Geographic Variations in Test Reactivity for the Serological Diagnosis of Trypanosoma cruzi Infection

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ABSTRACT

Chagas disease is a neglected disease caused by Trypanosoma cruzi parasites. Most diagnosis is based on serological tests, but the lack of a gold standard test complicates the measurement of test performance. To overcome this limitation, we used samples from a cohort of well-characterized T. cruzi-infected women to evaluate the reactivity of two rapid diagnostic tests and one enzyme-linked immunosorbent assay (ELISA). Our cohort was derived from a previous study on congenital transmission of T. cruzi and consisted of 481 blood/plasma samples from Argentina ( n = 149), Honduras ( n = 228), and Mexico ( n = 104), with at least one positive T. cruzi PCR. Reactivity of the three tests ranged from 70.5% for the Wiener ELISA to 81.0% for the T-Detect and 90.4% for the Stat-Pak rapid tests. Test reactivity varied significantly among countries and was highest in Argentina and lowest in Mexico. When considering at least two reactive serological tests to confirm seropositivity, over 12% of T. cruzi infection cases from Argentina were missed by serological tests, over 21% in Honduras, and an alarming 72% in Mexico. Differences in test performance among countries were not due to differences in parasitemia, but differences in antibody levels against ELISA antigens were observed. Geographic differences in T. cruzi parasite strains as well as genetic differences among human populations both may contribute to the discrepancies in serological testing. Improvements in serological diagnostics for T. cruzi infections are critically needed to ensure an optimum identification of cases.

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Most cited references 39

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Chagas disease

Anis Rassi, José Marin-Neto (2010)

The Lancet, 375(9723), 1388-1402

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Global economic burden of Chagas disease: a computational simulation model.

Kristina M. Bacon, Kuang-Yung Lee, Peter Hotez … (2013)

As Chagas disease continues to expand beyond tropical and subtropical zones, a growing need exists to better understand its resulting economic burden to help guide stakeholders such as policy makers, funders, and product developers. We developed a Markov simulation model to estimate the global and regional health and economic burden of Chagas disease from the societal perspective. Our Markov model structure had a 1 year cycle length and consisted of five states: acute disease, indeterminate disease, cardiomyopathy with or without congestive heart failure, megaviscera, and death. Major model parameter inputs, including the annual probabilities of transitioning from one state to another, and present case estimates for Chagas disease came from various sources, including WHO and other epidemiological and disease-surveillance-based reports. We calculated annual and lifetime health-care costs and disability-adjusted life-years (DALYs) for individuals, countries, and regions. We used a discount rate of 3% to adjust all costs and DALYs to present-day values. On average, an infected individual incurs US$474 in health-care costs and 0·51 DALYs annually. Over his or her lifetime, an infected individual accrues an average net present value of $3456 and 3·57 DALYs. Globally, the annual burden is $627·46 million in health-care costs and 806,170 DALYs. The global net present value of currently infected individuals is $24·73 billion in health-care costs and 29,385,250 DALYs. Conversion of this burden into costs results in annual per-person costs of $4660 and lifetime per-person costs of $27,684. Global costs are $7·19 billion per year and $188·80 billion per lifetime. More than 10% of these costs emanate from the USA and Canada, where Chagas disease has not been traditionally endemic. A substantial proportion of the burden emerges from lost productivity from cardiovascular disease-induced early mortality. The economic burden of Chagas disease is similar to or exceeds those of other prominent diseases globally (eg, rotavirus $2·0 billion, cervical cancer $4·7 billion) even in the USA (Lyme disease $2·5 billion), where Chagas disease has not been traditionally endemic, suggesting an economic argument for more attention and efforts towards control of Chagas disease. Bill & Melinda Gates Foundation, the National Institute of General Medical Sciences Models of Infectious Disease Agent Study. Copyright © 2013 Elsevier Ltd. All rights reserved.

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Sensitive detection and schizodeme classification of Trypanosoma cruzi cells by amplification of kinetoplast minicircle DNA sequences: use in diagnosis of Chagas' disease.

Nancy R. Sturm, Wim Degrave, Carlos Hernán Morel … (1989)

Amplification of DNA sequences from the kinetoplast minicircle DNA was employed as a method for the detection and classification of small numbers of Trypanosoma cruzi cells. Two overlapping fragments from the conserved 120 bp minirepeat regions of the minicircle DNA and one fragment covering the adjacent variable regions were amplified. The minimal amount of minicircle DNA required to detect a product by hybridization with an oligonucleotide probe was 0.015 fg, which represents approximately 10 molecules or 0.1% of the minicircle DNA component of a single cell. The amplification worked equally well with kDNA from several strains of T. cruzi and did not occur with kDNA from several other kinetoplastids. kDNA recovered from less than 10 trypanosomes in whole blood could be used as a template for amplification; the presence of a several billion fold excess of human DNA had no effect on the amplification process. Schizodeme analysis by hybridization with specific oligonucleotides or by direct restriction enzyme digestion could be performed on the amplified fragments representing the minicircle conserved region or variable regions. This method should prove useful as a rapid, specific and sensitive assay for Chagas' disease in chronic patients as well as for epidemiological studies of infected animals and insects.

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Author and article information

Contributors

Eric Dumonteil:

ORCID: https://orcid.org/0000-0001-9376-0209

Bobbi S. Pritt: Role: Editor

Journal

Journal ID (nlm-ta): J Clin Microbiol

Journal ID (iso-abbrev): J Clin Microbiol

Journal ID (publisher-id): JCM

Title: Journal of Clinical Microbiology

Publisher: American Society for Microbiology (1752 N St., N.W., Washington, DC )

ISSN (Print): 0095-1137

ISSN (Electronic): 1098-660X

Publication date (Electronic, preprint): 1 September 2021

Publication date (Electronic, pub): 18 November 2021

Publication date (Electronic, collection): December 2021

Volume: 59

Issue: 12

Electronic Location Identifier: e01062-21

Affiliations

[a ] Laboratory of Parasitology, Faculty of Medicine, and ULB Center for Research in Immunology (UCRI), Université Libre de Bruxelles, Brussels, Belgium

[b ] Department of Tropical Medicine, School of Public Health and Tropical Medicine, and Vector-Borne and Infectious Disease Research Center, Tulane Universitygrid.265219.b, , New Orleans, Louisiana, USA

[c ] Instituto de Enfermedades Infecciosas y Parasitología Antonio Vidal, Departamento de Laboratorio Clínico, Hospital Escuela, Facultad de Ciencias Médicas, UNAH, Tegucigalpa, Honduras

[d ] Unidad de Investigación Clínica y Epidemiológica Montevideo (UNICEM), Montevideo, Uruguay

[e ] Institute for Clinical Effectiveness and Health Policy, Buenos Aires, Argentina

[f ] Drugs for Neglected Diseases initiative-Latin America, Rio de Janeiro, Brazil

[g ] Epidemiology and Public Health Research Center (CIESP-CONICET), Buenos Aires, Argentina

[h ] Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane Universitygrid.265219.b, , New Orleans, Louisiana, USA

Mayo Clinic

Author notes

Carine Truyens and Eric Dumonteil contributed equally to the study.

Citation Truyens C, Dumonteil E, Alger J, Cafferata ML, Ciganda A, Gibbons L, Herrera C, Sosa-Estani S, Buekens P. 2021. Geographic variations in test reactivity for the serological diagnosis of Trypanosoma cruzi infection. J Clin Microbiol 59:e01062-21. https://doi.org/10.1128/JCM.01062-21.

Author information

Eric Dumonteil https://orcid.org/0000-0001-9376-0209

Claudia Herrera https://orcid.org/0000-0002-9009-4201

Article

Publisher ID: 01062-21 Publisher ID: jcm.01062-21

DOI: 10.1128/JCM.01062-21

PMC ID: 8601237

PubMed ID: 34469183

SO-VID: 5e85aa3e-ccc8-4742-9c50-e370019346bd

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

History

Date received : 4 May 2021

Date revision requested : 10 June 2021

Date accepted : 27 August 2021

Page count

Figures: 1, Tables: 3, Equations: 0, References: 39, Pages: 8, Words: 5776

Funding

Funded by: HHS | National Institutes of Health (NIH), FundRef https://doi.org/10.13039/100000002;

Award ID: R01AI083563

Award Recipient : Pierre Buekens

Funded by: HHS | National Institutes of Health (NIH), FundRef https://doi.org/10.13039/100000002;

Award ID: R01HD94955

Award Recipient : Claudia Patricia Herrera

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cover-date December 2021

ScienceOpen disciplines: Microbiology & Virology

Keywords: diagnostic performance,elisa,rapid test,reactivity,strain diversity,chagas disease,diagnostics,serology

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ScienceOpen disciplines: Microbiology & Virology

Keywords: diagnostic performance, elisa, rapid test, reactivity, strain diversity, chagas disease, diagnostics, serology

Geographic Variations in Test Reactivity for the Serological Diagnosis of Trypanosoma cruzi Infection

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ABSTRACT

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Most cited references 39

Chagas disease

Global economic burden of Chagas disease: a computational simulation model.

Sensitive detection and schizodeme classification of Trypanosoma cruzi cells by amplification of kinetoplast minicircle DNA sequences: use in diagnosis of Chagas' disease.

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