One hundred thirty-four germ line PU.1 variants and the agammaglobulinemic patients carrying them.

Leukopoiesis is lethally arrested in mice lacking the master transcriptional regulator PU.1. Depending on the animal model, subtotal PU.

Cost-effectiveness of leveraging existing HIV primary health systems and community health workers for hypertension screening and treatment in Africa: An individual-based modeling study.

Background: Cardiovascular disease (CVD) morbidity and mortality is increasing in Africa, largely due to undiagnosed and untreated hypertension. Approaches that leverage existing primary health systems could improve hypertension treatment and reduce CVD, but cost-effectiveness is unknown. We evaluated the cost-effectiveness of population-level hypertension screening and implementation of chronic care clinics across eastern, southern, central, and western Africa.

Community and familial dynamics influencing risk behavior for HIV acquisition among adolescent girls and young women in Uganda: Qualitative analysis using Protective Motivation Theory.

Background: In Uganda, adolescent girls', and young women's (AGYW-15-24 years) current HIV prevalence is fourfold compared with their male counterparts due to compounded social, economic, and environmental factors. Using the Protective Motivation Theory (PMT), we explored HIV-acquisition risk sources and perceived protective factors from AGYW and caregivers' perspective.

Materials And Methods: During 2018, we conducted a qualitative study guided by PMT to explore factors influencing HIV acquisition among AGYW.

Synthesis and preclinical evaluation of tigilanol tiglate analogs as latency-reversing agents for the eradication of HIV.

Tigilanol tiglate (EBC-46) is a selective modulator of protein kinase C (PKC) isoforms that is Food and Drug Administration (FDA) approved for the treatment of mast cell tumors in canines with up to an 88% cure rate. Recently, it has been FDA approved for the treatment of soft tissue sarcomas in humans. The role of EBC-46 and, especially, its analogs in efforts to eradicate HIV, treat neurological and cardiovascular disorders, or enhance antigen density in antigen-targeted chimeric antigen receptor-T cell and chimeric antigen receptor-natural killer cell immunotherapies has not been reported.

Acceptability, feasibility and appropriateness of intensified health education, SMS/phone tracing and transport reimbursement for uptake of voluntary medical male circumcision in a sexually transmitted infections clinic in Malawi: A mixed methods study.

Introduction: Uptake of voluntary medical male circumcision (VMMC) remains a challenge in many settings. Innovative implementation strategies are required to scale-up VMMC uptake.

Methodology: RITe was a multi-faceted intervention comprising transport reimbursement (R), intensified health education (IHE) and SMS/Telephone tracing (Te), which increased the uptake of VMMC among uncircumcised men with sexually transmitted infections (STIs) in Malawi.

Evidence of human exposure and associated risk factors to Rift Valley fever in selected districts of Central and Western Zambia.

Rift Valley fever (RVF) is an important viral zoonotic disease that not only affects ruminants but causes serious morbidity and mortality in humans. In humans, its symptoms range from mild flu-like signs to a severe form such as retinal damage, meningoencephalitis to haemorrhagic fever. In this study, 202 human serum samples were collected from central and western parts of Zambia and tested for RVF-specific antibodies using a commercially available ELISA kit.

Detection and analysis of Serpin and RP26 specific antibodies for monitoring Schistosoma haematobium transmission.

Background: Schistosoma haematobium is the causative pathogen for urogenital schistosomiasis. To achieve progress towards schistosomiasis elimination, there is a critical need for developing highly sensitive and specific tools to monitor transmission in near-elimination settings. Although antibody detection is a promising approach, it is usually unable to discriminate active infections from past ones.

Low agreement and frequent invalid controls in two SARS-CoV-2 T-cell assays in people with compromised immune function.

T-cell response plays an important role in SARS-CoV-2 immunogenicity. For people living with HIV (PWH) and solid organ transplant (SOT) recipients there is limited evidence on the reliability of commercially available T-cell tests. We assessed 173 blood samples from 81 participants (62 samples from 35 PWH; 111 samples from 46 SOT recipients [lung and kidney]) with two commercial SARS-CoV-2 Interferon-γ (IFN-γ) release assays (IGRA; SARS-CoV-2 IGRA by Euroimmun, and IGRA SARS-CoV-2 by Roche).

Phase 2 Randomised Study of Bulevirtide as Monotherapy or Combined With Peg-IFNα-2a as Treatment for Chronic Hepatitis Delta.

Background And Aim: Bulevirtide (BLV) leads to beneficial virologic and biochemical responses when given alone to treat hepatitis delta virus (HDV) infection, which causes the most severe form of chronic viral hepatitis. We evaluated 48 weeks of BLV monotherapy, BLV + tenofovir disoproxil fumarate (TDF) and BLV + pegylated interferon alfa-2a (Peg-IFNα-2a), with 24-week follow-up.

Methods: Ninety patients were enrolled into six arms of 15 each (A-F); 60 patients were included in the main randomisation (arms A-D), and 30 patients (arms E-F) were randomised to the extension phase: (A) Peg-IFNα-2a 180 μg once weekly (QW); (B) BLV 2 mg once daily (QD) + Peg-IFNα-2a 180 μg QW; (C) BLV 5 mg QD + Peg-IFNα-2a 180 μg QW; (D) BLV 2 mg QD; (E) BLV 10 mg QD + Peg-IFNα-2a 180 μg QW and (F) BLV 10 mg (5 mg twice daily) + TDF QD.

ATM Expression and Activation in Ataxia Telangiectasia Patients with and without Class Switch Recombination Defects.

Background: Ataxia telangiectasia mutated (ATM) kinase plays a critical role in DNA double-strand break (DSB) repair. Ataxia telangiectasia (A-T) patients exhibit abnormalities in immunoglobulin isotype expression and class switch recombination (CSR). This study investigates the role of residual ATM kinase expression and activity in the severity of A-T disease.

Chlamydia muridarum Causes Persistent Subclinical Infection and Elicits Innate and Adaptive Immune Responses in C57BL/6J, BALB/cJ, and J:ARC(S) Mice Following Exposure to Shedding Mice.

Chlamydia muridarum (Cm) has reemerged as a moderately prevalent infectious agent in research mouse colonies. Despite its experimental use, few studies evaluate Cm's effects on immunocompetent mice following its natural route of infection. A Cm field isolate was administered (orogastric gavage) to 8-wk-old female BALB/cJ (C) mice.

An Enigmatic Wild Passerine Mortality Event in the Eastern United States.

The ability to rapidly respond to wildlife health events is essential. However, such events are often unpredictable, especially with anthropogenic disturbances and climate-related environmental changes driving unforeseen threats. Many events also are short-lived and go undocumented, making it difficult to draw on lessons learned from past investigations.

Adenoviral Vector-Based Vaccine Expressing Hemagglutinin Stem Region with Autophagy-Inducing Peptide Confers Cross-Protection Against Group 1 and 2 Influenza A Viruses.

An effective universal influenza vaccine is urgently needed to overcome the limitations of current seasonal influenza vaccines, which are ineffective against mismatched strains and unable to protect against pandemic influenza. In this study, bovine and human adenoviral vector-based vaccine platforms were utilized to express various combinations of antigens. These included the H5N1 hemagglutinin (HA) stem region or HA2, the extracellular domain of matrix protein 2 of influenza A virus, HA signal peptide (SP), trimerization domain, excretory peptide, and the autophagy-inducing peptide C5 (AIP-C5).

The Long-Term Immunity of a Microneedle Array Patch of a SARS-CoV-2 S1 Protein Subunit Vaccine Irradiated by Gamma Rays in Mice.

Background/objectives: COVID-19 vaccines effectively prevent severe disease, but unequal distribution, especially in low- and middle-income countries, has led to vaccine-resistant strains. This highlights the urgent need for alternative vaccine platforms that are safe, thermostable, and easy to distribute. This study evaluates the immunogenicity, stability, and scalability of a dissolved microneedle array patch (MAP) delivering the rS1RS09 subunit vaccine, comprising the SARS-CoV-2 S1 monomer and RS09, a TLR-4 agonist peptide.

Strategic and Technical Considerations in Manufacturing Viral Vector Vaccines for the Biomedical Advanced Research and Development Authority Threats.

Over the past few decades, the world has seen a considerable uptick in the number of new and emerging infectious disease outbreaks. The development of new vaccines, vaccine technologies, and platforms are critical to enhance our preparedness for biological threats and prevent future pandemics. Viral vectors can be an important tool in the repertoire of technologies available to develop effective vaccines against new and emerging infectious diseases.

Development of a Recombinant Fusion Vaccine Candidate Against Lethal Neurotoxin Types A and B.

Background: Botulinum neurotoxins (BoNTs), produced by , are potent protein toxins that can cause botulism, which leads to death or neuroparalysis in humans by targeting the nervous system. BoNTs comprise three functional domains: a light-chain enzymatic domain (LC), a heavy-chain translocation domain (HC), and a heavy-chain receptor-binding domain (HC). The HC domain is critical for binding to neuronal cell membrane receptors and facilitating BoNT internalization via endocytosis.

Immunobridging Trials: An Important Tool to Protect Vulnerable and Immunocompromised Patients Against Evolving Pathogens.

Safeguarding patients from emerging infectious diseases demands strategies that prioritise patient well-being and protection. Immunobridging is an established trial methodology which has been increasingly employed to ensure patient protection and provide clinicians with swift access to vaccines. It uses immunological markers to infer the effectiveness of a new drug through a surrogate measure of efficacy.

Acute Febrile Illness Accompanied by 7th and 12th Cranial Nerve Palsy Due to Lyme Disease Following Travel to Rural Ecuador: A Case Report and Mini-Review.

The causative agent of Lyme disease, , is endemic to Canada, the northeastern United States, northern California, and temperate European regions. It is rarely associated with a travel-related exposure. In this report, we describe a resident of southern Ontario, Canada who developed rash, fever, and cranial nerve VII and XII palsies following a 12 day trip to Ecuador and the Galapagos islands approximately four weeks prior to referral to our center.

Serious Bacterial Infections and Hepatitis C Virus Among People Who Inject Drugs: A Syndemic or Intertwined Epidemics?

Limited research has examined the possible synergistic interrelationships between serious bacterial infections (SBIs) of the heart (i.e., endocarditis), bone, spine, brain, or joints (e.

New Diagnostics for Fungal Infections in Transplant Infectious Disease: A Systematic Review.

Fungal infections are common in highly immunosuppressed, solid organ transplant recipients. They can be quite difficult to diagnose in a timely manner; thus, we present a review of current studies focusing on broad categories of molecular diagnostics, i.e.

Implementation of a Hepatitis B Screening Program in Patients Receiving Systemic Anti-Cancer Therapy.

Cancer patients receiving non-endocrine therapies are at risk of hepatitis B virus (HBV) reactivation (HBVr). Guidelines recommend HBV screening prior to treatment. The Ottawa Hospital Cancer Center implemented a screening pilot for all patients receiving FOLFOX-based regimens between January and April 2023.

Public Health Travel Restrictions Implemented for Persons at Risk of Transmitting SARS-CoV-2 Infection-United States, January 1, 2020-April 6, 2022.

Context: Federal public health travel restrictions (FPHTR) in the United States are implemented for persons who meet specific criteria to prevent spread of communicable diseases of public health concern. FPHTR can mitigate the risk of disease transmission during air travel and mitigating disease translocation between geographic areas.

Objective: To characterize and determine the extent of FPHTR implementation during the COVID-19 pandemic.

Inflammation-Induced Th17 Cells Synergize with the Inflammation-Trained Microbiota to Mediate Host Resiliency Against Intestinal Injury.

Background And Aims: Inflammation can generate pathogenic Th17 cells and cause an inflammatory dysbiosis. In the context of inflammatory bowel disease (IBD), these inflammatory Th17 cells and dysbiotic microbiota may perpetuate injury to intestinal epithelial cells. However, many models of IBD like T-cell transfer colitis and IL-10-/- mice rely on the absence of regulatory pathways, so it is difficult to tell if inflammation can also induce protective Th17 cells.

Coronavirus Disease 2019 (COVID-19) Real World Data Infrastructure: A Big-Data Resource for Study of the Impact of COVID-19 in Patient Populations With Immunocompromising Conditions.

Background: We developed a United States-based real-world data resource to better understand the continued impact of the coronavirus disease 2019 (COVID-19) pandemic on immunocompromised patients, who are typically underrepresented in prospective studies and clinical trials.

Methods: The COVID-19 Real World Data infrastructure (CRWDi) was created by linking and harmonizing de-identified HealthVerity medical and pharmacy claims data from 1 December 2018 to 31 December 2023, with severe acute respiratory syndrome coronavirus 2 virologic and serologic laboratory data from major commercial laboratories and Northwell Health; COVID-19 vaccination data; and, for patients with cancer, 2010 to 2021 National Cancer Institute Surveillance, Epidemiology, and End Results registry data.

Results: The CRWDi contains 4 cohorts: patients with cancer; patients with rheumatic diseases receiving pharmacotherapy; noncancer solid organ and hematopoietic stem cell transplant recipients; and people from the general population including adults and pediatric patients.

Multidimensional 1-Year Outcomes After Intensive Care Admission for Multisystem Inflammatory Syndrome in Children.

Objectives: The COVID-19 pandemic gave rise to uncertainty concerning potential sequelae related to a severe acute respiratory syndrome coronavirus 2 infection. This landscape is currently unfolding with studies reporting sequelae on various domains (physical, cognitive, and psychosocial), although most studies focus on adults or only one domain. We sought to investigate concurrent sequelae on multiple domains 1 year after PICU admission for Multisystem Inflammatory Syndrome in Children (MIS-C).