Anthrax

This study is a clinical, multi-center, retrospective, case-control study. Patients clinically diagnosed with severe anthrax who meet the inclusion and exclusion criteria will be included in this study for analysis. Respiratory, circulation, nerve and other vital signs of patients with severe anthrax during hospitalization were recorded, and clinical data such as blood routine, blood biochemistry, coagulation function, myocardial injury, therapeutic drug use, and survival time of patients were recorded, as well as the survival situation of patients 28 days and 90 days after discharge.

This Phase 1 study is designed to assess the safety, tolerability, and pharmacokinetics of single and multiple intravenous doses of BWC0977 when administered to healthy adult volunteers. This is a randomized double-blind, placebo-controlled, ascending dose, multi-cohort trial. A total of 64 healthy volunteers are expected to be enrolled in 8 Cohorts. The study will be conducted in two phases: A single ascending dose (SAD) phase, followed by a multiple ascending dose (MAD) phase. In SAD, participants in Cohorts 1 - 2 will receive one dose of BWC0977 or placebo. In MAD, participants in cohorts 3 - 7 will receive multiple doses of BWC0977 or placebo for 7-10 consecutive days (as per the schedule). In both parts, sequential cohorts will be exposed to increasing doses of BWC0977.

This study will be conducted as a nested sub-study within a main longitudinal study implemented online. The baseline assessment of the longitudinal study was conducted between October and November 2025. Participants who agreed to be recontacted will be invited to join the randomized controlled trial (RCT) approximately four months after the baseline assessment, in February-March 2026. At that time, participants will be randomized in a 1:1 ratio into either the intervention or control group.

The major role of human genetic factors in the immune response to infections is now well established, particularly for viral infections. In the context of the COVID-19 pandemic, the following results have identified 1) several inborn errors of immunity (IEI) affecting the response or production of type I interferons (type I IFNs) in around 4% of adult patients with severe clinical disease, and 2) the presence of type I IFN-neutralizing autoantibodies (auto-Abs) in around 15% of severe cases, and 20% of deaths. The investigators would like to carry out a longitudinal immunological and clinical follow-up study on a prospective cohort of patients with either a genetic defect affecting the type I IFN-dependent immune response, or anti-IFN-I auto-Abs, to monitor the incidence of infectious and/or autoimmune events in these individuals, the evolution of neutralizing power, and the kinetics of auto-Abs. This should lead to a better understanding of the prevention and management of these patients. The research design is a national multicenter prospective cohort of adults with 1) anti-IFN-I auto-Abs or 2) IEI- IFN-I, with follow-up from 1 to 4 years. These individuals may be: 1) patients who have or have had clinical disease (related to COVID-19, other viral infections, autoimmune disorders); or 2) "healthy" participants (e.g. blood donors, relatives of an IEI patient). Follow-up will include: * yearly visits to the Clinical Investigation Center (CIC) or a clinical department with blood sampling; * specific visit in case of hospitalization for infectious events or adverse effects of vaccination, exacerbation or new diagnosis of auto-immune disease, new diagnosis of cancer, or SARS-CoV-2 infection whether or not patients are admitted to hospital, with blood sampling. In addition, a retrospective "passive" follow-up will be implemented through matching with the data from the SNDS (National Health Data System), in order to collect clinical events of and healthcare resource consumption. Moreover, matching with controls adults from the national CONSTANCES cohort, not carrying auto-Abs against type I IFNs nor IEI-IFN-I, will be performed. (ratio 3:1; matching on age (+/- 5 years), gender and geographic region of recruitment). Individuals under long-lasting immunosuppressive or immunomodulatory drugs will not be eligible. Follow-up of controls, which will be carried out as part of the CONSTANCES cohort, will include web-based questionnaires, every 12 months, in addition to linking with SNDS data as already done in this cohort. Inclusion visit: After signing the consent form, the following tests will be performed: * Demographic characteristics (sex, age, country of birth) * Medical history from participant and family member(s) including infectious and auto-immune diseases, cancers and vaccination status and side effects * Blood samples for: * full blood cell count; * classical autoimmune investigations (anti-nuclear, anti-ENA, native anti-DNA, anti- thyroid antibodies, rheumatoid factor); * immunophenotyping\*; * auto-Abs against type I IFNs, other cytokines\*, or other target proteins\* (dosage and neutralization activity); * Genetic explorations by whole-exome or whole-genome sequencing\*; * Biobanking (DNA, plasma/sera; cryopreserved peripheral blood mononuclear cells (PBMCs). * these biological analyses will be carried out as part of dedicated COVIFERON RHU5 workpackages. In addition, vaccination against SARS-CoV-2 and influenza will be offered to these subjects as a priority, as part of their usual care. Follow-up visits : Annual visits to the CIC : * Medical history since last visit, including infectious, auto-immune and oncologic events, vaccination status and side effects * Blood samples for: * full blood cell count; * classical autoimmune investigation (anti-nuclear, anti-ENA, native anti- DNA, anti-thyroid antibodies, rheumatoid factor); * immunophenotyping; * Auto-Abs against type I IFNs, other cytokines, or other target proteins (dosage and neutralization) * Biobanking (DNA, plasma, cryopreserved peripheral blood mononuclear cells (PBMCs)) Additional specific visit in the event of a clinical event of interest, at any time during follow-up: * In case of SARS-CoV-2 infection, whatever the severity of the disease: blood sampling for determination and neutralization of type I anti-IFN autoAbs, CBC, and biobanking (plasma and PBMC) and teleconsultation with the CIC in charge of patients, as soon as possible. * In the event of hospitalization for infectious events or exacerbation or new diagnosis of an auto-immune disease: blood sampling for determination and neutralization of anti-IFN-I autoAbs, CBC, and biobanking (plasma and PBMCs) and collection of the hospitalization report in the case report form on a dedicated page.

The intentional use of Bacillus anthracis in 2001 as a bioterrorism weapon with fatal consequences renewed interest in past epidemiologic and animal research about pathogenesis and posed new dilemmas about diagnosis and treatment. Cases in the October 2001 US outbreak were theoretically exposed via one dispersal method: aerosolization of Ames strain spores. While some developed the cutaneous anthrax form, others sustained the more serious inhalational disease. Inhaled spores are known to travel to alveolar macrophages and then onto the mediastinal lymph nodes where germination to the bacterium form and toxin release are thought to occur. Infective dose, significance of dormant spores after long-term antibiotic therapy, spectrum of disease and even precise cause of death remain unknown. This observational, prospective natural history study was developed during the 2001 outbreak and is set up to follow participants from the time of exposure through post-recovery (greater than ten years). Healthy vaccinated participants have been included to evaluate serum titers and cell markers in relation to dose and frequency of Anthrax Vaccine Adsorbed (AVA) vaccine.

Inappropriate antibiotic prescribing in primary care contributes to the development of antimicrobial resistance. Despite guidelines and public health efforts, overprescribing remains prevalent, especially for self-limiting infections which often resolve without antibiotic treatment. Digital tools such as a Prescription Search Support (PSS) may aid general practitioners (GPs) in making more informed prescribing decisions. This implementation project builds upon a previously conducted mixed-methods implementation study evaluating the usability of a PSS, which was approved by the Ethical Review Board UZ KU Leuven (Onderwijs-Begeleidingscommissie) on 27 September 2024 (MP031770). The PSS under study contains the current recommendations for the proper use of antimicrobial agents for common infections in ambulatory care in Belgium. In other words, it represents the BAPCOC guidelines in a digital and user-friendly environment, by using a decision tree. Advice for the following diagnoses (ICPC-2 codes) is included in the PSS: sore throat (R21, R74), pertussis (R71), common cold (R74), acute rhinosinusitis (R75), acute bronchitis / bronchiolitis (R78), influenza (R80), pneumonia (R81), ear pain (H01), otorrhea (H04), acute otitis media (H71), acute epiglottitis (R77), acute exacerbations of chronic obstructive pulmonary disease, aspiration pneumonia (R81), laryngitis stridulosa (R77), acute cystitis (U71), acute prostatitis (Y73), acute pyelonephritis (U70), acute vulvovaginitis (X84), asymptomatic bacteriuria, epididymo-orchitis (Y74), genital herpes (Y72, X90), partner treatment and treatment of asymptomatic sexually transmitted infections, pelvic inflammatory disease (X74), syphilis (X70, Y70), and urethritis (U72). This PSS was developed as part of the Belgian National Action Plan on AMR by the Federal Public Service Health, Food Chain Safety and Environment and the National Institute for Health and Disability Insurance (NIHDI; RIZIV-INAMI), in collaboration with various experts and stakeholders, including physicians, infectiologists, hygienists, policymakers, guideline developers, and software developers. The company Smals, under instruction of RIZIV-INAMI, developed the software for this application in close collaboration with the RIZIV-INAMI working group. Guideline recommendations regarding appropriate prescribing of antimicrobials in ambulatory care were converted into decision rules, which serve as the knowledge source for the PSS. Digital education offers several advantages, such as easy access without time or location constraints, varying possible forms and levels, and the ability to disseminate evidence on a large scale. Previous research has shown that standalone web- or smartphone-based applications in this context have the potential to increase physicians' knowledge of antimicrobials and guideline recommendations, potentially improving guideline adherence. In Belgium, antibiotic use in ambulatory care is closely monitored through the Antibiotic Barometer, a national surveillance system coordinated by the Academic Centre of General Practice of KU Leuven and financed by the National Institute for Health and Disability Insurance (RIZIV-INAMI). The Antibiotic Barometer was approved by the Sociaal-maatschappelijke Ethische Commissie (SMEC; G-2023-6352) and provides quarterly feedback to general practices based on routine health insurance claims data. This study evaluates the implementation and impact of the PSS in routine Belgian primary care using a stepped-wedge cluster randomized trial design. Participating general practices are recruited to ensure broad representation across Belgian primary care. General practices constitute the unit of randomization and are randomly allocated to one of four predefined implementation steps. All practices start in a control condition without access to the PSS and transition once to the intervention condition according to their assigned step. Each implementation step lasts three months, after which practices retain access to the PSS for the remainder of the study period. By the end of the study, all participating practices will have received access to the intervention. Data for this study are derived from routine sources and handled within the secure data infrastructure of KU Leuven. Prescribing data obtained via the Antibiotic Barometer are aggregated and pseudonymized at practice level prior to analysis, ensuring that individual patients cannot be identified. Data linkage, storage, and analysis are conducted in accordance with applicable data protection regulations. Quantitative and qualitative analyses are used to evaluate both the effectiveness and implementation of the PSS in real-world primary care. Findings from this study will inform future policy decisions regarding national rollout, optimization, and long-term integration of the PSS within Belgian antimicrobial stewardship strategies.

We are studying virologic and/or immunologic parameters of HIV infection and other infectious or non-infectious immune deficiency diseases in order to better understand the pathogenesis of HIV. Because of the lack of an adequate animal model it is generally necessary to utilize human peripheral blood cells for studying aspects of either in vivo or in vitro HIV infection. We wish to be able to continue to elucidate many pathogenic aspects of HIV infection in relation to other infectious or non-infectious immune regulation and dysregulation using human peripheral blood mononuclear cells as a model.