The Lancet Microbe

ObjectivesDiagnosis of community-acquired Legionnaires disease (CALD) relies on microbiological testing. Routine testing in hospitalised CAP patients has low positivity rates. We externally validated a Legionella prediction score, assessed its applicability in routine care, and explored potential updates. MethodsWe analysed data from 196 CALD patients from 20 Swiss hospitals and 196 Legionella-negative CAP controls matched by date of diagnosis ({+/-}14 days; August 2022-March 2024). We assessed...

BackgroundSalmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, continues to pose a major public health challenge in many low- and middle-income countries (LMICs). The World Health Organization recommended typhoid conjugate vaccine (TCV) use in countries with a high burden of disease, and/or high rates of antimicrobial resistance (AMR). Recent introductions of TCVs into national immunisation programmes are expected to substantially reduce this burden. However, the i...

BackgroundNeutralising antibody titres are widely used as key immunogenicity endpoints in Ebola virus (EBOV) vaccine and monoclonal antibody clinical trials. However, direct comparison of results across studies remains challenging due to the use of heterogeneous neutralisation platforms, ranging from pseudotyped viruses to live EBOV assays. These limitations restrict assay standardisation, validation, scalability, and compliance with good clinical laboratory practice (GCLP), particularly in outb...

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...

BackgroundThe effectiveness of current drug-resistant tuberculosis (DR-TB) regimens is limited by the absence of rapid diagnostics that comprehensively predict resistance to included drugs. Next-generation sequencing (NGS), through culture-free targeted sequencing (tNGS) and culture-based whole-genome sequencing (cWGS) of the Mycobacterium tuberculosis complex (MTBC), offers a powerful framework for precision diagnosis, surveillance, and trial applications. We evaluated two novel assays enabling...

Klebsiella pneumoniae is a major causative agent of hospital-acquired infections worldwide, contributing substantially to morbidity, mortality, and healthcare burden.. The emergence of strains that combine resistance to last-resort antimicrobials with hypervirulence has become a pressing public-health challenge. Despite extensive characterization of the genetic determinants of multidrug resistance and hypervirulence, the relationship between the genetic repertoire of K. pneumoniae and the clinic...

BackgroundThe never-ending emergence of superbugs casts a shadow over the victorious age of antibiotics. In fact, the triumph of antibiotics was previously viewed in retrospection as our final victory over bacteria. Bacteria like Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli are now raising an alarming number of infections across hospitals and communities around the globe. The objective was to evaluate the implications for antimicrobial stewardship based on identifying the...

BackgroundClostridium perfringens can cause life-threatening extraintestinal infections in immunocompromised patients, an area in which we have little information regarding strain factors that impact patient risks and outcomes. MethodsWe conducted genomic-epidemiologic analyses on C. perfringens isolates from 70 patients seen at Brigham and Womens Hospital over 2021-2024. Genomic analyses evaluated strain profiles within a broader context of 2,321 C. perfringens genomes from foodborne, veterina...

Candida auris is a multidrug-resistant fungal pathogen that presents substantial challenges for healthcare facilities due to its high mortality rates among vulnerable populations. Six C. auris clades have been identified based on their susceptibility to antifungal treatment and environmental stressors. Identifying the circulating C. auris clade(s) is critical for understanding transmission and selecting a disease control strategy. To inform targeted implementation of community wastewater monitor...

Clostridioides difficile (C. diff) is a leading cause of hospital-acquired infections with severity ranging from mild diarrhea to fulminant colitis and death. Current antigen tests lack adequate sensitivity and DNA-based nucleic acid amplification tests (DNA-NAATs) exhibit limited specificity for active infection, leading to either underdiagnosis or inappropriate treatment of colonized individuals. Unlike DNA, mRNA is expressed only by metabolically active bacteria and is rapidly hydrolyzed, pro...

Measles outbreaks have surged globally in recent years, but current surveillance systems have limited capacity to monitor measles virus (MeV) transmission and evolution at population scale. Although MeV can be detected in wastewater, the public health potential of wastewater genomic surveillance for MeV remains largely unexplored. Here, we deploy sensitive, low-cost MeV wastewater genomic surveillance combining virus concentration, whole-genome amplicon sequencing, and bioinformatic analysis alo...

BackgroundMycobacterium tuberculosis (Mtb) genomic epidemiology often relies on culturing patient sputum, a time and labor-intensive process. Hybrid capture approaches have been successfully used to enrich Mtb DNA from complex clinical samples, yet the accuracy of variant identification from captured samples has not been systematically evaluated. MethodsWe created artificial strain mixtures of two well-characterized Mtb isolates such that the minor strain comprised 0-50% of Mtb DNA and serially...

ObjectiveThis study investigates the prevalence of human pegivirus (HPgV) in SARS-CoV-2-positive patients within the context of viral co-infections that may modulate COVID-19 outcomes and assesses whether HPgV co-infection is associated with COVID-19 severity. HPgV is a widely circulating but rarely monitored human virus with documented immunomodulatory effects in other viral infections, including HIV and Ebola. While HPgV prevalence is low in the general U.S. population (1-2%), it rises markedl...

Mycobacterium tuberculosis (MTB) disease is a major global health threat with most tuberculosis (TB) cases occurring in low-and middle-income countries (LMIC) with limited healthcare infrastructure. Near-point-of-care testing which can be deployed at peripheral clinical settings is needed to start treatment earlier and thereby improve treatment outcomes. Here we report the development and preliminary characterization of an MTB detection assay that utilizes tongue swab or sputum specimens for The...

BackgroundFailure of rapid diagnostic tests (RDTs) to detect Plasmodium parasites in peripheral blood of individuals is a major barrier to successful case management and control of malaria in Ethiopia. Characterizing factors contributing to RDT failure is essential if malaria control and elimination strategies are to succeed. MethodsWe consented and enrolled 148 individuals with suspected malaria presenting to health clinics in Mizan Aman, Ethiopia. We administered a clinical questionnaire, dia...

BackgroundsFollowing an increase in mpox clade Ib cases in several African countries, the World Health Organization recognized mpox as a public health emergency of international concern, highlighting the need for reliable and accessible diagnostic tools. As several mpox clades are co-circulating in endemic countries, the analytical sensitivity of diagnostic assays should be evaluated for all of them in a comparative manner. MethodsThis study evaluated the analytical sensitivity of three rapid t...

BackgroundHousehold contact investigation for tuberculosis (TB) is limited by referral for clinic-based testing services. We evaluated the performance of in-home tongue swab (TS) testing among symptom-agnostic household contacts (HHC) to inform HCI screening strategies. MethodsWe conducted a prospective cohort study among HHC of TB patients in Eastern Cape, South Africa. In-home testing of sputum and TSs, with TSs pooled from up to three HHCs, was performed using Xpert Ultra on portable GeneExp...

BackgroundSpatial emanators disrupt mosquito behaviour by inducing movement away from chemical stimuli and interfering with host detection and feeding. These tools were recently endorsed by the World Health Organization (WHO) for malaria control, based largely on clinical evidence from East Africa. Mosquito ShieldTM is a passive, transfluthrin-based emanator designed to provide month-long protection in enclosed or semi-enclosed spaces. This study evaluated its entomological efficacy under experi...

BACKGROUNDDiagnostic performance of tongue swab Mycobacterium tuberculosis PCR has been evaluated for facility-based triage of symptomatic tuberculosis (TB). It is unknown whether tongue swab performance differs for detection of asymptomatic TB in community-based screening. METHODSTongue swabs were collected from adult household contacts of TB patients (HHC Cohort), and symptomatic adults presenting to clinics with presumptive TB (Clinic Cohort), at eight South African sites. TB Cases were defi...

ObjectivesTo evaluate the efficacy and safety of sitafloxacin-containing regimens versus non-sitafloxacin therapy in patients with nontuberculous mycobacterial (NTM) pulmonary disease, focusing on sputum/BALF conversion rate, time of sputum/BALF culture conversion and radiographic improvement. MethodsThis retrospective cohort study analyzed 149 adults (76 control group vs. 73 sitafloxacin group) with NTM pulmonary disease treated between 2021 to 2024. Inclusion criteria: (1) Sitafloxacin group:...