Immunological Identification of Trypanosoma cruzi Lineages in Human Infection Along the Endemic Area

Risso, Marikena Guadalupe; Sartor, Paula; Burgos, Juan Miguel; Briceño, Luis; Rodríguez, Eva M.; Guhl, Felipe; Triana-Chávez, Omar; Espinoza, Bertha; Monteón, Vı́ctor; Russomando, Graciela; Schijman, Alejandro G.; Bottasso, Óscar; Leguizamón, María Susana

doi:10.4269/ajtmh.2011.10-0177

Cited by 32 publications

(29 citation statements)

References 51 publications

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“…In Mexico, most T. cruzi strains have been genetically determined to belong to TcI (Bosseno et al 2002, Leó n-Pérez et al 2007, Gó mez-Hernández et al 2011 and TcII-TcVI strains have been reported only in a recent serological study, in wild mammals and the feces of vectors (Ló pez-Olmos et al 1998, Bosseno et al 2009, Risso et al 2011. In this work, we confirmed that the Mexican T. cruzi strains isolated from humans belonged to TcI, as reported in Guatemala, Colombia, and Venezuela (Añ ez et al 2004, Ruíz-Sánchez et al 2005, Falla et al 2009).…”

Section: Discussionsupporting

confidence: 86%

Microsatellite and Mini-Exon Analysis of Mexican Human DTU ITrypanosoma cruziStrains and Their Susceptibility to Nifurtimox and Benznidazole

Martı́nez

Nogueda

Martínez‐Hernández

et al. 2013

Vector-Borne and Zoonotic Diseases

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Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, and it affects as many as 10 million people in North and South America, where it represents a major public health problem. T. cruzi is a parasite with high genetic diversity, and it has been grouped into 6 discrete typing units (DTUs), designated as T. cruzi I (TcI) to T. cruzi VI (TcVI). Mexican isolates from humans and from vector insects have been primarily found to be TcI, and these isolates are likely to be the strains that cause the clinical manifestations observed in Mexico. However, genetic characterization and drug susceptibility assays are limited in Mexican TcI strains. In this work, 24 Mexican T. cruzi strains, obtained primarily from humans, were studied with 7 locus microsatellites and mini-exon gene by PCR. Also, drug susceptibility was evaluated by growth and mobility assays. All of the human strains belonged to TcI, and they could be further grouped through microsatellite analysis into 2 subgroups (microsatellite genotypes 1 and 2), which were not related to the host clinical status or biological origin of the strain. Two strains, both from wild mammals, belonged to the TcII-TcVI groups; these strains and the CL Brener strain constituted microsatellite genotype 3. The number of alleles in each locus was lower than reported for South American strains, and a departure from the Hardy-Weinberg equilibrium was observed. The susceptibility of these strains to nifurtimox and benznidazole was heterogeneous. T. cruzi strains characterized as microsatellite genotypes 2 and 3 were significantly more susceptible to benznidazole than strains of microsatellite genotype 1. Only 1 Mexican strain resistant to both drugs was found in this study.

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Section: Discussionsupporting

confidence: 86%

Microsatellite and Mini-Exon Analysis of Mexican Human DTU ITrypanosoma cruziStrains and Their Susceptibility to Nifurtimox and Benznidazole

Martı́nez

Nogueda

Martínez‐Hernández

et al. 2013

Vector-Borne and Zoonotic Diseases

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“…As previously shown (11), when used under more stringent conditions, a minimal fraction of Chagas-negative serum samples from patients affected by autoimmune and/or other endemic coinfection diseases reacted against bacterium-derived contaminants and/or the GST motif in TSSA-CL . On the other hand, p30-50 may contribute to improve the robustness of TSSA-based serologic methods in molecular epidemiology studies (17,18). The use of a more defined reagent lacking most of the sequences conserved across TSSA isoforms (14) may diminish its level of cross-recognition by antibodies elicited toward a different TSSA isoform.…”

Section: Discussionmentioning

confidence: 99%

“…Interstrain polymorphisms were shown to be focused on the central region of TSSA (12,14) and to have a major impact on its immunogenicity and antigenicity (11,12,16). Different attempts at using TSSA polymorphisms to design parasite lineage-specific serologic reagents as an indirect approach to allow for the typification of infecting T. cruzi strains have been undertaken (17,18). Although these methods can be improved, they showed good concordance with genotyping techniques (17) and support the differential predominance of T. cruzi lineages causing human infections in distinct areas that are endemic for the parasite (13,19,20).…”

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confidence: 99%

Mapping Antigenic Motifs in the Trypomastigote Small Surface Antigen from Trypanosoma cruzi

Balouz

Camara

Canepa

et al. 2015

Clin. Vaccine Immunol.

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The trypomastigote small surface antigen (TSSA) is a mucin-like molecule from Trypanosoma cruzi, the etiological agent of Chagas disease, which displays amino acid polymorphisms in parasite isolates. TSSA expression is restricted to the surface of infective cell-derived trypomastigotes, where it functions as an adhesin and engages surface receptors on the host cell as a prerequisite for parasite internalization. Previous results have established TSSA-CL, the isoform encoded by the CL Brener clone, as an appealing candidate for use in serology-based diagnostics for Chagas disease. Here, we used a combination of peptide-and recombinant protein-based tools to map the antigenic structure of TSSA-CL at maximal resolution. Our results indicate the presence of different partially overlapping B-cell epitopes clustering in the central portion of TSSA-CL, which contains most of the polymorphisms found in parasite isolates. Based on these results, we assessed the serodiagnostic performance of a 21-amino-acidlong peptide that spans TSSA-CL major antigenic determinants, which was similar to the performance of the previously validated glutathione S-transferase (GST)-TSSA-CL fusion molecule. Furthermore, the tools developed for the antigenic characterization of the TSSA antigen were also used to explore other potential diagnostic applications of the anti-TSSA humoral response in Chagasic patients. Overall, our present results provide additional insights into the antigenic structure of TSSA-CL and support this molecule as an excellent target for molecular intervention in Chagas disease. Chagas disease is a major health and economic problem in Latin America, for which no vaccine or appropriate drugs for largescale public health interventions are yet available (1). It is caused by the protozoan Trypanosoma cruzi, found throughout the American continents in a variety of wild and domestic mammalian reservoirs, and it is transmitted by the bite of infected bloodsucking triatomine bugs. It is estimated that 8 to 10 million people are currently infected with T. cruzi and that up to 120 million individuals living in areas that are endemic for the parasite are at risk of infection (1). Increasing travel and immigration have also brought the risk of T. cruzi infection into countries that are not endemic for the parasite (2). Several efforts have successfully been undertaken to control transmission in Latin America, with a concomitant decrease in the actual numbers of acute vector-borne infections (3). However, humans can also become infected with T. cruzi through the ingestion of tainted food and fluids, receipt of contaminated blood transfusion or organ transplantation, and from mother-to-child during pregnancy/delivery (4).The diagnosis of Chagas disease is challenging because it is often asymptomatic in its acute phase and evolves into a chronic stage in which the disease course takes different clinical forms (1). In addition, and due to a major decline in parasitemia during the chronic phase, the detection of T. cruzi in blood sample...

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“…The choice was based on previous results in which the TSSA isoform from DTU TcVI parasite stocks displayed a high reactivity with human infection sera from Southern Cone countries (15). Although the spectra of circulating parasite stocks, and therefore of their expressed TSSA isoforms, seem to vary in different areas of endemicity, a high frequency of TSSA VI recognition, as assessed by Western blotting, was also recently observed in patients with chronic Chagas' disease from Colombia, Venezuela, and Mexico (29). By using a much larger and more comprehensive serum panel, we estimated the overall sensitivity of GST-TSSA VI as 86.9% (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a Recombinant Trypanosoma cruzi Mucin-Like Antigen for Serodiagnosis of Chagas' Disease

Marchi

Noia

Frasch

et al. 2011

Clin Vaccine Immunol

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Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and is one of the most important endemic problems in Latin America. Lately, it has also become a health concern in the United States and Europe. Currently, a diagnosis of Chagas' disease and the screening of blood supplies for antiparasite antibodies are achieved by conventional serological tests that show substantial variation in the reproducibility and reliability of their results. In addition, the specificity of these assays is curtailed by antigenic crossreactivity with sera from patients affected by other endemic diseases, such as leishmaniasis. Here we used a highly sensitive chemiluminescent enzyme-linked immunosorbent assay (CL-ELISA) to evaluate a recombinant protein core of a mucin-like molecule (termed trypomastigote small surface antigen [TSSA]) for the detection of specific serum antibodies in a broad panel of human sera. The same samples were evaluated by CL-ELISA using as the antigen either a mixture of native T. cruzi trypomastigote mucins or an epimastigote extract and, for further comparison, by conventional serologic tests, such as an indirect hemagglutination assay and indirect immunofluorescence assay. TSSA showed ϳ87% sensitivity among the seropositive Chagasic panel, a value which was increased up to >98% when only parasitologically positive samples were considered. More importantly, TSSA showed a significant increase in specificity (97.4%) compared to those of currently used assays, which averaged 80 to 90%. Overall, our data demonstrate that recombinant TSSA may be a useful antigen for the immunodiagnosis of Chagas' disease.

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Immunological Identification of Trypanosoma cruzi Lineages in Human Infection Along the Endemic Area

Cited by 32 publications

References 51 publications

Microsatellite and Mini-Exon Analysis of Mexican Human DTU ITrypanosoma cruziStrains and Their Susceptibility to Nifurtimox and Benznidazole

Microsatellite and Mini-Exon Analysis of Mexican Human DTU ITrypanosoma cruziStrains and Their Susceptibility to Nifurtimox and Benznidazole

Mapping Antigenic Motifs in the Trypomastigote Small Surface Antigen from Trypanosoma cruzi

Evaluation of a Recombinant Trypanosoma cruzi Mucin-Like Antigen for Serodiagnosis of Chagas' Disease

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