Publications by authors named "Hilde Jansens"

25 Publications

  • Page 1 of 1

Monitoring the SARS-CoV-2 pandemic: screening algorithm with SNP detection for the rapid identification of established and emerging variants.

Clin Microbiol Infect 2021 Sep 16. Epub 2021 Sep 16.

Department of Microbiology and National Reference Centre for Respiratory Pathogens, University Hospital Antwerp, Edegem, Belgium; Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Wilrijk, Belgium; Laboratory of Medical Biochemistry, University of Antwerp, Wilrijk, Belgium. Electronic address:

Objectives: The current study evaluates a testing algorithm for the rapid identification of SARS-CoV-2 variants that includes the use of PCR-based targeted Single Nucleotide Polymorphism (SNP) detection assays preceded by a multiplex PCR sensitive to s-Gene Target Failure (SGTF).

Methods: PCR SNP assays targeting SARS-CoV-2 s-gene mutations ΔH69-V70, L452R, E484K, N501Y, H655Y, and P681R using melting curve analysis were performed on 567 samples in which SARS-CoV-2 viral RNA was detected by a multiplex PCR. Viral whole genome sequencing (WGS) was performed to confirm the presence of SNPs and to identify the Pangolin lineage. Additionally, 1133 SARS-CoV-2 positive samples with SGTF were further assessed by WGS to determine the presence of ΔH69-V70.

Results: The N501Y-specific assay (N=567) had an overall percent agreement (OPA) of 98.5%. The ΔH69-V70- (N=178) and E484K-specific (N=401) assays had an OPA of 96.6 and 99.7% respectively. Assessment of H655Y (N=139) yielded a 100.0% concordance when applied in the proposed algorithm. The L452R- (N=67) and P681R-specific (N=62) assays had an OPA of 98.2 and 98.1% respectively. The proposed algorithm identified six variants of concern/interest (VOC/VOI) - Alpha (N=149), Beta (N=65), Gamma (N=86), Delta (N=49), Eta (N=6), Kappa (N=6) - and 205 non-VOC/VOI strains - including the variants under monitoring B.1.214.2 (N=43) and B.1.1.318 (N=18) and Epsilon (N=1). An excellent concordance was observed for the identification of all SARS-CoV-2 lineages evaluated.

Conclusions: We present a flexible testing algorithm for the rapid detection of current and emerging SARS-CoV-2 VOC/VOIs which can be easily adapted based on the local endemicity of specific variants.
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http://dx.doi.org/10.1016/j.cmi.2021.09.007DOI Listing
September 2021

Serological response in health care workers after a single dose of SARS-CoV-2 vaccine using six automated SARS-CoV-2 antibody assays.

Diagn Microbiol Infect Dis 2021 Oct 10;101(2):115486. Epub 2021 Jul 10.

University Hospital Antwerp, Laboratory Medicine, Edegem, Belgium. Electronic address:

Spike (S)- and nucleocapsid (N)-specific serological assay responses were determined before and/or after first dose SARS-CoV-2 vaccination in 22 individuals. S-specific assays quantified antibodies after vaccination with significant higher levels in participants with a previous infection. Be cautious combining N-/S-specific assay results, potentially differentiating post-infection/vaccination immunization as assay-specific N-antibody waning was observed.
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http://dx.doi.org/10.1016/j.diagmicrobio.2021.115486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272050PMC
October 2021

Performance of three automated SARS-CoV-2 antibody assays and relevance of orthogonal testing algorithms.

Clin Chem Lab Med 2020 11 19;59(2):411-419. Epub 2020 Nov 19.

Department of Laboratory Medicine, University Hospital Antwerpen, Antwerpen, Belgium.

Objectives: Development and implementation of SARS-CoV-2 serologic assays gained momentum. Laboratories keep on investigating the performance of these assays. In this study, we compared three fully automated SARS-CoV-2 antibody assays.

Methods: A total of 186 samples from 84 PCR-positive COVID-19 patients and 120 control samples taken before the SARS-CoV-2 pandemic were analyzed using commercial serologic assays from Roche, Siemens and DiaSorin. Time after the positive COVID-19 PCR result and onset of symptoms was retrieved from the medical record. An extended golden standard, using the result of all three assays was defined, judging if antibodies are present or absent in a sample. Diagnostic and screening sensitivity/specificity and positive/negative predictive value were calculated.

Results: Diagnostic sensitivity (ability to detect a COVID-19 positive patient) ≥14 days after positive PCR testing was 96.7% (95% CI 88.5-99.6%) for DiaSorin, 93.3% (95% CI 83.8-98.2%) for Roche and 100% (95% CI 94.0-100%) for Siemens. Lower diagnostic sensitivities were observed <14 days after onset of symptoms for all three assay. Diagnostic specificity (ability to detect a COVID-19 negative patient) was 95.0% (95% CI 89.4-98.1%) for DiaSorin, 99.2% (95% CI 95.4-99.9%) for Roche and 100% (95% CI 97.0-100%) for Siemens. The sensitivity/specificity for detecting antibodies (ability of detecting absence (specificity) or presence (sensitivity) of COVID-19 antibodies) was 92.4% (95% CI 86.4-96.3%)/94.9% (95% CI 90.5-97.6%) for DiaSorin, 97.7% (95% CI 93.5-99.5%)/97.1% (95% CI 93.5-99.1%) for Roche and 98.5% (95% CI 94.6-99.8)/97.1 (95% CI 93.5-99.1%) for Siemens.

Conclusions: This study revealed acceptable performance for all three assays. An orthogonal testing algorithm using the Siemens and Roche assay achieved the highest positive predictive values for antibody detection in low seroprevalence settings.
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http://dx.doi.org/10.1515/cclm-2020-1378DOI Listing
November 2020

Symptomatic SARS-CoV-2 reinfection of a health care worker in a Belgian nosocomial outbreak despite primary neutralizing antibody response.

Clin Infect Dis 2020 Dec 14. Epub 2020 Dec 14.

Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

Background: It is currently unclear whether SARS-CoV-2 reinfection will remain a rare event, only occurring in individuals who fail to mount an effective immune response, or whether it will occur more frequently when humoral immunity wanes following primary infection.

Methods: A case of reinfection was observed in a Belgian nosocomial outbreak involving 3 patients and 2 health care workers. To distinguish reinfection from persistent infection and detect potential transmission clusters, whole genome sequencing was performed on nasopharyngeal swabs of all individuals including the reinfection case's first episode. IgA, IgM, and IgG and neutralizing antibody responses were quantified in serum of all individuals, and viral infectiousness was measured in the swabs of the reinfection case.

Results: Reinfection was confirmed in a young, immunocompetent health care worker as viral genomes derived from the first and second episode belonged to different SARS-CoV-2 clades. The symptomatic reinfection occurred after an interval of 185 days, despite the development of an effective humoral immune response following symptomatic primary infection. The second episode, however, was milder and characterized by a fast rise in serum IgG and neutralizing antibodies. Although contact tracing and virus culture remained inconclusive, the health care worker formed a transmission cluster with 3 patients and showed evidence of virus replication but not of neutralizing antibodies in her nasopharyngeal swabs.

Conclusion: If this case is representative of most Covid-19 patients, long-lived protective immunity against SARS-CoV-2 after primary infection might not be likely.
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http://dx.doi.org/10.1093/cid/ciaa1850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799230PMC
December 2020

Evaluating SARS-CoV-2 spike and nucleocapsid proteins as targets for antibody detection in severe and mild COVID-19 cases using a Luminex bead-based assay.

J Virol Methods 2021 02 20;288:114025. Epub 2020 Nov 20.

Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; University of Antwerp, Antwerp, Belgium. Electronic address:

Large-scale serosurveillance of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) will only be possible if serological tests are sufficiently reliable, rapid and affordable. Many assays are either labour-intensive and require specialised facilities (e.g. virus neutralization assays), or are expensive with suboptimal specificity (e.g. commercial ELISAs and RDTs). Bead-based assays offer a cost-effective alternative and allow for multiplexing to test for antibodies against multiple antigens and against other pathogens. Here, we compare the performance of spike (S) and nucleocapsid (NP) antigens for the detection of SARS-CoV-2 specific IgG, IgM and IgA antibodies in a panel of sera that includes recent (up to six weeks after symptom onset, severe n = 44; and mild cases n = 52) and old infections (five months after symptom onset, mild n = 104), using a Luminex-bead based assay and comparison to a virus neutralization test. While we show that neutralizing antibody levels are significantly lower in mild than in severe cases, we demonstrate that a combination of the recombinant nucleocapsid protein (NP) and receptor-binding domain (RBD) results in highly specific (99 %) IgG antibody detection five months after infection in 96 % of cases. Although most severe Covid-19 cases developed a clear IgM and IgA response, titers fell below the detection threshold in more than 20 % of mild cases in our bead-based assay. In conclusion, our data supports the use of RBD and NP for the development of SARS-CoV-2 serological IgG bead-based assays.
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http://dx.doi.org/10.1016/j.jviromet.2020.114025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678438PMC
February 2021

Fatal lymphocytic cardiac damage in coronavirus disease 2019 (COVID-19): autopsy reveals a ferroptosis signature.

ESC Heart Fail 2020 Sep 22. Epub 2020 Sep 22.

Infla-Med Research Consortium of Excellence, University of Antwerp, Antwerp, Belgium.

Aims: Cardiovascular complications, including myocarditis, are observed in coronavirus disease 2019 (COVID-19). Major cardiac involvement is a potentially lethal feature in severe cases. We sought to describe the underlying pathophysiological mechanism in COVID-19 lethal cardiogenic shock.

Methods And Results: We report on a 48-year-old male COVID-19 patient with cardiogenic shock; despite extracorporeal life support, dialysis, and massive pharmacological support, this rescue therapy was not successful. Severe acute respiratory syndrome coronavirus 2 RNA was detected at autopsy in the lungs and myocardium. Histopathological examination revealed diffuse alveolar damage, proliferation of type II pneumocytes, lymphocytes in the lung interstitium, and pulmonary microemboli. Moreover, patchy muscular, sometimes perivascular, interstitial mononuclear inflammatory infiltrates, dominated by lymphocytes, were seen in the cardiac tissue. The lymphocytes 'interlocked' the myocytes, resulting in myocyte degeneration and necrosis. Predominantly, T-cell lymphocytes with a CD4:CD8 ratio of 1.7 infiltrated the interstitial myocardium, reflecting true myocarditis. The myocardial tissue was examined for markers of ferroptosis, an iron-catalysed form of regulated cell death that occurs through excessive peroxidation of polyunsaturated fatty acids. Immunohistochemical staining with E06, a monoclonal antibody binding to oxidized phosphatidylcholine (reflecting lipid peroxidation during ferroptosis), was positive in morphologically degenerating and necrotic cardiomyocytes adjacent to the infiltrate of lymphocytes, near arteries, in the epicardium and myocardium. A similar ferroptosis signature was present in the myocardium of a COVID-19 subject without myocarditis. In a case of sudden death due to viral myocarditis of unknown aetiology, however, immunohistochemical staining with E06 was negative. The renal proximal tubuli stained positively for E06 and also hydroxynonenal (4-HNE), a reactive breakdown product of the lipid peroxides that execute ferroptosis. In the case of myocarditis of other aetiology, the renal tissue displayed no positivity for E06 or 4-HNE.

Conclusions: The findings in this case are unique as this is the first report on accumulated oxidized phospholipids (or their breakdown products) in myocardial and renal tissue in COVID-19. This highlights ferroptosis, proposed to detrimentally contribute to some forms of ischaemia-reperfusion injury, as a detrimental factor in COVID-19 cardiac damage and multiple organ failure.
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http://dx.doi.org/10.1002/ehf2.12958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607145PMC
September 2020

Transcriptomic profiling of different responder types in adults after a Priorix® vaccination.

Vaccine 2020 04 9;38(16):3218-3226. Epub 2020 Mar 9.

AUDACIS, Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium; Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.

Thanks to the recommendation of a combined Measles/Mumps/Rubella (MMR) vaccine, like Priorix®, these childhood diseases are less common now. This is beneficial to limit the spread of these diseases and work towards their elimination. However, the measles, mumps and rubella antibody titers show a large variability in short- and long-term immunity. The recent outbreaks worldwide of measles and mumps and previous studies, which mostly focused on only one of the three virus responses, illustrate that there is a clear need for better understanding the immune responses after vaccination. Our healthy cohort was already primed with the MMR antigens in their childhood. In this study, the adult volunteers received one Priorix® vaccine dose at day 0. First, we defined 4 different groups of responders, based on their antibody titers' evolution over 4 time points (Day 0, 21, 150 and 365). This showed a high variability within and between individuals. Second, we determined transcriptome profiles using 3'mRNA sequencing at day 0, 3 and 7. Using two analytical approaches, "one response group per time point" and "a time comparison per response group", we correlated the short-term gene expression profiles to the different response groups. In general, the list of differentially expressed genes is limited, however, most of them are clearly immune-related and upregulated at day 3 and 7, compared to the baseline day 0. Depending on the specific response group there are overlapping signatures for two of the three viruses. Antibody titers and transcriptomics data showed that an additional Priorix vaccination does not facilitate an equal immune response against the 3 viruses or among different vaccine recipients.
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http://dx.doi.org/10.1016/j.vaccine.2020.03.004DOI Listing
April 2020

A unilateral inguinofemoral granulomatous lymphadenitis in a two-year-old girl. A case report.

Acta Clin Belg 2021 Oct 10;76(5):381-383. Epub 2020 Mar 10.

Department of Pediatrics, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium.

is an environmental contaminant and is considered as an emerging human pathogen. We report the case of a granulomatous lymphadenitis in a two-year-old girl. A two-year-old, previously healthy, Caucasian girl developed a unilateral inguinofemoral granulomatous lymphadenitis with . The protracted course, the violaceous discoloration of the overlying skin, the mild tenderness without constitutional signs, the reactive tuberculin skin test with a negative interferon gamma release assay (IGRA) and the negative serology ranked non-tuberculous mycobacterial lymphadenitis high in our differential diagnosis. The ultrasonography showed signs of abcedation. We decided for surgical excision of the nodes. A granulomatous lymphadenitis was revealed. Treatment with an oral course of 2 weeks ciprofloxacin was prescribed. The course after treatment was uneventful and after one year of follow-up, the child is still doing well. Unusual clinical presentation should raise suspicion of uncommon pathogens and uncommon pathogens should raise suspicion of an underlying problem such as immunodeficiency, which was not the case in our patient.
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http://dx.doi.org/10.1080/17843286.2020.1740464DOI Listing
October 2021

Diagnosing enterovirus meningitis via blood transcriptomics: an alternative for lumbar puncture?

J Transl Med 2019 08 23;17(1):282. Epub 2019 Aug 23.

AUDACIS, Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium.

Background: Meningitis can be caused by several viruses and bacteria. Identifying the causative pathogen as quickly as possible is crucial to initiate the most optimal therapy, as acute bacterial meningitis is associated with a significant morbidity and mortality. Bacterial meningitis requires antibiotics, as opposed to enteroviral meningitis, which only requires supportive therapy. Clinical presentation is usually not sufficient to differentiate between viral and bacterial meningitis, thereby necessitating cerebrospinal fluid (CSF) analysis by PCR and/or time-consuming bacterial cultures. However, collecting CSF in children is not always feasible and a rather invasive procedure.

Methods: In 12 Belgian hospitals, we obtained acute blood samples from children with signs of meningitis (49 viral and 7 bacterial cases) (aged between 3 months and 16 years). After pathogen confirmation on CSF, the patient was asked to give a convalescent sample after recovery. 3' mRNA sequencing was performed to determine differentially expressed genes (DEGs) to create a host transcriptomic profile.

Results: Enteroviral meningitis cases displayed the largest upregulated fold change enrichment in type I interferon production, response and signaling pathways. Patients with bacterial meningitis showed a significant upregulation of genes related to macrophage and neutrophil activation. We found several significantly DEGs between enteroviral and bacterial meningitis. Random forest classification showed that we were able to differentiate enteroviral from bacterial meningitis with an AUC of 0.982 on held-out samples.

Conclusions: Enteroviral meningitis has an innate immunity signature with type 1 interferons as key players. Our classifier, based on blood host transcriptomic profiles of different meningitis cases, is a possible strong alternative for diagnosing enteroviral meningitis.
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http://dx.doi.org/10.1186/s12967-019-2037-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708255PMC
August 2019

Emergence of colistin resistance during treatment of recurrent pneumonia caused by carbapenemase producing Klebsiella pneumoniae.

Diagn Microbiol Infect Dis 2019 Aug 21;94(4):407-409. Epub 2019 Feb 21.

Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.

A 60-year-old woman received meropenem/colistin treatment for bilateral pneumonia caused by a ST15 carbapenemase producing Klebsiella pneumoniae. The patient recovered but re-infection with the same (ST15), but now colistin-resistant K. pneumoniae, occurred. The molecular mechanism of the emerged colistin resistance was identified as mgrB gene modification by insertion element (IS) IS903B.
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http://dx.doi.org/10.1016/j.diagmicrobio.2019.02.014DOI Listing
August 2019

Comparison of the Coris Influ A + B K-SeT® and BD Veritor Flu A + B® for rapid detection of influenza viruses in respiratory samples from 3 consecutive flu seasons in Belgium.

Diagn Microbiol Infect Dis 2019 07 25;94(3):227-230. Epub 2019 Jan 25.

Laboratory of Clinical Microbiology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Belgium.

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http://dx.doi.org/10.1016/j.diagmicrobio.2019.01.005DOI Listing
July 2019

Correction to: Biological tests carried out on serum/plasma samples from donors of human body material for transplantation: Belgian experience and practical recommendations.

Cell Tissue Bank 2018 12;19(4):835-836

Department of Clinical Chemistry, Microbiology and Immunology, Ghent University/University Hospital, De Pintelaan 185, 2P8, 9000, Ghent, Belgium.

The article Biological tests carried out on serum/plasma samples from donors of human body material for transplantation: Belgian experience and practical recommendations.
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http://dx.doi.org/10.1007/s10561-018-9728-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280857PMC
December 2018

Transcriptome profiling in blood before and after hepatitis B vaccination shows significant differences in gene expression between responders and non-responders.

Vaccine 2018 10 8;36(42):6282-6289. Epub 2018 Sep 8.

Department of Medical Genetics, University of Antwerp/Antwerp University Hospital, Edegem, Belgium; AUDACIS, Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium. Electronic address:

Introduction: As the hepatitis B virus is widely spread and responsible for considerable morbidity and mortality, WHO recommends vaccination from infancy to reduce acute infection and chronic carriers. However, current subunit vaccines are not 100% efficacious and leave 5-10% of recipients unprotected.

Methods: To evaluate immune responses after Engerix-B vaccination, we determined, using mRNA-sequencing, whole blood early gene expression signatures before, at day 3 and day 7 after the first dose and correlated this with the resulting antibody titer after two vaccine doses.

Results: Our results indicate that immune related genes are differentially expressed in responders mostly at day 3 and in non-responders mostly at day 7. The most remarkable difference between responders and non-responders were the differentially expressed genes before vaccination. The granulin precursor gene (GRN) was significantly downregulated in responders while upregulated in non-responders at day 0. Furthermore, absolute granulocytes numbers were significantly higher in non-responders at day 0.

Conclusion: The non-responders already showed an activated state of the immune system before vaccination. Furthermore, after vaccination, they exhibited a delayed and partial immune response in comparison to the responders. Our data may indicate that the baseline and untriggered immune system can influence the response upon hepatitis B vaccination.
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http://dx.doi.org/10.1016/j.vaccine.2018.09.001DOI Listing
October 2018

Biological tests carried out on serum/plasma samples from donors of human body material for transplantation: Belgian experience and practical recommendations.

Cell Tissue Bank 2018 Dec 29;19(4):681-695. Epub 2018 Aug 29.

Department of Clinical Chemistry, Microbiology and Immunology, Ghent University/University Hospital, De Pintelaan 185, 2P8, 9000, Ghent, Belgium.

This paper on the biological tests carried out on serum/plasma samples from donors of human body material (HBM) is the result of a project of the working Group of Superior Health Council of Belgium formed with experts in the field of HBM and infectious serology. Indeed, uncertainty about the interpretation of biological test results currently leads to the sometimes unjustified cancelling of planned donations or the rejection of harvested HBM, whilst more sophisticated diagnostic algorithms would still allow the use of organs or HBM that would otherwise have been rejected. NAT tests will not be discussed in this publication. In the first part some general aspects as the need for a formal agreement between the Tissue Establishment l and the laboratory responsible for the biological testing, but also some specifications regarding testing material, the choice of additional biological tests, and some general aspects concerning interpretation and reporting are discussed. In a second part, detailed information and recommendations concerning the interpretation are presented for each of the mandatory tests (human immunodeficiency virus, hepatitis B virus, hepatitis C virus and syphilis) is presented. A number of not mandatory, but regularly used optional serological tests (e.g. for the detection of antibodies to Toxoplasma gondii, Epstein-Barr virus, human T cell leukemia virus and cytomegalovirus) are also extensively discussed. Although the project was meant to provide clarification and recommendations concerning the Belgian legislation, the majority of recommendations are also applicable to testing of donors of tissues and cells in other (European) countries.
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http://dx.doi.org/10.1007/s10561-018-9721-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280847PMC
December 2018

Memory CD4 T cell receptor repertoire data mining as a tool for identifying cytomegalovirus serostatus.

Genes Immun 2019 03 15;20(3):255-260. Epub 2018 Jun 15.

AUDACIS, Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium.

Pathogens of past and current infections have been identified directly by means of PCR or indirectly by measuring a specific immune response (e.g., antibody titration). Using a novel approach, Emerson and colleagues showed that the cytomegalovirus serostatus can also be accurately determined by using a T cell receptor repertoire data mining approach. In this study, we have sequenced the CD4 memory T cell receptor repertoire of a Belgian cohort with known cytomegalovirus serostatus. A random forest classifier was trained on the CMV specific T cell receptor repertoire signature and used to classify individuals in the Belgian cohort. This study shows that the novel approach can be reliably replicated with an equivalent performance as that reported by Emerson and colleagues. Additionally, it provides evidence that the T cell receptor repertoire signature is to a large extent present in the CD4 memory repertoire.
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http://dx.doi.org/10.1038/s41435-018-0035-yDOI Listing
March 2019

Boerhaave's syndrome complicated by a Saccharomyces cerevisiae pleural empyema. Case report and review of the literature.

Acta Clin Belg 2018 Oct 5;73(5):377-381. Epub 2017 Nov 5.

a Department of Intensive Care Medicine , Antwerp University Hospital, University of Antwerp , Edegem (Antwerp) , Belgium.

Objective and Importance Boerhaave's syndrome is a sudden and rare form of oesophageal rupture and is often complicated by local or systemic infection of the mediastinum or pleural cavity. Several micro-organisms are documented as cause of pleural empyema in patients with Boerhaave's syndrome. Intervention (& Technique) We report on a previously healthy 74-year-old male who was admitted at a regional hospital with severe retrosternal and abdominal pain after an episode of vigorous vomiting the morning after ingestion of large quantity of beer. A CT-scan confirmed the diagnosis of Boerhaave's syndrome, an oesophageal stent was placed and a left-sided pleural empyema necessitated chest tube drainage. Pleural fluid samples were cultured every two days and were positive for Proteus mirabilis on day 2 after admission and for Saccharomyces cerevisiae on day 8 after admission. Intravenous fluconazole 800 mg per day was added to the antibacterial treatment. Pleural fluid culture became negative for P. mirabilis on day 23 and for S. cerevisiae on day 13. Recurrent empyema necessitated intrapleural thrombolysis. The patient could be discharged from the ICU after 43 days, from the normal ward to a rehabilitation centre after an additional 13 days. Conclusion Pleural empyema caused by S. cerevisiae, commonly known as 'Brewers' yeast', has never been described in such patients. Our case illustrates that clinicians should be aware of infection with S. cerevisiae after oesophageal perforation, soon after ingestion of beer. Adequate antimycotic treatment was successful and led to negative culture of pleural fluid after 5 days.
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http://dx.doi.org/10.1080/17843286.2017.1398439DOI Listing
October 2018

Cytomegalovirus seropositivity is associated with herpes zoster.

Hum Vaccin Immunother 2015 ;11(6):1394-9

a Centre for Health Economics Research & Modeling Infectious Diseases (CHERMID); Vaccine & Infectious Disease Institute (VAXINFECTIO); University of Antwerp ; Antwerp , Belgium.

Herpes zoster (HZ) is caused by VZV reactivation that is facilitated by a declined immunity against varicella-zoster virus (VZV), but also occurs in immunocompetent individuals. Cytomegalovirus (CMV) infection is associated with immunosenescence meaning that VZV-specific T-cells could be less responsive. This study aimed to determine whether CMV infection could be a risk factor for the development of HZ. CMV IgG serostatus was determined in stored serum samples from previously prospectively recruited ambulatory adult HZ patients in the UK (N = 223) in order to compare the results with those from UK population samples (N = 1545) by means of a logistic regression (controlling for age and gender). Furthermore, we compared the UK population CMV seroprevalence with those from population samples from other countries (from Belgium (N1 = 1741, N2 = 576), USA (N = 5572) and Australia (N = 2080)). Furthermore, CMV IgG titers could be compared between UK HZ patients and Belgium N2 population samples because the same experimental set-up for analysis was used. We found UK ambulatory HZ patients to have a higher CMV seroprevalence than UK population samples (OR 1.56 [1.11 2.19]). CMV IgG seropositivity was a significant risk factor for HZ in the UK (OR 3.06 [1.32 7.04]. Furthermore, high CMV IgG titers (exceeding the upper threshold) were less abundant in CMV-seropositive Belgian N2 population samples than in CMV-seropositive UK HZ patients (OR 0.51 [0.31 0.82]. We found CMV-seroprevalence to increase faster with age in the UK than in other countries (P < 0.05). We conclude that CMV IgG seropositivity is associated with HZ. This finding could add to the growing list of risk factors for HZ.
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http://dx.doi.org/10.1080/21645515.2015.1037999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514428PMC
March 2016

The duration of hypotension determines the evolution of bacteremia-induced acute kidney injury in the intensive care unit.

PLoS One 2014 12;9(12):e114312. Epub 2014 Dec 12.

Department of Critical Care Medicine, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium.

Background: Exploration of the impact of severe hypotension on the evolution of acute kidney injury in septic patients.

Methods And Results: We reviewed the hemodynamic parameters of 137 adults with septic shock and proven blood stream infection in the ICU. Severe hypotension was defined as a mean arterial blood pressure (MAP) ≤65 mmHg. The influence of the duration of severe hypotension on the evolution of acute kidney injury was evaluated according to the RIFLE classification, with day 0 defined as the day of a positive blood stream infection. After bloodstream infection, the probability for a patient to be in Failure was significantly higher than before blood stream infection (OR = 1.94, p = 0.0276). Patients have a significantly higher risk of evolving to Failure if the duration of severe hypotension is longer (OR = 1.02 for each 10 minutes increase in duration of a MAP <65 mmHg, p = 0.0472). A cut-off of at least 51 minutes of severe hypotension (<65 mmHg) or at least 5.5 periods of severe hypotension within 1 day identified patients with increased risk to evolve to Failure.

Conclusions: There is a significant influence of both the duration and the number of periods of severe hypotension on the evolution to Failure. Blood stream infection has a significantly negative effect on the relationship between severe hypotension and Failure.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0114312PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264756PMC
October 2015

Clinical and microbiological impact of discontinuation of fluoroquinolone prophylaxis in patients with prolonged profound neutropenia.

Eur J Haematol 2014 Oct 16;93(4):302-8. Epub 2014 May 16.

Department of Haematology, Antwerp University Hospital, Edegem, Belgium.

Background: Infections remain a leading cause of morbidity and mortality in patients with reduced immunity caused by haematological disease and chemotherapy-induced neutropenia. We evaluated the clinical and microbiological impact of discontinuing fluoroquinolone prophylaxis in these patients.

Methods: We analysed 154 admissions in three sequential periods of 8 months: long-standing use, discontinuation of prophylaxis and reintroduction of prophylaxis. Clinical endpoints were occurrence of febrile neutropenia, bacteraemia, severe sepsis, septic shock, response to antibiotic therapy, total antibiotic consumption and duration of hospital stay. Microbiological analysis included bacterial isolates from stool and blood cultures and their resistance pattern.

Results: No significant increase in serious infectious complications was seen with the discontinuation of prophylaxis. The overall incidence of bacteraemia did not change, but a higher proportion of bacterial isolates were Gram-negative (22.2% vs. 5.9% & 8.6%; P = 0.030), more often multisusceptible (50% vs. 0%) and less fluoroquinolone resistant (10% vs. 100%). Screening of stools showed a higher prevalence of organisms in the discontinuation period (86.7% vs. 37.3% & 55.2%; P ≤ 0.001), but they were more frequently multisusceptible (53.8% vs. 10.5% & 6.3%; P ≤ 0.001). After discontinuation of prophylaxis, fluoroquinolone resistance decreased rapidly from 73.7 to 7.7%, in association with a significant decrease in extended spectrum beta-lactamase (ESBL)-producing isolates from 42.1 to 10.3%. Resistance figures immediately returned to prediscontinuation values after reinstitution of prophylaxis.

Conclusions: No clinically relevant short-term drawbacks were observed with the discontinuation of fluoroquinolone prophylaxis in patients with chemotherapy-induced prolonged profound neutropenia, which led to a significant decrease in fluoroquinolone resistance as well as occurrence of ESBL-producing isolates.
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http://dx.doi.org/10.1111/ejh.12345DOI Listing
October 2014

Influence of frequent infectious exposures on general and varicella-zoster virus-specific immune responses in pediatricians.

Clin Vaccine Immunol 2014 Mar 15;21(3):417-26. Epub 2014 Jan 15.

Centre for Health Economics Research and Modeling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.

Reexposure to viruses is assumed to strengthen humoral and cellular immunity via the secondary immune response. We studied the effects of frequent exposure to viral infectious challenges on immunity. Furthermore, we assessed whether repetitive exposures to varicella-zoster virus (VZV) elicited persistently high immune responses. Blood samples from 11 pediatricians and matched controls were assessed at 3 time points and 1 time point, respectively. Besides the assessment of general immunity by means of measuring T-cell subset percentages, antibody titers and gamma interferon (IFN-γ)/interleukin 2 (IL-2)-producing T-cell percentages against adenovirus type 5 (AdV-5), cytomegalovirus (CMV), tetanus toxin (TT), and VZV were determined. Pediatricians had lower levels of circulating CD4(+)-naive T cells and showed boosting of CD8(+) effector memory T cells. Although no effect on humoral immunity was seen, repetitive exposures to VZV induced persistently higher percentages of IFN-γ-positive T cells against all VZV antigens tested (VZV glycoprotein E [gE], VZV intermediate-early protein 62 [IE62], and VZV IE63) than in controls. T cells directed against latency-associated VZV IE63 benefitted the most from natural exogenous boosting. Although no differences in cellular or humoral immunity were found between the pediatricians and controls for AdV-5 or TT, we did find larger immune responses against CMV antigens in pediatricians. Despite the high infectious burden, we detected a robust and diverse immune system in pediatricians. Repetitive exposures to VZV have been shown to induce a stable increased level of VZV-specific cellular but not humoral immunity. Based on our observations, VZV IE63 can be considered a candidate for a zoster vaccine.
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http://dx.doi.org/10.1128/CVI.00818-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3957663PMC
March 2014

Number of sites of perinatal Candida colonization and neutropenia are associated with nosocomial candidemia in the neonatal intensive care unit patient.

Pediatr Crit Care Med 2010 Mar;11(2):240-5

Department of Pediatrics, Division of Neonatology, Antwerp University Hospital, Belgium.

Objectives: To determine the role of perinatally acquired Candida colonization to invasive Candida infection (candidemia) and to assess risk factors associated with Candida colonization and candidemia in neonatal intensive care unit patients.

Design: Retrospective case-control study.

Setting: Neonatal intensive care unit of a teaching hospital.

Patients: A total of 39 of 3219 (1.2%) who were positive for Candida colonization at birth were compared with 117 noncolonized controls.

Interventions: Routine surveillance cultures for Candida of skin and meconium were performed at admission. All neonates with Candida colonization at birth during a 10-yr period were identified. Each case was matched to place of birth and date of admission with three noncolonized controls.

Measurements And Main Results: Perinatal and neonatal variables were collected. Blood or skin culture was obtained when signs of sepsis or dermatitis were present. Patients with Candida colonization were compared with their noncolonized controls, whereas in this cohort, patients with candidemia were compared with those without by multivariate analysis. Vaginal candidiasis (odds ratio [OR] 15.8, 95% confidence interval [CI] 2.63, 94.77), birth weight below 1000 g (OR 8.1, 95% CI 1.22, 52.26), and vaginal delivery (OR 7.08, 95% CI 1.17, 42.70) were associated with Candida colonization. An increased risk for nosocomial candidemia was independently associated with the number of sites of Candida colonization (OR 24.02, 95% CI 1.89, 304), early neonatal neutropenia (OR 7.15, 95% CI 0.98, 80.95) and illness severity (clinical risk index for babies [CRIB]) score at day 1 (OR 1.38, 95%CI 1.065, 1.811).

Conclusions: Maternal vaginal candidiasis and vaginal birth are risk factors for neonatal colonization. When controlling for illness severity, the number of sites colonized with Candida at birth contributes to neonatal nosocomial candidemia. Early neutropenia increases the risk further. These findings offer opportunities for prevention of Candida infection in neonatal intensive care unit patients.
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http://dx.doi.org/10.1097/PCC.0b013e3181b808fbDOI Listing
March 2010

Decreasing incidence of neonatal nosocomial bloodstream infections in a neonatal intensive care unit: antenatal corticosteroid treatment an innocent bystander?

Eur J Pediatr 2004 Mar 17;163(3):151-7. Epub 2004 Jan 17.

Department of Paediatrics, University Hospital of Antwerp and Faculty of Medicine, Wilrijkstraat 10, 2650, Edegem, Belgium.

Unlabelled: We studied the effect of the use of antenatal steroid treatment on the incidence of nosocomial bloodstream infections (NBSI). All episodes of culture proven NBSI occurring after 96 h of hospitalisation were identified retrospectively during a 10-year period (1991-2001). Throughout the study period, the use of antenatal steroids, demographic characteristics and morbidity of the patients were recorded prospectively. Since 1996 more efforts were made to use antenatal steroids to decrease neonatal morbidity and mortality. The incidence rates of NBSI were compared between period 1 (1991-1995) and period 2 (1996-2001). The overall incidence rate of NBSI dropped significantly from 7.4% (6.1%-8.9%) in period 1 to 5.0% (4.0%-6.2%) in period 2 and was most pronounced in the birth weight category 1000 g-1500 g (11.7%, 7.9%-15.0% to 6.9%, 4.3%-10.5%) and 1500 g-2500 g (3.6%, 2.2%-5.6% to 1.4%, 0.6%-2.8%). Antenatal use of steroids increased overall from 19% in 1991 to 51% in 2001 ( P<0.001). Since 1996 there was a decreasing number of ventilation days ( P=0.011) and decreasing incidence of patent ductus arteriosus ( P=0.001), while the incidence of neonatal surgery, chronic lung disease and duration of hospitalisation remained constant over time.

Conclusion: increased use of antenatal steroids is associated with a decreasing incidence rate of nosocomial bloodstream infections in neonates with birth weights between 1000 g and 2500 g, probably by decreasing the incidence of patent ductus arteriosus and/or due to improved respiratory outcome. This finding needs to be confirmed by randomised control trials or by a large prospective cohort study in similar population groups.
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http://dx.doi.org/10.1007/s00431-003-1388-3DOI Listing
March 2004

Hepatic abscesses associated with umbilical catheterisation in two neonates.

Eur J Pediatr 2003 Jun 27;162(6):406-9. Epub 2003 Mar 27.

Department of Paediatrics, Division of Neonatology, Faculty of Medicine, University of Antwerp, Wilrijkstraat 10, 2650 Edegem, Belgium.

Unlabelled: We describe two neonates with a liver abscess after umbilical venous catheterisation. The first case was a female neonate, born at 32 weeks of gestation. After persistence of elevated inflammatory parameters, an abscess in the right lobe of the liver was diagnosed. Percutaneous drainage under CT guidance was performed. The aspirated pus grew Staphylococcus epidermidis. Inflammatory parameters normalised after 27 days of antimicrobial therapy (vancomycin, cefotaxim, rifampicin). The second case was in a male neonate, born at 29 weeks of gestation. Percutaneously aspirated pus from the liver abscess was cultured and remained sterile. The patient received antimicrobial therapy (vancomycin, cefotaxim, amikacin) for 26 days and was cured with conservative treatment.

Conclusion: hepatic abscess should be considered in any infant with an umbilical catheter-associated sepsis and persistent inflammatory response in spite of adequate antimicrobial therapy, especially when signs of abdominal infection are present.
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http://dx.doi.org/10.1007/s00431-003-1178-yDOI Listing
June 2003

Strategies for selecting antibiotics in intensive care units.

Clin Microbiol Infect 1999 Mar;5 Suppl 1:S29-S34

Departments of Intensive Care.

Crowding of severely ill patients in intensive care units has led worldwide to important increases in nosocomial (ICU-related) infections. Moreover, the nature of these hospital-acquired infections is shifting towards Gram-positive microorganisms, yeast and Gram-negative rods, possessing important resistance genes (e.g. extended spectrum beta-lactamases and inducible Enterobacteriaceae). Ceftazidime and aztreonam are loosing their activity against the Gram-negative microorganisms. The fourth generation cephalosporins have an intrinsic high activity against the inducible Enterobacteriaceae. On our Hematology and Intensive Care units, the introduction of cefepime for nosocomial infections led to a remarkable drop in the number of Enterobacter isolates combined with important decreases in Enterobacter resistance towards several antibiotics.
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http://dx.doi.org/10.1111/j.1469-0691.1999.tb00722.xDOI Listing
March 1999
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