological agent. Conclusion: TFUO should be avoided during pregnancy and breastfeeding, and alternative therapies should be considered as first-line treatments. Summary: We provide clinical practice recommendations regarding the use of TFUO for IBD in women of childbearing age.

Published
2024
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2. Delphi consensus survey: the opinions of patients living with refractory ulcerative proctitis and the health care professionals who care for them

Author

Stuart Bloom, Christian Selinger, Ailsa Hart, Christopher Lamb, Anjan Dhar, Helen Steed, Matthew Brookes, Jonathan Macdonald, Ian Arnott, Shellie Radford, Susan Ritchie, Victoria Fletcher, Jonathan Segal, N Sharma, Daniel Gaya, J Butterworth, S Andrews, P Adams, Deborah Morris, Pearl Avery, Philip Oppong, Mario Guslandi, Maro Kyriacou, Rachel Linger, Madhoor Ramdeen, John Appleton, John Anneh, and B Kussel

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background Refractory ulcerative proctitis presents a huge clinical challenge not only for the patients living with this chronic, progressive condition but also for the professionals who care for them. Currently, there is limited research and evidence-based guidance, resulting in many patients living with the symptomatic burden of disease and reduced quality of life. The aim of this study was to establish a consensus on the thoughts and opinions related to refractory proctitis disease burden and best practice for management.Methods A three-round Delphi consensus survey was conducted among patients living with refractory proctitis and the healthcare experts with knowledge on this disease from the UK. A brainstorming stage involving a focus group where the participants came up with an initial list of statements was completed. Following this, there were three rounds of Delphi surveys in which the participants were asked to rank the importance of the statements and provide any additional comments or clarifications. Calculation of mean scores, analysis of comments and revisions were performed to produce a final list of statements.Results In total, 14 statements were suggested by the focus group at the initial brainstorming stage. Following completion of three Delphi survey rounds, all 14 statements reached consensus following appropriate revision.Conclusions We established consensus on the thoughts and opinions related to refractory proctitis from both the experts who manage this disease and the patients living with it. This represents the first step towards developing clinical research data and ultimately the evidence needed for best practice management guidance of this condition.

Published
2023
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3. Medication adherence in women with IBD of childbearing age likely associated with disease knowledge

Author

Robyn Laube, Christian Selinger, and Rupert W. Leong

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background: Medication adherence in inflammatory bowel disease (IBD) is crucial, particularly during pregnancy. Unplanned pregnancies are common; therefore, efforts to maximise adherence should not be restricted to pregnant women. Objectives: We aimed to assess medication adherence in women with IBD of childbearing age, regardless of their reproduction plans. Design: We performed a multi-centre pilot questionnaire study of women with IBD age 18–45 years. Methods: Survey questions included patient demographics, disease history, and validated assessments of IBD and pregnancy knowledge, medication adherence and quality of life. The primary outcome was rates and predictors of medication adherence. Results: In all, 72 women [58.3% Crohn’s disease (CD) and 37.5% ulcerative colitis] completed the survey. The median patient age was 30 years [interquartile range (IQR): 24.8–36.0) and 37.5% had children. Medication adherence was high (84%; median Medication Adherence Report Scale: 19.0/20; IQR: 17.0–20.0). Knowledge scores were adequate for both the Crohn’s and Colitis Knowledge (CCKnow; median: 15.5/30; IQR: 12.3–18.0) and Crohn’s and Colitis Pregnancy Knowledge (CCPKnow; median: 8.0/17; IQR: 4.0–11.0). Disease knowledge was predictive of high medication adherence (CCPKnow: p = 0.02; CCKnow: p ⩽ 0.01). Higher adherence was significantly associated with a diagnosis of CD ( p = 0.01), exposure to biological agents ( p = 0.03) and immunomodulators ( p = 0.04), childbearing after diagnosis with IBD ( p = 0.03), and correctly understanding the importance of delivery modality ( p = 0.02) and IBD activity in pregnancy ( p = 0.01). Conclusions: Following dedicated education at the IBD clinic, medication adherence, disease-specific and pregnancy-specific knowledge in women with IBD of childbearing age tends to be high. Unplanned pregnancies are frequent; therefore, we should aim to maximise medication adherence in all women of childbearing age to optimise maternofoetal outcomes if unexpected pregnancies occur.

Published
2022
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4. Predicting COVID-19 incidence in French hospitals using human contact network analytics

Author

Christian Selinger, Marc Choisy, and Samuel Alizon

Subjects
time series, human mobility, networks, infectious disease, Infectious and parasitic diseases, RC109-216
Abstract

Background COVID-19 was first detected in Wuhan, China, in 2019 and spread worldwide within a few weeks. The COVID-19 epidemic started to gain traction in France in March 2020. Subnational hospital admissions and deaths were then recorded daily and served as the main policy indicators. Concurrently, mobile phone positioning data have been curated to determine the frequency of users being colocalized within a given distance. Contrarily to individual tracking data, these can be a proxy for human contact networks between subnational administrative units.Methods Motivated by numerous studies correlating human mobility data and disease incidence, we developed predictive time series models of hospital incidence between July 2020 and April 2021. We added human contact network analytics, such as clustering coefficients, contact network strength, null links or curvature, as regressors.Findings We found that predictions can be improved substantially (by more than 50%) at both the national level and the subnational level for up to 2 weeks. Our subnational analysis also revealed the importance of spatial structure, as incidence in colocalized administrative units improved predictions. This original application of network analytics from colocalization data to epidemic spread opens new perspectives for epidemic forecasting and public health.

Published
2021
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5. Detecting Rapid Spread of SARS-CoV-2 Variants, France, January 26–February 16, 2021

Author

Stéphanie Haim-Boukobza, Bénédicte Roquebert, Sabine Trombert-Paolantoni, Emmanuel Lecorche, Laura Verdurme, Vincent Foulongne, Christian Selinger, Yannis Michalakis, Mircea T. Sofonea, and Samuel Alizon

Subjects
virus, epidemiology, variants, RT-PCR, screening, statistical modelling, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

Variants of severe acute respiratory syndrome coronavirus 2 raise concerns regarding the control of coronavirus disease epidemics. We analyzed 40,000 specific reverse transcription PCR tests performed on positive samples during January 26–February 16, 2021, in France. We found high transmission advantage of variants and more advanced spread than anticipated.

Published
2021
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6. Gastroenterology team members’ knowledge and practices with fertility therapy for women with inflammatory bowel disease

Author

Robyn Laube, Eleanor Liu, Ying Li, Rupert W. Leong, Jimmy Limdi, and Christian Selinger

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Introduction: Fecundity may be reduced in women with active inflammatory bowel disease (IBD) or prior IBD-related surgery, and these women may require assisted reproductive technology (ART). There are no guidelines for women with IBD to outline referral criteria for ART. Methods: We performed a prospective, multicentre, international questionnaire of gastroenterologists, gastroenterology trainees, and IBD nurses. The primary outcome was to establish clinical practices and fertility therapy referral patterns among gastroenterology team members. We hypothesised that the lack of knowledge and awareness may delay or prevent initiation of fertility consultation referrals. Discussion: Of 182 participants, most had never initiated a referral for fertility therapy (69.8%), and of respondents who do initiate referrals, 50% wait until the patient has been unsuccessfully attempting conception for 12 months. Participants were significantly more likely to initiate a fertility therapy referral if they believed ART was effective ( p = 0.038), not impeded by IBD-related surgery ( p = 0.053), and if they had access to a dedicated IBD-pregnancy clinic ( p = 0.027). Superior pregnancy knowledge was predictive of a greater likelihood of fertility therapy referrals ( p = 0.037). All participants thought they had inadequate knowledge about ART in IBD, and 96.2% expressed desire to improve their knowledge. Conclusion: Gastroenterology team members infrequently initiate referrals for fertility therapy consultation in women with IBD, increasing their risk of remaining childless. Implementation of dedicated IBD pregnancy clinics and targeted education programmes to increase awareness of ART in women with IBD might increase referral rates and reduce infertility.

Published
2022
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7. Concomitant and productive genital infections by HSV-2 and HPV in two young women: A case report

Author

Ilkay Başak Uysal, Vanina Boué, Carmen Lia Murall, Christelle Graf, Christian Selinger, Christophe Hirtz, Claire Bernat, Jacques Ravel, Jacques Reynes, Marine Bonneau, Massilva Rahmoun, Michel Segondy, Nathalie Boulle, Sophie Grasset, Soraya Groc, Tim Waterboer, Vincent Tribout, Ignacio G. Bravo, Sonia Burrel, Vincent Foulongne, Samuel Alizon, and Nicolas Tessandier

Subjects
Human papillomavirus, Herpes Simplex Virus-2, Co-infection, Interaction, Vaginal microbiota, qPCR, Infectious and parasitic diseases, RC109-216
Abstract

Human papillomaviruses (HPVs), the most oncogenic virus known to humans, are often associated with Herpes Simplex Virus-2 (HSV-2) infections. The involvement of the latter in cervical cancer is controversial but its long-term infections might modulate the mucosal microenvironment in a way that favors carcinogenesis. We know little about coinfections between HSV-2 and HPVs, and studying the immunological and microbiological dynamics in the early stages of these infections may help identify or rule out potential interactions. We report two cases of concomitant productive, although asymptomatic, HSV-2 and HPV infections in young women (aged 20 and 25). The women were followed up for approximately a year, with clinical visits every two months and weekly self-samples. We performed quantitative analyses of their HSV-2 and HPV viral loads, immunological responses (IgG and IgM antibodies and local cytokines expression profiles), vaginal microbiota composition, as well as demographic and behavior data. We detect interactions between virus loads, immune response, and the vaginal microbiota, which improve our understanding of HSV-2 and HPVs’ coinfections and calls for further investigation with larger cohorts.

Published
2022
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8. Episome partitioning and symmetric cell divisions: Quantifying the role of random events in the persistence of HPV infections.

Author

Thomas Beneteau, Christian Selinger, Mircea T Sofonea, and Samuel Alizon

Subjects
Biology (General), QH301-705.5
Abstract

Human Papillomaviruses (HPV) are one of the most prevalent sexually transmitted infections (STI) and the most oncogenic viruses known to humans. The vast majority of HPV infections clear in less than 3 years, but the underlying mechanisms, especially the involvement of the immune response, are still poorly known. Building on earlier work stressing the importance of randomness in the type of cell divisions in the clearance of HPV infection, we develop a stochastic mathematical model of HPV dynamics that combines the previous aspect with an explicit description of the intracellular level. We show that the random partitioning of virus episomes upon stem cell division and the occurrence of symmetric divisions dramatically affect viral persistence. These results call for more detailed within-host studies to better understand the relative importance of stochasticity and immunity in HPV infection clearance.

Published
2021
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9. Reconstructing contact network structure and cross-immunity patterns from multiple infection histories.

Author

Christian Selinger and Samuel Alizon

Subjects
Biology (General), QH301-705.5
Abstract

Interactions within a population shape the spread of infectious diseases but contact patterns between individuals are difficult to access. We hypothesised that key properties of these patterns can be inferred from multiple infection data in longitudinal follow-ups. We developed a simulator for epidemics with multiple infections on networks and analysed the resulting individual infection time series by introducing similarity metrics between hosts based on their multiple infection histories. We find that, depending on infection multiplicity and network sampling, multiple infection summary statistics can recover network properties such as degree distribution. Furthermore, we show that by mining simulation outputs for multiple infection patterns, one can detect immunological interference between pathogens (i.e. the fact that past infections in a host condition future probability of infection). The combination of individual-based simulations and analysis of multiple infection histories opens promising perspectives to infer and validate transmission networks and immunological interference for infectious diseases from longitudinal cohort data.

Published
2021
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10. Memory is key in capturing COVID-19 epidemiological dynamics

Author

Mircea T. Sofonea, Bastien Reyné, Baptiste Elie, Ramsès Djidjou-Demasse, Christian Selinger, Yannis Michalakis, and Samuel Alizon

Subjects
Mathematical epidemiology, Discrete-time modelling, Non-Markovian processes, Epidemiosurveillance, Reproduction number, Infectious and parasitic diseases, RC109-216
Abstract

SARS-CoV-2 virus has spread over the world rapidly creating one of the largest pandemics ever. The absence of immunity, presymptomatic transmission, and the relatively high level of virulence of the COVID-19 infection led to a massive flow of patients in intensive care units (ICU). This unprecedented situation calls for rapid and accurate mathematical models to best inform public health policies.We develop an original parsimonious discrete-time model that accounts for the effect of the age of infection on the natural history of the disease. Analysing the ongoing COVID-19 in France as a test case, through the publicly available time series of nationwide hospital mortality and ICU activity, we estimate the value of the key epidemiological parameters and the impact of lock-down implementation delay.This work shows that including memory-effects in the modelling of COVID-19 spreading greatly improves the accuracy of the fit to the epidemiological data. We estimate that the epidemic wave in France started on Jan 20 [Jan 12, Jan 28] (95% likelihood interval) with a reproduction number initially equal to 2.99 [2.59, 3.39], which was reduced by the national lock-down started on Mar 17 to 24 [21, 27] of its value. We also estimate that the implementation of the latter a week earlier or later would have lead to a difference of about respectively −13k and +50k hospital deaths by the end of lock-down.The present parsimonious discrete-time framework constitutes a useful tool for now- and forecasting simultaneously community incidence and ICU capacity strain.

Published
2021
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11. Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy

Author

Ameya R. Kirtane, Omar Abouzid, Daniel Minahan, Taylor Bensel, Alison L. Hill, Christian Selinger, Anna Bershteyn, Morgan Craig, Shirley S. Mo, Hormoz Mazdiyasni, Cody Cleveland, Jaimie Rogner, Young-Ah Lucy Lee, Lucas Booth, Farhad Javid, Sarah J. Wu, Tyler Grant, Andrew M. Bellinger, Boris Nikolic, Alison Hayward, Lowell Wood, Philip A. Eckhoff, Martin A. Nowak, Robert Langer, and Giovanni Traverso

Subjects
Science
Abstract

Poor adherence to daily antiretrovirals can significantly affect treatment efficacy, but oral long-acting antiretrovirals are currently lacking. Here, the authors develop a once-weekly oral dosage form for anti-HIV drugs, assess its pharmacokinetics in pigs, and model its impact on viral resistance and disease epidemics.

Published
2018
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12. Medication adherence in inflammatory bowel disease

Author

Webber Chan, Andy Chen, Darren Tiao, Christian Selinger, and Rupert Leong

Subjects
Medication adherence, Colitis, ulcerative, Crohn disease, Inflammatory bowel disease, Medicine, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory condition with intestinal and extraintestinal manifestations. Medications are the cornerstone of treatment of IBD. However, patients often adhere to medication poorly. Adherence to medications is defined as the process by which patients take their medications as prescribed. Treatment non-adherence is a common problem among chronic diseases, averaging 50% in developed countries and is even poorer in developing countries. In this review, we will examine the adherence data in IBD which vary greatly depending on the study population, route of administration, and methods of adherence measurement used. We will also discuss the adverse clinical outcomes related to non-adherence to medical treatment including increased disease activity, flares, loss of response to anti-tumor necrosis factor therapy, and so forth. There are many methods to measure medication adherence namely direct and indirect methods, each with their advantages and drawbacks. Finally, we will explore different intervention strategies to improve adherence to medications.

Published
2017
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13. Assessing the stability of polio eradication after the withdrawal of oral polio vaccine.

Author

Michael Famulare, Christian Selinger, Kevin A McCarthy, Philip A Eckhoff, and Guillaume Chabot-Couture

Subjects
Biology (General), QH301-705.5
Abstract

The oral polio vaccine (OPV) contains live-attenuated polioviruses that induce immunity by causing low virulence infections in vaccine recipients and their close contacts. Widespread immunization with OPV has reduced the annual global burden of paralytic poliomyelitis by a factor of 10,000 or more and has driven wild poliovirus (WPV) to the brink of eradication. However, in instances that have so far been rare, OPV can paralyze vaccine recipients and generate vaccine-derived polio outbreaks. To complete polio eradication, OPV use should eventually cease, but doing so will leave a growing population fully susceptible to infection. If poliovirus is reintroduced after OPV cessation, under what conditions will OPV vaccination be required to interrupt transmission? Can conditions exist in which OPV and WPV reintroduction present similar risks of transmission? To answer these questions, we built a multi-scale mathematical model of infection and transmission calibrated to data from clinical trials and field epidemiology studies. At the within-host level, the model describes the effects of vaccination and waning immunity on shedding and oral susceptibility to infection. At the between-host level, the model emulates the interaction of shedding and oral susceptibility with sanitation and person-to-person contact patterns to determine the transmission rate in communities. Our results show that inactivated polio vaccine (IPV) is sufficient to prevent outbreaks in low transmission rate settings and that OPV can be reintroduced and withdrawn as needed in moderate transmission rate settings. However, in high transmission rate settings, the conditions that support vaccine-derived outbreaks have only been rare because population immunity has been high. Absent population immunity, the Sabin strains from OPV will be nearly as capable of causing outbreaks as WPV. If post-cessation outbreak responses are followed by new vaccine-derived outbreaks, strategies to restore population immunity will be required to ensure the stability of polio eradication.

Published
2018
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14. MicroRNAs Establish Robustness and Adaptability of a Critical Gene Network to Regulate Progenitor Fate Decisions during Cortical Neurogenesis

Author

Tanay Ghosh, Julieta Aprea, Jeannette Nardelli, Hannes Engel, Christian Selinger, Cedric Mombereau, Thomas Lemonnier, Imane Moutkine, Leslie Schwendimann, Martina Dori, Theano Irinopoulou, Alexandra Henrion-Caude, Arndt G. Benecke, Sebastian J. Arnold, Pierre Gressens, Federico Calegari, and Matthias Groszer

Subjects
Biology (General), QH301-705.5
Abstract

Over the course of cortical neurogenesis, the transition of progenitors from proliferation to differentiation requires a precise regulation of involved gene networks under varying environmental conditions. In order to identify such regulatory mechanisms, we analyzed microRNA (miRNA) target networks in progenitors during early and late stages of neurogenesis. We found that cyclin D1 is a network hub whose expression is miRNA-dosage sensitive. Experimental validation revealed a feedback regulation between cyclin D1 and its regulating miRNAs miR-20a, miR-20b, and miR-23a. Cyclin D1 induces expression of miR-20a and miR-20b, whereas it represses miR-23a. Inhibition of any of these miRNAs increases the developmental stage-specific mean and dynamic expression range (variance) of cyclin D1 protein in progenitors, leading to reduced neuronal differentiation. Thus, miRNAs establish robustness and stage-specific adaptability to a critical dosage-sensitive gene network during cortical neurogenesis. Understanding such network regulatory mechanisms for key developmental events can provide insights into individual susceptibilities for genetically complex neuropsychiatric disorders.

Published
2014
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15. DECIDE: <u>D</u>elphi <u>E</u>xpert <u>C</u>onsensus Statement on <u>I</u>nflammatory Bowel Disease <u>D</u>ysplasia Shar<u>e</u>d Management Decision-Making

Author

Misha Kabir, Siwan Thomas-Gibson, Phil J Tozer, Janindra Warusavitarne, Omar Faiz, Ailsa Hart, Lisa Allison, Austin G Acheson, Semra Demirli Atici, Pearl Avery, Mantaj Brar, Michele Carvello, Matthew C Choy, Robin J Dart, Justin Davies, Anjan Dhar, Shahida Din, Bu'Hussain Hayee, Kesavan Kandiah, Konstantinos H Katsanos, Christopher Andrew Lamb, Jimmy K Limdi, Richard E Lovegrove, Pär Myrelid, Nurulamin Noor, Ioannis Papaconstantinou, Dafina Petrova, Polychronis Pavlidis, Thomas Pinkney, David Proud, Shellie Radford, Rohit Rao, Shaji Sebastian, Jonathan P Segal, Christian Selinger, Antonino Spinelli, Kathryn Thomas, Albert Wolthuis, and Ana Wilson

Subjects
dysplasia management, Gastroenterology, decision-making, General Medicine, Inflammatory bowel disease
Abstract

Background and Aims Inflammatory Bowel Disease colitis-associated dysplasia is managed with either enhanced surveillance and endoscopic resection or prophylactic surgery. The rate of progression to cancer after a dysplasia diagnosis remains uncertain in many cases and patients have high thresholds for accepting proctocolectomy. Individualised discussion of management options is encouraged to take place between patients and their multidisciplinary teams for best outcomes. We aimed to develop a toolkit to support a structured, multidisciplinary and shared decision-making approach to discussions about dysplasia management options between clinicians and their patients. Methods Evidence from systematic literature reviews, mixed-methods studies conducted with key stakeholders and decision-making expert recommendations were consolidated to draft consensus statements by the DECIDE steering group. These were then subjected to an international, multidisciplinary modified electronic Delphi process until an a priori threshold of 80% agreement was achieved to establish consensus for each statement. Results 31 members (15 gastroenterologists, 14 colorectal surgeons and two nurse specialists) from 9 countries formed the Delphi panel. We present the 18 consensus statements generated after two iterative rounds of anonymous voting. Conclusions By consolidating evidence for best practice using literature review, key stakeholder and decision-making expert consultation we have developed international consensus recommendations to support healthcare professionals counselling patients on the management of high cancer risk colitis-associated dysplasia. The final toolkit includes clinician and patient decision aids to facilitate shared decision-making.

Published
2023
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16. Viral and immune dynamics of HPV genital infections in young women

Author

Nicolas Tessandier, Baptiste Elie, Vanina Boué, Christian Selinger, Massilva Rahmoun, Claire Bernat, Sophie Grasset, Soraya Groc, Anne-Sophie Bedin, Thomas Beneteau, Marine Bonneau, Christelle Graf, Nathalie Jacobs, Tsukushi Kamiya, Marion Kerioui, Julie Lajoie, Imène Melki, Jean-Luc Prétet, Bastien Reyné, Géraldine Schlecht-Louf, Mircea T. Sofonea, Olivier Supplisson, Vincent Foulongne, Jérémie Guedj, Christophe Hirtz, Marie-Christine Picot, Jacques Reynes, Vincent Tribout, Édouard Tuaillon, Tim Waterboer, Michel Segondy, Ignacio G Bravo, Nathalie Boulle, Carmen Lia Murall, and Samuel Alizon

Abstract

Human papillomavirus (HPV) infections drive one in twenty new cancer cases. Despite the potential for improving treatment, screening, and vaccination strategies, little is known as to why most HPV infections clear spontaneously within two years. To untangle the dynamics of these non-persisting infections, we performed a combined quantitative analysis of virological, immunological, and clinical data from an original longitudinal cohort of 189 women with high temporal resolution. We find that HPV viral load reaches a plateau within two months, and clears within a median time of 14 months. Furthermore, we identify immune correlates associated with infection clearance, especially TCR-gamma-delta cells. Our results open new perspectives for understanding the frontier between acute and chronic infections and for controlling HPVassociated diseases.

Published
2023
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18. Managing Inflammatory Bowel Disease in Pregnancy: Health Care Professionals’ Involvement, Knowledge, and Decision Making

Author

Eleanor Liu, Robyn Laube, Rupert W Leong, Aileen Fraser, Christian Selinger, and Jimmy K Limdi

Subjects
Gastroenterology, Immunology and Allergy
Abstract

Background The management of pregnant women with inflammatory bowel disease (IBD) is complex. We aimed to assess health care professionals’ (HCPs) theoretical and applied knowledge of pregnancy-related IBD issues. Methods A cross-sectional international survey was distributed to HCPs providing IBD care between October 2020 and March 2021. Knowledge was assessed using the validated Crohn’s and Colitis Pregnancy Knowledge Score (CCPKnow; range, 0-17). Decision-making was assessed by free text responses to 3 clinical scenarios scored against predetermined scoring criteria (maximum score 70). Results Among 81 participants, median CCPKnow score was 16 (range, 8-17), and median total scenario score was 29 (range, 9-51). Health care professionals who treat >10 IBD patients per week (CCPKnow P = .03; scenarios P = .003) and are more regularly involved in pregnancy care (CCPKnow P = .005; scenarios P = .005) had significantly better scores. Although CCPKnow scoring was consistently high (median score ≥15) across all groups, consultants scored better than trainees and IBD nurses (P = .008 and P = .031). Median scenario scores were higher for consultants (32) and IBD nurses (33) compared with trainees (24; P = .018 and P = .022). There was a significant positive correlation between caring for greater numbers of pregnant IBD patients and higher CCPKnow (P = .001, r = .358) and scenario scores (P = .001, r = .377). There was a modest correlation between CCPKnow and scenario scores (r = .356; P Conclusions Despite “good” theoretical pregnancy-related IBD knowledge as assessed by CCPKnow, applied knowledge in the scenarios was less consistent. There is need for further HCP education and clinical experience to achieve optimal standardized care for IBD in pregnancy.

Published
2022
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19. Etrolizumab versus infliximab for the treatment of moderately to severely active ulcerative colitis (GARDENIA): a randomised, double-blind, double-dummy, phase 3 study

Author

Silvio Danese, Jean-Frederic Colombel, Milan Lukas, Javier P Gisbert, Geert D'Haens, Bu'hussain Hayee, Remo Panaccione, Hyun-Soo Kim, Walter Reinisch, Helen Tyrrell, Young S Oh, Swati Tole, Akiko Chai, Kirsten Chamberlain-James, Meina Tao Tang, Stefan Schreiber, Nazimuddin Aboo, Tariq Ahmad, Xavier Aldeguer Mante, Matthieu Allez, Sven Almer, Romain Altwegg, Montserrat Andreu Garcia, Ramesh Arasaradnam, Sandro Ardizzone, Alessandro Armuzzi, Ian Arnott, Guy Aumais, Irit Avni-Biron, Peter Barrow, Ian Beales, Fernando Bermejo San Jose, Abraham Bezuidenhout, Livia Biancone, Michael Blaeker, Stuart Bloom, Bernd Bokemeyer, Fabrizio Bossa, Peter Bossuyt, Guillaume Bouguen, Yoram Bouhnik, Gerd Bouma, Raymond Bourdages, Arnaud Bourreille, Christian Boustiere, Tomas Brabec, Stephan Brand, Carsten Buening, Anthony Buisson, Guillaume Cadiot, Xavier Calvet Calvo, Franck Carbonnel, Daniel Carpio, Jae Hee Cheon, Naoki Chiba, Camelia Chioncel, Nicoleta-Claudia Cimpoeru, Martin Clodi, Gino Roberto Corazza, Rocco Cosintino, Jose Cotter, Thomas Creed, Fraser Cummings, Gian Luigi de' Angelis, Marc De Maeyer, Milind Desai, Etienne Desilets, Pierre Desreumaux, Olivier Dewit, Johanna Dinter, Ecaterina Daniela Dobru, Tomas Douda, Dan Lucian Dumitrascu, Matthias Ebert, Ana Echarri Piudo, Magdy Elkhashab, Chang Soo Eun, Brian Feagan, Roland Fejes, Catarina Fidalgo, Sigal Fishman, Bernard Flourié, Sharyle Fowler, Walter Fries, Csaba Fulop, Mathurin Fumery, Gyula G Kiss, Sonja Gassner, Daniel Gaya, Bastianello Germanà, Liliana Simona Gheorghe, Cyrielle Gilletta de Saint Joseph, Paolo Gionchetti, Adrian-Eugen Goldis, Raquel Gonçalves, Jean-Charles Grimaud, Tibor Gyökeres, Herve Hagege, Andrei Haidar, Heinz Hartmann, Peter Hasselblatt, Buhussain Hayee, Xavier Hebuterne, Per Hellström, Pieter Hindryckx, Helena Hlavova, Frank Hoentjen, Stefanie Howaldt, Ludek Hrdlicka, Kyu Chan Huh, Maria Isabel Iborra Colomino, Florentina Ionita-Radu, Peter Irving, Jørgen Jahnsen, ByungIk Jang, Jeroen Jansen, Seong Woo Jeon, Rodrigo Jover Martinez, Pascal Juillerat, Per Karlén, Arthur Kaser, Radan Keil, Deepak Kejariwal, Dan Keret, Reena Khanna, Dongwoo Kim, Duk Hwan Kim, Hyo-Jong Kim, Joo Sung Kim, Kueongok Kim, Kyung-Jo Kim, Sung Kook Kim, Young-Ho Kim, Jochen Klaus, Anna Kohn, Vladimir Kojecky, Ja Seol Koo, Robert Kozak, Milan Kremer, Tunde Kristof, Frederik Kruger, David Laharie, Adi Lahat-zok, Evgeny Landa, Jonghun Lee, Kang-Moon Lee, Kook Lae Lee, YooJin Lee, Frank Lenze, Wee Chian Lim, Jimmy Limdi, James Lindsay, Pilar Lopez Serrano, Edouard Louis, Stefan Lueth, Giovanni Maconi, Fazia Mana, Steven Mann, John Mansfield, Santino Marchi, Marco Marino, John Marshall, Maria Dolores Martin Arranz, Radu-Bogdan Mateescu, John McLaughlin, Simon McLaughlin, Ehud Melzer, Jessica Mertens, Paul Mitrut, Tamas Molnar, Vinciane Muls, Pushpakaran Munuswamy, Charles Murray, Timna Naftali, Visvakuren Naidoo, Yusuf Nanabhay, Lucian Negreanu, Augustin Nguyen, Thomas Ochsenkuehn, Ambrogio Orlando, Julian Panes Diaz, Maya Paritsky, Dong Il Park, Jihye Park, Luca Pastorelli, Markus Peck-Radosavljevic, Farhad Peerani, Javier Perez Gisbert, Laurent Peyrin-Biroulet, Laurence Picon, Marieke Pierik, Terry Ponich, Francisco Portela, Maartens Jeroen Prins, Istvan Racz, Khan Fareed Rahman, Jean-Marie Reimund, Max Reinshagen, Xavier Roblin, Rodolfo Rocca, Francesca Rogai, Gerhard Rogler, Agnes Salamon, Ennaliza Salazar, Zoltan Sallo, Sunil Samuel, Miquel de los Santos Sans Cuffi, Edoardo Vincenzo Savarino, Vincenzo Savarino, Guillaume Savoye, Andrada Seicean, Christian Selinger, David Martins Serra, Hang Hock Shim, SungJae Shin, Britta Siegmund, Jesse Siffledeen, Wayne Simmonds, Jan Smid, Jose Sollano, Geun Am Song, Alexander Speight, Ioan Sporea, Dirk Staessen, George Stancu, Alan Steel, David Stepek, Victor Stoica, Andreas Sturm, Gyorgy Szekely, Teck Kiang Tan, Carlos Taxonera Samso, John Thomson, Michal Tichy, Gabor Tamas Toth, Zsolt Tulassay, Marcello Vangeli, Marta Varga, Ana Vieira, Stephanie Viennot, Erica Villa, Petr Vitek, Harald Vogelsang, Petr Vyhnalek, Peter Wahab, Jens Walldorf, Byong Duk Ye, Christopher Ziady, Danese S., Colombel J.-F., Lukas M., Gisbert J.P., D'Haens G., Hayee B., Panaccione R., Kim H.-S., Reinisch W., Tyrrell H., Oh Y.S., Tole S., Chai A., Chamberlain-James K., Tang M.T., Schreiber S., Aboo N., Ahmad T., Aldeguer Mante X., Allez M., Almer S., Altwegg R., Andreu Garcia M., Arasaradnam R., Ardizzone S., Armuzzi A., Arnott I., Aumais G., Avni-Biron I., Barrow P., Beales I., Bermejo San Jose F., Bezuidenhout A., Biancone L., Blaeker M., Bloom S., Bokemeyer B., Bossa F., Bossuyt P., Bouguen G., Bouhnik Y., Bouma G., Bourdages R., Bourreille A., Boustiere C., Brabec T., Brand S., Buening C., Buisson A., Cadiot G., Calvet Calvo X., Carbonnel F., Carpio D., Cheon J.H., Chiba N., Chioncel C., Cimpoeru N.-C., Clodi M., Corazza G.R., Cosintino R., Cotter J., Creed T., Cummings F., de' Angelis G.L., De Maeyer M., Desai M., Desilets E., Desreumaux P., Dewit O., Dinter J., Dobru E.D., Douda T., Dumitrascu D.L., Ebert M., Echarri Piudo A., Elkhashab M., Eun C.S., Feagan B., Fejes R., Fidalgo C., Fishman S., Flourie B., Fowler S., Fries W., Fulop C., Fumery M., G Kiss G., Gassner S., Gaya D., Germana B., Gheorghe L.S., Gilletta de Saint Joseph C., Gionchetti P., Goldis A.-E., Goncalves R., Grimaud J.-C., Gyokeres T., Hagege H., Haidar A., Hartmann H., Hasselblatt P., Hebuterne X., Hellstrom P., Hindryckx P., Hlavova H., Hoentjen F., Howaldt S., Hrdlicka L., Huh K.C., Iborra Colomino M.I., Ionita-Radu F., Irving P., Jahnsen J., Jang B., Jansen J., Jeon S.W., Jover Martinez R., Juillerat P., Karlen P., Kaser A., Keil R., Kejariwal D., Keret D., Khanna R., Kim D., Kim D.H., Kim H.-J., Kim J.S., Kim K., Kim K.-J., Kim S.K., Kim Y.-H., Klaus J., Kohn A., Kojecky V., Koo J.S., Kozak R., Kremer M., Kristof T., Kruger F., Laharie D., Lahat-zok A., Landa E., Lee J., Lee K.-M., Lee K.L., Lee Y., Lenze F., Lim W.C., Limdi J., Lindsay J., Lopez Serrano P., Louis E., Lueth S., Maconi G., Mana F., Mann S., Mansfield J., Marchi S., Marino M., Marshall J., Martin Arranz M.D., Mateescu R.-B., McLaughlin J., McLaughlin S., Melzer E., Mertens J., Mitrut P., Molnar T., Muls V., Munuswamy P., Murray C., Naftali T., Naidoo V., Nanabhay Y., Negreanu L., Nguyen A., Ochsenkuehn T., Orlando A., Panes Diaz J., Paritsky M., Park D.I., Park J., Pastorelli L., Peck-Radosavljevic M., Peerani F., Perez Gisbert J., Peyrin-Biroulet L., Picon L., Pierik M., Ponich T., Portela F., Prins M.J., Racz I., Rahman K.F., Reimund J.-M., Reinshagen M., Roblin X., Rocca R., Rogai F., Rogler G., Salamon A., Salazar E., Sallo Z., Samuel S., Sans Cuffi M.D.L.S., Savarino E.V., Savarino V., Savoye G., Seicean A., Selinger C., Serra D.M., Shim H.H., Shin S., Siegmund B., Siffledeen J., Simmonds W., Smid J., Sollano J., Song G.A., Speight A., Sporea I., Staessen D., Stancu G., Steel A., Stepek D., Stoica V., Sturm A., Szekely G., Tan T.K., Taxonera Samso C., Thomson J., Tichy M., Toth G.T., Tulassay Z., Vangeli M., Varga M., Vieira A., Viennot S., Villa E., Vitek P., Vogelsang H., Vyhnalek P., Wahab P., Walldorf J., Ye B.D., and Ziady C.

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Population, Antibodies, Monoclonal, Humanized, Injections, Subcutaneou, Placebo, Severity of Illness Index, Gastroenterology, Young Adult, Double-Blind Method, Internal medicine, Gastrointestinal Agent, Clinical endpoint, medicine, education, Adverse effect, Aged, Aged, 80 and over, education.field_of_study, Hepatology, business.industry, Middle Aged, medicine.disease, Ulcerative colitis, Infliximab, Treatment Outcome, Etrolizumab, Concomitant, Colitis, Ulcerative, Female, business, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], Human, medicine.drug
Abstract

Item does not contain fulltext BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of etrolizumab with infliximab in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, double-blind, double-dummy, parallel-group, phase 3 study (GARDENIA) across 114 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. Participants were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or intravenous infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter for 52 weeks. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All participants and study site personnel were masked to treatment assignment. The primary endpoint was the proportion of patients who had both clinical response at week 10 (MCS ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) and clinical remission at week 54 (MCS ≤2, with individual subscores ≤1); efficacy was analysed using a modified intention-to-treat population (all randomised patients who received at least one dose of study drug). GARDENIA was designed to show superiority of etrolizumab over infliximab for the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT02136069, and is now closed to recruitment. FINDINGS: Between Dec 24, 2014, and June 23, 2020, 730 patients were screened for eligibility and 397 were enrolled and randomly assigned to etrolizumab (n=199) or infliximab (n=198). 95 (48%) patients in the etrolizumab group and 103 (52%) in the infliximab group completed the study through week 54. At week 54, 37 (18·6%) of 199 patients in the etrolizumab group and 39 (19·7%) of 198 in the infliximab group met the primary endpoint (adjusted treatment difference -0·9% [95% CI -8·7 to 6·8]; p=0·81). The number of patients reporting one or more adverse events was similar between treatment groups (154 [77%] of 199 in the etrolizumab group and 151 [76%] of 198 in the infliximab group); the most common adverse event in both groups was ulcerative colitis (55 [28%] patients in the etrolizumab group and 43 [22%] in the infliximab group). More patients in the etrolizumab group reported serious adverse events (including serious infections) than did those in the infliximab group (32 [16%] vs 20 [10%]); the most common serious adverse event was ulcerative colitis (12 [6%] and 11 [6%]). There was one death during follow-up, in the infliximab group due to a pulmonary embolism, which was not considered to be related to study treatment. INTERPRETATION: To our knowledge, this trial is the first phase 3 maintenance study in moderately to severely active ulcerative colitis to use infliximab as an active comparator. Although the study did not show statistical superiority for the primary endpoint, etrolizumab performed similarly to infliximab from a clinical viewpoint. FUNDING: F Hoffmann-La Roche.

Published
2022
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20. Neutralising antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicentre cohort study

Author

Zhigang Liu, Kaixing Le, Xin Zhou, James L Alexander, Simeng Lin, Claire Bewshea, Neil Chanchlani, Rachel Nice, Timothy J McDonald, Christopher A Lamb, Shaji Sebastian, Klaartje Kok, Charlie W Lees, Ailsa L Hart, Richard C Pollok, Rosemary J Boyton, Daniel M Altmann, Katrina M Pollock, James R Goodhand, Nicholas A Kennedy, Tariq Ahmad, Nick Powell, Madiha Islam, Nick Croft, Bessie Cipriano, Caroline Francia, Nosheen Khalid, Ashley Kingston, Irish Lee, Anouk Lehmann, Kinnari Naik, Kevin Samuels, Nicolene Plaatjies, Hafiza Khatun, Farjana Bokth, Elise Pabriaga, Rebecca Saich, Hayley Cousins, Wendy Fraser, Rachel Thomas, Matthew Brown, Benjamin White, Nikolaos Kirkineziadis, Bernadette Tilley, Pennie Porter, Rachel Bryant, Natalia Robaczewska, Rafeeq Muhammed, Rehana Bi, Catherine Cotter, Jayne Grove, Kate Hong, Ruth Howman, Monica Mitchell, Sophie Clayton, Louise Rogers, Sugrah Sultan, Melanie Rooney, Charlotte Cottrill, Salil Singh, Chris Dawe, Robert Hull, Natalie Silva, Julie Chadwick, Laura Robertson, Jonathan Manning, Lauren Finlayson, Allison Roebuck, Joy Dawson, Sunil Sonwalkar, Naomi Chambers, Matthew Robinson, Andrew Haigh, Lear Matapure, Tim Raine, Varun George, Christina Kapizioni, Konstantina Strongili, Tina Thompson, Mohamed Ahmed, Christos Kontos, Claire Dawson, Christophe Bourges, Isabella Barbutti, Megan E Gozzard, Philip Hendy, Rhian Bull, Patricia Costa, Lisa Davey, Hayley Hannington, Kribashnie Nundlall, Catarina Martins, Laura Avanzi, Jaime Carungcong, Sabrina Barr, Richard Appleby, Emma Johnson, Eathar Shakweh, Kath Phillis, Rachel Gascoyne, Amanda Crowder, Amanda Whileman, Ian London, Jenny Grounds, Emmeline Martin, Susie Pajak, Jude Price, Kathryn Cawley, Sandra Powell, Nichola Kearsley, Anjan Dhar, Ellen Brown, Amanda Cowton, Kimberley Stamp, Ben Warner, Carmel Stuart, Louise Lacey, Shanika de Silva, Clare Allcock, Philip Harvey, Lesley Jones, Elise Cooke, Jayne Slater, Dominic King, Johanne Brooks, Pearl Baker, Hannah Beadle, Carina Cruz, Debbie Potter, Joe Collum, Farzana Masters, Aashish Kumar, Samantha Coetzee, Mihaela Peiu, Becky Icke, Jill Williams, Meena Raj, Edward Gaynor, Sibongile Chadokufa, Bonita Huggett, Hamza Meghari, Sara El-Khouly, Fevronia Kiparissi, Waffa Girshab, Lynda Russell-Walker, Christopher Jackson, Sara Sidler, Andrew Claridge, Emily Fowler, Laura McCafferty, Lesley Haxton, Peter Irving, Karolina Christodoulides, Angela Clifford, Patrick Dawson, Sailish Honap, Samuel Lim, Raphael Luber, Karina Mahiouz, Susanna Meade, Parizade Raymode, Rebecca Reynolds, Anna Stanton, Sherill Tripoli, Naomi Hare, Sopuluchukwu Odukwe, Senthuran Balachandran, Emma North, Jessica North, Bria Browne, Jessica Cordle, Ella Jameson, Yih Harn Siaw, Lane Manzano, Jonathan Segal, Ibrahim Al-Bakir, Imran Khakoo, Sofiya Portukhay, Nora Thoua, Katherine Davidson, Jagrul Miah, Lisa Canclini, Alex Hall, Hassina Furreed, Christine Mitchell-Inwang, Melony Hayes, Sally Myers, Alison Talbot, Jack Turnbull, Emma Whitehead, Katie Stamp, Alison Pattinson, Verghese Mathew, Leanne Sherris, Julie Wilcox, Sankaranarayanan Ramachandran, Hayley Robertson, Angela Harvey, Lucy Hicks, Tara-Marie Byrne, Leilani Cabreros, Hannah Downing-Wood, Sophie Hunter, Mohammad Aamir Saifuddin, Hemanth Prabhudev, Sharmili Balarajah, Jan Krucznski, Kalliopi Driva, Andrea D'Mello, Parith Shah, Rocio Castro-Seoane, Hajir Ibraheim, Laura E Constable, Jonathan W Lo, Melissa Torkizadeh, Sherine K Hermangild, Helen Sutherland, Elva Wilhelmsen, Katherine Mackintosh, Ajay M Verma, Juliemol Sebastian, Mohammad Farhad Peerally, Anne-marie Guerdette, Susan Coburn, Ching Yee Novem lam, Donna Durrant, Belinda Schaefer, Solange Serna, Muhammad Shahzad, Alexandra Kent, Lee Meng Choong, Benedetta Pantaloni, Pantelis Ravdas, Babu Vadamalayan, Stephen Foley, Becky Arnold, Cheryl Heeley, Wayne Lovegrove, Donna Sowton, Lynne Allsop, Heidi Gregory, Mandy Gill, Megan Holmes, Valeria Balan, Susan Smith, Sarah Turner, Philip J Smith, Alan Steel, Giovanna Bretland, Sarah King, Martina Lofthouse, Lindsey Rigby, Sreedhar Subramanian, David Tyrer, Kate Martin, Christopher Probert, Nikolaos Kamperidis, Temi Adedoyin, Manisha Baden, Jeannette Brown, Feba Chacko, Lisa Young, Michela Cicchetti, Mohammad Saifuddin, Priya Yesupatham, Rohit Gowda, Maureen Williams, Karen Kemp, Rima Akhand, Glaxy Gray, Anu John, Maya John, Tasnim Mohammed, Diamond Sathe, Natasha Jones, Jennifer Soren, Michael Sprakes, Julie Burton, Patricia Kane, Stephanie Lupton, Jacqueline Bartholomew, Elizabeth Denis, Alison Daniels, George MacFaul, Diane Scaletta, Loria Siamia, Felicity Williams, Chloe Green, Zeljka Ver, Chris Lamb, Mary Doona, Ashleigh Hogg, Lesley Jeffrey, Andrew King, R Alexander Speight, Jennifer Doyle, Ruth Owen, Jenny Haworth, Linda Patterson, Vithusa Varnaulasingam, Craig Mowat, Debbie Rice, Susan MacFarlane, Anne MacLeod, Samera Mohammed, Shona Murray, Anne Elliott, Mary Anne Morris, Louise Coke, Grace Hindle, Eirini Kolokouri, Catherine Wright, Claire Lee, Nicola Ward, Adele Dann, Melanie Lockett, Charlotte Cranfield, Louise Jennings, Ankur Srivastava, Lana Ward, Nouf Jeynes, Poonam Ranga, Praveen Rajasekhar, Lisa Gallagher, Jill Ward, Rae Basnett, Judy Murphy, Lauren Parking, Emma Lawson, Stacey Short, David Devadason, Gordon Moran, Neelam Khan, Lauren Tarr, Charmaine Olivia, Samantha Warbarton, Sian Kelly, Jimmy Limdi, Kay Goulden, Asad Javed, Lauren McKenzie, Julie Melville, Eleanor Liu, Joseph Sabine, Patricia Jacob, Denise McSorland, Nick Schofield, Lisa Cornwall, James Quirke, Emma Crook, Anne Turner, Pradeep Bhandari, Michelle Baker-Moffatt, Joanne Dash, Alison Le Poidevin, Hayley Downe, Lucille Bombeo, Helen Blackman, Rebecca Smith, Alan Wiles, Hannah Bloxham, Jose Dias, Evelyn Nadar, Hollie Curgenven, Ellie Gilham, Jonathan Macdonald, Shona Finan, Faye McMeeken, Misbah Mahmood, Stephanie Shields, John Paul Seenan, Des DeSilva, Susanna Malkakorpi, Rachel Carson, Holly Lawrence, Ofori Boateng, Felix Kpodo, Simon Whiteoak, Kelli Edger-Earley, Luke Vamplew, Joanna Samways, Sue Roffe, Sarah Ingram, Joel James, Sharon Botfield, Fiona Hammonds, Clare James, Zoe Berry, Gemma Aspinall, Sarah Hawkins, Marian Parkinson, Helen Gardner-Thorpe, Suzie Marriott, Clare Redstone, Halina Windak, Ana-Marie Adam, Hannah Mabb, Emma Stevenson, Jessica Record, Charles Murray, Cynthia Diaba, Fexy Joseph, Glykeria Pakou, Yvonne Gleeson, Annalyn Nunag, James Berrill, Natalie Stroud, Carla Pothecary, Lisa Roche, Keri Turner, Lisa Deering, Lynda Israel, Evelyn Baker, Maxine Nash, Andrew Fagbemi, Felicia Jennings, Imelda Mayor, Jill Wilson, Alice Wheeler, Nicola Phillips, John Gordon, Emma Levell, Silvia Zagalo, Ina Hoad, Bindu Anil, Richard Russell, Paul Henderson, Margaret Millar, Christopher Alexakis, Natalia Michalak, Cheryl Marriott, Sarah Stone, Veronika Pristopan, John Saunders, Helen Burton, Vanessa Cambridge, Tonia Clark, Charlotte Ekblad, Sarah Hierons, Joyce Katebe, Emma Saunsbury, Rachel Perry, Matthew Brookes, Kathryn Davies, Marie Green, Ann Plumbe, Clare Ormerod, Helen Christensen, Hannah Howlett, Anne Keen, Jonathan Ogor, Marie Greenhaigh, Karen Knowles, Shanzi Yin, Maria Poulaka, Alpha Anthony, Emily Newitt, Fiona Trim, Ruth Casey, Katherine Seymour, Catherine Reed, Lijo Joy, Edward Fogden, Kalisha Russell, Samia Hussain, Anne Phillips, Muaad Abdulla, Jeff Butterworth, Colene Adams, Mandy Carnahan, Elizabeth Buckingham, Danielle Childs, Alison Magness, Jo Stickley, Nichola Motherwell, Louise Tonks, Hannah Gibson, Kate Wistance, Caradog Thomas, Elaine Brinkworth, Lynda Connor, Amanda Cook, Tabitha Rees, Rachel Harford, Sean Farley, Marie Jones, Emma Wesley, Alison Moss, Jacob Lucas, Claire Lorimer, Maria Oleary, Maxine Dixon, Fiona Goodchild, Rebecca Twenlow, Corinne Pawley, Arvind Ramadas, Julie Tregonning, Olaku Okeke, Wendy Jackson, Ioannis Koumoutsos, Viji George, Swapna Kunhunny, Sophie Laverick, Isla Anderson, Sophie Smith, Joan Joyce, Sarala Janarthan, Kamal Patel, Mariam Ali, Hilda Mhandu, Aleem Rana, Katherine Spears, Joana Teixeira, Mark Mencias, Abigail Seaward, Jessica Sousa, Nooria Said, Mark Soomaroo, Valentina Raspa, Asha Tacouri, Nicholas Reps, Rebecca Martin, Tinashe Samakomva, Christian Selinger, Jenelyn Carbonell, Felicia Onovira, Doris Quartey, Alice L'Anson, Andrew Ashworth, Jessica Bailey, Angie Dunn, Gjuzel Bespaloi, Harold Rasalan, Zahid Mahmood, Racheal Campbell, Liane Marsh, Tricia Coughlan, Wisam Jafar, Janet Marrs, Christopher McPheat, Monira Rahman, Sarah Davies, Ruth Habibi, Ellen Jessup-Dunton, Teishel Joefield, Reina Layug, Vinod Patel, Joanne Vere, Victoria Turner, Susan Kilroy, Martina Coulding, Martyn Clark, Jacqueline McCormick, Attiya Nisar, Gareth Walker, Stacey Atkins, Jasmine Growdon, Becky George, Charlotte McNeill, Bryony Reed, Angela Foulds, Catherine Marshall, Michele Allison, Briony Dillon, Rachel Cooney, Lillie Bennett, Louise Bowlas, Sharafaath Shariff, Aileen Fraser, Dwayne Punnette, Rebecca Lambert, Charlotte Bishop-Hurman, Elizabeth Undrell, Katherine Belfield, Said Din, Catherine Addleton, Marie Appleby, Johanna Brown, Kathleen Holding, Catherine Fraser, Janice Birkenshaw, Jodie Williams, Kamille Maulion, Meg Lane, Arita Kravale, Claud Smith, Patricia Hooper, John deCaestecker, Olivia Watchorn, Ellie Clarke, Chris Hayward, Susan Inniss, Lucy Pritchard, Karen Rudge, Amanda Carney, Sarah Griffee, Jervoise Andreyev, Sathish Babu, Caroline Hayhurst, Carol Lockwood, Lynn Osborne, Amanda Roper, Karen Warner, Julia Hindle, Tara Lawrence, Kimberley Netherton, Caroline Watt, Kinga Szymiczek, Shameer Mehta, James Bell, William Blad, Lisa Whitley, Roman Jastrub, Dhamaraj Durai, Mark Baker, Elizabeth John Sivamurugan, Mim Evans, Fraser Cummings, Clare Harris, Amy Jones, Liga Krauze, Sohail Rahmany, Michelle Earl, Jenny Vowles, Audrey Torokwa, Mirela Petrova, Andrew Procter, Jo Stanley, Claudia Silvamoniz, Marion Bettey, Amar Wahid, Zoe Morrison, Rhian Thomas-Turner, Louise Yendle, Jennifer Muller, Marcus Mitchell, John Kirkwood, Anna Barnes, Rakesh Chaudhary, Melanie Claridge, Chiara Ellis, Cheryl Kemp, Ogwa Tobi, Jentus Milton, Emma Johnston, Metod Oblak, Carmen Winpenny, Marie-Louise Svensson, Jo Godden, Marium Ashhar, Debbie Alexander, Kate Covil, Lauranne Derikx, Sryros Siakavellas, Helen Baxter, Scott Robertson, Linda Smith, Beena Poulose, Anne Colemam, Margareta Balint, Gareth Rhys-Jones, Helen Watters, Susan Begg, Beatriz Grosalcalde, Judy Coyle, Kerrie Johns, Rachel Hughes, Janet Phipps, Abigail Taylor, Catherine MacPhee, Suzanne Brooks, Jolene John, Michelle Edwards, Katie Smith, Linda Howard, Dianne Wood, Ajay Muddu, Laura Barman, Janine Mallinson, Tania Neale, Diana Ionita, Kerry Elliot, Alison Turnball, Iola Thomas, Alice Thomas, Kelly Andrews, Jonathon Sutton, Caroline Mulvaney Jones, Julia Roberts, and Jeannie Bishop

Subjects
Hepatology, Gastroenterology, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5]
Abstract

Contains fulltext : 291657.pdf (Publisher’s version ) (Open Access) BACKGROUND: Anti-TNF drugs, such as infliximab, are associated with attenuated antibody responses after SARS-CoV-2 vaccination. We aimed to determine how the anti-TNF drug infliximab and the anti-integrin drug vedolizumab affect vaccine-induced neutralising antibodies against highly transmissible omicron (B.1.1.529) BA.1, and BA.4 and BA.5 (hereafter BA.4/5) SARS-CoV-2 variants, which possess the ability to evade host immunity and, together with emerging sublineages, are now the dominating variants causing current waves of infection. METHODS: CLARITY IBD is a prospective, multicentre, observational cohort study investigating the effect of infliximab and vedolizumab on SARS-CoV-2 infection and vaccination in patients with inflammatory bowel disease (IBD). Patients aged 5 years and older with a diagnosis of IBD and being treated with infliximab or vedolizumab for 6 weeks or longer were recruited from infusion units at 92 hospitals in the UK. In this analysis, we included participants who had received uninterrupted biological therapy since recruitment and without a previous SARS-CoV-2 infection. The primary outcome was neutralising antibody responses against SARS-CoV-2 wild-type and omicron subvariants BA.1 and BA.4/5 after three doses of SARS-CoV-2 vaccine. We constructed Cox proportional hazards models to investigate the risk of breakthrough infection in relation to neutralising antibody titres. The study is registered with the ISRCTN registry, ISRCTN45176516, and is closed to accrual. FINDINGS: Between Sept 22 and Dec 23, 2020, 7224 patients with IBD were recruited to the CLARITY IBD study, of whom 1288 had no previous SARS-CoV-2 infection after three doses of SARS-CoV-2 vaccine and were established on either infliximab (n=871) or vedolizumab (n=417) and included in this study (median age was 46·1 years [IQR 33·6-58·2], 610 [47·4%] were female, 671 [52·1%] were male, 1209 [93·9%] were White, and 46 [3·6%] were Asian). After three doses of SARS-CoV-2 vaccine, 50% neutralising titres (NT50s) were significantly lower in patients treated with infliximab than in those treated with vedolizumab, against wild-type (geometric mean 2062 [95% CI 1720-2473] vs 3440 [2939-4026]; p

Published
2023

21. Does exposure to different menstrual products affect the vaginal environment?

Author

Nicolas Tessandier, Ilkay Başak Uysal, Baptiste Elie, Christian Selinger, Claire Bernat, Vanina Boué, Sophie Grasset, Soraya Groc, Massilva Rahmoun, Bastien Reyné, Noemi Bender, Marine Bonneau, Christelle Graf, Vincent Tribout, Vincent Foulongne, Jacques Ravel, Tim Waterboer, Christophe Hirtz, Ignacio G. Bravo, Jacques Reynes, Michel Segondy, Carmen Lia Murall, Nathalie Boulle, Tsukushi Kamiya, and Samuel Alizon

Subjects
Genetics, Ecology, Evolution, Behavior and Systematics
Abstract

The vaginal ecosystem is a key component of women's health. It also represents an ideal system for ecologists to investigate the consequence of perturbations on species diversity and emerging properties between organizational levels. Here, we study how exposure to different types of menstrual products is linked to microbial, immunological, demographic, and behavioural measurements in a cohort of young adult women who reported using more often tampons (n = 107) or menstrual cups (n = 31). We first found that cup users were older and smoked less than tampon users. When analysing health indicators, we detected potential associations between cups use reporting and fungal genital infection. A multivariate analysis confirmed that in our cohort, reporting using cups over tampons was associated with the higher odds ratio to report a fungal genital infection diagnosis by a medical doctor within the last 3 months. We did not detect significant differences between groups in terms of their bacterial vaginal microbiota composition and found marginal differences in the level of expression of 20 cytokines. However, a multivariate analysis of these biological data identified some level of clustering based on the menstrual product type preferred (cups or tampons). These results suggest that exposure to different types of menstrual products could influence menstrual health. Larger studies and studies with a more powered setting are needed to assess the robustness of these associations and identify causal mechanisms.

Published
2022

22. Ustekinumab and Vedolizumab Are Equally Safe and Effective in Elderly Crohn's Disease Patients

Author

Gerum Gashaw Gebeyehu, Joseph Fiske, Eleanor Liu, Jimmy K. Limdi, Giacomo Broglio, Christian Selinger, Violeta Razsanskaite, Philip J. Smith, Paul K. Flanagan, and Sreedhar Subramanian

Subjects
Physiology, Gastroenterology
Abstract

Anti-tumour necrosis factor (anti-TNF) agents are associated with increased infection risk among elderly inflammatory bowel disease (IBD) patients, and thus, alternative biologics may be preferable. However, little comparative data exist on the safety and efficacy of vedolizumab and ustekinumab in elderly IBD patients.To compare the safety and effectiveness of ustekinumab and vedolizumab in elderly Crohn's disease patients.Patients ≥ 60 years old who commenced ustekinumab or vedolizumab for Crohn's disease (CD) were included. Primary outcome was serious infections, defined as requiring hospitalisation. Efficacy was assessed by treatment persistence and clinical response rates. We appropriately adjusted for confounders using propensity score-matched analysis weighted by the inverse predicted probability of treatment weighing and performed a logistic regression analysis to assess factors associated with serious infections and treatment persistence.Eighty-three patients commencing ustekinumab and 42 commencing vedolizumab therapy were included. In a propensity adjusted cohort, the rate of serious infection and treatment persistence were comparable between ustekinumab and vedolizumab. There was a significant reduction in HBI at 6 and 12 months compared to baseline in both groups. Male gender was positively associated with serious infection risk at 12 months, and penetrating disease behaviour was positively associated with 12-month treatment persistence. Baseline HBI score was negatively associated with 12-month treatment persistence. Cox regression analysis showed no overall difference in treatment discontinuation-free and serious infection-free survival by 12 months.We observed comparable safety and effectiveness for ustekinumab and vedolizumab in treating elderly CD patients.

Published
2022

23. Assessment, endoscopy, and treatment in patients with acute severe ulcerative colitis during the COVID-19 pandemic (PROTECT-ASUC): a multicentre, observational, case-control study

Author

Shaji Sebastian, Gareth J Walker, Nicholas A Kennedy, Thomas E Conley, Kamal V Patel, Sreedhar Subramanian, Alexandra J Kent, Jonathan P Segal, Matthew J Brookes, Neeraj Bhala, Haidee A Gonzalez, Lucy C Hicks, Shameer J Mehta, Christopher A Lamb, Shukri Abdale, Abdullah Abbasi, Anwar Abusrewil, Precious Aghimien, Saeed Ahmed, Akram Ali, Amjad Ali, Jad Alkhoury, Patrick Allen, Ammar Al-Rifaie, Richard Appleby, Ramesh Arasaradnam, Naila Arebi, Bradley Arms-Williams, Muteeb Ashraf, Andrea Au, Tamar Avades, Homira Ayubi, Saleha Azhar, Samantha Baillie, Sharmili Balarajah, Aaron Bancil, Abdul Basit, Murad Bayati, Andrew Bell, Alexander Berry, Shivaram Bhat, Joya Bhattacharyya, Sophia Bishop, Laura Blackmore, Ashley Bond, Simon Borg-Bartolo, Emma Botwright, Sonia Bouri, Stephen Boyle, Neil Bradley, Fiona Brailsford, Deborah Britton, Caitlin Brown, Rhys Butcher, Jeffrey Butterworth, Rachel Campbell, Roisin Campbell, Iona Campbell, Ruth Carr, Josiah Carter, Peter Cartlidge, Rajiv Chandy, Kelly Chatten, Rakesh Chaudhary, Desmond Chee, Jonathan Cheesbrough, Antonia Churchhouse, Sara Chughtai, Jennie Clough, Alexander Cole, Johannah Cook, Rachel Cooney, Sarah Cotton, Archibald Coulter, Tamsin Critchlow, Frederic Cuison, Chris Curran, Ana-Maria Darie, Robin Dart, Pantong Davwar, Kasamu Kabiru Dawa, Anjan Dhar, Shahida Din, Kok Leong Diong, Benjamin Disney, Emma Dooks, Louise Downey, Anita D'Souza, Lovesh Dyall, Ali El Rida El Masri, Mary Elias, Holli Evans, Richard Felwick, Michael Finegan, Paul Flanagan, Rishi Fofaria, Steven Chung Ming Fong, Richard Fox, Aileen Fraser, Christian Frunza, Alhassan Ghodeif, Nivedita Ghosh, Leah Gilroy, Larissa Good, John Gordon, Nicola Grasso, Aurelién M Guéroult, James Gulliver, Sarah Guthrie, Markus Gwiggner, Mina Hanna, Christopher Harlow, Wendy Harrison, Ailsa Hart, Barney Hawthorne, Julie Henshaw, Rosaleen Herdman-Grant, Patricia Hooper, Willow Howard, Nasir Hussain, Thomas Hutton, Aye Mya Htun, Peter Irving, Reema Jagdish, Anum Javed, Asima Javed, Nishani Jayasooriya, Matthew Johnson, Emma Johnston, Gareth-Rhys Jones, Cynthia Kanagasundaram, Fotein Karagkouni, Karen Kemp, Cheryl Kemp, Hesham Khalil, Najeebullah Khan, Mais Khasawneh, Bilal Khurshid, Andrew King, Beverley Kirkham, Fiona Kirkham, Flora Kokwaro, Mohamed Korani, Ioannis Koumoutsos, Aditi Kumar, Anish John Kuriakose Kuzhiyanjal, Martyn Lakeland, Sophie Laverick, Charlie Lees, Emma Levell, Scott Levison, Samuel Lim, Yuen-Hui Lim, Jimmy Limdi, James Oliver Lindsay, Jessica Lisle, Alan Lobo, Raphael Luber, Laura Lucaciu, Holly Lyne, Jonathan MacDonald, Aarani Mahalingam, Sara Mahgoub, Ridhima Malakar, Fenella Marley, Joy Mason, Zia Mazhar, Hannah McCaughan, Tracy Naughton, Adam McCulloch, Stuart McIlwaine, Nirmol Meah, Leila Mebarek, Mike Mendall, Radharetnas Meiarasu, Nasir Mir, Tilly Mills, Jentus Milton, Victoria Moffat, Gordon W Moran, Liam Morris, Gary Morrison, Graham Morrison, Robert Mulligan, Charles Murray, Jennifer Murray, Mutwakil Musharaf, Sally Myers, Pineshwari Naeck-Boolauky, Andres Naranjo, Janardhan Navaratnam, Deanna Naylor, Emma Nixon, Kirsty Nixon, Hesam Ahmadi Nooredinvand, Uche Nosegbe, Olaolu Olabintan, Elaine Ong Ming San, Comfort Okpeh, Hayley Owen, Ruth Owen, Christopher Palmer-Jones, Kalyan Peddada, Mohammad Peerally, Rebecca Perkins, Frank Phillips, Keith Pohl, Richard Pollok, Nick Powell, Farah Qayyum, Maria Qurashi, Mohammed Nabil Quraishi, Elizabeth Ratcliffe, Shellie Radford, Sohail Rahmany, Hanin Ramadan, Arvind Ramadas, Anne Reddington, Tom Riley, Peter Rimmer, Susan Ritchie, Jacqueline Roscoe, Konstantina Rosiou, Siobhan Rowland, Joseph Sabine, Aamir Saifuddin, Mark Samaan, Priya Sarkar, Shahzad Sarwar, Ayodele Sasegbon, Jayne Saunders, Gregory Sebepos-Rogers, John Paul Seenan, Christian Selinger, Solange Serna, Sonika Sethi, Matthew Shale, Richard Shenderey, Achuth Shenoy, Yousuf Sherifat, Roosey Sheth, Spyros Siakavellas, Rafid Sikafi, Amar Singh, Salil Singh, Updesh Singh, Ganesh Sivaji, Philip Smith, R Alexander Speight, Andy Spence, Catherine Stansfield, Helen Steed, Kishaani Suseeharan, Maria Tabuso, Donatas Taucius, Joanne Taylor, Amit Thakor, Tony Tham, Gill Townsend, Tristan Townsend, Thomas Troth, Ruth Tunney, Kelly Turner, Nosheen Umar, Vithushan Vakeeswarasarma, Ajay M Verma, Hazel Wallace, Katharina Wallis, Hannah Walton, Bo Wang, Eleanor Warner, Callum Watson, Eleanor Watson, Susie Wen, Monika Widlak, Maureen Williams, Amy Woods, Lisa Younge, and Mansoor Zafar

Subjects
medicine.medical_specialty, Hepatology, business.industry, Incidence (epidemiology), Gastroenterology, Case-control study, medicine.disease, Inflammatory bowel disease, Ulcerative colitis, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Severity of illness, Cohort, Medicine, 030211 gastroenterology & hepatology, business, Historical Cohort, Cohort study
Abstract

Summary Background There is a paucity of evidence to support safe and effective management of patients with acute severe ulcerative colitis during the COVID-19 pandemic. We sought to identify alterations to established conventional evidence-based management of acute severe ulcerative colitis during the early COVID-19 pandemic, the effect on outcomes, and any associations with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes. Methods The PROTECT-ASUC study was a multicentre, observational, case-control study in 60 acute secondary care hospitals throughout the UK. We included adults (≥18 years) with either ulcerative colitis or inflammatory bowel disease unclassified, who presented with acute severe ulcerative colitis and fulfilled the Truelove and Witts criteria. Cases and controls were identified as either admitted or managed in emergency ambulatory care settings between March 1, 2020, and June 30, 2020 (COVID-19 pandemic period cohort), or between Jan 1, 2019, and June 30, 2019 (historical control cohort), respectively. The primary outcome was the proportion of patients with acute severe ulcerative colitis receiving rescue therapy (including primary induction) or colectomy. The study is registered with ClinicalTrials.gov , NCT04411784 . Findings We included 782 patients (398 in the pandemic period cohort and 384 in the historical control cohort) who met the Truelove and Witts criteria for acute severe ulcerative colitis. The proportion of patients receiving rescue therapy (including primary induction) or surgery was higher during the pandemic period than in the historical period (217 [55%] of 393 patients vs 159 [42%] of 380 patients; p=0·00024) and the time to rescue therapy was shorter in the pandemic cohort than in the historical cohort (p=0·0026). This difference was driven by a greater use of rescue and primary induction therapies with biologicals, ciclosporin, or tofacitinib in the COVID-19 pandemic period cohort than in the historical control period cohort (177 [46%] of 387 patients in the COVID-19 cohort vs 134 [36%] of 373 patients in the historical cohort; p=0·0064). During the pandemic, more patients received ambulatory (outpatient) intravenous steroids (51 [13%] of 385 patients vs 19 [5%] of 360 patients; p=0·00023). Fewer patients received thiopurines (29 [7%] of 398 patients vs 46 [12%] of 384; p=0·029) and 5-aminosalicylic acids (67 [17%] of 398 patients vs 98 [26%] of 384; p=0·0037) during the pandemic than in the historical control period. Colectomy rates were similar between the pandemic and historical control groups (64 [16%] of 389 vs 50 [13%] of 375; p=0·26); however, laparoscopic surgery was less frequently performed during the pandemic period (34 [53%] of 64] vs 38 [76%] of 50; p=0·018). Five (2%) of 253 patients tested positive for SARS-CoV-2 during hospital treatment. Two (2%) of 103 patients re-tested for SARS-CoV-2 during the 3-month follow-up were positive 5 days and 12 days, respectively, after discharge from index admission. Both recovered without serious outcomes. Interpretation The COVID-19 pandemic altered practice patterns of gastroenterologists and colorectal surgeons in the management of acute severe ulcerative colitis but was associated with similar outcomes to a historical cohort. Despite continued use of high-dose corticosteroids and biologicals, the incidence of COVID-19 within 3 months was low and not associated with adverse COVID-19 outcomes. Funding None.

Published
2021
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25. The source of individual heterogeneity shapes infectious disease outbreaks

Author

Christian Selinger, Samuel Alizon, Baptiste Elie, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Alizon, Samuel, Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), and Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0106 biological sciences, Transmission rate, Secondary infection, Biology, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, 010603 evolutionary biology, 01 natural sciences, General Biochemistry, Genetics and Molecular Biology, Disease Outbreaks, 03 medical and health sciences, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, [SDV.BID.SPT] Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, [SDV.EE.ECO] Life Sciences [q-bio]/Ecology, environment/Ecosystems, [SDV.BID.EVO] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Humans, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Epidemics, Probability, 030304 developmental biology, General Environmental Science, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Ecology, Individual heterogeneity, General Immunology and Microbiology, Infectious disease transmission, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Outbreak, [SDV.EE.IEO] Life Sciences [q-bio]/Ecology, environment/Symbiosis, General Medicine, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Monitoring and control, 3. Good health, [SDE.BE] Environmental Sciences/Biodiversity and Ecology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Evolutionary biology, Infectious disease (medical specialty), [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.GEN.GPO] Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Epidemic model, General Agricultural and Biological Sciences, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract

International audience; Infectious disease transmission patterns in some outbreaks can be more heterogeneous than in others, with striking effects on the way epidemics unfold. Some studies show that the biological sources of heterogeneity may matter, but they tend to do so without controlling for the overall heterogeneity in the number of secondary cases caused by an infection. Here, we control for this important bias to explore the role of individual variation in infection duration and transmission rate on parasite emergence and spread. We simulate outbreaks using a stochastic SIR model, with and without parasite evolution. Consistently with existing studies, we show that the variance in the number of secondary infections has the strongest effect on outbreak emergence probability but has little effect on the epidemic dynamic once emergence is certain. The origin of heterogeneity also affects the probability of emergence, but its more striking effects are about properties of epidemics that do emerge. In particular, assuming more realistic variances in infection duration distributions lead to faster outbreaks and a higher peak of incidence. When the parasite requires evolutionary changes to be able to spread, the impact of heterogeneity depends on the underlying evolutionary model. If the parasite evolves within the host, decreasing the infection duration variance decreases the probability of emergence. These results show that using realistic distributions for infection duration is necessary to accurately capture the effect of individual heterogeneity on epidemiological dynamics, which has implications for the monitoring and control of infectious diseases, as well as data collection.

Published
2022
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26. Gastroenterology team members' knowledge and practices with fertility therapy for women with inflammatory bowel disease

Author

Robyn Laube, Eleanor Liu, Ying Li, Rupert W. Leong, Jimmy Limdi, and Christian Selinger

Subjects
Gastroenterology
Abstract

Introduction: Fecundity may be reduced in women with active inflammatory bowel disease (IBD) or prior IBD-related surgery, and these women may require assisted reproductive technology (ART). There are no guidelines for women with IBD to outline referral criteria for ART. Methods: We performed a prospective, multicentre, international questionnaire of gastroenterologists, gastroenterology trainees, and IBD nurses. The primary outcome was to establish clinical practices and fertility therapy referral patterns among gastroenterology team members. We hypothesised that the lack of knowledge and awareness may delay or prevent initiation of fertility consultation referrals. Discussion: Of 182 participants, most had never initiated a referral for fertility therapy (69.8%), and of respondents who do initiate referrals, 50% wait until the patient has been unsuccessfully attempting conception for 12 months. Participants were significantly more likely to initiate a fertility therapy referral if they believed ART was effective ( p = 0.038), not impeded by IBD-related surgery ( p = 0.053), and if they had access to a dedicated IBD-pregnancy clinic ( p = 0.027). Superior pregnancy knowledge was predictive of a greater likelihood of fertility therapy referrals ( p = 0.037). All participants thought they had inadequate knowledge about ART in IBD, and 96.2% expressed desire to improve their knowledge. Conclusion: Gastroenterology team members infrequently initiate referrals for fertility therapy consultation in women with IBD, increasing their risk of remaining childless. Implementation of dedicated IBD pregnancy clinics and targeted education programmes to increase awareness of ART in women with IBD might increase referral rates and reduce infertility.

Published
2021

27. Increased risk of fungal infection detection in women using menstrual cups vs. tampons: a cross-sectional study

Author

Nicolas Tessandier, Ilkay Başak Uysal, Baptiste Elie, Christian Selinger, Claire Bernat, Vanina Boué, Sophie Grasset, Soraya Groc, Tsukushi Kamiya, Massilva Rahmoun, Bastien Reyné, Noemi Bender, Marine Bonneau, Christelle Graf, Vincent Tribout, Vincent Foulongne, Jacques Ravel, Tim Waterboer, Christophe Hirtz, Ignacio G Bravo, Jacques Reynes, Michel Segondy, Carmen Lia Murall, Nathalie Boulle, and Samuel Alizon

Abstract

ObjectiveTo determine if the use of menstrual cups rather than tampons is associated with more or less health risk.DesignAnalysing biological, demographic, and behavioural data in a cohort of women who reported using mostly tampons (n = 81) or menstrual cups (n = 22).SettingA cross-sectional analysis using the inclusion data of a single centre longitudinal study.Population149 women from 18 to 25 years old living in the area of Montpellier (France) who reported having at least one new sexual partner over the last year.MethodsStatistical modelling (mainly binomial regression models and factor analyses of mixed data).Main Outcome MeasuresSelf-reported data from questionnaires (fungal infection, urinary tract infection, stress level) and biological data (HPV screening, vaginal microbiota profiling, circulating antibodies titration, and local cytokine concentrations).ResultsWe identify an increased risk of reporting fungal infections for women using menstrual cups over tampons. We do not detect significant differences in terms of vaginal microbiota composition or local cytokines expression profile but find that women fall into two different clusters in a factor analysis of mixed data depending on the type of menstrual product they use more (cups or tampons).ConclusionsThese results point to potential health risks in the use of menstrual cups and differences in local vaginal environments. In-depth studies are needed to better understand potential associations between menstrual product use and women’s health.FundingEuropean Research Council (EVOLPROOF, grant 648963)EthicsThe PAPCLEAR study ClinicalTrials.gov identifier is NCT02946346.Tweetable abstractA cross-sectional study finds a significant association between menstrual cup use and fungal infection risk.

Published
2021
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29. Non-Markovian modelling highlights the importance of age structure on Covid-19 epidemiological dynamics

Author

Christian Selinger, Ramsès Djidjou-Demasse, Quentin Richard, Samuel Alizon, Bastien Reyné, Camille Noûs, and Mircea T. Sofonea

Subjects
Structure (mathematical logic), education.field_of_study, Partial differential equation, Formalism (philosophy), Computer science, Workaround, Ordinary differential equation, Population, Econometrics, Tacit assumption, education, Rendering (computer graphics)
Abstract

The Covid-19 pandemic outbreak was followed by a huge amount of modelling studies in order to rapidly gain insights to implement the best public health policies. Most of these compartmental models involved ordinary differential equations (ODEs) systems. Such a formalism implicitly assumes that the time spent in each compartment does not depend on the time already spent in it, which is at odds with the clinical data. To overcome this “memoryless” issue, a widely used solution is to increase and chain the number of compartments of a unique reality (e.g. have infected individual move between several compartments). This allows for greater heterogeneity and thus be closer to the observed situation, but also tends to make the whole model more difficult to apprehend and parameterize. We develop a non-Markovian alternative formalism based on partial differential equations (PDEs) instead of ODEs, which, by construction, provides a memory structure for each compartment thereby allowing us to limit the number of compartments. We apply our model to the French 2021 SARS-CoV-2 epidemic and, while accounting for vaccine-induced and natural immunity, we analyse and determine the major components that contributed to the Covid-19 hospital admissions. The results indicate that the observed vaccination rate alone is not enough to control the epidemic, and a global sensitivity analysis highlights a huge uncertainty attributable to the age-structured contact matrix. Our study shows the flexibility and robustness of PDE formalism to capture national COVID-19 dynamics and opens perspectives to study medium or long-term scenarios involving immune waning or virus evolution.

Published
2021
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31. Analysing different exposures identifies that wearing masks and establishing COVID-19 areas reduce secondary-attack risk in aged-care facilities

Author

Mircea T. Sofonea, Hubert Blain, Amandine Pisoni, Samuel Alizon, Christian Selinger, Bastien Reyné, Stéphanie Miot, Edouard Tuaillon, Jean Bousquet, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Humboldt University Of Berlin, Berlin Institute of Health (BIH), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), EuroMov - Digital Health in Motion (Euromov DHM), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Montpellier (UM), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-20-COVI-0098,PHYEPI,Intégration de données de séquences et d'incidence pour analyser et contrôler les épidémies virales(2020), Génétique et évolution des maladies infectieuses (GEMI), and Alizon, Samuel

Subjects
Epidemiology, Generalised Linear Mixed Models, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, Corrections, law.invention, 0302 clinical medicine, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Infection control, aged care facilities, secondary-attack risk, 030212 general & internal medicine, aged-care facilities, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Likelihood Functions, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], secondary attack risk, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Masks, General Medicine, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Transmission (mechanics), [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Original Article, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 03 medical and health sciences, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Environmental health, Humans, AcademicSubjects/MED00860, Aged care, Epidemics, mask wearing, Aged, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], SARS-CoV-2, business.industry, Outbreak, COVID-19, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, generalized linear mixed models, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, business, 030217 neurology & neurosurgery, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract

Background The COVID-19 epidemic has spread rapidly within aged-care facilities (ACFs), where the infection-fatality ratio is high. It is therefore urgent to evaluate the efficiency of infection prevention and control (IPC) measures in reducing SARS-CoV-2 transmission. Methods We analysed the COVID-19 outbreaks that took place between March and May 2020 in 12 ACFs using reverse transcription–polymerase chain reaction (RT–PCR) and serological tests for SARS-CoV-2 infection. Using maximum-likelihood approaches and generalized linear mixed models, we analysed the proportion of infected residents in ACFs and identified covariates associated with the proportion of infected residents. Results The secondary-attack risk was estimated at 4.1%, suggesting a high efficiency of the IPC measures implemented in the region. Mask wearing and the establishment of COVID-19 zones for infected residents were the two main covariates associated with lower secondary-attack risks. Conclusions Wearing masks and isolating potentially infected residents appear to be associated with a more limited spread of SARS-CoV-2 in ACFs.

Published
2021
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32. Cytokine response following perturbation of the cervicovaginal milieu during HPV genital infection

Author

Vanina Boué, Carmen Lía Murall, Nathalie Jacobs, Claire Bernat, Massilva Rahmoun, Soraya Groc, Marine Bonneau, Jacques Reynes, Samuel Alizon, Christophe Hirtz, Christelle Graf, Christian Selinger, Sophie Grasset, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Liège, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Project: 648963,H2020,ERC-2014-CoG,EVOLPROOF(2015), Génétique et évolution des maladies infectieuses (GEMI), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Alizon, Samuel, Are HPV vaccines ‘evolution-proof’? Multilevel evolutionary ecology of human oncoviruses - EVOLPROOF - - H20202015-09-01 - 2020-08-31 - 648963 - VALID, and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
0301 basic medicine, Allergy, Cervix Uteri, Alphapapillomavirus, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, 0302 clinical medicine, Mucosal immunity, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Interleukin-1alpha, Medicine, Longitudinal Studies, Macrophage inflammatory protein, 0303 health sciences, Chlamydia, Interleukin-12 Subunit p40, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], HPV infection, virus diseases, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], female genital diseases and pregnancy complications, 3. Good health, Cytokine response, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, 030220 oncology & carcinogenesis, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Vagina, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cytokines, Female, Bacterial vaginosis, medicine.symptom, Oncovirus, Adult, Adolescent, Immunology, Natural history, Inflammation, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Young Adult, 03 medical and health sciences, Sexually active, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Humans, Sex organ, 030304 developmental biology, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, 030203 arthritis & rheumatology, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], business.industry, Macrophages, Papillomavirus Infections, Cancer, Human Papillomavirus, medicine.disease, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 030104 developmental biology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, business, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract

Human papillomaviruses (HPVs) are the most oncogenic viruses known to human, causing nearly all cervical cancers worldwide. Highly prevalent in young, sexually active women, most HPV infections are cleared within 3 years, and only a minority of those infections persist and lead to cancer later in life. To better characterize the immuno-modulatory impact of early HPV infection and more generally perturbations of the cervicovaginal milieu, we measured changes in a panel of 20 cytokines, known as highly dynamic effector molecules implicated in cell signaling. We analyzed 92 cervicovaginal samples collected from young, sexually active women who were tested for or diagnosed with HPV, chlamydia, and bacterial vaginosis. Also, symptoms associated with genital inflammation and infection were collected through self-reporting.Following a parsimonious multi-factor modeling approach, our statistical analyses revealed that increased IL-1Alpha and IL-12/IL-23p40 concentrations were associated with HPV infection. Cytokine network analysis further highlighted the role of IL-1Alpha and macrophage inflammatory proteins (MIP-3Alpha) in HPV-associated immuno-modulation.

Published
2021
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33. Optimizing the early detection of low pathogenic avian influenza H7N9 virus in live bird markets

Author

Timothée Vergne, Pawin Padungtod, Claire Guinat, Long Pham Thanh, Ramsès Djidjou-Demasse, Tifenn Corre, Christian Selinger, Thuy Nguyen Thi Thanh, Ken Inui, Damian Tago, Didier Raboisson, Mathilde Paul, Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Food and Agriculture Organization of the United Nations [Rome, Italie] (FAO), Observatoire des Programmes Communautaires de Développement Rural (US ODR), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Ministry of Agriculture and Rural Development [Hanoï] (MARD), The research was funded by the United States Agency for International Development (USAID) and the FEDER/Région Occitanie Recherche et Sociétés 2018—AI-TRACK., Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
China, [SDV]Life Sciences [q-bio], Biomedical Engineering, Biophysics, Early detection, low pathogenic H7N9 avian influenza virus, Bioengineering, Biology, medicine.disease_cause, Influenza A Virus, H7N9 Subtype, Biochemistry, Virus, Poultry, law.invention, transmission model, Biomaterials, 03 medical and health sciences, 0302 clinical medicine, law, Environmental health, Influenza, Human, Asian country, medicine, Animals, Humans, 030212 general & internal medicine, Research Articles, 030304 developmental biology, 0303 health sciences, live-bird markets, Diagnostic strategy, Low pathogenic, Influenza A virus subtype H5N1, 3. Good health, Virus detection, surveillance strategies, Transmission (mechanics), Vietnam, Influenza in Birds, Life Sciences–Mathematics interface, Biotechnology
Abstract

In Southeast Asia, surveillance at live bird markets (LBMs) has been identified as crucial for detecting avian influenza viruses (AIV) and reducing the risk of human infections. However, the design of effective surveillance systems in LBMs remains complex given the rapid turn-over of poultry. We developed a deterministic transmission model to provide guidance for optimizing AIV surveillance efforts. The model was calibrated to fit one of the largest LBMs in northern Vietnam at high risk of low pathogenic H7N9 virus introduction from China to identify the surveillance strategy that optimizes H7N9 detection. Results show that (i) using a portable diagnostic device would slightly reduce the number of infected birds leaving the LBM before the first detection, as compared to a laboratory-based diagnostic strategy, (ii) H7N9 detection could become more timely by sampling birds staying overnight, just before new susceptible birds are introduced at the beginning of a working day, and (iii) banning birds staying overnight would represent an effective intervention to reduce the risk of H7N9 spread but would decrease the likelihood of virus detection if introduced. These strategies should receive high priority in Vietnam and other Asian countries at risk of H7N9 introduction. ISSN:1742-5689 ISSN:1742-5662

Published
2021
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34. Detecting Rapid Spread of SARS-CoV-2 Variants, France, January 26–February 16, 2021

Author

Samuel Alizon, Emmanuel Lecorche, Stéphanie Haim-Boukobza, Sabine Trombert-Paolantoni, Christian Selinger, Laura Verdurme, Vincent Foulongne, Yannis Michalakis, Mircea T. Sofonea, Bénédicte Roquebert, Laboratoire CERBA [Saint Ouen l'Aumône], Laboratoire de Virologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), ANR-20-COVI-0098,PHYEPI,Intégration de données de séquences et d'incidence pour analyser et contrôler les épidémies virales(2020), Retiveau, Nolwenn, Intégration de données de séquences et d'incidence pour analyser et contrôler les épidémies virales - - PHYEPI2020 - ANR-20-COVI-0098 - COVID-19 - VALID, Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier], Génétique et évolution des maladies infectieuses (GEMI), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), and Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Epidemiology, Infectious and parasitic diseases, RC109-216, medicine.disease_cause, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, High transmission, Zoonoses, Severe acute respiratory syndrome coronavirus 2, 030212 general & internal medicine, Coronavirus, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Transmission (medicine), [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Dispatch, Variants, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Coronavirus disease, Virus, Infectious Diseases, Viruses, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Screening, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, France, Microbiology (medical), 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030231 tropical medicine, RT-PCR, Biology, 03 medical and health sciences, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, medicine, Humans, Transmission, Statistical modelling, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], SARS-CoV-2, COVID-19, Respiratory infections, Virology, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Detecting Rapid Spread of SARS-CoV-2 Variants, France, January 26–February 16, 2021, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, GLM, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract

International audience; Variants of severe acute respiratory syndrome coronavirus 2 raise concerns regarding the control of coronavirus disease epidemics. We analyzed 40,000 specific reverse transcription PCR tests performed on positive samples during January 26–February 16, 2021, in France. We found high transmission advantage of variants and more advanced spread than anticipated.

Published
2021
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35. Rapid SARS-CoV-2 variants spread detected in France using specific RT-PCR testing

Author

Mircea T. Sofonea, Yannis Michalakis, Christian Selinger, Bénédicte Roquebert, Emmanuel Lecorche, Samuel Alizon, Sabine Trombert-Paolantoni, S. Haïm-Boukobza, Laura Verdurme, and Vincent Foulongne

Subjects
0303 health sciences, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Biology, Virology, 3. Good health, law.invention, 03 medical and health sciences, 0302 clinical medicine, Transmission (mechanics), Real-time polymerase chain reaction, law, 030212 general & internal medicine, 030304 developmental biology
Abstract

SARS-CoV-2 variants raise major concerns regarding the control of COVID-19 epidemics. We analyse 40,000 specific RT-PCR tests performed on SARS-CoV-2-positive samples collected between Jan 26 and Feb 16, 2021. We find a high transmission advantage of variants and show that their spread in the country is more advanced than anticipated.

Published
2021
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36. Risk of Adverse Pregnancy Outcomes for Women with IBD in an Expert IBD Antenatal Clinic

Author

Gillian Lever, Hlupekile Chipeta, Tracey Glanville, and Christian Selinger

Subjects
inflammatory bowel disease, pregnancy, maternal outcomes, neonatal outcomes, General Medicine, digestive system, digestive system diseases
Abstract

Background: Patients with inflammatory bowel disease (IBD) are at increased risk of adverse outcomes from pregnancy. It is unclear whether IBD indications account for the higher rate of Caesarean section (CS) in IBD patients. Methods: A retrospective cohort study of 179 IBD patients cared for in a dedicated combined IBD antenatal clinic and 31,528 non-IBD patients was performed. The outcomes were method of delivery, preterm birth, birthweight, admission to neonatal intensive care unit (NICU), and stillbirth. We analysed the associations between disease activity, medication with method of delivery, and neonatal outcomes. Results: Delivery by CS was more common in IBD patients (RR 1.45, CI 1.16–1.81, p = 0.0021); emergency CS delivery was equally likely (RR 1.26, CI 0.78–2.07, p = 0.3). Forty percent of elective CS were performed for IBD indications. Stillbirth was five-fold higher in IBD patients (RR 5.14, CI 1.92–13.75, p < 0.001). Preterm delivery, low birthweight, and admission to NICU were not more common in patients with IBD, and IBD medications did not increase these risks. Active disease during pregnancy was not associated with adverse outcomes. Conclusions: Delivery by CS was more frequent in the IBD cohort, and most elective CSs were obstetrically indicated. A dedicated IBD antenatal clinic providing closer monitoring and early detection of potential issues may help improve outcomes.

Published
2022
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37. Wearing masks and establishing COVID-19 areas reduces secondary attack risk in nursing homes

Author

Mircea T. Sofonea, Hubert Blain, Amandine Pisoni, Bastien Reyné, Stéphanie Miot, Edouard Tuaillon, Jean Bousquet, Christian Selinger, Samuel Alizon, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])

Subjects
2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, 01 natural sciences, 03 medical and health sciences, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, 0302 clinical medicine, Environmental health, 0103 physical sciences, Medicine, Infection control, 030212 general & internal medicine, 010301 acoustics, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], business.industry, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Outbreak, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Nursing homes, business, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract

BackgroundCOVID-19 is spreading rapidly in nursing homes (NHs). It is urgent to evaluate the effect of infection prevention and control (IPC) measures to reduce COVID spreading.MethodsWe analysed COVID-19 outbreaks in 12 NH using rRT-PCR for SARS-CoV-2. We estimated secondary attack risks (SARs) and identified cofactors associated with the proportion of infected residents.ResultsThe SAR was below 5%, suggesting a high efficiency of IPC measures. Mask-wearing or establishment of COVID-19 zones for infected residents were associated with lower SAR.ConclusionsWearing masks and isolating potentially infected residents appear to limit SARS-CoV-2 spread in nursing homes.

Published
2020
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38. [Mathematical epidemiology and modeling of the Covid-19 pandemic: issues and diversity]

Author

Mircea T. Sofonea, Ramsès Djidjou-Demasse, and Christian Selinger

Subjects
medicine.medical_specialty, statistiques, media_common.quotation_subject, Psychological intervention, 030204 cardiovascular system & hematology, Mathematical modelling of infectious disease, Article, Analytical Chemistry, modelling, 03 medical and health sciences, 0302 clinical medicine, Pandemic, Epidemiology, medicine, Cumulative incidence, Environmental planning, media_common, modélisation, Biochemistry, medical, Biochemistry (medical), COVID-19, reproduction number, Variety (cybernetics), Medical Laboratory Technology, Geography, Work (electrical), statistics, 030220 oncology & carcinogenesis, épidémiologie, epidemiology, nombre de reproduction, Diversity (politics)
Abstract

Le champ de l’épidémiologie mathématique a connu, au cours de la pandémie de Covid-19, une production doublée d’une médiatisation exceptionnelle de ses travaux. Alors même que les données et les connaissances sur la maladie émergente étaient parcellaires, une grande diversité de modèles a été développée et appliquée dans des délais inédits, dans l’objectif d’estimer le nombre de reproduction, la date de début de l’épidémie ou l’incidence cumulée, mais aussi afin d’explorer différents scénarios d’interventions non pharmaceutiques. Leurs résultats ont largement contribué à l’épidémiosurveillance et éclairé la prise de décisions relatives aux politiques de santé publique.

Published
2020

39. HPV cervical infections and serological status in vaccinated and unvaccinated women

Author

Bastien Reyné, E. Picot, Tim Waterboer, Vanina Boué, Michel Segondy, Sophie Grasset, Carmen Lía Murall, Ignacio G. Bravo, Jacques Reynes, Soraya Groc, Christian Selinger, Claire Bernat, Massilva Rahmoun, Vincent Tribout, Nathalie Boulle, Samuel Alizon, Noemi Bender, Marine Bonneau, Christelle Graf, Marie-Christine Picot, Vincent Foulongne, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Biopathologie [CHRU Montpellier], Pathogénèse et contrôle des infections chroniques (PCCI), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Evolution Théorique et Expérimentale (MIVEGEC-ETE), Perturbations, Evolution, Virulence (PEV), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Project: 648963,H2020,ERC-2014-CoG,EVOLPROOF(2015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), and Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)

Subjects
cross-protection, Genital infections, Uterine Cervical Neoplasms, serology, Alphapapillomavirus, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, Serology, 0302 clinical medicine, acute infections, Genotype, Prevalence, 030212 general & internal medicine, Papillomaviridae, genital infections, biology, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Vaccination, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Infectious Diseases, Cohort, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Molecular Medicine, Female, France, Antibody, Cross-protection, Adult, medicine.medical_specialty, HPV, food.ingredient, Adolescent, 030231 tropical medicine, Young Adult, 03 medical and health sciences, food, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Internal medicine, medicine, genital infections 1, Humans, Papillomavirus Vaccines, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], General Veterinary, General Immunology and Microbiology, business.industry, Public health, Papillomavirus Infections, Public Health, Environmental and Occupational Health, Odds ratio, vaccination, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Confidence interval, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, business, Body mass index, Acute infections, Demography, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract

Background Understanding genital infections by Human papillomaviruses (HPVs) remains a major public health issue, especially in countries where vaccine uptake is low. Methods We investigate HPV prevalence and antibody status in 150 women (ages 18 to 25) in Montpellier, France. At inclusion and one month later, cervical swabs, blood samples and questionnaires (for demographics and behavioural variables) were collected. Results Oncogenic, non-vaccine genotypes HPV51, HPV66, HPV53, and HPV52 were the most frequently detected viral genotypes overall. Vaccination status, which was well-balanced in the cohort, showed the strongest (protective) effect against HPV infections, with an associated odds ratio for alphapapillomavirus detection of 0.45 (95% confidence interval: [0.22;0.58]). We also identified significant effects of age, number of partners, body mass index, and contraception status on HPV detection and on coinfections. Type-specific IgG serological status was also largely explained by the vaccination status. IgM seropositivity was best explained by HPV detection at inclusion only. Finally, we identify a strong significant effect of vaccination on genotype prevalence, with a striking under-representation of HPV51 in vaccinated women. Conclusions Variations in HPV prevalence correlate with key demographic and behavioural variables. The cross-protective effect of the vaccine against HPV51 merits further investigation.

Published
2020
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40. Memory is key in capturing COVID-19 epidemiological dynamics

Author

Baptiste Elie, Ramsès Djidjou-Demasse, Christian Selinger, Mircea T. Sofonea, Samuel Alizon, Bastien Reyné, Yannis Michalakis, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), ANR-20-COVI-0098,PHYEPI,Intégration de données de séquences et d'incidence pour analyser et contrôler les épidémies virales(2020), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), and Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Epidemiology, Reproduction number, Basic Reproduction Number, Infectious and parasitic diseases, RC109-216, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, law.invention, 0302 clinical medicine, law, Pandemic, 030212 general & internal medicine, Hospital Mortality, Mathematical epidemiology, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Incidence, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Epidemiosurveillance, 3. Good health, Intensive Care Units, Infectious Diseases, Geography, Transmission (mechanics), [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Epidemiological Monitoring, France, medicine.medical_specialty, 030231 tropical medicine, Microbiology, Article, Mathematical modelling of infectious disease, 03 medical and health sciences, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Virology, Intensive care, medicine, Humans, Non-Markovian processes, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], SARS-CoV-2, Public health, Public Health, Environmental and Occupational Health, COVID-19, Models, Theoretical, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Discrete-time modelling, Communicable Disease Control, Parasitology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Basic reproduction number, Demography, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis, Forecasting
Abstract

International audience; SARS-CoV-2 virus has spread over the world rapidly creating one of the largest pandemics ever. The absence of immunity, presymptomatic transmission, and the relatively high level of virulence of the COVID-19 infection led to a massive flow of patients in intensive care units (ICU). This unprecedented situation calls for rapid and accurate mathematical models to best inform public health policies. We develop an original parsimonious discrete-time model that accounts for the effect of the age of infection on the natural history of the disease. Analysing the ongoing COVID-19 in France as a test case, through the publicly available time series of nationwide hospital mortality and ICU activity, we estimate the value of the key epidemiological parameters and the impact of lock-down implementation delay. This work shows that including memory-effects in the modelling of COVID-19 spreading greatly improves the accuracy of the fit to the epidemiological data. We estimate that the epidemic wave in France started on Jan 20 [Jan 12, Jan 28] (95% likelihood interval) with a reproduction number initially equal to 2.99 [2.59, 3.39], which was reduced by the national lock-down started on Mar 17 to 24 [21, 27] of its value. We also estimate that the implementation of the latter a week earlier or later would have lead to a difference of about respectively −13k and +50k hospital deaths by the end of lock-down. The present parsimonious discrete-time framework constitutes a useful tool for now-and forecasting simultaneously community incidence and ICU capacity strain.

Published
2020
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41. Epidemiological monitoring and control perspectives: application of a parsimonious modelling framework to the COVID-19 dynamics in France

Author

Mircea T. Sofonea, Baptiste Elie, Ramsès Djidjou-Demasse, Samuel Alizon, Bastien Reyné, Yannis Michalakis, Christian Selinger, Evolution Théorique et Expérimentale (MIVEGEC-ETE), Perturbations, Evolution, Virulence (PEV), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), and Perturbations & Virulence in Populations & Communities (MIVEGEC-Perturbations & Virulence in Populations & Communities )

Subjects
medicine.medical_specialty, Computer science, Psychological intervention, Disease, memory effects, 03 medical and health sciences, 0302 clinical medicine, Intensive care, Pandemic, Epidemiology, medicine, [INFO]Computer Science [cs], 030212 general & internal medicine, [MATH]Mathematics [math], non-pharmaceutical interventions, 030304 developmental biology, 0303 health sciences, Actuarial science, Public health, public health, COVID-19, discrete time modelling, 3. Good health, reproduction number 1, epidemiology, Epidemiological Monitoring, Basic reproduction number
Abstract

SARS-Cov-2 virus has spread over the world creating one of the fastest pandemics ever. The absence of immunity, asymptomatic transmission, and the relatively high level of virulence of the COVID-19 infection it causes led to a massive flow of patients in intensive care units (ICU). This unprecedented situation calls for rapid and accurate mathematical models to best inform public health policies. We develop an original parsimonious model that accounts for the effect of the age of infection on the natural history of the disease. Analysing the ongoing COVID-19 in France, we estimate the value of the key epidemiological parameters, such as the basic reproduction number , and the efficiency of the national control strategy. We then use our deterministic model to explore several scenarios posterior to lock-down lifting and compare the efficiency of non pharmaceutical interventions (NPI) described in the literature.

Published
2020

43. Non-Markovian modelling highlights the importance of age structure on Covid-19 epidemiological dynamics

Author

Bastien Reyné, Quentin Richard, Christian Selinger, Mircea T. Sofonea, Ramsès Djidjou-Demasse, Samuel Alizon, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Swiss Tropical and Public Health Institute [Basel], Perturbations & Virulence in Populations & Communities (MIVEGEC-Perturbations & Virulence in Populations & Communities ), Perturbations, Evolution, Virulence (PEV), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Evolution Théorique et Expérimentale (MIVEGEC-ETE), and Reyné, Bastien

Subjects
[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Epidemiology, Epidemiology, infectious diseases modelling, contact matrix, partial differential equations, Covid-19, Applied Mathematics, infectious diseases modelling, contact matrix, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Modeling and Simulation, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, partial differential equations, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [MATH.MATH-AP] Mathematics [math]/Analysis of PDEs [math.AP], [MATH]Mathematics [math], Covid-19, MSC: 92D30
Abstract

The Covid-19 pandemic outbreak was followed by a huge amount of modelling studies in order to rapidly gain insights to implement the best public health policies. Most of these compartmental models involved ordinary differential equations (ODEs) systems. Such a formalism implicitly assumes that the time spent in each compartment does not depend on the time already spent in it, which is at odds with the clinical data. To overcome this “memoryless” issue, a widely used solution is to increase and chain the number of compartments of a unique reality (e.g. have infected individual move between several compartments). This allows for greater heterogeneity and thus be closer to the observed situation, but also tends to make the whole model more difficult to apprehend and parameterize. We develop a non-Markovian alternative formalism based on partial differential equations (PDEs) instead of ODEs, which, by construction, provides a memory structure for each compartment thereby allowing us to limit the number of compartments. We apply our model to the French 2021 SARS-CoV-2 epidemic and, while accounting for vaccine-induced and natural immunity, we analyse and determine the major components that contributed to the Covid-19 hospital admissions. The results indicate that the observed vaccination rate alone is not enough to control the epidemic, and a global sensitivity analysis highlights a huge uncertainty attributable to the age-structured contact matrix. Our study shows the flexibility and robustness of PDE formalism to capture national COVID-19 dynamics and opens perspectives to study medium or long-term scenarios involving immune waning or virus evolution.

Published
2022
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44. Evaluation of Anorectal Function in Perianal Crohn’s Disease: A Pilot Study

Author

Andreia Albuquerque, John Casey, Grace Fairlamb, Lesley A. Houghton, and Christian Selinger

Subjects
high-resolution anorectal manometry, balloon expulsion test, Medicine, General Medicine, perianal Crohn’s disease, anorectal function, 3D-endoanal ultrasound, Article
Abstract

Background: Perianal Crohn’s disease is a disabling condition, with little known about anorectal function in healed/inactive perianal Crohn’s disease; Aim: To evaluate anorectal function in a cohort of patients with treated/healed perianal Crohn’s disease; Methods: Prospective cohort study, including high-resolution anorectal manometry, balloon expulsion test, and 3D-endoanal ultrasound in all patients; Results: Of the 16 patients studied (mean age ± SD, 42 ± 13 years), 12 (75%) were men. A laceration of the internal anal sphincter and/or anal scarring was seen in nine (56%) patients; there was no laceration of the external anal sphincter. Five (56%) of these nine patients had never experienced faecal incontinence. All had normal anal resting and squeeze pressures. Manometry suggested dyssynergia in 11 (69%) patients, with only one (6%) fulfilling the criteria for obstructed defecation. Hyposensitivity for at least one sensory parameter was seen in 11 (69%) patients and hypersensitivity in five (31%) patients; Conclusions: This study detected sphincter abnormalities in more than half of patients, many of whom were asymptomatic. Alterations in rectal sensation were frequently seen, more commonly with rectal hyposensitivity. Trial registration: ClinicalTrials.gov (NCT03819257).

Published
2021
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45. Natural history, dynamics, and ecology of human papillomaviruses in genital infections of young women: protocol of the PAPCLEAR cohort study

Author

Guillaume Christophe, Aziza Seddiki, Ignacio G. Bravo, Christian Selinger, Julie Lajoie, Mathilde Buisson, Vincent Foulongne, Jacques Ravel, Giuseppe D'Auria, Vanina Boué, Martine Teirlinck, Carmen Lía Murall, Marine Bonneau, Edouard Tuaillon, Rémy Froissart, Christelle Graf, Nathalie Jacobs, Frédérique Lorcy, Thérèse Rousset, Tim Waterboer, Florence De Taroni, Jacques Reynes, E. Picot, Nathalie Boulle, Soraya Groc, Samuel Alizon, Claire Bernat, Christophe Hirtz, Massilva Rahmoun, Audrey Jaussent, Monique Baldellou, Vincent Tribout, Michel Segondy, Sophie Grasset, Marie-Christine Picot, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Virostyle (MIVEGEC-Virostyle), Perturbations, Evolution, Virulence (PEV), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Perturbations & Virulence in Populations & Communities (MIVEGEC-Perturbations & Virulence in Populations & Communities ), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CIBER de Epidemiología y Salud Pública (CIBERESP), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Laboratoire de Virologie [CHRU Montpellier], Du gène à l'écosystème (MIVEGEC-GeneSys), Pathogènes, Environnement, Santé Humaine (EPATH), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University of Manitoba [Winnipeg], University of Maryland School of Medicine, University of Maryland System, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA-Research), Université de Liège, Evolution Théorique et Expérimentale (MIVEGEC-ETE), Immunopathologie de l'Inflammation, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Washington [Seattle], Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre International de Recherches Médicales de Franceville, Laboratoire de Pathologie Comparée (LPC), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institute of Research in Biotherapy, Laboratory of Biochemistry and Clinical Proteomics, Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Institute for Genomic Sciences, School of Medicine (IGS), Recherches Translationnelles sur le VIH et les maladies infectieuses (TransVIHMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 1 (UM1)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Universtié Yaoundé 1 [Cameroun]-Université de Montpellier (UM), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Cellular and Molecular Immunology, GIGA-Research, university hospital, University Hospital, Alizon, Samuel, Génétique et évolution des maladies infectieuses (GEMI), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Génétique et évolution des maladies infectieuses (GEMI), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), and Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Longitudinal study, viruses, [SDV]Life Sciences [q-bio], viral kinetics, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, 0302 clinical medicine, Clinical Protocols, Surveys and Questionnaires, Epidemiology, Protocol, [SDV.EE.ECO] Life Sciences [q-bio]/Ecology, environment/Ecosystems, Longitudinal Studies, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], persistence, General Medicine, Hydrogen-Ion Concentration, Viral Load, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Natural history, Infectious Diseases, Vagina, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cytokines, Population study, Female, France, [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, Viral load, Cohort study, HPV, medicine.medical_specialty, Adolescent, Young Adult, 03 medical and health sciences, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, [SDV.BID.SPT] Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, microbiota, [SDV.BID.EVO] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], medicine, Humans, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Genotyping, 030304 developmental biology, Gynecology, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], business.industry, Papillomavirus Infections, [SDV.EE.IEO] Life Sciences [q-bio]/Ecology, environment/Symbiosis, virus load, immunity, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Human genetics, [SDE.BE] Environmental Sciences/Biodiversity and Ecology, Cross-Sectional Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.GEN.GPO] Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, business, acute infection, Genital Diseases, Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract

IntroductionHuman papillomaviruses (HPVs) are responsible for one-third of all cancers caused by infections. Most HPV studies focus on chronic infections and cancers, and we know little about the early stages of the infection. Our main objective is to better understand the course and natural history of cervical HPV infections in healthy, unvaccinated and vaccinated, young women, by characterising the dynamics of various infection-related populations (virus, epithelial cells, vaginal microbiota and immune effectors). Another objective is to analyse HPV diversity within hosts, and in the study population, in relation to co-factors (lifestyle characteristics, vaccination status, vaginal microbiota, human genetics).Methods and analysisThe PAPCLEAR study is a single center longitudinal study following 150 women, aged 18–25 years, for up to 2 years. Visits occur every 2 or 4 months (depending on HPV status) during which several variables are measured, such as behaviours (via questionnaires), vaginal pH, HPV presence and viral load (via qPCR), local concentrations of cytokines (via MesoScale Discovery technology) and immune cells (via flow cytometry). Additional analyses are outsourced, such as titration of circulating anti-HPV antibodies, vaginal microbiota sequencing (16S and ITS1 loci) and human genotyping. To increase the statistical power of the epidemiological arm of the study, an additional 150 women are screened cross-sectionally. Finally, to maximise the resolution of the time series, participants are asked to perform weekly self-samples at home. Statistical analyses will involve classical tools in epidemiology, genomics and virus kinetics, and will be performed or coordinated by the Centre National de la Recherche Scientifique (CNRS) in Montpellier.Ethics and disseminationThis study has been approved by the Comité de Protection des Personnes Sud Méditerranée I (reference number 2016-A00712-49); by the Comité Consultatif sur le Traitement de l’Information en matière de Recherche dans le domaine de la Santé (reference number 16.504); by the Commission Nationale Informatique et Libertés (reference number MMS/ABD/AR1612278, decision number DR-2016–488) and by the Agence Nationale de Sécurité du Médicament et des Produits de Santé (reference 20160072000007). Results will be published in preprint servers, peer-reviewed journals and disseminated through conferences.Trial registration numberNCT02946346; Pre-results.

Published
2019
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46. Targeting and vaccine durability are key for population-level impact and cost-effectiveness of a pox-protein HIV vaccine regimen in South Africa

Author

Timothy B. Hallett, Glenda Gray, Anna Bershteyn, Andrew N. Phillips, Linda-Gail Bekker, Paul Revill, Christian Selinger, Helen Rees, Dobromir T. Dimitrov, Blythe J.S. Adamson, Institute for Disease Modeling (IDM), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), University of York [York, UK], Imperial College London, University College of London [London] (UCL), The Desmond Tutu HIV Centre [Cape Town, South Africa], University of the Witwatersrand [Johannesburg] (WITS), South African Medical Research Council [Cape Town], and Bill & Melinda Gates Foundation

Subjects
Time Factors, HIV vaccine, Total cost, Cost effectiveness, Cost-Benefit Analysis, HIV Infections, South Africa, Immunogenicity, Vaccine, 0302 clinical medicine, Outcome Assessment, Health Care, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, AIDS Vaccines, 0303 health sciences, Incidence, Incidence (epidemiology), Vaccination, 11 Medical And Health Sciences, 3. Good health, Infectious Diseases, Population Surveillance, AIDSVAX, Molecular Medicine, medicine.medical_specialty, 030231 tropical medicine, Article, 03 medical and health sciences, Environmental health, Virology, medicine, Humans, 030304 developmental biology, General Veterinary, General Immunology and Microbiology, Immunization Programs, business.industry, Public health, Public Health, Environmental and Occupational Health, HIV, Models, Theoretical, 06 Biological Sciences, Regimen, Agent-based modeling, Economic evaluation, Cost-effectiveness, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 07 Agricultural And Veterinary Sciences, business
Abstract

BackgroundRV144 is to date the only HIV vaccine trial to demonstrate efficacy, albeit rapidly waning over time. The HVTN 702 trial is currently evaluating in South Africa a similar vaccine formulation to that of RV144 for subtype C HIV with additional boosters (pox-protein regimen). Using a detailed stochastic individualbased network model of disease transmission calibrated to the HIV epidemic, we investigate population-level impact and maximum cost of an HIV vaccine to remain cost-effective.MethodsConsistent with the original pox-protein regimen, we model a primary series of five vaccinations meeting the goal of 50% cumulative efficacy 24 months after the first dose and include two-yearly boosters that maintain durable efficacy over 10 years. We simulate vaccination programs in South Africa starting in 2027 under various vaccine targeting and HIV treatment and prevention assumptions.ResultsOur analysis shows that this partially effective vaccine could prevent, at catchup vaccination with 60% coverage, up to 941,000 (15.6%) new infections between 2027 and 2047 assuming current trends of antiretroviral treatment. An impact of up to 697,000 (11.5%) infections prevented could be achieved by targeting age cohorts of highest incidence. Economic evaluation indicates that, if treatment scale-up was achieved, vaccination could be cost-effective at a total cost of less than $385 and $62 per 10-year series (cost-effectiveness thresholds of $5,691 and $750).ConclusionsWhile a partially effective, rapidly waning vaccine could help to prevent HIV infections, it will not eliminate HIV as a public health priority in sub-Saharan Africa. Vaccination is expected to be most effective under targeted delivery to age groups of highest HIV incidence. Awaiting results of trial, the introduction of vaccination should go in parallel with continued innovation in HIV prevention, including studies to determine the costs of delivery and feasibility and further research into products with greater efficacy and durability.

Published
2019
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47. The future of a partially effective HIV vaccine: assessing limitations at the population level

Author

Philip A. Welkhoff, Christian Selinger, Anna Bershteyn, and Dobromir T. Dimitrov

Subjects
Adult, Male, HIV vaccine, Health (social science), Adolescent, Population level, Cost-Benefit Analysis, Hiv epidemic, HIV Infections, Epidemiological modeling, South Africa, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Immunity, Environmental health, Milestone (project management), Humans, Medicine, 030212 general & internal medicine, AIDS Vaccines, 030505 public health, Booster (rocketry), business.industry, Public Health, Environmental and Occupational Health, Limiting, Middle Aged, Models, Theoretical, Product development, Regimen, Original Article, Female, Mass vaccination, 0305 other medical science, business
Abstract

ObjectivesMathematical models have unanimously predicted that a first-generation HIV vaccine would be useful and cost-effective to roll out, but that its overall impact would be insufficient to reverse the epidemic. Here, we explore what factors contribute most to limiting the impact of such a vaccine.MethodsRanging from a theoretical ideal to a more realistic regimen, mirroring the one used in the currently ongoing trial in South Africa (HVTN 702), we model a nested hierarchy of vaccine attributes such as speed of roll-out, efficacy, and retention of booster doses.ResultsThe predominant reasons leading to a substantial loss of vaccine impact on the HIV epidemic are the time required to scale up mass vaccination, limited durability and waning of efficacy.ConclusionsA partially effective HIV vaccine will be a critical milestone for the development of a highly effective, durable, and scalable next-generation vaccine. Accelerated development, expedited vaccine availability, and improved immunogenicity are the main attributes of a vaccine that could dramatically reverse the course of the epidemic in highly endemic countries.

Published
2019
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49. The 1918 influenza virus PB2 protein enhances virulence through the disruption of inflammatory and Wnt-mediated signaling in mice

Author

Nicolas Tchitchek, Masato Hatta, Gongxun Zhong, Jason D. Berndt, Michael G. Katze, Adriana Forero, Jennifer Tisoncik-Go, Kristi Barker, Randall T. Moon, Laurence Josset, Christian Selinger, Tokiko Watanabe, Juliet Morrison, Jean Chang, Yoshihiro Kawaoka, University of Washington [Seattle], University of Wisconsin-Madison, Howard Hughes Medical Institute [Seattle], Howard Hughes Medical Institute (HHMI), Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Washington National Primate Research Center [Seattle], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Tchitchek, Nicolas, and Williams, B

Subjects
0301 basic medicine, Influenza Virus, Viral pathogenesis, viruses, [SDV]Life Sciences [q-bio], Reassortment, Hemagglutinin Glycoproteins, Influenza Virus, Medical and Health Sciences, Mice, Influenza A Virus, H1N1 Subtype, Influenza A Virus, 2.2 Factors relating to the physical environment, 2.1 Biological and endogenous factors, Aetiology, Lung, Wnt Signaling Pathway, Inbred BALB C, Mice, Inbred BALB C, Virulence, Wnt signaling pathway, Biological Sciences, [SDV] Life Sciences [q-bio], Infectious Diseases, RNA Replicase, Pneumonia & Influenza, Female, Host adaptation, Infection, Reassortant Viruses, Hemagglutinin Glycoproteins, Virulence Factors, 030106 microbiology, Immunology, Biology, Microbiology, Virus, Proinflammatory cytokine, Cell Line, Vaccine Related, 03 medical and health sciences, Viral Proteins, Orthomyxoviridae Infections, Biodefense, Virology, Genetics, Animals, Humans, H1N1 Subtype, Inflammation, Agricultural and Veterinary Sciences, Animal, Prevention, Gene Expression Profiling, RNA-Dependent RNA Polymerase, Influenza, respiratory tract diseases, Disease Models, Animal, 030104 developmental biology, Emerging Infectious Diseases, Good Health and Well Being, Viral replication, Insect Science, Disease Models, Pathogenesis and Immunity
Abstract

Author(s): Forero, Adriana; Tisoncik-Go, Jennifer; Watanabe, Tokiko; Zhong, Gongxun; Hatta, Masato; Tchitchek, Nicolas; Selinger, Christian; Chang, Jean; Barker, Kristi; Morrison, Juliet; Berndt, Jason D; Moon, Randall T; Josset, Laurence; Kawaoka, Yoshihiro; Katze, Michael G | Abstract: UnlabelledThe 1918-1919 influenza pandemic remains the single greatest infectious disease outbreak in the past century. Mouse and nonhuman primate infection models have shown that the 1918 virus induces overly aggressive innate and proinflammatory responses. To understand the response to viral infection and the role of individual 1918 genes on the host response to the 1918 virus, we examined reassortant avian viruses nearly identical to the pandemic 1918 virus (1918-like avian virus) carrying either the 1918 hemagglutinin (HA) or PB2 gene. In mice, both genes enhanced 1918-like avian virus replication, but only the mammalian host adaptation of the 1918-like avian virus through reassortment of the 1918 PB2 led to increased lethality. Through the combination of viral genetics and host transcriptional profiling, we provide a multidimensional view of the molecular mechanisms by which the 1918 PB2 gene drives viral pathogenicity. We demonstrate that 1918 PB2 enhances immune and inflammatory responses concomitant with increased cellular infiltration in the lung. We also show for the first time, that 1918 PB2 expression results in the repression of both canonical and noncanonical Wnt signaling pathways, which are crucial for inflammation-mediated lung regeneration and repair. Finally, we utilize regulatory enrichment and network analysis to define the molecular regulators of inflammation, epithelial regeneration, and lung immunopathology that are dysregulated during influenza virus infection. Taken together, our data suggest that while both HA and PB2 are important for viral replication, only 1918 PB2 exacerbates lung damage in mice infected with a reassortant 1918-like avian virus.ImportanceAs viral pathogenesis is determined in part by the host response, understanding the key host molecular driver(s) of virus-mediated disease, in relation to individual viral genes, is a promising approach to host-oriented drug efforts in preventing disease. Previous studies have demonstrated the importance of host adaptive genes, HA and PB2, in mediating disease although the mechanisms by which they do so are still poorly understood. Here, we combine viral genetics and host transcriptional profiling to show that although both 1918 HA and 1918 PB2 are important mediators of efficient viral replication, only 1918 PB2 impacts the pathogenicity of an avian influenza virus sharing high homology to the 1918 pandemic influenza virus. We demonstrate that 1918 PB2 enhances deleterious inflammatory responses and the inhibition of regeneration and repair functions coordinated by Wnt signaling in the lungs of infected mice, thereby promoting virus-associated disease.

Published
2016
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50. Integrated Omics Analysis of Pathogenic Host Responses during Pandemic H1N1 Influenza Virus Infection: The Crucial Role of Lipid Metabolism

Author

Young-Mo Kim, Thomas O. Metz, Jennifer E. Kyle, Karl K. Weitz, Richard Green, M. Suresh, Laurence Josset, David J. Gasper, Amie J. Eisfeld, Susan C. Tilton, Erika M. Zink, Masato Hatta, Juliet Morrison, Richard D. Smith, Carrie D. Nicora, Jennifer Tisoncik-Go, Xinxia Peng, Marcus J. Korth, Yoshihiro Kawaoka, Samuel O. Purvine, Athena A. Schepmoes, Michael G. Katze, Bobbie-Jo M. Webb-Robertson, Katrina M. Waters, and Christian Selinger

Subjects
0301 basic medicine, Cancer Research, Gene Expression, Influenza A Virus, H1N1 Subtype, 0302 clinical medicine, Pandemic, Influenza A Virus, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, Aetiology, Lung, Influenza research, Phenotype, Lipids, 3. Good health, medicine.anatomical_structure, Infectious Diseases, Medical Microbiology, Host-Pathogen Interactions, Pneumonia & Influenza, Infection, Human, T cell, Immunology, Biology, Microbiology, Article, Virus, Proinflammatory cytokine, Vaccine Related, 03 medical and health sciences, Virology, Immunology and Microbiology(all), Biodefense, Influenza, Human, medicine, Animals, Humans, Metabolomics, H1N1 Subtype, Molecular Biology, Animal, Prevention, Ferrets, Lipid metabolism, Omics, Lipid Metabolism, Influenza, Disease Models, Animal, 030104 developmental biology, Emerging Infectious Diseases, Disease Models, Parasitology, 030217 neurology & neurosurgery
Abstract

Pandemic influenza viruses modulate pro-inflammatory responses that can lead to immunopathogenesis. We present an extensive and systematic profiling of lipids, metabolites and proteins in respiratory compartments of ferrets infected with either 1918 or 2009 human pandemic H1N1 influenza viruses. Integrative analysis of high-throughput omics data with virologic and histopathologic data uncovered relationships between host responses and phenotypic outcomes of viral infection. Pro-inflammatory lipid precursors in the trachea following 1918 infection correlated with severe tracheal lesions. Using an algorithm to infer cell quantity changes from gene expression data, we found enrichment of distinct T cell subpopulations in the trachea. There was also a predicted increase in inflammatory monocytes in the lung of 1918 virus-infected animals that was sustained throughout infection. This study presents a unique resource to the influenza research community and demonstrates the utility of an integrative systems approach for characterization of lipid metabolism alterations underlying respiratory responses to viruses.

Published
2016

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