BACKGROUND Indoor residual spraying (IRS) is a malaria control strategy implemented before the rainy season. Nchelenge District, Zambia is a holoendemic setting where IRS has been conducted since 2008 with little impact on malaria incidence or parasite prevalence. Pre-rainy season IRS may not reduce the post-rainy season peak abundance of the major vector, Anopheles funestus. METHODS A controlled,

Background Despite immune restoration after initiation of antiretroviral treatment (ART), the risk of tuberculosis (TB) persists in children living with HIV (CLHIV). We determined patterns of immune restoration of mycobacteria-specific T cells following ART in CLHIV. Methods CD4 and CD8 T cell activation and memory phenotype and functional profiles before and 6 months after ART were evaluated in peripheral

Background Significant disparities in Group B Streptococcus (GBS) colonisation and neonatal disease rates have been documented across different geographical regions. For example, Bangladesh reports notably lower rates compared to the United Kingdom (UK) and Malawi. This study investigates whether this epidemiological variability correlates with the immune response to GBS in these regions. Methods Qualitative

Candida albicans catheter-related candidemia is largely driven by microbial adhesion and biofilm formation on central venous catheters. Cells that disperse from these biofilms can enter the bloodstream, spread to distant organs, and sustain the cycle of infection. In this study, we investigated the virulence potential of C. albicans isolates obtained from the blood of catheterized patients experiencing

Background Multiple studies have shown a positive relationship between weather events and, 1 to 2 weeks later, Legionnaires’ disease (LD) cases. Narrowing this time window of association can help determine whether the mechanism linking rainfall and relative humidity to sporadic LD is direct or indirect. Due to the large number of daily water interactions and low incidence of LD, we propose a new Bayesian

Background Guideline-based therapy (GBT) for Mycobacterium abscessus (Mab) lung disease achieves sputum culture conversion rates (SCC) of 35%. This poor GBT efficacy is mirrored in the hollow fiber system model of Mab (HFS-Mab). While imipenem is part of GBT, biological effect with or without β-lactamase inhibitors, is unproven. Methods We performed imipenem/relebactam minimum inhibitory concentration

Background To date, HIV molecular epidemiology (HIV ME) has been primarily used to identify clusters of related infections (cluster detection and response [CDR]) and then address interventions to these clusters. Community groups have raised concern regarding CDR regarding privacy and ethical concerns. Here we demonstrate how an alternative approach to HIV ME can provide public health benefit. Methods

Anelloviruses are among the most prevalent viruses within the human virome, detected in over 90% of healthy individuals. Despite their ubiquity, the role of anelloviruses in human health remains elusive. This review examines the potential associations of anelloviruses torque teno virus (TTV), torque teno midi virus (TTMDV), and torque teno mini virus (TTMV) with various cancers, highlighting the mixed

Background Information concerning sex differences in pneumococcal vaccine effectiveness in adults is scarce. The main aim of this study is to compare the differences in clinical effectiveness of pneumococcal vaccination between male and female adults. Methods Population-based cohort study involving 1,108,634 women and 951,011 men aged ≥50years in Catalonia, Spain. Baseline characteristics of cohort

Background SARS-CoV-2 antibody levels have been proposed as a correlate of protection (CoP) from infection. Yet, large-scale prospective studies of cost-effective scalable antibody measures as predictors of infection under real-world conditions are limited. We examined whether antibody levels measured using high-throughput variant-specific SARS-CoV-2 anti-spike immunoglobulin G (IgG) and ACE2-neutralization

BACKGROUND Studies on chronic hepatitis B virus (HBV) infection have shown immune dysfunction involving multiple cell types, including T cells. B cells have been evaluated more recently, but in contrast to T cells, more pronounced activation of circulating B cells has been reported. To gain more insight into the activation status of B cells, we investigated gene profiles of B cells in the blood and

Surges in infections caused by respiratory pathogens have been documented in multiple settings after relaxation of pandemic restrictions. Antibodies to major antigens from respiratory syncytial virus and Group A Streptococcus waned significantly in a longitudinal adult cohort throughout the pandemic. This waning may have contributed to the pathogen-surges that followed.

Utilizing transiently transfected cell lines could significantly reduce manufacturing timelines for protein subunit vaccines. This trial compared safety and immunogenicity of human immunodeficiency virus (HIV) envelope CH505TF gp120 vaccines produced by upstream stable and transient transfection (each admixed with GLA-SE adjuvant, a TL4 agonist). Both vaccines were safe and well tolerated. Serum IgG

Background The high-dose (HD) Fluzone influenza vaccine is currently recommended for individuals 65 and older, since it was shown in past studies to improve antibody responses and vaccine efficacy (VE) compared to a standard-dose (SD) formulation. Since influenza vaccines are frequently reformulated, monitoring any potential changes in VE is crucial. Traditional efficacy trials can be costly and time-consuming

Background Despite the global public health threat posed by carbapenem-resistant Enterobacter spp., clinical and molecular epidemiological studies on international isolates remain scarce. Historically, the taxonomy of Enterobacter has been challenging, limiting our understanding of the clinical characteristics and outcomes of carbapenemase-producing Enterobacter spp. infections. Methods Hospitalized

BACKGROUND We investigated the association of metabolic risk factors (MRFs) and statin use with liver and nonliver outcomes in a nationwide cohort of patients with chronic hepatitis B (CHB) in the United States. METHODS We conducted a retrospective cohort study of adult patients with CHB using the MarketScan Databases (January 2007-December 2021). Incidence of liver and nonliver outcomes (cardiovascular

While the role of breastmilk antibodies to protect infants from CMV has been investigated, the role of T-cells, have received little attention. We compared the frequency of memory T-cell populations in breastmilk between mothers of infants who acquired breastmilk HCMV (transmitters) and those with uninfected infants (non-transmitters). Non-transmitter moms had an increased frequency of CD8+ effector

Background Piperaquine, used in combination with dihydroartemisinin, has been identified as a promising partner drug for uncomplicated treatment and chemoprevention of Plasmodium falciparum malaria in Africa. In light of the earlier spread of piperaquine resistance in Southeast Asia, mediated primarily by mutations in the drug efflux transporter PfCRT, we have explored whether PfCRT mutations would

Background Identifying risk factors for HIV rebound after treatment interruption is crucial for designing effective remission strategies. Methods Peripheral blood mononuclear cells from participants in the Zurich HIV Primary Infection Cohort (ZPHI, N=73) and ACTG study A5345 (N=44) were analyzed before ART interruption. We measured cell-associated HIV RNA, total HIV DNA, and proviral diversity (env

Background Malaria remains a major public health concern with substantial morbidity and mortality worldwide. In Malaysia, the emergence of Plasmodium knowlesi has led to a surge in zoonotic malaria cases and deaths in recent years. Signs of cerebral involvement have been observed in a noncomatose, fatal case of knowlesi infection, but the potential impact of this malaria species on the brain remains

BACKGROUND People with HIV (PWH) experience a higher burden of ageing-associated comorbidities, the underlying mechanisms of which remain to be fully elucidated. We aimed to identify profiles based on immune, inflammatory, and ageing biomarkers in blood from PWH and controls, and explore their association with total comorbidities over time. METHODS Latent profile analysis was used to construct biomarker

Background The declaration of mpox as a Public Health Emergency of International Concern highlights the need for interventions to interrupt virus transmission, including transmission via fabrics. Current World Health Organization guidance on clothes washing is based on a general consensus of virus inactivation; however, there is uncertainty about the efficacy of laundry detergents and disinfectants

Background The COVID-19 pandemic may have disproportionally impacted vulnerable groups such as people who inject drugs (PWID) through reduced healthcare services as well as social changes from pandemic mitigation measures. Understanding how the COVID-19 pandemic and associated mitigation strategies subsequently changed the trajectory of hepatitis C virus (HCV) and HIV transmission is critical to estimating

Background Male urethritis cases, caused by a novel clade of nongroupable Neisseria meningitidis (NmUC, “the clade”), have been reported globally. Methods To test whether genetic features unique to NmUC confer a colonization and survival advantage to NmUC during urethral infection, NmUC, gonococcal, and nonclade meningococcal strains were comparatively evaluated in primary, human male, urethral epithelial

Background Hepatitis C virus (HCV) infects nearly one-fourth of people with HIV (PWH). The role of direct-acting antivirals (DAAs) on immune activation in PWH and HCV is poorly understood. Methods We quantified plasma HCV RNA and CXCL10 in persons with HCV mono- versus HIV/HCV co-infection receiving Sofosbuvir-Velpatasvir. Single-cell laser capture was applied to liver biopsies obtained before and

Background Persons with HIV (PWH) on contemporary antiretroviral therapy (ART) are at elevated risk for developing age-related cardiometabolic diseases. We hypothesized that integrative analysis of cross-tissue, multimodal data from PWH could provide insight into molecular programming that defines cardiometabolic phenotypes in this high-risk group. Methods We enrolled 93 PWH without diabetes who were

Myasthenia gravis (MG) is a rare autoimmune disorder characterised by muscle weakness resulting from autoantibody-mediated disruption of the neuromuscular junction. Notably, it is also frequently associated with thymic pathology. This study explores the relationship between MG and DNA viruses in the thymus, employing targeted NGS and qPCR to analyse thymic tissue samples from both MG patients and healthy

Background With the transition from the coronavirus disease 2019 (COVID-19) pandemic into endemicity, changes in group immunity and the effect of updated XBB.1.5 monovalent vaccine (MonoV) need to be investigated. Methods A multicenter vaccine cohort was followed for 3 years, and the investigation period was classified into the pre-Omicron, Omicron, and endemic eras. Thirteen sampling points were assessed

Fluoroquinolone-resistance in Shigella is among the serious antimicrobial resistance (AMR) threats. We investigated the genomic epidemiology of fluoroquinolone resistant (FQR) strains of S. sonnei and S. flexneri from 2015 to 2022 in Spain and Portugal. We determined the AMR profiles of 416 isolates (S. flexneri and S. sonnei) and FQR isolates were subjected to whole-genome sequencing. The percentage

BACKGROUND Rotavirus vaccines are moderately protective against illness in high mortality settings compared with low mortality settings. Vaccine effectiveness (VE) evaluations may clarify our understanding of these disparities, but estimates among key subpopulations and against rare outcomes are not available in many analyses due to sample size. We combined 25 datasets from test-negative design case-control

Asymptomatic influenza virus infection occurs but may vary by factors such as age, vaccination status, or season. We examined the frequency of influenza virus infection and symptoms using data from two case-ascertained household transmission studies (2017—2023) with prospective, systematic collection of respiratory specimens and symptoms. From the 426 influenza virus infected household contacts that

Background Population-level viral load distribution, measured by cycle threshold (Ct), has been demonstrated to enable real-time estimation of Rt for SARS-CoV-2 ancestral strain. The generalizability of the framework under different circulating variants and pre-existing immunity remains unclear. Methods We obtained the first Ct record of local COVID-19 cases from July 2020 to January 2023 in Hong Kong

We studied cervicovaginal β-/γ-human papillomavirus (HPV) and their relationship to cervical precancer in women with HIV (WWH); having previously reported strong positive associations of β-/γ-HPV with incident head and neck cancer in the general population. Cases (N=124) had cervical intraepithelial neoplasia (CIN)-3 or CIN-2. Controls (N=247) were individually matched 2:1 to cases. Unexpectedly, multivariate

Background Clesrovimab is a human half-life extended mAb in phase 3 evaluation for the prevention of RSV disease in infants. ADA were observed at late time points in a phase 1b/2a study where clesrovimab was well tolerated with an extended half-life of ∼45 days. Methods Serum samples at days 150, 365 and 545 post-dose were assayed for ADA titers. Samples with high ADA titers were characterized for

Mycobacterium abscessus (MAB) is intrinsically resistant to many antibiotics, but the evolution of acquired drug resistance is poorly understood. We analyzed published genomes of 5,617 clinical MAB isolates from 20 countries and searched for signals of ongoing evolution in 35 drug-resistance-associated genes. Of these, we found 14 genes were subject to positive selection and identified novel mutational

This study investigated potential Ross River virus (RRV) exposure sites in Greater Brisbane during the Queensland COVID-19 lockdown (January-July 2020). Using RRV notifications, cluster identification techniques, and mobile phone data for movement network analysis, the study examined 993 RRV cases and 9 million movement trajectories from residential RRV cluster areas (hot-spots). The findings revealed

Background It remains unclear how high-risk Escherichia coli lineages, like sequence type (ST) 131, initially adapt to carbapenem exposure in their progression to carbapenem resistance. Methods Carbapenem mutation frequency was measured in multiple subclades of extended-spectrum β-lactamase (ESBL) positive ST131 clinical isolates using a fluctuation assay followed by whole genome sequencing (WGS) characterization

Background Clesrovimab is an investigational monoclonal antibody with an extended half-life targeting site IV of the respiratory syncytial virus (RSV) fusion protein for the prevention of RSV disease in infants. Methods In this phase 1b/2a, double-blind study,183 healthy preterm and full-term infants 2 weeks to 8 months of age were randomized 4:1 within 5 panels (preterm: 20, 50, 75 or 100-mg, full-term:

BACKGROUND Acquired immunity to Plasmodium falciparum malaria is mainly mediated by immunoglobulin G (IgG) targeting erythrocyte membrane protein 1 (PfEMP1). These adhesins mediate infected erythrocyte (IE) sequestration, protecting IEs from splenic destruction. PfEMP1-specific IgG is therefore thought to protect mainly by inhibiting IE sequestration. VAR2CSA-type PfEMP1 mediates placental IE sequestration

Background China faces the highest burden of latent multidrug-resistant or rifampicin-resistant tuberculosis (MDR/RR-TB). We aim to evaluate the health and economic impacts of Vaccae (a novel TB vaccine) and enhanced drug-resistant TB (DR-TB) management strategies. Methods Using a compartmental model calibrated with national TB data, we evaluated nine interventions from 2025-2050: enhanced DR-TB management

Background Japanese encephalitis (JE) has been predominantly controlled through vaccination. However, the isolation of JE virus (JEV) genotype V (GV) in China in 2009, and the subsequent alarming increase in JE cases in the Republic of Korea since 2010, present a new challenge. Methods Serum samples from individuals vaccinated with genotype III (GIII)-based JE vaccines were analyzed for neutralizing

The diversity of Mycobacterium tuberculosis (Mtb) impacts the outcome of tuberculosis. We previously showed that Mtb isolates obtained from patients with severe disease induced low inflammasome activation and IL-1β production by infected macrophages. Here we questioned whether this differential modulation of macrophages by Mtb isolates depended on distinct metabolic reprogramming. We found that the

BACKGROUND Diphtheria is a recurrent threat with endemic still occurs in many parts of the world. The standard of care is horse serum-derived diphtheria antitoxin (eDAT), which is in critical short supply globally. S315 is a fully human, monoclonal immunoglobulin G1 neutralizing antibody, specific to the receptor-binding domain of diphtheria toxin. S315 is intended to be a safer, more readily available

In Scandinavia, HPV vaccination programs started in 2007/8; in Sweden and Denmark with HPV vaccination offered to multiple cohorts of young girls, while in Norway offered to a single cohort only. Interestingly, in Sweden and Denmark, cervical cancer incidence in young women decreased markedly from 2017/2018, while in Norway a steady increase was seen until 2020. As the three countries are very similar

Background Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infections in children <2 years of age. Prior infection in a child is usually determined by RSV antibodies; however, in young children, persisting maternal immunoglobulin G antibodies can incorrectly indicate past RSV infection. We developed and evaluated 4 immunoglobulin A (IgA) antibody enzyme immunoassays

Chlamydia psittaci is a zoonotic pathogen known to cause respiratory diseases in humans. Chlamydia infections are closely associated with apoptosis, in which miRNAs play regulatory roles. Herein, we demonstrated that C. psittaci infection induces apoptosis in human bronchial epithelial (HBE) cells and investigated regulatory mechanism involving miR-124-3p and the PI3K/AKT signaling pathway. Following

Background The persistence of latently infected cells prevents a cure of HIV. The intestinal mucosa contains numerous target cells, and high levels of HIV-1 DNA persist in this compartment under ART. While CD4+ T cells are the best characterized reservoir of HIV-1, the role of long-lived intestinal macrophages in HIV-1 persistence on ART remains controversial. Methods We collected duodenal and colonic

Background Sepsis is characterized by a life-threatening syndrome caused by an unbalanced host response to infection. Fibroblast Growth Factor 8 (FGF8) has been newly identified to play important roles in inflammation and innate immunity, but its role in host response to sepsis is undefined. Methods A cecal ligation and puncture (CLP) -induced mouse sepsis model was established to evaluate the immunomodulatory

Tuberculosis (TB) necrotic granulomas contain triglyceride-rich macrophages (foam cells) with reduced antimicrobial functions. We assessed the ability of two compounds to reduce triglyceride content and Mycobacterium tuberculosis (Mtb) burden in infected human monocyte-derived macrophages and in the lungs of Mtb-infected C3HeB/FeJ mice: A-922500 (DGATi), an inhibitor of diacylglycerol acyltransferase

We developed a model to project the expected annual clinical and economic burden of medically attended lower respiratory tract illnesses due to respiratory syncytial virus (RSV-LRTI) among US infants aged <12 months by combining information on population size, disease rates, mortality rates, and unit costs. Among the 3.7 million US infants aged <12 months each year, a total of 592,700 cases of RSV-LRTI

Background Approaches for determining whether influenza vaccination prevents infection, attenuates illness, or both, are important for developing improved vaccines. We estimated influenza infection incidence, and evaluated symptom ascertainment methodologies in children to inform future vaccine trial design. Methods We conducted a prospective cohort study among children aged 6-23 months from May-October

Protein subunit vaccines form a key pipeline for developing novel tuberculosis (TB) vaccines. Mycobacterium tuberculosis (Mtb) contains approximately 4000 individual proteins. However, only approximately 100 have been evaluated as antigens in the clinical and preclinical stages of vaccine development. Trained immunity-targeting vaccines induce innate immune memory against heterologous infections and