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In recent decades, enhancing scientific literacy has been the ultimate goal of science education worldwide. This effort aims to develop the skills by individuals to cope with the challenges of the modern world, which requires scientific knowledge and thinking. This research study aimed to investigate and compare the scientific literacy level of Greek pre-service teachers and primary school students. The total number of participants was 787, of which 362 were pre-service teachers and 425 primary school students. Scientific literacy was assessed with the selected response measure of demonstrated scientific literacy (SLA-D). According to descriptive analyses and statistical hypothesis tests, pre-service teachers' scientific literacy level was considered significantly higher than students, as was expected. However, the scientific literacy level of both pre-service teachers and students in the sample remained low. This work provides recommendations for actions that can help improve the scientific literacy level of both students and teachers so that schools become a source of scientifically literate future citizens.

Modelling Data (MODA) reporting guidelines have been proposed for common terminology and for recording metadata for physics-based materials modelling and simulations in a CEN Workshop Agreement (CWA 17284:2018). Their purpose is similar to that of the Quantitative Structure-Activity Relationship (QSAR) model report form (QMRF) that aims to increase industry and regulatory confidence in QSAR models, but for a wider range of model types. Recently, the WorldFAIR project’s nanomaterials case study suggested that both QMRF and MODA templates are an important means to enhance compliance of nanoinformatics models, and their underpinning datasets, with the FAIR principles (Findable, Accessible, Interoperable, Reusable). Despite the advances in computational modelling of materials properties and phenomena, regulatory uptake of predictive models has been slow. This is, in part, due to concerns about lack of validation of complex models and lack of documentation of scientific simulations. The models are often complex, output can be hardware- and software-dependent, and there is a lack of shared standards. Despite advocating for standardised and transparent documentation of simulation protocols through its templates, the MODA guidelines are rarely used in practice by modellers because of a lack of tools for automating their creation, sharing, and storage. They also suffer from a paucity of user guidance on their use to document different types of models and systems. Such tools exist for the more well-established QMRF and have aided widespread implementation of QMRFs. To address this gap, a simplified procedure and online tool, Easy-MODA, has been developed to guide users through MODA creation for physics-based and data-based models, and their various combinations. Easy-MODA is available as a web-tool on the Enalos Cloud Platform (https://www.enaloscloud.novamechanics.com/insight/moda/). The tool streamlines the creation of detailed MODA documentation, even for complex multi-model workflows, and facilitates the registration of MODA workflows and documentation in a database, thereby increasing their Findability and thus Re-usability. This enhances communication, interoperability, and reproducibility in multiscale materials modelling and improves trust in the models through improved documentation. The use of the Easy-MODA tool is exemplified by a case study for nanotoxicity evaluation, involving interlinked models and data transformation, to demonstrate the effectiveness of the tool in integrating complex computational methodologies and its significant role in improving the FAIRness of scientific simulations.

NanoBioAccumulate is a free-to-use web-based tool hosted on the Enalos DIAGONAL Cloud Platform (https://www.enaloscloud.novamechanics.com/diagonal/pbpk/) that provides users with the capability to model and predict the uptake and bioaccumulation of nanomaterials (NMs) by soil and aquatic invertebrates using two common first-order one-compartment biokinetic models. NanoBioAccumulate offers an approach for comprehensively analyzing the kinetics of different forms of NMs via a nonlinear fitting feature, integrating them with environmental fate models, and considering important physiological processes. NanoBioAccumulate overcomes the constraint of requiring prior knowledge of kinetic rate constants associated with the biokinetic models and eliminates the need for external statistical analysis software as it quantifies the kinetic rate constants and other constants through the application of nonlinear regression, using user-provided experimental data. Furthermore, NanoBioAccumulate incorporates statistical analysis measures like the adjusted R-squared and the bias-corrected Akaike information criterion, allowing for assessment of the goodness-of-fit of the two different biokinetic models, assisting in the identification of the best-performing model for a specific nanoform and its uptake kinetics by a specific invertebrate. The tool also includes model scenarios, retrieved from literature, which involve examining the exposure of soil and aquatic invertebrates to various types of NMs such as TiO2, SiO2, C60, graphene, graphene oxide (GO), Au, Ag and its ionic control AgNO3. These model scenarios aim to enhance understanding of the uptake and elimination rates exhibited by different NM-species. NanoBioAccumulate features advanced integration capabilities, enabled by an extensive Application Programming Interface (API). This functionality promotes efficient data exchange and interoperability with other software and web applications, significantly expanding its utility in research, regulatory risk assessment and environmental surveillance and monitoring contexts. The inclusion of a user-friendly Graphical User Interface (GUI) in NanoBioAccumulate greatly improves the overall user experience by simplifying complex tasks and eliminating the need for programming proficiency, thereby expanding the tool's applicability to a diverse range of users across various fields such as environmental research, monitoring, and regulation.

NanoTube Construct is a web tool for the digital construction of nanotubes based on real and hypothetical single-layer materials including carbon-based materials such as graphene, graphane, graphyne polymorphs, graphidiyene and non-carbon materials such as silicene, germanene, boron nitride, hexagonal bilayer silica, haeckelite silica, molybdene disulfide and tungsten disulfide. Contrary to other available tools, NanoTube Construct has the following features: a) it is not limited to zero thickness materials with specific symmetry, b) it applies energy minimisation to the geometrically constructed Nanotubes to generate realistic ones, c) it derives atomistic descriptors (e.g., the average potential energy per atom, the average coordination number, etc.), d) it provides the primitive unit cell of the constructed Nanotube which corresponds to the selected rolling vector (i.e., the direction in which the starting nanosheet is rolled to form a tube), e) it calculates whether the Nanotube or its corresponding nanosheet is more energetically stable and f) it allows negative chirality indexes. Application of NanoTube Construct for the construction of energy minimised graphane and molybdenum disulfide nanotubes are presented, showcasing the tool's capability. NanoTube Construct is freely accessible through the Enalos Cloud Platform (https://enaloscloud.novamechanics.com/diagonal/nanotube/).

ASCOT (an acronym derived from Ag-Silver, Copper Oxide, Titanium Oxide) is a user-friendly web tool for digital construction of electrically neutral, energy-minimized spherical nanoparticles (NPs) of Ag, CuO, and TiO2 (both Anatase and Rutile forms) in vacuum, integrated into the Enalos Cloud Platform (https://www.enaloscloud.novamechanics.com/sabydoma/ascot/). ASCOT calculates critical atomistic descriptors such as average potential energy per atom, average coordination number, common neighbour parameter (used for structural classification in simulations of crystalline phases), and hexatic order parameter (which measures how closely the local environment around a particle resembles perfect hexatic symmetry) for both core (over 4 Å from the surface) and shell (within 4 Å of the surface) regions of the NPs. These atomistic descriptors assist in predicting the most stable NP size based on lowest per atom energy and serve as inputs for developing machine learning models to predict the toxicity of these nanomaterials. ASCOT's automated backend requires minimal user input in order to construct the digital NPs: inputs needed are the material type (Ag, CuO, TiO2-Anatase, TiO2-Rutile), target diameter, a Force-Field from a pre-validated list, and the energy minimization parameters, with the tool providing a set of default values for novice users.

Background To reduce leprosy risk in contacts of patients with leprosy by around 50%, the World Health Organization (WHO) recommends leprosy post-exposure prophylaxis (PEP) using single-dose rifampicin (SDR). Results from a cluster randomized trial in the Comoros and Madagascar suggest that PEP with a double dose of rifampicin led to a similar reduction in incident leprosy, prompting the need for stronger PEP. The objective of this Phase 2 trial was to assess safety of a bedaquiline-enhanced PEP regimen (intervention arm, bedaquiline 800 mg with rifampicin 600 mg, BE-PEP), relative to the WHO recommended PEP with rifampicin 600 mg alone (control arm, SDR-PEP). Methods and findings From July 2022 to January 2023, consenting participants were screened for eligibility, including a heart rate-corrected QT interval (QTc) Conclusions In this study, we observed that safety of single-dose bedaquiline 800 mg in combination with rifampicin is comparable to rifampicin alone, although non-inferiority of QTc changes was demonstrated in children only after adjusting for the baseline QTc measurements. A Phase 3 cluster randomized efficacy trial is currently ongoing in the Comoros. Trial Registration ClinicalTrials.gov NCT05406479., Author(s): Bouke Catherine de Jong 1,*, Said Nourdine 2, Auke Thomas Bergeman 3, Zahara Salim 2, Silahi Halifa Grillone 2, Sofie Marijke Braet 1, Mohamed Wirdane Abdou 2, Rian Snijders [...]

BackgroundTo reduce leprosy risk in contacts of patients with leprosy by around 50%, the World Health Organization (WHO) recommends leprosy post-exposure prophylaxis (PEP) using single-dose rifampicin (SDR). Results from a cluster randomized trial in the Comoros and Madagascar suggest that PEP with a double dose of rifampicin led to a similar reduction in incident leprosy, prompting the need for stronger PEP. The objective of this Phase 2 trial was to assess safety of a bedaquiline-enhanced PEP regimen (intervention arm, bedaquiline 800 mg with rifampicin 600 mg, BE-PEP), relative to the WHO recommended PEP with rifampicin 600 mg alone (control arm, SDR-PEP).Methods and findingsFrom July 2022 to January 2023, consenting participants were screened for eligibility, including a heart rate-corrected QT interval (QTc) 50 ms or exceeded 450 ms after PEP administration. Per protocol, all children were analyzed together, with no significant difference in mean QTc increase for BE-PEP compared to SDR-PEP, although non-inferiority of BE-PEP in children was not demonstrated in unadjusted analysis, as the upper limit of the 95% CI of 10.4 ms exceeded the predefined margin of 10 ms. Adjusting for baseline QTc, the regression coefficient and 95% CI (3.3; -1.4, 8.0) met the 10 ms non-inferiority margin. No significant differences in ALT or AST levels were noted between the intervention and control arms, although a limitation of the study was false elevation of ALT/AST during adult recruitment due to a technical error. In both study arms, one serious adverse event was reported, both considered unlikely related to the study drugs. Dizziness, nausea, headache, and diarrhea among adults, and headaches in children, were nonsignificantly more frequently observed in the BE-PEP group.ConclusionsIn this study, we observed that safety of single-dose bedaquiline 800 mg in combination with rifampicin is comparable to rifampicin alone, although non-inferiority of QTc changes was demonstrated in children only after adjusting for the baseline QTc measurements. A Phase 3 cluster randomized efficacy trial is currently ongoing in the Comoros.Trial registrationClinicalTrials.gov NCT05406479.

Mathematical modeling is widely used for describing infection transmission and evaluating interventions. The lack of reliable social parameters in the literature has been mentioned by many modeling studies, leading to limitations in the validity and interpretation of the results. Using data from the European MSM Internet survey 2017, we developed a network model to describe sex acts among MSM in Belgium. The model simulates daily sex acts among steady, persistent casual and one-off partners in a population of 10,000 MSM, grouped as low- or high-activity by using three different definitions. Model calibration was used to estimate partnership duration and homophily rates to match the distribution of cumulative sex partners over 12 months. We estimated an average duration between 1065 and 1409 days for steady partnerships, 4–6 and 251–299 days for assortative high- and low-activity individuals and 8–13 days for disassortative persistent casual partnerships, respectively, varying across the three definitions. High-quality data on social network and behavioral parameters are scarce in the literature. Our study addresses this lack of information by providing a method to estimate crucial parameters for network specification.

Abstract Some anti‐mycobacterial drugs are known to cause QT interval prolongation, potentially leading to life‐threatening ventricular arrhythmia. However, the highest leprosy and tuberculosis burden occurs in settings where electrocardiographic monitoring is challenging. The feasibility and accuracy of alternative strategies, such as the use of automated measurements or a mobile electrocardiogram (mECG) device, have not been evaluated in this context. As part of the phase II randomized controlled BE‐PEOPLE trial evaluating the safety of bedaquiline‐enhanced post‐exposure prophylaxis (bedaquiline and rifampicin, BE‐PEP, versus rifampicin, SDR‐PEP) for leprosy, all participants had corrected QT intervals (QTc) measured at baseline and on the day after receiving post‐exposure prophylaxis. The accuracy of mECG measurements as well as automated 12L‐ECG measurements was evaluated. In total, 635 mECGs from 323 participants were recorded, of which 616 (97%) were of sufficient quality for QTc measurement. Mean manually read QTc on 12L‐ECG and mECG were 394 ± 19 and 385 ± 18 ms, respectively (p

Light controls the developmental, physiological, morphological, and metabolic responses of many fungi. Most fungi respond primarily to blue, red, and green light through their respective photoreceptors. In this study, a screening of different light wavelengths’ effects on submerged Pleurotus ostreatus cultivation in baffled flasks was conducted. P. ostreatus growth was not inhibited in all tested conditions, while an equal or higher protein content was observed in comparison with dark conditions. Red and green light favored exopolysaccharide (EPS) production while red and blue light favored intracellular polysaccharide (IPS) production. To focus on EPS production, the effect of red and green light wavelengths on the production of the polysaccharide via submerged cultivation of P. ostreatus LGAM 1123 was tested. Submerged cultivation using red light in baffled flasks resulted in EPS production of 4.1 ± 0.4 g/L and IPS content of 23.1 ± 1.4% of dry weight (dw), while green light resulted in EPS production of 4.1 ± 0.2 g/L and 44.8 ± 5.2% dw IPS content. Similar production levels were achieved in a 3.5 L bioreactor using red light. The EPS produced using red light revealed a polysaccharide with a higher antioxidant activity compared to the polysaccharides produced by green light. In addition, the analysis of the crude polysaccharides has shown differences in biochemical composition. The structural differences and β glucan’s existence in the crude polysaccharides were confirmed by FT-IR analysis. Overall, these polysaccharides could be used in the food industry as they can enhance the functional health-promoting, physicochemical, and sensory properties of food products.

Objectives: High-dose rifampicin (R) and isoniazid (H) are known to be safe but were not yet combined in a single regimen. The primary objective of the TRIple-DOse RE-treatment (TRIDORE) study is to determine whether a 6-month firstline regimen with triple dose of both R and H (intervention arm; 6R3H3ZE) is non-inferior in terms of safety compared to a normal-dose regimen (6RHZE) in previously treated patients with R-susceptible (Rs) recurrent tuberculosis (TB). Design/methods: TRIDORE is an ongoing pragmatic open-label multi-stage randomized clinical trial. Results: Between March 2021 and February 2022, 127 consenting patients were randomly assigned to either the intervention or control arm: 62 and 65 were treated with 6R3H3ZE and 6RHZE, respectively. Of 127, 111 (87.4%) were male and the median age (interquartile range) was 37 (30-48) years. The median body mass index at enrollment was 18.1 (16.3-19.7) kg/m2. Drugrelated severe adverse events (AEs) (grade III-V) were significantly more frequent when 6R3H3ZE was used (5/62 vs 0/65, P = 0.03, difference weighted for site 8% [95% confidence interval: 1.0,14.3]). The Data and Safety Monitoring Board recommended publishing our interim safety data analysis. Conclusion: We show that the combination of triple-dose R with triple-dose H in a re-treatment regimen for patients with Rs-TB causes excess drug-related AEs.

In recent decades, enhancing scientific literacy has been the ultimate goal of science education worldwide. This effort aims to develop the skills by individuals to cope with the challenges of the modern world, which requires scientific knowledge and thinking. This research study aimed to investigate and compare the scientific literacy level of Greek pre-service teachers and primary school students. The total number of participants was 787, of which 362 were pre-service teachers and 425 primary school students. Scientific literacy was assessed with the selected response measure of demonstrated scientific literacy (SLA-D). According to descriptive analyses and statistical hypothesis tests, pre-service teachers’ scientific literacy level was considered significantly higher than students, as was expected. However, the scientific literacy level of both pre-service teachers and students in the sample remained low. This work provides recommendations for actions that can help improve the scientific literacy level of both students and teachers so that schools become a source of scientifically literate future citizens.

Abstract Background Leprosy is an ancient infectious disease with an annual global incidence of around 200,000 over the past decade. Since 2018, the World Health Organization (WHO) recommends single-dose rifampicin as post-exposure prophylaxis (SDR-PEP) for contacts of leprosy patients. The Post ExpOsure Prophylaxis for Leprosy (PEOPLE) trial evaluated PEP with a double dose of rifampicin in Comoros and Madagascar. Preliminary results of this trial show some reduction in leprosy incidence in intervention villages but a stronger regimen may be beneficial. The objective of the current Bedaquiline Enhanced ExpOsure Prophylaxis for LEprosy trial (BE-PEOPLE) is to explore effectiveness of a combination of bedaquiline and rifampicin as PEP. Methods BE-PEOPLE is a cluster-randomized trial in which 44 clusters in Comoros will be randomized to two study arms. Door-to-door screening will be conducted annually during four years, leprosy patients identified will be offered standard of care treatment. Based on study arm, contacts aged five years and above and living within a 100-meter radius of an index case will either receive bedaquiline (400-800 mg) and rifampicin (150-600 mg) or only rifampicin (150–600 mg). Contacts aged two to four years will receive rifampicin only. Household contacts randomized to the bedaquiline plus rifampicin arm will receive a second dose four weeks later. Incidence rate ratios of leprosy comparing contacts who received either of the PEP regimens will be the primary outcome. We will monitor resistance to rifampicin and/or bedaquiline through molecular surveillance in all incident tuberculosis and leprosy patients nationwide. At the end of the study, we will assess anti-M. leprae PGL-I IgM seropositivity as a proxy for the population burden of M. leprae infection in 8 villages (17,000 individuals) that were surveyed earlier as part of the PEOPLE trial. Discussion The COLEP trial on PEP in Bangladesh documented a reduction of 57% in incidence of leprosy among contacts treated with SDR-PEP after two years, which led to the WHO recommendation of SDR-PEP. Preliminary results of the PEOPLE trial show a lesser reduction in incidence. The BE-PEOPLE trial will explore whether reinforcing SDR-PEP with bedaquiline increases effectiveness and more rapidly reduces the incidence of leprosy, compared to SDR-PEP alone. Trial registration NCT05597280. Protocol version 5.0 on 28 October 2022.

In mediaeval Europe, the term “commons” described the way that communities managed land that was held “in common” and provided a clear set of rules for how this “common land” was used and developed by, and for, the community. Similarly, as we move towards an increasingly knowledge-based society where data is the new oil, new approaches to sharing and jointly owning publicly funded research data are needed to maximise its added value. Such common management approaches will extend the data’s useful life and facilitate its reuse for a range of additional purposes, from modelling, to meta-analysis to regulatory risk assessment as examples relevant to nanosafety data. This “commons” approach to nanosafety data and nanoinformatics infrastructure provision, co-development, and maintenance is at the heart of the “NanoCommons” project and underpins its post-funding transition to providing a basis on which other initiatives and projects can build. The present paper summarises part of the NanoCommons infrastructure called the NanoCommons Knowledge Base. It provides interoperability for nanosafety data sources and tools, on both semantic and technical levels. The NanoCommons Knowledge Base connects knowledge and provides both programmatic (via an Application Programming Interface) and a user-friendly graphical interface to enable (and democratise) access to state of the art tools for nanomaterials safety prediction, NMs design for safety and sustainability, and NMs risk assessment, as well. In addition, the standards and interfaces for interoperability, e.g., file templates to contribute data to the NanoCommons, are described, and a snapshot of the range and breadth of nanoinformatics tools and models that have already been integrated are presented Finally, we demonstrate how the NanoCommons Knowledge Base can support users in the FAIRification of their experimental workflows and how the NanoCommons Knowledge Base itself has progressed towards richer compliance with the FAIR principles.

Introduction Autistic individuals identify with a wider range of sexual orientations than non-autistic individuals, including higher rates of bisexual orientation in autistic men. Gay, bisexual and other men who have sex with men are at greater risk for HIV. Prevalence data of autistic traits in people living with HIV or using Pre-Exposure Prophylaxis (PrEP) for HIV are lacking so far. Such data, combined with insights in barriers and facilitators for safer sex in autistic people living with HIV or using PrEP, are a first step to improve health support for autistic people in HIV clinics. This support is crucial since autistic individuals have worse physical and mental health outcomes. The objective of this research is to determine the prevalence of autistic traits within the group of people living with HIV or using PrEP in Belgium and to describe specific facilitators and barriers for sexual safer behaviour in people living with HIV and PrEP users with autistic traits.Methods and analysis The research is a cross-sectional, observational and multicentre study with recruitment of individual participants. The research consists of two phases. In phase 1, adults coming for HIV/AIDS care or HIV PrEP in participating Belgian HIV Reference Centres will be invited to fill in the validated Autism Spectrum Quotient questionnaire. In phase 2, participants with a score above the predefined cut-off for autistic traits (>26), who agreed to be informed about this score, will be invited to complete an additional survey, inquiring facilitators and barriers for sexual safer behaviour.Ethics and dissemination of results Institutional Review Board Institute of Tropical Medicine Antwerp, 25 July 2022, REF 1601/22 and University Hospital of Antwerp, 12 September 2022, Project ID 3679: BUN B3002022000111. Study results will be published in peer-reviewed journals and presented to Belgian HIV Reference Centres and at conferences.

Surgery of the thyroid takes place in a body part with complicated anatomy and several vital physiologic functions. Thyroidectomy is rarely associated with mortality but can be followed by significant complications, (i.e. hypoparathyroidism, hemorrhage, upper airway obstruction, laryngeal nerve injuries and thyrotoxic storm). This review aims to indicate surgical tips and techniques to sustain a low level of complications.

In December 2019, the new coronavirus infection (COVID-19) was declared a pandemic by the World Health Organization after rapidly spreading over the world in just a few months. All elective operations and nonemergency treatments have been postponed worldwide. However, some patients require surgical therapy as well, and the time spent waiting should not have a negative impact on the surgical outcome or disease course. Following the initial onset of the COVID-19 epidemic, instructions for proper and safe surgery for healthcare staff and patients should develop. Thyroid surgeries have decreased during the COVID-19 pandemic. Most of them can be postponed for a long time. Assessment of thyroid nodules recommends clinical examination, imaging studies, fine needle aspiration (FNA) and vocal cord examination. All these procedures are necessary, and sometimes they cannot be postponed. To determine the best timing, a thorough preoperative assessment should be undertaken, taking into account both oncological and anatomical features. Furthermore, COVID-19 status must be negative prior to any intervention, and hospital infrastructure must be ready to deal with the demanding situation.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare autoimmune disorder characterised by the progressive demyelination of peripheral nerves, resulting in motor and sensory deficits. While much research has focused on clinical and electrophysiological aspects of CIDP, there is an emerging interest in exploring its impact on the visual system through visual evoked potentials (VEPs). This comprehensive review synthesises existing literature on VEP findings in CIDP patients, shedding light on their potential diagnostic and prognostic value. The review thoroughly examines studies spanning the last two decades, exploring VEP abnormalities in CIDP patients. Notably, VEP studies have consistently revealed prolonged latencies and reduced amplitudes in CIDP patients compared to healthy controls. These alterations in VEP parameters suggest that the demyelinating process extends beyond the peripheral nervous system to affect the central nervous system, particularly the optic nerve and its connections. The correlation between VEP abnormalities and clinical manifestations of CIDP, such as visual impairment and sensory deficits, underscores the clinical relevance of VEP assessment in CIDP management. Furthermore, this review addresses the potential utility of VEPs in aiding CIDP diagnosis and monitoring disease progression. VEP abnormalities may serve as valuable biomarkers for disease activity, helping clinicians make timely therapeutic decisions. Moreover, this review discusses the limitations and challenges associated with VEP assessment in CIDP, including variability in recording techniques and the need for standardised protocols. In conclusion, this review highlights the evolving role of VEPs as a non-invasive tool in CIDP evaluation. The consistent VEP abnormalities observed in CIDP patients suggest the involvement of the central nervous system in this demyelinating disorder. As our understanding of CIDP and its pathophysiology continues to evolve, further research in this area may lead to improved diagnostic accuracy and monitoring strategies, ultimately enhancing the clinical management of CIDP patients.

Mucinous cystadenomas are among the most common benign adnexal masses. The peak incidence of mucinous cystadenoma appears between the third and fifth decades of life, but rare cases in younger and older women have also been reported. Ovarian cystic formations are usually asymptomatic at early stages, until they grow in size and various compression symptoms appear, such as abdominal discomfort, distention, nausea, vomiting, and increased urination.

Abstract Background Persistent fever, defined as fever lasting for 7 days or more at first medical evaluation, has been hardly investigated as a separate clinical entity in the tropics. This study aimed at exploring the frequencies and diagnostic predictors of the ubiquitous priority (i.e., severe and treatable) infections causing persistent fever in the tropics. Methods In six different health settings across four countries in Africa and Asia (Sudan, Democratic Republic of Congo [DRC], Nepal, and Cambodia), consecutive patients aged 5 years or older with persistent fever were prospectively recruited from January 2013 to October 2014. Participants underwent a reference diagnostic workup targeting a pre-established list of 12 epidemiologically relevant priority infections (i.e., malaria, tuberculosis, HIV, enteric fever, leptospirosis, rickettsiosis, brucellosis, melioidosis, relapsing fever, visceral leishmaniasis, human African trypanosomiasis, amebic liver abscess). The likelihood ratios (LRs) of clinical and basic laboratory features were determined by pooling all cases of each identified ubiquitous infection (i.e., found in all countries). In addition, we assessed the diagnostic accuracy of five antibody-based rapid diagnostic tests (RDTs): Typhidot Rapid IgM, Test-itTM Typhoid IgM Lateral Flow Assay, and SD Bioline Salmonella typhi IgG/IgM for Salmonella Typhi infection, and Test-itTM Leptospira IgM Lateral Flow Assay and SD Bioline Leptospira IgG/IgM for leptospirosis. Results A total of 1922 patients (median age: 35 years; female: 51%) were enrolled (Sudan, n = 667; DRC, n = 300; Nepal, n = 577; Cambodia, n = 378). Ubiquitous priority infections were diagnosed in 452 (23.5%) participants and included malaria 8.0% (n = 154), tuberculosis 6.7% (n = 129), leptospirosis 4.0% (n = 77), rickettsiosis 2.3% (n = 44), enteric fever 1.8% (n = 34), and new HIV diagnosis 0.7% (n = 14). The other priority infections were limited to one or two countries. The only features with a positive LR ≥ 3 were diarrhea for enteric fever and elevated alanine aminotransferase level for enteric fever and rickettsiosis. Sensitivities ranged from 29 to 67% for the three RDTs targeting S. Typhi and were 9% and 16% for the two RDTs targeting leptospirosis. Specificities ranged from 86 to 99% for S. Typhi detecting RDTs and were 96% and 97% for leptospirosis RDTs. Conclusions Leptospirosis, rickettsiosis, and enteric fever accounted each for a substantial proportion of the persistent fever caseload across all tropical areas, in addition to malaria, tuberculosis, and HIV. Very few discriminative features were however identified, and RDTs for leptospirosis and Salmonella Typhi infection performed poorly. Improved field diagnostics are urgently needed for these challenging infections. Trial registration NCT01766830 at ClinicalTrials.gov.

Background The purpose of this exploratory study was to evaluate different accelerated tick-borne encephalitis (TBE) vaccine schedules for last-minute travellers. Methods In a single-centre, open-label pilot study, 77 TBE-naïve Belgian soldiers were randomized to one of the following five schedules with FSME-Immun®: group 1 ('classical accelerated' schedule) received one intramuscular (IM) dose at Day 0 and Day 14, group 2 two IM doses at Day 0, group 3 two intradermal (ID) doses at Day 0, group 4 two ID doses at Day 0 and Day 7 and group 5 two ID doses at Day 0 and Day 14. The last dose(s) of the primary vaccination scheme were given after 1 year: IM (1 dose) or ID (2 doses). TBE virus neutralizing antibodies were measured in a plaque reduction neutralization test (PRNT90 and 50) at Days 0, 14, 21, 28, Months 3, 6, 12 and 12+21 days. Seropositivity was defined as neutralizing antibody titres ≥10. Results The median age was 19–19.5 years in each group. Median time to seropositivity up to Day 28 was shortest for PRNT90 in ID-group 4 and for PRNT50 in all ID groups. Seroconversion until Day 28 peaked highest for PRNT90 in ID-group 4 (79%) and for PRNT50 in ID-groups 4 and 5 (both 100%). Seropositivity after the last vaccination after 12 months was high in all groups. Previous yellow fever vaccination was reported in 16% and associated with lower geometric mean titres of TBE-specific antibodies at all-time points. The vaccine was generally well tolerated. However, mild to moderate local reactions occurred in 73–100% of ID compared with 0–38% of IM vaccinations, and persistent discolouration was observed in nine ID vaccinated individuals. Conclusion The accelerated two-visit ID schedules might offer a better immunological alternative to the recommended classical accelerated IM schedule, but an aluminium-free vaccine would be preferable. [ABSTRACT FROM AUTHOR]