A Systematic Review of High Quality Diagnostic Tests for Chagas Disease

Abstract

BackgroundThere is significant heterogeneity in reported sensitivities and specificities of diagnostic serological assays for Chagas disease, as might be expected from studies that vary widely according to setting, research design, antigens employed, and reference standard. The purpose of this study is to summarize the reported accuracy of serological assays and to identify sources of heterogeneity including quality of research design. To avoid associated spectrum bias, our analysis was limited to cohort studies.MethodsWe completed a search of PubMed, a bibliographic review of potentially relevant articles, and a review of articles identified by a study author involved in this area of research. Studies were limited to prospective cohort studies of adults published since 1985. Measures of diagnostic accuracy were pooled using a Der Simonian Laird Random Effects Model. A subgroup analysis and meta regression were employed to identify sources of heterogeneity. The QUADAS tool was used to assess quality of included studies and Begg's funnel plot was used to assess publication bias.ResultsEighteen studies and 61 assays were included in the final analysis. Significant heterogeneity was found in all pre-determined subgroups. Overall sensitivity was 90% (95% CI: 89%–91%) and overall specificity was 98% (95% CI: 98%–98%).ConclusionSensitivity and specificity of serological assays for the diagnosis of Chagas disease appear less accurate than previously thought. Suggestions to improve the accuracy of reporting include the enrollment of patients in a prospective manner, double blinding, and providing an explicit method of addressing subjects that have an indeterminate diagnosis by either the reference standard or index test.

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

“…At present, the most widely used serologic methods are indirect hemagglutination assay (IHA), indirect immunofluorescence (IIF), and enzyme-linked immunosorbent assay (ELISA) using total parasite homogenates or semipurified antigenic fractions. Despite their simplicity and low cost, these tests show variations in their reproducibility and reliability that can be attributed to poor standardization of the reagents (7). In the absence of a single reference test showing ϳ100% specificity and sensitivity, the current guidelines developed by the World Health Organization advise the use of two serologic tests for reaching a conclusive diagnosis.…”

Evaluación preliminar de la prueba comercial “Chagas (Trypanosoma cruzi) IgG-ELISA®” en individuos colombianos

“…Actualmente, existen numerosas pruebas seroló-gicas de ELISA para la detección de anticuerpos IgG contra el parásito T. cruzi (28), las cuales difieren en el antígeno empleado según su naturaleza (proteínas de lisados totales del parásito, fracciones o proteínas purificadas, proteínas recombinantes, péptidos sintéticos o proteínas de fusión que contienen epítopos de distintas proteínas del parásito), según su expresión en algún estadio de diferenciación particular del parásito (epimastigote, amastigote o tripomastigote), o según la unidad discreta de tipificación de la cepa del parásito de donde se originó el antígeno (DTU-I a VI). Esta diversidad en la oferta de pruebas de ELISA, unida a las diferencias en los aislamientos circulantes en cada región, la prevalencia de la enfermedad en cada población y en los protocolos utilizados, resulta en una considerable fuente de variación en una misma prueba y entre pruebas (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20).…”

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

“…4 The specimens used for the rapid test evaluation were triply concordant by commercial ELISA, IFA, and radioimmunoprecipitation assay (RIPA) and therefore, may represent an overestimate of sensitivity of the evaluated tests. 3 Lower sensitivity has also been observed for some assays in specimens from Panama 5,6 and Mexico. 7 These differences may be caused by variations in the T. cruzi strains inhabiting these different geographic ranges, because antigenic variation between strains or infectivity of the strains may alter the quality or quantity of the antibody response, leading to differential sensitivities to serodiagnostic tests.…”

“…1 No single serological test for Chagas disease has sufficient sensitivity and specificity to be used alone; a confirmed diagnosis relies on concordant results on at least two tests using different antigens and/or formats. 3 There is evidence that the sensitivity of serological assays may differ depending on the geographic source of the specimens. Two different rapid diagnostic tests showed sensitivities of 87.5% and 90% in specimens from Bolivia compared with 30% and 54% in specimens from Peru.…”