Haemostasis and Virus infections

__Abstract__ Het ontstaan van een bloeding of trombose gedurende of kort volgend op een infectie is een van de meest prominente oorzaken van morbiditeit en sterfte ten gevolge van infectieziekten. Hoewel aanzienlijke vooruitgang is geboekt in het ontrafelen van ziekte mechanismen in bijvoorbeeld bloedvergiftiging (sepsis) en chronische virus infecties (HIV, hepatitis B,C), is de kennis over de mechanismen die verantwoordelijk zijn voor het ontstaan van bloedingen en/ of trombose ten tijde van virale infecties zeer beperkt. In dit proefschrift hebben wij enerzijds verspreiding en diagnostiek van virale bloedende koortsen bestudeerd. Anderzijds onderzochten wij de interactie tussen virale infecties en de stollingscascade. Samengevat heeft het onderzoek beschreven in dit proefschrift bijgedragen aan de kennis van virale infecties en interactie met daarachterliggende mechanismen van trombose en bloedi ng. Uit het epidemiologische onderzoek bleek dat een hantavirus infectie, met als mogelijk gevolg een bloedende koorts, een diagnose is die in ieder geval in Nederland en Suriname nog al eens over het hoofd wordt gezien gebaseerd op de resultaten van de Hanta-Hunting studie. Wat betreft de ziekte mechanisme stud ies lijken op het eerste gezicht zowel virussen die bloedingen veroorzaken als virussen die juist verstopping van een bloedvat kunnen veroorzaken een vergelijkbaar effect te hebben op de bloedstolling, namelijk activatie van de stolling. Factoren die bepalend zijn of een virus infectie leidt tot trombose of bloeding zullen gezocht moeten worden in zeer subtiele verschillen. Hierin lijkt dat zowel de hevigheid van de respons op infectie als het orgaan dat is aangedaan van groot belang kan zijn. Het proefschrift eindigt met een tweetal hoofdstukken gericht op het voorkomen van de infecties behandeld in de eerdere delen. Wij toonden een sterke associatie aan tussen selenium concentratie in gewassen en de incidentie van hant avirus infecties in China. Op basis van vervolg studies in patiënten en experimenten gebruik makende van een endotheelcel model suggereren wij dat de variaties in selenium concentratie zeer waarschijnlijk effect hebben op de verspreiders van hantavirus infecties in Ch ina, ratten en bosmuizen. Of en hoe uiteindelijk selenium suppletie het aantal hantavirus infecties kan doen dalen, zal moeten worden uitgewezen in vervolg studies. de effectiviteit en veiligheid zien van preventie door middel van vaccinatie met een gemodificeerd pokkenvirus (MVA). Op het oppervlakte van dit ongevaarlijke virus is een belangrijk oppervlakte eiwit van het zeer gevaarlijke vogelgriepvirus tot expressie gebracht. Het gebruik van vector als vaccinatie biedt een veelbelovend perspectief voor bescherming tegen vele andere virussen, zoals bijvoorbeeld hantavirussen

Fat embolism syndrome in a patient that sustained a femoral neck fracture: A case report

BackgroundWe present a case of a patient with a femoral neck fracture that shows neurological impairment and respiratory distress 1 day after trauma, caused by the Fat Embolism Syndrome with the presence of Cerebral Fat Embolisms.Case summaryA 75 year old female remained unresponsive after a hemi arthroplasty was performed because of a 1 day old femoral neck fracture. She rapidly developed respiratory insufficiency and an obstructive shock with right ventricle dilatation on transthoracic echocardiography. The diffusion-weighted MRI brain images showed the “Starfield” pattern, a radiologic phenomenon typical for FES. During 3 weeks of ICU admission the neurologic state slowly ameliorated.ConclusionThe rare FES is a clinical diagnosis with mainly respiratory, neurologic and dermatologic symptoms in the setting of a trauma patient. Fat embolisms are able to reach the brain without the presence of a patent foramen ovale to cause neurological symptoms. Diagnosing FES remains challenging but the distinctive “Starfield” pattern on MRI scans is promising

Determinants of vaccination uptake in risk populations: A comprehensive literature review

Vaccination uptake has decreased globally in recent years, with a subsequent rise of vaccine-preventable diseases. Travellers, immunocompromised patients (ICP), and healthcare workers (HCW) are groups at increased risk for (severe) infectious diseases due to their behaviour, health, or occupation, respectively. While targeted vaccination guidelines are available, vaccination uptake seems low. In this review, we give a comprehensive overview of determinants—based on the integrated change model—predicting vaccination uptake in these groups. In travellers, low perceived risk of infection and low awareness of vaccination recommendations contributed to low uptake. Additionally, ICP were often unaware of the recommended vaccinations. A physician’s recommendation is strongly correlated with higher uptake. Furthermore, ICP appeared to be mainly concerned about the risks of vaccination and fear of deterioration of their underlying disease. For HCW, perceived risk of (the severity of) infection for themselves and for their patients together with perceived benefits of vaccination contribute most to their vaccination behaviour. As the determinants that affect uptake are numerous and diverse, we argue that future studies and interventions should be based on multifactorial health behaviour models, especially for travellers and ICP as only a limited number of such studies is available yet

Establishment of Valid Laboratory Case Definition for Human Leptospirosis

Laboratory case definition of leptospirosis is scarcely de ned by a solid evaluation that determines cut-off values in the tests that are applied. This study describes the process of determining optimal cut-off titers of laboratory tests for leptospirosis for a valid case definition of leptospirosis. In this case the tests are the microscopic agglutination test (MAT) and an in-house IgM enzyme-linked immunosorbent assay (ELISA) both on single serum and paired samples using a positive culture as the reference test in the Dutch population. The specificity was assessed using panels of sera from healthy donors, cases with known other diseases and non-leptospirosis cases with symptoms compatible with leptospirosis. Cases were divided into three periods corroborating the acute phase (1-10 days post onset of illness (DPO)), the early convalescent (11-20 DPO) and the late convalescent phase (>20 DPO). Cut-off titers for MAT and IgM ELISA were determined as 1:160 and 1:80 respectively for all three periods. These cut-off titers combined 100% specificity with a sensitivity that changed according to the stage of disease for both tests. The low sensitivities in the early acute phase are consistent with the dynamics of the humoral immune response. IgM ELISA yielded higher sensitivities compared to MAT in the acute and early convalescent stages. Moreover, the optimal sensitivity of MAT, the gold standard was < 82%, implying that a significant part of global cases is missed by this recommended test. MAT and IgM ELISA manifested partly complementary, resulting in a higher sensitivity when combining the results of these two tests. The availability of paired samples and of adequate clinical and epidemiological data are other parameters that

Predicted enhanced human propensity of current avian-like H1N1 swine influenza virus from China

Influenza A virus (IAV) subtypes against which little or no pre-existing immunity exists in humans represent a serious threat to global public health. Monitoring of IAV in animal hosts is essential for early and rapid detection of potential pandemic IAV strains to prevent their spread. Recently, the increased pandemic potential of the avian-like swine H1N1 IAV A/swine/Guangdong/104/2013 has been suggested. The virus is infectious in humans and the general population seems to lack neutralizing antibodies against this virus. Here we present an in silico analysis that shows a strong human propensity of this swine virus further confirming its pandemic potential. We suggest mutations which would further enhance its human propensity. We also propose conserved antigenic determinants which could serve as a component of a prepandemic vaccine. The bioinformatics tool, which can be used to further monitor the evolution of swine influenza viruses towards a pandemic virus, are described here and are made publically available (http://www.vin.bg.ac.rs/180/tools/iav-mon.php; http://www.biomedprotection.com/iav-mon.php)

Specific Disease Knowledge as Predictor of Susceptibility to Availability Bias in Diagnostic Reasoning:a Randomized Controlled Experiment

BACKGROUND: Bias in reasoning rather than knowledge gaps has been identified as the origin of most diagnostic errors. However, the role of knowledge in counteracting bias is unclear. OBJECTIVE: To examine whether knowledge of discriminating features (findings that discriminate between look-alike diseases) predicts susceptibility to bias. DESIGN: Three-phase randomized experiment. Phase 1 (bias-inducing): Participants were exposed to a set of clinical cases (either hepatitis-IBD or AMI-encephalopathy). Phase 2 (diagnosis): All participants diagnosed the same cases; 4 resembled hepatitis-IBD, 4 AMI-encephalopathy (but all with different diagnoses). Availability bias was expected in the 4 cases similar to those encountered in phase 1. Phase 3 (knowledge evaluation): For each disease, participants decided (max. 2 s) which of 24 findings was associated with the disease. Accuracy of decisions on discriminating features, taken as a measure of knowledge, was expected to predict susceptibility to bias. PARTICIPANTS: Internal medicine residents at Erasmus MC, Netherlands. MAIN MEASURES: The frequency with which higher-knowledge and lower-knowledge physicians gave biased diagnoses based on phase 1 exposure (range 0-4). Time to diagnose was also measured. KEY RESULTS: Sixty-two physicians participated. Higher-knowledge physicians yielded to availability bias less often than lower-knowledge physicians (0.35 vs 0.97; p = 0.001; difference, 0.62 [95% CI, 0.28-0.95]). Whereas lower-knowledge physicians tended to make more of these errors on subjected-to-bias than on not-subjected-to-bias cases (p = 0.06; difference, 0.35 [CI, - 0.02-0.73]), higher-knowledge physicians resisted the bias (p = 0.28). Both groups spent more time to diagnose subjected-to-bias than not-subjected-to-bias cases (p = 0.04), without differences between groups. CONCLUSIONS: Knowledge of features that discriminate between look-alike diseases reduced susceptibility to bias in a simulated setting. Reflecting further may be required to overcome bias, but succeeding depends on having the appropriate knowledge. Future research should examine whether the findings apply to real practice and to more experienced physicians

Zika virus and the current outbreak:an overview

Zika virus (ZIKV), a mosquito-borne flavivirus closely related to yellow fever virus and dengue virus, is currently causing a large outbreak in the Americas. Historically, ZIKV infection was considered a sporadic, relatively mild disease characterised by fever, maculopapular rash, conjunctivitis and often arthralgia. However, current observational studies suggest that ZIKV may cause more severe neurological sequelae such as Guillain-Barre syndrome, and birth defects, mainly microcephaly, in babies of whom the mother was infected with ZIKV during pregnancy. This article provides a clinically focussed overview of ZIKV, with emphasis on the current outbreak, clinical manifestations, diagnostic tools and caveats. </p