Regional Variation in the Correlation of Antibody and T-Cell Responses to Trypanosoma cruzi

Martin, Diana L.; Marks, Morgan; Galdos-Cardenas, Gerson; Gilman, Robert H.; Goodhew, Brook; Ferrufino, Lisbeth; Halperin, Anthony; Sánchez, Gerardo; Verástegui, Manuela; Escalante, Patricia; Náquira, César; Levy, Michael Z.; Bern, Caryn

doi:10.4269/ajtmh.13-0391

Cited by 20 publications

(21 citation statements)

References 33 publications

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“…Similarly, low sensitivities of recombinant antigen ELISA and rapid tests have also been reported from Panama [262,263] and Mexico [264] . No clear correlation between serodiagnostic test reactivity and local T. cruzi DTU has been observed; instead, these discrepancies may reflect weaker adaptive immune responses to parasite antigens between endemic populations [265] .…”

Section: T Cruzi Lineage In Chagas Disease Diagnostics and mentioning

confidence: 97%

Between a bug and a hard place:Trypanosoma cruzigenetic diversity and the clinical outcomes of Chagas disease

Messenger

Miles

Bern

2015

Expert Review of Anti-infective Therapy

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Over the last 30 years, concomitant with successful transnational disease control programs across Latin America, Chagas disease has expanded from a neglected, endemic parasitic infection of the rural poor to an urbanized chronic disease, and now a potentially emergent global health problem. Trypanosoma cruzi infection has a highly variable clinical course, ranging from complete absence of symptoms to severe and often fatal cardiovascular and/or gastrointestinal manifestations. To date, few correlates of clinical disease progression have been identified. Elucidating a putative role for T. cruzi strain diversity in Chagas disease pathogenesis is complicated by the scarcity of parasites in clinical specimens and the limitations of our contemporary genotyping techniques. This article systematically reviews the historical literature, given our current understanding of parasite genetic diversity, to evaluate the evidence for any association between T. cruzi genotype and chronic clinical outcome, risk of congenital transmission or reactivation and orally transmitted outbreaks.

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Section: T Cruzi Lineage In Chagas Disease Diagnostics and mentioning

confidence: 97%

Between a bug and a hard place:Trypanosoma cruzigenetic diversity and the clinical outcomes of Chagas disease

Messenger

Miles

Bern

2015

Expert Review of Anti-infective Therapy

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163

170

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“…Figure 1 illustrates the diagnostic process used by the CECD in Los Angeles, which has screened over 8000 people in the U.S. for T. cruzi since 2007. Assays have shown varying performance characteristics in different settings and patient populations [ 25 ], which may be due to T. cruzi genetic diversity [ 26 ] and/or geographically patterned variations in immune responses [ 27 ]. This is an especially critical point in light of the heterogeneous nature of the Latin American-origin population in the U.S. A World Health Organization comparative evaluation provides performance characteristics for several assays based on a multinational panel [ 23 ], while a recent meta-analysis includes summary estimates of sensitivity and specificity for both the Wiener Chagatest ELISA (93.7 and 99.0%, respectively) and the Ortho T. cruzi ELISA (99.2 and 99.1%, respectively).…”

Section: Screening and Diagnosismentioning

confidence: 99%

Treatment of Chagas Disease in the United States

Meymandi

Hernández

Park

et al. 2018

Curr Treat Options Infect Dis

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Purpose of ReviewChagas disease (CD) is endemic to much of Latin America, but also present in the United States (U.S.). Following a lengthy asymptomatic period, CD produces serious cardiac or gastrointestinal complications in 30–40% of people. Less than 1% of the estimated six million cases in the Americas, including 326,000–347,000 in the U.S., are diagnosed. Infected persons are typically unaware and the bulk of clinicians are unfamiliar with current treatment guidelines. This review provides U.S. and other clinicians with the latest knowledge of CD treatment.Recent FindingsChagas cardiomyopathy (CCM) causes severe fibrosis and autonomic damage in the myocardium. Eliminating the parasite through antitrypanosomal therapy with benznidazole, a nitroimidazole derivative or nifurtimox, a nitrofuran compound, potentially prevents heart failure and other sequelae of advanced CCM. Benznidazole, recently approved by the U.S. Food and Drug Administration (FDA) for children 2–12 years old, is the first-line therapy; optimal dosages are currently being studied. Antitrypanosomal therapy prevents congenital transmission; produces high cure rates for acute, congenital, and early chronic cases; and improves clinical outcomes in adult chronic indeterminate cases. However, this benefit was not observed in a large clinical trial that included patients with advanced CCM.SummaryTreatment with antitrypanosomal drugs can cure CD in acute, congenital, and early chronic cases and provides improved clinical outcomes for chronic indeterminate cases. This treatment should be offered as early as possible, before advanced CCM develops.

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“…Diagnosis of T. cruzi infection has not hitherto been lineage-specific. The search for a TcIspecific antigen applicable to animals and humans remains an important current research goal, and may elucidate the reported differences in serological and immune responses in regions endemic for different lineages [44][45][46].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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Trypanosoma cruzi, the protozoan agent of Chagas disease in the Americas, is comprised of six genetic lineages (TcI-TcVI) and a possible seventh (TcBat, related to TcI). Identification of T. cruzi lineages infecting reservoir mammalian species is fundamental to resolving transmission cycles. However, this is hindered by the limited sensitivity and technical complexity of parasite isolation and genotyping. An alternative approach is serology using T. cruzi lineage-specific epitopes, such as those of the trypomastigote small surface antigen (TSSA). For surveillance of T. cruzi lineage infections in mammal species from diverse Brazilian regions, we apply a novel rapid diagnostic test (RDT, Chagas Sero K-SeT), which incorporates the TSSA peptide epitope specific to TcII/V/VI (TSSApep-II/V/VI) and Protein G detection of antibodies. Chagas Sero K-SeT RDT results with sera from experimentally infected mice, from tamarin primates (Leontopithecus spp.) and from canines (Canis familiaris) were concordant with corresponding TSSApep-II/V/VI ELISAs. The Chagas Sero K-Set detected TcII/V/VI infections in Leontopithecus spp. from the Atlantic forest (n = 46), in C. familiaris (n = 16) and Thrichomys laurentius (n = 2) from Caatinga biome and Chiroptera (n = 1) from Acre, Amazonia. The Chagas Sero K-SeT RDT is directly applicable to TcII/V/ VI-specific serological surveillance of T. cruzi infection in several different mammalian Orders. It can replace ELISAs and provides efficient, point-of-sampling, low-cost detection of TcII/V/VI infections, with at least equivalent sensitivity, although some mammals may be difficult to trap, and, not unexpectedly, Chagas Sero K-SeT could not recognise feline IgG. Knowledge of sylvatic hosts of T. cruzi can be expanded, new reservoir species discovered, and the ecology of transmission cycles clarified, particularly with adaptation to further mammalian Orders.

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Regional Variation in the Correlation of Antibody and T-Cell Responses to Trypanosoma cruzi

Cited by 20 publications

References 33 publications

Between a bug and a hard place:Trypanosoma cruzigenetic diversity and the clinical outcomes of Chagas disease

Between a bug and a hard place:Trypanosoma cruzigenetic diversity and the clinical outcomes of Chagas disease

Treatment of Chagas Disease in the United States

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

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