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Summary: Pathogen exposure, including but not limited to herpesviruses, moulds the shape of the immune system, both at a basal state and in response to immune challenge. However, little is known about the impact of high exposure to other viruses on baseline immune signatures and how the immune system copes with repetitive exposures to maintain a balanced functionality. Here we investigated baseline immune signatures, including detailed T cell phenotyping, antigen‐specific CD4+ and CD8+ T cell responses and cytokine profile in paediatric (PED) nurses, who have high occupational exposure to viral pathogens including varicella zoster virus (VZV) and respiratory viruses, and in neonatal intensive care unit (NICU) nurses, as a control group with infrequent occupational exposure. Our results show a lower CD4+ T cell response to two VZV proteins (IE62 and gE) and to tetanus toxoid (TT) in PED nurses who are cytomegalovirus (CMV)‐seronegative, compared to CMV‐seronegative NICU nurses, and that the decline might be more pronounced the more sustained the exposure. This decline might be due to an attrition of VZV‐ and TT‐specific T cells as a result of the continuous pressure on the CD4+ T cell compartment. Moreover, our data suggest that the distinct T cell phenotypes known to be associated with CMV‐seropositivity might be less prominent in PED nurses compared to NICU nurses, implying a plausible attenuating effect of occupational exposure on CMV‐associated immunosenescence. Overall, this pilot study reveals an impact of occupational exposure to viral pathogens on CD4+ T cell immunity and supports further investigation in a larger cohort. Nurses who are CMV‐naïve and occupationally exposed to viral pathogens show a lower CD4+ T‐cell response to varicella zoster virus and tetanus toxoid, and the decline may be more pronounced the more sustained the exposure is. Moreover, CMV‐induced T‐cell immunosenescence may be less prominent in occupationally exposed nurses, implying a plausible attenuating effect of such exposure. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infections (UTIs) are one of the most commonly reported infections in Belgian nursing home residents. In older adults, UTI diagnosis and management is complex, often leading to over-diagnosis and irrational antimicrobial use, stressing the need for a guideline approach., Objectives and Methods: A consensus statement on the prevention, diagnosis and treatment of UTIs in older adults residing in nursing homes was developed in a collaborative effort between the Flemish Hospital Outbreak Support Teams, the Flemish Agency for Care and Health, the Association of the Flemish Coordinating and Advising General Practitioners, the Belgian Association of Urology, the Belgian Society for Gerontology and Geriatrics and PhD researchers based on a combination of clinical expertise, (inter)national guidelines and peer-reviewed studies., Results: Optimizing fluid intake, appropriate toilet behaviour and posture, mobilization and local estrogen therapy in women are of proven value in UTI prevention, whereas the use of cranberry and probiotics is not to be advocated. The importance of avoiding bladder catheterization is stressed. In older nursing home residents, the diagnosis of UTIs remains challenging, mostly due to atypical systemic symptoms. A consensus diagnostic algorithm for UTI among residents with and without a urinary catheter was developed, including the presence of suggestive clinical symptoms and a positive urine culture. Urine dipsticks have a high negative but a low positive predictive value. C-reactive protein point-of-care testing is not recommended. Asymptomatic bacteriuria should not be screened for, in order to avoid unnecessary triggers for treatment. In cystitis, nitrofurantoin is the primary choice for treatment, with fosfomycin as an alternative; in prostatitis and uncomplicated pyelonephritis a fluoroquinolone is the advocated empirical antimicrobial.

Objectives: Linezolid-resistant opportunistic human pathogens Enterococcus faecalis and Enterococcus faecium are emerging health threats as limited therapeutic options remain. The aim of this study was to investigate the epidemiology, resistance mechanisms, and genetic diversity of linezolid-resistant enterococci (LRE) isolated between 2013 and 2021 and received at the Belgian National Reference Centre (NRC) for Enterococci., Methods: Linezolid susceptibility testing was performed upon request on 2458 submitted enterococci strains. Whole-genome sequencing was performed on all LRE strains., Results: Seventy-eight LRE human isolates, of which 63 (81%) E. faecalis and 15 (19%) E. faecium strains, were submitted to the Belgian NRC for Enterococci. Of the linezolid-resistant E. faecalis strains, 97% harboured the optrA gene (56% wild-type pE349) and 3% the poxtA gene. Of the linezolid-resistant E. faecium strains, 54% harboured the G2576T point mutation in the V domain of the 23S rRNA genes, 23% the poxtA, and 23% the optrA gene. Furthermore, two E. faecium strains were identified with a combination of two resistance mechanisms ([i] optrA and poxtA, and [ii] cfr(B) and G2576T point mutation, respectively). Vancomycin resistance was observed in 15% (n = 12) of the LRE. ST480 (n = 42/63 typed strains, 67%) was the most frequently detected sequence type (ST) in linezolid-resistant E. faecalis strains, while ST203 (n = 5/15 typed strains, 33%) was the most frequently detected ST in linezolid-resistant E. faecium strains., Conclusions: E. faecalis isolates harbouring optrA were the predominant LRE in Belgium, with ST480 as the most prominent multilocus sequence typing. Linezolid resistance in E. faecium could be attributed to either chromosomal mutations or transferable resistance determinants., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The role of T cell receptor (TCR) diversity in infectious disease susceptibility is not well understood. We use a systems immunology approach on three cohorts of herpes zoster (HZ) patients and controls to investigate whether TCR diversity against varicella-zoster virus (VZV) influences the risk of HZ. We show that CD4 + T cell TCR diversity against VZV glycoprotein E (gE) and immediate early 63 protein (IE63) after 1-week culture is more restricted in HZ patients. Single-cell RNA and TCR sequencing of VZV-specific T cells shows that T cell activation pathways are significantly decreased after stimulation with VZV peptides in convalescent HZ patients. TCR clustering indicates that TCRs from HZ patients co-cluster more often together than TCRs from controls. Collectively, our results suggest that not only lower VZV-specific TCR diversity but also reduced functional TCR affinity for VZV-specific proteins in HZ patients leads to lower T cell activation and consequently affects the susceptibility for viral reactivation., Competing Interests: Declaration of interests K.L., P.M., and B.O. are co-founders, board directors, and shareholders of ImmuneWatch. None of the work presented here was influenced in any way by this. ImmuneWatch had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Nontyphoidal Salmonella serovars predominantly cause gastrointestinal infections. However, other clinical presentations, including urogenital infections, have been reported, although they are rather rare., Case Presentation: This case is about a 33-year-old woman diagnosed with Salmonella enterica serovar Hvittingfoss ( S. Hvittingfoss) bacteremia and endometritis six days post uterine aspiration in the context of a missed abortion. She had traveled to Indonesia two weeks prior to the positive blood and cervical culture. She never developed gastrointestinal symptoms but was found to carry S. Hvittingfoss in her stool sample. The patient was successfully treated with a seven-day course of iv ciprofloxacin., Conclusions: S. Hvittingfoss is a rare serovar that has caused a few outbreaks of foodborne infections in Asia, the United States, and Australia. To the best of our knowledge, this is the first reported case of Salmonella urogenital infection caused by this serovar. Salmonella as a cause of urogenital infections is rare but not uncommon. Therefore, it should be considered in identifying members of the Enterobacterales among urogenital flora in cases of severe urogenital infections, especially when other cultures remain negative.

The global prevalence and spread of multidrug-resistant organisms (MDROs) represent an emerging public health threat. Day care centre (DCC) attendance is a risk factor for MDRO carriage in children and their environment. This study aimed to map the epidemiology of carriage and potential transmission of these organisms within 18 Flemish DDCs (Belgium). An MDRO prevalence survey was organised between November 2018 and February 2019 among children attending the centres. Selective chromogenic culture media were used for the detection of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E), carbapenemase-producing Enterobacterales (CPE), and vancomycin-resistant Enterococci (VRE) in faecal swabs obtained from diapers or jars (n = 448). All isolated MDROs were subjected to resistance gene sequencing. A total of 71 of 448 samples (15.8%) yielded isolates of ESBL-E with a predominance of Escherichia coli (92.2% of ESBL-E) and ESBL resistance gene bla CTX-M-15 (50.7% of ESBL coding genes in E. coli ). ESBL-E prevalence varied between DCCs, ranging from 0 to 50%. Transmission, based on the clonal relatedness of ESBL-E strains, was observed. CPE was identified in only one child carrying an E. coli with an OXA-244 gene. VRE was absent from all samples. The observed prevalence of ESBL-E in Flemish DCCs is high compared with previous studies, and our findings re-emphasise the need for rigorous hygiene measures within such centres to control the further spread of MDROs in the community.

Background and Importance: Different triage systems can be used to screen for sepsis and are often incorporated into local electronic health records. Often the design and interface of these digitalizations are not audited, possibly leading to deleterious effects on screening test performance., Objective: To audit a digital version of the MTS for detection of sepsis during triage in the ED., Design: A single-center retrospective study SETTINGS AND PARTICIPANTS: Patients (n=29766) presenting to an ED of a tertiary-care center who received formal triage were included., Outcome Measures and Analysis: Calculated performance measures included sensitivity, specificity, likelihood ratios, and AUC for the detection of sepsis. Errors in the application of the specific sepsis discriminator of the MTS were recorded., Main Results: A total of 189 (0.7%) subjects met the Sepsis-3 criteria, with 47 cases meeting the criteria for septic shock. The MTS had a low sensitivity of 47.6% (95% CI 40.3 to 55.0) for allocating sepsis patients to the correct triage category. However, specificity was high at 99.4% (95% CI 99.3 to 99.5)., (© 2022. The Author(s).)

Introduction: The B.1.617.2 SARS-CoV-2 or Delta variant, first detected in India, has shown a rapid global spread due to its high transmissibility and now represents more than 99% of the currently circulating variants in Europe., Methods and Result: In May 2021, two ships that had recently arrived in the Port of Antwerp reported crew members with COVID-like symptoms. SARS-CoV-2 RNA was detected in nasopharyngeal swabs in 30 out of 45 skippers and the B.1.617.2 variant was identified via whole genome sequencing. Crew members were isolated or quarantined and repeatedly tested to assess the evolution of their SARS-CoV-2 viral load based on the cycle threshold (CT) values of the PCR reaction. Viral cultures were also taken at day 7 to detect viable virus and were compared with the subjects CT value at that moment. The shipper's clinical condition was closely observed using a digital home monitoring tool. Eleven crew members (37%) required hospitalization, with CT values of SARS-CoV-2 RNA being a good predictive factor for the hospitalization need. Furthermore, a clear correlation between CT values and positive viral culture was observed, hinting infectiousness even longer than 10 days after the intitial positive PCR test., Conclusion: Our study of 2 Delta variant clusters shows that the initial CT value is a good predictor for hospitalization need and suggests that patients infected with this variant may remain infectious for a longer time period.

The use of saliva for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sparks debate due to presumed lower sensitivity and lack of standardization. Our aim was to evaluate the performance characteristics of (i) saliva collected by the ORAcollect TM device as a matrix for SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR), and (ii) 2 saliva rapid antigen tests (AgRDT). From 342 ambulatory individuals, both a nasopharyngeal swab and saliva sample via ORAcollect TM were obtained for a SARS-CoV-2 RT-PCR test. Furthermore, 54 and 123 additionally performed the V-Chek TM or Whistling TM saliva AgRDT. In total, 35% of individuals screened positive for SARS-CoV-2 via nasopharyngeal swab. Saliva, as a matrix for the RT-PCR, had a specificity of 96.5% and a negative predictive value (NPV) of 91.3%. Interestingly, 6 out of 8 patients thought to be false positive in saliva re-tested positive by nasopharyngeal sampling after 2 to 9 days. Both V-Chek TM and Whistling TM AgRDT had a lack of sensitivity, resulting in an NPV of 66.9 and 67.3%, respectively. Saliva proved to be a sensitive and specific matrix for SARS-CoV-2 detection by the RT-PCR. In this setting, saliva might have an earlier window of detection than the nasopharyngeal swab. By contrast, both AgRDT showed an unacceptably low sensitivity and NPV.

Antigen recognition through the T cell receptor (TCR) αβ heterodimer is one of the primary determinants of the adaptive immune response. Vaccines activate naïve T cells with high specificity to expand and differentiate into memory T cells. However, antigen-specific memory CD4 T cells exist in unexposed antigen-naïve hosts. In this study, we use high-throughput sequencing of memory CD4 TCRβ repertoire and machine learning to show that individuals with preexisting vaccine-reactive memory CD4 T cell clonotypes elicited earlier and higher antibody titers and mounted a more robust CD4 T cell response to hepatitis B vaccine. In addition, integration of TCRβ sequence patterns into a hepatitis B epitope-specific annotation model can predict which individuals will have an early and more vigorous vaccine-elicited immunity. Thus, the presence of preexisting memory T cell clonotypes has a significant impact on immunity and can be used to predict immune responses to vaccination., Competing Interests: GE, PM, EB, ND, NK, AS, HJ, AS, HD, ME, ES, EL, PT, GM, PV, PB, KL, VV, BO No competing interests declaredNo competing interests declared, (© 2022, Elias et al.)

Objectives: To evaluate a testing algorithm for the rapid identification of severe acute respiratory syndrome coronavirus 2 (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 percentage agreement (OPA) of 98.5%. The ΔH69-V70-specific (n = 178) and E484K-specific (n = 401) assays had 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-specific (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., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: There is currently no consensus on optimal duration of antibiotic treatment in febrile neutropenia. We report on the clinical impact of implementation of antibiotic de-escalation and discontinuation strategies based on the Fourth European Conference on Infections in Leukaemia (ECIL-4) recommendations in high-risk hematological patients., Methods: We studied 446 admissions after introduction of an ECIL-4-based protocol (hereafter "ECIL-4 group") in comparison to a historic cohort of 512 admissions. Primary clinical endpoints were the incidence of infectious complications including septic shock, infection-related intensive care unit (ICU) admission, and overall mortality. Secondary endpoints included the incidence of recurrent fever, bacteremia, and antibiotic consumption., Results: Bacteremia occurred more frequently in the ECIL-4 group (46.9% [209/446] vs 30.5% [156/512]; P  < .001), without an associated increase in septic shock (4.7% [21/446] vs 4.5% [23/512]; P  = .878) or infection-related ICU admission (4.9% [22/446] vs 4.1% [21/512]; P  = .424). Overall mortality was significantly lower in the ECIL-4 group (0.7% [3/446] vs 2.7% [14/512]; P  = .016), resulting mainly from a decrease in infection-related mortality (0.4% [2/446] vs 1.8% [9/512]; P  = .058). Antibiotic consumption was significantly reduced by a median of 2 days on antibiotic therapy (12 vs 14; P  = .001) and 7 daily antibiotic doses (17 vs 24; P  < .001) per admission period., Conclusions: Our results support implementation of ECIL-4 recommendations to be both safe and effective based on real-world data in a large high-risk patient population. We found no increase in infectious complications and total antibiotic exposure was significantly reduced., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Pseudomonas monteilii is an environmental contaminant and is considered as an emerging human pathogen. We report the case of a Pseudomonas monteilii granulomatous lymphadenitis in a two-year-old girl. Clinical Presentation and Intervention: A two-year-old, previously healthy, Caucasian girl developed a unilateral inguinofemoral granulomatous lymphadenitis with Pseudomonas monteilii . 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 Bartonella henselae 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 P.monteilii 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. Conclusions: 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.

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., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

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.

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.

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.

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.

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.

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.

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.