Latest Publications
Xavier Didelot publications
Integrated analysis of patient networks and plasmid genomes reveals a regional, multi-species outbreak of carbapenemase-producing Enterobacterales carrying both blaIMP and mcr-9 genes
Y Wan, AC Myall, A Boonyasiri, F Bolt, A Ledda, S Mookerjee, AY Weiße, M Getino, JF Turton, H Abbas, R Prakapaite, A Sabnis, A Abdolrasouli, K Malpartida-Cardenas, L Miglietta, H Donaldson, M Gilchrist, KL Hopkins, MJ Ellington, JA Otter, G Larrouy-Maumus, M Edwards, J Rodriguez-Manzano, X Didelot, M Barahona, AH Holmes, E Jauneikaite, F Davies
Carbapenemase-producing Enterobacterales (CPE) are challenging in healthcare, with resistance to multiple classes of antibiotics. This study describes the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 across a London regional network. Our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of blaIMPCPE, which remained unidentified during standard investigations. With DNA sequencing and multi-modal data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Plasmid-level outbreak analysis reveals that resistance spread may be wider than suspected, allowing more interventions to stop transmission within hospital networks.
Journal of Infectious Diseases. January 2024
Genomic epidemiology of the clinically dominant clonal complex 1 in the Listeria monocytogenes population in the UK
Emily T. Fotopoulou, Claire Jenkins, Clare R. Barker, Anais Painset, Xavier Didelot, Ameze Simbo, Amy Douglas, Gauri Godbole, Frieda Jorgensen, Saheer Gharbia, Jim McLauchlin
Listeria monocytogenes is a food-borne pathogen, typically affecting the elderly, immunocompromised patients and pregnant women. The aim of this study was to determine the population structure of L. monocytogenes clonal complex 1 (CC1) in the UK and describe the genomic epidemiology of this clinically significant CC. We interrogated a working dataset of 4073 sequences of L. monocytogenes isolated between January 2015 and December 2020 from human clinical specimens, food and/or foodproduction environments. Analysis of demographic and clinical outcome data identified CC1 as a clinically significant cause of invasive listeriosis in the elderly population and in women of child-bearing age. Phylogenetic analysis revealed the population structure of CC1 in the UK comprised small, sparsely populated genomic clusters. Only clusters containing isolates from an implicated food vehicle, or food processing or farming environments, were resolved, emphasizing the need for clinical, food and animal-health agencies to share sequencing data in real time, and the importance of a One Health approach to public-health surveillance of listeriosis.
Temporal changes in the positivity rate of common enteric viruses among paediatric admissions in coastal Kenya, during the COVID-19 pandemic, 2019-2022
Arnold W. Lambisia, Nickson Murunga, Martin Mutunga, Robinson Cheruiyot, Grace Maina, Timothy O. Makori, D. James Nokes and Charles N. Agoti
The non-pharmaceutical interventions (NPIs) implemented to curb the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the coronavirus disease 2019 (COVID-19) pandemic, substantially disrupted the activity of other respiratory viruses. However, there is limited data from low-and-middle income countries (LMICs) to determine whether these NPIs also impacted the transmission of common enteric viruses. Here, we investigated the changes in the positivity rate of five enteric viruses among hospitalised children who presented with diarrhoea to a referral hospital in coastal Kenya, during COVID-19 pandemic period. Our study finds that in 2020 the transmission of common enteric viruses, especially RVA and astrovirus, in Kilifi Kenya may have been disrupted due to the COVID-19 NPIs. After 2020, local enteric virus transmission patterns appeared to return to pre-pandemic levels coinciding with the removal of most of the government COVID-19 NPIs.
Inference of infectious disease transmission through a relaxed bottleneck using multiple genomes per host
Jake Carson, Matt Keeling, David Wyllie, Paolo Ribeca, Xavier Didelot
Here we present a new methodology that can use any number of genomes sampled from a set of individuals to reconstruct their transmission network. Furthermore, we remove the need for the assumption of a complete transmission bottleneck. We use simulated data to show that our method becomes more accurate as more genomes per host are provided, and that it can infer key infectious disease parameters such as the size of the transmission bottleneck, within-host growth rate, basic reproduction number and sampling fraction. We demonstrate the usefulness of our method in applications to real datasets from an outbreak of Pseudomonas aeruginosa amongst cystic fibrosis patients and a nosocomial outbreak of Klebsiella pneumoniae.
Rapid diversification of grey mangroves (Avicennia marina) driven by geographic isolation and extreme environmental conditions in the Arabian Peninsula
Guillermo Friis, Edward G. Smith, Catherine E. Lovelock, Alejandra Ortega, Alyssa Marshell, Carlos M. Duarte, John A. Burt
Biological systems occurring in ecologically heterogeneous and spatially discontinuous habitats provide an ideal opportunity to investigate the relative roles of neutral and selective factors in driving lineage diversification. The grey mangroves (Avicennia marina) of Arabia occur at the northern edge of the species' range and are subject to variable, often extreme, environmental conditions, as well as historic large fluctuations in habitat availability and connectivity resulting from Quaternary glacial cycles. Here, we analyse fully sequenced genomes sampled from 19 locations across the Red Sea, the Arabian Sea and the Persian/Arabian Gulf (PAG) to reconstruct the evolutionary history of the species in the region and to identify adaptive mechanisms of lineage diversification. Our results support a process of rapid diversification resulting from the combined effects of historical factors and ecological selection and reveal mangrove peripheral environments as relevant drivers of lineage diversity.
Identification of dynamical changes of rabies transmission under quarantine : community-based measures towards rabies elimination
Rysava, Kristyna and Tildesley, Michael J
Here, we present a quantitative framework using a series of progressively more biologically realistic models of canine rabies in domestic dogs and from dogs to humans, a suitable example system to characterize dynamical changes under varying levels of dog quarantine. We explicitly incorporate health-seeking behaviour data to inform the modelling of contact-tracing and exclusion of rabies suspect and probable dogs that can be identified through bite-histories of patients presenting at anti-rabies clinics. We find that a temporary quarantine of rabies suspect and probable dogs provides a powerful tool to curtail rabies transmission, especially in settings where optimal vaccination coverage is yet to be achieved, providing a critical stopgap to reduce the number of human and animal deaths due to rabid bites.
Screening of Hydrophilic Polymers Reveals Broad Activity in 2 Protecting Phages during Cryopreservation
Huba L Marton, Apoorva Bhatt, Antonia P Sagona, Peter Kilbride, Matthew I Gibson
Bacteriophages have many biotechnological and therapeutic applications, but as with other biologics, cryopreservation is essential for storage and distribution. Macromolecular cryoprotectants are emerging for a range of biologics, but the chemical space for polymer-mediated phage cryopreservation has not been explored. Here we screen the cryoprotective effect of a panel of polymers against five distinct phages, showing that nearly all the tested polymers provide a benefit. This work shows that phages are amenable to protection with hydrophilic polymers and opens up new opportunities for advanced formulations for future phage therapies and to take advantage of the additional functionality brought by the polymers.