Changes in enterovirus epidemiology after easing of lockdown measures.

INTRODUCTION: Public health measures aimed at controlling transmission of SARS-CoV-2, otherwise known as "lockdown" measures, had profound effects on circulation of non-SARS viruses, many of which decreased to very low levels.  The interrupted transmission of these viruses may have lasting effects. Some of the influenza clades seem to have disappeared during this period, a phenomenon which is described as a "funnel effect". It is currently unknown if the lockdown measures had any effect on the diversity of circulating viruses, other than influenza. Enteroviruses are especially interesting in this context, as the clinical presentation of an infection with a particular enterovirus-type may be clade-dependent. METHODS AND MATERIALS: Enteroviruses were detected in clinical materials using a 5'UTR-based detection PCR, and partial VP-1 sequences were obtained, using methods described before. All samples with EV detections from a large part of the Netherlands were included in the study. The samples originated from general practitioners, general hospitals, university hospitals and public health offices. RESULTS: Five EV-genotypes circulated in significant numbers before and after the lockdown, EV-D68, E-11, CV-A6, CV-B5 and CV-A2. All five genotypes showed decreased genetic diversity after the lockdown, and four indicate a significant number of sequences clustering together with a very high sequence homology. Moreover, children with E-11 and CV-B5 detections were significantly older after the lockdown than before. CONCLUSIONS: The reduced enterovirus transmission in the Netherlands during the pandemic, seems to have led to a decrease in genetic diversity in the five most commonly detected enterovirus serotypes.

Risk factors for acute toxoplasmosis in the Netherlands.

Toxoplasmosis caused by the protozoan parasite Toxoplasma gondii occurs worldwide. Infections range from asymptomatic to life-threatening. T. gondii infection is acquired either via bradyzoites in meat or via oocysts in the environment, but the relative importance of these path ways and the different sources remains unclear. In this study, possible risk factors for toxoplasmosis in the Netherlands were investigated. A case-control study was conducted including persons with recent infection and individuals with a negative test result for IgM and IgG for T. gondii between July 2016 and April 2021. A total of 48 cases and 50 controls completed the questionnaire. Food history and environmental exposure were compared using logistic regression. Consumption of different meats was found to be associated with recent infection. In the multivariable model, adjusted for age, gender, and pregnancy, consumption of large game meat (adjusted odds ratio (aOR) 8.2, 95% confidence interval 1.6-41.9) and sometimes (aOR 4.1, 1.1-15.3) or never (aOR 15.9, 2.2-115.5) washing hands before food preparation remained. These results emphasize the value of the advice to be careful with the consumption of raw and undercooked meat. Good hand hygiene could also be promoted in the prevention of T. gondii infection.

Trends in Occurrence and Phenotypic Resistance of Coagulase-Negative Staphylococci (CoNS) Found in Human Blood in the Northern Netherlands between 2013 and 2019.

BACKGROUND: For years, coagulase-negative staphylococci (CoNS) were not considered a cause of bloodstream infections (BSIs) and were often regarded as contamination. However, the association of CoNS with nosocomial infections is increasingly recognized. The identification of more than 40 different CoNS species has been driven by the introduction of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Yet, treatment guidelines consider CoNS as a whole group, despite increasing antibiotic resistance (ABR) in CoNS. This retrospective study provides an in-depth data analysis of CoNS isolates found in human blood culture isolates between 2013 and 2019 in the entire region of the Northern Netherlands. METHODS: In total, 10,796 patients were included that were hospitalized in one of the 15 hospitals in the region, leading to 14,992 CoNS isolates for (ABR) data analysis. CoNS accounted for 27.6% of all available 71,632 blood culture isolates. EUCAST Expert rules were applied to correct for errors in antibiotic test results. RESULTS: A total of 27 different CoNS species were found. Major differences were observed in occurrence and ABR profiles. The top five species covered 97.1% of all included isolates: S. epidermidis, S. hominis, S. capitis, S. haemolyticus, and S. warneri. Regarding ABR, methicillin resistance was most frequently detected in S. haemolyticus (72%), S. cohnii (65%), and S. epidermidis (62%). S. epidermidis and S. haemolyticus showed 50-80% resistance to teicoplanin and macrolides while resistance to these agents remained lower than 10% in most other CoNS species. CONCLUSION: These differences are often neglected in national guideline development, prompting a focus on 'ABR-safe' agents such as glycopeptides. In conclusion, this multi-year, full-region approach to extensively assess the trends in both the occurrence and phenotypic resistance of CoNS species could be used for evaluating treatment policies and understanding more about these important but still too often neglected pathogens.

Treatment and Outcome of Culture-Confirmed Mycobacterium marinum Disease.

Background: Mycobacterium marinum is a nontuberculous mycobacterium that causes skin and soft tissue infections. Treatment consists of multiple antibiotics, sometimes combined with surgical debridement. There is little evidence for the choice of antibiotics, the duration of treatment, and the role of susceptibility testing. Methods: We performed a retrospective cohort study of culture-confirmed M. marinum infections in the Netherlands in the 2011-2018 period. Clinical characteristics, in vitro susceptibility, extent of disease, treatment regimens, and outcomes were analyzed. Incidence was assessed from laboratory databases. Results: Forty cases of M. marinum infection could be studied. Antibiotic treatment cured 36/40 patients (90%) after a mean treatment duration of 25 weeks. Failure/relapse occurred in 3 patients, and 1 patient was lost to follow-up. Antibiotic treatment consisted of monotherapy in 35% and 2-drug therapy in 63%. Final treatment contained mostly ethambutol-macrolide combinations (35%). Eleven patients (28%) received additional surgery. We recorded high rates of in vitro resistance to tetracyclines (36% of isolates). Tetracycline resistance seemed correlated with poor response to tetracycline monotherapy. The annual incidence rate was 0.15/100 000/year during the study period. Conclusions: Prolonged and susceptibility-guided treatment results in a 90% cure rate in M. marinum disease. Two-drug regimens of ethambutol and a macrolide are effective for moderately severe infections. Tetracycline monotherapy in limited disease should be used vigilantly, preferably with proven in vitro susceptibility.

High rates of anorectal chlamydia in women: a cross-sectional study in general practice.

BACKGROUND: Genital and anorectal Chlamydia trachomatis (CT) frequently present together in sexually transmitted infection (STI) clinics. AIM: To investigate the prevalence of co-occurrent genital and anorectal chlamydia infection, and to study whether sexual behaviour is associated with anorectal infection. DESIGN & SETTING: A cross-sectional study in general practices in the north of the Netherlands. METHOD: Women attending general practice with an indication for genital chlamydia testing were included and asked to complete a structured questionnaire on sexual behaviour. Anorectal infection prevalence was compared according to testing indications: standard versus experimental (based on questionnaire answers). Variables associated with anorectal chlamydia were analysed by univariate and multivariate logistic regression analyses. RESULTS: Data could be analysed for 497 of 515 women included. Overall, 17.8% (n = 87/490) were positive for CT; of these, 72.4% (n = 63/87) had co-occurrent genital and anorectal infection, 13.8% (n = 12/87) had genital infection only, and 12.6% (n = 11/87) had anorectal infection only. Rectal infection was missed in 69.3% of cases using the standard indication alone, while adding the sexual history still missed 20.0%. Age was the only variable significantly associated with anorectal infection. CONCLUSION: The prevalence of anorectal disease is high among women who visit their GP with an indication for genital CT testing. Many anorectal infections are missed despite taking comprehensive sexual histories, meaning that standard treatment of genital infection with azithromycin may result in rectal persistence. Performing anorectal testing in all women with an indication for genital CT testing is, therefore, recommended.

A prospective multicentre screening study on multidrug-resistant organisms in intensive care units in the Dutch-German cross-border region, 2017 to 2018: the importance of healthcare structures.

BackgroundAntimicrobial resistance poses a risk for healthcare, both in the community and hospitals. The spread of multidrug-resistant organisms (MDROs) occurs mostly on a local and regional level, following movement of patients, but also occurs across national borders.AimThe aim of this observational study was to determine the prevalence of MDROs in a European cross-border region to understand differences and improve infection prevention based on real-time routine data and workflows.MethodsBetween September 2017 and June 2018, 23 hospitals in the Dutch (NL)-German (DE) cross-border region (BR) participated in the study. During 8 consecutive weeks, patients were screened upon admission to intensive care units (ICUs) for nasal carriage of meticillin-resistant Staphylococcus aureus (MRSA) and rectal carriage of vancomycin-resistant Enterococcus faecium/E. faecalis (VRE), third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE) and carbapenem-resistant Enterobacteriaceae (CRE). All samples were processed in the associated laboratories.ResultsA total of 3,365 patients were screened (median age: 68 years (IQR: 57-77); male/female ratio: 59.7/40.3; NL-BR: n = 1,202; DE-BR: n = 2,163). Median screening compliance was 60.4% (NL-BR: 56.9%; DE-BR: 62.9%). MDRO prevalence was higher in DE-BR than in NL-BR, namely 1.7% vs 0.6% for MRSA (p = 0.006), 2.7% vs 0.1% for VRE (p < 0.001) and 6.6% vs 3.6% for 3GCRE (p < 0.001), whereas CRE prevalence was comparable (0.2% in DE-BR vs 0.0% in NL-BR ICUs).ConclusionsThis first prospective multicentre screening study in a European cross-border region shows high heterogenicity in MDRO carriage prevalence in NL-BR and DE-BR ICUs. This indicates that the prevalence is probably influenced by the different healthcare structures.

Who is providing HIV diagnostic testing? Comparing HIV testing by general practitioners and sexual health centres in five regions in the Netherlands, 2011-2018.

OBJECTIVES: General practitioners (GPs) and sexual health centres (SHCs) are the main providers of HIV testing and diagnose two-thirds of HIV infections in the Netherlands. We compared regional HIV testing and positivity by GPs versus SHCs to gain insight into strategies to improve HIV testing, to enable timely detection of HIV infections. METHODS: Laboratory data (2011-2018) on HIV testing by GPs and SHCs in five Dutch regions with varying levels of urbanisation were evaluated. Regional HIV testing rates per 10 000 residents ≥15 years (mean over period and annual) were compared between providers using negative binomial generalised additive models and additionally stratified by sex and age (15-29 years, 30-44 years, 45-59 years, ≥60 years). χ2 tests were used to compare positivity percentage between the two groups of providers. RESULTS: In the study period, 505 167 HIV tests (GP 36%, SHC 64%) were performed. The highest HIV testing rates were observed in highly urbanised regions, with large regional variations. The HIV testing rates ranged from 28 to 178 per 10 000 residents by GPs and from 30 to 378 per 10 000 by SHCs. Testing rates by GPs were lower than by SHCs in three regions and comparable in two. In all regions, men were tested less by GPs than by SHCs; for women, this varied by region. Among those aged 15-29 years old, GPs' testing rates were lower than SHCs', while this was reversed in older age categories in four out of five regions. The overall mean HIV positivity was 0.4%. In contrast to other regions, positivity in Amsterdam was significantly higher among individuals tested by GPs than by SHCs. CONCLUSIONS: This retrospective observational study shows that besides SHCs, who perform opt-out testing for key groups, GPs play a prominent role in HIV testing, especially in non-key populations, such as women and older individuals. Large regional variation exists, requiring region-specific interventions to improve GPs' HIV testing practices.

Predominance of CTX-M-15-producing ST131 strains among ESBL-producing Escherichia coli isolated from asylum seekers in the Netherlands.

OBJECTIVES: Numerous studies show increased prevalence of MDR bacteria amongst asylum seekers, but data on the molecular profiles of such strains are limited. We aimed to evaluate the molecular profiles of ESBL-producing Escherichia coli (ESBL-E. coli) strains isolated from asylum seekers and investigate their phylogenetic relatedness. METHODS: WGS data of ESBL-E. coli isolates from asylum seekers, retrieved from 1 January to 31 December 2016, were analysed to assess MLST STs, fim types, phylogroups and resistance genes. Fifty-two ESBL-E. coli isolates from the Dutch-German border region were used for genome comparison purposes as a control group. RESULTS: Among 112 ESBL-E. coli isolates from asylum seekers, originating mostly from Syria (n = 40) and Iraq (n = 15), the majority belonged to ST131 (21.4%) and ST10 (17.0%). The predominant gene for ß-lactam resistance was blaCTX-M-15 (67.9%), followed by the often co-detected blaTEM-1B (39.3%). No mcr or carbapenemase genes were detected. The majority of the strains belonged to phylogroups B2 (38.4%) and A (32.1%), carrying fimH27 (25%) and fimH30 (19.6%). A core genome MLST minimum spanning tree did not reveal clusters containing strains from the asylum seekers and the control group. Five clusters were formed within the asylum seeker group, by strains isolated from people originating from different countries. CONCLUSIONS: The most frequently isolated clones in this study were isolated on a regular basis within the Dutch population before the increase in the asylum seeker population. No mcr- or carbapenemase-producing clones were detected among the asylum seeker population. Minor clustering was observed amongst the asylum seeker strains.

Yeast Infections after Esophagectomy: A Retrospective Analysis.

Esophageal malignancy is a disease with poor prognosis. Curative therapy incorporates surgery and is burdensome with high rates of infection morbidity and mortality. The role of yeast as causative organisms of post-esophagectomy infections is poorly defined. Consequently, the benefits of specific antifungal prophylactic therapy in improving patient outcome are unclear. Therefore, this study aimed at investigating the incidence of yeast infections at the University Medical Center Groningen among 565 post-esophagectomy patients between 1991 and 2017. The results show that 7.3% of the patients developed a yeast infection after esophageal resection with significantly increased incidence among patients suffering from diabetes mellitus. For patients with yeast infections, higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores, more frequent intensive care unit readmissions, prolonged hospital stays and higher mortality rates were observed. One-year survival was significantly lower for patients with a yeast infection, as well as diabetes mellitus and yeast-positive pleural effusion. We conclude that the incidence of yeast infections following esophagectomy is considerable, and that patients with diabetes mellitus are at increased risk. Furthermore, yeast infections are associated with higher complication rates and mortality. These observations encourage further prospective investigations on the possible benefits of antifungal prophylactic therapy for esophagectomy patients.

Heterogeneous antimicrobial activity in broncho-alveolar aspirates from mechanically ventilated intensive care unit patients.

Pneumonia is an infection of the lungs, where the alveoli in the affected area are filled with pus and fluid. Although ventilated patients are at risk, not all ventilated patients develop pneumonia. This suggests that the sputum environment may possess antimicrobial activities. Despite the generally acknowledged importance of antimicrobial activity in protecting the human lung against infections, this has not been systematically assessed to date. Therefore, the objective of the present study was to measure antimicrobial activity in broncho-alveolar aspirate ('sputum") samples from patients in an intensive care unit (ICU) and to correlate the detected antimicrobial activity with antibiotic levels, the sputum microbiome, and the respective patients' characteristics. To this end, clinical metadata and sputum were collected from 53 mechanically ventilated ICU patients. The antimicrobial activity of sputum samples was tested against Streptococcus pneumoniae, Staphylococcus aureus and Streptococcus anginosus. Here we show that sputa collected from different patients presented a high degree of variation in antimicrobial activity, which can be partially attributed to antibiotic therapy. The sputum microbiome, although potentially capable of producing antimicrobial agents, seemed to contribute in a minor way, if any, to the antimicrobial activity of sputum. Remarkably, despite its potentially protective effect, the level of antimicrobial activity in the investigated sputa correlated inversely with patient outcome, most likely because disease severity outweighed the beneficial antimicrobial activities.

Proportion of asylum seekers carrying multi-drug resistant microorganisms is persistently increased after arrival in the Netherlands.

Background: Several studies have shown a high prevalence of multi-drug resistant organisms (MDRO) amongst asylum seekers when compared to the general population. The aim of this study is to assess the duration of MDRO carriage in this population. Methods: Data were retrospectively collected between January 1st 2014 through December 31st 2016. Study material included screening samples for MDRO carriage and clinical samples from asylum seekers in need of medical care. The study focused on methicillin-resistant Staphylococcus aureus (MRSA) and multi-drug resistant Enterobacteriaceae (MDRE). The rates of MRSA and MDRE detected were calculated every four weeks after arrival in the Netherlands. Results: Samples from 2091 asylum seekers were included. 1270 (60.7%) were female, median age was 26 years (IQR 20-34) and median number of days in the Netherlands until first sample was 67 (IQR 4-235). In the patients' first obtained samples, the rate of MRSA varied between 4.5 and 13.0% per time interval after arrival. The rate of MDRE fluctuated between 7.4% and 25.0%. No particular decline in positivity rates in first obtained samples was observed after arrival in the Netherlands. In the group of asylum seekers who arrived more than one year ago, MRSA was isolated in a percentage of 5.1% (n = 273, median months after arrival 34.1 (IQR 16.5-63.1)) and MDRE in 9.4% (n = 276, median months after arrival 35.4 (IQR 17-65)). Conclusion: To our knowledge, this is the first study demonstrating that carriage rate of MDRO in asylum seekers remains high even after prolonged stay in the Netherlands. Longitudinal data on MDRO carriage after arrival in countries with a low MDRO prevalence are needed to determine optimal screening strategies, infection control measures and empirical antibiotic therapy.

Clinical Presentation of Laboratory Confirmed Neurosyphilis in a Recent Cases Series.

OBJECTIVE: The worldwide increase in the incidence of syphilis necessitates alertness to the occurrence of neurosyphilis. Early recognition of neurosyphilis allows for timely treatment, leading to a better treatment outcome. This retrospective study aims to describe the clinical presentation of neurosyphilis in a recent series of neurosyphilis patients. METHOD: All patients were included with a new, laboratory confirmed, diagnosis of neurosyphilis in the period 2004-2018. The clinical data were analysed. RESULTS: 34 neurosyphilis patients (1 woman and 33 men) were identified. Age varied from 31-84 years (median age: 44 years). A history of syphilis infection was known for 11 (32%) patients; 12 (35%) patients were HIV seropositive. The distribution of the clinical syndromes was as follows: 16 patients with early neurosyphilis (acute meningitis, meningovasculitis and/or uveitis), 9 patients with late neurosyphilis (General Paralysis of the Insane and/or Tabes Dorsalis), 2 patients with symptoms of both early and late neurosyphilis, 6 patients with asymptomatic neurosyphilis and in 1 patient insufficient data were available to determine a clinical syndrome. Early neurosyphilis was seen in all age categories, late neurosyphilis only occurred in patients > 40 years. CONCLUSIONS: Neurosyphilis occurs in adults in all age groups, in men more frequent than in women, often in HIV-infected patients, and can present with a wide range of clinical syndromes. Usually no previous infection with syphilis is known.

Asymptomatic bacteriuria and urinary tract infection in pregnant women with and without diabetes: Cohort study.

OBJECTIVE: To compare the prevalence of asymptomatic bacteriuria (ASB) and the incidence of urinary tract infection (UTI) in pregnant women with and without diabetes mellitus (DM) or gestational DM (GDM). STUDY DESIGN: We performed a cohort study in five hospitals and two midwifery clinics in the Netherlands. Pregnant women with and without DM or GDM were screened for the presence of ASB around 12 and 32 weeks' gestation. Characteristics of participants as well as outcome data were collected from questionnaires and medical records. ASB was defined as the growth of at least 10e5 cfu/ml isolated from the urine of a woman without UTI complaints. UTI was considered to be present when a treating physician had diagnosed UTI and prescribed antibiotics. RESULTS: We studied 202 women with and 272 women without DM or GDM. Of all women 31.7% with and 94.9% without DM or GDM provided a week 12 sample. The prevalence of ASB was comparable in women with and without DM or GDM (12 weeks' n = 322; 4.7% and 2.3%; relative risk (RR) 2.02; 95% confidence interval (CI) 0.52-7.84; 32 weeks' n = 422; 3.2% and 3.0%; RR 1.06; 95% CI 0.36-3.09), as was the incidence of UTI (16.8% and 12.9%; RR 1.31; 95% CI 0.85-2.02). Neither ASB nor UTI were associated with preterm birth or babies being small for gestational age. CONCLUSION: In pregnant women with and women without DM or GDM, the overall prevalence of ASB was low. Neither ASB nor UTI did differ significantly between the groups. Our data discourage a routine ASB screen and treat policy in pregnant women with DM or GDM.

Malaria Fever Therapy for General Paralysis of the Insane: A Historical Cohort Study.

BACKGROUND/AIMS: This year marks the 100th anniversary of the first malaria fever treatment (MFT) given to patients with general paralysis of the insane (GPI) by the Austrian psychiatrist and later Nobel laureate, Julius Wagner-Jauregg. In 1921 Wagner-Jauregg reported an impressive therapeutic success of MFT and it became the standard treatment for GPI worldwide. In this study, MFT practice in the Dutch Vincent van Gogh psychiatric hospital in GPI patients who had been admitted in the period 1924-1954 is explored. METHODS: To identify patients with GPI, cause-of-death statistics was used. Data on MFT were retrieved from annual hospital reports and individual patient records. RESULTS: Data on MFT were mentioned in the records of 43 out of 105 GPI patients. MFT was practiced in a wide range of patients with GPI, including those with disease duration of more than 1 year, up to 70 years of age, and those with a broad array of symptoms and comorbidities, such as (syphilitic) cardiac disease. Inoculation with malaria was done by patient-to-patient transmission of infected blood. CONCLUSIONS: MFT practice and mortality rates in MFT-treated patients correspond to similar findings worldwide. MFT was well tolerated and MFT-treated patients had a significantly longer survival.

High prevalence of MRSA and ESBL among asylum seekers in the Netherlands.

Migration is one of the risk factors for the spread of multidrug-resistant organisms (MDRO). The increasing influx of migrants challenges local health care systems. To provide evidence for both hospital hygiene measure and empirical antibiotic therapy, we analysed all cultures performed in asylum seekers between January 1st 2014 and December 31st 2015 for methicillin resistant Staphylococcus aureus (MRSA) and for multidrug-resistant Enterobacteriaceae (MDRE). We compared these with cultures from the Dutch patient population with risk factors for carriage of MDRO. A total of 7181 patients were screened for MRSA. 7357 S. aureus were isolated in clinical cultures. Of 898 screened asylum seekers, almost 10% were MRSA positive. Of 118 asylum seekers with S. aureus in clinical cultures almost 19% were MRSA positive. The general patient population had a 1.3% rate of MRSA in S. aureus isolates. A higher rate of Panton-Valentine leukocidin (PVL) positive strains (RR: 2.4; 95% CI: 1.6-3.4) was found in asylum seekers compared to the general patient population. In 33475 patients one or more Enterobacteriaceae were obtained. More than 21% of the asylum seekers were carrier of MDRE, most of them producing extended spectrum beta-lactamases (20.3%). 5.1% of the general patient population was MDRE carrier. It can be concluded that asylum seekers present with higher rate of MDRO compared to the general patient population. These results justify continued screening of asylum seekers to anticipate multidrug-resistant organisms during hospital care of patients.

Dientamoeba fragilis colonization is not associated with gastrointestinal symptoms in children at primary care level.

BACKGROUND: Dientamoeba fragilis is commonly identified in children in primary care and is suspected to cause gastrointestinal disease. OBJECTIVE: To determine the association between D. fragilis colonization and gastrointestinal symptoms in children. METHODS: We performed a cross-sectional study with children who presented in primary care with gastrointestinal symptoms. The associations between D. fragilis colonization and specific symptoms were explored by means of logistic regression analyses. Asymptomatic siblings of these cases were invited as control subjects for a case-control analysis, where we explored the association between D. fragilis and gastrointestinal symptoms with conditional logistic regression analysis. RESULTS: In the cross-sectional study, 107 children were included. Their median age was 9 years (interquartile range = 6-12) and 38 (35.5%) were boys. Colonization of D. fragilis was present in 59 children (55.1%). The absence of D. fragilis was associated with soft to watery stool [odds ratio (OR) = 0.29; 95% confidence interval (CI) = 0.10-0.85], chronic diarrhoea (OR = 0.42; 95% CI = 0.18-0.97) and fatigue (OR = 0.45; 95% CI = 0.20-0.99). The case-control analyses included 44 children in each group. Dientamoeba fragilis colonization was not observed more often in cases than in controls after adjustment for age and sex (OR = 1.02; 95% CI = 0.28-3.65). CONCLUSION: Dientamoeba fragilis is a common parasite in children with and without gastrointestinal symptoms. The anomalous finding of the association between the absence of D. fragilis with soft to watery stools, chronic diarrhoea and fatigue are inexplicable. Our study suggests that D. fragilis colonization does not increase the risk for gastrointestinal symptoms.

High Prevalence of Infectious Diseases and Drug-Resistant Microorganisms in Asylum Seekers Admitted to Hospital; No Carbapenemase Producing Enterobacteriaceae until September 2015.

INTRODUCTION: The current refugee crisis emphasizes the need for information on infectious diseases and resistant microorganisms in asylum seekers with possible consequences for public health and infection control. METHODS: We collected data from asylum seekers admitted to our university hospital or who presented at the Emergency Department (n = 273). We collected general and demographic characteristics including country of origin, the reason of presentation, and the screening results of multi-drug resistant organisms. RESULTS: 67% of the patients were male with a median age of the study group of 24 years (IQR 15-33); 48% of the patients had an infectious disease-predominantly malaria with P. vivax or tuberculosis. Patients also reported with diseases which are less common-e.g. leishmaniasis, or even conditions rarely diagnosed in Europe-e.g. louse borne relapsing fever. A carriage rate of 31% for multi-drug resistant microorganisms (MDRO) was observed, with ESBL-expressing E.coli (n = 20) being the most common MDRO. No carriage of Carbapenemase Producing Enterobacteriaceae was found. CONCLUSION: The current refugee crisis in Europe challenges hospitals to quickly identify and respond to communicable diseases and the carriage of MDRO. A rapid response is necessary to optimize the treatment of infectious diseases amongst asylum seekers to maximize infection control.

A comparison of Percutaneous femoral access in Endovascular Repair versus Open femoral access (PiERO): study protocol for a randomized controlled trial.

BACKGROUND: Access for endovascular repair of abdominal aortic aneurysms (EVAR) is obtained through surgical cutdown or percutaneously. The only devices suitable for percutaneous closure of the 20 French arteriotomies of the common femoral artery (CFA) are the Prostar(™) and Proglide(™) devices (Abbott Vascular). Positive effects of these devices seem to consist of a lower infection rate, and shorter operation time and hospital stay. This conclusion was published in previous reports comparing techniques in patients in two different groups (cohort or randomized). Access techniques were never compared in one and the same patient; this research simplifies comparison because patient characteristics will be similar in both groups. METHODS/DESIGN: Percutaneous access of the CFA is compared to surgical cutdown in a single patient; in EVAR surgery, access is necessary in both groins in each patient. Randomization is performed on the introduction site of the larger main device of the endoprosthesis. The contralateral device of the endoprosthesis is smaller. When we use this type of randomization, both groups will contain a similar number of main and contralateral devices. Preoperative nose cultures and perineal cultures are obtained, to compare colonization with postoperative wound cultures (in case of a surgical site infection). Furthermore, patient comfort will be considered, using VAS-scores (Visual analog scale). Punch biopsies of the groin will be harvested to retrospectively compare skin of patients who suffered a surgical site infection (SSI) to patients who did not have an SSI. DISCUSSION: The PiERO trial is a multicenter randomized controlled clinical trial designed to show the consequences of using percutaneous access in EVAR surgery and focuses on the occurrence of surgical site infections. TRIAL REGISTRATION: NTR4257 10 November 2013, NL44578.042.13.

Maternal and neonatal consequences of treated and untreated asymptomatic bacteriuria in pregnancy: a prospective cohort study with an embedded randomised controlled trial.

BACKGROUND: Existing approaches for the screening and treatment of asymptomatic bacteriuria in pregnancy are based on trials that were done more than 30 years ago. In this study, we reassessed the consequences of treated and untreated asymptomatic bacteriuria in pregnancy. METHODS: In this multicentre prospective cohort study with an embedded randomised controlled trial, we screened women (aged ≥18 years) at eight hospitals and five ultrasound centres in the Netherlands with a singleton pregnancy between 16 and 22 weeks' gestation for asymptomatic bacteriuria. Screening was done with a single dipslide and two culture media. Dipslides were judged positive when the colony concentration was at least 1×10(5) colony-forming units (CFU) per mL of a single microorganism or when two different colony types were present but one had a concentration of at least 1×10(5) CFU per mL. Asymptomatic bacteriuria-positive women were eligible to participate in the randomised controlled trial comparing nitrofurantoin with placebo treatment. In this trial, participants were randomly assigned 1:1 to receive either nitrofurantoin 100 mg or identical placebo tablets, and were instructed to self-administer these tablets twice daily for 5 consecutive days. Randomisation was done by a web-based application with a computer-generated list with random block sizes of two, four, or six participants rendered by an independent data manager. 1 week after the end of treatment, they provided us with a follow-up dipslide. Women, treating physicians, and researchers all remained unaware of the bacteriuria status and treatment allocation. Women who refused to participate in the randomised controlled trial did not receive any antibiotics, but their outcomes were collected for analysis in the cohort study. We compared untreated and placebo-treated asymptomatic bacteriuria-positive women with asymptomatic bacteriuria-negative women and nitrofurantoin-treated asymptomatic bacteriuria-positive women. The primary endpoint was a composite of pyelonephritis with or without preterm birth at less than 34 weeks, analysed by intention to treat at 6 weeks post-partum. This trial is registered with the Dutch Trial Registry, number NTR3068. FINDINGS: Between Oct 11, 2011, and June 10, 2013, we enrolled 5621 women into our screening cohort, of whom 5132 were eligible for screening. After exclusions for contaminated dipslides and patients lost to follow-up, in our final cohort of 4283 women, 248 were asymptomatic bacteriuria positive, of whom 40 were randomly assigned to nitrofurantoin and 45 to placebo for the randomised controlled trial, whereas the other 163 asymptomatic bacteriuria-positive women were followed without treatment. The proportion of women with pyelonephritis, preterm birth, or both did not differ between untreated or placebo-treated asymptomatic bacteriuria-positive women and asymptomatic bacteriuria-negative women (6 [2·9%] of 208 vs 77 [1·9%] of 4035; adjusted odds ratio [OR] 1·5, 95% CI 0·6-3·5) nor between asymptomatic bacteriuria-positive women treated with nitrofurantoin versus those who were untreated or received placebo (1 [2·5%] of 40 vs 6 [2·9%] of 208; risk difference -0·4, 95% CI -3·6 to 9·4). Untreated or placebo-treated asymptomatic bacteriuria-positive women developed pyelonephritis in five [2·4%] of 208 cases, compared with 24 [0·6%] of 4035 asymptomatic bacteriuria-negative women (adjusted OR 3·9, 95% CI 1·4-11·4). INTERPRETATION: In women with an uncomplicated singleton pregnancy, asymptomatic bacteriuria is not associated with preterm birth. Asymptomatic bacteriuria showed a significant association with pyelonephritis, but the absolute risk of pyelonephritis in untreated asymptomatic bacteriuria is low. These findings question a routine screen-treat-policy for asymptomatic bacteriuria in pregnancy. FUNDING: ZonMw (the Netherlands Organisation for Health Research and Development).

Clinical Presentation of General Paralysis of the Insane in a Dutch Psychiatric Hospital, 1924-1954.

General paralysis of the insane (GPI) or dementia paralytica was once a fatal complication of syphilitic infection and a major reason for psychiatric hospitalization. Nowadays, physicians consider GPI to be exceptional. It should be noted, however, that syphilis re-emerged worldwide at the turn of the 20th to 21st century and a revival of GPI can, therefore, be expected. Advanced diagnosis is crucial in that treatment in the early, inflammatory phase is warranted before irreversible tissue damage occurs. Therefore, a renewed clinical awareness of the broad spectrum of psychiatric and neurologic signs and symptoms of GPI is needed. In this historical cohort study, comprising 105 patients with GPI admitted to the Dutch Vincent van Gogh Psychiatric Hospital in the period 1924-1954, the clinical presentation of this invalidating disorder is investigated and described in detail.