Interferon-Gamma Release Assay (Modified QuantiFERON) as a Potential Marker of Infection for Leishmania donovani, a Proof of Concept Study

Visceral leishmaniasis is caused by a parasite of the Leishmania species, but infection does not always lead to overt clinical disease. To detect infection, the Montenegro test or Leishmanin Skin Test (LST) is used along with serological markers. The LST is a test of the delayed-type hypersensitivity response read 48–72 hours after intradermal injection of leishmanin antigen. LST has many drawbacks, as complex administration and reading, boosting of anamnestic immune responses and difficult sourcing of GMP-compliant product and alternative tools for epidemiological research are badly needed. We evaluated whether a Interferon-γ Release Assay based on the QuantiFERON-TB test format, which was approved by the Food and Drug Administration (FDA) as a test for detecting latent Mycobacterium tuberculosis infection, could become an in vitro diagnostic aid for the measurement of cell-mediated immune reactivity against L.donovani. We obtained good results with one of five of the antigens we evaluated and confirm the potential of this assay

Age specific aetiological agents of diarrhoea in hospitalized children aged less than five years in Dar es Salaam, Tanzania

\ud This study aimed to determine the age-specific aetiologic agents of diarrhoea in children aged less than five years. The study also assessed the efficacy of the empiric treatment of childhood diarrhoea using Integrated Management of Childhood Illness (IMCI) guidelines. This study included 280 children aged less than 5 years, admitted with diarrhoea to any of the four major hospitals in Dar es Salaam. Bacterial pathogens were identified using conventional methods. Enzyme Linked Immunosorbent Assay (ELISA) and agglutination assay were used to detect viruses and intestinal protozoa, respectively. Antimicrobial susceptibility was determined using Kirby-Bauer disk diffusion method. At least one of the searched pathogens was detected in 67.1% of the cases, and mixed infections were detected in 20.7% of cases. Overall, bacteria and viruses contributed equally accounting for 33.2% and 32.2% of all the cases, respectively, while parasites were detected in 19.2% patients. Diarrhoeagenic Escherichia coli (DEC) was the most common enteric pathogen, isolated in 22.9% of patients, followed by Cryptosporidium parvum (18.9%), rotavirus (18.1%) and norovirus (13.7%). The main cause of diarrhoea in children aged 0 to 6 months were bacteria, predominantly DEC, while viruses predominated in the 7-12 months age group. Vibrio cholerae was isolated mostly in children above two years. Shigella spp, V. cholerae and DEC showed moderate to high rates of resistance to erythromycin, ampicillin, chloramphenicol and tetracycline (56.2-100%). V. cholerae showed full susceptibility to co-trimoxazole (100%), while DEC and Shigella showed high rate of resistance to co-trimoxazole; 90.6% and 93.3% respectively. None of the bacterial pathogens isolated showed resistance to ciprofloxacin which is not recommended for use in children. Cefotaxime resistance was found only in 4.7% of the DEC. During the dry season, acute watery diarrhoea is the most common type of diarrhoea in children under five years in Dar es Salaam and is predominantly due to DEC, C. parvum, rotaviruses and noroviruses. Constant antibiotic surveillance is warranted as bacteria were highly resistant to various antimicrobial agents including co-trimoxazole and erythromycin which are currently recommended for empiric treatment of diarrhoea.\u

Reweighting a parton shower using a neural network: the final-state case

The use of QCD calculations that include the resummation of soft-collinear logarithms via parton-shower algorithms is currently not possible in PDF fits due to the high computational cost of evaluating observables for each variation of the PDFs. Unfortunately the interpolation methods that are otherwise applied to overcome this issue are not readily generalised to all-order parton-shower contributions. Instead, we propose an approximation based on training a neural network to predict the effect of varying the input parameters of a parton shower on the cross section in a given observable bin, interpolating between the variations of a training data set. This first publication focuses on providing a proof-of-principle for the method, by varying the shower dependence on $\alpha_\text{S}$ for both a simplified shower model and a complete shower implementation for three different observables, the leading emission scale, the number of emissions and the Thrust event shape. The extension to the PDF dependence of the initial-state shower evolution that is needed for the application to PDF fits is left to a forthcoming publication.Comment: additional references added in introductio

Therapeutic potential of KLF2-induced exosomal microRNAs in pulmonary hypertension

Pulmonary arterial hypertension (PAH) is a severe disorder of lung vasculature that causes right heart failure. Homeostatic effects of flow-activated transcription factor Krüppel-like factor 2 (KLF2) are compromised in PAH. Here we show that KLF2-induced exosomal microRNAs, miR-181a-5p and miR-324-5p act together to attenuate pulmonary vascular remodeling and that their actions are mediated by Notch4 and ETS1 and other key regulators of vascular homeostasis. Expressions of KLF2, miR-181a-5p and miR-324-5p are reduced, while levels of their target genes are elevated in pre-clinical PAH, idiopathic PAH and heritable PAH with missense p.H288Y KLF2 mutation. Therapeutic supplementation of miR-181a-5p and miR-324-5p reduces proliferative and angiogenic responses in patient-derived cells and attenuates disease progression in PAH mice. This study shows that reduced KLF2 signaling is a common feature of human PAH and highlights the potential therapeutic role of KLF2-regulated exosomal miRNAs in PAH and other diseases associated with vascular remodelling

Neglected Tropical Diseases in Sub-Saharan Africa: Review of Their Prevalence, Distribution, and Disease Burden

The neglected tropical diseases (NTDs) are the most common conditions affecting the poorest 500 million people living in sub-Saharan Africa (SSA), and together produce a burden of disease that may be equivalent to up to one-half of SSA's malaria disease burden and more than double that caused by tuberculosis. Approximately 85% of the NTD disease burden results from helminth infections. Hookworm infection occurs in almost half of SSA's poorest people, including 40–50 million school-aged children and 7 million pregnant women in whom it is a leading cause of anemia. Schistosomiasis is the second most prevalent NTD after hookworm (192 million cases), accounting for 93% of the world's number of cases and possibly associated with increased horizontal transmission of HIV/AIDS. Lymphatic filariasis (46–51 million cases) and onchocerciasis (37 million cases) are also widespread in SSA, each disease representing a significant cause of disability and reduction in the region's agricultural productivity. There is a dearth of information on Africa's non-helminth NTDs. The protozoan infections, human African trypanosomiasis and visceral leishmaniasis, affect almost 100,000 people, primarily in areas of conflict in SSA where they cause high mortality, and where trachoma is the most prevalent bacterial NTD (30 million cases). However, there are little or no data on some very important protozoan infections, e.g., amebiasis and toxoplasmosis; bacterial infections, e.g., typhoid fever and non-typhoidal salmonellosis, the tick-borne bacterial zoonoses, and non-tuberculosis mycobaterial infections; and arboviral infections. Thus, the overall burden of Africa's NTDs may be severely underestimated. A full assessment is an important step for disease control priorities, particularly in Nigeria and the Democratic Republic of Congo, where the greatest number of NTDs may occur

The Global Burden of Disease Study 2010: Interpretation and Implications for the Neglected Tropical Diseases

This article analyzes the "Global Burden of Disease Study 2010" and examines the study's implications for neglected tropical diseases

Control of Visceral Leishmaniasis in Latin America—A Systematic Review

Visceral leishmaniasis is a vector-borne disease characterized by fever, spleen and liver enlargement, and low blood cell counts. In the Americas VL is zoonotic, with domestic dogs as main animal reservoirs, and is caused by the intracellular parasite Leishmania infantum (syn. Leishmania chagasi). Humans acquire the infection through the bite of an infected sand fly. The disease is potentially lethal if untreated. VL is reported from Mexico to Argentina, with recent trends showing a rapid spread in Brazil. Control measures directed against the canine reservoir and insect vectors have been unsuccessful, and early detection and treatment of human cases remains as the most important strategy to reduce case fatality. Well-designed studies evaluating diagnosis, treatment, and prevention/control interventions are scarce. The available scientific evidence reasonably supports the use of rapid diagnostic tests for the diagnosis of human disease. Properly designed randomized controlled trials following good clinical practices are needed to inform drug policy. Routine control strategies against the canine reservoirs and insect vectors are based on weak and conflicting evidence, and vector control strategies and vaccine development should constitute research priorities

Geometry and field theory in multi-fractional spacetime

We construct a theory of fields living on continuous geometries with fractional Hausdorff and spectral dimensions, focussing on a flat background analogous to Minkowski spacetime. After reviewing the properties of fractional spaces with fixed dimension, presented in a companion paper, we generalize to a multi-fractional scenario inspired by multi-fractal geometry, where the dimension changes with the scale. This is related to the renormalization group properties of fractional field theories, illustrated by the example of a scalar field. Depending on the symmetries of the Lagrangian, one can define two models. In one of them, the effective dimension flows from 2 in the ultraviolet (UV) and geometry constrains the infrared limit to be four-dimensional. At the UV critical value, the model is rendered power-counting renormalizable. However, this is not the most fundamental regime. Compelling arguments of fractal geometry require an extension of the fractional action measure to complex order. In doing so, we obtain a hierarchy of scales characterizing different geometric regimes. At very small scales, discrete symmetries emerge and the notion of a continuous spacetime begins to blur, until one reaches a fundamental scale and an ultra-microscopic fractal structure. This fine hierarchy of geometries has implications for non-commutative theories and discrete quantum gravity. In the latter case, the present model can be viewed as a top-down realization of a quantum-discrete to classical-continuum transition.Comment: 1+82 pages, 1 figure, 2 tables. v2-3: discussions clarified and improved (especially section 4.5), typos corrected, references added; v4: further typos correcte