Plasma Lysophosphatidylcholine and Phospholipase A2 Activity in Chagas Disease Patients: A Comparative Analysis

Chagas disease (CD) affects 21 countries in the Americas and is caused by the parasite Trypanosoma cruzi. A key molecule involved in CD is lysophosphatidylcholine (LPC), which has been studied in various contexts: in the saliva of insect vectors, during the establishment of infection in the vertebrate host, and for the parasite itself. This lipid can be produced by the action of phospholipases A2 (PLA2), enzymes that catalyze the hydrolysis of phospholipids releasing fatty acids and lysophospholipids, such as LPC. This study investigates LPC levels and PLA2 activities in the plasma of CD patients and compares these levels with those in healthy individuals and patients with idiopathic dilated cardiomyopathy (IDCM). Plasma from 64 CD patients, 54 healthy individuals, and 16 IDCM patients were analyzed. LPC levels and the activity of two types of phospholipase A2: secreted (sPLA2) and lipoprotein-associated (Lp-PLA2) were measured. LPC levels and sPLA2 activity were similar between CD patients and the control groups. However, there were notable differences in LPC levels and sPLA2 activity between subgroups of CD patients and IDCM patients. This study is the first to identify LPC in patients with CD across various stages of the disease. It also offers new insights into the biochemical changes observed in the plasma of patients with IDCM.

Evaluation of parasitemia by qPCR in patients with chronic Chagas disease treated with benznidazole

Objective:To evaluate parasitemia by qPCR in patients undergoing etiological treatment and followed in a Brazilian reference center.Methods:Parasite load was quantified by qPCR in 32 participants with chronic Chagas disease who were treated with benznidazole.Serological analyses were performed before and after the treatment and parasite loads were compared prior and 12/18 months post the treatment.Results:Thirty-two participants were recruited and treated with benznidazole,and 20 were followed-up.Adverse events(AE)were observed in 22 out of 29 participants that had safety data(76%),and dermatological alterations were the most frequently observed AE.Of the 20 participants analyzed,13 and 7 completed 12 and 18 months follow-up after the treatment,respectively.12 Months after the final treatment,Trypanosoma cruzi was detectable in 3 patients by qPCR;18 months after the final treatment,Trypanosoma cruzi was detectable per qPCR in 4 of the 7 participants.Thus,between 12 and 18 months,7 participants of the 20 initial follow-up cases showed positive qPCR,indicating treatment failures.Conclusions:qPCR can be used as an alternative method for evaluating the effectiveness of the etiological treatment of CD,and can be applied to analyze early therapeutic failures.The study showed that benznidazole therapy had limited effectiveness in treating chronic CD patients,thus emphasizing the importance of conducting continued research for developing more effective therapies and diagnosis for CD.

Interferon-γ and other inflammatory mediators in cardiomyocyte signaling during Chagas disease cardiomyopathy

Chagas disease cardiomyopathy(CCC), the main consequence of Trypanosoma cruzi(T.cruzi) infection, is an inflammatory cardiomyopathy that develops in up to 30% of infected individuals. The heart inflammation in CCC patients is characterized by a Th1 T cell-rich myocarditis with increased production of interferon(IFN)-γ, produced by the CCC myocardial infiltrate and detected at high levels in the periphery. IFN-γ has a central role in the cardiomyocyte signaling during both acute and chronic phases of T.cruzi infection. In this review, we have chosen to focus in its pleiotropic mode of action during CCC, which may ultimately be the strongest driver towards pathological remodeling and heart failure. We describe here the antiparasitic protective and pathogenic dual role of IFN-γ in Chagas disease.

Chemical Control of Chagas Disease Vectors

This paper presents the reasons why countries to which Chagas disease is endemic should carry out the relevant research themselves. A local technical capability for a rational improvement in the chemical control of vectors is being developed. This research includes (1) the triatomicidal activity of chemical insecticides, (2) determination of the mechanisms of action of these chemicals, (3) search for new synergists of these insecticides, (4) development of fumigation canisters which may be more widely used, and (5) development of new chemicals with a greater potential for use as triatomicides. 1989 Academic Press, Inc.

Molecular diagnosis of Chagas disease:a systematic review and meta-analysis

Background The complexity of the Chagas disease and its phases is impossible to have a unique test for both phases and a lot of different epidemiological scenarios.Currently,serology is the reference standard technique;occasionally,results are inconclusive,and a different diagnostic technique is needed.Some guidelines recommend molecular testing.A systematic review and meta-analysis of available molecular tools/techniques for the diagnosis of Chagas disease was performed to measure their heterogeneity and efficacy in detecting Trypanosoma cruzi infection in blood samples.Methods A systematic review was conducted up to July 27,2022,including studies published in international databases.Inclusion and exclusion criteria were defined to select eligible studies.Data were extracted and presented according to PRISMA 2020 guidelines.Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2(QUADAS-2).A random-effects model was used to calculate pooled sensitivity,specificity,and diagnostic odds ratio(DOR).Forest plots and a summary of the receiving operating characteristics(SROC)curves displayed the outcomes.Heterogeneity was determined by I^(2)and Tau^(2)statistics and P values.Funnel plots and Deek's test were used to assess publication bias.A quantitative meta-analysis of the different outcomes in the two different clinical phases was performed.Results We identified 858 records and selected 32 papers.Studies pertained to endemic countries and nonendemic areas with adult and paediatric populations.The sample sizes ranged from 17 to 708 patients.There were no concerns regarding the risk of bias and applicability of all included studies.A positive and nonsignificant correlation coefficient(S=0.020;P=0.992)was obtained in the set of studies that evaluated diagnostic tests in the acute phase population(ACD).A positive and significant correlation coefficient(S=0.597;P<0.000)was obtained in the case of studies performed in the chronic phase population(CCD).This resulted in high heterogeneity between studies,with the master mix origin and guanidine addition representing significant sources.Interpretation/Conclusions and relevance The results described in this meta-analysis(qualitative and quantitative analyses)do not allow the selection of the optimal protocol of molecular method for the study of Trypanosoma cruzi infection in any of its phases,among other reasons due to the complexity of this infection.Continuous analysis and optimization of the different molecular techniques is crucial to implement this efficient diagnosis in endemic areas.

Implementing a vector surveillanceresponse system for chagas disease control:a 4-year field trial in Nicaragua

Background:Chagas disease is one of the neglected tropical diseases(NTDs).International goals for its control involve elimination of vector-borne transmission.Central American countries face challenges in establishing sustainable vector control programmes,since the main vector,Triatoma dimidiata,cannot be eliminated.In 2012,the Ministry of Health in Nicaragua started a field test of a vector surveillance-response system to control domestic vector infestation.This paper reports the main findings from this pilot study.Methods:This study was carried out from 2012 to 2015 in the Municipality of Totogalpa.The Japan International Cooperation Agency provided technical cooperation in designing and monitoring the surveillance-response system until 2014.This system involved 1)vector reports by householders to health facilities,2)data analysis and planning of responses at the municipal health centre and 3)house visits or insecticide spraying by health personnel as a response.We registered all vector reports and responses in a digital database.The collected data were used to describe and analyse the system performance in terms of amount of vector reports as well as rates and timeliness of responses.Results:During the study period,T.dimidiata was reported 396 times.Spatiotemporal analysis identified some high-risk clusters.All houses reported to be infested were visited by health personnel in 2013 and this response rate dropped to 39%in 2015.Rates of insecticide spraying rose above 80%in 2013 but no spraying was carried out in the following 2 years.The timeliness of house visits improved significantly after the responsibility was transferred from a vector control technician to primary health care staff.Conclusions:We argue that the proposed vector surveillance-response system is workable within the resourceconstrained health system in Nicaragua.Integration to the primary health care services was a key to improve the system performance.Continual efforts are necessary to keep adapting the surveillance-response system to the dynamic health systems.We also discuss that the goal of eliminating vector-borne transmission remains unachievable.This paper provides lessons not only for Chagas disease control in Central America,but also for control efforts for other NTDs that need a sustainable surveillance-response system to support elimination.

Preparedness for Chagas disease spreading worldwide

Chagas disease remains a serious problem for public health due to the high disease burden together with its global spreading patterns.However,current treatment and vector control are highly challenged by drug and insecticide resistance.Chemotherapy and vector control have been proved to be effective attempts to minimize the disease burden.Continued efforts are necessary to keep adapting the surveillance-response systems to the dynamic health systems.More attention and investments are needed to improve appropriate strategy and technology in different settings.This may be accomplished by creating effective risk early warning,addressing vulnerability and building resilience systems,implementing a vector surveillance system,as well as innovating research and technology.

Chagas heart disease:An overview of diagnosis,manifestations,treatment,and care

Chagas heart disease(CHD)affects approximately 30%of patients chronically infected with the protozoa Trypanosoma cruzi.CHD is classified into four stages of increasing severity according to electrocardiographic,echocardiographic,and clinical criteria.CHD presents with a myriad of clinical manifestations,but its main complications are sudden cardiac death,heart failure,and stroke.Importantly,CHD has a higher incidence of sudden cardiac death and stroke than most other cardiopathies,and patients with CHD complicated by heart failure have a higher mortality than patients with heart failure caused by other etiologies.Among patients with CHD,approximately 90%of deaths can be attributed to complications of Chagas disease.Sudden cardiac death is the most common cause of death(55%–60%),followed by heart failure(25%–30%)and stroke(10%–15%).The high morbimortality and the unique characteristics of CHD demand an individualized approach according to the stage of the disease and associated complications the patient presents with.Therefore,the management of CHD is challenging,and in this review,we present the most updated available data to help clinicians and cardiologists in the care of these patients.We describe the clinical manifestations,diagnosis and classification criteria,risk stratification,and approach to the different clinical aspects of CHD using diagnostic tools and pharmacological and non-pharmacological treatments.

Community‑based screening of Chagas disease among Latin American migrants in a non‑endemic country: an observational study

Background:Chagas disease is a parasitic disease endemic to Latin America,but it has become a disease of global concern due to migration fows.Asymptomatic carriers may host the parasite for years,without knowing they are infected.The aim of this study is to assess prevalence of Chagas disease and evaluate the participants’level of knowl‑edge between Latin American migrants attending a community-based screening campaign.Methods:Three community-based campaigns were performed in Alicante(Spain)in 2016,2017 and 2018,including educational chats and blood tests for Trypanosoma cruzi serology.Participants completed a questionnaire assessing knowledge about the mechanisms of transmission,disease presentation,diagnosis,and treatment.People seroposi‑tive for T.cruzi underwent diagnostic confrmation by two diferent tests.Results were analyzed by multivariable logistic regression and expressed as adjusted odds ratios(aORs),adjusting for age,sex,and time in Spain.Results:A total of 596 participants were included in the study;17%were aged under 18 years.Prevalence in adults was 11%[54/496;95%confdence interval(CI):8.3–14.5%]versus 0%among children.All but one case were in Bolivians.Diagnosis was independently associated with having been born in Bolivia(aOR:102,95%CI:13–781)and a primary school-level education(aOR:2.40,95%CI:1.14–5.06).Of 54 people diagnosed with Chagas disease(most of whom were asymptomatic),42(77.7%)returned to the clinic at least once,and 24(44.4%)received treatment.Multivariable analysis showed that coming from Argentina(aOR:13,95%CI:1.61–1188)or Bolivia(aOR:1.90,95%CI:1.19–3.39)and having received information about Chagas disease in Spain(aOR:4.63,95%CI:2.54–8.97)were associ‑ated with a good level of knowledge on the disease.Having primary level studies(aOR:0.59,95%CI:0.34–0.98)and coming from Ecuador(aOR:4.63,95%CI:2.52–847)were independently associated with a lower level of knowledge.Conclusions:Community-based interventions are a good strategy for diagnosing neglected diseases such as Chagas disease in non-endemic countries and for identifying and treating infected,asymptomatic individuals.

Integrated vector control of Chagas disease in Guatemala: a case of social innovation in health

Background:Improved access to health care and quality of services require integrated efforts and innovations,including community empowerment and participation in transformation processes.Chagas disease is a neglected tropical disease that is generally controlled by insecticide spraying.To achieve community empowerment in a health program,actions for social innovations may include:community-based research,interdisciplinary and intersectoral participation,community perception of direct benefits and participation in health or environmental improvements.The aim of this study was to describe and analyze the processes by which an interdisciplinary team,in collaboration with communities of Comapa,Guatemala,developed an effective solution to address the risk for Chagas disease.Methods:A qualitative study involving interviews semi-structured and direct observation was conducted using a case study approach to describe and understand the community-based research and intervention process developed by researchers from the Laboratory of Applied Entomology and Parasitology of the Universidad de San Carlos of Guatemala(Laboratorio de Entomologia y Parasitologia Aplicada).Nine interviews were conducted with the investigators,innovators,members of the community in which the intervention had been implemented.NVivo software(version 12)was used for the emergent coding and analysis of the interviews.Results:Processes of social transformation were evident within households,and the communities that transcended the mere improvement of walls and floors.New social dynamics that favored the household economy and conditions of hygiene and home care that positively impacted the health of the community.We describe how the integration of criteria of social innovation into a home improvement strategy for Chagas disease control,can generate processes of transformation in health by considering sociocultural conditions,encouraging dialogue between public health approaches and traditional practices.We identify and discuss processes for Social Innovations in Health and identify their potential in improving community health in Latin America.Conclusions:When social innovation criteria are included in a health control initiative,the community-based research and the interdisciplinary and intersectoral participation facilitate the implementation of the control strategy,the perceived benefits by the community and its empowerment to sustain and share the strategy.The case study provided understanding of the intersectoral and interdisciplinary dynamics in particular contexts,and documented the relevance of innovation criteria in health processes.

Simulations of a logistic-type model with delays for Chagas disease with insecticide spraying

This work studies and numerically simulates a logistic-type model for the dynamics of Chagas disease, which is caused by the parasite T. cruzi and affects millions of humans and domestic mammals throughout rural areas in Central and South America. A basic model for the disease dynamics that includes insecticide spraying was developed in Spagnuolo et al. （2010） [271 and consists of a delay-differential equation for the vectors and three nonlinear ordinary differential equations for the populations of the infected vectors, infected humans and infected domestic mammals. In this work, the vector equation is modified by using a logistic term with zero, one or two delays or time lags. The aim of this study is three-fold： to numerically study the effects of using different numbers of delays on the model behavior; to find if twice yearly insecticide spraying schedules improve vector control; and to study the sensitivity of the system to the delays in the case of two delays, by introducing randomness in the delays. It is found that the vector equation with different number of delays has very different solutions. The ＂best＂ day of spraying is the middle of Spring and twice annual sprayings cause only minor improvements in disease control. Finally, the model is found to be insensitive to the values of the delays, when the delays are randomly distributed within rather narrow intervals or ranges centered on the parameter values used in Coffield et al. （2014） [8].

Clinicopathological alterations in wild mammals from the reservoir system of Trypanosoma cruzi:a scoping review

Trypanosoma cruzi is the etiologic agent of Chagas disease.This flagellated protozoan is transmitted to humans as well as different species of domestic and wild animals via vectors from the Reduviidae family(known as"kissing bugs").Despite the fact that hundreds of species of wild mammals are part of the reservoir system,the morphologi-cal changes and clinical manifestations resulting from the pathogenesis of the infection have been largely neglected.The aim of this review is to systematically compile the available information regarding clinicopathological altera-tions in wild mammals due to natural infection by T.cruzi.Information was obtained from six online bibliographic data search platforms,resulting in the identification of 29 publications that met the inclusion criteria.Mortality was the most common clinical manifestation,cardiac damage was the main finding at necropsy,and lymphoplas-macytic inflammation was the most frequent microscopic injury.Thus,regardless of its role as a reservoir,T.cruzi has the potential to affect the health status of wild mammals,a situation that highlights the need for further research to analyze,measure,and compare its effects at both the individual and population levels.

Surgical risk for patients with Chagasic achalasia and its correlation with the degree of esophageai dilation

AIM： To analyze the risk of cardiovascular complications in patients with indication for surgical treatment of Chagasic esophageal achalasia and to correlate the surgical risks with the degree of esophageal dilation, thereby proposing a risk scale index. METHODS： One hundred and twenty-four patients with Chagasic esophageal achalasia, who received surgical treatment at the Hospital das Clinicas of the Federal University of Goiás, were included in this study. The patients were mostly related to the postoperative complications due to the cardiovascular system. All the patients were submitted to： （1） clinical history to define the cardiac functional class （New York Heart Association）; （2） conventional 12-lead electrocardiogram at rest; and （3） contrast imaging of the esophagus to determine esophageal dilatation according to Rezende＇s classification of Chagasic megaesophagus. RESULTS： An assessment of the functional classification （FC） of heart failure during the preoperative period determined that 67 patients （54.03%） were assigned functional class Ⅰ （FC Ⅰ）, 46 patients （37.09%） were assigned functional class Ⅱ （FC Ⅱ）, and 11 patients （8.87%） were assigned functional class Ⅲ （FC Ⅲ）. None of the patients were assigned to functional class Ⅳ （FC Ⅳ）. There was a positive correlation between the functional class and the postoperative complications （FC Ⅰ×FC Ⅱ： P〈0.001; FC Ⅰ×FC Ⅲ： P〈0.001）. The ECG was normal in 44 patients （35.48%） and presented abnormalities in 80 patients （64.52%）. There was a significant statistical correlation between abnormal ECG （arrhythmias and primary change in ventricular repolarization） and postoperative complications （P〈0.001）. With regard to the classification of the Chagasic esophageal achalasia, the following distribution was observed： group Ⅱ, 53 patients （42.74%）; group Ⅲ, 37 patients （29.83%）; and group Ⅳ, 34 patients （27.41%）. There was a positive correlation between the degree of esophageal dilation and the increase in postoperative complications （grade Ⅱ×grade Ⅲ achalasia： P〈0.001; grade Ⅱ×grade Ⅳ achalasia： P〈0.001; and grade Ⅲ×grade Ⅳ achalasia： P = 0.017）. Analyzing these results and using a multivariate regression analysis associated with the probability decision analysis, a risk scale was proposed as follows： up to 21 points （mild risk）; from 22 to 34 points （moderate risk）; and more than 34 points （high risk）. The scale had 82.4% accuracy for mild risk patients and up to 94.6% for the high risk cases. CONCLUSION： The preoperative evaluation of the cardiovascular system, through a careful anamnesis, an ECG and contrast imaging of the esophagus, makes possible to estimate the surgical risks for Chagas＇ disease patients who have to undergo surgical treatment for esophageal achalasia.

Unlocking the in vitro anti-Trypanosoma cruzi activity of halophyte plants from the southern Portugal

Objective:To evaluate the in vitro anti-Trypanosoma cruzi（T.cruzi） activity of organic extracts prepared from halophyte species collected in the southern coast of Portugal（Algarve）,and chemically characterize the most active samples.Methods:Acetone,dichloromethane and methanol extracts were prepared from 31 halophyte species and tested in vitro against trypomastigotes and intracellular amastigotes of the Tulahuen strain of T.cruzi.The most active extract was fractionated by preparative HPLC-DAD,affording 11 fractions.The most selective fraction was fully characterized by 1H-NMR.Results:From 94 samples tested,one was active,namely the root dichloromethane extract of Juncus acutus(IC50 < 20 μg/mL).This extract was fractionated by HPLC,affording 11 fractions,one of them containing only a pure compound（juncunol）,and tested for anti-parasitic activity.Fraction 8(IC50 = 4.1 μg/mL) was the most active,and was further characterized by 1H-NMR.The major compounds were phenanthrenes,9,10-dihydrophenanthrenes and benzocoumarins.Conclusion:Our results suggest that the compounds identified in fraction 8 are likely responsible for the observed anti parasitic activity.Further research is in progress aiming to isolate and identify the specific active molecules.To the best of our knowledge,this is the first report on the in vitro anti T.cruzi activity of halophyte species.

Trypanosoma cruzi invasion in non-phagocytic cells:an ultrastructural study

Trypanosoma cruzi is the causative agent of Chagas disease.This parasite requires the intracellular niche in order to proliferate and disseminate the infection.After invasion,T.cruzi resides temporarily in an acidic vacuole which is lysed by a not well-understood mechanism.Transmission electron microscopy was used to describe the process of T.cruzi escape from the parasitophorous vacuole over the time.Using HeLa(non-professional phagocytic cells)as host cell,we observed that recently internalized parasites reside in a membrane-bounded vacuole.A few hours later,the first sign of vacuole disruption appeared as membrane discontinuities.This observation was followed by a progressive vacuole swelling as evidenced by an electron-lucent halo between the parasite and the vacuole membrane.Apparently,the vacuole membrane remnants reorganized as small vesicles that eventually disappeared from the vicinity of the parasites.Finally,parasites reach the host cell cytosol where replication takes place.The thorough ultrastructural description of this process set the base for a comprehensive understanding of the parasite-host cell interaction and,thus open the possibility of new therapeutic intervention strategies.

Evaluation of the Anti-Trypanosoma cruzi Effects of the Antipsychotic Drug Levomepromazine

Chagas disease, caused by the protozoan Trypanosoma cruzi, is a relevant parasitic disease in the Americas. Current chemotherapy relies on Nifurtimox and Benznidazole, which present serious drawbacks, including high toxicity, low efficiency and the emergence of resistant strains. In the present work, the perspectives of levomepromazine, a tri-cyclic compound belonging to the family of phenotiazines with well-known properties as antipsychotics were evaluated as a potential anti-T. cruzi drug. We show that this drug is able to inhibit the proliferation of epimastigotes (IC50 = 0.41 ± 0.01 mM) and to interfere with the infection of the host cells (IC50 = 0.34 ± 0.01 mM). Interestingly, the treatment with levomepromazine affected the ability of metabolites such as glucose, proline and glutamate to fuel the recovery of epi-mastigotes after being submitted to metabolic stress. These findings prompt levomepromazine as a promising leader drug to obtain new trypanocidal activities.

Cardiomyopathies in Tropical Countries:Causes and Nosological Perspective

Background: Cardiomyopathy is the main cause of heart failure in developing countries, mainly in Africa. In those areas the concept of “tropical cardiomyopathy” is still used to design all unexplained cardiomyopathy. The primary aim of this review is first to review the main etiologies of cardiomyopathies observed in tropical countries and second to gain a better understanding of the nosological place of the so-called “tropical cardiomyopathies” in the current framework of cardiomyopathies. Methods and Results: We reviewed relevant references over the last forty years (June, 1976 to May 2012). Given literature data, endomyocardial fibrosis (EMF) is mainly diagnosed in sub-Saharan countries, as well as Brazil and India. Peripartum cardiomyopathy (PPCM) is observed with a higher prevalence than in temperate countries. Sickle cell anemia does not induce specific cardiomyopathy in all echocardiographic studies. Malnutrition and chronic anemia can induce reversible cardiac dysfunction. Myocardial involvement in parasitic infections is restricted to Chagas disease and probably to human African trypanosomiasis. Helminthiasis is not involved in the pathogenesis of cardiomyopathy except for the deleterious effect of high eosinophilia induced by some endemic diseases (filariasis, schistosomiasis). Primary cardiomyopathies (dilated, hypertrophic, and restrictive cardiomyopathy) have no specificity. Arrhythmogenic right ventricular dysplasia and left ventricular noncompaction are also reported and do not differ from elsewhere. Conclusions: The concept of tropical cardiomyopathy is no longer relevant as most of the cardiomyopathies observed in tropical countries have no specificity, with few exceptions (PPCM, EMF, Chagas disease). In this context, the European Society of Cardiology classification offers a simpler clinical approach and allows the inclusion of the rare tropical specificities.

Control of malaria and other vector-borne protozoan diseases in the tropics: enduring challenges despite considerable progress and achievements

Vector-borne protozoan diseases represent a serious public health challenge,especially in the tropics where poverty together with vector-favorable climates are the aggravating factors.Each of the various strategies currently employed to face these scourges is seriously inadequate.Despite enormous efforts,vaccines-which represent the ideal weapon against these parasitic diseases—are yet to be sufficiently developed and implemented.Chemotherapy and vector control are therefore the sole effective attempts to minimize the disease burden.Nowadays,both strategies are also highly challenged by the phenomenon of drug and insecticide resistance,which affects virtually all interventions currently used.The recently growing support from international organizations and governments of some endemic countries is warmly welcome,and should be optimally exploited in the various approaches to drug and insecticide research and development to overcome the burden of these prevalent diseases,especially malaria,leishmaniasis,Human African Trypanosomiasis(HAT),and Chagas disease.

Neglected tropical diseases in Brazilian children and adolescents:data analysis from 2009 to 2013

Background:Neglected tropical diseases(NTDs)prevail in conditions of poverty and contribute to the maintenance of social inequality.Out of the NTDs prioritized by the Brazilian Ministry of Health,four parasitic infections require mandatory notification:acute Chagas disease,leishmaniasis,malaria,and schistosomiasis.Data on the behaviour of these NTDs in the young population are currently limited.This study seeks to analyse the epidemiological aspects of these parasitic infections in children and adolescents in Brazil.Methods:A retrospective exploratory ecological study was conducted.A spatial analysis of the cases reported between 2009 and 2013 in individuals aged between 0 and 19 years that were notified through the Health Notification Aggravation Information System(SINAN)was performed.Results:In total,64,567 cases of cutaneous and visceral leishmaniasis,malaria,schistosomiasis,and acute Chagas disease were recorded in the SINAN database,representing a rate of 20.15 cases per 100,000 inhabitants.The average age of the cases was 12.2 years and 62.32%were male.Four hundred and three deaths related to these obligatorily reported parasites were recorded,indicating a case fatality rate of 0.62%.Visceral leishmaniasis and acute Chagas disease had the highest rates of lethality.A heterogeneous spatial distribution of the studied parasites was observed.Conclusions:The number of cases and the lethality rate described in this study show that these diseases still represent a serious problem for public health in Brazil.This points to the need to encourage new research and the reformulation of social,economic,and public health policies aimed at ensuring better health and living conditions for all individuals,especially those among the populations considered vulnerable,as is the case of the young.

CXCL9 and CXCL10 display an agedependent profile in Chagas patients:a cohort study of aging in Bambui,Brazil

Background:Chagas disease is endemic in Latin America and still represents an important public health problem in the region.Chronic cardiomyopathy is the most significant chronic form due to its association with morbidity and mortality.The last decade has seen increasing evidence that inflammatory cytokines and chemokines are responsible for the generation of inflammatory infiltrate and tissue damage,with chronic chagasic cardiomyopathy patients presenting a pro-inflammatory immune response.Although studies have evaluated the role of chemokines in experimental T.cruzi infection,few have addressed their systemic profile,especially for human infection and in aging populations.The present work aimed to use the data from a large population based study of older adults,conducted in an endemic area for Chagas disease,to examine the association between serum levels of cytokines and chemokines,T.cruzi infection and electrocardiogram(ECG)abnormality.Methods:The present work evaluated serum levels of CCL2,CXCL9,CXCL10,CCL5,CXCL8,IL-1β,IL-6,TNF,IL-12 and IL-10 by Flow Cytometric Bead Array assay(CBA)and the results expressed in pg/ml.The baseline survey started in January 1st 1997,with 1284 participants of an aged population-based cohort.Participants signed an informed consent at baseline and at each subsequent visit and authorized death certificate and medical records verification.Results:Our results demonstrated that Chagas disease patients had higher serum levels of CXCL9,CXCL10 and IL-1βand lower serum levels of CCL5 than non-infected subjects.Moreover,our data demonstrated that CXCL9 and CXCL10 increased in an age-dependent profile in Chagas disease patients.Conclusion:Together,this study provided evidences that serum biomarkers increase along the age continuum and may have potential implications for establishing clinical management protocols and therapeutic intervention in Chagas disease patients.