- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- HIV/AIDS Research and Interventions
- Actinomycetales infections and treatment
- Tuberculosis Research and Epidemiology
- Infectious Diseases and Mycology
- Antibiotic Use and Resistance
- Antibiotic Resistance in Bacteria
- Bacterial Identification and Susceptibility Testing
- Pneumocystis jirovecii pneumonia detection and treatment
- Antibiotics Pharmacokinetics and Efficacy
- HIV-related health complications and treatments
- Immune Response and Inflammation
- Urinary Tract Infections Management
- Mycobacterium research and diagnosis
- Legionella and Acanthamoeba research
- Pneumonia and Respiratory Infections
- Fungal Infections and Studies
- Immune Cell Function and Interaction
- HIV, Drug Use, Sexual Risk
- Hepatitis C virus research
- Antimicrobial Resistance in Staphylococcus
- Nosocomial Infections in ICU
- Antifungal resistance and susceptibility
- Cytomegalovirus and herpesvirus research
Erasmus MC
2016-2025
University Medical Center Utrecht
2021-2025
Utrecht University
2022-2025
Erasmus University Rotterdam
2013-2024
Anna Needs Neuroblastoma Answers
2021
Maastricht University Medical Centre
2003-2018
Maastricht University
2007-2014
International Center for Public Health
2011
St. Elisabeth Hospital
2010
Netherlands Institute for Health Services Research
2010
Key questions in COVID-19 are the duration and determinants of infectious virus shedding. Here, we report that shedding is detected by cultures 23 129 patients (17.8%) hospitalized with COVID-19. The median 8 days post onset symptoms (IQR 5-11) drops below 5% after 15.2 (95% confidence interval (CI) 13.4-17.2). Multivariate analyses identify viral loads above 7 log10 RNA copies/mL (odds ratio [OR] 14.7 (CI 3.57-58.1; p < 0.001) as independently associated isolation SARS-CoV-2 from...
Although Toll-like receptors (TLRs) are critical mediators of the immune response to pathogens, influence polymorphisms in this gene family on human susceptibility infection is poorly understood. We demonstrated recently that TLR5 recognizes flagellin, a potent inflammatory stimulus present flagellar structure many bacteria. Here, we show common stop codon polymorphism ligand-binding domain (TLR5392STOP) unable mediate flagellin signaling, acts dominant fashion, and associated with pneumonia...
Interleukin (IL)—1 signaling is required for the containment of infections with intracellular microorganisms, such as Listeria monocytogenes and Leishmania major. To determine role IL-1 in host response to tuberculosis, we infected type I receptor—deficient (IL-1R−/−) mice, which does not exert effects, Mycobacterium tuberculosis. IL-1R−/− mice were more susceptible pulmonary reflected by an increased mortality enhanced mycobacterial outgrowth lungs distant organs, was associated defective...
During TB cytokines play a role in host defence. To determine the cytokine pattern during various disease stages of TB, serum levels IL-12, interferon-gamma (IFN-gamma), IL-4, IL-6 and IL-10 were measured 81 patients with active 15 therapy 26 after anti-tuberculous as well 16 persons who had been close contact smear-positive 17 healthy controls. IFN-gamma was elevated when compared controls, declining treatment. IL-12 (p40 p70) not significantly higher any other groups. IL-4 low all In...
Abstract Mycobacterium tuberculosis bacilli are intracellular organisms that reside in phagosomes of alveolar macrophages (AMs). To determine the vivo role AM depletion host defense against M. infection, mice with pulmonary induced by intranasal administration virulent were treated intranasally either liposome-encapsulated dichloromethylene diphosphonate (AM− mice), liposomes, or saline (AM+ mice). AM− completely protected lethality, which was associated a reduced outgrowth mycobacteria...
Recommendations of first choice antibiotic therapy need to be based on actual susceptibility data. We determined the E. coli in uncomplicated UTI among women and compared results with 2004 2009. In 30 sentinel general practitioner practices Nivel Primary Care database, urine samples were collected from symptoms UTI. Patient characteristics, susceptibility, ESBL production analyzed. Six hundred eighty-nine collected; was most isolated uropathogen (83%). Antibiotic stable over time except for...
The immunogenetic factors that influence susceptibility to pneumonia are poorly understood. Recent studies suggest an association of toll-like receptor 4 (TLR4) polymorphisms with increased some infections. Here, we examined whether in TLR4 Legionnaires' disease (LD) by using a case-control study compare the allele frequencies two SNPs (A896G and C1196T). Cases ( n = 108) were obtained from LD outbreak Netherlands 1999. Controls exposed at same outbreak, did not develop pneumonia, either...
The development of active tuberculosis after infection with Mycobacterium is almost invariably caused by a persistent or transient state relative immunodeficiency. Leptin, the product obese (ob) gene, pleiotropic protein produced mainly adipocytes and down-regulated during malnutrition starvation, conditions closely connected tuberculosis. To investigate role leptin in tuberculosis, we intranasally infected wild-type (Wt) leptin-deficient ob/ob mice live virulent M. Ob/ob displayed higher...
Eight monoclonal antibodies (MAbs) directed against the 14,000-molecular-weight (14K) antigen of Mycobacterium tuberculosis reacted specifically with mycobacteria M. complex. The nucleotide sequence gene encoding 14K was determined by using recombinant DNA clones isolated from lambda gt11 and cosmid libraries genome. protein coded for a polypeptide 144 amino acids calculated molecular mass 16,277 Da. has marked homology proteins belonging to alpha-crystallin family low-molecular-weight heat...
Background. The aim of this study was to investigate the association between immunodeficiency, viremia, and non–AIDS-defining malignancies (NADM). Methods. Patients starting combination antiretroviral therapy (cART) as 1 January 1996 were selected from AIDS Therapy Evaluation in Netherlands (ATHENA) cohort. In Cox models, risk factors for NADM investigated. These included age, sex, transmission route, smoking, alcohol abuse, prior diagnosis, duration exposure cART, estimated human...
In a three-arm randomized trial conducted among adult patients in HIV treatment centers The Netherlands, Marlous Grijsen and colleagues examine the effects of temporary combination antiretroviral therapy during primary infection.
We studied clinical characteristics, appropriateness of initial antibiotic treatment, and other factors associated with day 30 mortality in patients bacteremia caused by extended-spectrum-β-lactamase (ESBL)-producing bacteria eight Dutch hospitals. Retrospectively, information was collected from 232 consecutive ESBL (due to Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae) between 2008 2010. In this cohort (median age 65 years; 24 were <18 years age), many had comorbidities,...
The Netherlands has provided unrestricted access to direct-acting antivirals (DAAs) since November 2015. We analyzed the nationwide hepatitis C virus (HCV) treatment uptake among patients coinfected with human immunodeficiency (HIV) and HCV.Data were obtained from ATHENA HIV observational cohort in which >98% of HIV-infected ever registered 1998 are included. Patients included if they had 1 positive HCV RNA result, did not have spontaneous clearance, known still be care. Treatment outcome...
COVID-19 induces haemocytometric changes. Complete blood count changes, including new cell activation parameters, from 982 confirmed adult patients 11 European hospitals were retrospectively analysed for distinctive patterns based on age, gender, clinical severity, symptom duration, and hospital days. The observed formed the basis to develop a multi-haemocytometric-parameter prognostic score predict, during first three days after presentation, which will recover without ventilation or...
An innovative approach to eliminate HIV-1-infected cells emerging out of latency, the major hurdle HIV-1 cure, is pharmacologically reactivate viral expression and concomitantly trigger intracellular pro-apoptotic pathways in order selectively induce cell death (ICD) infected cells, without reliance on extracellular immune system. In this work, we demonstrate effect DDX3 inhibitors inducing latent lines, primary CD4+ T from cART-suppressed people living with (PLWHIV). We used single-cell...
Eumycetoma is a chronic subcutaneous neglected tropical disease that can be caused by more than 40 different fungal causative agents. The most common agents produce black grains and belong to the orders Sordariales Pleosporales. current antifungal used treat eumycetoma are itraconazole or terbinafine, however, their cure rates low. To find novel drugs for eumycetoma, we screened 400 diverse drug-like molecules from Pandemic Response Box against as part of Open Source Mycetoma initiative...
Abstract CD14 is a receptor for cell wall components of Gram-negative and Gram-positive bacteria that has been implicated in the initiation inflammatory response to sepsis. To determine role LPS-induced effects humans, 16 healthy subjects received an i.v. injection LPS (4 ng/kg) preceded (−2 h) by IC14, recombinant chimeric mAb against human CD14, at dose 1 mg/kg over h, or placebo. In receiving saturation on circulating monocytes granulocytes was &gt;90% time injection. IC14 attenuated...
Abstract After a large outbreak of Legionnaires’ disease in the Netherlands, we determined risk factors for intensive care unit (ICU) admission and death impact adequate therapy on ICU-free survival among 141 hospitalized patients. Overall mortality rate was 13%, ICU 36%. Smoking, temperature >38.5°C, bilateral infiltrates shown chest x-ray were independent or (all p<0.05). Starting within 24 hours after resulted higher compared to initiation hours: 78% versus 54%, respectively (p=0.005)....
Soluble Triggering Receptor Expressed on Myeloid cells-1 (sTREM-1) has proven to be a good biomarker for sepsis. For the diagnosis ventilator-associated pneumonia (VAP), however, there have only been few, relatively small, studies role of this receptor. The aim study was evaluate usefulness sTREM-1 in bronchoalveolar lavage fluid (BALF) from Intensive Care Unit patients as rapid diagnostic test VAP.The concentration 240 BALF samples measured using quantitative sandwich enzyme immunoassay....
Antimicrobial susceptibility was analyzed for 354 typhoidal Salmonella isolates collected during 1999-2012 in the Netherlands. In 16.1% of all and 23.8% that showed increased MICs ciprofloxacin, MIC azithromycin increased. This resistance may complicate empirical treatment enteric fever.
The cyclic GMP-AMP synthase (cGAS)-STING pathway is central for innate immune sensing of various bacterial, viral and protozoal infections. Recent studies identified the common HAQ R232H alleles TMEM173/STING, but functional consequences these variants primary infections are unknown. Here we demonstrate that cGAS- STING-deficient murine macrophages as well human cells individuals carrying TMEM173/STING were severely impaired in producing type I IFNs pro-inflammatory cytokines response to...