Chagas disease affects an estimated 300,000 individuals in the United States. Diagnosis in the chronic phase requires positive results from two different IgG serological tests. Three enzyme-linked immunosorbent assays (ELISAs) (Hemagen, Ortho, and Wiener) and one rapid test (InBios) are FDA cleared, but comparative data in U.S. populations are sparse. We evaluated 500 seropositive and 300 seronegative blood donor plasma samples.

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Confirmed diagnosis of chronic Chagas disease (CD) requires positive results by two different IgG serology tests. Variable sensitivity has been reported among tests and in different endemic regions. Inadequate specificity presents a particular challenge in low prevalence settings such as the United States. This study provides a direct comparison of the latest-generation IgG serology assays with four previously assessed FDA-cleared tests. Seven hundred and ten blood donor plasma specimens were evaluated by Wiener Lisado and Wiener v.4.0 enzyme-linked immunosorbent assays (ELISAs) and Abbott PRISM Chagas chemiluminescent assay (ChLIA). Sensitivity and specificity were assessed relative to infection status as determined by the original blood donation testing algorithm. All three latest-generation assays demonstrated 100% specificity (95% confidence interval [CI]: 98.6, 100.0). Wiener Lisado, Wiener v.4.0 and Abbott PRISM had sensitivities of 97.1% (95% CI: 95.1, 98.4), 98.9% (95% CI: 97.4, 99.6) and 95.5% (95% CI: 93.2, 97.3), respectively. As with previously evaluated FDA-cleared tests, all three assays had the highest reactivity and sensitivity in samples from donors born in South America and lowest reactivity and sensitivity in specimens from those born in Mexico, with intermediate results in specimens from Central American donors. Wiener v.4.0 had the highest diagnostic sensitivity in all comparisons. Our findings suggest that the latest-generation CD serology tests could improve diagnostic sensitivity without affecting specificity.

25Background: Chagas disease affects an estimated 300,000 individuals in the US. Diagnosis in 26 the chronic phase requires positive results by two different IgG serological tests. Three ELISAs 27(Hemagen, Ortho, Wiener) and one rapid test (InBios) are FDA-cleared, but comparative data in 28 US populations are sparse. 30Methods: We evaluated 500 seropositive and 300 seronegative blood donor plasma samples. 31Country of birth was known for 255 seropositive specimens and grouped into regions: Mexico 32 (n=94), Central America (n=88) and South America (n=73). Specimens were tested by the four 33 FDA-cleared IgG serological assays. Test performance was evaluated by two comparators and 34 latent class analysis. 36Results: InBios had the highest sensitivity (97.4-99.3%), but lowest specificity (87.5-92.3%). 37Hemagen had the lowest sensitivity (88.0-92.0%), but high specificity (99.0-100.0%). Sensitivity 38 was intermediate for Ortho (92.4-96.5%) and Wiener (94.0-97.1%); both had high specificity 39 (98.8-100.0% and 96.7-99.3%, respectively). Antibody reactivity and clinical sensitivity was 40 lowest in donors from Mexico, intermediate in those from Central America and highest in those 41 from South America. 42 43 Conclusions: Our findings provide an initial evidence base to improve laboratory diagnosis of 44 Chagas disease in the US. The best current testing algorithm would employ a high sensitivity45screening test followed by a high specificity confirmatory test.