Background Virologic endpoints are used in Phase 2 trials for COVID-19 therapeutics, but they have not been established as surrogates for clinical endpoints. No meta-analysis using individual participant data (IPD) has been undertaken to identify viral load outcomes for which treatment effects are best associated with effects on hospitalization/death. Methods This meta-analysis combined IPD from 23

Background Solid organ transplant recipients (SOTRs) suffer increased morbidity and mortality due, in part, to chronic immunosuppression. The determination of an individual's immune competence is currently difficult but would improve risk assessment and inform medical decisions. We reasoned that correlating qualitative and quantitative measures of the B-cell compartment with serologic responses to

Background Invasive mold infections (IMI) can lead to severe morbidity and mortality, but routine public health surveillance is lacking. Although extensive evaluation is needed for clinical diagnosis, case classification prediction models may inform surveillance efforts, which are essential to better characterize epidemiologic trends and assess the value of a more inclusive IMI case definition. Methods

Some common COVID-19 vaccines elicit antibody responses that most serological tests are unable to differentiate from an infection response. This presents a challenge for COVID-19 surveillance and epidemiology. In this perspective, we examine the potential scale of this problem.

Background The main protease (Mpro) is one of the most attractive targets for antiviral drug discovery against SARS-CoV-2. Mutations in Mpro have been linked to resistance against nirmatrelvir-ritonavir (NIR-RIT), an important therapy for SARS-CoV-2 infection. This study aimed to identify low-frequency antiviral resistance mutations in Mpro from NIR-RIT-treated patients and to analyze the enzymatic

Background As individuals progress through adolescence, their risk of tuberculosis (TB) increases and the type of disease that develops changes, with increasing cavitary formation and parenchymal tissue destruction. While it is widely assumed that the changes in risk and disease phenotype are due to puberty exerting an impact on host immune responses to Mycobacterium tuberculosis, this relationship

The Panton-Valentine leukocidin (PVL) of Staphylococcus aureus can be associated with severe and recurrent skin and soft tissue infections (SSTI). The prevalence of PVL is particularly high in Sub-Saharan Africa. We assessed in a multi-center cross-sectional study whether host-related factors could explain this high PVL prevalence. We find higher serum anti-PVL-IgG levels in participants from Africa

Background Staphylococcus aureus infections are frequently complicated by metastatic foci, recurrence, and death. Antimicrobial resistance and intracellular bacterial persistence limit the effectiveness of conventional antimicrobials. Host-directed therapies could improve outcomes, but the interpretive complexity of pathogen-host interactions impedes identification of critical responses suitable for

Introduction Fatal acute febrile illness (fAFI) is a known predecessor of many infant mortality events in low-resource settings, yet early risk markers for this condition remain poorly understood. Nasopharyngeal (NP) microbiome patterns may influence the severity of these infections. Methods We analyzed longitudinal changes in the NP microbiota of Zambian infants with fAFI onset compared to healthy

Background Men who have sex with men are at high risk of HIV acquisition through unprotected receptive anal intercourse (RAI). Behaviorally-congruent HIV PrEP has long been advocated by individuals who find adherence challenging or prefer minimizing systemic drug concentrations. We developed an event-driven, behaviorally-congruent rectal tenofovir (TFV) douche as a PrEP option for RAI and demonstrated

Enterococcus faecalis is an opportunistic pathogen that causes infective endocarditis. Despite in vitro synergy of the recommended combination ampicillin and ceftriaxone (AC), E. faecalis infective endocarditis (EFIE) mortality remains high. We characterized 119 isolates from EFIE patients in our health system from 2018 to 2023 genomically and phenotypically. Three genetic lineages (ST6, ST40, and

Background Differences in absolute neutrophil count (ANC) between African and non-African populations have been reported. Neutropenia has also been reported during rifamycin use. ANC values in current tables that assign severity grades to clinical or laboratory events (The National Cancer Institute Common Terminology Criteria for Adverse Events [CTCAE] and the National Institute of Allergy and Infectious

Background RTS,S/AS01 vaccine efficacy (VE) was previously shown as lower in African adults than in malaria-naïve US adults, potentially due to concurrent Plasmodium falciparum (Pf) infections. We investigated whether treatment of infection prior to vaccination would lead to improved VE and immunogenicity. Methods A Phase 2b study in Kenyan adults evaluated the efficacy of RTS,S/AS01E in conjunction

Background The rapid evolution of SARS-CoV-2 and population-level vaccine administration significantly shift the population immunity. In Hong Kong, these shifts, coupled with the emergence of Omicron BA.5 with a strong ability of immune evasion, necessitate a deeper understanding of how population immunity and public health and social measures have shaped the epidemic dynamics across age groups within

Transplantation of kidneys from donors with HIV to recipients with HIV (HIV D+/R+) has been shown to be safe and effective, but there is a unique risk of donor-derived HIV-superinfection (HIV-SI) in these recipients. Recipients from a multicenter observational HIV D+/R+ study were examined for HIV-SI using site-directed next-generation sequencing (Illumina). Eighteen HIV D+/R+ kidney transplant recipients

Background The 2022 dengue outbreak in Karachi, Pakistan, posed a severe threat to the region, yet no study has investigated the origins of the causal strain. Methods This study aimed to trace the origins and transmission route of the dengue virus serotype 1 (DENV-1) strain responsible for the 2022 epidemic through genome sequencing and phylogenetic analyses. We successfully sequenced 135 complete

Background Human infection with Trypanosoma cruzi leads to Chagas disease that induces profound changes in the immune response across different cell subsets, influencing parasite control and disease pathology. Dissecting the functional characteristics of distinct immune cells in patients with the asymptomatic (indeterminate – IND) or with the cardiac (CCC) clinical forms is crucial for unveiling mechanisms

Mendelian randomisation (MR) is an increasingly common study design in infectious diseases (ID). It holds promise for identifying causes and consequences of infections where conventional epidemiology has struggled, and can highlight plausible drug targets, as predating successful COVID-19 trials (baricitinib, tocilizumab). However, many current applications provide limited insight due to violations

Background The first clinical trial on eumycetoma was recently conducted in Sudan, comparing oral fosravuconazole, prodrug of active ravuconazole, with the standard-of-care oral itraconazole. Building on this trial, the present study aimed to characterize the pharmacokinetics-pharmacodynamics (PK-PD) of ravuconazole, itraconazole and hydroxyitraconazole in patients with eumycetoma and guide selection

Background The precise mechanisms of respiratory infection caused by oral anaerobic bacteria remain elusive. Unexpectedly, bacterial microbiota analysis using 16S rRNA revealed “hidden” mixed infections of anaerobic bacteria and commensal oral Streptococcus species in patients with community-acquired pneumonia (CAP). The study aimed to elucidate the mechanisms by which Prevotella intermedia exacerbates

Molecular epidemiological surveillance for zoonotic strongyloidiasis is confounded by a genus-specific TaqMan probe assay that conflates Strongyloides fuelleborni fuelleborni with Strongyloides stercoralis. To improve surveillance, we developed and validated a novel duplex species-specific TaqMan probe assay, screening a representative collection of available clinical samples. Our assay was highly

Background The geographic range of flaviviruses is expanding, as evidenced by the increase in dengue virus (DENV) cases and the recent emergence of Zika virus (ZIKV) in the Americas. Studying seroprevalence of flaviviruses in (hyper)endemic regions is challenging due to extensive antibody cross-reactivity. Over the past decade, Aruba and Curaçao have experienced DENV and ZIKV outbreaks, of which the

The ability of herpes simplex virus (HSV) to establish lifelong latency in sensory neurons makes it one of the most pervasive viruses worldwide. Although most HSV infections are asymptomatic or cause limited cutaneous symptoms, some give rise to serious central nervous system (CNS) manifestations. Both primary HSV infection and subsequent reactivation events can cause viral replication and spread within

Background Central nervous system (CNS) infections pose a significant public health challenge in resource-limited settings. Traditional culture-based and targeted molecular diagnostic methods have limitations in sensitivity and speed. This study retrospectively analysed the data and CSF samples from our previous study to assess the diagnostic efficacy of untargeted 16S ONT sequencing compared to conventional

Community-wide screening for bacteriologically confirmed pulmonary tuberculosis may reduce tuberculosis burden, although concerns of overtreatment remain because of false positive diagnoses due to subpar specificity of current bacteriological tests for screening. Our review and data analysis shows that clinic-based test specificity estimates of Xpert against culture underestimate performance in communities

Background The coronavirus disease 2019 (COVID-19) pandemic has had a profound global impact. Therapeutic strategies to bridge the crucial ‘lockdown’ timespan between the emergence of a new virus and vaccine rollout are needed. Methods We recently demonstrated that intranasal (i.n.) administration of COVID-19 convalescent plasma (CCP) in sentinel hamsters can limit severe acute respiratory syndrome

Background and Aim Lipid metabolism is altered in human immunodeficiency virus (HIV) infection and chronic liver diseases, but common and unique pathways have not been elucidated, limiting prevention and treatment strategies. The aim of this study was to discover lipid metabolite signatures for persons with HIV (PWH), PWH with HCV coinfection (PWH-HCV), and individuals with metabolic dysfunction-associated

Background Escherichia coli has an extensive accessory genome, though its role in impacting patient mortality is unknown. Methods We performed whole genome sequencing with E. coli bloodstream infection isolates from inpatients at Duke University. Pan-genome analysis was used to identify flexible genomic islands associated with in-hospital attributable mortality (death due to infection). The functions

Background Arboviruses—short for "arthropod-borne viruses"—are transmitted to humans and animals by infected arthropods. Aedes mosquito-borne arboviral diseases such as dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) impose major public health burdens in Southeast Asia. The potential role of sylvatic reservoirs, such as macaques, in maintaining arboviral transmission remains unclear. Methods We

Human Cytomegalovirus (HCMV) is a common herpesvirus that typically causes asymptomatic infection but can lead to severe complications in transplant patients due to reactivation. The Human Leukocyte Antigen (HLA) plays a crucial role in antigen presentation and T cell activation, essential for an effective immune response. Understanding HLA-pathogen interactions can help predict susceptibility or resistance

Background Immunological memory to vaccination and viral infection involves the coordinated action of B and T cells; thus, integrated analysis of these 2 components is critical for understanding their respective contributions to protection against breakthrough infections (BIs) after vaccination. Methods We investigated cellular and humoral immune responses to severe acute respiratory syndrome coronavirus

The burden of hepatitis C virus (HCV) among persons who inject drugs is determined by dynamics of infection, spontaneous clearance, treatment clearance, treatment failure, and reinfection. Although analysis of HCV sequences is often used to infer the net contribution of these factors, those inferences are complicated by the quasispecies distribution and continued evolution of infection within each

Background Vulvovaginal candidiasis (VVC), mainly caused by Candida albicans, affects approximately 75% of women at least once during their lifetime. VVC is characterized by fungal colonization, which leads to inappropriate local hyperinflammation and symptoms. Although the trigger of C. albicans pathogenicity is often unknown, antibiotic use and vaginal dysbiosis are associated with increased susceptibility

BACKGROUND Little is known on the vertical transmission of human papillomavirus (HPV) and on the dynamics of HPV among children. Our objective was to determine the risk of HPV recurrence, persistence, and incidence over 2 years of age among children born to HPV-positive mothers. METHODS We conducted the HERITAGE study among pregnant women recruited between 2010 and 2016 in Canada. HPV DNA testing was

Background Placental malaria is characterized by the accumulation of Plasmodium falciparum-infected erythrocytes and maternal inflammation in the intervillous spaces of the placenta. These features are associated with placental damage and fetal compromise. However, understanding of the mechanisms that lead to poor pregnancy outcome and interventions targeting excessive host responses to placental malaria

Antifungal susceptibility testing among 1,740 Candida parapsilosis blood isolates submitted to a U.S. reference laboratory (2015–2024) revealed a significant increase in fluconazole resistance from 8.2% to 20.3% (odds ratio [OR] per year: 1.13; 95% confidence interval [CI]: 1.06–1.20; p<0.001), with notable acceleration since 2021. Voriconazole resistance remained stable over this period. Micafungin

A daycare teacher presented with complaints of headache, neck stiffness, and fever. Because of initial concerns about meningococcal meningitis, families of daycare attendees were notified and 10 children from the daycare presented for evaluation. CSF from the teacher and nasal swabs from four febrile children were RT-PCR positive for enterovirus. A novel recombinant enterovirus was cultured from the

Background Mandatory public health reporting of influenza laboratory results and vaccine doses administered in the state of California can provide estimates of seasonal influenza vaccine effectiveness (VE). Methods We analyzed linked influenza immunization registry and laboratory reporting data among California residents aged ≥6 months tested for influenza during the 2023–24 influenza season (October

Background Measles-Mumps-Rubella (MMR) is an effective live-virus vaccine against measles but is poorly immunogenic in infants and contraindicated for pregnant and immunocompromised persons. Methods We evaluated immunogenicity and protective efficacy of a novel recombinant dimeric MeV hemagglutinin protein vaccine (rMeV) in rhesus macaques. Macaques (n=4) in four experimental groups were injected at

Introduction Gastrointestinal dysfunction, including microbiome changes and increased bacterial translocation across a compromised gastrointestinal barrier plays a role in the chronic systemic inflammation experienced by people with HIV (PWH). It is unknown whether autonomic neuropathy (AN) may contribute to these mechanisms by altering gastrointestinal motility. Methods This is a cross-sectional study

Japan recently experienced a record surge in streptococcal toxic shock syndrome (STSS). Our environmental surveillance study reveals that Streptococcus pyogenes persists seasonally, peaking in autumn and winter in rural Japan. The dominant emm1 M1UK sublineage and csrS mutations heighten virulence, highlighting the urgent need for targeted surveillance and interventions.

The ongoing spread of antimicrobial resistance has generated an urgent need for new antibiotics, especially against multidrug-resistant (MDR) gram-negative pathogens. Taniborbactam (previously VNRX-5133) is a novel bicyclic boronate β-lactamase inhibitor with potent, selective, and direct inhibitory activity against Ambler class A, B, C, and D enzymes, including serine and metallo-β-lactamases. Taniborbactam

Background Widespread immunity through vaccination or natural infection has altered the predictive ability of wastewater for hospitalization and mortality. Methods Between January 2022 and August 2024, we conducted a longitudinal observational study aimed to examine the correlation between symptomatic COVID-19 in healthcare employees and the SARS-CoV-2 wastewater community levels. Wastewater was analyzed

Vaccines have encountered evolving beliefs due to factors that include historical events, political movements, and unique community values. To combat vaccine hesitancy, dialogue addressing politicization, employing trusted messengers, and acknowledging individuals’ experiences are necessary to build trust.

BACKGROUND High-resolution metabolomics has shown promise for identifying blood-based biomarkers of tuberculosis (TB). We sought to discover a metabolic signature to detect pulmonary TB disease and monitor treatment response. METHODS Plasma from Ethiopian persons with pulmonary TB at diagnosis (n=82) was compared to household contacts with TB symptoms (n=104) and 2, 6, and 12 months after treatment

BACKGROUND Traditional treatment of methicillin-susceptible Staphylococcus aureus (MSSA) native valve endocarditis is based on cloxacillin/cefazolin monotherapy. Antibiotics with high activity against MSSA such as ceftaroline and daptomycin have been marketed last years, but there are no clinical trials evaluating them as monotherapy or combination therapy in patients with MSSA endocarditis. OBJECTIVES

Background Dengue virus (DENV) serotype -2 and -3 infections are associated with more severe disease outcomes than -1 and -4, though a biological explanation for this has not been identified. Methods DENV serotype effects on human T cell activation were assessed by measuring T cell receptor (TCR)-mediated IL-2 release following TCR stimulation. DENV envelope (env) proteins were expressed in Jurkat

Background Islatravir, a nucleoside reverse transcriptase translocation inhibitor, exhibits high potency against HIV-1, with a long intracellular half-life. The safety, tolerability, and pharmacokinetics of once-monthly oral islatravir were evaluated in adults at low risk of acquiring HIV-1. Methods In this double-blind placebo-controlled trial, participants were randomized 2:2:1 to receive 6 once-monthly

Background Cell-associated HIV has been found in tissues whose architecture can limit antiretroviral drug penetration, including the genital tract. Methods In healthy and SHIV-infected rhesus macaques dosed for 10 days with four-drug combination therapy, we evaluated the spatial distribution of six antiretroviral drugs (ARVs) within the male and female genital tract by mass spectrometry imaging (MSI)

Clostridioides difficile poses a significant public health challenge as it is the leading cause of antibiotic-associated diarrhea and is associated with significant morbidity and mortality. C. difficile’s metabolism and pathogenesis are strongly influenced by nutrient availability from the host and gut commensals. This has caused increasing interest in dietary intake and diet-derived metabolites’ role