A Systematic Review of High Quality Diagnostic Tests for Chagas Disease

Background: There 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. Methods: We 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. Results: Eighteen 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%). Conclusion: Sensitivity 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. Author Summary: Chagas disease, an infectious disease endemic to Latin America, is caused by the protozoan parasite Trypanosoma cruzi. T. cruzi can be transmitted through blood transfusions, organ transplants, or from mother to fetus, although it is most commonly transmitted through insect vectors. Infections can remain silent for many years before manifesting as potentially fatal damage to the cardiac and/or digestive system. Diagnosis of Chagas disease during its chronic asymptomatic phase is crucial to preventing future infections with T. cruzi and is often performed using serological tests that detect antibodies in the blood. Because there is currently no gold standard for serological diagnostic tests, multiple forms of serologic testing are often used in conjunction. The purpose of this study was to compare reports on the accuracy of serological tests. After limiting studies by certain criteria, the authors found a lower estimate of accuracy than has previously been reported in the literature and suggest quality improvements that can be made to standardize future reports.