ORCID Profile
0000-0003-4602-5388
Current Organisation
Oncology department - UNIL/CHUV
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Publisher: Public Library of Science (PLoS)
Date: 18-10-2023
Publisher: Cold Spring Harbor Laboratory
Date: 10-03-2022
DOI: 10.1101/2022.03.07.22272001
Abstract: Reliable estimates of human mobility are important for understanding the spatial spread of infectious diseases and the effective targeting of control measures. However, when modelling infectious disease dynamics, data on human mobility at an appropriate temporal or spatial resolution are not always available, leading to the common use of model-derived mobility proxies. In this study we reviewed the different data sources and mobility models that have been used to characterise human movement in Africa. We then conducted a simulation study to better understand the implications of using human mobility proxies when predicting the spatial spread and dynamics of infectious diseases. We found major gaps in the availability of empirical measures of human mobility in Africa, leading to mobility proxies being used in place of data. Empirical data on subnational mobility were only available for 17/54 countries, and, in most instances, these data characterised long-term movement patterns, which were unsuitable for modelling the spread of pathogens with short generation times (time between infection of a case and their infector). Results from our simulation study demonstrated that using mobility proxies can have a substantial impact on the predicted epidemic dynamics, with complex and non-intuitive biases. In particular, the predicted times and order of epidemic invasion, and the time of epidemic peak in different locations can be underestimated or overestimated, depending on the types of proxies used and the country of interest. Our work underscores the need for regularly updated empirical measures of population movement within and between countries to aid the prevention and control of infectious disease outbreaks. At the same time, there is a need to establish an evidence base to help understand which types of mobility data are most appropriate for describing the spread of emerging infectious diseases in different settings.
Publisher: Cold Spring Harbor Laboratory
Date: 12-07-2023
DOI: 10.1101/2023.07.10.23292424
Abstract: Recent Marburg virus disease (MVD) outbreaks in Equatorial Guinea and Tanzania highlighted the importance of better understanding this highly lethal infectious pathogen. Past epidemics of Ebola, COVID-19, and other pathogens have re-emphasised the usefulness of mathematical models in guiding public health responses during outbreaks. We conducted a systematic review, registered with PROSPERO (CRD42023393345) and reported according to PRISMA guidelines, of peer-reviewed papers reporting historical out-breaks, modelling studies and epidemiological parameters focused on MVD, including contextual information. We searched PubMed and Web of Science until 31st March 2023. Two reviewers evaluated all titles and abstracts, with consensus-based decision-making. To ensure agreement, 31% (13/42) of studies were double-extracted and a custom-designed quality assessment questionnaire was used to assess the risk of bias. We present detailed outbreak, model and parameter information on 970 reported cases and 818 deaths from MVD until 31 March 2023. Analysis of historical outbreaks and sero-prevalence estimates suggests the possibility of undetected MVD outbreaks, asymptomatic transmission and/or cross-reactivity with other pathogens. Only one study presented a mathematical model of MVD transmission. We estimate an unadjusted, pooled total random effect case fatality ratio for MVD of 61.9% (95% CI: 38.8-80.6%, I 2 =93%). We identify key epidemiological parameters relating to transmission and natural history for which there are few estimates. This review provides a comprehensive overview of the epidemiology of MVD, identifying key knowledge gaps about this pathogen. The extensive collection of knowledge gathered here will be crucial in developing mathematical models for use in the early stages of future outbreaks of MVD. All data are published alongside this article with functionality to easily update the database as new data become available. MRC Centre for Global Infectious Disease Analysis Evidence before this study We searched Web of Science and PubMed up to 31 March 2023 using the search terms Marburg virus, epidemiology, outbreaks, models, transmissibility, severity, delays, risk factors, mutation rates and seroprevalence. We found five systematic reviews, all of which considered MVD alongside Ebola virus disease (EVD). One modelling study of Marburg virus disease (MVD) focused on animals, and not on computational models to understand past or project future disease transmission. One systematic review collated risk factors for transmission based on four MVD studies, but did not report attack rates due to missing underlying MVD estimates another systematic review pooled estimates of MVD case fatality ratios (CFR): 53.8% (95% CI: 26.5–80.0%) and seroprevalence: 1.2% (95% CI: 0.5–2.0%). No systematic review covered transmission models of MVD, and the impact of public health and social measures is unknown. Added value of this study We provide a comprehensive summary of the available, peer-reviewed literature of historical outbreaks, transmission models and parameters for MVD. Meta-analysis of existing estimates of CFRs, and our original estimates based on historical outbreak information, illustrate the severity of MVD with our pooled random effect estimated CFR of 61.9% (95% CI: 38.8-80.6%, I 2 =93%). We demonstrate the sparsity of evidence on MVD transmission and disease dynamics, particularly on transmissibility and natural history, which are key input parameters for computational models supporting outbreak response. Our work highlights key areas where further disease characterization is necessary. Implications of all the available evidence Previous outbreaks of infectious pathogens emphasized the usefulness of computational modelling in assessing epidemic trajectories and the impact of mitigation strategies. Our study provides necessary information for using mathematical models in future outbreaks of MVD, identifies uncertainties and knowledge gaps in MVD transmission and natural history, and highlights the severity of MVD.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 27-01-2023
DOI: 10.1126/SCIIMMUNOL.ADE7953
Abstract: Interferon regulatory factor 4 (IRF4) is a transcription factor (TF) and key regulator of immune cell development and function. We report a recurrent heterozygous mutation in IRF4, p.T95R, causing an autosomal dominant combined immunodeficiency (CID) in seven patients from six unrelated families. The patients exhibited profound susceptibility to opportunistic infections, notably Pneumocystis jirovecii , and presented with agammaglobulinemia. Patients’ B cells showed impaired maturation, decreased immunoglobulin isotype switching, and defective plasma cell differentiation, whereas their T cells contained reduced T H 17 and T FH populations and exhibited decreased cytokine production. A knock-in mouse model of heterozygous T95R showed a severe defect in antibody production both at the steady state and after immunization with different types of antigens, consistent with the CID observed in these patients. The IRF4 T95R variant maps to the TF’s DNA binding domain, alters its canonical DNA binding specificities, and results in a simultaneous multimorphic combination of loss, gain, and new functions for IRF4. IRF4 T95R behaved as a gain-of-function hypermorph by binding to DNA with higher affinity than IRF4 WT . Despite this increased affinity for DNA, the transcriptional activity on IRF4 canonical genes was reduced, showcasing a hypomorphic activity of IRF4 T95R . Simultaneously, IRF4 T95R functions as a neomorph by binding to noncanonical DNA sites to alter the gene expression profile, including the transcription of genes exclusively induced by IRF4 T95R but not by IRF4 WT . This previously undescribed multimorphic IRF4 pathophysiology disrupts normal lymphocyte biology, causing human disease.
Publisher: Cold Spring Harbor Laboratory
Date: 28-11-2021
DOI: 10.1101/2021.11.26.21266899
Abstract: Recent months have demonstrated that emerging variants may set back the global COVID-19 response. The ability to rapidly assess the threat of new variants in real-time is critical for timely optimisation of control strategies. We extend the EpiEstim R package, designed to estimate the time-varying reproduction number ( R t ), to estimate in real-time the effective transmission advantage of a new variant compared to a reference variant. Our method can combine information across multiple locations and over time and was validated using an extensive simulation study, designed to mimic a variety of real-time epidemic contexts. We estimate that the SARS-CoV-2 Alpha variant is 1.46 (95% Credible Interval 1.44-1.47) and 1.29, (95% CrI 1.29-1.30) times more transmissible than the wild type, using data from England and France respectively. We further estimate that Beta and Gamma combined are 1.25 (95% CrI 1.24-1.27) times more transmissible than the wildtype (France data). All results are in line with previous estimates from literature, but could have been obtained earlier and more easily with our off-the-shelf open-source tool. Our tool can be used as an important first step towards quantifying the threat of new variants in real-time. Given the popularity of EpiEstim, this extension will likely be used widely to monitor the co-circulation and/or emergence of multiple variants of infectious pathogens. Early assessment of the transmissibility of new variants of an infectious pathogen is critical for anticipating their impact and designing appropriate interventions. However, this often requires complex and bespoke analyses relying on multiple data streams, including genomic data. Here we present a novel method and software to rapidly quantify the transmission advantage of new variants. Our method is fast and requires only routinely collected disease surveillance data, making it easy to use in real-time. The ongoing high level of SARS-CoV-2 circulation in a number of countries makes the emergence of new variants highly likely. Our work offers a powerful tool to help public health bodies monitor such emerging variants and rapidly detect those with increased transmissibility.
No related grants have been discovered for Romane Thouenon.