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1.
Pathogens ; 13(3)2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38535589

ABSTRACT

The diagnosis of canine leishmaniasis (CanL) still represents a challenge due to the variable clinical manifestations and the large number of asymptomatic dogs. Serological tests are most commonly used to detect infected animals, revealing anti-Leishmania antibodies, mainly of the IgG isotype. Recently, a new diagnostic antigen, rKLi8.3, containing 8.3 kinesin tandem repeats (TR) from a Leishmania infantum strain from Sudan, has been shown to provide excellent specificity and sensitivity for the detection of Leishmania-infected humans and dogs. However, asymptomatic animals with very low antibody titers are often difficult to detect by serodiagnosis. Thus, we wondered whether the addition of an anti-IgG-enhancing step in the protein A/G-based rKLi8.3-ELISA will improve the diagnostic performance without decreasing the specificity. For this, parasitologically confirmed CanL cases with low or high clinical scores, uninfected healthy controls and dogs with other infections were tested by rKLi8.3-ELISA as well as two different immunochromatographic rapid tests, rKLi8.3-lateral flow test (LFT) and Dual Path Platform (DPP®) based on the rK28 antigen. Our results show that the diagnostic accuracies of the rKLi8.3-ELISA and LFT were similar to that of DPP, missing several asymptomatic animals. However, the addition of a secondary, amplifying anti-dog IgG antibody in the protein A/G-based rKLi8.3-ELISA enabled the detection of nearly all asymptomatic dogs without compromising its specificity.

2.
Exp Parasitol ; 255: 108647, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37914151

ABSTRACT

Chagas disease (CD) remains neglected and causes high morbidity and mortality. The great difficulty is the lack of effective treatment. The current drugs cause side effects and have limited therapeutic efficacy in the chronic phase. This study aims to fulfil some gaps in studies of the natural substance lychnopholide nanoencapsulated LYC-PLA-PEG-NC (LYC-NC) and free (Free-LYC): the activity in epimastigotes and amastigotes to determine its selectivity index (SI), the therapeutic efficacy in mice infected with Colombian Trypanosoma cruzi strain and insight of the mechanism of LYC-NC action on T. cruzi. The SI was obtained by calculation of the ratio between the IC50 value toward H9c2 cells divided by the IC50 value in the anti-T. cruzi test. Infected Swiss mice were treated with 2 and 12 mg/kg/day via intravenous and oral, respectively, and the therapeutic efficacy was determined. The IC50 of LYC-NC and Free-LYC for epimastigotes of T. cruzi were similar. Both were active against amastigotes in cell culture, particularly Free-LYC. The SI of LYC-NC and Free-LYC were 45.38 and 32.11, respectively. LYC-NC 2 and 12 mg/kg/day cured parasitologically, 62.5% and 80% of the animals, respectively, infected with a strain resistant to treatment. The fluorescent NC was distributed in the cardiomyocyte cytoplasm, infected or not, and interacted with the trypomastigotes. Together, these results represent advances in demonstrating LYC as a potent new therapeutic option for treating CD.


Subject(s)
Chagas Disease , Nanocapsules , Nitroimidazoles , Trypanocidal Agents , Trypanosoma cruzi , Animals , Mice , Nifurtimox/therapeutic use , Nitroimidazoles/pharmacology , Nitroimidazoles/therapeutic use , Chagas Disease/drug therapy , Polyesters/pharmacology , Polyesters/therapeutic use , Trypanocidal Agents/pharmacology , Trypanocidal Agents/therapeutic use
3.
Future Med Chem ; 15(16): 1469-1489, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37650735

ABSTRACT

Background: Chagas disease is a life-threatening illness caused by Trypanosoma cruzi. The involvement of serine-/arginine-rich protein kinase in the T. cruzi life cycle is significant. Aims: To synthesize, characterize and evaluate the trypanocidal activity of diamides inspired by kinase inhibitor, SRPIN340. Material & Methods: Synthesis using a three-step process and characterization by infrared, nuclear magnetic resonance and high-resolution mass spectrometry were conducted. The selectivity index was obtained by the ratio of CC50/IC50 in two in vitro models. The most active compound, 3j, was evaluated using in vitro cytokine assays and assessing in vivo trypanocidal activity. Results: 3j activity in the macrophage J774 lineage showed an anti-inflammatory profile, and mice showed significantly reduced parasitemia and morbidity at low compound dosages. Conclusion: Novel diamide is active against T. cruzi in vitro and in vivo.

4.
Rev Soc Bras Med Trop ; 55: e0065, 2022.
Article in English | MEDLINE | ID: mdl-36134858

ABSTRACT

BACKGROUND: After decentralizing the actions of the Chagas Disease Control Program (CDCP) in Brazil, municipalities were now responsible for control measures against this endemic, supervised by the Regional Health Superintendencies (RHS). We aimed to evaluate the recent entomological surveillance of Chagas disease in the Regional Health Superintendence of Governador Valadares (RHS/GV) from 2014 to 2019. METHODS: Triatomines captured by residents during entomological surveillance were sent to the reference laboratory, where the species and evolutionary stages were identified, place of capture, and presence of Trypanosoma cruzi. A database was created, and the following were calculated: the rate of infection by T. cruzi (overall rate and rate by species), monthly seasonality, spatial distribution of species, number of captures, and infected triatomines/health microregions. RESULTS: We identified 1,708 insects; 1,506 (88.2%) were triatomines, most were adult instars (n=1,469), and few were nymphs (n=37). The identified species were Triatoma vitticeps, Panstrongylus megistus, Panstrongylus diasi, Rhodnius neglectus, and Panstrongylus geniculatus. The first three were most frequently captured and distributed throughout the study area. Most bugs were captured intradomicile (72.5%), mainly in the second semester, between September and November, with an average infection rate of 41.5% (predominantly T. vitticeps, 49.2%). All municipalities sent triatomines, especially in the microregions of Governador Valadares. CONCLUSIONS: These data reinforce the need and importance of improving Chagas disease control measures in the region to establish active and participatory entomological surveillance.


Subject(s)
Chagas Disease , Panstrongylus , Triatoma , Trypanosoma cruzi , Animals , Brazil/epidemiology , Chagas Disease/epidemiology , Humans , Insect Vectors
5.
Exp Parasitol ; 238: 108266, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35490799

ABSTRACT

Treatment for Chagas disease has limited efficacy in the chronic phase. We evaluated benznidazole (BZ) and itraconazole (ITZ) individually and in association in dogs 16 months after infection with a BZ-resistant Trypanosoma cruzi strain. Four study groups (20 animals) were evaluated and treated for 60 days with BZ, ITZ, or BZ + ITZ, and maintained in parallel to control group infected and not treated (INT). All dogs were evaluated in the first, sixth, 12th, 18th and 24th months of study. Polymerase chain reaction (PCR) was negative in 2 of 3 animals in the BZ + ITZ group, 2 of 5 in the BZ group, and 4 of 5 in the ITZ group. Hemoculture performed in the 24th month was negative in all groups. Enzyme-linked immunoassay remained reactive in all treated animals. Echocardiography differentiated treated animals from control animals. Quantitative PCR analysis of cardiac tissue was negative in the BZ + ITZ and BZ groups, positive in 2 of 5 dogs in the ITZ group and in 2 of 3 dogs in the control group, but negative in colon tissue in all groups. Inflammation was significantly reduced in the right atrium and left ventricle of dogs treated with BZ + ITZ and BZ compared with those receiving ITZ alone. Fibrosis was absent in most dogs treated with BZ + ITZ, mild in those treated with BZ or ITZ alone, and intense in the control group. Parasitological and histopathological evaluations showed that BZ + ITZ treatment improved or stabilized the clinical condition of the dogs.


Subject(s)
Chagas Disease , Nitroimidazoles , Trypanocidal Agents , Trypanosoma cruzi , Animals , Chagas Disease/drug therapy , Chagas Disease/pathology , Chagas Disease/veterinary , Dogs , Itraconazole/therapeutic use , Nitroimidazoles/therapeutic use , Trypanocidal Agents/therapeutic use
6.
Rev. Soc. Bras. Med. Trop ; 55: e0065, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1406968

ABSTRACT

ABSTRACT Background: After decentralizing the actions of the Chagas Disease Control Program (CDCP) in Brazil, municipalities were now responsible for control measures against this endemic, supervised by the Regional Health Superintendencies (RHS). We aimed to evaluate the recent entomological surveillance of Chagas disease in the Regional Health Superintendence of Governador Valadares (RHS/GV) from 2014 to 2019. Methods: Triatomines captured by residents during entomological surveillance were sent to the reference laboratory, where the species and evolutionary stages were identified, place of capture, and presence of Trypanosoma cruzi. A database was created, and the following were calculated: the rate of infection by T. cruzi (overall rate and rate by species), monthly seasonality, spatial distribution of species, number of captures, and infected triatomines/health microregions. Results: We identified 1,708 insects; 1,506 (88.2%) were triatomines, most were adult instars (n=1,469), and few were nymphs (n=37). The identified species were Triatoma vitticeps, Panstrongylus megistus, Panstrongylus diasi, Rhodnius neglectus, and Panstrongylus geniculatus. The first three were most frequently captured and distributed throughout the study area. Most bugs were captured intradomicile (72.5%), mainly in the second semester, between September and November, with an average infection rate of 41.5% (predominantly T. vitticeps, 49.2%). All municipalities sent triatomines, especially in the microregions of Governador Valadares. Conclusions: These data reinforce the need and importance of improving Chagas disease control measures in the region to establish active and participatory entomological surveillance.

7.
Acta Trop ; 167: 108-120, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27908747

ABSTRACT

The clonal evolution of Trypanosoma cruzi sustains scientifically the hypothesis of association between parasite's genetic, biological behavior and possibly the clinical aspects of Chagas disease in patients from whom they were isolated. This study intended to characterize a range of biological properties of TcI, TcII and TcVI T. cruzi samples in order to verify the existence of these associations. Several biological features were evaluated, including in vitro epimastigote-growth, "Vero"cells infectivity and growth, along with in vivo studies of parasitemia, polymorphism of trypomastigotes, cardiac inflammation, fibrosis and response to treatment by nifurtimox during the acute and chronic murine infection. The global results showed that the in vitro essays (acellular and cellular cultures) TcII parasites showed higher values for all parameters (growth and infectivity) than TcVI, followed by TcI. In vivo TcII parasites were more virulent and originated from patients with severe disease. Two TcII isolates from patients with severe pathology were virulent in mice, while the isolate from a patient with the indeterminate form of the disease caused mild infection. The only TcVI sample, which displayed low values in all parameters evaluated, was also originated of an indeterminate case of Chagas disease. Response to nifurtimox was not associated to parasite genetic and biology, as well as to clinical aspects of human disease. Although few number of T. cruzi samples have been analyzed, a discreet correlation between parasite genetics, biological behavior in vitro and in vivo (murine model) and the clinical form of human disease from whom the samples were isolated was verified.


Subject(s)
Chagas Disease/parasitology , Nifurtimox/pharmacology , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Trypanosoma cruzi/pathogenicity , Animals , Cells, Cultured , Disease Models, Animal , Humans , Mice , Trypanosoma cruzi/isolation & purification , Virulence
8.
Antimicrob Agents Chemother ; 60(9): 5215-22, 2016 09.
Article in English | MEDLINE | ID: mdl-27324760

ABSTRACT

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 it with LYC-NC administered to mice by the oral and intravenous routes during the chronic phase (CP). The therapeutic efficacy was evaluated by fresh blood examination, hemoculture, PCR, and enzyme-linked immunosorbent assay (ELISA). The cure rates in the AP and CP were 62.5% and 55.6%, respectively, upon oral administration of LYC-poly(d,l-lactide)-polyethylene glycol nanocapsules (LYC-PLA-PEG-NC) and 57.0% and 30.0%, respectively, with LYC-poly-ε-caprolactone nanocapsules (LYC-PCL-NC). These cure rates were significantly higher than that of free LYC, which did not cure any animals. LYC-NC formulations administered orally during the AP showed cure rates similar to that of benznidazole, but only LYC-NC cured mice in the CP. Similar results were achieved with intravenous treatment during the CP. The higher cure rates obtained with LYC loaded in PLA-PEG-NC may be due to the smaller particle size of these NC and the presence of PEG, which influence tissue diffusion and the controlled release of LYC. Furthermore, PLA-PEG-NC may improve the stability of the drug in the gastrointestinal tract. This work is the first report of cure of experimental Chagas disease via oral administration during the CP. These findings represent a new and important perspective for oral treatment of Chagas disease.


Subject(s)
Chagas Disease/drug therapy , Delayed-Action Preparations/pharmacology , Lactones/pharmacology , Nanocapsules/chemistry , Sesquiterpenes/pharmacology , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Acute Disease , Administration, Intravenous , Administration, Oral , Animals , Chagas Disease/mortality , Chagas Disease/parasitology , Chagas Disease/pathology , Chronic Disease , Delayed-Action Preparations/chemistry , Disease Models, Animal , Drug Compounding/methods , Humans , Lactones/chemistry , Mice , Nanocapsules/administration & dosage , Nitroimidazoles/pharmacology , Polyethylene Glycols/chemistry , Sesquiterpenes/chemistry , Survival Analysis , Treatment Outcome , Trypanocidal Agents/chemistry , Trypanosoma cruzi/growth & development , Trypanosoma cruzi/pathogenicity
9.
Mem Inst Oswaldo Cruz ; 110(1): 86-94, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25742267

ABSTRACT

Trypanosoma cruzi strains from distinct geographic areas show differences in drug resistance and association between parasites genetic and treatment response has been observed. Considering that benznidazole (BZ) can reduce the parasite burden and tissues damage, even in not cured animals and individuals, the goal is to assess the drug response to BZ of T. cruzi II strains isolated from children of the Jequitinhonha Valley, state of Minas Gerais, Brazil, before treatment. Mice infected and treated with BZ in both phases of infection were compared with the untreated and evaluated by fresh blood examination, haemoculture, polymerase chain reaction, conventional (ELISA) and non-conventional (FC-ALTA) serologies. In mice treated in the acute phase, a significant decrease in parasitaemia was observed for all strains. Positive parasitological and/or serological tests in animals treated during the acute and chronic (95.1-100%) phases showed that most of the strains were BZ resistant. However, beneficial effect was demonstrated because significant reduction (p < 0.05%) and/or suppression of parasitaemia was observed in mice infected with all strains (acute phase), associated to reduction/elimination of inflammation and fibrosis for two/eight strains. BZ offered some benefit, even in not cured animals, what suggest that BZ use may be recommended at least for recent chronic infection of the studied region.


Subject(s)
Chagas Disease/drug therapy , Nitroimidazoles/pharmacology , Parasitemia/drug therapy , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Animals , Antibodies, Protozoan/isolation & purification , Area Under Curve , Brazil , Chagas Disease/parasitology , Chagas Disease/pathology , Child , Disease Models, Animal , Drug Resistance , Enzyme-Linked Immunosorbent Assay , Female , Fibrosis , Flow Cytometry , Humans , Inflammation/drug therapy , Mice , Myocardium/pathology , Polymerase Chain Reaction , Primary Cell Culture , Remission Induction , Statistics, Nonparametric , Trypanosoma cruzi/classification , Trypanosoma cruzi/immunology , Trypanosoma cruzi/isolation & purification
10.
Mem. Inst. Oswaldo Cruz ; 110(1): 86-94, 03/02/2015. tab, graf
Article in English | LILACS | ID: lil-741617

ABSTRACT

Trypanosoma cruzi strains from distinct geographic areas show differences in drug resistance and association between parasites genetic and treatment response has been observed. Considering that benznidazole (BZ) can reduce the parasite burden and tissues damage, even in not cured animals and individuals, the goal is to assess the drug response to BZ of T. cruzi II strains isolated from children of the Jequitinhonha Valley, state of Minas Gerais, Brazil, before treatment. Mice infected and treated with BZ in both phases of infection were compared with the untreated and evaluated by fresh blood examination, haemoculture, polymerase chain reaction, conventional (ELISA) and non-conventional (FC-ALTA) serologies. In mice treated in the acute phase, a significant decrease in parasitaemia was observed for all strains. Positive parasitological and/or serological tests in animals treated during the acute and chronic (95.1-100%) phases showed that most of the strains were BZ resistant. However, beneficial effect was demonstrated because significant reduction (p < 0.05%) and/or suppression of parasitaemia was observed in mice infected with all strains (acute phase), associated to reduction/elimination of inflammation and fibrosis for two/eight strains. BZ offered some benefit, even in not cured animals, what suggest that BZ use may be recommended at least for recent chronic infection of the studied region.


Subject(s)
Humans , Drug Discovery , Industrial Waste/analysis , Nootropic Agents/isolation & purification , Plant Extracts/chemistry , Plant Shoots/chemistry , Stilbenes/isolation & purification , Vitis/chemistry , Agriculture/economics , Amyloid beta-Peptides/antagonists & inhibitors , Amyloid beta-Peptides/metabolism , Benzofurans/analysis , Benzofurans/chemistry , Benzofurans/economics , Benzofurans/isolation & purification , Chromatography, High Pressure Liquid , France , Industrial Waste/economics , Molecular Structure , Neuroprotective Agents/chemistry , Neuroprotective Agents/economics , Neuroprotective Agents/isolation & purification , Neuroprotective Agents/pharmacology , Nootropic Agents/chemistry , Nootropic Agents/economics , Nootropic Agents/pharmacology , Protein Aggregation, Pathological , Peptide Fragments/antagonists & inhibitors , Peptide Fragments/metabolism , Phenols/chemistry , Phenols/economics , Plant Extracts/economics , Protein Aggregates/drug effects , Spectrometry, Mass, Electrospray Ionization , Stereoisomerism , Stilbenes/analysis , Stilbenes/chemistry , Stilbenes/economics , Stilbenes/pharmacology
11.
Rev. Soc. Bras. Med. Trop ; 47(2): 186-192, Mar-Apr/2014. tab, graf
Article in English | LILACS | ID: lil-710358

ABSTRACT

Introduction Açucena Municipality, Rio Doce Valley, State of Minas Gerais, Brazil temporarily (2001-2005) interrupted epidemiological surveillance for Chagas disease. The objective of this work was to evaluate the Chagas Disease Control Program (CDCP) in Açucena and to offer suggestions for improving local epidemiological surveillance. Methods This study was conducted in three phases: I) a serological investigation of schoolchildren aged 5 to 15 years using an enzyme-linked immunosorbent assay (ELISA) test performed on blood collected on filter paper followed by ELISA, indirect immunofluorescence (IIF) and indirect hemaglutination (IHA) on venous blood for borderline cases and those in the gray zone of reactivity; II) vector evaluation using the data obtained by local health agents during 2006-2010; and III) examination by ELISA, IIF and IHA of serum samples from the inhabitants of houses where infected Triatoma vitticeps was found and evaluation of their knowledge about Chagas disease. Results Five individuals had inconclusive results in the ELISA screening but were seronegative for Chagas disease. The triatomine evaluation revealed the presence of three species: Triatoma vitticeps, Panstrongylus megistus and Panstrongylus diasi. Triatoma vitticeps was the most prevalent and widespread, with a higher (67%) index of Trypanosoma cruzi flagellates and evidence of colonization. Most of the inhabitants of the infested houses recognized triatomines and had basic knowledge about Chagas disease. Conclusions Although T. vitticeps is not clearly associated with Chagas disease transmission, these results highlight the importance of maintaining CDCP in endemic areas and the need for greater emphasis on epidemiological surveillance, especially in areas with important vectorial changes or that have been modified by human intervention. .


Subject(s)
Adolescent , Animals , Child , Child, Preschool , Humans , Chagas Disease/prevention & control , Insect Control , Insect Vectors/classification , Trypanosoma cruzi/immunology , Brazil/epidemiology , Chagas Disease/diagnosis , Chagas Disease/epidemiology , Enzyme-Linked Immunosorbent Assay , Fluorescent Antibody Technique, Indirect , Hemagglutination Tests , Housing , Insect Vectors/parasitology , Population Surveillance , Prevalence , Program Evaluation , Panstrongylus/classification , Panstrongylus/parasitology , Triatoma/classification , Triatoma/parasitology
12.
Mem. Inst. Oswaldo Cruz ; 108(7): 873-880, 1jan. 2013. tab, graf
Article in English | LILACS | ID: lil-696007

ABSTRACT

The etiological treatment of Chagas disease is recommended for all patients with acute or recent chronic infection, but controversies remain regarding the benefit of chemotherapy and interpretations of the parasitological cure after etiological treatment. This study compares the laboratory and clinical evaluations of Chagas disease patients who were diagnosed 13 years earlier. Fifty-eight Chagas disease patients (29 treated with benznidazole and 29 untreated) were matched at the time of treatment based on several variables. Conventional serology revealed the absence of seroconversion in all patients. However, lower serological titres were verified in the treated group, primarily among patients who had the indeterminate form of the disease. Haemoculture performed 13 years after the intervention was positive for 6.9% and 27.6% of the treated and untreated patients, respectively. Polymerase chain reaction tests were positive for 44.8% and 13.8% of the treated and untreated patients, respectively. Patients who presented with the indeterminate form of the disease at the beginning of the study exhibited less clinical progression (17.4%) compared with the untreated group (56.5%). Therefore, this global analysis revealed that etiological treatment with benznidazole may benefit patients with respect to the clinical progression of Chagas disease and the prognosis, particularly when administered to patients with the indeterminate form of the disease.


Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Young Adult , Chagas Disease/drug therapy , Nitroimidazoles/therapeutic use , Trypanocidal Agents/therapeutic use , Trypanosoma cruzi/immunology , Case-Control Studies , Chagas Disease/parasitology , Disease Progression , Polymerase Chain Reaction , Prognosis , Retrospective Studies
13.
Mem Inst Oswaldo Cruz ; 108(7): 873-80, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24037109

ABSTRACT

The etiological treatment of Chagas disease is recommended for all patients with acute or recent chronic infection, but controversies remain regarding the benefit of chemotherapy and interpretations of the parasitological cure after etiological treatment. This study compares the laboratory and clinical evaluations of Chagas disease patients who were diagnosed 13 years earlier. Fifty-eight Chagas disease patients (29 treated with benznidazole and 29 untreated) were matched at the time of treatment based on several variables. Conventional serology revealed the absence of seroconversion in all patients. However, lower serological titres were verified in the treated group, primarily among patients who had the indeterminate form of the disease. Haemoculture performed 13 years after the intervention was positive for 6.9% and 27.6% of the treated and untreated patients, respectively. Polymerase chain reaction tests were positive for 44.8% and 13.8% of the treated and untreated patients, respectively. Patients who presented with the indeterminate form of the disease at the beginning of the study exhibited less clinical progression (17.4%) compared with the untreated group (56.5%). Therefore, this global analysis revealed that etiological treatment with benznidazole may benefit patients with respect to the clinical progression of Chagas disease and the prognosis, particularly when administered to patients with the indeterminate form of the disease.


Subject(s)
Chagas Disease/drug therapy , Nitroimidazoles/therapeutic use , Trypanocidal Agents/therapeutic use , Trypanosoma cruzi/immunology , Adolescent , Adult , Case-Control Studies , Chagas Disease/parasitology , Child , Disease Progression , Female , Humans , Male , Polymerase Chain Reaction , Prognosis , Retrospective Studies , Young Adult
14.
Rev Soc Bras Med Trop ; 46(4): 433-40, 2013.
Article in English | MEDLINE | ID: mdl-23982097

ABSTRACT

INTRODUCTION: The biological diversity of Trypanosoma cruzi strains plays an important role in the clinical and epidemiological features of Chagas disease. METHODS: Eight T. cruzi strains isolated from children living in a Chagas disease vector-controlled area of Jequitinhonha Valley, State of Minas Gerais, Brazil, were genetically and biologically characterized. RESULTS: The characterizations demonstrated that all of the strains belonged to T. cruzi II, and showed high infectivity and a variable mean maximum peak of parasitemia. Six strains displayed low parasitemia, and two displayed moderate parasitemia. Later peaks of parasitemia and a predominance of intermediate and large trypomastigotes in all T. cruzi strains were observed. The mean pre-patent period was relatively short (4.2 ± 0.25 to 13.7 ± 3.08 days), whereas the patent period ranged from 3.3 ± 1.08 to 34.5 ± 3.52 days. Mortality was observed only in animals infected with strain 806 (62.5%). Histopathological analysis of the heart showed that strains 501 and 806 caused inflammation, but fibrosis was observed only in animals infected with strain 806. CONCLUSIONS: The results indicate the presence of an association between the biological behavior in mice and the genetic characteristics of the parasites. The study also confirmed general data from Brazil where T. cruzi II lineage is the most prevalent in the domiciliary cycle and generally has low virulence, with some strains capable of inducing inflammatory processes and fibrosis.


Subject(s)
Chagas Disease/parasitology , Parasitemia/parasitology , Trypanosoma cruzi/pathogenicity , Animals , Brazil , Child , DNA, Protozoan/genetics , Disease Models, Animal , Female , Genotype , Humans , Mice , Parasitemia/pathology , Trypanosoma cruzi/enzymology , Trypanosoma cruzi/genetics , Trypanosoma cruzi/isolation & purification , Virulence
15.
Rev Soc Bras Med Trop ; 45(1): 35-44, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22370826

ABSTRACT

INTRODUCTION: The goal was to develop an in-house serological method with high specificity and sensitivity for diagnosis and monitoring of Chagas disease morbidity. METHODS: With this purpose, the reactivities of anti-T. cruzi IgG and subclasses were tested in successive serum dilutions of patients from Berilo municipality, Jequitinhonha Valley, Minas Gerais, Brazil. The performance of the in-house ELISA was also evaluated in samples from other relevant infectious diseases, including HIV, hepatitis C (HCV), syphilis (SYP), visceral leishmaniasis (VL), and American tegumentary leishmaniasis (ATL), and noninfected controls (NI). Further analysis was performed to evaluate the applicability of this in-house methodology for monitoring Chagas disease morbidity into three groups of patients: indeterminate (IND), cardiac (CARD), and digestive/mixed (DIG/Mix), based on their clinical status. RESULTS: The analysis of total IgG reactivity at serum dilution 1:40 was an excellent approach to Chagas disease diagnosis (100% sensitivity and specificity). The analysis of IgG subclasses showed cross-reactivity, mainly with NI, VL, and ATL, at all selected serum dilutions. Based on the data analysis, the IND group displayed higher IgG3 levels and the DIG/Mix group presented higher levels of total IgG as compared with the IND and CARD groups. CONCLUSIONS: These findings demonstrated that methodology presents promising applicability in the analysis of anti-T. cruzi IgG reactivity for the differential diagnosis and evaluation of Chagas disease morbidity.


Subject(s)
Antibodies, Protozoan/immunology , Chagas Disease/diagnosis , Enzyme-Linked Immunosorbent Assay/methods , Immunoglobulin G/immunology , Trypanosoma cruzi/immunology , Adolescent , Adult , Antibodies, Protozoan/blood , Antigen-Antibody Reactions , Chagas Cardiomyopathy/diagnosis , Chagas Disease/complications , Diagnosis, Differential , Female , Humans , Immunoglobulin G/blood , Male , Middle Aged , Sensitivity and Specificity , Young Adult
16.
Rev. Soc. Bras. Med. Trop ; 45(1): 35-44, Jan.-Feb. 2012. ilus
Article in English | LILACS | ID: lil-614906

ABSTRACT

INTRODUCTION: The goal was to develop an in-house serological method with high specificity and sensitivity for diagnosis and monitoring of Chagas disease morbidity. METHODS: With this purpose, the reactivities of anti-T. cruzi IgG and subclasses were tested in successive serum dilutions of patients from Berilo municipality, Jequitinhonha Valley, Minas Gerais, Brazil. The performance of the in-house ELISA was also evaluated in samples from other relevant infectious diseases, including HIV, hepatitis C (HCV), syphilis (SYP), visceral leishmaniasis (VL), and American tegumentary leishmaniasis (ATL), and noninfected controls (NI). Further analysis was performed to evaluate the applicability of this in-house methodology for monitoring Chagas disease morbidity into three groups of patients: indeterminate (IND), cardiac (CARD), and digestive/mixed (DIG/Mix), based on their clinical status. RESULTS: The analysis of total IgG reactivity at serum dilution 1:40 was an excellent approach to Chagas disease diagnosis (100 percent sensitivity and specificity). The analysis of IgG subclasses showed cross-reactivity, mainly with NI, VL, and ATL, at all selected serum dilutions. Based on the data analysis, the IND group displayed higher IgG3 levels and the DIG/Mix group presented higher levels of total IgG as compared with the IND and CARD groups. CONCLUSIONS: These findings demonstrated that methodology presents promising applicability in the analysis of anti-T. cruzi IgG reactivity for the differential diagnosis and evaluation of Chagas disease morbidity.


INTRODUÇÃO: O objetivo foi desenvolver um método sorológico in-house de alta especificidade e sensibilidade para diagnosticar e monitorar a morbidade da doença de Chagas. MÉTODOS: Para tal, a reatividade sorológica de IgG e subclasses foi testada em soros de pacientes chagásicos de Berilo, Vale do Jequitinhonha/MG/Brasil. A reatividade sorológica foi também avaliada em amostras de pacientes com outras doenças infecto-contagiosas relevantes, incluindo o HIV, vírus da hepatite C (VHC), sífilis (SYP), leishmaniose visceral (LV), leishmaniose tegumentar americana (LTA) e controles não infectados (NI) para verificar o desempenho do método. Outras análises foram feitas para avaliar a aplicabilidade desta metodologia no monitoramento da morbidade da doença de Chagas. Com este propósito os pacientes com doença de Chagas foram anteriormente classificados em três grupos: indeterminados (IND), cardíacos (CARD) e digestivos/mistos (DIG/Mis) conforme seu estado clínico. RESULTADOS: A análise da reatividade sorológica de IgG total na diluição 1:40 mostrou ser uma abordagem importante no diagnóstico da doença de Chagas (100 por cento de sensibilidade e especificidade e ausência de reação cruzada com as demais infecções). A análise das subclasses de IgG mostrou reação cruzada principalmente com NI, LV e LTA em todas as diluições. O grupo IND apresentou a maior reatividade para IgG3 e o grupo DIG/Mis apresentou nível mais elevado de IgG se comparados aos grupos IND e CARD. CONCLUSÕES: Estes achados demonstram que o método de ELISA in-house apresenta uma promissora aplicabilidade no diagnóstico diferencial e na avaliação da morbidade da doença de Chagas.


Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Antibodies, Protozoan/immunology , Chagas Disease/diagnosis , Enzyme-Linked Immunosorbent Assay/methods , Immunoglobulin G/immunology , Trypanosoma cruzi/immunology , Antigen-Antibody Reactions , Antibodies, Protozoan/blood , Chagas Cardiomyopathy/diagnosis , Chagas Disease/complications , Diagnosis, Differential , Immunoglobulin G/blood , Sensitivity and Specificity
17.
Pharmacia Bras ; 12(85): 22-26, Mar.-Maio 2012. ilus
Article in Portuguese | HISA - History of Health | ID: his-27942

ABSTRACT

Quatro de abril de 1839. É criada a Escola de Farmácia de Ouro Preto, fruto das transformações que o Brasil passara a experimentar, com a vinda da Família Real para o País. A Escola foi o embrião da própria Universidade Federal de Ouro Preto (UFOP) à qual pertence. A Escola, que possui o Museu da Farmácia, desde a década de 60, ganhou nova sede. O Museu integra o circuito cultural e educativo de Ouro Preto, uma das cidades mais visitadas, no País. É uma prova do zelo da UFOP em preservar a memória farmacêutica. (AU)


Subject(s)
Pharmacy/history , Education, Pharmacy/history , Schools, Pharmacy/history , Museums/history , Public Health/history , Brazil
18.
Mem. Inst. Oswaldo Cruz ; 104(8): 1139-1147, Dec. 2009. ilus, tab
Article in English | LILACS | ID: lil-538174

ABSTRACT

Twenty-eight Chagas disease patients (CD), 22 with the indeterminate clinical form (IND) and six with the cardiac or digestive form (CARD/DIG), were treated with benznidazole and underwent clinical and laboratorial analysis before (IND and CARD/DIG) and nine years after [patients after treatment (CDt), patients with the indeterminate clinical form at treatment onset (INDt) and with the cardiac or digestive form at treatment onset (CARD/DIGt)] treatment. The data demonstrate that 82.1 percent of CDt patients (23/28) remained clinically stable and 95.4 percent of the INDt (21/22) and 33.3 percent of the CARD/DIGt (2/6) patients showed unaltered physical and laboratorial examinations. The clinical evolution rate was 2 percent/year and was especially low in INDt patients (0.5 percent/year) relative to CARD/DIGt patients (7.4 percent/year). Positive haemoculture in treated patients was observed in 7.1 percent of the cases. None of the INDt (0/21) and 33.3 percent of the CARD/DIGt (2/6) patients displayed positive cultures. The PCR presented a positive rate significantly higher (85.2 percent, 23/27) than haemoculture and two samples from the same patient revealed the same result 57.7 percent of the patients. Conventional serology-ELISA on 16 paired samples remained positive in all individuals. Semi-quantitative ELISA highlighted significant decreases in reactivity, particularly in INDt relative to IND. Non-conventional serology-FC-ALTA-IgG, after treatment, showed positive results in all sera and 22 paired samples examined at seven and nine years after treatment, demonstrated significantly lower reactivity, particularly in INDt patients. This study was retrospective in nature, had a low number of samples and lacked an intrinsic control group, but the data corroborate other results found in the literature. The data also demonstrate that, even though a cure has not been detected in the none-treated patients, the benefits for clinical evolution ...


Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Young Adult , Chagas Disease/drug therapy , Nitroimidazoles/therapeutic use , Trypanocidal Agents/therapeutic use , Trypanosoma cruzi/immunology , Antibodies, Protozoan/blood , Brazil , Chronic Disease , Chagas Cardiomyopathy/drug therapy , Chagas Cardiomyopathy/immunology , Chagas Disease/immunology , Enzyme-Linked Immunosorbent Assay , Immunoglobulin G/immunology , Treatment Outcome , Young Adult
19.
Rev. Soc. Bras. Med. Trop ; 42(6): 615-621, Dec. 2009. ilus, graf, mapas, tab
Article in English | LILACS | ID: lil-539505

ABSTRACT

This study aimed to evaluate the Chagas Disease Control Program which has operated since 1982 in the municipality of Berilo in the Jequitinhonha Valley, Minas Gerais, Brazil, based on evaluation of 5,242 domiciliary units (DUs) and 7,807 outbuildings over an eight-year period of epidemiological surveillance implanted in 1997. A total of 391 triatomines (280 Panstrongylus megistus and 111 Triatoma pseudomaculata) were captured, indicating the continued predominance of the former species. However, Triatoma pseudomaculata is clearly becoming more important in this region, with intradomiciliary colonies being detected in recent years. Entomological parameters, such as dispersion (17 percent) and intradomiciliary infestation (0.15 percent) indices, are compatible with the results of the epidemiological surveillance. The majority of DUs were of construction type A (plaster over bricks) or C (plaster over adobe). Twenty-five percent of the inhabitants of the DUs infested by triatomines were reactive in ELISA, IHA and IIF tests for Trypanosoma cruzi antigens.


O objetivo deste estudo foi avaliar o Programa de Controle de doença de Chagas instalado desde 1982 no município de Berilo, Vale do Jequitinhonha, MG, Brasil, baseado na avaliação de 5.242 unidades domiciliares e 7.807 anexos após oito anos de implantação da vigilância epidemiológica que ocorreu em 1997. Um total de 391 triatomíneos (280 Panstrongylus megistus e 111 Triatoma pseudomaculata) foram capturados, indicando o contínuo predomínio da primeira espécie. No entanto, Triatoma pseudomaculata está claramente se tornando mais importante nesta região, com colônias intradomiciliares sendo detectadas recentemente. Parâmetros entomológicos, como os índices de dispersão (17 por cento) e infestação intradomiciliar (0,15 por cento), são compatíveis com a fase de vigilância epidemiológica. A maioria das UDs apresenta padrão de construção tipo A (tijolo com reboco) e C (adobe com reboco). Dentre os habitantes das unidades domiciliares infestadas por triatomíneos, 25 por cento apresentavam testes reativos na ELISA, HAI e IFI para antígenos de Trypanosoma cruzi.


Subject(s)
Adolescent , Adult , Animals , Female , Humans , Male , Middle Aged , Young Adult , Chagas Disease/prevention & control , Insect Vectors/parasitology , Panstrongylus/parasitology , Triatoma/parasitology , Brazil/epidemiology , Chagas Disease/epidemiology , Housing , Population Surveillance , Prevalence , Program Evaluation , Trypanosoma cruzi/immunology , Young Adult
20.
Rev Soc Bras Med Trop ; 42(6): 615-21, 2009.
Article in English | MEDLINE | ID: mdl-20209342

ABSTRACT

This study aimed to evaluate the Chagas Disease Control Program which has operated since 1982 in the municipality of Berilo in the Jequitinhonha Valley, Minas Gerais, Brazil, based on evaluation of 5,242 domiciliary units (DUs) and 7,807 outbuildings over an eight-year period of epidemiological surveillance implanted in 1997. A total of 391 triatomines (280 Panstrongylus megistus and 111 Triatoma pseudomaculata) were captured, indicating the continued predominance of the former species. However, Triatoma pseudomaculata is clearly becoming more important in this region, with intradomiciliary colonies being detected in recent years. Entomological parameters, such as dispersion (17%) and intradomiciliary infestation (0.15%) indices, are compatible with the results of the epidemiological surveillance. The majority of DUs were of construction type A (plaster over bricks) or C (plaster over adobe). Twenty-five percent of the inhabitants of the DUs infested by triatomines were reactive in ELISA, IHA and IIF tests for Trypanosoma cruzi antigens.


Subject(s)
Chagas Disease/prevention & control , Insect Vectors/parasitology , Panstrongylus/parasitology , Triatoma/parasitology , Adolescent , Adult , Animals , Brazil/epidemiology , Chagas Disease/epidemiology , Female , Housing , Humans , Male , Middle Aged , Population Surveillance , Prevalence , Program Evaluation , Trypanosoma cruzi/immunology , Young Adult
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