The importance of the multidisciplinary approach to deal with the new epidemiological scenario of Chagas disease (global health)

There are currently two major factors that have modified the epidemiology of Chagas disease in the last decades: climate change and migration flows. In this new scenario, there are new challenges to control and prevent Trypanosoma cruzi infection in endemic countries, such as the control of a wider distribution of triatomine vectors or the reinforcement of vertical transmission programs. In non-endemic areas, few countries are aware of the emergence of this new disease and have established changes in their health systems. To address this new public health challenge, the priorities should be control programs to avoid new cases of T. cruzi infection acquired through vertical transmission, blood transfusion or organ transplant. In both, endemic and non-endemic areas, the international community and all the actors involved in Chagas disease must join efforts mainly in two directions: better management of the infection in affected individuals and more research to cover the knowledge gap mainly in physiopathology, diagnosis and treatment

Pulmonary Infiltrates and Eosinophilia in a 25-Year-Old Traveler

A 25-year-old Spanish male travelled to Senegal in September 2009, where he swam near the Dindefelo fresh-water falls. Five weeks later, he presented with fever, myalgia, and dry cough. His complete blood count showed a hemoglobin level of 157 g/L, platelet count of 123.000 platelets/µL, and a leukocyte count of 8.670 cells/µL, with 9% eosinophils. Malaria smear, blood cultures, and serologies for common viral and bacterial infections were negative. Titers of an indirect hemagglutination test for Schistosoma mansoni were 1∶80. The patient was treated with a single dose of praziquantel (40 mg/kg) and prednisone (30 mg) for three days. After treatment, the dry cough increased and he developed moderate dyspnea, with increasing malaise and myalgia. A second blood sample revealed eosinophilia of 1.200 cells/µL. A chest X-ray showed patchy infiltrates in both lungs (Figure 1), and a CT scan showed multiple peripheral bilateral pseudonodular lesions with surrounding ground-glass-opacity halo

Clinkering of calcium sulfoaluminate clinkers: polymorphism of ye'elimite

The manufacture of CSA cements is more environmentally friendly than that of OPC as it releases less CO2. This reduction depends on CSA composition and is due to three factors: i) less emissions from decarbonation in the kilns; ii) lower clinkering temperature, consequently less fuel is needed, and iii) it is easier to grind, implying a depletion in indirect emissions. CSA cements are prepared by mixing the clinker with different amounts of calcium sulfate as a set regulator. Their main performances are fast setting time (followed by a rapid hardening), good chemical resistance and, depending on the amount of the added sulfate source they can work as shrinkage controllers. CSA cements present a wide range of phase assemblages, but all of them contain over 50 wt% of ye'elimite (C4A3s) jointly with belite (C2S), tetracalcium aluminoferrite (C4AF) and other minor components such as CA, Cs, CsH2 and so on [1]. Ye'elimite is also included (~25 wt%) in BYF (Belite- Ye'elimite-Ferrite) or BAY (Belite-Alite-Ye'elimite) clinkers. Ye'elimite has a sodalite type structure with general composition, M4[T6O12]X. Stoichiometric ye'elimite crystal structure at room temperature will be described in detailed. The role of different amounts of minor elements on the synthetic procedure and crystal structures will be also presented [2,3]. This keynote will be also focused on a revision of the effect of raw materials on the mineralogical composition of CSA, BYF and BAY. Specifically, the role of main elements contents in the ye'elimite formation in these systems will be described. Moreover, the effect of minor elements on the polymorphism of both ye'elimite and belite, especially on BYF and BAY clinkers, will be presented [4,5,6].Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Spanish MINECO and FEDER [BIA2017-82391-R] research project and I3 [IEDI-2016-0079] program

In silico Design of an Epitope-Based Vaccine Ensemble for Chagas Disease

Trypanosoma cruzi infection causes Chagas disease, which affects 7 million people worldwide. Two drugs are available to treat it: benznidazole and nifurtimox. Although both are efficacious against the acute stage of the disease, this is usually asymptomatic and goes undiagnosed and untreated. Diagnosis is achieved at the chronic stage, when life-threatening heart and/or gut tissue disruptions occur in ∼30% of those chronically infected. By then, the drugs’ efficacy is reduced, but not their associated high toxicity. Given current deficiencies in diagnosis and treatment, a vaccine to prevent infection and/or the development of symptoms would be a breakthrough in the management of the disease. Current vaccine candidates are mostly based on the delivery of single antigens or a few different antigens. Nevertheless, due to the high biological complexity of the parasite, targeting as many antigens as possible would be desirable. In this regard, an epitope-based vaccine design could be a well-suited approach. With this aim, we have gone through publicly available databases to identify T. cruzi epitopes from several antigens. By means of a computer-aided strategy, we have prioritized a set of epitopes based on sequence conservation criteria, projected population coverage of Latin American population, and biological features of their antigens of origin. Fruit of this analysis, we provide a selection of CD8+ T cell, CD4+ T cell, and B cell epitopes that have <70% identity to human or human microbiome protein sequences and represent the basis toward the development of an epitope-based vaccine against T. cruzi

Host-Derived Molecules as Novel Chagas Disease Biomarkers: Hypercoagulability Markers in Plasma

The most severe clinical symptomatology of Chagas disease affects ~30% of those chronically infected with the Trypanosoma cruzi parasite. The pathogenic mechanisms that lead to life-threatening heart and gut tissue disruptions occur "silently" for a longtime in a majority of cases. As a result, despite there are several serological and molecular methods available to diagnose the infection in its acute and chronic stages, diagnosis is often achieved only after the onset of clinical symptoms in the chronic phase of the disease. Furthermore, although there are two drugs to treat it, the assessment of their performance is impractical with current parasite-derived diagnostics, and therapeutic efficacy cannot be acknowledged in a timely manner.In this chapter we present two procedures to measure host-derived molecules as surrogates of therapeutic response against chronic T. cruzi infection. Their outputs relate to the generation and activity of thrombin, a major component of the blood coagulation cascade. This is due to the fact that a hypercoagulability state has been described to occur in chronic Chagas disease patients and revert after treatment with benznidazole

Diagnosis of Trypanosoma cruzi Infection Status using Saliva of Infected Subjects

Chagas disease has the highest prevalence of any parasitic disease in the Americas, affecting 6-7 million people. Conventional diagnosis requires a well-equipped laboratory with experienced personnel. The development of new diagnostic tools that are easy to use and adapted to the reality of affected populations and health systems is still a significant challenge. The main objective of this study was to measure Trypanosoma cruzi infection status using saliva samples of infected subjects. Blood and saliva samples from 20 T. cruzi-seropositive individuals and 10 controls were tested for T. cruzi infection using two different commercial serological tests. We have shown that detection of T. cruzi infection is possible using saliva samples, supporting the potential use of saliva to diagnose Chagas disease in humans. This method could provide a simple, low-cost but effective tool for the diagnosis of T. cruzi infection. Its noninvasive nature makes it particularly well suited for endemic areas

State-of-the-art in host-derived biomarkers of Chagas disease prognosis and early evaluation of anti-Trypanosoma cruzi treatment response

Chagas disease is caused by infection with the parasite Trypanosoma cruzi, which might lead to a chronic disease state and drive to irreversible damage to the heart and/or digestive tract tissues. Endemic in 21 countries in the Americas, it is the neglected disease with a highest burden in the region. Current estimates point at ~6 million people infected, of which ~30% will progress onto the symptomatic tissue disruptive stage. There is no vaccine but there are two anti-parasitic drugs available: benznidazole and nifurtimox. However, their efficacy is variable at the chronic symptomatic stage and both have frequent adverse effects. Since there are no prognosis markers, drugs should be administered to all T. cruzi-infected individuals in the indeterminate and early symptomatic stages. Nowadays, there are no tests-of-cure either, which greatly undermines patients' follow-up and the search of safer and more efficacious drugs. Therefore, the identification and validation of biomarkers of disease progression and/or treatment response on which to develop tests of prognosis and/or cure is a major research priority. Both parasite- and host-derived markers have been investigated. In the present manuscript we present an updated outlook of the latter

Structure of stratlingite and effect of hydration methodology on microstructure

Stratlingite, Ca4Al2(OH)12[AlSi(OH)8]2•2H2O, is an AFm phase which appears as hydration product of aluminum-rich cements. These binders may be calcium aluminate cements, calcium sulfoaluminate cements and also Belite Calcium Sulfo-Aluminate (BCSA) cements. The structure of stratlingite is known from single crystal studies of tiny minerals but their bulk formation, crystal structure and microstructure of powders is poorly understood. Here, we report the synthesis of stratlingite and a complete structural and microstructural characterization by synchrotron X-ray powder diffraction, nuclear magnetic resonance, scanning electron microscopy and thermal analyses. The structural and microstructural models have important implications for a correct quantitative phase analysis of stratlingite in cement pastes (for instance, in pastes of BCSA cements). The microstructure of stratlingite formed in cement pastes is highly dependent on the hydration conditions. In BCSA pastes, the (003) line position of stratlingite appears slightly shifted towards higher diffracting angles (lower inter-layered distance) after stopping hydration compared to that of a similar phase present in a paste analyzed without stopping hydration. This is related to dehydration and disorder. This shift and peak broadening is even larger when the paste has suffered partial dehydration during curing (apart from stopping hydration). A microstructural study is reportedThis work has been supported by Junta de Andalucía through P11-FQM-07517 research project. I. Santacruz thanks a Ramón y Cajal fellowship, RYC-2008-03523. Synchrotron experiments were performed in MSPD beamline at ALBA Synchrotron Light Facility with the collaboration of François Fauth

Amaryllidaceae alkaloids with anti-Trypanosoma cruzi activity

Background: Chagas disease, caused by the protozoan Trypanosoma cruzi, is a neglected disease that afects ~7 million people worldwide. Development of new drugs to treat the infection remains a priority since those currently available have frequent side efects and limited efcacy at the chronic stage. Natural products provide a pool of diver sity structures to lead the chemical synthesis of novel molecules for this purpose. Herein we analyzed the anti-T. cruzi activity of nine alkaloids derived from plants of the family Amaryllidaceae. Methods: The activity of each alkaloid was assessed by means of an anti-T. cruzi phenotypic assay. We further evalu ated the compounds that inhibited parasite growth on two distinct cytotoxicity assays to discard those that were toxic to host cells and assure parasite selectivity. Results: We identifed a single compound (hippeastrine) that was selectively active against the parasite yielding selectivity indexes of 12.7 and 35.2 against Vero and HepG2 cells, respectively. Moreover, it showed specifc activity against the amastigote stage (IC50=3.31 μM). Conclusions: Results reported here suggest that natural products are an interesting source of new compounds for the development of drugs against Chagas disease. Keywords: Chagas disease, Trypanosoma cruzi, Alkaloids, Amaryllidaceae, Hippeastrine, Phenotypic assays, Cytotoxicit

Characterization of digestive involvement in patients with chronic T. cruzi infection in Barcelona, Spain

Background: Digestive damage due to Chagas disease (CD) occurs in 15-20% of patients diagnosed as a result of peristaltic dysfunction in some endemic areas. The symptoms of chronic digestive CD are non-specific, and there are numerous confounders. Diagnosis of CD may easily be missed if symptoms are not evaluated by a well trained physician. Regular tests, as barium contrast examinations, probably lack the necessary sensitivity to detect early digestive damage. Methods: 71 individuals with T. cruzi infection (G1) and 18 without (G2) coming from Latin American countries were analyzed. They were asked for clinical and epidemiological data, changes in dietary habits, and history targeting digestive and cardiac CD symptoms. Serological tests for T. cruzi, barium swallow, barium enema, an urea breath test, and esophageal manometry were requested for all patients. Principal findings: G1 and G2 patients did not show differences in lifestyle and past history. Fifteen (21.1%) of G1 had digestive involvement. Following Rezende criteria, esophagopathy was observed in 8 patients in G1 (11.3%) and in none of those in G2. Manometry disorders were recorded in 34 G1 patients and in six in G2. Isolated hypotensive lower esophageal sphincter (LES) was found in sixteen G1 patients (23.9%) and four G2 patients (28.8%). Achalasia was observed in two G1 patients. Among G1 patients, ineffective esophageal motility was seen in six (five with symptoms), diffuse esophageal spasm in two (one with dysphagia and regurgitation), and nutcracker esophagus in three (all with symptoms). There were six patients with hypertonic upper esophageal sphincter (UES) among G1. Following Ximenes criteria, megacolon was found in ten G1 patients (13.9%), and in none of the G2 patients. Conclusions: The prevalence of digestive chronic CD in our series was 21.1%. Dysphagia is a non-pathognomonic symptom of CD, but a good marker of early esophageal involvement. Manometry could be a useful diagnostic test in selected cases, mainly in patients with T. cruzi infection and dysphagia in whose situation barium swallow does not evidence alterations. Constipation is a common but non-specific symptom that can be easily managed. Testing for CD is mandatory in a patient from Latin America with constipation or dysphagia, and if diagnosis is confirmed, megacolon and esophageal involvement should be investigated