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

Abstract

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. 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. 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.