Matt J. Keeling, Edward M. Hill, Stavros Petrou, Phuong Bich Tran, May Ee Png, Sophie Staniszewska, Corinna Clark, Katie Hassel, Julia Stowe, Nick Andrews

In England, and many other countries, immunity to SARS-CoV-2 infection and COVID-19 disease is highly heterogeneous.. During the height of the pandemic in England, the main aim was to rapidly protect the population and large supplies of vaccine were pre-purchased, eliminating the need for cost-effective calculations. As we move to an era where for the majority of the population SARS-CoV-2 infections cause relatively mild disease, and vaccine stocks need to be re-purchased, it is important we consider the cost-effectiveness and economic value of COVID-19 vaccination programmes. Here using data from 2023 and 2024 in England on COVID-19 hospital admissions, ICU admissions and deaths, coupled with bespoke health economic costs, we consider the willingness to pay threshold for COVID-19 vaccines in different age and risk groups.

Vaccine. March 2025

Michaël Dagne Tadesse, Nala Ali, Martha White, Lijiang Song, Fabrizio Alberti, Antonia P. Sagona 

There is an urgent need for novel antimicrobial therapies, chemical and nonantibiotic. The basidiomycota-derived, secondary metabolite pleurotin has been shown to be effective against Gram-positive bacteria, while bacteriophages could be the ultimate nonantibiotic alternative. In this study, the combination of pleurotin and phage K targeting S. aureus was examined. Pleurotin was isolated from the basidiomycota fungus Hohenbuehelia grisea. The cytotoxicity of pleurotin was assessed in two human cell lines in comparison to pleuromutilin, vancomycin, and phage K. The antibiotics were then tested independently or in combination with phage K against two S. aureus strains. Cytotoxicity of pleurotin in human cells was comparable to vancomycin and pleuromutilin. Results suggest that adding phage K has a synergistic effect and can lower the MIC for pleurotin, pleuromutilin, and vancomycin. This demonstrates that pleurotin could be a viable antistaphylococcal drug.

ACS Omega. March 2025

Matevz Papp-Rupar, Emily R. Grace, Naina Korotania, Maria-Laura Ciusa, Robert W. Jackson, Mojgan Rabiey

Isolation of phages targeting the cherry pathogen Pseudomonas syringae pv. syringae (Pss) led to five distinct phage genotypes. Building on previous in vitro coevolution experiments, the coevolution of the five phages (individually and as a cocktail) with Pss on cherry leaves was conducted in glasshouse and field experiments. Phages effectively reduced Pss numbers on detached leaves, with no evidence of phage resistance emerging in the bacterial population. Field application of phages in a cherry orchard in Southeast England evaluated phage survival, viability and impact on bacterial populations and the microbial community. The bacterial population and phages persisted in the leaf and shoot environment as long as the bacterial host was present. In contrast to in vitro studies, the plant environment constrained the emergence of phage resistant Pss populations.

Environmental Microbiology. March 2025

Niba Rawlings, Ngwa, Bailey, Mark and Courtenay, Orin

This systematic review and meta-analysis of data specific to military populations aims to identify knowledge gaps to mitigate sand fly exposure and Leishmania transmission during deployments. Regular use of long-lasting insecticidal nets to mitigate sand fly exposure demonstrated high potential effectiveness than other reported personal protective measures (PPMs) which yielded mixed or inconclusive results. In summary, the systematic review revealed the substantial variability between study designs and statistical integrity. There is need for more consistent and robustly designed studies including well-define controls and replication. Future studies would be advised to explore the long-term effectiveness and practicality of PPMs, both individually and in combination, across diverse deployment settings.

PLoS Neglected Tropical Diseases. March 2025

Glen Guyver-Fletcher, Erin E. Gorsich, Chris Jewell, Michael J. Tildesley

In this article we present a spatially-explicit stochastic metapopulation model to simulate the spread and control of foot-and-mouth disease (FMD) in an endemic setting. We parameterise and validate the model using detailed outbreak data from the Republic of Turkey, 2001–2012. Subsequently, we assess the efficacy of ring vaccination, mass vaccination, and livestock movement restrictions with regards to incidence-reduction and likelihood of eradication. Our results suggest countries wishing to control the disease within their borders should focus on comprehensive surveillance and vaccination campaigns as their main policy goals. In summary, vaccination-based policies are more effective than movement restrictions in the endemic context.

Infectious Disease Modelling.; February 2025

Zuyu Yang, Heather Davies, Jane Clapham, Liza Lopez, Holly B Bratcher, Audrey Tong, Xavier Didelot, Martin C.J. Maiden, Philip E. Carter, Xiaoyun Ren

Neisseria meningitidis is the causative agent of invasive meningococcal disease (IMD), a form of bacterial meningitis and septicaemia, leading to isolated cases, outbreaks, and epidemics worldwide. Between 1991 and 2008, Aotearoa/New Zealand (NZ) experienced a prolonged hyperendemic group B IMD outbreak caused by the NZMenB epidemic strain. To understand NZMenB origin and initiation we used phylodynamic tools to analyse approximately 97 % of all NZMenB isolates submitted to the NZ Meningococcal Reference Laboratory from 1990 to 2019.. Our evidence from molecular dating and clonal expansion analysis suggests that NZMenB was circulating and had expanded before the epidemic. Comparison with international data showed multiple importations and re-introductions of NZMenB into NZ, while not suggesting close relationships with international variants. We propose the NZMenB epidemic may have been triggered by increasing societal inequality and household crowding resulting from government policies at the time.

Infection, Genetics and Evolution. February 2025

Alexander R Kaye, Giorgio Guzzetta, Michael J Tildesley

For many infectious diseases, the risk of outbreaks varies seasonally. If a pathogen is usually absent from a host population, a key public health policy question is whether the pathogen’s arrival will initiate local transmission, which depends on the season in which arrival occurs. This question can be addressed by estimating the “probability of a major outbreak” (the probability that introduced cases will initiate sustained local transmission). We have devised an approach for inferring outbreak risks for seasonal pathogens (involving calculating the Threshold Epidemic Risk; TER). Estimation of the TER involves calculating the probability that introduced cases will initiate a local outbreak in which a threshold number of cumulative infections is exceeded before outbreak extinction. For simple seasonal epidemic models, such as the stochastic Susceptible-Infectious-Removed model, the TER can be calculated numerically (without model simulations). For more complex models, such as stochastic host-vector models, the TER can be estimated using model simulations.

PLoS Computational Biology. February 2024

Sarbjit Nijjar, Deborah Brotherton, Jack Butler, Valentin-Mihai Dospinescu, Harry G Gannon, Victoria Linthwaite, Martin Cann, Alexander Cameron, Nicholas Dale 

CO2 directly modifies the gating of connexin26 (Cx26) gap junction channels and hemichannels. This gating depends upon Lys125, and the proposed mechanism involves carbamylation of Lys125 to allow formation of a salt bridge with Arg104 on the neighbouring subunit. We demonstrate via carbamate trapping and tandem mass spectrometry that five Lys residues within the cytoplasmic loop, including Lys125, are indeed carbamylated by CO2 . Our findings directly demonstrate carbamylation in connexins, provide further insight into the differential action of CO2 on Cx26 hemichannels and gap junction channels, and increase support for the role of the N-terminus in gating the Cx26 channel. KEY POINTS: Direct evidence of carbamylation of multiple lysine residues in the cytoplasmic loop of Cx26. Concentration-dependent carbamylation at lysines 108, 122 and 125. Only carbamylation of lysine 125 is essential for hemichannel opening to CO2. Carbamylation of lysine 108 along with lysine 125 is essential for CO2-dependent gap junction channel closure.

Journal of Physiology. February 2025

Julia A. Fairbairn, Rachel V. Kerr, Nika-Kare A. Pierre-White, Anthony Jacovides, Becca W. A. Baileeves, Phillip J. Stansfeld, Gerhard Bringmann, Andrew T. Merritt and Timothy D. H. Bugg

Escherichia coli translocase MraY is the target for bacteriolytic protein E from bacteriophage fX174, interacting at a site close to Phe-288 on helix 9, on the extracellular face of the protein. A peptide motif Arg-Trp-x-x-Trp from protein E was used to design a set of triazinedione peptidomimetics, which inhibit particulate MraY (6d IC50 48 µM), and show antimicrobial activity against Gram-negative and Gram-positive antibiotic-resistant clinical strains (7j MIC Acinetobacter baumannii 16 µg/mL, Staphyloccoccus aureus MRSA 2-4 µg/mL). Docking against a predicted structure for E. coli MraY revealed two possible binding sites close to helix 9, the binding site for protein E. Antimicrobial activity of analogue 6j was found to be synergistic with bacitracin in Micrococcus flavus, consistent with a link between this inhibition site and undecaprenyl phosphate uptake. Alkaloid michellamine B, also predicted to bind in the cleft adjacent to helix 9, was also found to be synergistic with bacitracin. These data provide experimental evidence that the unusual hydrophobic cleft adjacent to helix 9 in MraY is involved in uptake of undecaprenyl phosphate, in addition to recently identified transporters UptA and PopT, and that this process can be targetted by small molecules as a novel antibacterial mechanism.

RSC Medicinal Chemistry. January 2025

Helekal, David, Koskela, Jere and Didelot, Xavier

Here we consider the problem of detecting the presence of multiple mergers in the context of dating a phylogeny, that is determining the date of each of the nodes. We use the Lambda-coalescent theory as a modelling framework and show how Bayesian inference can be efficiently performed using a Billera-Holmes- Vogtmann space embedding and a customised Markov Chain Monte Carlo sampling scheme. We applied this new analysis methodology to a large number of simulated datasets to show that it is possible to infer if and when multiple merger events occurred, and that the phylogenetic dating is improved as a result of taking this information into account. We also analysed real datasets of Vibrio cholerae and Mycobacterium tuberculosis to demonstrate the relevance of our approach to real pathogen evolutionary epidemiology. We have implemented our new methodology in a R package which is freely available at https://github.com/dhelekal/MMCTime.

Systematic Biology. January 2025

Zdouc, Mitja M. et al inc. Alberti, F

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015. Here, we describe MIBiG version 4.0, an extensive update to the data repository and the underlying data standard.

Nucleic Acids Research. January 2025

Kelsey Cremin, Gabriel N. Meloni, Orkun S. Soyer, Patrick R. Unwin

This work presents an experimental platform combining scanning ion conductance microscopy (SICM) with confocal laser scanning microscopy (CLSM), using intra- and extracellular pH indicator dyes to study the impact of acid delivery on individual HeLa cells within a population.. We find a strong dependency between the intracellular pH and the extracellular pH gradient imposed by local acid delivery. Postdelivery intracellular pH recovery depends on the extent of the acid challenge, with cells exposed to lower pH not returning to basal intracellular pH values after the extracellular pH recovers. This is a unique method for concentration-gradient challenge studies of cell populations that will have broad applications in cell biology. SICM can be used to deliver different chemicals and enables a wide range of local conditions to be applied across a cell population, for which the effects can be investigated at the single-cell level.

ACS Measurement Science. January 2025

Pawel K Lysyganicz, Antonio D Barbosa, Shoily Khondker, Nicolas A Stewart, George M Carman, Phillip J Stansfeld, Marcus K Dymond, Symeon Siniossoglou

Here we demonstrate that a lipid-degradation pathway inhibits expansion of the endoplasmic reticulum (ER) membrane. Phospholipid diacylglycerol acyltransferases (PDATs) use endogenous phospholipids as fatty-acyl donors to generate triglyceride stored in lipid droplets. The significance of this non-canonical triglyceride biosynthesis pathway has remained elusive. We show that active Lro1 mediates retraction of ER membrane expansion driven by phospholipid synthesis. Furthermore, subcellular distribution and membrane turnover activity of Lro1 are controlled by diacylglycerol produced by the activity of Pah1, a conserved member of the lipin family. Collectively, our findings reveal a lipid-metabolic network that regulates endoplasmic reticulum biogenesis by converting phospholipids into storage lipids.

EMBO Journal. January 2025

Structure of the Nipah virus polymerase complex

Esra Balıkçı, Franziska Günl, Loïc Carrique, Jeremy R Keown, Ervin Fodor, Jonathan M Grimes

Nipah virus is a highly virulent zoonotic paramyxovirus causing severe respiratory and neurological disease. Despite its lethality, there is no approved treatment for Nipah virus infection. The viral polymerase complex, composed of the polymerase (L) and phos-phoprotein (P), replicates and transcribes the viral RNA genome. Here, we describe structures of the Nipah virus L-P polymerase complex and the L-protein’s Connecting Domain (CD). Our findings offer insights into the structural details of the L-P polymerase complex and the molecular interactions between L-proteinand P-protein, shedding light on the mechanisms of the replicationmachinery. This work will underpin efforts to develop antiviraldrugs that target the polymerase complex of Nipah virus.

EMBO Journal. December 2024.

Structural characterization of the full-length Hantaan virus polymerase

Hantaviridae are a family of segmented negative-sense RNA viruses that contain important human and animal pathogens. Hantaviridae contain a viral RNA-dependent RNA polymerase that replicates and transcribes the viral genome. Here we establish the expression and purification of the polymerase from the Old World Hantaan virus and characterise the structure using Cryo-EM. The insights gained here guide future mechanistic studies of both the transcription and replication activities of the hantavirus polymerase and for the development of therapeutic targets.

PLoS Pathogens. December 2024

Felipe J Medina-Aguayo, Xavier Didelot, Richard G Everitt

Bacteria reproduce clonally but most species recombine frequently, so that the ancestral process is best captured using an ancestral recombination graph. This graph model is often too complex to be used in an inferential setup, but it can be approximated for example by the ClonalOrigin model. Inference in the ClonalOrigin model is performed via a Reversible-Jump Markov Chain Monte Carlo algorithm, however this often performs poorly due to the complexity of the target distribution since it needs to explore spaces of different dimensions. Recent developments in Bayesian computation methodology have provided ways to improve existing methods and code, but are not well-known outside the statistics community. We show how exploiting one of these new computational methods can lead to faster inference under the ClonalOrigin model.

Bayesian Analysis. December 2024

Diana Vinchira-Villarraga, Sabrine Dhaouadi, Vanja Milenkovic, Jiaqi Wei, Emily R. Grace, Katherine G. Hinton, Amy J. Webster, Andrea Vadillo-Dieguez, Sophie E. Powell, Naina Korotania, Leonardo Castellanos, Freddy A. Ramos, Richard J. Harrison, Mojgan Rabiey & Robert W. Jackson

This study aimed to develop a methodological approach to obtain extracts from different tree species with the highest reproducibility and chemical diversity possible, to ensure proper coverage of the trees’ metabolome. Each tree species has a unique metabolic profile, which means that no single protocol is universally effective. Extraction at 50 °C for three cycles using 80% methanol or chloroform/methanol/water showed the best results and is suggested for studying wood metabolome. These observations highlight the need to tailor extraction protocols to each tree species to ensure comprehensive metabolome coverage for metabolic profiling.

Metabolomics. December 2024

Valeriya Bezkorovayna, Brooke K. Hayes, Francesca N. Gillett, Amy Wright, David I. Roper, Marina Harper, Sheena McGowan, John D. Boyce

Acinetobacter baumannii is a Gram-negative opportunistic pathogen and is a common cause of nosocomial infections.). Here we define the regions of interaction between Tae17 and its cognate delivery protein VgrG17 and identify that amino acids G1069 and W1075 in VgrG17 are essential for Tae17 delivery via the T6SS, the first time such specific delivery determinants of T6SS cargo effectors have been defined. Furthermore, we determine that the Tae17 effector is a multidomain, bifunctional, peptidoglycan-degrading enzyme that has both amidase activity, which targets the sugar-peptide bonds, and lytic transglycosylase activity, which targets the peptidoglycan sugar backbone. Moreover, we show that the Tae17 transglycosylase activity is more important than amidase activity for the killing of Escherichia coli. This study provides molecular insight into how the T6SS allows A. baumannii strains to gain dominance in polymicrobial communities and thus improve their chances of survival and transmission.

mBio. December 2024

The impact of natural climate variability on the global distribution of Aedes aegypti : a mathematical modelling study

Kaye, A. R., Obolski, U., Sun, L., Hart, W. S., Hurrell, J. W., Tildesley, M. J. and Thompson, R. N.

Aedes aegypti spread pathogens affecting humans, including dengue, Zika, and yellow fever viruses. Anthropogenic climate change is altering the spatial distribution of Ae aegypti and therefore the locations at risk of vector-borne disease. In addition to climate change, natural climate variability, resulting from internal atmospheric processes and interactions between climate system components (eg, atmosphere–land and atmosphere–ocean interactions), determines climate outcomes. However, the role of natural climate variability in modifying the effects of anthropogenic climate change on future environmental suitability for Ae aegypti has not been assessed fully. In this study, we aim to assess uncertainty arising from natural climate variability in projections of Ae aegypti suitability up to the year 2100. Lancet Planetary Health. December 2024

The time between symptom onset and various clinical outcomes : a statistical analysis of MERS-CoV patients in Saudi Arabia

Althobaity, Yehya, Alkhudaydi, Muhammad, Hill, Edward M., Thompson, Robin N. and Tildesley, Michael J

In this study, we investigate the impact of demographic characteristics on MERS-CoV cases in Saudi Arabia, specifically focusing on the time intervals between symptom onset and key events such as hospitalization, case confirmation, reporting and death. Importantly, we observe age-based differences in the risk of hospitalization and other measures of infection severity, including the probability of death conditional on hospitalization. Careful quantification of epidemiological characteristics, including inference of key epidemiological periods and assessments of differences between cases of different ages, plays a crucial role in understanding the progression of MERS-CoV outbreaks and formulating effective public health strategies to mitigate their impact.

Royal Society Open Society. November 2024

Kołodziej, Marta, Tsapras, Panagiotis, Cameron, Alexander and Nezis, Ioannis P

LC3 (microtubule-associated protein 1 light chain 3, called Atg8 in yeast and Drosophila) is one of the most well-studied autophagy-related proteins. LC3 controls the selectivity of autophagic degradation by interacting with LIR (LC3-interacting region) motifs also known as AIM (Atg8-interacting motifs) on selective autophagy receptors that carry cargo for degradation. Although the function of Atg8 family proteins is primarily cytoplasmic, they are also enriched in the nucleus. Here, we used yeast two-hybrid screening, and we identified transcription factor Deformed wings (Dwg) as an Atg8a-interacting protein in Drosophila. Dwg-Atg8a interaction is LIR motif-dependent. We have created Dwg Y129A/I132A LIR mutant flies and shown that they exhibit elevated autophagy, improved resistance to oxidative stress, and starvation. Our results provide novel insights into the transcriptional regulation of autophagy in Drosophila.

Cells. November 2024

Claudia Simm, Tzong-Hsien Lee, Harshini Weerasinghe, Dean Walsh, Ioanna T Nakou, Madhu Shankar, Wai Chung Tse, Rebecca Inman, Robert J Mulder, Freya Harrison, Marie-Isabel Aguilar, Gregory L Challis, Ana Traven

Amphotericin B (AmpB) is an effective but toxic antifungal drug.. AmpB disrupts fungal membranes by two proposed mechanisms: ergosterol sequestration from the membrane and pore formation. Whether these two mechanisms operate in conjunction and how they could be potentiated remains to be fully understood. Here, we report that gladiolin, a polyketide antibiotic produced by Burkholderia gladioli, is a strong potentiator of AmpB and acts synergistically against Cryptococcus and Candida species, including drug-resistant C. auris. Gladiolin also synergizes with AmpB against drug-resistant fungal biofilms, while exerting no mammalian cytotoxicity.. Collectively, our findings shed light on AmpB’s mechanism of action and characterize gladiolin as an AmpB potentiator, showing an antifungal mechanism distinct from its proposed antibiotic activity. We shed light on the synergistic mechanism at the membrane, and provide insights into potentiation strategies to improve AmpB’s activity/toxicity relationship.

mBio. November 2024

Chris L B Graham, Jack Bryant, David I Roper, Manuel Banzhaf 

Here we describe a method for in vivo phospholipid labelling by fluorescent imaging in Pseudomonas aeruginosa using a phosphatidylcholine (PC) mimic, “propargyl-choline”(PCho). This click-chemistry liable headgroup mimic is visible by microscopy and allows the covalent labelling of lipids. Fluorescence of the cell membranes, visible in heterogenous patches, is dependent on PCho concentration and is localised in the membrane fraction of cells, demonstrating that it is suitable for membrane labelling and cell imaging.

Access Microbiology. November 2024

Nathan J. Burton, Luís D R. Melo, Michaël F D. Tadesse, Bethany Pearce, Evangelos Vryonis, Antonia P. Sagona

In this study, we produced a cocktail of novel bacteriophages and assessed their viability to eradicate nosocomial staphylococcal biofilms. Here, we used clinical isolates from prosthetic joint infections to isolate and identify four new bacteriophages from sewage effluent. These novel phages were characterized through electron microscopy and full genome sequencing. Subsequently, we combined them into a phage cocktail, which effectively re-sensitized biofilms to vancomycin and flucloxacillin. Notably, this phage cocktail demonstrated low cytotoxicity in vitro to human epithelial cells, even when used alongside antibiotic treatments. These findings highlight the potential of the phage cocktail as a tool to increase antibiotic treatment success in prosthetic joint infections.

Sustainable Microbiology. November 2024

Rawlings, Ngwa Niba, Bailey, Mark, Craig, Peter, Courtenay, Orin

British soldiers undergoing jungle training in Belize typically experience a relatively low risk of developing cutaneous leishmaniasis. However, an uncharacteristically large outbreak of cutaneous leishmaniasis occurred in 2022. This study aimed to determine the cumulative incidence of the disease and highlight potential shortcomings in personal protective measures to mitigate exposure to sand fly vector bites. A retrospective analysis was conducted on medical records of cutaneous leishmaniasis cases between 2005 and 2022, as well as on questionnaire responses regarding personal protective measures administered to cutaneous leishmaniasis cases in 2022. The reasons behind the unusually high numbers of cutaneous leishmaniasis cases and cumulative incidence in 2022 remain unclear, emphasising the need to improve personal protective measures provision and implement a comprehensive health education programme for troops undergoing jungle training in Belize.

Parasite Epidemiology and Control. November 2024

Praneet Prakash, Xue Jiang , Luke Richards, Zoe Schofield, Patrick Schafer Marco Polin, Orkun S. Soyer & Munehiro Asally

Many species of soil fungi grow in the form of branched networks that enable long-range communication and mass flow of nutrient. While there have been investigations on the branching of the fungal networks, their long-term growth dynamics in space and time is still not very well understood. In this study, we monitor the spatio-temporal growth dynamics of the plant-promoting filamentous fungus Serendipita indica for several days in a controlled environment within a microfluidic chamber. We find that S. indica cells display synchronised growth oscillations with the onset of sporulation and at a period of 3 hours. Quantifying this experimental synchronisation of oscillatory dynamics, we show that the synchronisation can be recapitulated by the nearest neighbour Kuramoto model with a millimetre-scale cell-cell coupling.

Royal Society Interface. October 2024

Georgina Benn, Christian Bortolini, David M Roberts, Alice L B Pyne, Seamus Holden, Bart W Hoogenboom

Complement proteins eliminate Gram-negative bacteria in the blood via the formation of membrane attack complex (MAC) pores in the outer membrane. However, it remains unclear how outer membrane poration leads to inner membrane permeation and cell lysis. Using atomic force microscopy (AFM) on living Escherichia coli (E. coli), we probed MAC-induced changes in the cell envelope and correlated these with subsequent cell death. We conclude that bacterial cell lysis is only an indirect effect of MAC formation; outer membrane poration leads to mechanical destabilization of the cell envelope, reducing its ability to contain the turgor pressure, leading to inner membrane permeation and cell death.

EMBO Journal. October 2024

Luke Richards, Kelsey Cremin, Mary Coates, Finley Vigor, Patrick Schäfer, and Orkun S Soyer

Soil microbial communities host a large number of microbial species that support important ecological functions such as biogeochemical cycling and plant nutrition. The extent and stability of these functions are affected by inter-species interactions among soil microorganisms, yet the different mechanisms underpinning microbial interactions in the soil are not fully understood. Here, we study the extent of nutrient-based interactions among two model, plant-supporting soil microorganisms, the fungi Serendipita indica, and the bacteria Bacillus subtilis. Our findings highlight that ammonia based N-sharing can be a previously under-appreciated mechanism underpinning interaction among soil microorganisms and could be influenced by microbial or abiotic alteration of pH in microenvironments.

ISME Journal. September 2024

Keeling, Matthew James and Dyson, Louise

We discuss the invasion of the Omicron BA.1 variant into England as a paradigm for real-time model fitting and projection. Here we use a mixture of simple SIR-type models, analysis of the early data and a more complex age-structure model fit to the outbreak to understand the dynamics. In particular, we highlight that early data shows that the invading Omicron variant had a substantial growth advantage over the resident Delta variant. However, early data does not allow us to reliably infer other key epidemiological parameters - such as generation time and severity - which influence the expected peak hospital numbers. With more complete epidemic data from January 2022 are we able to capture the true scale of the epidemic in terms of both infections and hospital admissions, driven by different infection characteristics of Omicron compared to Delta and a substantial shift in estimated precautionary behaviour during December. This work highlights the challenges of real time forecasting, in a rapidly changing environment with limited information on the variant’s epidemiological characteristics.

PLoS Computational Biology. September 2024

Matthew Higgins, Mojca Kristan, Emma L. Collins, Louisa A. Messenger, Jamille G. Dombrowski, Leen N. Vanheer, Debbie Nolder, Christopher J. Drakeley, William Stone, Almahamoudou Mahamar, Teun Bousema, Michael Delves, Janvier Bandibabone, Sévérin N’Do, Chimanuka Bantuzeko, Bertin Zawadi, Thomas Walker, Colin J. Sutherland, Claudio R. F. Marinho, Mary M. Cameron, Taane G. Clark & Susana Campino

Malaria caused by neglected Plasmodium parasites is often underestimated due to the lack of rapid diagnostic tools that can accurately detect these species. Here, we present a Pan Plasmodium recombinase polymerase amplification lateral flow (RPA–LF) assay, capable of detecting all six human infecting Plasmodium species in low resource settings.. When combined with crude nucleic acid extraction, the assay can serve as a point-of-need tool for molecular xenomonitoring. This utility was demonstrated by screening laboratory-reared Anopheles stephensi mosquitoes fed with Plasmodium-infected blood, as well as field samples of An. funestus s.l. and An. gambiae s.l. collected from central Africa. Overall, our proof-of-concept Pan Plasmodium diagnostic tool has the potential to be applied for clinical and xenomonitoring field surveillance, and after further evaluation, could become an essential tool to assist malaria control and elimination.

Scientific Reports. August 2024

de Klerk, Joanna N., Tildesley, Michael J., Labuschagne, Karien and Gorsich, Erin E

Culicoides biting midges exhibit a global spatial distribution and are the main vectors of several viruses of veterinary importance, including bluetongue (BT) and African horse sickness (AHS). The aim of this study was to model distributions for two primary vectors for BT and AHS (Culicoides imicola and Culicoides bolitinos) using random forest (RF) machine learning and explore the relative importance of environmental and anthropological factors in a region of South Africa with frequent AHS and BT outbreaks. This study yielded novel insight into the spatial abundance and drivers of abundance of competent vectors of BT and AHS. It also provided valuable data to inform mathematical models exploring disease outbreaks so that Culicoides-transmitted diseases in South Africa can be further analysed.

Parasites & Vectors. August 2024

Christian Vanhille-Campos, Kevin D. Whitley, Philipp Radler, Martin Loose, Seamus Holden & Anđela Šarić

Filaments in the cell commonly treadmill. Driven by energy consumption, they grow on one end while shrinking on the other, causing filaments to appear motile even though individual proteins remain static. This process is characteristic of cytoskeletal filaments and leads to collective filament self-organization. Here we show that treadmilling drives filament nematic ordering by dissolving misaligned filaments. Taking the bacterial FtsZ protein involved in cell division as an example, we show that this mechanism aligns FtsZ filaments in vitro and drives the organization of the division ring in living Bacillus subtilis cells. We find that ordering via local dissolution also allows the system to quickly respond to chemical and geometrical biases in the cell, enabling us to quantitatively explain the ring formation dynamics in vivo. Beyond FtsZ and other cytoskeletal filaments, our study identifies a mechanism for self-organization via constant birth and death of energy-consuming filaments.

Nature Physics. August 2024

Huba L. Marton, Antonia P. Sagona, Peter Kilbride and Matthew I. Gibson

Poly(carboxylic acids) have been reported to inhibit phages’ ability to infect their bacterial hosts and hence offer an exciting route to discover additives to prevent infection. Here, we report the role of pH in inactivating phages to determine if the polymers are unique or simply acidic. It is shown that lower pH (= 3) triggered by either acidic polymers or similar changes in pH using HCl lead to inhibition. There is no inhibitory activity at higher pHs (in growth media). It is also shown that poly(acrylic acid) leads to reversible deactivation of phage, but when the pH is adjusted using HCl alone the phage is irreversibly deactivated. Further experiments using metal binders ruled out ion depletion as the mode of action.  These results show that polymeric phage inhibitors may work by unique mechanisms of action and that pH alone cannot explain the observed effects whilst also placing constraints on the practical utility of poly(acrylic acid).

RSC Applied Polymers. August 2024

Prioritising older individuals for COVID-19 booster vaccination leads to optimal public health outcomes in a range of socio-economic settings

Bouros, Ioana, Hill, Edward M., Keeling, Matt J., Moore, Sam and Thompson, Robin N.

The rapid development of vaccines against SARS-CoV-2 altered the course of the COVID-19 pandemic. In most countries, vaccinations were initially targeted at high-risk populations, including older individuals and healthcare workers. Policy makers must now determine how to deploy booster vaccinations, particularly when constraints in vaccine supply, delivery and cost mean that booster vaccines cannot be administered to everyone. A key question is whether older individuals should again be prioritised for vaccination, or whether alternative strategies (e.g. offering booster vaccines to the individuals who have most contacts with others and therefore drive infection) can instead offer indirect protection to older individuals. Here, we use mathematical modelling to address this question, considering SARS-CoV-2 transmission in a range of countries with different socio-economic backgrounds. We show that the population structures of different countries can have a pronounced effect on the impact of booster vaccination, even when identical booster vaccination targeting strategies are adopted. However, under the assumed transmission model, prioritising older individuals for booster vaccination consistently leads to the most favourable public health outcomes in every setting considered. PLoS Computational Biology. August 2024

Modelling timelines to elimination of sleeping sickness in the Democratic Republic of Congo, accounting for possible cryptic human and animal transmission

Sleeping sickness (gambiense human African trypanosomiasis, gHAT) is a vector-borne disease targeted for global elimination of transmission (EoT) by 2030. There are, however, unknowns that have the potential to hinder the achievement and measurement of this goal. These include asymptomatic gHAT infections (inclusive of the potential to self-cure or harbour skin-only infections) and whether gHAT infection in animals can contribute to the transmission cycle in humans. Using modelling, we explore how cryptic (undetected) transmission impacts the monitoring of progress towards and the achievement of the EoT goal. This study is the first to simulate an (as-yet-to-be available) screen-and-treat strategy and found that removing a parasitological confirmation step was predicted to have a more noticeable benefit to transmission reduction under the asymptomatic model compared with the others. Our simulations suggest vector control could greatly impact all transmission routes in all models, although this resource-intensive intervention should be carefully prioritised. Parasites & Vectors. August 2024

Collette S. Guy, James A. Gott, Jonathan Ramírez-Cárdenas, Christopher de Wolf, Christopher M. Furze, Geoff West, Juan C. Muñoz-García, Jesus Angulo and Elizabeth Fullam 

The sensitive, rapid and accurate diagnosis of Mycobacterium tuberculosis (Mtb) infection is a central challenge in controlling the global tuberculosis (TB) pandemic. Yet the detection of mycobacteria is often made difficult by the low sensitivity of current diagnostic tools, with over 3.6 million TB cases missed each year. To overcome these limitations there is an urgent need for next-generation TB diagnostic technologies. Here we report the use of a discrete panel of native 19F-trehalose (F-Tre) analogues to label and directly visualise Mtb by exploiting the uptake of fluorine-modified trehalose analogues via the mycobacterial trehalose LpqY-SugABC ATP-binding cassette (ABC) importer.. This rapid one-step labelling approach facilitates the direct visualisation of F-Tre-labelled Mtb by Focused Ion Beam (FIB) Secondary Ion Mass Spectrometry (SIMS), enabling detection of the Mtb pathogen. Collectively, our findings highlight that F-Tre analogues have potential as tools to probe and unravel Mtb biology and can be exploited to detect and image TB

Chemical Science.August 2024

Peter Wotherspoon, Hannah Johnston, David J. Hardy, Rachel Holyfield, Soi Bui, Giedrė Ratkevičiūtė, Pooja Sridhar, Jonathan Colburn, Charlotte B. Wilson, Adam Colyer, Benjamin F. Cooper, Jack A. Bryant, Gareth W. Hughes, Phillip J. Stansfeld, Julien R. C. Bergeron & Timothy J. Knowles

The Maintenance of Lipid Asymmetry (Mla) pathway is a multicomponent system found in all gram-negative bacteria that contributes to virulence, vesicle blebbing and preservation of the outer membrane barrier function. Here, we report the structure of E. coli MlaC in complex with the MlaD hexamer in two distinct stoichiometries. Utilising in vivo complementation assays, an in vitro fluorescence-based transport assay, and molecular dynamics simulations, we confirm key residues, identifying the MlaD β6-β7 loop as essential for MlaCD function. We also provide evidence that phospholipids pass between the C-terminal helices of the MlaD hexamer to reach the central pore, providing insight into the trajectory of GPL transfer between MlaC and MlaD.

Nature Communications. July 2024

Behzad Dehghani, Christopher D. A. Rodrigues

During spore development in bacteria, a polar septum separates two transcriptionally distinct cellular compartments, the mother cell and the forespore. The conserved serine phosphatase SpoIIE is known for its critical role in the formation of this septum and activation of compartment-specific transcription in the forespore. Signaling between the mother cell and forespore then leads to activation of mother cell transcription and a phagocytic-like process called engulfment, which involves dramatic remodeling of the septum and requires a balance between peptidoglycan synthesis and hydrolysis to ensure septal stability and compartmentalization. Using Bacillus subtilis, we identify an additional role for SpoIIE in maintaining septal stability and compartmentalization at the onset of engulfment. Our data support a model whereby SpoIIE and its interactions with the peptidoglycan synthetic machinery contribute to the stabilization of the asymmetric septum early in engulfment, thereby ensuring compartmentalization during spore development.

Journal of Bacteriology. July 2024

Michelle Kendall, Luca Ferretti, Chris Wymant, Daphne Tsallis, James Petrie, Andrea di Francia, Franceso di Lauro, Lucie Abeler-Dorner, Harrison Manley, Jasmina Panovska-Griffiths, Alice Ledda, Xavier Didelot and Christophe Fraser

Understanding the drivers of respiratory pathogen spread is challenging, particularly in a timely manner during an ongoing epidemic. Here we present insights obtained using daily data from the NHS COVID-19 app for England and Wales and shared with health authorities in almost real time. Our indicator of the reproduction number R(t) was available days earlier than other estimates, with a novel capability to decompose R(t) into contact rates and probabilities of infection. When Omicron arrived, the main epidemic driver switched from contacts to transmissibility. We separate contacts and transmissions by day of exposure and setting, finding pronounced variability over days of the week and during Christmas holidays and events. As an example, during the Euro football tournament in 2021, days with England matches showed sharp spikes in exposures and transmissibility. Digital contact tracing technologies can help control epidemics not only by directly preventing transmissions but also by enabling rapid analysis at scale and with unprecedented resolution.  

Science. July 2024

Tailise Carolina de Souza-Guerreiro, Letícia Huan Bacellar, Thyerre Santana da Costa, Conor LA Edwards, Ljubica Tasic & Munehiro Asally

Membrane potential is a useful marker for antimicrobial susceptibility testing (AST) due to the fundamental characteristic of vital cells. However, the difficulties associated with measuring the membrane potential in microbes restrict its broad application. In this study, we present Bioelectrical AST (BeAST) using the model fungus Saccharomyces cerevisiae . The results suggest that BeAST holds promise for screening anti-fungal compounds, offering a valuable approach to tackling antimicrobial resistance.

mBio. July 2024

When should lockdown be implemented? Devising cost-effective strategies for managing epidemics amid vaccine uncertainty

Doyle, Nathan, Cumming, Fergus, Thompson, Robin N. and Tildesley, Michael J.

We combine features of existing models to develop a novel model for vectorial capacity that considers both climate and vector control. This model considers how vector control tools affect vectors at each stage of their feeding cycle, and incorporates host availability and preference. Applying this model to arboviruses of veterinary importance in Europe, we show that African horse sickness virus (AHSV) has a higher peak predicted vectorial capacity than bluetongue virus (BTV), Schmallenberg virus (SBV), and epizootic haemorrhagic disease virus (EHDV). However, AHSV has a shorter average infectious period due to high mortality; therefore, the overall basic reproduction number of AHSV is similar to BTV. Overall, this model can be used to consider both climate and vector control interventions either currently utilised or for potential use in an outbreak, and could help guide policy makers seeking to mitigate the impact of climate change on disease control. PLoS Computational Biology. July 2024

Modelling the Influence of Climate and Vector Control Interventions on Arbovirus Transmission

We combine features of existing models to develop a novel model for vectorial capacity that considers both climate and vector control. This model considers how vector control tools affect vectors at each stage of their feeding cycle, and incorporates host availability and preference. Applying this model to arboviruses of veterinary importance in Europe, we show that African horse sickness virus (AHSV) has a higher peak predicted vectorial capacity than bluetongue virus (BTV), Schmallenberg virus (SBV), and epizootic haemorrhagic disease virus (EHDV). However, AHSV has a shorter average infectious period due to high mortality; therefore, the overall basic reproduction number of AHSV is similar to BTV. Overall, this model can be used to consider both climate and vector control interventions either currently utilised or for potential use in an outbreak, and could help guide policy makers seeking to mitigate the impact of climate change on disease control. Viruses. July 2024

Joshua C. Macdonald, Hayriye Gulbudak, Brianna Beechler, Erin E. Gorsich, Simon Gubbins, Eva Pérez-Martin and Anna E. Jolles

We investigated within-host dynamics and among-host transmission of three strains (SAT-1, -2, -3) of foot-and-mouth disease viruses (FMDVs) in their wildlife host, African buffalo. Our data reveals contrasting within-host dynamics among viral strains, with SAT-2 eliciting more rapid and effective immune responses than SAT-1 and SAT-3. Within-host viral fitness was overwhelmingly determined by variation among hosts in immune response activation rates but not by variation among individual hosts in viral growth rate. Our analyses investigating across-scale linkages indicate that viral replication rate in the host correlates with transmission rates among buffalo and that adaptive immune activation rate determines the infectious period. These parameters define the virus’s relative basic reproductive number (ℛ0), suggesting that viral invasion potential may be predictable from within-host dynamics.

American Naturalist. July 2024

Mojgan Rabiey, Emily R. Grace, Paulina Pawlos, Muscab Bihi, Haleem Ahmed, Georgina E. Hampson, Amna Al Riyami, Leena Alharbi, Rosa Sanchez-Lucas, Naina Korotania, Maria Laura Ciusa, Olivia Mosley, Michelle T. Hulin, Laura Baxter, Sabrine Dhaouadi, Diana Vinchira-Villarraga, Robert W. Jacks

Pseudomonas syringae pathovar syringae (Pss) is a major pathogen of cherry (Prunus avium) causing bacterial canker of the stem, leaf and fruit, impacting productivity and leading to a loss of trees. In an attempt to find a treatment for this disease, naturally occurring bacteriophage (phage) that specifically target Pss is being investigated as a biocontrol strategy. However, before using them as a biocontrol treatment, it is important to both understand their efficacy in reducing the bacterial population and determine if the bacterial pathogens can evolve resistance to evade phage infection. To investigate this, killing curve assays of five MR phages targeting Pss showed that phage resistance rapidly emerges in vitro, even when using a cocktail of the five phages together. This study shows that understanding the genetic mechanisms of bacterial pathogen resistance to phages is important for helping to design a more effective approach to kill the bacteria while minimizing the opportunity for phage resistance to manifest.

Microbial Biotechnology. June 20204

Rodrigo Barquera, Oana Del Castillo-Chávez, Kathrin Nägele, Patxi Pérez-Ramallo, Diana Iraíz Hernández-Zaragoza, András Szolek, Adam Benjamin Rohrlach, Pablo Librado, Ainash Childebayeva, Raffaela Angelina Bianco, Bridget S. Penman, Victor Acuña-Alonzo, Mary Lucas, Julio César Lara-Riegos, María Ermila Moo-Mezeta, Julio César Torres-Romero, Patrick Roberts, Oliver Kohlbacher, Christina Warinner & Johannes Krause

Here we present genome-wide data obtained from 64 subadult individuals dating to around AD 500-900 that were found in a subterranean mass burial near the Sacred Cenote (sinkhole) in the ceremonial centre of Chichén Itzá. Genetic analyses showed that all analysed individuals were male and several individuals were closely related, including two pairs of monozygotic twins. Twins feature prominently in Mayan and broader Mesoamerican mythology, where they embody qualities of duality among deities and heroes, but until now they had not been identified in ancient Mayan mortuary contexts. Genetic comparison to present-day people in the region shows genetic continuity with the ancient inhabitants of Chichén Itzá, except at certain genetic loci related to human immunity, including the human leukocyte antigen complex, suggesting signals of adaptation due to infectious diseases introduced to the region during the colonial period. Nature. June 2024

Carvalho, Bruno M., Maia, Carla, Courtenay, Orin, Llabrés-Brustenga, Alba, Lotto Batista, Martín, Moirano, Giovenale, van Daalen, Kim R., Semenza, Jan C. and Lowe, Rachel

Leishmaniases are neglected diseases transmitted by sand flies. The aim of this modelling study was to develop an indicator that tracks climatic suitability for Leishmania infantum transmission in Europe at the subnational level. Historical records of sand fly vectors, human leishmaniasis, bioclimatic indicators, and environmental variables were integrated in a machine learning framework (XGBoost) to predict suitability in two past periods (2001–2010 and 2011–2020. This study demonstrates how key epidemiological data can be combined with open-source climatic and environmental information to develop an indicator that effectively tracks spatiotemporal changes in climatic suitability and disease risk. The positive association between the model predictions and human disease incidence demonstrates that this indicator could help target leishmaniasis surveillance to transmission hotspots.

The Lancet Regional Health - Europe. June 2024

Stuart Middlemiss, Matthieu Blandenet, David M. Roberts, Andrew McMahon, James Grimshaw, Joshua M. Edwards, Zikai Sun, Kevin D. Whitley, Thierry Blu, Henrik Strahl & Seamus Holden

Most rod-shaped bacteria elongate by inserting new cell wall material into the inner surface of the cell sidewall. This is performed by class A penicillin binding proteins (PBPs) and a highly conserved protein complex, the elongasome, which moves processively around the cell circumference and inserts long glycan strands that act as barrel-hoop-like reinforcing structures, thereby giving rise to a rod-shaped cell. However, it remains unclear how elongasome synthesis dynamics and termination events are regulated to determine the length of these critical cell-reinforcing structures. To address this, we developed a method to track individual elongasome complexes around the entire circumference of Bacillus subtilis cells for minutes-long periods using single-molecule fluorescence microscopy. Our results demonstrate that molecular motor tug-of-war is a key regulator of elongasome dynamics in B. subtilis, which likely also regulates the cell shape via modulation of elongasome processivity.

Nature Communications. June 2024

Harrison Manley,Thomas Bayley,Gabriel Danelian, Lucy Burton, Thomas Finnie, Andre Charlett, Nicholas A. Watkins, Paul Birrell, Daniela De Angelis, Matt Keeling, Sebastian Funk, Graham Medley, Lorenzo Pellis, Marc Baguelin, Graeme J. Ackland, Johanna Hutchinson, Steven Riley and Jasmina Panovska-Griffiths

Mathematical modelling has played an important role in offering informed advice during the COVID-19 pandemic. In England, a cross government and academia collaboration generated medium-term projections (MTPs) of possible epidemic trajectories over the future 4–6 weeks from a collection of epidemiological models. In this article, we outline this collaborative modelling approach and evaluate the accuracy of the combined and individual model projections against the data over the period Learning from our experience of ensemble modelling during the COVID-19 epidemic, our findings highlight the importance of developing cross-institutional multi-model infectious disease hubs for future outbreak control.

Royal Society Open Science. May 2024

Claire L. Jeffries, Luciano M Tantely, Perparim Kadriaj, Marcus S C Blagrove, Ioanna Lytra, James Orsborne, Hasan Mohammad Al-Amin, Abdul Rahim Mohammed, Mohammad Shafiul Alam, Romain Girod, Yaw A Afrane, Silvia Bino, Vincent Robert, Sebastien Boyer, Matthew Baylis, Enkelejda Velo, Grant L Hughes, Thomas Walker

In this study, we used laboratory vector competence experiments to determine if Cx. tritaeniorhynchus from a Southern European population were competent JEV vectors. We obtained samples from multiple geographically dispersed Cx. tritaeniorhynchus populations from countries within Europe, Africa, Eurasia and Asia to perform phylogenetic analysis to measure the level of mitochondrial divergence using the cytochrome oxidase subunit 1 (CO1) gene. We also undertook bacterial 16S rRNA gene amplicon sequencing to determine microbial diversity and used multi-locus sequence typing (MLST) to determine any evidence for the presence of strains of the naturally occurring endosymbiotic bacterium Wolbachia. Cx. tritaeniorhynchus from a Greek population were shown be be competent vectors of JEV with high levels of virus present in saliva. We found a signficant level of mitochondrial genetic diversity using the mosquito CO1 gene between geographically dispersed populations. Furthermore, we report diverse microbiomes identified by 16S rRNA gene amplicon sequencing within and between geographical populations. Evidence for the detection of the endosymbiotic bacteria Wolbachia was confirmed using Wolbachia-specific PCR and MLST.

Wellcome Open Research. May 2024

Andriko von Kügelgen, C. Keith Cassidy, Sofie van Dorst, Lennart L. Pagani, Christopher Batters, Zephyr Ford, Jan Löwe, Vikram Alva, Phillip J. Stansfeld & Tanmay A. M. Bharat

Nitrosopumilus maritimus is an ammonia-oxidizing archaeon that is crucial to the global nitrogen cycle. A critical step for nitrogen oxidation is the entrapment of ammonium ions from a dilute marine environment at the cell surface and their subsequent channelling to the cell membrane of N. maritimus. Here we elucidate the structure of the molecular machinery responsible for this process, comprising the surface layer (S-layer), using electron cryotomography and subtomogram averaging from cells. We supplemented our in situ structure of the ammonium-binding S-layer array with a single-particle electron cryomicroscopy structure, revealing detailed features of this immunoglobulin-rich and glycan-decorated S-layer. This in situ structural study illuminates the biogeochemically essential process of ammonium binding and channelling, common to many marine microorganisms that are fundamental to the nitrogen cycle.

Nature. May 2024

Presence of phage-plasmids in multiple serovars of Salmonella enterica

Satheesh Nair​, Clare R. Barker​, Matthew Bird​, David R. Greig​, Caitlin Collins, Anaïs Painset​Marie Chattaway​, Derek Pickard​, Lesley Larkin​, Saheer Gharbia,​ Xavier Didelot​ and Paolo Ribeca

Evidence is accumulating in the literature that the horizontal spread of antimicrobial resistance (AMR) genes mediated by bacteriophages and bacteriophage-like plasmid (phage-plasmid) elements is much more common than previously envisioned. For instance, we recently identified and characterized a circular P1-like phage-plasmid harbouring a blaCTX-M-15 gene conferring extended-spectrum beta-lactamase (ESBL) resistance in Salmonella enterica serovar Typhi. As the prevalence and epidemiological relevance of such mechanisms has never been systematically assessed in Enterobacterales, in this study we carried out a follow-up retrospective analysis of UK Salmonella isolates previously sequenced as part of routine surveillance protocols between 2016 and 2021. In addition to providing a first comprehensive view of the presence of phage-plasmids in Salmonella, our work highlights the need for a better surveillance and understanding of phage-plasmids as AMR carriers, especially through their characterization with long-read sequencing. Microbial Genomics. May 2024

Rapid expansion and international spread of M1UK in the post-pandemic UK upsurge of Streptococcus pyogenes

The UK observed a marked increase in scarlet fever and invasive group A streptococcal infection in 2022 with severe outcomes in children and similar trends worldwide. Here we report lineage M1UK to be the dominant source of invasive infections in this upsurge. Compared with ancestral M1global strains, invasive M1UK strains exhibit reduced genomic diversity and fewer mutations in two-component regulator genes covRS. The emergence of M1UK is dated to 2008. Following a bottleneck coinciding with the COVID-19 pandemic, three emergent M1UK clades underwent rapid nationwide expansion, despite lack of detection in previous years. All M1UK isolates thus-far sequenced globally have a phylogenetic origin in the UK, with dispersal of the new clades in Europe. While waning immunity may promote streptococcal epidemics, the genetic features of M1UK point to a fitness advantage in pathogenicity, and a striking ability to persist through population bottlenecks. Nature Communications. May 2024

Vasconcelos, Andreia, King, Jonathan D., Nunes-Alves, Cláudio, Anderson, Roy, Argaw, Daniel, Basáñez, Maria-Gloria, Bilal, Shakir, Blok, David J., Blumberg, Seth, Borlase, Anna, Brady, Oliver J., Browning, Raiha, Chitnis, Nakul, Coffeng, Luc E., Crowley, Emily H, Cucunubá, Zulma M., Cummings, Derek A. T., Davis, Christopher N., Davis, Emma L., Dixon, Matthew, Dobson, Andrew, Dyson, Louise et al

Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021–2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets.

Clinical Infectious Diseases. May 2024

Susie Cant, G. Dennis Shanks, Matt J. Keeling and Bridget S. Penman

In 1911, Rotuma in Fiji was hit by a measles pidemic, which killed 13% of the island population. Detailed records show two mortality peaks, with individuals reported as dying solely from measles in the first and from measles and diarrhoea in the second. MeHere, we investigate whether the pattern of mortality on Rotuma in 1911 was a consequence of the immunosuppressive effects of measles. We use a compartmental model to simulate measles infection and immunosuppression. Whilst immunosuppressed, we assume that individuals are vulnerable to dysfunctional reactions triggered by either (i) a newly introduced infectious agent arriving at the same time as measles or (ii) microbes already present in the population in a pre-existing equilibrium state. We show that both forms of the immunosuppression model provide a plausible fit to the data and that the inclusion of immunosuppression in the model leads to more realistic estimates of measles epidemiological parameters than when immunosuppression is not included.

Epidemiology & Infection. May 2024

Kim R van Daalen et al incl. Orin Courtenay

The Lancet Countdown in Europe was established in 2021, to assess the health profile of climate change aiming to stimulate European social and political will to implement rapid health-responsive climate mitigation and adaptation actions. In 2022, the collaboration published its indicator report, tracking progress on health and climate change via 33 indicators and across five domains. This new report tracks 42 indicators highlighting the negative impacts of climate change on human health, the delayed climate action of European countries, and the missed opportunities to protect or improve health with health-responsive climate action. Considering that negative climate-related health impacts and the responsibility for climate change are not equal at the regional and global levels, this report also endeavours to reflect on aspects of inequality and justice by highlighting at-risk groups within Europe and Europe's responsibility for the climate crisis.

Lancet Public Heath. May 2024