Virus Evolution

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.

The emergence of vaccine covered serotypes causing invasive pneumococcal disease (IPD) is a serious concern worldwide. We investigated the unexpected rise of serotype 4 causing IPD primarily in non-vaccinated young adults after the COVID-19 pandemic that further spread to adults [≥] 65 years in recent years. For this purpose, we conducted a retrospective study of serotype 4 IPD cases (n=827) reported in Spain between 2009 and 2024. Whole-genome sequencing was performed to assess clonal lineag...

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...

BackgroundElimination of Plasmodium vivax is challenging due to its dormant liver stages (hypnozoites), which can reactivate weeks or months after the primary infection, causing relapses and ongoing transmission of the parasite. Despite these challenges, P. vivax clinical case numbers have declined over the past decade in Cambodia. We used parasite genotyping to assess whether the decline in case numbers was reflected in parasite diversity and relatedness as a proxy to transmission. MethodsGeno...

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...

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...

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...

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 ...

BackgroundCambodia has made great progress in reducing malaria transmission and is targeting elimination. While this progress is particularly marked for Plasmodium falciparum, the situation is different for Plasmodium vivax. It is generally assumed that symptomatic patients are effectively diagnosed using rapid diagnostic tests (RDTs), regardless of transmission intensity. MethodsIn 2023 we conducted a cross-sectional survey among 986 treatment-seeking patients in 6 provinces of Cambodia with v...

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...

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 ...

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...

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...

Serological surveillance is fundamental to infectious disease research and informed public-health decision making. Immunoassays used in the study of pathogen-specific immunity have historically relied on the collection of venous blood. While critical for many public-health applications, this sample collection method is invasive and resource intensive. The costs and logistical barriers associated with venous blood collection are exacerbated in resource-limited regions, and the shift to less invas...

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 ...

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 ...

BackgroundNo randomized clinical trial comparing the most established new modalities of treatment for patients with localized prostate cancer has been published, and there is scarce comparative effectiveness research assessing Patient-Reported Outcome Measures (PROMs). Objectiveto compare the impact of active surveillance, robot-assisted radical prostatectomy (RARP), Intensity-modulated radiotherapy (IMRT), and real-time brachytherapy on patients, through PROMs, from pre-treatment to five years...

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...

BackgroundCandidemia is a rare but life-threatening bloodstream infection that remains difficult to predict using conventional risk stratification approaches, highlighting the need for improved predictive strategies. As a result, empiric antifungal therapy is often delayed even in high-risk patients. MethodsWe developed a deep learning model (PyTorch_EHR) to predict 7-day candidemia risk by using electronic health record data from two large cohorts (Houston Methodist Hospital System [HMHS] and ...