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a therapeutic nanoparticle vaccine against trypanosoma cruzi in a balb/c mouse model of chagas disease.chagas disease, caused by trypanosoma cruzi, results in an acute febrile illness that progresses to chronic chagasic cardiomyopathy in 30% of patients. current treatments have significant side effects and poor efficacy during the chronic phase; therefore, there is an urgent need for new treatment modalities. a robust th1-mediated immune response correlates with favorable clinical outcomes. a therapeutic vaccine administered to infected individuals could bolster the immune response, thereby slowi ...201626890466
an nmr biochemical assay for fragment-based drug discovery: evaluation of an inhibitor activity on spermidine synthase of trypanosoma cruzi.although nmr in fragment-based drug discovery is utilized almost exclusively to evaluate physical binding between molecules, it should be also a powerful tool for biochemical assay, evaluating inhibitory effect of compounds on enzymatic activity. time-dependent spectral change in real-time monitoring or inhibitor concentration-dependent spectral change after constant-time reaction was processed by factor analysis, by which reaction rate or ic50 value was obtained. applications to spermidine synt ...201626881725
in vitro and in vivo identification of tetradentated polyamine complexes as highly efficient metallodrugs against trypanosoma cruzi.in order to identify new compounds to treat chagas disease during the acute phase with higher activity and lower toxicity than the reference drug benznidazole (bz), a series of tetraamine-based compounds was prepared and their trypanocidal effects against trypanosoma cruzi were evaluated by light microscopy through the determination of ic50 values. cytotoxicity was determined by flow cytometry assays against vero cells. in vivo assays were performed in balb/c mice, in which the parasitemia level ...201626874306
computational drug repositioning by target hopping: a use case in chagas disease.drug repositioning aims to identify novel indications for existing drugs. one approach to repositioning exploits shared binding sites between the drug targets and other proteins. here, we review the principle and algorithms of such target hopping and illustrate them in chagas disease, an in latin america widely spread, but neglected disease.201626873186
amazonian triatomine biodiversity and the transmission of chagas disease in french guiana: in medio stat sanitas.the effects of biodiversity on the transmission of infectious diseases now stand as a cornerstone of many public health policies. the upper amazonia and guyana shield are hot-spots of biodiversity that offer genuine opportunities to explore the relationship between the risk of transmission of chagas disease and the diversity of its triatomine vectors. over 730 triatomines were light-trapped in four geomorphological landscapes shaping french-guiana, and we determined their taxonomic status and in ...201626867025
low-dose benznidazole treatment results in parasite clearance and attenuates heart inflammatory reaction in an experimental model of infection with a highly virulent trypanosoma cruzi strain.chagas disease, caused by trypanosoma cruzi, is the main cause of dilated cardiomyopathy in the americas. antiparasitic treatment mostly relies on benznidazole (bzl) due to nifurtimox shortage or unavailability. both induce adverse drug effects (ade) of varied severity in many patients, leading to treatment discontinuation or abandonment. since dosage may influence ade, we aimed to assess bzl efficacy in terms of parasiticidal and anti-inflammatory activity, using doses lower than those previous ...201626862474
the trypanosomatid pr77-hallmark contains a downstream core promoter element essential for transcription activity of the trypanosoma cruzi l1tc retrotransposon.trypanosomatid genomes are highly colonized by non-ltr retroelements that make up to 5% of the nuclear genome. these elements are mainly accumulated in the strand switch regions (ssrs) where polycistronic transcription is initiated and have a 77 nt-long sequence--pr77--at their 5' ends. l1tc is the best represented retrotransposon in the trypanosoma cruzi genome and is a potentially functional autonomous element that encodes its own retrotransposition machinery. the pr77 of the t. cruzi l1tc ele ...201626861854
mice with genetic deletion of group via phospholipase a2β exhibit impaired macrophage function and increased parasite load in trypanosoma cruzi-induced myocarditis.trypanosoma cruzi infection, which is the etiological agent of chagas disease, is associated with intense inflammation during the acute and chronic phases. the pathological progression of chagas disease is influenced by the infiltration and transmigration of inflammatory cells across the endothelium to infected tissues, which are carefully regulated processes involving several molecular mediators, including adhesion molecules and platelet-activating factor (paf). we have shown that paf productio ...201626857573
trypanosoma cruzi causes paralyzing systemic necrotizing vasculitis driven by pathogen-specific type i immunity in mice.infectious agents are often considered potential triggers of chronic inflammatory disease, including autoimmunity; however, direct evidence is usually lacking. here we show that following control of acute infection of mice with the myotropic colombiana strain of trypanosoma cruzi, parasites persisted in tissue at low levels associated with development of systemic necrotizing vasculitis. lesions occurred in many but not all organs and tissues, with skeletal muscle arteries being the most severely ...201626857570
rapidly progressing chagas cardiomyopathy.chagas disease, caused by the parasite trypanosoma cruzi, can cause a potentially life-threatening cardiomyopathy in approximately 10-40% of afflicted individuals. the decline in cardiac function characteristically progresses over the course of many years. we report a case of chagas disease in which the patient experienced an atypical rapid deterioration to severe cardiomyopathy over the course of 16 months. this case argues the need for increased routine surveillance for patients with confirmed ...201626856912
environmental determinants of the distribution of chagas disease vector triatoma dimidiata in colombia.triatoma dimidiata (hemiptera: reduviidae) is a secondary vector of trypanosoma cruzi in colombia and represents an important epidemiological risk mainly in the central and oriental regions of the country where it occupies sylvatic, peridomestic, and intradomestic ecotopes, and because of this complex distribution, its distribution and abundance could be conditioned by environmental factors. in this work, we explored the relationship between t. dimidiata distribution and environmental factors in ...201626856910
putative role of the aldo-keto reductase from trypanosoma cruzi in benznidazole metabolism.benznidazole (bz), the drug used for treatment of chagas' disease (caused by the protozoan trypanosoma cruzi), is activated by a parasitic nadh-dependent type i nitroreductase (ntr i). however, several studies have shown that other enzymes are involved. the aim of this study was to evaluate whether the aldo-keto reductase from t. cruzi (tcakr), a nadph-dependent oxido-reductase previously described by our group, uses bz as the substrate. we demonstrated that both recombinant and native tcakr enz ...201626856844
in vitro and in vivo trypanosomicidal action of novel arylimidamides against trypanosoma cruzi.arylimidamides (aias) have been shown to have considerable biological activity against intracellular pathogens, includingtrypanosoma cruzi, which causes chagas disease. in the present study, the activities of 12 novel bis-aias and 2 mono-aias against different strains oft. cruziin vitroandin vivowere analyzed. the most active wasm-terphenyl bis-aia (35dap073), which had a 50% effective concentration (ec50) of 0.5 μm for trypomastigotes (y strain), which made it 26-fold more effective than benzni ...201626856830
effect of secondary anchor amino acid substitutions on the immunogenic properties of an hla-a*0201-restricted t cell epitope derived from the trypanosoma cruzi kmp-11 protein.the tctle peptide (tleefsakl) is a cd8(+) t cell hla-a*0201-restricted epitope derived from the trypanosoma cruzi kmp-11 protein that is efficiently processed, presented and recognized by cd8(+) t cells from chagasic patients. since the immunogenic properties of wild-type epitopes may be enhanced by suitable substitutions in secondary anchor residues, we have studied the effect of introducing specific mutations at position 3, 6 and 7 of the tctle peptide. mutations (e3l, s6v and a7f) were chosen ...201626854383
phthalimido-thiazoles as building blocks and their effects on the growth and morphology of trypanosoma cruzi.chagas disease is a parasitic infection caused by protozoan trypanosoma cruzi that affects approximately 6-7 million people worldwide. benznidazole is the only drug approved for treatment during the acute and asymptomatic chronic phases; however, its efficacy during the symptomatic chronic phase is controversial. the present work reports the synthesis and anti-t. cruzi activities of a novel series of phthalimido-thiazoles. some of these compounds showed potent inhibition of the trypomastigote fo ...201626854377
proteins involved on tgf-β pathway are up-regulated during the acute phase of experimental chagas disease.studies developed by our group in the last years have shown the involvement of tgf-β in acute and chronic chagas heart disease, with elevated plasma levels and activated tgf-β cell signaling pathway as remarkable features of patients in the advanced stages of this disease, when high levels of cardiac fibrosis is present. imbalance in synthesis and degradation of extracellular matrix components is the basis of pathological fibrosis and tgf-β is considered as one of the key regulators of this proc ...201626852285
prevalence of trypanosoma cruzi's discrete typing units in a cohort of latin american migrants in spain.chagas disease is caused by the protozoan trypanosoma cruzi. this is an endemic disease in the americas, but increased migration to europe has made it emerge in countries where it was previously unknown, being spain the second non endemic country in number of patients. t. cruzi is a parasite with a wide genetic diversity, which has been grouped by consensus into 6 discrete typing units (dtus) affecting humans. some authors have linked these dtus either to a specific epidemiological context or to ...201626851167
host-feeding sources and infection with trypanosoma cruzi of triatoma infestans and triatoma eratyrusiformis (hemiptera: reduviidae) from the calchaqui valleys in northwestern argentina.we assessed the prevalence of infection with trypanosoma cruzi, parasite genotypes (discrete typing units, dtus), and the host-feeding sources of domestic and peridomestic triatoma infestans klug and triatoma eratyrusiformis del ponte in eight rural communities of the subandean calchaqui valleys in northwestern argentina. we sought to analyze their epidemiological role in the context of routine vector surveillance and control actions. infection with t. cruzi was determined by optic microscopy or ...201626849898
trypanosoma cruzi -infected triatoma gerstaeckeri (hemiptera: reduviidae) from nuevo león, méxico, and pathogenicity of the regional strain.four species of triatomines have been reported in nuevo león, northeast (ne) méxico, but triatoma gerstaeckeri has only been recorded from a peridomestic dwelling.201626849699
reconsideration of the seven discrete typing units within the species trypanosoma cruzi, a new proposal of three reliable mitochondrial clades.it is generally acknowledged that trypanosoma cruzi, responsible for chagas disease, is structured into six or seven distinct discrete typing units (dtus), and termed tci through tcvi and tcbat for the seventh, by a collective of researchers. however, such structuring can be validated only when the species is analyzed over its entire distribution area with the same genetic markers. many works have dealt with several dtus in limited areas, generally one country, others have dealt with only one dt ...201626845347
biological approaches to characterize the mode of action of two 5-nitroindazolinone prototypes on trypanosoma cruzi bloodstream trypomastigotes.the phenotypic activity of two 5-nitroindazolinones, i.e. 2-benzyl-1-propyl (22) and 2-benzyl-1-butyl (24) derivatives, previously proposed as anti-trypanosoma cruzi prototypes, was presently assayed on bloodstream trypomastigotes (bt) of the moderately drug-resistant y strain. further exploration of putative targets and cellular mechanisms involved in their activity was also carried out. therefore, transmission electron microscopy, high-resolution respirometry and flow cytometry procedures were ...201627312370
chagas cardiomyopathy: usefulness of ekg and echocardiogram in a non-endemic country.chagas disease (cd) is a major cause of cardiomyopathy in latin america, and migration movements have now spread the disease worldwide. however, data regarding chagas cardiomyopathy (cc) and the usefulness of echocardiography in non endemic countries are still scarce.201627308824
multivalent sialylation of β-thio-glycoclusters by trypanosoma cruzi trans sialidase and analysis by high performance anion exchange chromatography.the synthesis of multivalent sialylated glycoclusters is herein addressed by a chemoenzymatic approach using the trans-sialidase of trypanosoma cruzi (tcts). multivalent β-thio-galactopyranosides and β-thio-lactosides were used as acceptor substrates and 3'-sialyllactose as the sialic acid donor. high performance anion exchange chromatography with pulsed amperometric detection (hpaec-pad) was shown to be an excellent technique for the analysis of the reaction products. different eluting conditio ...201627306205
synthesis, biological evaluation and molecular docking of new benzenesulfonylhydrazone as potential anti-trypanosoma cruzi agents.chagas disease is a public health problem caused by trypanosoma cruzi. cruzain is a pharmacological target for designing a new drug against this parasite. hydrazone and n-acylhydrazone derivatives have been traditionally associated as potential cruzain inhibitors. additionally, benzenesulfonyl derivatives show trypanocidal activity. therefore, in this study, the combination of both structures has been taken into account for drug design.201627396731
corrigendum to "fluctuations in trypanosoma cruzi discrete typing unit composition in two naturally infected triatomines: mepraia gajardoi and m. spinolai after laboratory feeding" [acta trop. (2016) 9-14]. 201627393242
bioenergetic profiling of trypanosoma cruzi life stages using seahorse extracellular flux technology.energy metabolism is an attractive target for the development of new therapeutics against protozoan pathogens, including trypanosoma cruzi, the causative agent of human chagas disease. despite emerging evidence that mitochondrial electron transport is essential for the growth of intracellular t. cruzi amastigotes in mammalian cells, fundamental knowledge of mitochondrial energy metabolism in this parasite life stage remains incomplete. the clark-type electrode, which measures the rate of oxygen ...201627392747
the structure of a trypanosoma cruzi glucose-6-phosphate dehydrogenase reveals differences from the mammalian enzyme.the enzyme glucose-6-phosphate dehydrogenase from trypanosoma cruzi (tcg6pdh) catalyses the first step of the pentose phosphate pathway (ppp) and is considered a promising target for the discovery of a new drug against chagas diseases. in the present work, we describe the crystal structure of tcg6pdh obtained in a ternary complex with the substrate β-d-glucose-6-phosphate (g6p) and the reduced 'catalytic' cofactor nadph, which reveals the molecular basis of substrate and cofactor recognition. a ...201627391210
temporizin and temporizin-1 peptides as novel candidates for eliminating trypanosoma cruzi.tropical diseases caused by parasitic infections continue to cause socioeconomic distress worldwide. among these, chagas disease has become a great concern because of globalization. caused by trypanosoma cruzi, there is an increasing need to discover new, more effective methods to manage infections that minimize disease onset. antimicrobial peptides represent a possible solution to this challenge. as effector molecules of the innate immune response against pathogens, they are the first line of d ...201627384541
calculation of the elisa's cut-off based on the change-point analysis method for detection of trypanosoma cruzi infection in bolivian dogs in the absence of controls.in elisas, sera of individuals infected by trypanosoma cruzi show absorbance values above a cut-off value. the cut-off is generally computed by means of formulas that need absorbance readings of negative (and sometimes positive) controls, which are included in the titer plates amongst the unknown samples. when no controls are available, other techniques should be employed such as change-point analysis. the method was applied to bolivian dog sera processed by elisa to diagnose t. cruzi infection. ...201627384081
quantification by real-time pcr of trypanosoma cruzi dna in samples of triatoma infestans used in xenodiagnosis of chronic chagas disease patients.trypanosoma cruzi multiplies and differentiates in the digestive tract of triatomine insects. xenodiagnosis (xd) is a parasitological tool in which the insect vectors acts as a biological culture medium to amplify and detect t. cruzi infection in mammals. the sensitivity of xd has been overcome by the application of pcr in fecal samples (fs) of xd (pcr-xd). in this study, t. cruzi amplified in triatoma infestans fed by xd on individuals with chronic chagas disease (cchd) is quantified by real-ti ...201627377063
[the third and new face of chagas disease].after the publication of the results of the benefit study concluding that the benznidazole (5 mg/kg/d/60 d) is ineffective to stop the progression of the established chagas' cardiomyopathy in adults, the author evokes the new experiences and the new challenges of 2016 regarding chagas disease while speculating on its future and by calling back some elements little known of his history, in particular the fact that it is chagas who invented about it to some extent the concept of "neglected disease ...201627376642
detection and treatment of trypanosoma cruzi: a patent review (2011-2015).trypanosoma cruzi is the etiologic agent of american trypanosomiasis (chagas disease), which is one of the important parasitic diseases worldwide. the number of infected people with t. cruzi diminished from 18 million in 1991 to 6 million in 2010, but it is still the most prevalent parasitic disease in the americas. the existing chemotherapy is still deficient and based on two drugs: nifurtimox and benznidazole, which are not fda-approved in the united states.201627376456
complexity and multi-factoriality of trypanosoma cruzi sylvatic cycle in coatis, nasua nasua (procyonidae), and triatomine bugs in the brazilian pantanal.trypanosoma cruzi is dispersed in nature through many transmission mechanisms among a high diversity of vectors and mammalian species, representing particular behaviors and habitats. thus, each locality has a unique set of conditions underlying the maintenance of this parasite in the wild. the aim of the present study was to evaluate the life-cycle of t. cruzi in free-ranging coatis from the central region of the brazilian pantanal using a multi-factorial approach.201627370106
blocking of cd1d decreases trypanosoma cruzi-induced activation of cd4-cd8- t cells and modulates the inflammatory response in patients with chagas heart disease.the control of inflammatory responses to prevent the deadly cardiac pathology in human chagas disease is a desirable and currently unattained goal. double-negative (dn) t cells are important sources of inflammatory and antiinflammatory cytokines in patients with chagas heart disease and those with the indeterminate clinical form of chagas disease, respectively. given the importance of dn t cells in immunoregulatory processes and their potential as targets for controlling inflammation-induced pat ...201627368347
unique behavior of trypanosoma cruzi mevalonate kinase: a conserved glycosomal enzyme involved in host cell invasion and signaling.mevalonate kinase (mvk) is an essential enzyme acting in early steps of sterol isoprenoids biosynthesis, such as cholesterol in humans or ergosterol in trypanosomatids. mvk is conserved from bacteria to mammals, and localizes to glycosomes in trypanosomatids. during the course of t. cruzi mvk characterization, we found that, in addition to glycosomes, this enzyme may be secreted and modulate cell invasion. to evaluate the role of tcmvk in parasite-host cell interactions, tcmvk recombinant protei ...201627113535
geographical variation of deltamethrin susceptibility of triatoma infestans (hemiptera: reduviidae) in argentina with emphasis on a resistant focus in the gran chaco.chagas disease is one of the most important parasitic infections in latin america. the main vector of the protozoan trypanosoma cruzi in america is triatoma infestans, a blood-sucking triatomine bug who is widely distributed in the gran chaco ecoregion. control programs in endemic countries are focused in the elimination of triatomine vectors with pyrethroid insecticides. however, chemical control has failed in the gran chaco over the last two decades because of several factors. previous studies ...201627113106
fluctuations in trypanosoma cruzi discrete typing unit composition in two naturally infected triatomines: mepraia gajardoi and m. spinolai after laboratory feeding.mepraia species are hematophagous insects and the most important wild vectors of trypanosoma cruzi, the causative agent of chagas disease in southeastern south america. because the domestic triatoma infestans is already controlled, the transmission of different t. cruzi discrete typing units (dtus) by mepraia species deserves attention. our aim is to gather information on the diversity of t. cruzi dtus circulating in natural insect populations. two groups of naturally infected bugs 21 mepraia ga ...201627109041
chromatin proteomics reveals variable histone modifications during the life cycle of trypanosoma cruzi.histones are well-conserved proteins that form the basic structure of chromatin in eukaryotes and undergo several post-translational modifications, which are important for the control of transcription, replication, dna damage repair, and chromosome condensation. in early branched organisms, histones are less conserved and appear to contain alternative sites for modifications, which could reveal evolutionary unique functions of histone modifications in gene expression and other chromatin-based pr ...201627108550
trypanosoma cruzi infection prevalence and bloodmeal analysis in triatomine vectors of chagas disease from rural peridomestic locations in texas, 2013-2014.protozoan pathogen trypanosoma cruzi (chagas, 1909) is the etiologic agent of chagas disease, which affects millions of people in latin america. recently, the disease has been gaining attention in texas and the southern united states. transmission cycle of the parasite involves alternating infection between insect vectors and vertebrate hosts (including humans, wildlife, and domestic animals). to evaluate vector t. cruzi parasite burden and feeding patterns, we tested triatomine vectors from 23 ...201627106934
correction: first documented transmission of trypanosoma cruzi infection through blood transfusion in a child with sickle-cell disease in belgium. 201627096415
diagnosis of congenital chagas disease using an iron superoxide dismutase excreted as antigen, in mothers and their children during the first year of life.chagas disease caused by trypanosoma cruzi is endemic in latin america. human infection is mainly spread by triatominae insects. other forms of transmission are congenital, blood transfusion and organ transplantation.201627088584
bioactivity-guided isolation of laevicarpin, an antitrypanosomal and anticryptococcal lactam from piper laevicarpu (piperaceae).crude ch2cl2 extract from leaves of piper laevicarpu (piperaceae) displayed antitrypanosomal activity against trypomastigote forms of trypanosoma cruzi (y strain) and antimicrobial potential against cryptococcus gattii (strain-type wm 178). bioactivity-guided fractionation of crude extract afforded one new natural bioactive lactam derivative, named laevicarpin. the structure of isolated compound, which displayed a very rare ring system, was elucidated based on nmr, ir and ms spectral analysis. u ...201627083380
identification of trypanocidal activity for known clinical compounds using a new trypanosoma cruzi hit-discovery screening cascade.chagas disease is a significant health problem in latin america and the available treatments have significant issues in terms of toxicity and efficacy. there is thus an urgent need to develop new treatments either via a repurposing strategy or through the development of new chemical entities. a key first step is the identification of compounds with anti-trypanosoma cruzi activity from compound libraries. here we describe a hit discovery screening cascade designed to specifically identify hits th ...201627082760
antiparasitic evaluation of betulinic acid derivatives reveals effective and selective anti-trypanosoma cruzi inhibitors.betulinic acid is a pentacyclic triterpenoid with several biological properties already described, including antiparasitic activity. here, the anti-trypanosoma cruzi activity of betulinic acid and its semi-synthetic amide derivatives (ba1-ba8) was investigated. the anti-trypanosoma cruzi activity and selectivity were enhanced in semi-synthetic derivatives, specially on derivatives ba5, ba6 and ba8. to understand the mechanism of action underlying betulinic acid anti-t. cruzi activity, we investi ...201627080160
molecular epidemiology of trypanosoma cruzi and triatoma dimidiata in costal ecuador.chagas disease is a neglected tropical disease caused by the protozoan parasite trypanosoma cruzi. in ecuador, triatoma dimidiata and rhodnius ecuadoriensis are the main vector species, responsible for over half of the cases of t. cruzi infection in the country. t. dimidiata is believed to have been introduced in ecuador during colonial times, and its elimination from the country is thus believed to be feasible. we investigated here the molecular ecology of t. dimidiata and t. cruzi in costal ec ...201627079265
attenuated salmonella sp. as a dna delivery system for trypanosoma cruzi antigens.chagas disease is an important neglected disease affecting thousands of people in the americas. novel strategies for prophylactic and therapeutic vaccines against the etiological agent, the intracellular protozoan trypanosoma cruzi, are urgently needed. vaccines based on attenuated virus and bacteria as a foreign dna delivery system represent a strong advantage over naked dna-based vaccines. here we describe the use of attenuated salmonella carrying a eukaryotic expression plasmid encoding a t. ...201627076330
vaccination of dogs with trypanosoma rangeli induces antibodies against trypanosoma cruzi in a rural area of córdoba, argentina.dogs play a major role in the domestic cycle of trypanosoma cruzi, acting as reservoirs. in a previous work we have developed a model of vaccination of dogs in captivity with nonpathogenic trypanosoma rangeli epimastigotes, resulting in the production of protective antibodies against t. cruzi, with dramatic decrease of parasitaemia upon challenge with 100,000 virulent forms of this parasite. the aim of this work was to evaluate the immunogenicity of this vaccine in dogs living in a rural area. d ...201627074257
a 12-mer repetitive antigenic epitope from trypanosoma cruzi is a potential marker of therapeutic efficacy in chronic chagas' disease.the objective was to characterize a trypanosoma cruzi repetitive amino acid sequence that can be used as a marker of therapeutic drug efficacy in patients with chronic chagas' disease.201627073267
advances and progress in chagas disease drug discovery.chagas disease represents a serious burden for millions of people worldwide. transmitted by the protozoan parasite trypanosoma cruzi, this neglected tropical disease causes more than 10,000 deaths each year and is the main cause of heart failure in latin america, where it is endemic. although most cases are concentrated in latin american countries, chagas disease has been increasingly reported in non-endemic regions, where the low level of public awareness on the subject contributes to the growi ...201627072717
tci isolates of trypanosoma cruzi exploit the antioxidant network for enhanced intracellular survival in macrophages and virulence in mice.trypanosoma cruzi species is categorized into six discrete typing units (tci to tcvi) of which tci is most abundantly noted in the sylvatic transmission cycle and considered the major cause of human disease. in our study, the tci strains colombiana (col), sylviox10/4 (syl), and a cultured clone (tcc) exhibited different biological behavior in a murine model, ranging from high parasitemia and symptomatic cardiomyopathy (syl), mild parasitemia and high tissue tropism (col), to no pathogenicity (tc ...201627068090
clomipramine and benznidazole act synergistically and ameliorate the outcome of experimental chagas disease.chagas disease is an important public health problem in latin america, and its treatment by chemotherapy with benznidazole (bz) or nifurtimox remains unsatisfactory. in order to design new alternative strategies to improve the current etiological treatments, in the present work, we comprehensively evaluated the in vitro and in vivo anti-trypanosoma cruzi effects of clomipramine (cmp) (a parasite-trypanothione reductase-specific inhibitor) combined with bz. in vitro studies, carried out using a c ...201627067322
interactions between trypanosoma cruzi secreted proteins and host cell signaling pathways.chagas disease is one of the prevalent neglected tropical diseases, affecting at least 6-7 million individuals in latin america. it is caused by the protozoan parasite trypanosoma cruzi, which is transmitted to vertebrate hosts by blood-sucking insects. after infection, the parasite invades and multiplies in the myocardium, leading to acute myocarditis that kills around 5% of untreated individuals. t. cruzi secretes proteins that manipulate multiple host cell signaling pathways to promote host c ...201627065960
a case of chagas' disease panniculitis after kidney transplantation.chagas' disease carries high morbidity and mortality due to acute parasitemia or cardiac, digestive, cutaneous or neurologic chronic lesions. latin american countries have the majority of infected or at risk people. transplanted patients using immunosuppressive agents may develop severe and even fatal forms of the disease. the available treatment causes frequent severe side-effects. a 59 years-old woman with end stage renal disease and positive serology for chagas` disease, but without any clini ...201627049374
role of trypanosoma cruzi trans-sialidase on the escape from host immune surveillance.chagas disease is caused by the flagellate protozoan trypanosoma cruzi, affecting millions of people throughout latin america. the parasite dampens host immune response causing modifications in diverse lymphoid compartments, including the thymus. t. cruzi trans-sialidase (ts) seems to play a fundamental role in such immunopathological events. this unusual enzyme catalyses the transference of sialic acid molecules from host glycoconjugates to acceptor molecules placed on the parasite surface. ts ...201627047464
transcriptome remodeling in trypanosoma cruzi and human cells during intracellular infection.intracellular colonization and persistent infection by the kinetoplastid protozoan parasite, trypanosoma cruzi, underlie the pathogenesis of human chagas disease. to obtain global insights into the t. cruzi infective process, transcriptome dynamics were simultaneously captured in the parasite and host cells in an infection time course of human fibroblasts. extensive remodeling of the t. cruzi transcriptome was observed during the early establishment of intracellular infection, coincident with a ...201627046031
enteric neuronal damage, intramuscular denervation and smooth muscle phenotype changes as mechanisms of chagasic megacolon: evidence from a long-term murine model of tripanosoma cruzi infection.we developed a novel murine model of long-term infection with trypanosoma cruzi with the aim to elucidate the pathogenesis of megacolon and the associated adaptive and neuromuscular intestinal disorders. our intent was to produce a chronic stage of the disease since the early treatment should avoid 100% mortality of untreated animals at acute phase. treatment allowed animals to be kept infected and alive in order to develop the chronic phase of infection with low parasitism as in human disease. ...201627045678
kissing bug (triatoma spp.) intrusion into homes: troublesome bites and domiciliation.kissing bugs (triatoma spp.) frequently enter homes and bite human and pet occupants. bites may lead to severe allergic reactions and, in some cases, death. kissing bugs are also vectors of trypanosoma cruzi, the cause of chagas disease. in general, modern houses in the united states are not conducive to domiciliation of kissing bugs (bugs living out their entire life within the home with the presence of eggs, nymphs, adults, and exuviae). construction features such as concrete foundations, soli ...201627042091
american tegumentary leishmaniasis: t-cell differentiation profile of cutaneous and mucosal forms-co-infection with trypanosoma cruzi.american tegumentary leishmaniasis displays two main clinical forms: cutaneous (cl) and mucosal (ml). ml is more resistant to treatment and displays a more severe and longer evolution. since both forms are caused by the same leishmania species, the immunological response of the host may be an important factor determining the evolution of the disease. herein, we analyzed the differentiation and memory profile of peripheral cd4(+) and cd8(+) t lymphocytes of patients with cl and ml and their leish ...201627040974
modulation of inflammatory and oxidative status by exercise attenuates cardiac morphofunctional remodeling in experimental chagas cardiomyopathy.the rational basis that explains the benefits of exercise therapy on chagas cardiomyopathy (chc) is poorly understood. this study investigated the impact of an exercise program on exercise performance, heart parasitism, immunoinflammatory response, fibrogenesis, oxidative damage, and cardiomyocytes contractility in experimental chc.201627040670
analysis of the transmission of trypanosoma cruzi infection through hosts and vectors.calculating epidemiological measures of infection by trypanosoma cruzi, the causative agent of chagas disease, is complex, because it involves several species, different stages of infection in humans and multiple transmission routes. using the next-generation matrix method, we analysed a model which considers the three stages of human infection, triatomines and dogs (the main domestic reservoirs of t. cruzi when triatomines are present) and the main transmission routes. we derived r 0 and type-r ...201627039662
host cell invasion and oral infection by trypanosoma cruzi strains of genetic groups tci and tciv from chagasic patients.outbreaks of acute chagas disease by oral infection have been reported frequently over the last ten years, with higher incidence in northern south america, where trypanosoma cruzi lineage tci predominates, being responsible for the major cause of resurgent human disease, and a small percentage is identified as tciv. mechanisms of oral infection and host-cell invasion by these parasites are poorly understood. to address that question, we analyzed t. cruzi strains isolated from chagasic patients i ...201627038796
how trypanosoma cruzi deals with oxidative stress: antioxidant defence and dna repair pathways.trypanosoma cruzi, the causative agent of chagas disease, is an obligatory intracellular parasite with a digenetic life cycle. due to the variety of host environments, it faces several sources of oxidative stress. in addition to reactive oxygen species (ros) produced by its own metabolism, t. cruzi must deal with high ros levels generated as part of the host's immune responses. hence, the conclusion that t. cruzi has limited ability to deal with ros (based on the lack of a few enzymes involved w ...201627036062
development of a novel multiplex immunoassay multi-cruzi for the serological confirmation of chagas disease.chagas disease is due to the parasite trypanosoma cruzi, a protist disseminated by a triatome vector. this disease is endemic to latin america and considered by who as one of the 17 world's neglected diseases. in europe and in north america, imported cases are also detected, due to migration of population outside of the endemic region. diagnosis of t. cruzi infection is usually made indirectly by the detection of specific antibodies to t. cruzi antigens. following initial diagnostic evaluation o ...201627035146
il18 gene variants influence the susceptibility to chagas disease.chagas disease is a parasitic disorder caused by the infection with the flagellated protozoan trypanosoma cruzi. according to the world health organization, more than six million people are currently infected in endemic regions. genetic factors have been proposed to influence predisposition to infection and development of severe clinical phenotypes like chronic chagas cardiomyopathy (ccc). interleukin 18 (il18) encodes a proinflammatory cytokine that has been proposed to be involved in controlli ...201627027876
overexpression of bromodomain factor 3 in trypanosoma cruzi (tcbdf3) affects differentiation of the parasite and protects it against bromodomain inhibitors.the bromodomain is the only protein domain known to bind acetylated lysine. in the last few years many bromodomain inhibitors have been developed in order to treat diseases such as cancer caused by aberrant acetylation of lysine residues. we have previously characterized trypanosoma cruzi bromodomain factor 3 (tcbdf3), a bromodomain with an atypical localization that binds acetylated α-tubulin. in the present work we show that parasites overexpressing tcbdf3 exhibit altered differentiation patte ...201627007774
kinetic and molecular characterization of the pyruvate phosphate dikinase from trypanosoma cruzi.trypanosoma cruzi, like other trypanosomatids analyzed so far, can use both glucose and amino acids as carbon and energy source. in these parasites, glycolysis is compartmentalized in glycosomes, authentic but specialized peroxisomes. the major part of this pathway, as well as a two-branched glycolytic auxiliary system, are present in these organelles. the first enzyme of one branch of this auxiliary system is the ppi-dependent pyruvate phosphate dikinase (ppdk) that converts phosphoenolpyruvate ...201627003459
cost-effectiveness of blood donation screening for trypanosoma cruzi in mexico.an estimated 2 million inhabitants are infected with chagas disease in mexico, with highest prevalence coinciding with highest demographic density in the southern half of the country. after vector-borne transmission, trypanosoma cruzi is principally transmitted to humans via blood transfusion. despite initiation of serological screening of blood donations or donors for t. cruzi since 1990 in most latin american countries, mexico only finally included mandatory serological screening nationwide in ...201627002523
curcumin enhances the anti-trypanosoma cruzi activity of benznidazole-based chemotherapy in acute experimental chagas disease.although curcumin can increase the effectiveness of drugs against malaria, combination therapies using the molecule have never been investigated in chagas disease (chd). therefore, we evaluated the efficacy of curcumin as a complementary strategy to benznidazole (bz)-based chemotherapy in mice acutely infected with trypanosoma cruzi eighty-four 12-week-old swiss mice were equally randomized into seven groups: uninfected (ni), t. cruzi infected and untreated (inf), infected and treated with 100 m ...201627001816
binding mode and selectivity of steroids towards glucose-6-phosphate dehydrogenase from the pathogen trypanosoma cruzi.glucose-6-phosphate dehydrogenase (g6pdh) plays a housekeeping role in cell metabolism by generating reducing power (nadph) and fueling the production of nucleotide precursors (ribose-5-phosphate). based on its indispensability for pathogenic parasites from the genus trypanosoma, g6pdh is considered a drug target candidate. several steroid-like scaffolds were previously reported to target the activity of g6pdh. epiandrosterone (ea) is an uncompetitive inhibitor of trypanosomal g6pdh for which it ...201626999093
tgf-β receptor type ii costameric localization in cardiomyocytes and host cell tgf-β response is disrupted by trypanosoma cruzi infection.transforming growth factor beta (tgf-β) cytokine is involved in chagas disease establishment and progression. since trypanosoma cruzi can modulate host cell receptors, we analysed the tgf-β receptor type ii (tβrii) expression and distribution during t. cruzi - cardiomyocyte interaction. tβrii immunofluorescent staining revealed a striated organization in cardiomyocytes, which was co-localized with vinculin costameres and enhanced (38%) after tgf-β treatment. cytochalasin d induced a decrease of ...201626996782
molecular docking and binding mode analysis of plant alkaloids as in vitro and in silico inhibitors of trypanothione reductase from trypanosoma cruzi.trypanothione reductase (tryr) is a key enzyme in the metabolism of trypanosoma cruzi, the parasite responsible for chagas disease. the available repertoire of tryr inhibitors relies heavily on synthetic substrates of limited structural diversity, and less on plant-derived natural products. in this study, a molecular docking procedure using a lamarckian genetic algorithm was implemented to examine the protein-ligand binding interactions of strong in vitro inhibitors for which no x-ray data is av ...201626996020
differential parasitological, molecular, and serological detection of trypanosoma cruzi i, ii, and iv in blood of experimentally infected mice.trypanosoma cruzi is the etiological agent of american trypanosomiasis (chagas' disease), which affects 6-7 million people worldwide, mainly in latin america. it presents great genetic and biological variability that plays an important role in the clinical and epidemiological features of the disease. our working hypothesis is that the genetic diversity of t. cruzi has an important impact on detection of the parasite using diagnostic techniques. the present study evaluated the diagnostic performa ...201626995535
mechanisms of vascular dysfunction in acute phase of trypanosoma cruzi infection in mice.vascular disorders have a direct link to mortality in the acute phase of trypanosoma cruzi infection. however, the underlying mechanisms of vascular dysfunction in this phase are largely unknown. we hypothesize that t. cruzi invades endothelial cells causing dysfunction in contractility and relaxation of the mouse aorta. immunodetection of t. cruzi antigen tcrbp28 was observed in endothelial cells. there was a decreased endothelial nitric oxide synthase (enos)-derived no-dependent vascular relax ...201626988253
trypanosoma cruzi-infected panstrongylus geniculatus and rhodnius robustus adults invade households in the tropics of cochabamba region of bolivia.there are hardly any data available on the relationships between the parasite and the vector or regarding potential reservoirs involved in the natural transmission cycle of trypanosoma cruzi in the tropics of cochabamba, bolivia. local families from communities were responsible for the capture of triatomine specimens, following a strategic methodology based on entomological surveillance with community participation developed by the national chagas programme of the ministry of health of bolivia.201626984679
risk factors associated with seropositivity for leishmania spp. and trypanosoma cruzi in dogs in the state of paraiba, brazil.the aim of this survey was to determine the seropositivity and risk factors for leishmania spp. and trypanosoma cruzi in dogs in the state of paraíba, northeastern brazil. a total of 1,043 dogs were tested, and the serological diagnoses of chagas disease (cd) and canine visceral leishmaniasis (cvl) was performed by the indirect fluorescent antibody test (ifat). animals that tested seropositive for both diseases (by ifat) were further subjected to elisa. of the 1,043 dogs 81 (7.8%; 95% ci = 6.1-9 ...201626982555
pharmacokinetic and pharmacodynamic responses in adult patients with chagas disease treated with a new formulation of benznidazole.pharmacological treatment of chagas disease with benznidazole (bnz) is effective in children in all stages, but it is controversial in chronically infected adults. we report the pharmacokinetics and pharmacodynamics in six adult patients with chagas disease treated with the new bnz formulation (abarax®) in doses between 2.5-5.5 mg/kg/day. all but one patient had plasmatic bnz concentrations within the expected range. all patients finalised treatment with nondetectable trypanosoma cruzi quantitat ...201626982179
a novel vaccine approach for chagas disease using rare adenovirus serotype 48 vectors.due to the increasing amount of people afflicted worldwide with chagas disease and an increasing prevalence in the united states, there is a greater need to develop a safe and effective vaccine for this neglected disease. adenovirus serotype 5 (ad5) is the most common adenovirus vector used for gene therapy and vaccine approaches, but its efficacy is limited by preexisting vector immunity in humans resulting from natural infections. therefore, we have employed rare serotype adenovirus 48 (ad48) ...201626978385
chronic chagas disease diagnosis: a comparative performance of commercial enzyme immunoassay tests.there is a significant heterogeneity in reported performance of serological assays for chagas disease diagnosis. the conventional serology testing in laboratory diagnosis and in blood banks is unsatisfactory because of a high number of inconclusive and misclassified results. we aimed to assess the quality of four commercially available enzyme-linked immunosorbent assay tests for their ability to detect trypanosoma cruzi antibodies in 685 sera samples. cross-reactivity was assessed by using 748 s ...201626976886
altered cardiomyocyte function and trypanosoma cruzi persistence in chagas disease.chagas disease, caused by the triatominae trypanosoma cruzi, is one of the leading causes of heart malfunctioning in latin america. the cardiac phenotype is observed in 20-30% of infected people 10-40 years after their primary infection. the cardiac complications during chagas disease range from cardiac arrhythmias to heart failure, with important involvement of the right ventricle. interestingly, no studies have evaluated the electrical properties of right ventricle myocytes during chagas disea ...201626976879
resveratrol inhibits trypanosoma cruzi arginine kinase and exerts a trypanocidal activity.arginine kinase catalyzes the reversible transphosphorylation between adp and phosphoarginine which plays a critical role in the maintenance of cellular energy homeostasis. arginine kinase from the protozoan parasite trypanosoma cruzi, the etiologic agent of chagas disease, meets the requirements to be considered as a potential therapeutic target for rational drug design including being absent in its mammalian hosts. in this study a group of polyphenolic compounds was evaluated as potential inhi ...201626976067
promiscuous recognition of a trypanosoma cruzi cd8+ t cell epitope among hla-a2, hla-a24 and hla-a1 supertypes in chagasic patients.tctle is a nonamer peptide from trypanosoma cruzi kmp-11 protein that is conserved among different parasite strains and that is presented by different hla-a molecules from the a2 supertype. because peptides presented by several major histocompatibility complex (mhc) supertypes are potential targets for immunotherapy, the aim of this study was to determine whether mhc molecules other than the a2 supertype present the tctle peptide.201626974162
the role of the c-terminal region on the oligomeric state and enzymatic activity of trypanosoma cruzi hypoxanthine phosphoribosyl transferase.hypoxanthine phosphoribosyl transferase from trypanosoma cruzi (tchprt) is a critical enzyme for the survival of the parasite. this work demonstrates that the full-length form in solution adopts a stable and enzymatically active tetrameric form, exhibiting large inter-subunit surfaces. although this protein irreversibly aggregates during unfolding, oligomerization is reversible and can be modulated by low concentrations of urea. when the c-terminal region, which is predicted as a disordered stre ...201626969784
novel drug discovery for chagas disease.chagas disease is a chronic infection associated with long-term morbidity. increased funding and advocacy for drug discovery for neglected diseases have prompted the introduction of several important technological advances, and chagas disease is among the neglected conditions that has mostly benefited from technological developments. a number of screening campaigns, and the development of new and improved in vitro and in vivo assays, has led to advances in the field of drug discovery.201626967915
compound profiling and 3d-qsar studies of hydrazone derivatives with activity against intracellular trypanosoma cruzi.chagas disease is a tropical disease caused by the parasite trypanosoma cruzi, which is endemic in central and south america. few treatments are available with effectiveness limited to the early (acute) stage of disease, significant toxicity and widespread drug resistance. in this work we report the outcome of a hts-ready assay chemical library screen to identify novel, nontoxic, small-molecule inhibitors of t. cruzi. we have selected 50 compounds that possess hydrazone as a common group. the co ...201626964673
the driving of immune response by th1 adjuvants in immunization of mice with trypanosoma cruzi marinkellei elicits a controversial infection control.in previous studies, we have demonstrated that inoculation with a trypanosoma cruzi marinkellei (avirulent rm1 strain) was able to reduce parasitemia in mice challenged with t. cruzi, although it was not able to prevent histopathological lesions. th1 response stimulation by immunization is necessary for t. cruzi infection control, but the resistance is also dependent on immunoregulatory mechanisms, which can be induced by adjuvants. thus, we evaluated whether inoculation of t. cruzi marinkellei ...201626959861
risk factors and screening for trypanosoma cruzi infection of dutch blood donors.blood donors unaware of trypanosoma cruzi infection may donate infectious blood. risk factors and the presence of t. cruzi antibodies in at-risk dutch blood donors were studied to assess whether specific blood safety measures are warranted in the netherlands.201626950434
the mitogen-activated protein kinase (mapk) pathway: role in immune evasion by trypanosomatids.leishmania spp. and trypanosoma cruzi are the causative agents of leishmaniasis and chagas disease, respectively, two neglected tropical diseases that affect about 25 million people worldwide. these parasites belong to the family trypanosomatidae, and are both obligate intracellular parasites that manipulate host signaling pathways and the innate immune system to establish infection. mitogen-activated protein kinases (mapks) are serine and threonine protein kinases that are highly conserved in e ...201626941717
comparative proteomic analysis of the saliva of the rhodnius prolixus, triatoma lecticularia and panstrongylus herreri triatomines reveals a high interespecific functional biodiversity.triatomines are hematophagous arthropods that transmit trypanosoma cruzi and trypanosoma rangeli. feeding behavior and pathogen transmission is known to vary between the different species, and this characteristic is directly or indirectly dependent on the bioactive molecules of the saliva that facilitate the vector-host-parasite interaction. here, we identify, characterize and compare the sialoproteomic (from the greek sialo: saliva) repertoire of important species of the main triatomine genera ...201626940473
mode of action of the sesquiterpene lactones psilostachyin and psilostachyin c on trypanosoma cruzi.trypanosoma cruzi is the causative agent of chagas' disease, which is a major endemic disease in latin america and is recognized by the who as one of the 17 neglected tropical diseases in the world. psilostachyin and psilostachyin c, two sesquiterpene lactones isolated from ambrosia spp., have been demonstrated to have trypanocidal activity. considering both the potential therapeutic targets present in the parasite, and the several mechanisms of action proposed for sesquiterpene lactones, the ai ...201626939119
control and management of congenital chagas disease in europe and other non-endemic countries: current policies and practices.identifying pregnant women infected with trypanosoma cruzi is one of the major challenges for preventing and controlling chagas disease (cd) in non-endemic countries. the aim of this paper was to perform a policy evaluation of the current practices of congenital chagas disease (ccd) control in non-endemic countries and to propose specific targets for enhanced interventions to tackle this emerging health problem outside the endemic areas of latin america.201626932338
promising efficacy of benznidazole nanoparticles in acute trypanosoma cruzi murine model: in-vitro and in-vivo studies.the aim of this study was to evaluate the effectiveness of benznidazole nanoparticles (bnz-nps) on trypomastigote forms and on intracellular infection in mammalian cells and primary cardiac myocyte cells. its effectiveness was also evaluated on acute trypanosoma cruzi nicaragua mice infection. trypomastigotes from culture were treated with different concentrations of bnz-nps to determine the drug concentration that lyses 50% of trypomastigotes (lc50). infected mammalian cells were incubated with ...201627246447
evasion and immuno-endocrine regulation in parasite infection: two sides of the same coin in chagas disease?chagas disease is a serious illness caused by the protozoan parasite trypanosoma cruzi. nearly 30% of chronically infected people develop cardiac, digestive, or mixed alterations, suggesting a broad range of host-parasite interactions that finally impact upon chronic disease outcome. the ability of t. cruzi to persist and cause pathology seems to depend on diverse factors like t. cruzi strains, the infective load and the route of infection, presence of virulence factors, the parasite capacity to ...201627242726
modulation of cell sialoglycophenotype: a stylish mechanism adopted by trypanosoma cruzi to ensure its persistence in the infected host.trypanosoma cruzi, the etiological agent of chagas disease exhibits multiple mechanisms to guarantee its establishment and persistence in the infected host. it has been well demonstrated that t. cruzi is not able to synthesize sialic acids (sia). to acquire the monosaccharide, the parasite makes use of a multifunctional enzyme called trans-sialidase (tc-ts). since this enzyme has no analogous in the vertebrate host, it has been used as a target in drug therapy development. tc-ts preferentially c ...201627242722
structural analysis and molecular docking of trypanocidal aryloxy-quinones in trypanothione and glutathione reductases: a comparison with biochemical data.a set of aryloxy-quinones, previously synthesized and evaluated against trypanosoma cruzi epimastigotes cultures, were found more potent and selective than nifurtimox. one of the possible mechanisms of the trypanocidal activity of these quinones could be inhibition of trypanothione reductase (tr). considering that glutathione reductase (gr) is the equivalent of tr in humans, biochemical, kinetic, and molecular docking studies in tr and gr were envisaged and compared with the trypanocidal and cyt ...201627232454
invasion of rural houses by wild triatominae in the arid chaco.triatomines are the vectors of trypanosoma cruzi, the etiologic agent of chagas disease, the main endemic disease affecting five to seven million people in latin america. besides triatoma infestans, the most important t. cruzi vector in the gran chaco region, other triatomine species associated with sylvatic birds and mammals are responsible for the maintenance of the wild cycle of t. cruzi. the present study aimed at evaluating the house invasion by sylvatic triatomine species in rural communit ...201627232130
vector capacity of members of triatoma brasiliensis species complex: the need to extend chagas disease surveillance to triatoma melanica.we conducted a lab-based comparative study on vector capacity features of two species of triatomines: triatoma brasiliensis and t. melanica. both are members of the t. brasiliensis species complex. the former is the most important chagas disease vector in the northeastern region of brazil. to date, no transmission via t. melanica has been recorded. immature insects exhibited distinct intermoult periods without a direct relationship to a given species. females of t. brasiliensis consumed an avera ...201627232124
what is the 'true' effect of trypanosoma rangeli on its triatomine bug vector?the phrase, "t. rangeli is pathogenic to its insect vector," is commonly found in peer-reviewed publications on the matter, such that it has become the orthodox view of this interaction. in a literature survey, we identified over 20 papers with almost the exact phrase and several others alluding to it. the idea is of particular importance in triatomine population dynamics and the study of vector-borne t. cruzi transmission, as it could mean that triatomines infected with t. rangeli have lower fi ...201627232121
survey of feral swine ( sus scrofa ) infection with the agent of chagas disease ( trypanosoma cruzi ) in texas, 2013-14.: feral swine ( sus scrofa ) are an invasive species and reservoir of numerous zoonotic pathogens in the us, and texas leads the nation in the estimated population size of feral hogs. texas also harbors enzootic transmission cycles of the protozoan parasite trypanosoma cruzi , agent of chagas disease. given previous evidence that swine can serve as reservoirs of t. cruzi in latin america and new evidence of triatomines (kissing bugs) feeding on swine in texas, we measured the prevalence of t. cr ...201627224214
innate immunomodulation to trypanosomatid parasite infections.the recognition of invading pathogens by the innate immune system is essential for host protection against human parasites and the initiation of an effective adaptive immune response. innate immune cells such as macrophages and dendritic cells (dcs) are involved in the first line of defense against protozoan parasites via sensing the invaders through pattern recognition receptors (prrs), such as toll-like receptors (tlrs). activation of macrophages and dendritic cells starts with the interaction ...201627223816
serological based monitoring of a cohort of patients with chronic chagas disease treated with benznidazole in a highly endemic area of northern argentina.this study aimed to evaluate well-documented diagnostic antigens, named b13, 1f8 and jl7 recombinant proteins, as potential markers of seroconversion in treated chagasic patients. prospective study, involving 203 patients treated with benznidazole, was conducted from endemic areas of northern argentina. follow-up was possible in 107 out of them and blood samples were taken for serology and pcr assays before and 2, 3, 6, 12, 24 and 36 months after treatment initiation. reactivity against trypanos ...201627223650
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