Noninvasive Diagnosis of Visceral Leishmaniasis:Development and Evaluation of Two Urine-Based Immunoassays for Detection of Leishmania donovani Infection in India

Visceral leishmaniasis (VL), one of the most prevalent parasitic diseasesin the developing world causes serious health concerns. Post kala-azar dermal leishmaniasis (PKDL) is a skin disease which occurs after treatment as a sequel to VL. Parasitological diagnosis involves invasive tissue aspiration which is tedious and painful. Commercially available immunochromatographic rapid diagnostic test such as rK39-RDT is used for field diagnosis of VL, detects antibodiesin serum samples. Urine sample is however, much easier in collection,storage and handling than serum and would be a better alternative where collection of tissue aspirate or blood is impractical. In this study, we have developed and evaluated the performance of two urine-based diagnostic assays, ELISA and dipstick test, and compared the results with serologicalrK39-RDT. Our study shows the capability of urinebased tests in detecting anti-Leishmania antibodies effectively for both VL and PKDL diagnosis. The ability of dipstick test to demonstrate negative results after six months in 90% of the VL cases after treatment could be useful as a test of clinical cure. Urine-based tests can therefore replace the need for invasive practices and ensure better diagnosi

A historical overview of the classification, evolution, and dispersion of Leishmania parasites and sandflies

Background The aim of this study is to describe the major evolutionary historical events among Leishmania, sandflies, and the associated animal reservoirs in detail, in accordance with the geographical evolution of the Earth, which has not been previously discussed on a large scale. Methodology and Principal Findings Leishmania and sandfly classification has always been a controversial matter, and the increasing number of species currently described further complicates this issue. Despite several hypotheses on the origin, evolution, and distribution of Leishmania and sandflies in the Old and New World, no consistent agreement exists regarding dissemination of the actors that play roles in leishmaniasis. For this purpose, we present here three centuries of research on sandflies and Leishmania descriptions, as well as a complete description of Leishmania and sandfly fossils and the emergence date of each Leishmania and sandfly group during different geographical periods, from 550 million years ago until now. We discuss critically the different approaches that were used for Leishmana and sandfly classification and their synonymies, proposing an updated classification for each species of Leishmania and sandfly. We update information on the current distribution and dispersion of different species of Leishmania (53), sandflies (more than 800 at genus or subgenus level), and animal reservoirs in each of the following geographical ecozones: Palearctic, Nearctic, Neotropic, Afrotropical, Oriental, Malagasy, and Australian. We propose an updated list of the potential and proven sandfly vectors for each Leishmania species in the Old and New World. Finally, we address a classical question about digenetic Leishmania evolution: which was the first host, a vertebrate or an invertebrate? Conclusions and Significance We propose an updated view of events that have played important roles in the geographical dispersion of sandflies, in relation to both the Leishmania species they transmit and the animal reservoirs of the parasites

Clin Transl Sci

Adenosine boasts promising preclinical and clinical data supporting a vital role in modulating vascular homeostasis. Its widespread use as a diagnostic and therapeutic agent have been limited by its short half-life and complex biology, though adenosine-modulators have shown promise in improving vascular healing. Moreover, circulating adenosine has shown promise in predicting cardiovascular (CV) events. We sought to delineate whether circulating plasma adenosine levels predict CV events in patients undergoing invasive assessment for coronary artery disease. Patients undergoing invasive angiography had clinical data prospectively recorded in the Cardiovascular and Percutaneous ClInical TriALs (CAPITAL) revascularization registry and blood samples collected in the CAPITAL Biobank from which adenosine levels were quantified. Tertile-based analysis was used to assess prediction of major adverse cardiovascular events (MACE; composite of death, myocardial infarction, unplanned revascularization, and cerebrovascular accident). Secondary analyses included MACE subgroups, clinical subgroups and adenosine levels. There were 1,815 patients undergoing angiography who had blood collected with adenosine quantified in 1,323. Of those quantified, 51.0% were revascularized and 7.3% experienced MACE in 12 months of follow-up. Tertile-based analysis failed to demonstrate any stratification of MACE rates (log rank, P = 0.83), when comparing low-to-middle (hazard ratio (HR) 1.10, 95% confidence interval (CI) 0.68-1.78, P = 0.70) or low-to-high adenosine tertiles (HR 0.95, 95% CI 0.56-1.57, P = 0.84). In adjusted analysis, adenosine similarly failed to predict MACE. Finally, adenosine did not predict outcomes in patients with acute coronary syndrome nor in those revascularized or treated medically. Plasma adenosine levels do not predict subsequent CV outcomes or aid in patient risk stratification

Physics-Based Earthquake Ground Shaking Scenarios in Large Urban Areas

With the ongoing progress of computing power made available not only by large supercomputer facilities but also by relatively common workstations and desktops, physics-based source-to-site 3D numerical simulations of seismic ground motion will likely become the leading and most reliable tool to construct ground shaking scenarios from future earthquakes. This paper aims at providing an overview of recent progress on this subject, by taking advantage of the experience gained during a recent research contract between Politecnico di Milano, Italy, and Munich RE, Germany, with the objective to construct ground shaking scenarios from hypothetical earthquakes in large urban areas worldwide. Within this contract, the SPEED computer code was developed, based on a spectral element formulation enhanced by the Discontinuous Galerkin approach to treat non-conforming meshes. After illustrating the SPEED code, different case studies are overviewed, while the construction of shaking scenarios in the Po river Plain, Italy, is considered in more detail. Referring, in fact, to this case study, the comparison with strong motion records allows one to derive some interesting considerations on the pros and on the present limitations of such approach

Retrospective Prediction of Macroseismic Intensities Using Strong Ground Motion Simulation: The Case of the 1978 Thessaloniki (Greece) Earthquake (M6.5)

Abstract. The densely populated city of Thessaloniki (Northern Greece) is situated in the vicinity of active seismic faults, capable of producing moderate to strong earthquakes. The city has been severely affected by such events several times during the last 15 centu-ries. The most recent event occurred on 20 June 1978 (M6.5) in the Mygdonian graben, with an epicentral distance of about 30 km, causing extended damage in the city, with macroseismic intensities between MSK V+ and VIII+. The majority of buildings affected by the earthquake were of reinforced-concrete typology, typical to many southern European metropolitan areas. The source properties of the normal-faulting causative event and the source-to-city propaga-tion path are well known from previous studies. The soil structure under the metropolitan area of Thessaloniki is assigned NEHRP categories B, C, D on the basis of geotechnical and geologic information and single-station ambient-noise measurements. A finite source model and various rupture scenarios of the June 1978 earthquake are used to perform forward sto-chastic modeling of strong ground motion in terms of peak ground and spectral acceleration