Benznidazole: Hero or villain of cellular immune response in chronic Chagas disease patients?

Although the treatment of chronic Chagas disease (CCD) patients with Benznidazole (Bz) is still controversial, its use may prevent or delay the progression of the disease to the most severe forms. One of the main factors that can influence the effectiveness of the treatment is the possible cooperation between drug effect and the host immune response. Herein, we evaluated the immune response of peripheral blood mononuclear cells (PBMCs) infected with Trypanosoma cruzi and submitted to Bz treatment.

Acute Chagas disease in Brazil from 2001 to 2018: A nationwide spatiotemporal analysis.

Background: In Brazil, acute Chagas disease (ACD) surveillance involves mandatory notification, which allows for population-based epidemiological studies. We conducted a nationwide population-based ecological analysis of the spatiotemporal patterns of ACD notifications in Brazil using secondary surveillance data obtained from the Notifiable Diseases Information System (SINAN) maintained by Brazilian Ministry of Health.

Methodology/principal Findings: In this nationwide population-based ecological all cases of ACD reported in Brazil between 2001 and 2018 were included.

Performance of recombinant chimeric proteins in the serological diagnosis of Trypanosoma cruzi infection in dogs.

Background: Dogs are considered sentinels in areas of Trypanosoma cruzi transmission risk to humans. ELISA is generally the method of choice for diagnosing T. cruzi exposure in dogs, but its performance substantially depends on the antigenic matrix employed.

Cross-Reactivity Using Chimeric Trypanosoma cruzi Antigens: Diagnostic Performance in Settings Where Chagas Disease and American Cutaneous or Visceral Leishmaniasis Are Coendemic.

Chimeric antigens have been proposed as a diagnostic tool for chronic Chagas disease (CD) in both settings where Chagas disease is endemic and those where it is not endemic. Antibody response varies in accordance to each strain, presenting challenges to the use of antigens lacking demonstrated cross-reactivity with spp. Our group expressed four chimeric proteins (IBMP-8.

Immune reactivity to Trypanosoma cruzi chimeric proteins for Chagas disease diagnosis in immigrants living in a non-endemic setting.

Background: Chronic Chagas Disease (CD) diagnosis is based on serological methods employing crude, semipurified or recombinant antigens, which may result in low sensitivity or cross-reactivity. To reduce these restrictions, we developed a strategy involving use of molecules containing repetitive fragments of Trypanosoma cruzi conserved proteins. Diagnostic performance of IBMP-8.

Highly Accurate Chimeric Proteins for the Serological Diagnosis of Chronic Chagas Disease: A Latent Class Analysis.

The existence of an imperfect reference standard presents complications when evaluating the unbiased performance of novel diagnostic techniques. This is especially true in the absence of a gold standard, as is the case in chronic Chagas disease (CD) diagnosis. To circumvent this constraint, we elected to use latent class analysis (LCA).

Binding capacity of mannose-binding lectin (MBL) is associated with the severity of chronic Chagas cardiomyopathy.

Chagas disease (CD) is a global problem. Currently, it affects approximately 15 million individuals in Latin America. It is well know that the human immune response is related to different clinical manifestations.

Genetic susceptibility to chronic Chagas disease: an overview of single nucleotide polymorphisms of cytokine genes.

Chagas disease is a parasitic infection that is a significant public health problem in Latin America. The mechanisms responsible for susceptibility to the infection and the mechanisms involved in the development of cardiac and digestive forms of chronic Chagas disease remain poorly understood. However, there is growing evidence that differences in susceptibility in endemic areas may be attributable to host genetic factors.

Characterization of novel Leishmania infantum recombinant proteins encoded by genes from five families with distinct capacities for serodiagnosis of canine and human visceral leishmaniasis.

To expand the available panel of recombinant proteins that can be useful for identifying Leishmania-infected dogs and for diagnosing human visceral leishmaniasis (VL), we selected recombinant antigens from L. infantum, cDNA, and genomic libraries by using pools of serum samples from infected dogs and humans. The selected DNA fragments encoded homologs of a cytoplasmic heat-shock protein 70, a kinesin, a polyubiquitin, and two novel hypothetical proteins.

Immunoglobulin M antibodies against CRA and FRA recombinant antigens of Trypanosoma cruzi in chronic chagasic patients.

Previous works of our research group have demonstrated aspects of the humoral immune response of chronic Chagas disease using the cytoplasmatic repetitive antigen (CRA) and the flagellar repetitive antigen (FRA) of Trypanosoma cruzi. The aim of this work was to analyze the presence of specific immunoglobulin M (IgM) antibodies in chronic chagasic patients using these recombinant antigens of T. cruzi.

Increased levels of IgA antibodies against CRA and FRA recombinant antigens of Trypanosoma cruzi differentiate digestive forms of Chagas disease.

In the chronic phase of Chagas disease, individuals infected by Trypanosoma cruzi may be asymptomatic or may present cardiac and/or digestive complications. Our aim here was to analyze the relationship between the presence of specific immunoglobulin A antibodies and the different chronic clinical forms of Chagas disease using two recombinant antigens of Trypanosoma cruzi, cytoplasmatic repetitive antigen and flagellar repetitive antigen. The association of this immunoglobulin isotype with the digestive and cardio-digestive forms of the disease determined by indirect enzyme-linked immunosorbent assay, strongly suggests that IgA antibodies against these recombinant antigens of T.

Diagnosis of Chagas disease: what has been achieved? What remains to be done with regard to diagnosis and follow up studies?

In the acute phase and in the chronic forms of Chagas disease, the etiological diagnosis may be performed by detection of the parasite using direct or indirect parasitological methods and by the presence of antibodies in the serum by way of serological tests. Several techniques are easily available, ranging from the simplest wet smear preparation to immuno-enzymatic assays with recombinant antigens that will meet most diagnostic needs. Other tests under evaluation include a molecular test using polymerase chain reaction, which has shown promising results and may be used as a confirmatory test both in the acute and chronic phases of the disease.

Cellular immune response from Chagasic patients to CRA or FRA recombinant antigens of Trypanosoma cruzi.

We propose to analyze the relation between the cellular immune response of Chagas' disease patients after in vitro stimulation of peripheral blood mononuclear cells (PBMC) with recombinant antigens cytoplasmatic repetitive antigen (CRA) or flagellar repetitive antigen (FRA) of T. cruzi and the chronic clinical forms of disease. Cells were stimulated using phytohemagglutinin, CRA, FRA, or a soluble antigen of Epimastigota (Ag-Epi) for 24 hr, 72 hr, or 6 days.

[Family screening for HBB*S gene and detection of new cases of sickle cell trait in Northeastern Brazil].

Objective: To estimate the additional number of affected individuals based on the prevalence of sickle-cell syndromes among relatives of index cases.

Methods: Cross-sectional study of relatives of a random sample of index cases identified through a neonatal screening program in Northeastern Brazil, between 2001 and 2005. The extended family trial model included 463 relatives of 21 index cases.

Molecular variations linked to the grouping of beta- and alpha-globin genes in neonatal patients with sickle cell disease in the State of Pernambuco, Brazil.

Various factors have been described as phenotypic modulators of sickle cell disease, such as levels of fetal hemoglobin (Hb F), presence of alpha-thalassemia (thal), and haplotypes of the beta-globin genes. In order to characterize and determine the frequency of the betaS and betaC mutations and the prevalence of -alpha3.7-thal, 74 patients with sickle cell disease detected during neonatal screening in the State of Pernambuco, Brazil, were studied.

Humoral and cellular immune responses in BALB/c and C57BL/6 mice immunized with cytoplasmic (CRA) and flagellar (FRA) recombinant repetitive antigens, in acute experimental Trypanosoma cruzi infection.

In previous studies, cytoplasmic repetitive antigen (CRA) and flagellar repetitive antigen (FRA) proteins induced specific humoral and cellular immune responses in susceptible and resistant mice in the absence of Trypanosoma cruzi infection with a significant induction of the Interferon-gamma (IFN-gamma) production in those animals. In this follow-up paper, the immunostimulatory and protective effects of these proteins were evaluated by immunizing with CRA or FRA antigens, BALB/c and C57BL/6 mice and challenging with a T. cruzi (Y strain).

Elevated concentrations of CCL2 and tumor necrosis factor-alpha in chagasic cardiomyopathy.

Chronic myocarditis is the main pathological finding associated with Chagas disease-related morbidity. Concentrations of CCL2, CCL3, tumor necrosis factor (TNF)-alpha, and brain natriuretic peptide (BNP) were evaluated in plasma samples obtained from patients with different clinical forms of chronic chagasic cardiomyopathy. Patients with more-severe Chagas disease had elevated plasma concentrations of TNF-alpha, CCL2, and BNP, and there was a good correlation between levels of these proteins (especially TNF-alpha ) and the degree of heart dysfunction.

Mitogenic activity of Cratylia mollis lectin on human lymphocytes.

The mitogenic effect of Cratylia mollis seed lectin preparations containing two (Cramoll 1,4) or one molecular form (Cramoll 1) showed activity similar to the well known T-cell mitogen, concanavalin A (Con A). The effect on human lymphocytes was analyzed through a colorimetric assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). Inhibition of lymphocyte proliferation with methyl-alpha-d-mannoside (both preparations) indicated that the mitogenic effect involved carbohydrate lectin binding sites.

Antibody isotype responses in Balb/c mice immunized with the cytoplasmic repetitive antigen and flagellar repetitive antigen of Trypanosoma cruzi.

In the present report we analyzed the levels of IgG1, IgG2a, IgG2b and IgG3 isotypes from Balb/c mice immunized with cytoplasmic repetitive antigen (CRA), and flagellar repetitive antigen (FRA) of Trypanosoma cruzi. The immunization was done by subcutaneous route three times (20 days apart) and the analysis was performed 14 days after each treatment. CRA-immunized mice produced high levels of all IgG isotypes, mainly IgG3 and IgG1.

Impedimetric evaluation for diagnosis of Chagas' disease: antigen-antibody interactions on metallic electrodes.

A polypeptide chain formed by recombinant antigens, cytoplasmic repetitive antigen (CRA) and flagellar repetitive antigen (FRA) (CF-Chimera) of Trypanosoma cruzi, was adsorbed on gold and platinum electrodes and investigated by electrochemical impedance spectroscopy on phosphate buffer saline solutions (PBS) containing a redox couple. It was found that the adsorption is strongly sensitive to the oxide layer on the electrode surface. In the majority of the experiments the antigens retained their activity as observed through their interaction with sera from chronic chagasic patients.

Antibody isotype responses to egg antigens in human chronic Schistosomiasis mansoni before and after treatment.

In the present communication we analyzed the levels of IgG1, IgG2, IgG3, IgG4 and IgE isotypes to soluble egg antigen of Schistosoma mansoni by ELISA in individuals from an endemic area for schistosomiasis in Northeast Brazil. The analysis was performed before and after treatment to evaluate the age-dependent pattern, and to identify differences in the reactivities to antigens. Our results suggest that schistosomiasis treatment would not interfere with this sort of immune response.

Use of the EIE-recombinant-Chagas-biomanguinhos kit to monitor cure of human Chagas' disease.

We used the EIE-Recombinant-Chagas-Biomanguinhos kit (EIE-Rec kit) developed by the Oswaldo Cruz Foundation, Brazil, to monitor cure of chagasic patients who were treated during the acute phase of T. cruzi infection. Treated patients were previously studied by parasitological and serological tests and classified as cured patients (CP) (n = 10), dissociated patients (DP) (n = 6), and noncured patients (NCP) (n = 6).