mSphere

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 ...

Wastewater monitoring enables non-invasive, population-scale tracking of community infections independent of healthcare-seeking behavior and clinical diagnosis. Metagenomic sequencing extends this capability by enabling broad, pathogen-agnostic detection, genomic characterization, and identification of novel or unexpected threats. Here, we present data from CASPER (the Coalition for Agnostic Sequencing of Pathogens from Environmental Reservoirs), a U.S.-based wastewater metagenomic sequencing ne...

Syphilis remains a major public health concern. However, current serologic assays are limited in their ability to distinguish active from previously treated disease. We applied tandem mass tag-based quantitative proteomics to plasma from 10 adults with active syphilis and 10 age- and gender-matched non-diseased controls. We identified 54 differentially regulated proteins (36 upregulated, 18 downregulated). Those proteins map to immune and inflammatory responses, acute-phase signaling, coagulatio...

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...

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...

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...

Vaccination frequently elicits suboptimal immunogenicity in organ transplant recipients, particularly those on long-term immunosuppressive therapy, highlighting the need for improved understanding of immunosuppression mechanisms and optimized vaccination strategies. This study enrolled a cohort of 132 individuals and observed significantly lower antibody levels in kidney transplant recipients (KTRs) compared to non-transplant controls (non-KTRs). Antibody levels were inversely associated with bo...

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.

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 ...

The rapid diagnosis of Campylobacter infections is important for the management of infectious gastroenteritis. Although stool culture is considered the gold standard, its sensitivity is limited and it requires prolonged incubation times. We performed a prospective multicenter study at nine healthcare facilities in Japan to evaluate a Campylobacter rapid antigen test using stool specimens between March 2024 and August 2025. Patients with suspected infectious gastroenteritis were consecutively enr...

From 2021 to 2025, MRSA emerged as a major multidrug-resistant pathogen in the study area. Among 545 S. aureus isolates, 67.2% were MRSA, disproportionately affecting children under five (26.5%) and males (55.5%). Case incidence more than doubled by 2025, suggesting rising transmission or resistance. Most isolates were hospital-associated (85.2%), predominantly from outpatients (88.5%), with middle ear discharge as the main source (67%). Gentamicin showed the highest susceptibility (72.1%), whil...

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...

Wastewater-based epidemiology (WBE) is an effective surveillance approach for monitoring viruses of public health relevance at the community level, complementing clinical surveillance systems. Molecular methods such as PCR/qPCR are widely used for targeted detection, while next-generation sequencing (NGS) with targeted enrichment panels has emerged as a complementary strategy for broader viral detection and genomic characterization. This study comparatively evaluated conventional PCR/qPCR and a ...

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...

BackgroundThe 2024 blood culture bottle shortage brought diagnostic resource allocation to the forefront, reflecting persistent, foundational challenges with low-value testing and empiric treatment approaches under clinical uncertainty. ObjectiveTo determine whether a machine learning approach using electronic medical record data can predict bacteremia more effectively than existing systems and practices to guide diagnostic testing and empiric treatment strategies. MethodsIn a retrospective co...

Background Short-chain fatty acids (SCFAs) are widely used as functional readouts of gut microbial activity in vivo. The growing adoption of decentralised study designs and self-collection protocols has amplified the need for reliable room-temperature storage and shipment strategies. However, SCFAs volatility and the persistence of post-collection microbial metabolism raise concerns regarding pre-analytical stability and the interpretability of measured concentrations. Methods We assessed the te...

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...

BackgroundRespiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in children, often leading to hospitalisation in infants. In low-resource settings where routine RSV diagnostics are unavailable, clinical overlap with bacterial pneumonia frequently results in unnecessary antibiotic use, contributing to antimicrobial resistance. ObjectiveTo evaluate the frequency and clinical determinants of antibiotic use among RSV-positive children under two years at a tertiary...

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...