Re-evaluation of routine dengue virus serology in travelers in the era of Zika virus emergence

Background Diagnostic requests for both Zika virus (ZIKV) and dengue virus (DENV) infections in returning travelers have significantly increased during the recent ZIKV outbreak in the Americás. These flaviviruses have overlapping clinical syndromes and geographical distribution, but diagnostic differentiation is important because of different clinical consequences. As flaviviruses are known to have a short viremic period, diagnostics often rely on serological methods, which are challenging due to extensive cross-reactive antibodies. Objective To re-evaluate the performance of DENV serological assays in laboratory confirmed ZIKV-infected travelers. Study design The extent of cross-reactivity of the DENV NS1 antigen, IgM and IgG ELISA was analyzed in 152 clinical blood samples collected from 69 qRT-PCR and 24 virus neutralization titer (VNT) confirmed ZIKV-infected travelers. Results The majority of travelers in the presented cohort returned to the Netherlands from Suriname and presented with symptoms of fever and rash. Twenty-three percent of the female travelers were pregnant. None of the 39 ZIKV RNA positive blood samples were cross-reactive in the DENV NS1 antigen ELISA. The rates of cross-reactivity of the DENV IgM and IgG ELISÁs were 31% and 54%, respectively, after excluding travelers with (potential) previous DENV exposure. Conclusions Althoug

Safety, Immunogenicity, and Protective Efficacy of Intradermal Immunization with Aseptic, Purified, Cryopreserved Plasmodium falciparum Sporozoites in Volunteers Under Chloroquine Prophylaxis

Immunization of volunteers under chloroquine prophylaxis by bites of *Plasmodium falciparum* sporozoite (PfSPZ)–infected mosquitoes induces > 90% protection against controlled human malaria infection (CHMI). We studied intradermal immunization with cryopreserved, infectious PfSPZ in volunteers taking chloroquine (PfSPZ chemoprophylaxis vaccine [CVac]). Vaccine groups 1 and 3 received 3x monthly immunizations with 7.5 x 10^4 PfSPZ. Control groups 2 and 4 received normal saline. Groups 1 and 2 underwent CHMI (#1) by mosquito bite 60 days after the third immunization. Groups 3 and 4 were boosted 168 days after the third immunization and underwent CHMI (#2) 137 days later. Vaccinees (11/20, 55%) and controls (6/10, 60%) had the same percentage of mild to moderate solicited adverse events. After CHMI #1, 8/10 vaccinees (group 1) and 5/5 controls (group 2) became parasitemic by microscopy; the two negatives were positive by quantitative real-time polymerase chain reaction (qPCR). After CHMI #2, all vaccinees in group 3 and controls in group 4 were parasitemic by qPCR. Vaccinees showed weak antibody and no detectable cellular immune responses. Intradermal immunization with up to 3 x 10^5 PfSPZ-CVac was safe, but induced only minimal immune responses and no sterile protection against Pf CHMI. INTRODUCTIO

Mortality related to Verona Integron-encoded Metallo-β-lactamase-positive Pseudomonas aeruginosa: Assessment by a novel clinical tool

Background: Verona Integron-encoded Metallo-β-lactamase-positive Pseudomonas aeruginosa (VIM-PA) can cause nosocomial infections and may be responsible for increased mortality. Multidrug resistance in VIM-PA complicates treatment. We aimed to assess the contribution of VIM-PA to mortality in patients in a large tertiary care hospital in the Net

Molecular characterization of MRSA collected during national surveillance between 2008 and 2019 in the Netherlands

Background.Although the Netherlands is a country with a low endemic level, methicillin-resistant Staphylococcus aureus (MRSA) poses a significant health care problem. Therefore, high coverage national MRSA surveillance has been in place since 1989. To monitor possible changes in the type-distribution and emergence of resistance and virulence, MRSA isolates are molecularly characterized.Methods.All 43,321 isolates from 36,520 persons, collected 2008-2019, were typed by multiple-locus variable number tandem repeats analysis (MLVA) with simultaneous PCR detection of the mecA, mecC and lukF-PV genes, indicative for PVL. Next-generation sequencing data of 4991 isolates from 4798 persons were used for whole genome multi-locus sequence typing (wgMLST) and identification of resistance and virulence genes.Results.We show temporal change in the molecular characteristics of the MRSA population with the proportion of PVL-positive isolates increasing from 15% in 2008-2010 to 25% in 2017-2019. In livestock-associated MRSA obtained from humans, PVL-positivity increases to 6% in 2017-2019 with isolates predominantly from regions with few pig farms. wgMLST reveals the presence of 35 genogroups with distinct resistance, virulence gene profiles and specimen origin. Typing shows prolonged persistent MRSA carriage with a mean carriage period of 407 days. There is a clear spatial and a weak temporal relationship between isolates that clustered in wgMLST, indicative for regional spread of MRSA strains.Conclusions.Using molecular characterization, this exceptionally large study shows genomic changes in the MRSA population at the national level. It reveals waxing and waning of types and genogroups and an increasing proportion of PVL-positive MRSA.A group of bacteria that cause difficult-to-treat infections in humans is methicillin-resistant Staphylococcus aureus (MRSA). The aim of this study was to monitor changes in the spread of MRSA, their disease causing potential and resistance to antibiotics used to treat MRSA infections. MRSA from patients and their contacts in the Netherlands were collected over a period of 12 years and characterized. This revealed new types of MRSA emerged and others disappeared. An increasing number of MRSA produces a protein called PVL toxin, enabling MRSA to cause more severe infections. Also, some people appear to carry MRSA without any disease for more than a year. These findings suggest an increasing disease potential of MRSA and possible unnoticed sources of infection. Consequently, it is important to maintain monitoring of these infections to minimize MRSA spread.Schouls et al. characterize 43,321 methicillin-resistant Staphylococcus aureus (MRSA) isolates obtained between 2008 and 2019 in the Netherlands. Genomic changes occur in the MRSA population, with increases in the proportion of PVL-positive MRSA.Molecular basis of bacterial pathogenesis, virulence factors and antibiotic resistanc

Brain reorganization after experimental stroke: functional and structural MRI correlates

Ischemic stroke is a major cause of death and long-term disability in the Western society. The disease leads to debilitating effects like neuronal death, loss of anatomical connections between neurons and subsequent loss of function. Although such ischemic stroke damage can be devastating, many patients survive the insult and undergo a certain degree of recovery in the following weeks and months. An increasing number of animal and human stroke studies has attributed this spontaneous functional recovery at later stages to the brain’s capability to reorganize and remodel the affected bilateral neuronal networks. Yet, the underlying mechanisms of functional and structural plasticity processes and their relationship with improved behavioral outcome remain incompletely understood. Evidently, elucidation of the neuronal substrates and the spatiotemporal characteristics of brain reorganization associated with improved function may guide the development of new therapeutic strategies at later time points after cerebral ischemia. This thesis deals with the spatiotemporal characterization of changes in functional and structural organization of the bilateral sensorimotor network in relation to behavioral recovery after stroke in rats, using different magnetic resonance imaging (MRI) methods. Furthermore, the mutual link between functional and structural modifications of neuronal circuitry was investigated. Therefore, a relatively new technique, resting-state functional MRI (rs-fMRI), in combination with MRI of structural connectivity (i.e., manganese-enhanced MRI (MEMRI) and diffusion tensor imaging (DTI)) was applied to allow non-invasive and serial measurements of changes in organization of functional networks after unilateral stroke in rats. Our data have revealed that rapid and mainly perilesional remodeling with transient disturbance of functional network organization is related to almost complete functional recovery after subcortical stroke, whereas prolonged and extensive bilateral reorganization including increased contralesional connectivity is correlated with partial restoration of function after large stroke involving cortical areas. Independent of stroke severity, intact interhemispheric synchronization of neuronal activity (i.e., interhemispheric functional connectivity) seems to be crucial for improved behavioral outcome, which for its part may also reciprocally stabilize and strengthen new functional connections. Next to a strong direct correlation between functional and structural connectivity changes, an indirect and probably reciprocal relationship exists between the reinstatement of interhemispheric signal synchronization and recovery of the structural integrity in the ipsilesional corticospinal tract. Moreover, despite strong correlations between recovery and MRI measures of functional reorganization, preserved structural integrity of the unilateral ipsilesional corticospinal tract appears to be the most essential basis for good functional outcome after unilateral stroke in rats. This may indicate that regained balance of somatosensory input and motor output signals between bilateral corticospinal tracts is essential for recovery of interhemispheric functional connectivity and subsequent sensorimotor function. The MRI findings discussed in this thesis corroborate the concept that a network perspective is fundamental to improve our understanding of underlying neuronal mechanisms of spontaneous functional recovery, and for developing novel therapeutic or rehabilitative strategies in stroke subjects. Moreover, the unique information about the specific pattern of functional reorganization, as obtained with rs-fMRI, could be used to tailor therapeutic interventions (e.g., brain stimulation) to the individual situation of the stroke patient

Feed uses for barley

Cereal grains with their high starch content are fed to livestock predominantly as a source of energy for rapid growth or high milk yield and also for subsistence in times of poor pasture availability. Results from the Premium Grains for Livestock Program show there are large variations across cereal grain species, cultivars, individual grain samples and animal types in the energy released during digestion and in the amount of grain eaten. The digestive system of an animal has a major effect on the energy value of individual barley samples. Some samples provide more energy for ruminants but less for pigs and poultry, and vice versa. Several grain characteristics that contribute to these differences have been identified. Chemical composition of the grain and nature of the endosperm cell walls have a major impact on the energy made available to different animal types. The rate of starch digestion and chances of causing acidosis are important characteristics for determining the energy value of barley for ruminants. Specific grain characteristics that could be included in barley breeding programs for different types of livestock production have been identified. NIR calibrations have been developed for many of these characteristics and should result in more effective evaluation of grains within breeding programs and for sale to the livestock industries

Clinically unsuspected orthopedic implants during S. aureus bacteremia do not require additional diagnostic work-up.

PURPOSE: To assess the likelihood of occult infection in patients with clinically unsuspected orthopedic implants during Staphylococcus aureus bacteremia (SAB). METHODS: In a retrospective study in two Dutch hospitals, we included all patients with SAB between 2013 and 2020 with one or more orthopedic implants in whom [(18)F]FDG-PET/CT was performed. The primary outcome was the percentage of patients who had an orthopedic implant-related infection by S. aureus. We also compared clinical parameters in patients with clinically suspected and unsuspected implants. RESULTS: Fifty-five of 191 (29%) orthopedic implants in 118 SAB patients included had clinical signs of infection. Of all 136 unsuspected implants, 5 (3%, all arthroplasties), showed increased [(18)F]FDG uptake around the prosthesis on [(18)F]FDG-PET/CT. The clinical course of these patients without clinically overt infection or relapse of bacteremia during follow-up of a median of 48 months (range 0-48), however, argued against prosthetic joint infection. CONCLUSION: Although orthopedic implants are evidently a risk factor for metastatic infection during SAB, the absence of clinical symptoms obviate the need of additional investigations or prolonged antibiotic treatment

A quantitative method for microstructural analysis of myelinated axons in the injured rodent brain

textabstractMRI studies (e.g. using diffusion tensor imaging) revealed that injury to white matter tracts, as observed in for instance perinatal white matter injury and multiple sclerosis, leads to compromised microstructure of myelinated axonal tracts. Alterations in white matter microstructure are also present in a wide range of neurological disorders including autism-spectrum disorders, schizophrenia and ADHD. Whereas currently myelin quantity measures are often used in translational animal models of white matter disease, it can be an important valuable addition to study the microstructural organization of myelination patterns in greater detail. Here, we describe methods to extensively study the microstructure of cortical myelination by immunostaining for myelin. To validate these methods, we carefully analyzed the organization of myelinated axons running from the external capsule towards the outer layers of the cortex in three rodent models of neonatal brain injury and in an adult stroke model, that have all been associated with myelination impairments. This unique, relatively easy and sensitive methodology can be applied to study subtle differences in myelination patterns in animal models in which aberrations in myelination integrity are suspected. Importantly, the described methods can be applied to determine efficacy of novel experimental treatments on microstructural organization of cortical myelination