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[Here, we describe the initial clinical experience with comparative PET/CT and PET/MR imaging in four human AE patients at an Austrian reference centre.PET/MR imaging showed comparable diagnostic capacity for liver lesions attributable to E. multilocularis infection, with a discrepancy only in the assessment of calcifications in one patient. Effective doses of radiation were 30.4-31 mSV for PET/CT, which were reduced in PET/MRI to the exposure ofPET/MRI provides comparable diagnostic information for AE management. The reduction in radiation exposure compared to PET/CT may be of particular importance for children and young patients not amenable for curative surgery requiring repeated long-term follow-up with dual imaging modalities. Further studies are warranted to prospectively evaluate the potential of PET/MRI in the management of AE.DONNÉES DE BASE: L'imagerie par la tomographie par émission de positrons au [18F]-2-fluoro-2-désoxy-D-glucose (18F-FDG)/tomodensitométrie (TEP/TDM) fournit des informations importantes sur la taille et l'activité métabolique des lésions causées par Echinococcus multilocularis et est donc recommandée pour l’évaluation initiale et le suivi de l’échinococcose alvéolaire (EA) humaine. L'introduction de la tomographie par émission de positons/imagerie par résonance magnétique (TEP/IRM) dans la pratique clinique des systèmes de soins de santé aisés offre une alternative de modalité d'imagerie double, qui n'a pas encore été évaluée pour l’EA. OBJECTIF: Nous décrivons ici l'expérience clinique initiale comparant les imageries TEP/TDM et TEP/IRM chez quatre patients humains atteints d’EA dans un centre de référence autrichien. RÉSULTATS: L'imagerie TEP/IRM a montré une capacité de diagnostic comparable pour les lésions hépatiques imputables à une infection à E. multilocularis, avec une divergence uniquement lors de l’évaluation des calcifications chez un patient. Les doses efficaces de rayonnement étaient de 30,4 à 31 mSV pour la TEP/TDM, qui ont été réduites dans la TEP/IRM à une exposition au

Personal protective equipment and adherence to disinfection protocols are essential to prevent nosocomial severe acute respiratory syndrome coronavirus (SARS-CoV-2) transmission. Here, we evaluated infection control measures in a prospective longitudinal single-center study at the Vienna General Hospital, the biggest tertiary care center in Austria, with a structurally planned low SARS-CoV-2 exposure. SARS-CoV-2-specific antibodies were assessed by Abbott ARCHITECT chemiluminescent assay (CLIA) in 599 health care workers (HCWs) at the start of the SARS-CoV-2 epidemic in early April and two months later. Neutralization assay confirmed CLIA-positive samples. A structured questionnaire was completed at both visits assessing demographic parameters, family situation, travel history, occupational coronavirus disease 2019 (COVID-19) exposure, and personal protective equipment handling. At the first visit, 6 of 599 participants (1%) tested positive for SARS-CoV-2-specific antibodies. The seroprevalence increased to 1.5% (8/553) at the second visit and did not differ depending on the working environment. Unprotected SARS-CoV-2 exposure (p = 0.003), positively tested family members (p = 0.04), and travel history (p = 0.09) were more frequently reported by positively tested HCWs. Odds for COVID-19 related symptoms were highest for congestion or runny nose (p = 0.002) and altered taste or smell (p &lt, 0.001). In conclusion, prevention strategies proved feasible in reducing the risk of transmission of SARS-CoV-2 from patients and among HCWs in a low incidence hospital, not exceeding the one described in the general population.

Respiratory syncytial virus (RSV) testing is generally available in most care centres, but it is rarely performed because clinicians’ seldom suspect RSV to be the underlying pathogen in adults with respiratory disease. Here, we evaluate the impact of broad combined influenza/RSV testing on the clinical practice. Overall, 103 patients were tested positively for RSV. Our study indicates that positively tested patients were mostly of advanced age and suffered from chronic diseases. Mortality was significant in our cohort and higher in patients with advanced age. Further, we report a significant increase in detected RSV cases but also in detection rate. Together, these findings suggest that implementation of a combined influenza/RSV testing led to a significant increase in detection rate, supported clinicians establishing the correct diagnosis and allowed a safe and controlled handling of RSV patients.

Background: Aspiration community-acquired pneumonia (ACAP) and community-acquired pneumonia (CAP) in patients with aspiration risk factors (AspRFs) are infections associated with anaerobes, but limited evidence suggests their pathogenic role. Research Question: What are the aspiration risk factors, microbiology patterns, and empiric anti-anaerobic use in patients hospitalized with CAP? Study Design and Methods: This is a secondary analysis of GLIMP, an international, multicenter, point-prevalence study of adults hospitalized with CAP. Patients were stratified into three groups: (1) ACAP, (2) CAP/AspRF+ (CAP with AspRF), and (3) CAP/AspRF- (CAP without AspRF). Data on demographics, comorbidities, microbiological results, and anti-anaerobic antibiotics were analyzed in all groups. Patients were further stratified in severe and nonsevere CAP groups. Results: We enrolled 2,606 patients with CAP, of which 193 (7.4%) had ACAP. Risk factors independently associated with ACAP were male, bedridden, underweight, a nursing home resident, and having a history of stroke, dementia, mental illness, and enteral tube feeding. Among non-ACAP patients, 1,709 (70.8%) had CAP/AspRF+ and 704 (29.2%) had CAP/AspRF-. Microbiology patterns including anaerobes were similar between CAP/AspRF-, CAP/AspRF+ and ACAP (0.0% vs 1.03% vs 1.64%). Patients with severe ACAP had higher rates of total gram-negative bacteria (64.3% vs 44.3% vs 33.3%, P =.021) and lower rates of total gram-positive bacteria (7.1% vs 38.1% vs 50.0%, P 50% in all groups) independent of AspRFs or ACAP received specific or broad-spectrum anti-anaerobic coverage antibiotics. Interpretation: Hospitalized patients with ACAP or CAP/AspRF+ had similar anaerobic flora compared with patients without aspiration risk factors. Gram-negative bacteria were more prevalent in patients with severe ACAP. Despite having similar microbiological flora between groups, a large proportion of CAP patients received anti-anaerobic antibiotic coverage.

Human toxocariasis occurs worldwide and is caused by nematodes of the species of the genus Toxocara. Infection occurs by the ingestion of eggs and is usually asymptomatic or oligosymptomatic. However, severe manifestations occur. The burden of disease and its public health impact remain ill-defined. The aim of this review was to summarize all available data on the seroprevalence of toxocariasis on the African continent and factors associated with seropositivity.Twenty-seven original papers published between 1991 and 2017 were identified that provided data suitable for this review. Case-control studies were included and the seroprevalence in the (healthy) control group was used as a surrogate parameter.Antibodies against Toxocara spp. were found to be frequent in most populations and regions in Africa with the exception of two publications, one from the Democratic Republic of the Congo and one from Djibouti, where all participants were seronegative. The highest proportion of participants with antibodies was found on the island of La Réunion with 359 out 387 study participants being positive (92.8%). Factors associated with seropositivity were reported across studies, including-among others-older age, contact with soil via geophagia, agricultural activity or playing with soil, contact with animals, especially dogs, and low socio-economic status, defined as absence of water supply or poor housing. Three Egyptian studies found male gender to be associated with toxocariasis, whereas in La Réunion females were at increased risk.Exposure to toxocariasis seems to be very frequent and common in large parts of the African continent. However, no data are available for most countries. The public health impact of human toxocariasis and the frequency of severe manifestations remain unclear.

Between January 2018 and May 2019, 349 cases of Candida auris were reported in the European Union/European Economic Area*, 257 (73.6%) colonisations, 84 (24.1%) bloodstream infections, seven (2.0%) other infections and one case of unknown infection/colonisation status (0.3%). Most cases (97.1%, n = 339) were reported from Spain or the United Kingdom, but also for the first time in Greece, the Netherlands and Poland. Laboratory capacity and preparedness has improved since January 2018.

Background Invasive pneumococcal disease (IPD) is associated with high morbidity and mortality, with immunocompromised patients (ICPs) at particular risk. Therefore, guidelines recommend pneumococcal vaccination for these patients. However, guidelines are scarcely underpinned with references to incidence studies of IPD in this population. This, potentially results in unawareness of the importance of vaccination and low vaccination rates. The objective of this systematic review and meta-analysis was to assess the incidence of IPD in ICPs. Methods We systematically searched PubMed and Embase to identify studies in English published before December 6th, 2017 that included terms related to ‘incidence’, ‘rate’, ‘pneumococcal’, ‘pneumoniae’, ‘meningitis’, ‘septicemia’, or ‘bacteremia’. We focused on patients with HIV, transplantation and chronic inflammatory diseases. Results We included 45 studies in the systematic review reporting an incidence or rate of IPD, defined as isolation of Streptococcus pneumoniae from a normally sterile site. Random effects meta-analysis of 38 studies showed a pooled IPD incidence of 331/100,000 person years in patients with HIV in the late-antiretroviral treatment era in non-African countries, and 318/100,000 in African countries; 696 and 812/100,000 in patients who underwent an autologous or allogeneic stem cell transplantation, respectively; 465/100,000 in patients with a solid organ transplantation; and 65/100,000 in patients with chronic inflammatory diseases. In healthy control cohorts, the pooled incidence was 10/100,000. Discussion ICPs are at increased risk of contracting IPD, especially those with HIV, and those who underwent transplantation. Based on our findings, we recommend pneumococcal vaccination in immunocompromised patients. Prospero registration ID: CRD42016048438.

Fosmidomycin–piperaquine is being developed as nonartemisinin-based combination therapy to meet the challenge of emerging artemisinin resistance. The combination appeared to have high efficacy and be safe and well tolerated despite observed transient changes in electrocardiogram with prolongation of the QT interval., Background Fosmidomycin–piperaquine is being developed as nonartemisinin-based combination therapy to meet the challenge of emerging artemisinin resistance. Methods The study was a phase 2, single-arm, proof-of-concept study of the efficacy, tolerability, and safety of fosmidomycin–piperaquine for the treatment of uncomplicated Plasmodium falciparum monoinfection in Gabon. Adults and children of both sexes with initial parasite counts between 1000 and 150000/µL received oral treatment with fosmidomycin (twice daily doses of 30 mg/kg) and piperaquine (once daily dose of 16 mg/kg) for 3 days and followed-up for 63 days. The primary efficacy endpoint was the per-protocol polymerase chain reaction (PCR)–corrected day 28 adequate clinical and parasitological response (ACPR). Results One hundred patients were enrolled. The PCR-corrected day 28 ACPR rate was 83/83, or 100% (95% confidence interval, 96–100). Fourteen patients had asexual parasitaemia between day 28 and day 63; all were typed by PCR as new infections. Fosmidomycin–piperaquine therapy led to rapid parasite clearance (median, 36 hours; interquartile range [IQR], 6–60) and fever clearance time (median, 12 hours; IQR, 6–48). The electrocardiogram assessments showed 2 patients with prolonged QT interval >500 msec following study drug administration. The majority of adverse events affected the gastrointestinal and respiratory tracts and were transient and mild to moderate in severity. Conclusions This is the first report of the use of the combination fosmidomycin–piperaquine. The combination appeared to have high efficacy and be safe and well tolerated despite observed transient changes in electrocardiogram with prolongation of the QT interval. Clinical Trials Registration. NCT02198807.

Background The recent West African Ebola virus disease (EVD) outbreak had catastrophic impact on populations, health care systems and economies of the affected countries. Somatic symptoms have been reported to persist long beyond the acute infection. This review was conducted to provide an overview on neuro- and socio-psychological long-term sequelae of EVD survivors. Methods Utilizing Pubmed and PsycInfo databases, a systematic review prepared according to PRISMA guidelines. Only studies reporting quantitative data on neuropsychological sequelae three weeks or later after discharge from the Ebola-treating unit were included. Pooled proportions of common outcomes were calculated. Results In total, 224 papers were identified, of which 10 were included. Depression, insomnia, fatigue, anxiety and post-traumatic stress were common sequelae in EVD survivors. However, data from high-quality studies were scarce. Conclusions EVD survivors have been thought to commonly face neuropsychological long-term sequelae. Methodological drawbacks and heterogeneity of current studies limit conclusions of the impact and magnitude of such sequelae. We advocate the preparation of a prospective, controlled cohort study protocol in preparation for a future outbreak.

An alert regarding an outbreak of carbapenem-resistant Klebsiella pneumoniae carrying bla NDM-1 and bla OXA-48 carbapenemase-encoding genes was sent by Germany to European Union (EU)/European Economic Area (EEA) countries in October 2019. Since only limited whole genome sequencing (WGS) data on bla NDM-1- and bla OXA-48-positive K. pneumoniae were available in the public domain, national public health reference or equivalent expert laboratories from EU/EEA countries were invited to share WGS data from their national collections with the European Centre for Disease Prevention and Control (ECDC) to investigate the international dissemination of this epidemic strain. The analysis identified a Finnish case with an isolate closely related to the German outbreak strain and with an epidemiological link to St. Petersburg, Russia. In addition, several other clusters of genetically related bla NDM-1- and bla OXA-48-positive K. pneumoniae unrelated to the German outbreak strain but affecting numerous EU/EEA countries were identified. The aim of this follow-up investigation was to characterise these clusters based on the integrated analysis of the WGS dataset on bla NDM-1 - and bla OXA-48-positive K. pneumoniae submitted from 13 EU/EEA countries and additional epidemiological data.

Background Toxocariasis is a globally distributed zoonosis. The most important definitive hosts are dogs, whereas humans serve as paratenic hosts. Transmission to humans occurs by accidental ingestion of eggs, e.g. by consumption of contaminated fruits or vegetables. Although exposure to Toxocara is usually considered as relatively benign, it is implicated in a range of neurological, ophthalmologic and other organ-specific conditions, some of them with grave consequences. This review provides an overview on the epidemiology, presentation and risk factors of exposure to Toxocara in Africa. Methods A systematic search was performed for studies published after January 1st, 1990, in English, French, Portuguese, Spanish, Dutch or German. The review was prepared according to PRISMA guidelines. Studies on toxocariasis in human populations and contamination in human environments were included. Results Sixty-five papers were included. Antibodies against Toxocara spp. in humans were found to be very common across Africa. Severe manifestations have been reported mainly from North Africa. Environmental contamination including soil, vegetables and fruits sold on markets was demonstrated in various locations in Africa. Conclusions Exposure to Toxocara is prevalent across the African continent. However, the complication frequency, the impact of the condition on the individual and the public health relevance of this zoonosis, and the economic impact have never been systematically evaluated.

Cystic echinococcosis (CE) is a widespread zoonosis caused by the species complex Echinococcus granulosus. Albendazole (ABZ)—the first-line anthelminthic drug for medical treatment of CE—is metabolized in vivo to the active derivative ABZ-sulphoxide (ABZ-SO). Target-site ABZ-SO concentrations in the hydatid cyst mediate the anthelminthic effect in CE. Primary outcome of this systematic review of individual patient data was the intra-cystic ABZ-SO concentration stratified by cyst size, location, calcification status and use of praziquantel. Studies reporting intra-cystic ABZ-SO concentrations in humans were identified by a systematic search. A pooled analysis of individual patient data was performed to assess intra-cystic concentrations. Pharmacokinetic data of 121 individual cysts were analysed. There was no correlation between plasma and intra-cystic ABZ-SO concentrations (rho = −0.03, p = 0.76). Intra-cystic drug concentrations were also not associated with sex and treatment duration. Use of praziquantel in combination with ABZ was associated with higher plasma (median 540 vs. 240 μg/L; p = 0.04) but not intra-cystic ABZ-SO concentrations (median 220 vs. 199 μg/L; p = 0.36). Relative drug concentrations in hepatic cysts were higher than in other cysts (0.8 vs. 0.4; p = 0.05). Intra-cystic concentrations were higher in calcified than non-calcified cysts (median 897 vs. 245 μg/L; p = 0.03). There was a trend towards higher intra-cystic concentrations in smaller sized cysts (β = −17.2 μg/L/cm; 95th CI, −35.9 to 1.6; p = 0.07). This study demonstrates that mean intra-cystic drug concentrations are similar to plasma concentrations on a population level. However, in individual patients plasma concentrations are not directly predictive for intra-cystic concentrations. The use of booster drugs was not associated with higher intra-cystic ABZ-SO concentrations in this analysis. Electronic supplementary material The online version of this article (doi:10.1007/s00436-016-5054-x) contains supplementary material, which is available to authorized users.

Background Cystic echinococcosis (CE) is a globally occurring zoonosis, whereas alveolar echinococcosis (AE) is endemic only in certain parts of the Northern Hemisphere. The socioeconomic impact of human echinococcosis has been shown to be considerable in highly endemic regions. However, detailed data on direct healthcare-related costs associated with CE and AE are scarce for high income countries. The aim of this study was to evaluate direct costs of human disease caused by CE and AE in Austria. Methods Clinical data from a registry maintained at a national reference center for echinococcosis at the Medical University of Vienna were obtained for the years 2012–2014. These data were used in conjunction with epidemiological data from Austria’s national disease reporting system and diagnostic reference laboratory for echinococcosis to assess nationwide costs attributable to CE and AE. Results In Austria, total modelled direct costs were 486,598€ (95%CI 341,825€ – 631,372€) per year for CE, and 683,824€ (95%CI 469,161€ - 898,486€) for AE. Median costs per patient with AE from diagnosis until the end of a 10-year follow-up period were 30,832€ (25th– 75th percentile: 23,197€ - 31,220€) and 62,777€ (25th– 75th percentile: 60,806€ - 67,867€) for inoperable and operable patients, respectively. Median costs per patients with CE from diagnosis until end of follow-up after 10 years were 16,253€ (25th– 75th percentile: 8,555€ - 24,832€) and 1,786€ (25th– 75th percentile: 736€ - 2,146€) for patients with active and inactive cyst stages, respectively. The first year after inclusion was the most cost-intense year in the observed period, with hospitalizations and albendazole therapy the main contributors to direct costs. Conclusions This study provides detailed information on direct healthcare-related costs associated with CE and AE in Austria, which may reflect trends for other high-income countries. Surgery and albendazole therapy, due to surprisingly high drug prices, were identified as important cost-drivers. These data will be important for cost-effectiveness analyses of possible prevention programs., Author summary Cystic and alveolar echinococcosis, caused by E. granulosus and E. multilocularis, both occur in humans in Austria. Lesions may develop at any site, with the liver being most frequently affected. Morbidity–especially for alveolar echinococcosis–can be significant and treatment may include major surgery or long-term suppressive medical therapy. The present study was performed to investigate direct healthcare-related costs of cystic and alveolar echinococcosis in Austria based on the data from a clinical registry maintained at the reference center for echinococcosis, the reference laboratory for echinococcosis and data from the national disease reporting system. Annual incidences of AE and CE were estimated at λ = 12 and λ = 40 newly diagnosed cases per year, respectively. Estimated costs due to cystic echinococcosis were 486,598€ (95%CI 341,825€ – 631,372€) per year, and 683,824€ (95%CI 469,161€ - 898,486€) for AE. Major cost drivers were surgical interventions with hospitalizations and drug costs. These data will provide a basis for cost-effectiveness analyses of prevention programs, and highlight possible targets for cost reduction strategies.

Cystic echinococcosis (CE) is a globally endemic zoonosis caused by the larval stage of the Echinococcus granulosus sensu lato (s.l.) complex. Although the disease is known to be highly prevalent in certain parts of North and East Africa, data on CE, both in humans and definitive hosts, are extremely scarce for Central Africa. The present study assessed the epidemiology of CE in humans and dogs in rural Gabon. An ultrasound and serologic survey was conducted in volunteers from rural villages in Gabon. A two-step approach was used for serological testing with an indirect hemagglutination assay as a screening test and Western Blot as a confirmatory test. Fecal dog samples were analyzed microscopically, and polymerase chain reaction (PCR) amplification of nad1 and cox1 genes was performed when taeniid eggs were visible. Regional hospitals and the national reference center for parasitology in Gabon were contacted for information about previous cases of CE. Randomly selected communities were invited to participate. Three hundred and forty-eight human volunteers from these communities were screened. No suspected cases of CE were detected. Definitive host screening was performed from 128 fecal samples from representative subregions, but no eggs from E. granulosus s.l. were found. No documented cases of echinococcosis were reported from the local health-care institutions and the national diagnostic reference center in Gabon. Cystic echinococcosis seems to be very rare or absent in Gabon. The reason for this lack of evidence for echinococcosis is unknown, but the absence of livestock may play a major role.

Malaria is among the major threats to global health with the main burden of disease being in rural areas of developing countries where accurate diagnosis based on non-invasive samples is in high demand. We here present a novel molecular assay for detection of malaria parasites based on technology that may be adapted for low-resource settings. Moreover, we demonstrate the exploitation of this assay for detection of malaria in saliva. The setup relies on pump-free microfluidics enabled extraction combined with a DNA sensor substrate that is converted to a single-stranded DNA circle specifically by topoisomerase I expressed by the malaria causing Plasmodium parasite. Subsequent rolling circle amplification of the generated DNA circle in the presence of biotin conjugated deoxynucleotides resulted in long tandem repeat products that was visualized colorimetrically upon binding of horse radish peroxidase (HRP) and addition of 3,3′,5,5′-Tetramethylbenzidine that was converted to a blue colored product by HRP. The assay was directly quantitative, specific for Plasmodium parasites, and allowed detection of Plasmodium infection in a single drop of saliva from 35 out of 35 infected individuals tested. The results could be determined directly by the naked eye and documented by quantifying the color intensity using a standard paper scanner.

Rapid and reliable diagnosis is essential in the fight against malaria, which remains one of the most deadly infectious diseases in the world. In the present study we take advantage of a droplet microfluidics platform combined with a novel and user-friendly biosensor for revealing the main malaria-causing agent, the Plasmodium falciparum (P. falciparum) parasite. Detection of the parasite is achieved through detection of the activity of a parasite-produced DNA-modifying enzyme, topoisomerase I (pfTopoI), in the blood from malaria patients. The assay presented has three steps: (1) droplet microfluidics-enabled extraction of active pfTopoI from a patient blood sample, (2) pfTopoI-mediated modification of a specialized DNA biosensor, (3) readout. The setup is quantitative and specific for the detection of Plasmodium topoisomerase I. The procedure is a considerable improvement of the previously published Rolling Circle Enhanced Enzyme Activity Detection (REEAD) due to the advantages of involving no signal amplification steps combined with a user-friendly readout. In combination these alterations represent an important step towards exploiting enzyme activity detection in point-of-care diagnostics of malaria.

Summary Objectives On the background of a high prevalence of HHV-8 infection in pre-pubertal Central African children, this study investigated the potential for in utero transmission of HHV-8. Patients Gabonese pregnant women were invited to provide peripheral and cord blood samples for serological and PCR diagnostics of HHV-8 infection at delivery for this cross-sectional survey. Results Out of 344 participants 120 (35%, 95% CI: 30-40%) were serologically positive for HHV-8. 31% (95% CI: 22-40%) of cord blood samples of seropositive women had detectable IgG antibodies. Among all seropositive participants HHV-8 was detected by PCR in one maternal peripheral blood sample at delivery (1%, 95% CI: 0.2-7%) and in none of cord blood samples. There was no association between demographic characteristics and infection status. Similarly, there was no difference in risk for premature delivery, low birth weight, and maternal anaemia in HHV-8 seropositive women. Discussion These data suggest a high seroprevalence of HHV-8 infection in pregnant women, however viraemia at delivery does not commonly occur in Central Africa. Based on these observations it may be speculated that infection of children may occur more commonly either antepartum or later on in infancy and childhood.

Trichuris trichiura is a common soil-transmitted helminthic pathogen with considerable impact on human health. To achieve appropriate control of trichuriasis from a public health perspective, effective treatments and regular education of populations most at risk such as children and pregnant women are essential. Currently available drugs show however only unsatisfying cure rates when used in short-course regimens, and egg reduction rates are disappointingly low. An improvement in efficacy of drug therapy has been demonstrated for a prolonged 3-day dosing regimen of albendazole as well as for a combination therapy of albendazole and oxantel pamoate or mebendazole and albendazole. However, even these regimens do not reach the widely accepted threshold for a satisfactory cure rate of at least 90 %. While this lack of efficacy of current anthelminthic drugs may be explained by specific single nucleotide polymorphisms in the β-tubulin gene of T. trichiura, these findings highlight the need for further research to develop highly efficacious short-course treatments for human trichuriasis.

The risk for occurrence of venous thromboembolism (VTE) in cancer patients has been the aim of numerous investigations. Chronic kidney disease (CKD) is a frequent comorbidity in cancer patients and has been found to be a risk factor for VTE in the general population. We investigated the association of CKD with VTE and mortality in cancer patients.Patients were recruited into the prospective cohort study, Vienna Cancer and Thrombosis Study (CATS). CKD was estimated with equations for glomerular filtration rate (eGFR) based on serum creatinine by Modification of Diet in Renal Disease (MDRD), CKD Epidemiology collaboration (CKD-EPI) and Cockcroft-Gault equation (C-G). Patients were subsequently classified to stages of CKD according to the Kidney Diseases Outcomes Quality Initiative. Primary endpoint was occurrence of VTE and secondary endpoint was death.The cohort of 1100 patients was prospectively followed over a median of 723 days. CKD with an eGFR of under 90 ml/min was common with a prevalence of 71.1%, 67.0% or 51.5% of patients calculated with MDRD, CKD-EPI and C-G equations, respectively, but severe CKD (eGFR30 ml/min) was rare. Patients with a moderately decreased eGFR (90-60 ml/min/1.73 m(2)) based on CKD-EPI had a subdistribution hazard ratio of 0.68 (95% confidence interval 0.43-1.06). An association between CKD and occurrence of VTE or mortality could also not be shown with the other equations.In our investigation of a large cohort of cancer patients with a high prevalence of CKD, a reduced eGFR was not an independent risk factor for occurrence of VTE or death.

Toxocara spp. are zoonotic parasites with global distribution infecting humans by incidental ingestions of eggs shed in feces of dogs or cats. High seroprevalences have been reported from several regions of Africa, however data from the Central African region remain limited. Although several clinical entities caused by larvae of Toxocara spp. have been described, the public heath impact of this infection has so far often been neglected. This study was conducted to estimate the prevalence in a rural central African population.The population based study was performed in volunteers in a rural region of Gabon. A two-step testing approach was applied using an ELISA as screening test and a Western Blot (immunoblot) as confirmatory assay. Basic demographic data and risk factors were collected and compared between seropositive and negative participants.In total, 199 out of 332 serum samples were tested positive for Toxocara spp. antibodies (59.9%). After standardization for age to the overall Gabonese population seroprevalence was 53.6% (95% CI 48.2–59.0%). There was a trend towards higher seroprevalence in participants with agricultural activity.Seroprevalence of antibodies against Toxocara spp. is high in this rural population in Gabon. These results are comparable with previous reports from other sub-regions of Africa and add to our understanding of the epidemiology of toxocariasis in Africa. Given the high prevalence of toxocariasis in tropical regions, it may be speculated that clinically relevant presentations (e.g. visceral or ocular larva migrans syndrome) may occur in considerable numbers. A formal assessment of the burden of disease and the public health impact of human toxocariasis is therefore warranted.

BACKGROUND: Antibiotic resistance is a major global health problem and pathogens such as meticillin-resistant Staphylococcus aureus (MRSA) have become of particular concern in the management of lower respiratory tract infections. However, few data are available on the worldwide prevalence and risk factors for MRSA pneumonia. We aimed to determine the point prevalence of MRSA pneumonia and identify specific MRSA risk factors in community-dwelling patients hospitalised with pneumonia.METHODS: We did an international, multicentre study of community-dwelling, adult patients admitted to hospital with pneumonia who had microbiological tests taken within 24 h of presentation. We recruited investigators from 222 hospitals in 54 countries to gather point-prevalence data for all patients admitted with these characteristics during 4 days randomly selected during the months of March, April, May, and June in 2015. We assessed prevalence of MRSA pneumonia and associated risk factors through logistic regression analysis.FINDINGS: 3702 patients hospitalised with pneumonia were enrolled, with 3193 patients receiving microbiological tests within 24 h of admission, forming the patient population. 1173 (37%) had at least one pathogen isolated (culture-positive population). The overall prevalence of confirmed MRSA pneumonia was 3·0% (n=95), with differing prevalence between continents and countries. Three risk factors were independently associated with MRSA pneumonia: previous MRSA infection or colonisation (odds ratio 6·21, 95% CI 3·25-11·85), recurrent skin infections (2·87, 1·10-7·45), and severe pneumonia disease (2·39, 1·55-3·68).INTERPRETATION: This multicountry study shows low prevalence of MRSA pneumonia and specific MRSA risk factors among community-dwelling patients hospitalised with pneumonia.FUNDING: None.

To the Editor: Loa loa, the African eye worm, is a filarial pathogen of Central African rainforest regions. As of 2013, it had affected an estimated 2–3 million persons in Central Africa (1,2). Adult worm migrations in humans may intermittently cause Calabar swelling, and microfilariae are commonly found in blood and body fluids. Loiasis is a chronic infection persisting for many years; a considerable proportion of women in loiasis-endemic regions are infected during gestation. To date, the epidemiology of loiasis in pregnant women has not been investigated, and the effects of loiasis on maternal and fetal health outcomes are unknown. We investigated the epidemiology of loiasis in a cohort of pregnant women participating in a drug trial for preventing malaria during pregnancy.

We present an 18-year-old, immunocompetent Austrian military conscript with cervical lymphadenopathy, fever, back-pain, and persistent inflammation markers despite two weeks of antimicrobial therapy with ampicillin/sulbactam. All specific laboratory investigations for identification of a specific etiology, including blood cultures and autoantibodies, were inconspicuous. Abdominal computed tomography showed multiple hypodense hepatosplenic lesions and osteomyelitis of the thoracic and lumbar spine with base plate fracture. Based on the patient’s history, clinical presentation, and radiological findings, serology for cat scratch disease (CSD) was performed and highB. henselaespecific IgM and IgG antibodies were detected. Due to its variety of clinical presentations, diagnosis of CSD is challenging, especially in the absence of a history of specific exposure. This case report shall remind the physician that cat scratch disease is a common disease, mainly presenting with fever and lymphadenopathy in young patients. Nevertheless CSD has many different and rare forms of presentations, including hepatosplenic lesions and bone involvement as shown in this case.

Objectives Streptococcus agalactiae constitutes an important cause of neonatal infections in sub-Saharan Africa. Sulfadoxine/pyrimethamine—the current intermittent preventive treatment of malaria in pregnancy (IPTp)—has proven in vitro activity against group B Streptococcus (GBS). Because of specific drug resistance to sulfadoxine/pyrimethamine, mefloquine—an antimalarial without in vitro activity against GBS—was evaluated as a potential alternative. This study assessed the potential of sulfadoxine/pyrimethamine-IPTp to reduce the prevalence of GBS colonization in pregnant women in Gabon when compared with the inactive control mefloquine-IPTp. Methods Pregnant women participating in a randomized controlled clinical trial evaluating mefloquine-IPTp versus sulfadoxine/pyrimethamine-IPTp were invited to participate and recto-vaginal swabs were collected at delivery for detection of GBS colonization. Prevalence of recto-vaginal GBS colonization was compared between IPTp regimens and risk factor and birth outcome analyses were computed. Results Among 549 participants, 106 were positive for GBS colonization at delivery (19%; 95% CI = 16%–23%). Prevalence of maternal GBS colonization showed no significant difference between the two IPTp regimens (mefloquine-IPTp: 67 of 366 women = 18%; 95% CI = 14%–22%; sulfadoxine/pyrimethamine-IPTp: 39 of 183 women = 21%; 95% CI = 15%–27%). Risk factor analysis for GBS colonization demonstrated a significant association with illiteracy (adjusted OR = 2.03; 95% CI = 1.25–3.30). GBS colonization had no impact on birth outcome, anaemia at delivery, gestational age and birth weight. Conclusions Sulfadoxine/pyrimethamine did not reduce colonization rates when used as the IPTp drug during pregnancy. Illiteracy was associated with GBS colonization.

The objective of this study was to evaluate adherence and causes for non-adherence to antihypertensive therapy in Austrian patients. A special focus was placed on social parameters and behavioural theories. Patients were invited via advertisements in community pharmacies in Austria to complete an online survey. Inclusion criteria were an age of 18 years or older, a diagnosis of arterial hypertension and a current prescription of antihypertensive medication. Adherence was measured by the four-item Morisky scale. Non-adherence was defined by at least one point in the Morisky scale. Several demographic, social and behavioural parameters were analysed as potential co-variables associated with adherence. A total of 323 patients completed the online survey, of which 109 (33.7 %) met the criteria for non-adherence. In a multivariable model, self-efficacy and age were associated with adherence, whereas intention and barriers were linked to non-adherence; 56 patients (17.3 %) were classified as intentionally non-adherent. This study demonstrates that non-adherence affects an important proportion of patients in the treatment of arterial hypertension. Young age was a particularly important risk factor for non-adherence, and this patient population is, therefore, in need of special attention. Modifiable risk factors were identified that could help improving the treatment of arterial hypertension and potentially other chronic conditions.

Introduction Patients with cancer are at risk of venous thromboembolism (VTE). Statin-use has been shown to be associated with low risk of VTE in patients without cancer, but data in cancer patients is scarce. The objective of this study was to evaluate the association of statins with risk of VTE in cancer patients in a prospective observational cohort study. Materials and Methods Patients with newly diagnosed cancer or progression of disease after remission were included and prospectively followed for a maximum of 2 years. Study endpoint was occurrence of symptomatic VTE. Results Patients (n = 1434) were followed over a median observation period of 729 days. VTE occurred in 107 (7.5%) patients. At study inclusion, 170 (11.9%) patients took statins. Simvastatin (n = 96) and atorvastatin (n = 48) were the most frequently prescribed statins. VTE occurred in 6 (3.5%) patients with statins. Patients with statins had a lower risk of VTE than patients without (subhazard ratio 0.43, 95% confidence interval 0.19 to 0.98; p = 0.04). In competing risk analysis, the cumulative probability of VTE in patients with statins was 2.94% after 12 months and 3.54% after 24 months, compared to 7.13% and 8.13% in the group without statins (Gray’s test: p = 0.04). Conclusion This study provides observational evidence for an association between statin use and low risk of VTE in patients with cancer. The role of statins for prevention of cancer-associated VTE needs to be confirmed in randomized, controlled trials.

Summary Background Artemisinin derivatives are the mainstay of antimalarial treatment, both for uncomplicated malaria and for severe disease. Artemisinins are known for their rapid onset of action, good tolerability, and safety. However, besides the sporadic but worrying reports of delayed parasite clearance after treatment with artemisinins, there have been an increasing number of reports of acute haemolytic anaemia following their use and the safety of this class of antimalarials is being questioned. Methods In this systematic review, all reports of patients experiencing haemolysis following the use of artemisinins for the treatment of malaria were identified and collated into an electronic database. Summary statistics were calculated to characterize the epidemiology and clinical features of this safety concern related to artemisinin derivatives. Results A total of 37 patients were identified suffering from haemolysis following the treatment of severe malaria with artemisinin derivatives. Thirty-one cases had received intravenous artesunate, while the remaining cases were attributed to other parenteral or oral regimens of artemisinin derivatives. The majority of patients were returning travellers ( n =30), and six clinical cases had been reported in paediatric patients. The median onset of haemolysis was 15 (interquartile range (IQR) 13–15) days after the initiation of treatment for the ‘delayed-onset' pattern and 17 (IQR 13–22) days for the ‘persistent' haemolysis pattern. The median reduction in haemoglobin due to haemolysis was 6 g/dl (IQR 4–8 g/dl). The estimated proportion of patients suffering from severe malaria experiencing haemolysis after treatment with artemisinin derivatives was 13% (95% confidence interval 9–18%), and 73% of these (i.e., 9% of the total population) required blood transfusions. No fatal outcome has been reported in the literature to date. Conclusions Haemolysis is commonly associated with the class of artemisinin drugs when used for the treatment of severe malaria. Potential causes of this safety issue are discussed. Although no deaths attributed to haemolysis have been reported so far, this safety issue may lead to life-threatening anaemia and is particularly worrying for regions where safe blood products are not readily available.

Background Cancer patients are at high risk of developing venous thromboembolism (VTE). Red cell distribution width (RDW) has been reported to be associated with arterial and venous thrombosis and mortality in several diseases. Here, we analyzed the association between RDW and other red blood cell (RBC) parameters with risk of VTE and mortality in patients with cancer. Methods RBC parameters were measured in 1840 patients with cancers of the brain, breast, lung, stomach, colon, pancreas, prostate, kidney; lymphoma, multiple myeloma and other tumor sites, that were included in the Vienna Cancer and Thrombosis Study (CATS), which is an ongoing prospective, observational cohort study of patients with newly diagnosed or progressive cancer after remission. Primary study outcome is occurrence of symptomatic VTE and secondary outcome is death during a maximum follow-up of 2 years. Results During a median follow-up of 706 days, 131 (7.1%) patients developed VTE and 702 (38.2%) died. High RDW (>16%) was not associated with a higher risk of VTE in the total study cohort; in competing risk analysis accounting for death as competing variable the univariable subhazard ratio (SHR) was 1.34 (95% confidence interval [CI]: 0.80–2.23, p = 0.269). There was also no significant association between other RBC parameters and risk of VTE. High RDW was associated with an increased risk of mortality in the total study population (hazard ratio [HR, 95% CI]: 1.72 [1.39–2.12], p

Summary. Background: Cancer patients are at increasedrisk of venous thromboembolism (VTE). Objective: Weinvestigated the association of a history of VTE, superfi-cial thrombophlebitis, or the presence of varicose veinswith the occurrence of VTE during the course of cancer.Methods: Cancer patients were recruited in a prospectivecohort study, the Vienna Cancer and Thrombosis Study.Patients who had VTE within 3 months before studyinclusion were excluded. At study inclusion, history ofVTE, history of superficial thrombophlebitis, and pres-ence of varicose veins were recorded. Primary end pointwas the occurrence of symptomatic VTE. Hazard ratioswere obtained using the competing risk analysis accordingto Fine and Gray. Results: The cohort consisted of 1270patients followed over a median of 590 days. A history ofVTE was found in 66 patients (5.2%), superficial throm-bophlebitis in 79 patients (6.2%), and varicose veins in160 patients (12.6%). Ninety-eight patients (7.7%) devel-oped VTE during follow-up. The hazard ratios for therisk of VTE in patients with a history of VTE or superfi-cial thrombophlebitis were 1.44 (95% confidence interval:0.67–3.07) and 1.94 (1.04–3.61), respectively, and 2.01(1.26–3.21) in those with varicose veins. In multivariableanalysis including history of VTE, history of superficialthrombophlebitis, presence of varicose veins, and otherpatient-related factors, the presence of varicose veins(2.10 [1.29–3.41]) remained significantly associated withan increased risk of VTE. Conclusion: The presence ofvaricose veins is associated with an elevated risk of VTEin cancer patients. This clinical parameter could be usefulfor individual risk assessment of VTE in these patients.Keywords: neoplasm; risk; thrombophlebitis; varicoseveins; venous thromboembolism.IntroductionThe association of cancer and venous thromboembolism(VTE) is well established. Since VTE events in cancerpatients are accompanied with high mortality and morbid-ity [1–4], further research into the details of the associationbetween cancer and VTE is necessary. In the general pop-ulation, many risk factors for VTE have been identified.Superficial thrombophlebitis, varicose veins, and a historyof VTE in particular increase the risk of VTE [1,5,6].In cancer patients, several patient-specific risk factorsfor cancer-associated VTE have been described [7,8]. Sim-ilar to the general population, a history of previous VTEhas been regarded as a risk factor for recurrent VTEevents in cancer patients. For instance, Agnelli et al.reported that surgical cancer patients with a history ofVTE had a six-fold increased risk of new VTE eventsafter surgery [9]. Similarly, a four-fold increased VTE riskwas found for multiple myeloma patients and a 20-foldincreased VTE risk was found for patients with ovariancancer and a history of VTE [10,11]. In another prospec-tive observational study on a cohort of medical patientswith different cancer entities, a two-fold increase in VTEevents was found in patients with history of VTE [8].Prandoni et al. further demonstrated that cancer patientsare still at higher risk of recurrent VTE compared withnon-cancer patients, even while receiving anticoagulationtherapy [12].However, it has not been entirely elucidated whethera history of previous VTE that did not occur in close

BackgroundBacteraemia is a frequent and severe condition with a high mortality rate. Despite profound knowledge about the pre-test probability of bacteraemia, blood culture analysis often results in low rates of pathogen detection and therefore increasing diagnostic costs. To improve the cost-effectiveness of blood culture sampling, we computed a risk prediction model based on highly standardizable variables, with the ultimate goal to identify via an automated decision support tool patients with very low risk for bacteraemia.MethodsIn this retrospective hospital-wide cohort study evaluating 15,985 patients with suspected bacteraemia, 51 variables were assessed for their diagnostic potency. A derivation cohort (n = 14.699) was used for feature and model selection as well as for cut-off specification. Models were established using the A2DE classifier, a supervised Bayesian classifier. Two internally validated models were further evaluated by a validation cohort (n = 1,286).ResultsThe proportion of neutrophile leukocytes in differential blood count was the best individual variable to predict bacteraemia (ROC-AUC: 0.694). Applying the A2DE classifier, two models, model 1 (20 variables) and model 2 (10 variables) were established with an area under the receiver operating characteristic curve (ROC-AUC) of 0.767 and 0.759, respectively. In the validation cohort, ROC-AUCs of 0.800 and 0.786 were achieved. Using predefined cut-off points, 16% and 12% of patients were allocated to the low risk group with a negative predictive value of more than 98.8%.ConclusionApplying the proposed models, more than ten percent of patients with suspected blood stream infection were identified having minimal risk for bacteraemia. Based on these data the application of this model as an automated decision support tool for physicians is conceivable leading to a potential increase in the cost-effectiveness of blood culture sampling. External prospective validation of the model's generalizability is needed for further appreciation of the usefulness of this tool.

Tropheryma whipplei is the causative agent of Whipple's disease and has been detected in stools of asymptomatic carriers. Colonization has been associated with precarious hygienic conditions. There is a lack of knowledge about the epidemiology and transmission characteristics on a population level, so the aim of this study was to determine the overall and age-specific prevalence of T. whipplei and to identify risk factors for colonization. This molecular epidemiological survey was designed as a cross-sectional study in a rural community in Central African Gabon and inhabitants of the entire community were invited to participate. Overall prevalence assessed by real-time PCR and sequencing was 19.6% (95% CI 16–23.2%, n = 91) in 465 stool samples provided by the study participants. Younger age groups showed a significantly higher prevalence of T. whipplei colonization ranging from 40.0% (95% CI 27.8–52.2) among the 0–4 year olds to 36.4% (95% CI 26.1–46.6) among children aged 5–10 years. Prevalence decreased in older age groups (p