Diagnostic Performance and Kinetics of Hepatitis E Viral RNA and IgM Antibody Test Positivity in a Genotype 1 Outbreak in South Sudan

Abstract

Background. Diagnostics are essential for understanding hepatitis E epidemiology, but the field performance of available tests remains unclear. We evaluated the performance of polymerase chain reactions (PCR), IgM ELISA, and the Assure hepatitis E virus (HEV) IgM rapid diagnostic test (RDT) during a HEV genotype 1 outbreak and assessed the duration of viremia and antibodies responses. Methods. We used data from enhanced surveillance at a health facility in Bentiu internally displaced persons camp, South Sudan (March-December 2022). As part of a vaccine effectiveness study, suspected hepatitis E cases underwent testing with all 3 diagnostics at enrollment with a follow-up sample. We used a latent class model to estimate test performance and accelerated failure time models to estimate time from jaundice onset to a negative test for PCR and ELISA. Results and Conclusions. Among 893 suspected cases, test sensitivity declined with time from jaundice onset. Within 30 days of jaundice onset, PCR sensitivity was 73% (95% Credible Interval [CrI] 27, 90), compared to 86% for RDT (95% CrI: 74, 93), and 95% for ELISA (95% CrI: 91, 98). Specificity was high across tests: PCR at 98% (95% CrI: 98, 99), RDT at 95% (95% CrI: 93, 96), and ELISA at 95% (95% CrI: 93, 96). Median time from jaundice onset to negative test was 19 days (95% CI: 17, 21) for PCR and 113 days (95% CI: 87, 163) for ELISA. The Assure IgM RDT showed higher sensitivity for identifying hepatitis E than PCR and similar specificity to IgM ELISA, supporting its use in surveillance. Care seeking delays can greatly influence the interpretation of diagnostic tests.