Lineage-specific rapid diagnostic tests can resolve Trypanosoma cruzi TcII/V/VI ecological and epidemiological associations in the Argentine Chaco

Abstract Background Trypanosoma cruzi, the protozoan agent of Chagas disease, is comprised of at least 6 genetic lineages (TcI-TcVI). Their geographical distribution, clinical associations and reservoir hosts are not fully elucidated, as genotyping is hampered due to the difficulty in isolating representative populations of organisms. Lineage-specific serological techniques may address these issues. Methods Trypanosoma cruzi lineage-specific serological assays were performed on human, canine, feline and armadillo sera from the Gran Chaco in northern Argentina, a region of ongoing transmission. Synthetic peptides representing lineage-specific epitopes of the trypomastigote small surface antigen (TSSA) were used in ELISA, and the TcII/V/VI shared epitope peptide (TSSApep-II/V/VI) was used in the Chagas Sero K-SeT rapid diagnostic test (RDT). Results Chagas Sero K-SeT RDT, using Protein G to detect human and canine IgG, was at least as sensitive as TSSApep-II/V/VI ELISA using specific secondary antibodies. For sera from humans TSSApep-II/V/VI seroprevalence by Chagas Sero K-SeT was 273/393 (69.5%), for dogs 48/73 (65.8%) and for armadillos 1/7 (14.3%); by ELISA for cats 5/19 (26.3%). The seroprevalence for humans was similar to that for Bolivian patients, amongst whom we previously observed an association of TSSApep-II/V/VI seropositivity with severity of cardiomyopathy. In humans, prevalence of TSSApep-II/V/VI recognition was associated with locality, and with increasing and decreasing age within the Qom and Creole populations, respectively. For dogs TSSApep-II/V/VI recognition was associated with being born before community-wide insecticide spraying (P = 0.05) and with Qom household (P < 0.001). Conclusions We show here that Chagas Sero K-SeT RDT can replace ELISA for TSSApep-II/V/VI serology of humans and dogs; for humans there were statistically significant associations between a positive Chagas Sero K-SeT RDT and being resident in Area IV, and for dogs association with Qom household or with being born before the mass spraying campaign; we also show that with cats the TcII/V/VI epitope can be detected by ELISA. We assessed the lineage distribution in an unprecedented 83% of the human T. cruzi-seropositive population. These results form the basis for more detailed studies, enabling rapid in-the-field surveillance of the distribution and clustering of these lineages among humans and mammalian reservoirs of T. cruzi infection.

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Glycosylation of Trypanosoma cruzi TcI antigen reveals recognition by chagasic sera

Scientific Reports ◽

10.1038/s41598-020-73390-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Niamh Murphy ◽

Barrie Rooney ◽

Tapan Bhattacharyya ◽

Omar Triana-Chavez ◽

Anja Krueger ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Periodate Oxidation ◽

Heat Denaturation ◽

Parasitic Disease ◽

Small Surface ◽

Genetic Lineages ◽

Gastrointestinal Pathology ◽

Endemic Malaria ◽

Clinical Presentations ◽

Host Tissues

Abstract Chagas disease is considered the most important parasitic disease in Latin America. The protozoan agent, Trypanosoma cruzi, comprises six genetic lineages, TcI-TcVI. Genotyping to link lineage(s) to severity of cardiomyopathy and gastrointestinal pathology is impeded by the sequestration and replication of T. cruzi in host tissues. We describe serology specific for TcI, the predominant lineage north of the Amazon, based on expression of recombinant trypomastigote small surface antigen (gTSSA-I) in the eukaryote Leishmania tarentolae, to allow realistic glycosylation and structure of the antigen. Sera from TcI-endemic regions recognised gTSSA-I (74/146; 50.7%), with no cross reaction with common components of gTSSA-II/V/VI recombinant antigen. Antigenicity was abolished by chemical (periodate) oxidation of gTSSA-I glycosylation but retained after heat-denaturation of conformation. Conversely, non-specific recognition of gTSSA-I by non-endemic malaria sera was abolished by heat-denaturation. TcI-specific serology facilitates investigation between lineage and diverse clinical presentations. Glycosylation cannot be ignored in the search for immunogenic antigens.

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A Trypanosoma cruzi Small Surface Molecule Provides the First Immunological Evidence that Chagas' Disease Is Due to a Single Parasite Lineage

Journal of Experimental Medicine ◽

10.1084/jem.20011433 ◽

2002 ◽

Vol 195 (4) ◽

pp. 401-413 ◽

Cited By ~ 108

Author(s):

Javier M. Di Noia ◽

Carlos A. Buscaglia ◽

Claudia R. De Marchi ◽

Igor C. Almeida ◽

Alberto C.C. Frasch

Keyword(s):

Trypanosoma Cruzi ◽

Chagas Disease ◽

Cross Reactivity ◽

Economic Problem ◽

Future Research ◽

Biological Traits ◽

Small Surface ◽

Genetic Lineages ◽

Human Infections ◽

Glycosylphosphatidyl Inositol

Chagas' disease is a major health and economic problem caused by the protozoan Trypanosoma cruzi. Multiple independently evolving clones define a complex parasite population that can be arranged into two broad genetic lineages termed T. cruzi I and II. These lineages have different evolutionary origin and display distinct ecological and biological traits. Here we describe a novel molecule termed TSSA for trypomastigote small surface antigen that provides the first immunological marker allowing discrimination between lineages. TSSA is a surface, glycosylphosphatidyl inositol (GPI)-anchored mucin-like protein, highly antigenic during the infection. TSSA sequences from different parasite isolates reveal a population dimorphism that perfectly matches with the two T. cruzi lineages. Interestingly, this dimorphism is restricted to the central region of the molecule, which comprises the immunodominant B cell epitopes. This sequence variability has a major impact on TSSA antigenicity, leading to no immunological cross-reactivity between both isoforms for antibodies present either in immunization or infection sera. Furthermore, the absolute seroprevalence for TSSA in confirmed Chagasic patients is restricted to T. cruzi II isoform, strongly suggesting that human infections are due to this particular subgroup. Even though association of T. cruzi II with Chagas' disease has been proposed based on molecular markers, this is the first immunological evidence supporting this hypothesis. The implications of these results for the future research on Chagas' disease could be envisaged.

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Chapter 11: General epidemiology of TBE

Tick-borne encephalitis - The Book ◽

10.33442/26613980_11-3 ◽

2020 ◽

Keyword(s):

Eastern Siberia ◽

Genetic Lineages ◽

Phylogenetic Studies ◽

Tick Borne Encephalitis ◽

Natural Foci ◽

Genetic Sequences ◽

Tick Borne Encephalitis Virus ◽

Almost All ◽

Far Eastern ◽

Reservoir Hosts

Tick-borne encephalitis virus (TBEV) exists in natural foci, which are areas where TBEV is circulating among its vectors (ticks of different species and genera) and reservoir hosts (usually rodents and small mammals). Based on phylogenetic studies, four TBEV subtypes (Far-Eastern, Siberian, European, Baikalian) and two putative subtypes (Himalayan and “178-79” group) are known. Within each subtype, some genetic lineages are described. The European subtype (TBEV-EU) (formerly known also as the “Western subtype”) of TBEV is prevalent in Europe, but it was also isolated in Western and Eastern Siberia in Russia and South Korea. The Far-Eastern subtype (TBEV-FE) was preferably found in the territory of the far-eastern part of Eurasia, but some strains were isolated in other regions of Eurasia. The Siberian (TBEV-SIB) subtype is the most common and has been found in almost all TBEV habitat areas. The Baikalian subtype is prevalent around Lake Baikal and was isolated several times from ticks and rodents. In addition to the four TBEV subtypes, one single isolate of TBEV (178-79) and two genetic sequences (Himalayan) supposed to be new TBEV subtypes were described in Eastern Siberia and China. The data on TBEV seroprevalence in humans and animals can serve as an indication for the presence or absence of TBEV in studied area.

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Chagas' disease in the Brazilian Amazon: I - a short review

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46651994000400009 ◽

1994 ◽

Vol 36 (4) ◽

pp. 363-368 ◽

Cited By ~ 27

Author(s):

José Rodrigues Coura ◽

Angela Cristina Verissimo Junqueira ◽

Cristina Maria Giordano ◽

Ilra Renata Komoda Funatsu

Keyword(s):

Trypanosoma Cruzi ◽

Chagas Disease ◽

Human Population ◽

Brazilian Amazon ◽

Short Review ◽

Ecological Balance ◽

Domestic Cycle ◽

Endemic Areas ◽

Reservoir Hosts

At least eighteen species of triatominae have been found in the Brazilian Amazon, nine of them naturally infected with Trypanosoma cruzi or "cruzi-like" trypanosomes and associated with numerous wild reservoirs. Despite the small number of human cases of Chagas' disease described to date in the Brazilian Amazon the risk that the disease will become endemic in this area is increasing for the following reasons: a) uncontrolled deforestation and colonization altering the ecological balance between reservoir hosts and wild vectors; b) the adaptation of reservoir hosts of T.cruzi and wild vectors to peripheral and intradomiciliary areas, as the sole feeding alternative; c) migration of infected human population from endemic areas, accompanied by domestic reservoir hosts (dogs and cats) or accidentally carrying in their baggage vectors already adapted to the domestic habitat. In short, risks that Chagas' disease will become endemic to the Amazon appear to be linked to the transposition of the wild cycle to the domestic cycle in that area or to transfer of the domestic cycle from endemic areas to the Amazon.

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A lineage-specific rapid diagnostic test (Chagas Sero K-SeT) identifies Brazilian Trypanosoma cruzi II/V/VI reservoir hosts among diverse mammalian orders

PLoS ONE ◽

10.1371/journal.pone.0227828 ◽

2020 ◽

Vol 15 (1) ◽

pp. e0227828 ◽

Cited By ~ 1

Author(s):

Mairi C. W. McClean ◽

Tapan Bhattacharyya ◽

Pascal Mertens ◽

Niamh Murphy ◽

Quentin Gilleman ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Diagnostic Test ◽

Rapid Diagnostic Test ◽

Reservoir Hosts

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Extracellular Trap Formation in Response to Trypanosoma cruzi Infection in Granulocytes Isolated From Dogs and Common Opossums, Natural Reservoir Hosts

Frontiers in Microbiology ◽

10.3389/fmicb.2018.00966 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 10

Author(s):

Nicole de Buhr ◽

Marta C. Bonilla ◽

Mauricio Jimenez-Soto ◽

Maren von Köckritz-Blickwede ◽

Gaby Dolz

Keyword(s):

Trypanosoma Cruzi ◽

Natural Reservoir ◽

Trap Formation ◽

Extracellular Trap ◽

Reservoir Hosts ◽

Cruzi Infection

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Trypanosoma cruzi transmission in the wild and its most important reservoir hosts in Brazil

Parasites & Vectors ◽

10.1186/s13071-018-3067-2 ◽

2018 ◽

Vol 11 (1) ◽

Cited By ~ 29

Author(s):

Ana Maria Jansen ◽

Samanta Cristina das Chagas Xavier ◽

André Luiz Rodrigues Roque

Keyword(s):

Trypanosoma Cruzi ◽

In The Wild ◽

Reservoir Hosts

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The Trypomastigote Small Surface Antigen from Trypanosoma cruzi Improves Treatment Evaluation and Diagnosis in Pediatric Chagas Disease

Journal of Clinical Microbiology ◽

10.1128/jcm.01317-17 ◽

2017 ◽

Vol 55 (12) ◽

pp. 3444-3453 ◽

Cited By ~ 8

Author(s):

Virginia Balouz ◽

Luciano J. Melli ◽

Romina Volcovich ◽

Guillermo Moscatelli ◽

Samanta Moroni ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Chagas Disease ◽

Surface Antigen ◽

Rapid Assessment ◽

Drug Efficacy ◽

Enzyme Linked Immunosorbent Assay ◽

Serological Tests ◽

Small Surface ◽

Content Type

ABSTRACTChagas disease is caused by the protozoan parasiteTrypanosoma cruzi. Assessment of parasitological cure upon treatment with available drugs relies on achieving consistent negative results in conventional parasitological and serological tests, which may take years to assess. Here, we evaluated the use of a recombinantT. cruziantigen termed trypomastigote small surface antigen (TSSA) as an early serological marker of drug efficacy inT. cruzi-infected children. A cohort of 78 pediatric patients born toT. cruzi-infected mothers was included in this study. Only 39 of the children were infected withT. cruzi, and they were immediately treated with trypanocidal drugs. Serological responses against TSSA were evaluated in infected and noninfected populations during the follow-up period using an in-house enzyme-linked immunosorbent assay (ELISA) and compared to conventional serological methods. Anti-TSSA antibody titers decreased significantly faster than anti-whole parasite antibodies detected by conventional serology both inT. cruzi-infected patients undergoing effective treatment and in those not infected. The differential kinetics allowed a significant reduction in the required follow-up periods to evaluate therapeutic responses or to rule out maternal-fetal transmission. Finally, we present the case of a congenitally infected patient with an atypical course in whom TSSA provided an early marker forT. cruziinfection. In conclusion, we showed that TSSA was efficacious both for rapid assessment of treatment efficiency and for early negative diagnosis in infants at risk of congenitalT. cruziinfection. Based upon these findings we propose the inclusion of TSSA for refining the posttherapeutic cure criterion and other diagnostic needs in pediatric Chagas disease.

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