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proteomic profile of circulating immune complexes in chronic chagas disease.immune complexes (ics) are the direct and real-time products of humoral immune responses. the identification of constituent foreign or autoantigens within ics might bring new insights into the pathology of infectious diseases. we applied immune complexome analysis of plasma to the study of chagas disease caused by trypanosoma cruzi. twenty seropositive plasma samples including cardiac and/or megacolon determinate patients (n = 11) and indeterminate (n = 9) were analysed along with 10 seronegativ ...201627223052
the active transport of histidine and its role in atp production in trypanosoma cruzi.trypanosoma cruzi, the aetiological agent of chagas's disease, metabolizes glucose, and after its exhaustion, degrades amino acids as energy source. here, we investigate histidine uptake and its participation in energy metabolism. no putative genes for the histidine biosynthetic pathway have been identified in genome databases of t. cruzi, suggesting that its uptake from extracellular medium is a requirement for the viability of the parasite. from this assumption, we characterized the uptake of ...201627222029
first finding of trypanosoma cruzi ii in vampire bats from a district free of domestic vector-borne transmission in northeastern argentina.establishing the putative links between sylvatic and domestic transmission cycles of trypanosoma cruzi, the etiological agent of chagas disease, is of public health relevance. we conducted three surveys to assess t. cruzi infection in wild mammals from a rural and a preserved area in misiones province, northeastern argentina, which had recently been declared free of vector- and blood-borne transmission of human t. cruzi infection. a total of 200 wild mammals were examined by xenodiagnosis (xd) a ...201627220254
novel cruzipain inhibitors for the chemotherapy of chronic chagas disease.despite current efforts worldwide to develop new medications against chagas disease, only two drugs are available, nifurtimox and benznidazole. both drugs require prolonged treatment and have multiple side effects and limited efficacy on adult patients chronically infected with trypanosoma cruzi. recently, computer-guided drug repositioning led to the discovery of the trypanocidal effects of clofazimine and benidipine. these compounds showed inhibitory effects on cruzipain, the major cysteine pr ...201627216381
phenotypic screening in vitro of novel aromatic amidines against trypanosoma cruzi.the current treatment of chagas disease (cd), based on nifurtimox and benznidazole (bz), is unsatisfactory. in this context, we performed the phenotypic in vitro screening of novel mono- and diamidines and drug interaction assays with selected compounds. ten novel amidines were tested for their activities against bloodstream trypomastigote (bt) and amastigote forms of trypanosoma cruzi (y and tulahuen strains) and their toxicities for mammalian host cells (l929 cells and cardiac cells). seven of ...201627216059
chagas cardiomyopathy: the potential effect of benznidazole treatment on diastolic dysfunction and cardiac damage in dogs chronically infected with trypanosoma cruzi.cardiac involvement represents the main cause of mortality among patients with chagas disease, and the relevance of trypanocidal treatment to improving diastolic dysfunction is still doubtful. in the present study, we used a canine model infected with the benznidazole-sensitive berenice-78 trypanosoma cruzi strain to verify the efficacy of an etiologic treatment in reducing the parasite load and ameliorating cardiac muscle tissue damage and left ventricular diastolic dysfunction in the chronic p ...201627215760
highly diluted medication reduces tissue parasitism and inflammation in mice infected by trypanosoma cruzi.to evaluate the effects of kalium causticum, conium maculatum, and lycopodium clavatum 13ch in mice infected by trypanosoma cruzi.201627211326
new sex-determination system in the genus  panstrongylus (hemiptera: reduviidae) revealed by chromosomal analysis of panstrongylus lutzi.panstrongylus lutzi (neiva & pinto, 1923) is a triatomine species native to caatinga habitats in north-eastern brazil. it is considered an important vector of chagas disease in this region, presenting high rates of natural infection with trypanosoma cruzi chagas, 1909, and readily invading houses by flight. this study describes a previously unknown chromosomal sex system in the genus panstrongylus based on p. lutzi.201627209318
simple methodology to directly genotype trypanosoma cruzi discrete typing units in single and mixed infections from human blood samples.different dna markers to genotype trypanosoma cruzi are now available. however, due to the low quantity of parasites present in biological samples, dna markers with high copy number like kinetoplast minicircles are needed. the aim of this study was to complete a dna assay called minicircle lineage specific-pcr (mls-pcr) previously developed to genotype the t. cruzi dtus tcv and tcvi, in order to genotype dtus tci and tcii and to improve tcvi detection. we screened kinetoplast minicircle hypervar ...201627208806
trypanosoma teixeirae: a new species belonging to the t. cruzi clade causing trypanosomosis in an australian little red flying fox (pteropus scapulatus).little is known about the genetic diversity and pathogenicity of trypanosomes in australian bats. recently a novel trypanosome species was identified in an adult female little red flying fox (pteropus scapulatus) with clinical and pathological evidence of trypanosomosis. the present study used morphology and molecular methods to demonstrate that this trypanosome is a distinct species and we propose the name trypanosoma teixeirae sp. n. morphological comparison showed that its circulating trypoma ...201627198803
apoptotic cd8 t-lymphocytes disable macrophage-mediated immunity to trypanosoma cruzi infection.chagas disease is caused by infection with the protozoan trypanosoma cruzi. cd8 t-lymphocytes help to control infection, but apoptosis of cd8 t cells disrupts immunity and efferocytosis can enhance parasite infection within macrophages. here, we investigate how apoptosis of activated cd8 t cells affects m1 and m2 macrophage phenotypes. first, we found that cd8 t-lymphocytes and inflammatory monocytes/macrophages infiltrate peritoneum during acute t. cruzi infection. we show that treatment with a ...201627195678
extraction of trypanosoma cruzi dna from food: a contribution to the elucidation of acute chagas disease outbreaks.before 2004, the occurrence of acute chagas disease (acd) by oral transmission associated with food was scarcely known or investigated. originally sporadic and circumstantial, acd occurrences have now become frequent in the amazon region, with recently related outbreaks spreading to several brazilian states. these cases are associated with the consumption of açai juice by waste reservoir animals or insect vectors infected with trypanosoma cruzi in endemic areas. although guidelines for processin ...201627192588
trypanosoma cruzi isolated from a triatomine found in one of the biggest metropolitan areas of latin america.to characterize trypanosoma cruzi (tci) isolated from a panstrongylus megistus specimen found in one of the biggest metropolitan areas of latin america, the relationship between the tci group of t. cruzi and the transmission cycle in the urban environment was studied.201627192587
gold(iii) complexes with ons-tridentate thiosemicarbazones: toward selective trypanocidal drugs.tridentate thiosemicarbazone ligands with an ons donor set, h2l(r) (r = me and et) were prepared by reactions of 1-phenyl-1,3-butanedione with 4-r-3-thiosemicarbazides. h2l(r) reacts with na[aucl4]·2h2o in meoh in a 1:1 m ratio under formation of green gold(iii) complexes of composition [aucl(l(r))]. these compounds represent the first examples of gold(iii) complexes with ons chelate-bonded thiosemicarbazones. the in vitro anti-trypanosoma cruzi activity against both trypomastigote and amastigot ...201627191616
serum cytokines as biomarkers of early trypanosoma cruzi infection by congenital exposure.trypanosoma cruzi, the causing agent of chagas disease, leads to an activation of the immune system in congenitally infected infants. in this study, we measured a set of cytokines/chemokines and the levels of parasitemia by quantitative pcr in the circulation of neonates born to t. cruzi-infected mothers to evaluate the predictive value of these mediators as biomarkers of congenital transmission. we conducted a retrospective cohort study of 35 infants with congenital t. cruzi infection, of which ...201627183607
genomic african and native american ancestry and chagas disease: the bambui (brazil) epigen cohort study of aging.the influence of genetic ancestry on trypanosoma cruzi infection and chagas disease outcomes is unknown.201627182885
trypanosoma cruzi-trypanosoma rangeli co-infection ameliorates negative effects of single trypanosome infections in experimentally infected rhodnius prolixus.trypanosoma cruzi, causative agent of chagas disease, co-infects its triatomine vector with its sister species trypanosoma rangeli, which shares 60% of its antigens with t. cruzi. additionally, t. rangeli has been observed to be pathogenic in some of its vector species. although t. cruzi-t. rangeli co-infections are common, their effect on the vector has rarely been investigated. therefore, we measured the fitness (survival and reproduction) of triatomine species rhodnius prolixus infected with ...201627174360
the tctasv proteins are novel promising antigens to detect active trypanosoma cruzi infection in dogs.in regions where chagas disease is endemic, canine trypanosoma cruzi infection is highly correlated with the risk of transmission of the parasite to humans. herein we evaluated the novel tctasv protein family (subfamilies a, b, c), differentially expressed in bloodstream trypomastigotes, for the detection of naturally infected dogs. a gene of each tctasv subfamily was cloned and expressed. indirect enzyme-linked immunosorbent assays (elisa) were developed using recombinant antigens individually ...201627173912
characteristics of triatomine infestation and natural trypanosoma cruzi infection in the state of rio grande do norte, brazil.introduction natural and artificial ecotope infestation by the kissing bug triatomines and their colonization and infection by trypanosoma cruzi , the chagas disease agent, were evaluated in nine municipalities of the state of rio grande do norte, brazil. methods following identification, triatomine intestinal contents were analyzed by direct microscopic examination, xenoculture, and polymerase chain reaction (pcr) for parasite detection. trypanosoma cruzi isolates were genotyped using three dif ...201627163565
combination chemotherapy with suboptimal doses of benznidazole and pentoxifylline sustains partial reversion of experimental chagas' heart disease.chronic chagasic cardiomyopathy (ccc) progresses with parasite persistence, fibrosis, and electrical alterations associated with an unbalanced immune response such as high plasma levels of tumor necrosis factor (tnf) and nitric oxide (no). presently, the available treatments only mitigate the symptoms of ccc. to improve ccc prognosis, we interfered with the parasite load and unbalanced immune response using the trypanocidal drug benznidazole (bz) and the immunoregulator pentoxifylline (ptx). c57 ...201627161638
electrocardiographic abnormalities and treatment with benznidazole among children with chronic infection by trypanosoma cruzi: a retrospective cohort study.chronic infection by trypanosoma cruzi could cause heart conduction disturbances. we sought to analyze electrocardiographic abnormalities among children with chronic t. cruzi infection with and without trypanocidal treatment with benznidazole.201627158908
transmission capacity of trypanosoma cruzi (trypanosomatida: trypanosomatidae) by three subspecies of meccus phyllosomus (heteroptera: reduviidae) and their hybrids.three behaviors of epidemiological importance: the time lapse for the onset of feeding, actual feeding, and defecation time for meccus phyllosomus pallidipennis (stål), meccus phyllosomus longipennis (usinger), meccus phyllosomus picturatus (usinger), and their laboratory hybrids were evaluated in this study. the mean time lapse for the beginning of feeding was between 0.5 and 8.3 min considering all instars in each cohort, with highly significant differences only among fifth-instar nymphs, fema ...201627146680
assessing the mitochondrial dna diversity of the chagas disease vector triatoma sordida (hemiptera: reduviidae).triatoma sordida is a species that transmits trypanosoma cruzi to humans. in brazil, t. sordida currently deserves special attention because of its wide distribution, tendency to invade domestic environments and vectorial competence. for the planning and execution of control protocols to be effective against triatominae, they must consider its population structure. in this context, this study aimed to characterise the genetic variability of t. sordida populations collected in areas with persiste ...201627143491
detection and quantification of viable and nonviable trypanosoma cruzi parasites by a propidium monoazide real-time polymerase chain reaction assay.molecular techniques based on real-time polymerase chain reaction (qpcr) allow the detection and quantification of dna but are unable to distinguish between signals from dead or live cells. because of the lack of simple techniques to differentiate between viable and nonviable cells, the aim of this study was to optimize and evaluate a straightforward test based on propidium monoazide (pma) dye action combined with a qpcr assay (pma-qpcr) for the selective quantification of viable/nonviable epima ...201627139452
immunoregulatory mechanisms in chagas disease: modulation of apoptosis in t-cell mediated immune responses.chronic chagas disease presents different clinical manifestations ranging from asymptomatic (namely indeterminate) to severe cardiac and/or digestive. previous results have shown that the immune response plays an important role, although no all mechanisms are understood. immunoregulatory mechanisms such as apoptosis are important for the control of chagas disease, possibly affecting the morbidity in chronic clinical forms. apoptosis has been suggested to be an important mechanism of cellular res ...201627138039
life cycle, feeding, and defecation patterns of panstrongylus chinai (hemiptera: reduviidae: triatominae) under laboratory conditions.chagas disease is caused by the protozoan trypanosoma cruzi panstrongylus chinai (del ponte) is highly domiciliated in the peruvian and ecuadorian andes and has been found naturally infected with t. cruzi the objective of this study was to describe the life cycle, feeding, and defecation patterns of p. chinai in the loja province within southern ecuador. to characterize its life cycle, a cohort of 70 individuals was followed from egg to adult. at each stage of development, prefeeding time, feedi ...201627131311
the combined deficiency of immunoproteasome subunits affects both the magnitude and quality of pathogen- and genetic vaccination-induced cd8+ t cell responses to the human protozoan parasite trypanosoma cruzi.the β1i, β2i and β5i immunoproteasome subunits have an important role in defining the repertoire of mhc class i-restricted epitopes. however, the impact of combined deficiency of the three immunoproteasome subunits in the development of protective immunity to intracellular pathogens has not been investigated. here, we demonstrate that immunoproteasomes play a key role in host resistance and genetic vaccination-induced protection against the human pathogen trypanosoma cruzi (the causative agent o ...201627128676
treatment success in trypanosoma cruzi infection is predicted by early changes in serially monitored parasite-specific t and b cell responses.chagas disease is the highest impact parasitic disease in latin america. we have proposed that changes in trypanosoma cruzi-specific immune responses might serve as surrogate indicators of treatment success. herein, we addressed in a long-term follow-up study whether cure achieved after treatment can be predicted by changes in non-conventional indexes of anti-parasite serological and t cell activities.201627128444
endophytic actinobacteria from the brazilian medicinal plant lychnophora ericoides mart. and the biological potential of their secondary metabolites.endophytic actinobacteria from the brazilian medicinal plant lychnophora ericoides were isolated for the first time, and the biological potential of their secondary metabolites was evaluated. a phylogenic analysis of isolated actinobacteria was accomplished with 16s rrna gene sequencing, and the predominance of the genus streptomyces was observed. all strains were cultured on solid rice medium, and ethanol extracts were evaluated with antimicrobial and cytotoxic assays against cancer cell lines. ...201627128202
nucleologenesis in trypanosoma cruzi.nucleolar assembly is a cellular event that requires the synthesis and processing of ribosomal rna, in addition to the participation of pre-nucleolar bodies (pnbs) at the end of mitosis. in mammals and plants, nucleolar biogenesis has been described in detail, but in unicellular eukaryotes it is a poorly understood process. in this study, we used light and electron microscopy cytochemical techniques to investigate the distribution of nucleolar components in the pathway of nucleolus rebuilding du ...201627126372
analysis of association of foxo3 gene with trypanosoma cruzi infection and chronic chagasic cardiomyopathy.foxo3, a member of the forkhead family of proteins, plays a role in controlling immune response. foxo3 gene variant rs12212067 has been associated to differential severity of infectious diseases like malaria. in this study, we assessed whether this foxo3 gene polymorphism is related to susceptibility to infection by trypanosoma cruzi and/or chronic chagasic cardiomyopathy. a total of 1171 individuals from a colombian region endemic for chagas disease, classified as seronegative (n = 595), seropo ...201627125259
chemical shift assignments and secondary structure prediction for q4dy78, a conserved kinetoplastid-specific protein from trypanosoma cruzi.trypanosoma cruzi, trypanosma brucei and leishmania spp. are kinetoplastid protozoa causative agents of chagas disease, sleeping sickness and leishmaniasis, respectively, neglected tropical diseases estimated to infect millions of people worldwide. their genome sequencing has revealed approximately 50 % of genes encoding hypothetical proteins of unknown function, opening possibilities for novel target identification and drug discovery. q4dy78 is a putative essential protein from t. cruzi conserv ...201627356988
challenges in chagas disease drug discovery: a review.chagas disease or american trypanosomiasis is a neglected tropical disease caused by the parasite trypanosoma cruzi. although the number of infected individuals has decreased, about 6-7 million people are infected worldwide. the chemotherapy drugs currently used are limited to benznidazole and nifurtimox. they are effective in acute phase, congenital transmission and children with chronic infection; however, recent clinical trials have shown limitations in adults with chronic infection, presenti ...201627356544
long-term immunity to trypanosoma cruzi in the absence of immunodominant trans-sialidase-specific cd8+ t cells.trypanosoma cruzi infection drives the expansion of remarkably focused cd8(+) t cell responses targeting epitopes encoded by variant trans-sialidase (ts) genes. infection of c57bl/6 mice with t. cruzi results in up to 40% of all cd8(+) t cells committed to recognition of the dominant tskb20 and subdominant tskb18 ts epitopes. however, despite this enormous response, these mice fail to clear t. cruzi infection and subsequently develop chronic disease. one possible reason for the failure to cure t ...201627354447
chronic chagas cardiopathy in chile. importance of trypanosoma cruzi burden and clinical evaluation.currently there are no biological markers to indicate which individuals with chronic indeterminate period of chagas disease develop heart disease and who will remain all his life in this phase. the aim of this survey was to determine if trypanosoma cruzi burden is related to the presence of heart disease in patients with chronic chagas disease. 200 patients who had not been treated, 100 with cardiopathy and 100 without, groups a and b respectively, were submitted to clinical study and electrocar ...201627353063
could cross-immunological reactivity to trypanosoma cruzi antigens be considered a rational strategy for designing vaccines against cancer? 201627352084
author's reply to: could cross-immunological reactivity to trypanosoma cruzi antigens be considered a rational strategy for designing vaccines against cancer? 201627352000
online fast biospeckle monitoring of drug action in trypanosoma cruzi parasites by motion history image.this paper reports on the application of the motion history image (mhi) method on dynamic laser speckle processing as a result of a specific drug action on trypanosoma cruzi parasites. the mhi procedure is based on human action recognition, and unlike other methods which use a sequence consisting of several frames for recognition, this method uses only an mhi per action sequence for recognition. mhi method avoids the complexity as well as the large computation in sequence matching-based methods ...201627349247
feeding profile of mepraia spinolai, a sylvatic vector of chagas disease in chile.american trypanosomiasis is a chronic disease transmitted mainly by vectors. the hematophagous triatomine vectors transmit trypanosoma cruzi to a wide variety of mammals, which usually are their food source. this study determined the feeding profile of mepraia spinolai, a sylvatic triatomine vector, present in endemic areas of chile. vectors were captured in the north-central area of chile. samples of intestinal contents were analyzed by an enzyme-linked immunosorbent assay (elisa) that identifi ...201627349188
afap-1l1-mediated actin filaments crosslinks hinder trypanosoma cruzi cell invasion and intracellular multiplication.host actin cytoskeleton polymerization has been shown to play an important role during trypanosoma cruzi internalization into mammalian cell. the structure and dynamics of the actin cytoskeleton in cells are regulated by a vast number of actin-binding proteins. here we aimed to verify the impact of afap-1l1, during invasion and multiplication of t. cruzi. knocking-down afap-1l1 increased parasite cell invasion and intracellular multiplication. thus, we have shown that the integrity of the machin ...201627349187
novel drug design for chagas disease via targeting trypanosoma cruzi tubulin: homology modeling and binding pocket prediction on trypanosoma cruzi tubulin polymerization inhibition by naphthoquinone derivatives.chagas disease, also called american trypanosomiasis, is a parasitic disease caused by trypanosoma cruzi (t. cruzi). recent findings have underscored the abundance of the causative organism, (t. cruzi), especially in the southern tier states of the us and the risk burden for the rural farming communities there. due to a lack of safe and effective drugs, there is an urgent need for novel therapeutic options for treating chagas disease. we report here our first scientific effort to pursue a novel ...201627345756
parasite cathepsin d-like peptidases and their relevance as therapeutic targets.inhibition of aspartic cathepsin d-like peptidases (apds) has been often discussed as an antiparasite intervention strategy. apds have been considered as virulence factors of trypanosoma cruzi and leishmania spp., and have been demonstrated to have important roles in protein trafficking mechanisms of apicomplexan parasites. apds also initiate blood digestion as components of multienzyme proteolytic complexes in malaria, platyhelminths, nematodes, and ticks. increasing dna and rna sequencing data ...201627344362
cd73 inhibition shifts cardiac macrophage polarization toward a microbicidal phenotype and ameliorates the outcome of experimental chagas cardiomyopathy.increasing evidence demonstrates that generation of extracellular adenosine from atp, which is hydrolyzed by the cd39/cd73 enzyme pair, attenuates the inflammatory response and deactivates macrophage antimicrobial mechanisms. although cd73 is emerging as a critical pathway and therapeutic target in cardiovascular disorders, the involvement of this ectonucleotidase during myocardial infection has not been explored. using a murine model of infection with trypanosoma cruzi, the causal agent of chag ...201627335499
a human trypanosome suppresses cd8+ t cell priming by dendritic cells through the induction of immune regulatory cd4+ foxp3+ t cells.although cd4+ foxp3+ t cells are largely described in the regulation of cd4+ t cell responses, their role in the suppression of cd8+ t cell priming is much less clear. because the induction of cd8+ t cells during experimental infection with trypanosoma cruzi is remarkably delayed and suboptimal, we raised the hypothesis that this protozoan parasite actively induces the regulation of cd8+ t cell priming. using an in vivo assay that eliminated multiple variables associated with antigen processing ...201627332899
high trypanosoma cruzi infection prevalence associated with minimal cardiac pathology among wild carnivores in central texas.infection with the zoonotic vector-borne protozoal parasite trypanosoma cruzi causes chagas disease in humans and dogs throughout the americas. despite the recognized importance of various wildlife species for perpetuating trypanosoma cruzi in nature, relatively little is known about the development of cardiac disease in infected wildlife. using a cross-sectional study design, we collected cardiac tissue and blood from hunter-donated wildlife carcasses- including raccoon (procyon lotor), coyote ...201627330982
caspase-8 activity is part of the bewo trophoblast cell defense mechanisms against trypanosoma cruzi infection.congenital chagas disease is caused by the protozoan parasite trypanosoma cruzi that must cross the placental barrier during transmission. the trophoblast constitutes the first tissue in contact with the maternal-blood circulating parasite. importantly, the congenital transmission rates are low, suggesting the presence of local placental defense mechanisms. cellular proliferation and differentiation as well as apoptotic cell death are induced by the parasite and constitute part of the epithelial ...201627328973
efficacy of lychnopholide polymeric nanocapsules after oral and intravenous administration in murine experimental chagas disease.the etiological treatment of chagas disease remains neglected. the compounds available show several limitations, mainly during the chronic phase. lychnopholide encapsulated in polymeric nanocapsules (lyc-nc) was efficacious in mice infected with trypanosoma cruzi and treated by intravenous administration during the acute phase (ap). as the oral route is preferred for treatment of chronic infections, such as chagas disease, this study evaluated the use of oral lyc-nc in the ap and also compared i ...201627324760
where do trypanosoma cruzi go? the distribution of parasites in blood components from fractionated infected whole blood.platelets (plts) are the blood component most frequently involved in trypanosoma cruzi transfusion transmission cases reported in the literature, although whole blood (wb) and red blood cells (rbcs) have also been incriminated. however, there is little knowledge of the parasite distribution among blood components.201627321651
design, synthesis and antitrypanosomal activity of some nitrofurazone 1,2,4-triazolic bioisosteric analogues.chagas disease, caused by trypanosoma cruzi, is a parasitosis that predominates in latin america. it is estimated that 25 million people are under the risk of infection and, in 2008, more than 10 thousand deaths were registered. the only two drugs available in the therapeutics, nifurtimox and benznidazole, showed to be more effective in the acute phase of the disease. however, there is no standard treatment protocol effective for the chronic phase. nitrofurazone (nf), an antimicrobial drug, has ...201627318979
differential gel electrophoresis (dige) evaluation of naphthoimidazoles mode of action: a study in trypanosoma cruzi bloodstream trypomastigotes.the obligate intracellular protozoan trypanosoma cruzi is the causative agent of chagas disease, a neglected illness affecting millions of people in latin america that recently entered non-endemic countries through immigration, as a consequence of globalization. the chemotherapy for this disease is based mainly on benznidazole and nifurtimox, which are very efficient nitroderivatives against the acute stage but present limited efficacy during the chronic phase. our group has been studying the tr ...201627551855
[maternal-fetal transmission of trypanosoma cruzi, a health problem slightly studied in mexico: case chiapas].to determine the trypanosoma cruzi infection prevalence in 1125 pregnant women and the transmission frequency to their children from tapachula and palenque, chiapas.201627598936
expanding the knowledge of the chemical structure of glycoconjugates from trypanosoma cruzi tci genotype. contribution to taxonomic studies.one of the main obstacles to the treatment of chagas disease is the genetic and phenotypical variance displayed by t. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. to better understand the role of glycoconjungates in chagas disease, we performed the molecular characterization of the o-linked chains from mucins and glycoinositolphospholipids (gipls) of the silvio x10 clone 1 strain. we demonstrated the presence of a β-galactofuranose (β-g ...201627556227
a local innate immune response against trypanosoma cruzi in the human placenta: the epithelial turnover of the trophoblast.congenital chagas disease, caused by trypanosoma cruzi, is partially responsible for the progressive globalization of chagas disease despite of its low transmission rate. the probability of congenital transmission depends on complex interactions between the parasite, the maternal and fetus/newborn immune responses and placental factors, being the latter the least studied one. during transplacental transmission, the parasite must cross the placental barrier where the trophoblast, a continuous ren ...201627554274
analogues of marine guanidine alkaloids are in vitro effective against trypanosoma cruzi and selectively eliminate leishmania (l.) infantum intracellular amastigotes.synthetic analogues of marine sponge guanidine alkaloids showed in vitro antiparasitic activity against leishmania (l.) infantum and trypanosoma cruzi. guanidines 10 and 11 presented the highest selectivity index when tested against leishmania. the antiparasitic activity of 10 and 11 was investigated in host cells and in parasites. both compounds induced depolarization of mitochondrial membrane potential, upregulation of reactive oxygen species levels, and increased plasma membrane permeability ...201627586460
ecological scenario and trypanosoma cruzi dtu characterization of a fatal acute chagas disease case transmitted orally (espírito santo state, brazil).trypanosoma cruzi infection via oral route results in outbreaks or cases of acute chagas disease (acd) in different brazilian regions and poses a novel epidemiological scenario. in the espírito santo state (southeastern brazil), a fatal case of a patient with acd led us to investigate the enzootic scenario to avoid the development of new cases. at the studied locality, triatoma vitticeps exhibited high t. cruzi infection rates and frequently invaded residences.201627580853
first report of sapajus cay naturally infected by trypanosoma cruzi in san pedro department, paraguay.to verify the occurrence of natural trypanosoma cruzi infection in non-human primates from a rural endemic area of the east region of paraguay, xenodiagnosis was performed in 35 animals belonging to two species. for genotyping and t. cruzi discrete typing unit (dtu) assignment, a combination of four markers was used, including amplification products of the small (18s) and large (24sα) subunits of ribosomal ribonucleic acid gene, the intergenic region of mini-exon gene and the heat shock protein ...201627579529
glycogen synthase kinase-3 is involved in glycogen metabolism control and embryogenesis of rhodnius prolixus.rhodnius prolixus is a blood-feeding insect that transmits trypanosoma cruzi and trypanosoma rangeli to vertebrate hosts. rhodnius prolixus is also a classical model in insect physiology, and the recent availability of r. prolixus genome has opened new avenues on triatomine research. glycogen synthase kinase 3 (gsk-3) is classically described as a key enzyme involved in glycogen metabolism, also acting as a downstream component of the wnt pathway during embryogenesis. gsk-3 has been shown to be ...201627574112
over six thousand trypanosoma cruzi strains classified into discrete typing units (dtus): attempt at an inventory.trypanosoma cruzi, the causative agent of chagas disease, presents wide genetic diversity. currently, six discrete typing units (dtus), named tci to tcvi, and a seventh one called tcbat are used for strain typing. beyond the debate concerning this classification, this systematic review has attempted to provide an inventory by compiling the results of 137 articles that have used it. a total of 6,343 dtu identifications were analyzed according to the geographical and host origins. ninety-one perce ...201627571035
unlocking the in vitro anti-trypanosoma cruzi activity of halophyte plants from the southern portugal.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.201627569881
predominance of th1 response, increase of megakaryocytes and kupffer cells are related to survival in trypanosoma cruzi infected mice treated with lycopodium clavatum.we investigated the number of megakaryocytes, kupffer cells and ratios of th1/th2 and th1/th17 cytokines in survival of mice infected with y strain of trypanosoma cruzi and treated with lycopodium clavatum. in a blind, randomized and controlled assay, swiss male mice, 8weeks-old, infected with 1400 trypomastigotes (y strain) were divided into groups and treated with: gly - lycopodium clavatum dynamization13c and gci - alcohol solution 7° gl (vehicle medicine). the treatment was offered two days ...201627565835
morphological and phylogenetic description of trypanosoma noyesi sp. nov.: an australian wildlife trypanosome within the t. cruzi clade.a number of trypanosome isolates from australian marsupials are within the clade containing the human pathogen trypanosoma cruzi. trypanosomes within this clade are thought to have diverged from a common ancestral bat trypanosome. here, we characterise trypanosoma noyesi sp. nov. isolated from the critically endangered woylie (bettongia pencillata) using phylogenetic inferences from three gene regions (18s rdna, ggapdh, and cytb) coupled with morphological and behavioural observations in vitro. ...201627561173
oesophageal motility disorders in infected immigrants with chagas disease in a non-endemic european area.immigration-related new diseases pose a growing challenge for healthcare services in receptor countries. following latin american migration, chagas disease has inevitably appeared in europe.201627536373
alkaline phosphatase activity in salivary gland cells of rhodnius neglectus and r. prolixus (hemiptera, triatominae).alkaline phosphatase activity was detected in salivary gland cells of the rhodnius neglectus lent, 1954, and r. prolixus stal, 1859, vectors of trypanosoma cruzi chagas, 1909 (etiological agent of chagas disease) and t. rangeli tejera, 1920 (pathogenic to insect). the gomori technique was used to demonstrate alkaline phosphatase activity. alkaline phosphatase activity was observed throughout the entire gland, with an increased activity in the posterior region of the principal gland. in particula ...201627525888
chagas disease: a solvable problem, ignored.chagas disease is the highest impact parasitic disease in the americas, yet remains virtually unknown and untreated, despite the fact that the infection is curable and the global problem of chagas disease is manageable. the causes of this situation and how it can be changed are the focus of this communication.201627523778
performance assessment of four chimeric trypanosoma cruzi antigens based on antigen-antibody detection for diagnosis of chronic chagas disease.the performance of serologic tests in chronic chagas disease diagnosis largely depends on the type and quality of the antigen preparations that are used for detection of anti-trypanosoma cruzi antibodies. whole-cell t. cruzi extracts or recombinant proteins have shown variation in the performance and cross-reactivity. synthetic chimeric proteins comprising fragments of repetitive amino acids of several different proteins have been shown to improve assay performances to detect chagasic infections ...201627517281
congenital chagas' disease transmission in the united states: diagnosis in adulthood.two brothers with congenitally-acquired chagas' disease (cd) diagnosed during adulthood are reported. the patients were born in the usa to a mother from bolivia who on subsequent assessment was found to be serologically positive for trypanosoma cruzi. serologic screening of all pregnant women who migrated from countries with endemic cd is strongly recommended.201627516969
habitat management to reduce human exposure to trypanosoma cruzi and western conenose bugs (triatoma protracta).chagas disease, which manifests as cardiomyopathy and severe gastrointestinal dysfunction, is caused by trypanosoma cruzi, a vector-borne parasite. in california, the vector triatoma protracta frequently colonizes woodrat (neotoma spp.) lodges, but may also invade nearby residences, feeding upon humans and creating the dual risk of bite-induced anaphylaxis and t. cruzi transmission. our research aimed to assess t. cruzi presence in woodrats in a previously unstudied northern california area, sta ...201627515118
high-resolution molecular typing of trypanosoma cruzi in 2 large outbreaks of acute chagas disease in colombia.oral transmission of trypanosoma cruzi has gained relevance because of its association with high morbidity and lethality rates. this transmission route is responsible for maintaining the infection of the parasite in sylvatic cycles, and human cases have been associated mainly with the consumption of food contaminated with triatomine feces or didelphid secretions. several ecological changes allow the intrusion of sylvatic reservoirs and triatomines to the domestic environments with subsequent foo ...201627511897
community resilience and chagas disease in a rural region of mexico.to explore the pillars of community resilience in a region where chagas disease is endemic, with the aim of promoting participatory processes to deal with this condition from the resilience of the population.201627509012
comparative transcriptome profiling of human foreskin fibroblasts infected with the sylvio and y strains of trypanosoma cruzi.trypanosoma cruzi, the causative agent of chagas disease, is phylogeneticaly distributed into nearly identical genetic strains which show divergent clinical presentations including differences in rates of cardiomyopathy in humans, different vector species and transmission cycles, differential congenital transmission in a mouse model, and differing immune and heart inflammation response in dogs. the population structure of these strains divides into two groups, which are geographically and clinic ...201627505626
synthesis and trypanocidal activity of novel benzimidazole derivatives.the present work reports the synthesis and biological activity of a series of 14 benzimidazole derivatives designed to act on the enzyme triosephosphate isomerase of trypanosoma cruzi (tctim). this enzyme is involved in the metabolism of glucose, the only source of energy for the parasite. in this study, we found four compounds that inhibit tctim moderately and lack inhibitory activity against human tim (hstim). in vitro studies against t. cruzi epimastigotes showed two compounds that were more ...201627503677
conservation and divergence within the clathrin interactome of trypanosoma cruzi.trypanosomatids are parasitic protozoa with a significant burden on human health. african and american trypanosomes are causative agents of nagana and chagas disease respectively, and speciated about 300 million years ago. these parasites have highly distinct life cycles, pathologies, transmission strategies and surface proteomes, being dominated by the variant surface glycoprotein (african) or mucins (american) respectively. in african trypanosomes clathrin-mediated trafficking is responsible f ...201627502971
evaluation of vdr gene polymorphisms in trypanosoma cruzi infection and chronic chagasic cardiomyopathy.vitamin d is an important modulator of the immune response. it acts over several immune cell types where the vitamin d receptor (vdr) is expressed. due to the high relevance of this signaling pathway, several studies have investigated the possible influence of genes involved in the metabolism of vitamin d and its receptor in different human diseases. here, we analyzed whether four single-nucleotide polymorphisms of the vdr gene (rs731236, rs7975232, rs1544410 and rs2228570) are involved in the s ...201627502545
the n-myristoylome of trypanosoma cruzi.protein n-myristoylation is catalysed by n-myristoyltransferase (nmt), an essential and druggable target in trypanosoma cruzi, the causative agent of chagas' disease. here we have employed whole cell labelling with azidomyristic acid and click chemistry to identify n-myristoylated proteins in different life cycle stages of the parasite. only minor differences in fluorescent-labelling were observed between the dividing forms (the insect epimastigote and mammalian amastigote stages) and the non-di ...201627492267
functional evaluation of heat shock proteins 70 (hsp70/hsc70) on rhodnius prolixus (hemiptera, reduviidae) physiological responses associated with feeding and starvation.blood-sucking vectors must overcome thermal stress caused by intake of proportionally large amounts of warm blood from their hosts. in response to this, heat shock proteins (hsps) such as the widely studied hsp70 family (the inducible hsp70 and the cognate form hsc70, known for their role in preserving essential cellular functions) are rapidly up-regulated in their tissues. the triatomine rhodnius prolixus is an important vector of trypanosoma cruzi, the causative pathogen of chagas' disease, an ...201627491440
lipid body organelles within the parasite trypanosoma cruzi: a role for intracellular arachidonic acid metabolism.most eukaryotic cells contain varying amounts of cytosolic lipidic inclusions termed lipid bodies (lbs) or lipid droplets (lds). in mammalian cells, such as macrophages, these lipid-rich organelles are formed in response to host-pathogen interaction during infectious diseases and are sites for biosynthesis of arachidonic acid (aa)-derived inflammatory mediators (eicosanoids). less clear are the functions of lbs in pathogenic lower eukaryotes. in this study, we demonstrated that lbs, visualized b ...201627490663
success of benznidazole chemotherapy in chronic trypanosoma cruzi-infected patients with a sustained negative pcr result.cure assessment in chronic trypanosoma cruzi infection is controversial, mainly because of the lack of reliable tests to ensure parasite elimination. here, we assess the impact of benznidazole therapy on the conventional serology and parasitaemia in chronic chagas disease. a total of 455 patients with long-term trypanosoma cruzi infection underwent specific chemotherapy with benznidazole. their parasitological status was assessed by polymerase chain reaction (pcr) detection of t. cruzi dna. drop ...201627488437
the sympathetic nervous system affects the susceptibility and course of trypanosoma cruzi infection.trypanosoma cruzi (t. cruzi) is an intracellular parasite that causes chagas' disease, a major health problem in latin america. using a murine model of infection with this parasite, we have previously shown that corticosterone blood levels are markedly elevated during the course of the disease in c57bl/6 male mice and that this increase is protective for the host by restricting the production of pro-inflammatory cytokines. since the hypothalamus-pituitary-adrenal (hpa) axis usually operates in a ...201627485039
1,3,4-thiadiazole derivatives of r-(+)-limonene benzaldehyde-thiosemicarbazones cause death in trypanosoma cruzi through oxidative stress.this work evaluated the in vitro and in vivo activity of tdz 2 on trypanosoma cruzi amastigotes and determined the possible mechanism of action of this compound on t. cruzi death. tdz 2 inhibited t. cruzi proliferation in vitro and had low haemolytic potential. it also induced morphological and ultrastructural alterations. we observed a reduction of cell volume, the depolarization of the mitochondrial membrane, an increase in ros production, lipoperoxidation of the cell membrane, lipid bodies fo ...201627484335
surface molecules released by trypanosoma cruzi metacyclic forms downregulate host cell invasion.the question whether metacylic trypomastigote (mt) forms of different t. cruzi strains differentially release surface molecules, and how they affect host cell invasion, remains to be fully clarified. we addressed that question using t. cruzi strains that differ widely in the ability to invade cells.201627483135
the aryl hydrocarbon receptor modulates production of cytokines and reactive oxygen species and development of myocarditis during trypanosoma cruzi infection.the aryl hydrocarbon receptor (ahr) is a ligand-activated transcription factor involved in controlling several aspects of immune responses, including the activation and differentiation of specific t cell subsets and antigen-presenting cells, thought to be relevant in the context of experimental trypanosoma cruzi infection. the relevance of ahr for the outcome of t. cruzi infection is not known and was investigated here. we infected wild-type (wt) mice and ahr knockout (ahr ko) mice with t. cruzi ...201627481250
loss of the cytostome-cytopharynx and endocytic ability are late events in trypanosoma cruzi metacyclogenesis.trypanosoma cruzi epimastigotes uptake nutrients by endocytosis via the cytostome-cytopharynx complex - an anterior opening (cytostome) continuous with a funnel-shaped invagination (cytopharynx) that extends to the posterior of the cell, accompanied by microtubules. during metacyclogenesis - the transformation of epimastigotes into human-infective metacyclic trypomastigotes - the cytostome-cytopharynx complex disappears, as trypomastigotes lose endocytic ability. to date, no studies have examine ...201627480509
design, synthesis, molecular docking and biological evaluation of thiophen-2-iminothiazolidine derivatives for use against trypanosoma cruzi.in this study, we designed and synthesized a series of thiophen-2-iminothiazolidine derivatives from thiophen-2-thioureic with good anti-trypanosoma cruzi activity. several of the final compounds displayed remarkable trypanocidal activity. the ability of the new compounds to inhibit the activity of the enzyme cruzain, the major cysteine protease of t. cruzi, was also explored. the compounds 3b, 4b, 8b and 8c were the most active derivatives against amastigote form, with significant ic50 values b ...201627475533
dendritic cells: a double-edged sword in immune responses during chagas disease.dendritic cells (dcs) are the most important member of the antigen presenting cells group due to their ability to recognize antigen at the infection site and their high specialized antigen internalization capacity. these cells have central role in connecting the innate and adaptive immune responses against trypanosoma cruzi, the causative agent of chagas disease. these first line defense cells modulate host immune response depending on type, maturation level, cytokine milieu and dc receptor invo ...201627471496
diagnosis and treatment of congenital chagas disease in a premature infant. 201627466398
differentiation of trypanosoma cruzi i (tci) and t. cruzi ii (tcii) genotypes using genes encoding serine carboxypeptidases.the parasite trypanosoma cruzi (kinetoplastida, trypanosomatidae) can be classified based on biochemical and molecular markers, into six lineages or discrete typing units (dtus), t. cruzi i-vi (tci-vi), from which tci and tcii are the parental genotypes. trying to understand the dispersion of the subpopulations of t. cruzi in nature and its complex transmission cycles, the serine carboxypeptidase genes of t. cruzi were used as a molecular marker in the present study. dtus of 25 t. cruzi isolates ...201627465563
the characterization of anti-t. cruzi activity relationships between ferrocenyl, cyrhetrenyl complexes and ros release.trypanosoma cruzi (t. cruzi) is the parasite that causes chagas disease. nifurtimox is the most used drug against the t. cruzi, this drug increases intermediaries nitro group, being mainly responsible for the high toxicity component, for this reason it is important to study new organic compounds and thus improve therapeutic strategies against chagas disease. the electronic effects of ferrocenyl and cyrhetrenyl fragments were investigated by dft calculation. a close correlation was found between ...201627460450
importation of hybrid human-associated trypanosoma cruzi strains of southern south american origin, colombia.we report the characterization of trypanosoma cruzi of southern south american origin among humans, domestic vectors, and peridomestic hosts in colombia using high-resolution nuclear and mitochondrial genotyping. expanding our understanding of the geographic range of lineage tcvi, which is associated with severe chagas disease, will help clarify risk of human infection for improved disease control.201627434772
safety profile of nifurtimox for treatment of chagas disease in the united states.nifurtimox is 1 of only 2 medications available for treating chagas disease (cd) and currently the only drug available in the united states, but its safety and tolerance have not been extensively studied. this is the first study to evaluate tolerance of nifurtimox in us patients with cd.201627432838
an aromatic diamidine that targets kinetoplast dna, impairs the cell cycle in trypanosoma cruzi, and diminishes trypomastigote release from infected mammalian host cells.trypanosoma cruzi is the etiological agent of chagas disease, affecting approximately 10 million people in the americas and with some 40 million people at risk. the objective of this study was to evaluate the anti-t. cruzi activity of three new diamidines that have a 3,4-ethylenedioxy extension of the thiophene core, designated mb17, mb19, and mb38. all three diamidines exhibited dose-dependent inhibition of epimastigote replication. the mechanisms of action of these diamidines were investigated ...201627431229
pathology of chronic chagas cardiomyopathy in the united states:  a detailed review of 13 cardiectomy cases.the pathologic features of chronic chagas cardiomyopathy may not be widely appreciated in the united states. we sought to describe the gross, microscopic, immunohistochemical, and molecular pathology features useful to diagnose chronic chagas cardiomyopathy.201627425387
new record and cytogenetic analysis of psammolestes tertius lent & jurberg, 1965 (hemiptera, reduviidae, triatominae) from bahia state, brazil.this paper reports on the first occurrence of psammolestes tertius in the chapada diamantina region, located in the city of seabra, bahia state, in northeastern brazil. following an active search, 24 p. tertius specimens were collected from phacellodomus rufifrons (rufous-fronted thornbird) nests. the insects did not present any symptoms of infection by trypanosoma cruzi. p. tertius males were cytogenetically analyzed, and the results were compared with those of other specimens from the brazilia ...201627420943
circulation of tc ia discrete type unit trypanosoma cruzi in yucatan mexico.the etiologic agent trypanosoma cruzi (tc) has been grouped into six discrete type units (dtu i-vi); within dtu-i exists four subgroups defined ia-id. in colombia, the genotype ia is associated with human infection and domiciliated rhodnius vector. in the yucatan peninsula of mexico, the main vector involved in t. cruzi transmission is triatoma dimidiata predominantly via sylvatic and peridomiciliated cycles. in this study, multiple sequence analysis of mini-exon intergenic regions of t. cruzi i ...201627413339
correlation between infection rate of triatominies and chagas disease in southwest of bahia, brazil: a warning sign?chagas disease, caused by the trypanosoma cruzi, has a wide distribution in south america, and its main method of control is the elimination of triatomines. it is presented here the geographic distribution and the rate of natural infection by t. cruzi of triatomines collected and evaluated from 2008 to 2013 in southwest of bahia. triatomines were captured in the intradomiciliary and peridomiciliary areas of five cities located in the southwest of bahia state, identified, and analyzed for the pre ...201627411071
selective testing of at-risk blood donors for trypanosoma cruzi and plasmodium spp. in switzerland.population migrations and overseas recreational travel to regions at risk for tropical diseases are increasing. a major challenge in non-endemic countries is to decrease the number of blood donor deferrals due those tropical disease pathogens, without compromising the high level of blood safety. the protozoans trypanosoma cruzi and plasmodium spp., the causative organisms of chagas disease (cd) and malaria are becoming a major focus in the blood transfusion community.201627403088
what do we know about chagas disease in the united states?chagas disease, caused by the parasite trypanosoma cruzi, affects more than 5 million people worldwide leading to serious heart and gastrointestinal disease in a proportion of chronically infected patients. important modes of transmission include vector-borne, congenital, and via blood transfusion or organ transplant from an infected donor. vector-borne transmission of chagas disease occurs in the americas, including the southern half of north america, where the specific vector insects (triatomi ...201627402515
the phosphatidylinositol 3-kinase class iii complex containing tcvps15 and tcvps34 participates in autophagy in trypanosoma cruzi.autophagy is a degradative process by which eukaryotic cells digest their own components to provide aminoacids that may function as energy source under nutritional stress conditions. there is experimental evidence for autophagy in parasitic protists belonging to the family trypanosomatidae. however, few proteins implicated in this process have been characterized so far in these parasites. moreover, it has been shown that autophagy is involved in trypanosoma cruzi differentiation and thus might h ...201627603757
synthesis of xylitan derivatives and preliminary evaluation of in vitro trypanocidal activity.a series of novel xylitan derivatives derived from xylitol were synthesized using operationally simple procedures. a xylitan acetonide was the key intermediate used to prepare benzoate, arylsulfonate esters and 1,2,3-triazole derivatives of xylitan. these compounds were evaluated for their in vitro anti-trypanosoma cruzi activity against trypomastigote and amastigote forms of the parasite in t. cruzi-infected cell lineages. benznidazole was used as positive control against t. cruzi and cytotoxic ...201627735872
does native trypanosoma cruzi calreticulin mediate growth inhibition of a mammary tumor during infection?for several decades now an antagonism between trypanosoma cruzi infection and tumor development has been detected. the molecular basis of this phenomenon remained basically unknown until our proposal that t. cruzi calreticulin (tccrt), an endoplasmic reticulum-resident chaperone, translocated-externalized by the parasite, may mediate at least an important part of this effect. thus, recombinant tccrt (rtccrt) has important in vivo antiangiogenic and antitumor activities. however, the relevant que ...201627619675
recombination-driven generation of the largest pathogen repository of antigen variants in the protozoan trypanosoma cruzi.the protozoan parasite trypanosoma cruzi, causative agent of chagas disease, depends upon a cell surface-expressed trans-sialidase (ts) to avoid activation of complement-mediated lysis and to enhance intracellular invasion. however these functions alone fail to account for the size of this gene family in t. cruzi, especially considering that most of these genes encode proteins lacking ts enzyme activity. previous whole genome sequencing of the cl brener clone of t. cruzi identified ~1400 ts vari ...201627619017
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