Science

Ambient air pollution has been associated with increased incidence of chronic disease and is estimated to contribute towards 4.2 million early deaths annually. Whilst the health impacts are well described, less is understood about the underlying biological mechanisms, particularly when considering the co-occurrence of multiple pollutants. Using an atmospheric chemistry transportation model (EMEP4UK), we generate pre-baseline sampling pollution exposure estimates for eight pollutants in Generatio...

Biological fitness quantifies the efficiency and selective advantage of pathogens and hosts in their bilateral interaction. Key questions--such as how much more infectious an emerging variant is compared with its predecessor, or how much protection vaccination offers relative to no vaccination--require fitness to be measured systematically, in real time, and ideally beyond controlled laboratory settings. We propose an approach that infers biological fitness from mostly non-biological data on inf...

Background: Human-to-human transmission of pathogens fundamentally depends on interactions among infectious and susceptible individuals, yet traditional population-scale models often overlook the stochastic, behaviour-driven, and highly heterogeneous nature of these interactions. Methods: Here, we develop a large-scale actor-based model capturing early epidemic dynamics of a novel respiratory pathogen on dynamic contact networks. We build these networks upon explicitly integrating detailed demog...

Biological ageing begins before birth, with early-life exposures shaping late-life health. These exposures drive health inequities early, yet specific exposures and the composition of the ageing exposome remain largely undefined. This gap may persist as the field lacks agnostic investigations accounting for non-linearity, interactions and subtle signals. We aimed to identify exposures predictive of epigenetic ageing accumulated during childhood and adolescence and explore the composition of the...

Visceral leishmaniasis (VL) is considerably more severe among individuals infected with human immunodeficiency virus (HIV), leading to higher parasite loads, frequent relapse, and increased mortality. To examine the epidemiological interaction between the two diseases, we develop a comprehensive VL-HIV co-infection model that incorporates transmission pathways, treatment effects, and relapse dynamics. The model is parameterized using real-time data from Bihar, India, including monthly VL-only an...

Strengthening in-country sequencing capacity generated 28 Lassa virus genomes from human clinical cases, expanding our knowledge of Lassa fever in Guinea. Phylogeographic analysis revealed cross-border exchange between Liberia and the NZerekore region, and a Sierra Leone introduction into the Gueckedou area. Enhanced genomic surveillance is crucial to guide future public health actions.

Nipah virus (NiV) is a sporadic yet extremely deadly zoonotic pathogen, with reported case fatality rates of 40%-75% in impacted areas. Prolonged incubation, documented relapse, and delayed-onset encephalitis following apparent recovery indicate that NiV dynamics are influenced by intricate temporal processes. However, mechanistic contributions of these processes to epidemic persistence remain poorly understood. In this study, we develop and analyze a delay differential equation model for NiV tr...

Background and ObjectivesAssociations of common infections with Alzheimer disease (AD) risk have been reported. A hypothesized mechanism to explain these is cerebral amyloid-beta (A{beta}) aggregation as a defence in response to infection, with subsequent tau accumulation. However, few studies have assessed associations of infections with tau and A{beta} pathology. We investigated associations of serological measures of several common infections with plasma p-tau217 and A{beta} status measured b...

BackgroundHeartland virus (HRTV) is an emerging tick-borne virus capable of causing severe illness and death. The burden of disease is likely underestimated due to limited seroprevalence studies, lack of commercially available diagnostic tests, and an overlapping clinical syndrome with more commonly diagnosed bacterial diseases such as spotted fever group rickettsiosis or ehrlichiosis. MethodsActive surveillance for Heartland virus disease was conducted at a large academic center from March to ...

With significant population fractions in many societies who refuse vaccines, it is important to reconsider how vaccination is incorporated into compartmental epidemiology models. It is still most common to apply the vaccination rate to the entire class of susceptibles, rather than to use the more realistic assumption that the vaccination rate function should depend only on the population of susceptibles who are willing and able to receive a vaccination. This study uses a simple generic disease m...

We present results from the second season of Influcast, a multi-model collaborative forecasting hub focused on influenza in Italy. During the 2024/25 winter season, Influcast collected one-to four-week-ahead probabilistic forecasts of influenza-like illness (ILI) incidence alongside influenza A and B ILI+ incidence signals. New ILI+ targets were constructed integrating syndromic surveillance data with virological detections collected weekly by the Italian National Institute of Health. Forecasts ...

Wastewater is increasingly being recognized as an important data stream that can contribute to infectious disease surveillance and forecasting. With this recognition, a growing number of statistical inference approaches are being developed to use wastewater data to provide quantitative insights into epidemiological dynamics. However, few existing approaches have allowed for systematic integration of data streams for inference, for example by combining case incidence data and/or serological data ...

RIG-I is a cytosolic immune receptor that provides the first line of defense by detecting viral RNA and triggering antiviral responses. Its physiological role in humans remains unclear, as no patients with complete RIG-I deficiency have yet been reported. We identified a critically ill COVID-19 patient with severe RIG-I deficiency caused by heterozygous RIG-I G731R, a novel dominant loss-of-function variant. The G731R mutation in helicase motif VI disrupts the arginine finger, impairing the ATPa...

BackgroundMeasurement of human antibodies against Anopheles salivary proteins that are injected during mosquito bites may serve as biomarkers of mosquito biting exposure. These biomarkers have been suggested as surrogate outcomes in trials of vector control intervention effectiveness, however, studies to-date have been largely descriptive and do not directly quantify the instantaneous nor cumulative effects of the intervention on antibody outcomes. In this study, we sought to explore the use of ...

Introduction: Neurodegenerative diseases (NDDs) including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and non-AD dementias share chronic neuroinflammatory mechanisms that contribute to neuronal injury and disease progression. While anti-inflammatory therapies (AITs) are associated with reduced neurodegenerative disease risk, knowledge regarding the impact of biological sex and treatment duration across multiple NDDs remains li...

Understanding host susceptibility to Mycobacterium tuberculosis (Mtb) is critical for the development of new vaccines. Certain individuals "resist" becoming infected with Mtb despite intensive exposure; however, it is unknown whether there is a genetic basis for "resistance" to Mtb infection across populations. Here we conducted a genome-wide association study (GWAS) of resistance to Mtb infection by carefully characterizing exposure to TB patients among 4,058 close contacts in India, Brazil, an...

Linezolid is a critical last-resort antimicrobial for multidrug-resistant Enterococcus faecium, particularly against vancomycin-resistant lineages where therapeutic options are severely limited. While resistance has historically arisen through de novo chromosomal mutations, the global emergence of transferable resistance mechanisms threatens to render more infections untreatable. Here, we characterise a recent (2023-2024) hospital-associated outbreak of linezolid-resistant E. faecium in Queensla...

Students who frequently miss school are at greater risk for academic difficulty. High levels of absenteeism as early as kindergarten have been associated with long-term consequences, such as low reading proficiency in Grade 3 and low academic achievement in Grade 5, both of which have been associated with lower rates of high school graduation and enrollment in post-secondary education. The prevalence of school absenteeism has increased significantly since the COVID-19 pandemic and there have bee...

BackgroundLarval source management (LSM) was once central to malaria control before insecticide-treated nets and indoor residual spraying dominated. Renewed interest in LSM raises questions about its effectiveness in rural Africa, where habitats are dispersed, and vector species contribute unequally, and whether species-targeted larviciding could offer greater gains than broadcast approaches. MethodsThis modelling study quantified the potential impact of larviciding in African settings where mu...

OBJECTIVEUsing two cohorts and synthetic datasets, we estimated effects of prospectively reported alcohol use on memory outcomes across middle age. METHODSData were from National Longitudinal Study of Youth 1979 (NLSY79, n=7540, alcohol reports from ages 18-26), Health and Retirement Study (HRS age 50-56 at enrollment, n=13,090), and a synthetic cohort matching early life exposure information from 3,259 NLSY79 participants to later life memory information from 5,451 HRS participants. Covariate-...