ELISA versus PCR for diagnosis of chronic Chagas disease: systematic review and meta-analysis

Pedro Eaa Brasil,Alejandro M Hasslocher-Moreno,José U Braga,Liane De Castro,Luiz Hc Sangenis

doi:10.1186/1471-2334-10-337

Abstract

BackgroundMost current guidelines recommend two serological tests to diagnose chronic Chagas disease. When serological tests are persistently inconclusive, some guidelines recommend molecular tests. The aim of this investigation was to review chronic Chagas disease diagnosis literature and to summarize results of ELISA and PCR performance.MethodsA systematic review was conducted searching remote databases (MEDLINE, LILACS, EMBASE, SCOPUS and ISIWeb) and full texts bibliography for relevant abstracts. In addition, manufacturers of commercial tests were contacted. Original investigations were eligible if they estimated sensitivity and specificity, or reliability -or if their calculation was possible - of ELISA or PCR tests, for chronic Chagas disease.ResultsHeterogeneity was high within each test (ELISA and PCR) and threshold effect was detected only in a particular subgroup. Reference standard blinding partially explained heterogeneity in ELISA studies, and pooled sensitivity and specificity were 97.7% [96.7%-98.5%] and 96.3% [94.6%-97.6%] respectively. Commercial ELISA with recombinant antigens studied in phase three investigations partially explained heterogeneity, and pooled sensitivity and specificity were 99.3% [97.9%-99.9%] and 97.5% [88.5%-99.5%] respectively. ELISA's reliability was seldom studied but was considered acceptable. PCR heterogeneity was not explained, but a threshold effect was detected in three groups created by using guanidine and boiling the sample before DNA extraction. PCR sensitivity is likely to be between 50% and 90%, while its specificity is close to 100%. PCR reliability was never studied.ConclusionsBoth conventional and recombinant based ELISA give useful information, however there are commercial tests without technical reports and therefore were not included in this review. Physicians need to have access to technical reports to understand if these serological tests are similar to those included in this review and therefore correctly order and interpret test results. Currently, PCR should not be used in clinical practice for chronic Chagas disease diagnosis and there is no PCR test commercially available for this purpose. Tests limitations and directions for future research are discussed.

Highlights

Most current guidelines recommend two serological tests to diagnose chronic Chagas disease
The following strategy was developed in PubMed/Medline using clinical queries for diagnostic studies maximizing the sensitivity of the search: ("Chagas Disease"[MeSH] OR “Trypanosoma cruzi"[MeSH]) AND (ELISA OR OR polymerase chain reaction (PCR) OR)) AND
Because of some perceptions during the review, such as: few phase three investigations; few commercial tests investigations sponsored by manufacturers; reports published mainly in immunology and parasitology journals; absence of products monographs or technical reports; as well as the amount of missing information is considerably higher in the commercial tests reports; it seems that in this field there is a considerable gap between the academic production, manufacturer interests and clinical practice

Summary

Introduction

Most current guidelines recommend two serological tests to diagnose chronic Chagas disease. When serological tests are persistently inconclusive, some guidelines recommend molecular tests The aim of this investigation was to review chronic Chagas disease diagnosis literature and to summarize results of ELISA and PCR performance. Chagas disease is an infection, in which the necessary cause is a parasite called Trypanosoma cruzi This disease is endemic in Latin American countries and approximately 15 million people are estimated to be infected [1]. One significant difficulty in diagnosing Chagas disease is that most patients have no symptoms in acute or chronic phase [2,15,16] Another difficulty in diagnosis is that, unlike most infectious diseases, the direct or parasitological tests for Chagas disease (thick or thin smear, microhematocrit, hemocultures or xenodiagnosis) have unacceptably low sensitivity in the chronic phase, ranging from 50% to 70%,[17] and are not recommended [15,16,17,18,19]. Due to potential transmission of Chagas disease through blood transfusion, the United States of America, Spain and other non Latin American countries screen blood donors for Chagas disease [20,21]

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