Diagnostic Accuracy and Dynamics of HEV RNA and IgM During Genotype 1 Outbreak

Overview

During a hepatitis E genotype 1 outbreak in South Sudan, PCR, IgM ELISA, and IgM rapid diagnostic tests (RDTs) were evaluated for diagnostic accuracy. IgM ELISA showed the highest sensitivity within 30 days of jaundice onset, followed by RDT and PCR, with all tests demonstrating high specificity. The median duration of detectable HEV RNA was 19 days, while IgM antibodies persisted for a median of 113 days.

Background

Hepatitis E virus (HEV) causes millions of symptomatic acute hepatitis cases annually, with high fatality risks in pregnant women. Large outbreaks of HEV genotypes 1 and 2 occur mainly due to fecal contamination of drinking water, especially in low-resource settings. Diagnostic confirmation is often delayed due to limited laboratory infrastructure, impeding timely outbreak response and vaccination efforts. Rapid diagnostic tests (RDTs) offer point-of-care testing but require real-world performance validation, particularly during outbreaks of genotype 1 HEV.

Data Highlights

Key Findings

• IgM ELISA demonstrated the highest sensitivity (95%) within 30 days of jaundice onset among the three tests evaluated.
• The Assure IgM RDT showed higher sensitivity (86%) than PCR (73%) and comparable specificity to IgM ELISA.
• All tests exhibited high specificity, with PCR achieving the highest at 98%.
• Median duration of detectable HEV RNA by PCR was 19 days post-jaundice onset, indicating a relatively short viremic phase.
• IgM antibodies detected by ELISA persisted for a median of 113 days, suggesting prolonged antibody presence after acute infection.
• Delays in care seeking significantly affect diagnostic test interpretation due to declining sensitivity over time.

Clinical Implications

The high sensitivity and specificity of the Assure IgM RDT support its use as a practical tool for hepatitis E surveillance and outbreak response in resource-limited settings. Understanding the temporal dynamics of HEV RNA and IgM antibodies is critical for interpreting diagnostic results accurately, especially considering the short viremic period and prolonged antibody persistence. Early testing after symptom onset is essential to maximize diagnostic yield and guide timely public health interventions.

Conclusion

This study provides real-world evidence that IgM RDTs are effective for hepatitis E diagnosis during genotype 1 outbreaks and highlights the importance of timing in test interpretation. These findings can inform improved surveillance strategies and outbreak management in low-resource settings.

References

1. WHO 2022 -- Hepatitis E diagnostics and vaccine recommendations
2. MSF 2022 -- Reactive vaccination campaign in South Sudan
3. SAGE IVD 2022 -- WHO list of essential in vitro diagnostics