Application of predictive degree day model for field development of sandfly vectors of visceral leishmaniasis in northwest of Iran

Background & objectives: Temperature plays a significant role in insect’s development where arise in temperature, accelerates the insect’s metabolic rates, increases egg production and makesblood feeding more frequent. It also shortens the time period required for the development ofpathogens within insects. Visceral leishmaniasis (VL) is one of the most important vector-bornediseases transmitted by different sandfly species. In this study, a phenological model was used toestimate the number of generations, peak activity and temporal variability of sandflies in the mainVL foci in northwest Iran.Methods: Development requirements of different life stages of a Phlebotomus papatasi laboratorycolony were measured and were subjected to the formula for calculation of accumulated degree day(ADD) for field sandflies using the online soft (UC IPM), using horizontal cut-off method andsingle triangle model. Sandflies population dynamics was monitored in the field during the seasonalactivity in the region and its association with the ADD was tested using SAS software.Results: Populations of sandflies accommodated well with the amount of accumulated degree days(ADD) in the region. During the seasonal activity, a total of 639 ADD were produced which wasenough to support one complete life cycle and growth of the next generation up to late larvalinstar. Larvae of the second generation hibernate through winter and the first adult populationappears in the mid to late June of the next year when they receive at least 182 ADD from thebeginning of the spring. The highest population density of sandflies was observed in early August,followed by a rapid decrease in early September, with the adult population disappearing completelyin late September. This is the first degree day model related to sandflies in the most important VLfoci of Iran.Interpretation & conclusion: Further studies in various regions with variable climate arerecommended in order to better estimate and understand the development time, population dynamicsand activities of the vectors which in turn could be used in proper implementation of effectivevector control programmes

Benefit of Early Invasive Therapy in Acute Coronary Syndromes A Meta-Analysis of Contemporary Randomized Clinical Trials

ObjectivesThis study sought to systematically determine whether early invasive therapy improves survival and reduces adverse cardiovascular events in the management of non–ST-segment elevation acute coronary syndromes.BackgroundAlthough early invasive therapy reduces recurrent unstable angina, the magnitude of benefit on other important adverse outcomes is unknown.MethodsClinical trials that randomized non–ST-segment elevation acute coronary syndrome patients to early invasive therapy versus a more conservative approach were included for analysis.ResultsIn all there were 7 trials with 8,375 patients available for analysis. At a mean follow-up of 2 years, the incidence of all-cause mortality was 4.9% in the early invasive group, compared with 6.5% in the conservative group (risk ratio [RR] = 0.75, 95% confidence interval [CI] 0.63 to 0.90, p = 0.001), and at 1 month (RR = 0.82, 95% CI 0.50 to 1.34, p = 0.43). At 2 years of follow-up, the incidence of nonfatal myocardial infarction was 7.6% in the invasive group, versus 9.1% in the conservative group (RR = 0.83, 95% CI 0.72 to 0.96, p = 0.012), and at 1 month (RR = 0.93, 95% CI 0.73 to 1.19, p = 0.57). At a mean of 13 months of follow-up, there was a reduction in rehospitalization for unstable angina (RR = 0.69, 95% CI 0.65 to 0.74, p < 0.0001).ConclusionsManaging non–ST-segment elevation acute coronary syndromes by early invasive therapy improves long-term survival and reduces late myocardial infarction and rehospitalization for unstable angina

Species and habitats in danger : estimating the relative risk posed by oil spills in the northern Baltic Sea

Large-scale oil spills can have adverse effects on biodiversity in coastal areas where maritime oil transportation is intense. In this article we conducted a spatial risk assessment to study the risk that potential tanker accidents pose to threatened habitat types and species living in the northern Baltic Sea, which has witnessed a rapid increase in maritime oil transportation within the past two decades. We applied a probabilistic method, which combines three components: a Bayesian network describing tanker accidents and uncertainties related to them, probabilistic maps showing the movement of oil, and a database of threatened species and habitats in the area. The results suggest that spatial risk posed by oil spills varies across the area, and does not correspond, for example, to the frequency of accidents in a given area. The relative risk is highest for seashore meadows, which is important to take into account when managing these habitats. Our analysis underlines the importance of a thorough risk assessment, which is not only based solely on one or two specific factors such as accident probabilities or the trajectories of spilled oil but also contains as broad a view of the consequences as possible. We believe that the probabilistic methodology applied in the study will be of high interest to people who have to cope with uncertainties typical for environmental risk assessment and management.Peer reviewe

Benznidazole biotransformation and multiple targets in <i>Trypanosoma</i> cruzi revealed by metabolomics

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The first line treatment for Chagas disease, a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, involves administration of benznidazole (Bzn). Bzn is a 2-nitroimidazole pro-drug which requires nitroreduction to become active, although its mode of action is not fully understood. In the present work we used a non-targeted MS-based metabolomics approach to study the metabolic response of T. cruzi to Bzn.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methodology/Principal findings&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Parasites treated with Bzn were minimally altered compared to untreated trypanosomes, although the redox active thiols trypanothione, homotrypanothione and cysteine were significantly diminished in abundance post-treatment. In addition, multiple Bzn-derived metabolites were detected after treatment. These metabolites included reduction products, fragments and covalent adducts of reduced Bzn linked to each of the major low molecular weight thiols: trypanothione, glutathione, γ-glutamylcysteine, glutathionylspermidine, cysteine and ovothiol A. Bzn products known to be generated in vitro by the unusual trypanosomal nitroreductase, TcNTRI, were found within the parasites, but low molecular weight adducts of glyoxal, a proposed toxic end-product of NTRI Bzn metabolism, were not detected.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions/significance&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Our data is indicative of a major role of the thiol binding capacity of Bzn reduction products in the mechanism of Bzn toxicity against T. cruzi

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

The Receptor Slamf1 on the Surface of Myeloid Lineage Cells Controls Susceptibility to Infection by Trypanosoma cruzi

Trypanosoma cruzi, the protozoan parasite responsible for Chagas' disease, causes severe myocarditis often resulting in death. Here, we report that Slamf1−/− mice, which lack the hematopoietic cell surface receptor Slamf1, are completely protected from an acute lethal parasite challenge. Cardiac damage was reduced in Slamf1−/− mice compared to wild type mice, infected with the same doses of parasites, as a result of a decrease of the number of parasites in the heart even the parasitemia was only marginally less. Both in vivo and in vitro experiments reveal that Slamf1-defIcient myeloid cells are impaired in their ability to replicate the parasite and show altered production of cytokines. Importantly, IFN-γ production in the heart of Slamf1 deficient mice was much lower than in the heart of wt mice even though the number of infiltrating dendritic cells, macrophages, CD4 and CD8 T lymphocytes were comparable. Administration of an anti-Slamf1 monoclonal antibody also reduced the number of parasites and IFN-γ in the heart. These observations not only explain the reduced susceptibility to in vivo infection by the parasite, but they also suggest human Slamf1 as a potential target for therapeutic target against T. cruzi infection

The Potential Economic Value of a Trypanosoma cruzi (Chagas Disease) Vaccine in Latin America

The substantial burden of Chagas disease, especially in Latin America, and the limitations of currently available treatment and control strategies have motivated the development of a Trypanosoma cruzi (T. cruzi) vaccine. Evaluating a vaccine's potential economic value early in its development can answer important questions while the vaccine's key characteristics (e.g., vaccine efficacy targets, price points, and target population) can still be altered. This can assist vaccine scientists, manufacturers, policy makers, and other decision makers in the development and implementation of the vaccine. We developed a computational economic model to determine the cost-effectiveness of introducing a T. cruzi vaccine in Latin America. Our results showed vaccination to be very cost-effective, in many cases providing both cost savings and health benefits, even at low infection risk and vaccine efficacy. Moreover, our study suggests that a vaccine may actually “pay for itself”, as even a relatively higher priced vaccine will generate net cost savings for a purchaser (e.g., a country's ministry of health). These findings support continued investments in and efforts toward the development of a human T. cruzi vaccine

Assessment of vitamin D intake among Libyan women - adaptation and validation of specific food frequency questionnaire

Vitamin D deficiency (VDD) has pandemic proportions worldwide. Numerous studies report on high prevalence of VDD in sunny regions like Near East and North Africa (NENA). Previous studies indicated that Libyan population was at risk of VDD. To contribute to the body of evidence, measurement of vitamin D status on children, adults, in Misurata region was conducted, and confirmed with validated dietary intake study. Serum 25(OH)D was analysed using electrochemiluminescence protein binding assay. Existing Food Frequency Questionnaires (FFQ) were adapted to Libyan Women Food Frequency Questionnaire (LW-FFQ). Repeated 24h dietary recalls and LW-FFQ were employed in vitamin D intake evaluation. LW-FFQ was validated using 24h dietary recall and vitamin D status as referent methods. The questionnaires included anthropometry and lifestyle information. Vitamin D status assessment revealed inadequate levels (25(OH)D lt 50nmol/l) in almost 80% of participants. Women (25-64y) were identified as the most vulnerable group with vitamin D inadequacy present in 82% (61.6% had 25(OH)D lt 25nmol/l, and 20.2% had 25-50nmol/l 25(OH)D). Average Vitamin D intake within the study sample (n=316) was 3.9 +/- 7.9 mu g/d, with 92% participants below both Institute of Medicine (IOM) (10 mu g/d) and European Food Safety Authority (15 mu g/d) recommendations. Measured vitamin D status, in 13% of this group, correlated significantly (p=0.015) with intake estimates. Based on self-report, consumption of vitamin D supplements does not exist among study participants. Additional lifestyle factors influencing vitamin D status were analysed. Only 2% of study participants spend approximately 11 min on the sun daily, 60.4% were obese, 23.1% were overweight and 71.2% reported low physical activity. These findings confirm previous reports on high prevalence of VDD in women across NENA, and in Libya. The situation calls for multi-sectoral actions and public health initiatives to address dietary and lifestyle habits

Global Metabolomic Profiling of Acute Myocarditis Caused by Trypanosoma cruzi Infection

© 2014 Gironès et al. Chagas disease is caused by Trypanosoma cruzi infection, being cardiomyopathy the more frequent manifestation. New chemotherapeutic drugs are needed but there are no good biomarkers for monitoring treatment efficacy. There is growing evidence linking immune response and metabolism in inflammatory processes and specifically in Chagas disease. Thus, some metabolites are able to enhance and/or inhibit the immune response. Metabolite levels found in the host during an ongoing infection could provide valuable information on the pathogenesis and/or identify deregulated metabolic pathway that can be potential candidates for treatment and being potential specific biomarkers of the disease. To gain more insight into those aspects in Chagas disease, we performed an unprecedented metabolomic analysis in heart and plasma of mice infected with T. cruzi. Many metabolic pathways were profoundly affected by T. cruzi infection, such as glucose uptake, sorbitol pathway, fatty acid and phospholipid synthesis that were increased in heart tissue but decreased in plasma. Tricarboxylic acid cycle was decreased in heart tissue and plasma whereas reactive oxygen species production and uric acid formation were also deeply increased in infected hearts suggesting a stressful condition in the heart. While specific metabolites allantoin, kynurenine and p-cresol sulfate, resulting from nucleotide, tryptophan and phenylalanine/tyrosine metabolism, respectively, were increased in heart tissue and also in plasma. These results provide new valuable information on the pathogenesis of acute Chagas disease, unravel several new metabolic pathways susceptible of clinical management and identify metabolites useful as potential specific biomarkers for monitoring treatment and clinical severity in patients.This work was supported by ‘‘Ministerio de Ciencia e Innovación’’ (SAF2010-17833); ‘‘Fondo de Investigaciones Sanitarias’’ (PS09/00538 and PI12/00289); ‘‘Red de Investigación de Centros de Enfermedades Tropicales’’ (RICET RD12/0018/0004); European Union (HEALTH-FE-2008-22303, ChagasEpiNet);‘‘Universidad Autónoma de Madrid’’ and ‘‘Comunidad de Madrid’’ (CC08-UAM/SAL-4440/08); AECID Cooperation with Argentine (A/025417/09 and A/031735/10), Comunidad de Madrid (S-2010/BMD-2332) and ‘‘Fundación Ramón Areces’Peer Reviewe