Search

Background & Aims Approximately 5%-10% of the general population respond inadequately to licensed recombinant hepatitis B vaccines. We assessed the immunogenicity and safety of a new HBAI20 vaccine, consisting of a new AI20 adjuvant (20-mu g recombinant human IL-2 attached to 20-mu g aluminium hydroxide) in combination with HBVaxPro (R)-10 mu g.Methods In a double-blinded, randomised, controlled phase 2 trial, 18- to 59-year-old healthy non-responders (titre = 10 mIU/ml) measured 1-3 months following the third vaccination.Results A total of 133 participants were randomised to receive either HBAI20 vaccine (n = 101) or HBVaxPro (R)-10 mu g (n = 32). In the modified intention-to-treat analysis, the seroprotection rate after the third vaccination was 92.0% (80/87) in the HBAI20 group and 79.3% (23/29) in the HBVaxPro (R)-10-mu g group, P = .068. Using a generalised linear mixed model to adjust for stratification factors, a higher odds of seroprotection with HBAI20 vaccine was shown (adjusted odds ratio = 3.48, P = .028). Frequency of mild and moderate local adverse events was greater in the HBAI20 group than in the HBVaxPro (R)-10 mu g. Rates of severe local adverse events and systemic adverse events were low and similar in both groups.Conclusions In this group of hepatitis B vaccine non-responders, the HBAI20 vaccine demonstrated a higher seroprotection rate when adjusting for stratification factors and a similar safety profile compared to the licensed recombinant HBVaxPro (R)-10 mu g. The study was partially sponsored by CyTuVax BV, and the sponsor was involved in the study design, interpretation of the data, review and approval of the manuscript in accordance with good clinical practice. The funding source had no input in data collection and statistical analysis of the data. ÖK, CK, NH and AOL had full access to all the data in the study and the corresponding CyTuVax BV sponsored the study. The authors would like to thank the many participants and would like to acknowledge Mohannad Altabban (CyTuVax BV, Maastricht, the Netherlands), the staffs of the Ease Travel Clinic & Health Support (Maastricht, the Netherlands), the Department of Gastroenterology and Hepatology (Genk, Belgium) and Centre for the Evaluation of Vaccination, Vaccine & Infectious Disease Institute (Antwerp, Belgium) for their careful performance of the study.

Background Hepatitis B virus (HBV) immunity is recommended to optimize outcomes after solid organ transplantation (SOT). This study assessed the prevalence and predictors of HBV immunity at the time patients were placed on transplant waiting list over a period from 1997 to 2019 in a low HBV endemic region. Methods Data were obtained from the University Hospitals Leuven transplant database. Minors and patients with past/current HBV infection were excluded. From 1986, Belgian patients are covered by the universal infant vaccination; therefore, birth cohort was stratified in those born >= 1986 vs The study population consisted of 3297 SOT candidates. HBV immunity rate was superior in renal transplant candidates (55.3%), and this number was 21.5%, 15.4% and 16.8% for liver, cardiac and pulmonary transplant candidates, respectively,P < .001. Among liver transplant candidates, HBV immunity rate was 14.8% in decompensated cirrhotic patients and 27.9% in those without advanced cirrhosis (P < .001). The overall immunity rate increased from 19.3% in period 1997-2008 to 32.8% in 2009-2019,P < .001. In multivariable analyses, younger age (odds ratio (OR) 95% confidence interval (CI): 0.97-0.98,P < .001) and birth cohort >= 1986 (OR 95% CI: 1.18-2.66,P = .006) were associated with increased HBV immunity. Conclusion An increase in HBV immunity was observed over a 20-year period related to the introduction of universal infant HBV vaccination. Nevertheless, this study highlights the low overall HBV immunity at the time of listing for organ transplantation and points out the need of an increased awareness and vaccination strategy at an early disease stage. This research is part of the Limburg Clinical Research Center (LCRC) UHasselt-ZOL-Jessa, supported by the foundation Limburg Sterk Merk, province of Limburg, Flemish government, Hasselt University, Jessa Hospital and Ziekenhuis Oost-Limburg. The authors specially thank Bruno Desschans and Albert Herelixka for the management of the transplant database. Koc, OM (corresponding author), Hasselt Univ, Fac Med & Life Sci, Martelarenlaan 42, B-3500 Hasselt, Belgium. ozgur.koc@uhasselt.be

Background and Aims Hepatitis B virus (HBV) vaccination is recommended to all employees who have an occupational risk in the Netherlands. This study assessed the determinants of the immune response to primary standard three-dose HBV vaccination (0, 1, 6 months), with the main focus on ethnicity. Methods Out of 76 239 individuals who received HBV vaccination between April 1983 and December 2017, 11 567 persons with a known country of birth and complete vaccination schedule were included in this study. Weighted multiple logistic regression with Firth's bias adjustment was used to assess the determinants of nonresponse (anti-HBs < 10 mIU/mL) and low response (anti-HBs 10-99 mIU/mL). Results Baseline characteristics of the study population (n = 11 567) were as follows: mean age 27.5 years (95% confidence interval [CI], 27.23-27.72), 99.4% born in the Netherlands and 93.5% of Western European origin. Of all identified subjects, 180 (1.6%) were HBV vaccine nonresponders and 549 (4.8%) were low responders. When compared with individuals aged 40 years in comparison with those younger than 40 years, P < .001. All nonresponders were born in the Netherlands. Although no significant association was found between nonresponse and individuals of Western European origin (adjusted odds ratio [aOR] = 1.20; 95% CI, 0.66-2.44; P = .163), low response to HBV vaccination was significantly associated with Western European origin (aOR = 2.21; 95% CI, 1.41-3.86; P = .001). Significant determinants for nonresponse were older age at vaccination (aOR = 1.06; 95% CI, 1.06-1.07; P < .001) and male gender (aOR = 2.51; 95% CI, 1.97-3.22; P < .001). Conclusions The nonresponse rate was low in our study population. Our findings suggest that the vaccines being used for the primary vaccination are probably less immunogenic for older individuals, males, and persons of Western European origin. foundation Limburg Sterk Merk; province of Limburg; Flemish government; Hasselt University; Ziekenhuis OostLimburg; Jessa Hospital

IntroductionEarly differentiation between emergency department (ED) patients with and without corona virus disease (COVID-19) is very important. Chest CT scan may be helpful in early diagnosing of COVID-19. We investigated the diagnostic accuracy of CT using RT-PCR for SARS-CoV-2 as reference standard and investigated reasons for discordant results between the two tests.MethodsIn this prospective single centre study in the Netherlands, all adult symptomatic ED patients had both a CT scan and a RT-PCR upon arrival at the ED. CT results were compared with PCR test(s). Diagnostic accuracy was calculated. Discordant results were investigated using discharge diagnoses.ResultsBetween March 13(th)and March 24(th)2020, 193 symptomatic ED patients were included. In total, 43.0% of patients had a positive PCR and 56.5% a positive CT, resulting in a sensitivity of 89.2%, specificity 68.2%, likelihood ratio (LR)+ 2.81 and LR- 0.16. Sensitivity was higher in patients with high risk pneumonia (CURB-65 score >= 3; n = 17, 100%) and with sepsis (SOFA score >= 2; n = 137, 95.5%). Of the 35 patients (31.8%) with a suspicious CT and a negative RT-PCR, 9 had another respiratory viral pathogen, and in 7 patients, COVID-19 was considered likely. One of nine patients with a non-suspicious CT and a positive PCR had developed symptoms within 48 hours before scanning.DiscussionThe accuracy of chest CT in symptomatic ED patients is high, but used as a single diagnostic test, CT can not safely diagnose or exclude COVID-19. However, CT can be used as a quick tool to categorize patients into "probably positive" and "probably negative" cohorts.

BackgroundThe course of the disease in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in mechanically ventilated patients is unknown. To unravel the clinical heterogeneity of the SARS-CoV-2 infection in these patients, we designed the prospective observational Maastricht Intensive Care COVID cohort;MaastrICCht. We incorporated serial measurements that harbour aetiological, diagnostic and predictive information. The study aims to investigate the heterogeneity of the natural course of critically ill patients with SARS-CoV-2 infection.Study populationMechanically ventilated patients admitted to the Intensive Care with SARS- CoV-2 infection.Main messageWe will collect clinical variables, vital parameters, laboratory variables, mechanical ventilator settings, chest electrical impedance tomography, electrocardiograms, echocardiography as well as other imaging modalities to assess heterogeneity of the natural course of SARS-CoV-2 infection in critically ill patients. TheMaastrICChtcohort is, also designed to foster various other studies and registries and intends to create an open-source database for investigators. Therefore, a major part of the data collection is aligned with an existing national Intensive Care data registry and two international COVID-19 data collection initiatives. Additionally, we create a flexible design, so that additional measures can be added during the ongoing study based on new knowledge obtained from the rapidly growing body of evidence.ConclusionThe spread of the COVID-19 pandemic requires the swift implementation of observational research to unravel heterogeneity of the natural course of the disease of SARS- CoV-2 infection in mechanically ventilated patients. Our design is expected to enhance aetiological, diagnostic and prognostic understanding of the disease. This paper describes the design of theMaastrICChtcohort.Strengths and limitations of this studySerial measurements that characterize the disease course of SARS-CoV-2 infection in mechanically ventilated patientsData collection and analysis according to a predefined protocolFlexible, evolving design enabling the study of multiple aspects of SARS-CoV-2 infection in mechanically ventilated patientsSingle centre, including only ICU patients

To understand the dynamics behind the worldwide spread of the mcr-1 gene, we determined the population structure of Escherichia coli and of mobile genetic elements (MGEs) carrying the mcr-1 gene. After a systematic review of the literature we included 65 E. coli whole genome sequences (WGS), adding 6 recently sequenced travel related isolates, and 312 MLST profiles. We included 219 MGEs described in 7 Enterobacteriaceae species isolated from human, animal and environmental samples. Despite a high overall diversity, 2 lineages were observed in the E. coli population that may function as reservoirs of the mcr-1 gene, the largest of which was linked to ST10, a sequence type known for its ubiquity in human faecal samples and in food samples. No genotypic clustering by geographical origin or isolation source was observed. Amongst a total of 13 plasmid incompatibility types, the IncI2, IncX4 and IncHI2 plasmids accounted for more than 90% of MGEs carrying the mcr-1 gene. We observed significant geographical clustering with regional spread of IncHI2 plasmids in Europe and IncI2 in Asia. These findings point towards promiscuous spread of the mcr-1 gene by efficient horizontal gene transfer dominated by a limited number of plasmid incompatibility types.

Contains fulltext : 177025.pdf (Publisher’s version ) (Closed access) Combining voriconazole and flucloxacillin is indicated in patient cohorts experiencing both invasive aspergillosis and Gram-positive infections (e.g., patients with chronic granulomatous disease or postinfluenza pulmonary aspergillosis). We report a highly relevant interaction between voriconazole and flucloxacillin, resulting in subtherapeutic plasma voriconazole concentrations in more than 50% of patients, that poses a severe threat if not managed properly.

Background: Recently, the first plasmid-mediated colistin-resistance gene, mcr-1, was reported. Colistin is increasingly used as an antibiotic of last resort for the treatment of infections caused by carbapenem-resistant bacteria, which have been rapidly disseminating worldwide in recent years. Objectives: The reported carriage rate of mcr-1 in humans remains sporadic thus far, except for those reported in Chinese populations. We aimed to determine its presence in the faecal metagenomes of healthy Dutch travellers between 2010 and 2012. Methods: Faecal metagenomic DNA of pre-and post-travel samples from 122 healthy Dutch long-distance travellers was screened for the presence of mcr-1 using a TaqMan quantitative PCR assay, which was designed in this study. All positive samples were confirmed by sequencing of the amplicons. Results: The mcr-1 gene was detected in 6 (4.9%, 95% CI = 2.1%-10.5%) of 122 healthy Dutch long-distance travellers after they had visited destinations in South(-east) Asia or southern Africa between 2011 and 2012. One of these participants was already found to be positive before travel. Conclusions: Our study highlights the potential of PCR-based targeted metagenomics as an unbiased and sensitive method to screen for the carriage of the mcr-1 gene and suggests that mcr-1 is widespread in various parts of the world. The observation that one participant was found to be positive before travel suggests that mcr-1 may already have disseminated to the microbiomes of Dutch residents at a low prevalence, warranting a more extensive investigation of its prevalence in the general population and possible sources.

Contains fulltext : 172306.pdf (Publisher’s version ) (Closed access) A survey of diagnosis and treatment of invasive aspergillosis was conducted in eight University Medical Centers (UMCs) and eight non-academic teaching hospitals in the Netherlands. Against a background of emerging azole resistance in Aspergillus fumigatus routine resistance screening of clinical isolates was performed primarily in the UMCs. Azole resistance rates at the hospital level varied between 5% and 10%, although rates up to 30% were reported in high-risk wards. Voriconazole remained first choice for invasive aspergillosis in 13 out of 16 hospitals. In documented azole resistance 14 out of 16 centres treated patients with liposomal amphotericin B.

Background Sepsis leads to high mortality, therefore risk stratification is important. The abbMEDS (abbreviated Mortality Emergency Department Sepsis) score assesses sepsis severity and predicts mortality. In community-acquired pneumonia, the CURB-65 (Confusion, Urea, Respiration, Blood pressure, Age) also provides support in clinical decisions regarding antibiotic treatment and clinical disposition. We investigated the predictive value and feasibility of the abbMEDS and CURB-65 in sepsis patients at the ED and the relationship between the scores and antibiotic treatment and clinical disposition (i.e. admission and type of ward). Methods In this retrospective cohort study, we included 725 sepsis patients at the ED. We investigated the value in predicting 28-day mortality and feasibility of both scores. We calibrated the abbMEDS. We further assessed the relationship between the three risk categories per score and antibiotic treatment (i.e. oral and intravenous narrow or broad-spectrum) and clinical disposition. Results Both abbMEDS and CURB-65 were good predictors of 28-day mortality (13.0 %) (AUC 0.77 [95 % CI 0.72 – 0.83] and 0.73 [95 % CI 0.67 - 0.78], respectively) and feasible (complete score 92.7 and 93.9 %, respectively). In the high risk category of the abbMEDS, all patients were admitted and treated with intravenous broad-spectrum antibiotics. In the high risk category of the CURB-65, 2.5 % were not admitted and 4.4 % received no antibiotics. Conclusion Both abbMEDS and CURB-65 are good predictors of 28-day mortality in septic ED patients. The abbMEDS is well calibrated and matches current clinical decisions concerning antibiotic treatment and clinical disposition, while this is less so for the CURB-65. In the future, use of the abbMEDS at the ED may improve sepsis care when its value as a decision support tool can be confirmed. Electronic supplementary material The online version of this article (doi:10.1186/s12873-015-0056-z) contains supplementary material, which is available to authorized users.

We investigated the effect of international travel on the gut resistome of 122 healthy travelers from the Netherlands by using a targeted metagenomic approach. Our results confirm high acquisition rates of the extended-spectrum β-lactamase encoding gene blaCTX-M, documenting a rise in prevalence from 9.0% before travel to 33.6% after travel (p

Background Hospital HIV care and public sexual health care (a Sexual Health Care Centre) services were integrated to provide sexual health counselling and sexually transmitted infections (STIs) testing and treatment (sexual health care) to larger numbers of HIV patients. Services, need and usage were assessed using a patient perspective, which is a key factor for the success of service integration. Methods The study design was a one-group pre-test and post-test comparison of 447 HIV-infected heterosexual individuals and men who have sex with men (MSM) attending a hospital-based HIV centre serving the southern region of the Netherlands. The intervention offered comprehensive sexual health care using an integrated care approach. The main outcomes were intervention uptake, patients’ pre-test care needs (n=254), and quality rating. Results Pre intervention, 43% of the patients wanted to discuss sexual health (51% MSM; 30% heterosexuals). Of these patients, 12% to 35% reported regular coverage, and up to 25% never discussed sexual health topics at their HIV care visits. Of the patients, 24% used our intervention. Usage was higher among patients who previously expressed a need to discuss sexual health. Most patients who used the integrated services were new users of public health services. STIs were detected in 13% of MSM and in none of the heterosexuals. The quality of care was rated good. Conclusions The HIV patients in our study generally considered sexual health important, but the regular counselling and testing at the HIV care visit was insufficient. The integration of public health and hospital services benefited both care sectors and their patients by addressing sexual health questions, detecting STIs, and conducting partner notification. Successful sexual health care uptake requires increased awareness among patients about their care options as well as a cultural shift among care providers.

We report a patient, which we believe is the first, with a thoracoabdominal aortic aneurysm, Crawford type IV, caused by Q fever (Coxiella burnetii). Treatment consisted of antibiotic therapy started preoperatively and continued postoperatively and an open repair, including resection of the infected aneurysm, replacement with a rifampin-soaked polyester graft, and an ()mental wrap covering the grafts. After 13 months of follow-up, the patient had no signs of infection, and results of laboratory findings were normal. (J Vase Surg 2011;53:1402-4.)

Item does not contain fulltext BACKGROUND: Ocular candidiasis is a major complication of candidemia. The incidence, risk factors, and outcome of eye involvement during candidemia are largely unknown. We prospectively studied the ocular manifestations of candidemia in a large, worldwide, randomized multicenter trial that compared voriconazole with amphotericin B followed by fluconazole for the treatment of candidemia. METHODS: Nonneutropenic patients with blood cultures positive for Candida species were assigned treatment with voriconazole or with amphotericin B followed by fluconazole in a randomized 2:1 ratio. Dilated fundoscopy was performed in each patient at baseline, on day 7, at 2 and 6 weeks after the end of treatment (EOT), and, if clinically indicated, at 12 weeks after EOT. RESULTS: Of 370 patients, 49 had findings consistent with the diagnosis of ocular candidiasis at baseline, and an additional 11 patients developed abnormalities during treatment, totaling 60 patients with eye involvement (16%). Of these patients, probable Candida eye infection was diagnosed in 40 patients (6 with endophthalmitis, 34 with chorioretinitis), and possible Candida eye infection in 20 (all with chorioretinitis). The duration of candidemia was significantly longer in patients with ocular candidiasis (median, 4 days; range, 1-18 days) compared with patients without ocular involvement (median, 3 days; range 1-26 days; log rank, P = .026). Therapy with either voriconazole (44 cases) or amphotericin B followed by fluconazole (16 cases) was successful in 65% of patients; outcome was not evaluable in 32% and was unfavorable in 3%. CONCLUSIONS: Ocular involvement occurred in 16% of patients with candidemia; however, endophthalmitis was uncommon (1.6%). Treatment with either voriconazole or amphotericin B followed by fluconazole was successful for ocular candidiasis in most cases with follow-up.

Contains fulltext : 58102.pdf (Publisher’s version ) (Closed access) Resolution of invasive fungal infections is often dependent on recovery from an immunocompromised state, which indicates that host defense mechanisms are extremely important in the clearance of fungal pathogens. Immunotherapy aimed at enhancement of host defense mechanisms may improve clinical outcome of invasive mycoses. The design of trials of immunotherapy against fungal pathogens requires profound knowledge of the host defense mechanisms that are involved in invasive fungal infections. Prospective phase II studies with recombinant granulocyte colony-stimulating factor and interferon-gamma have been done. Recombinant interferon-gamma is a candidate for phase III trials of adjunctive immunotherapy for cryptococcal meningitis, invasive aspergillosis, and candidemia, but the proper design of future trials will be crucial to establish whether immunotherapy is of clinical value in the treatment of invasive fungal infections.