Avidity as a marker of protection against hepatitis E during a genotype 1 outbreak in South Sudan
- 1Institute of Global Health, University of Geneva, Geneva, Switzerland
Abstract
BackgroundIn settings where hepatitis E virus (HEV) is highly endemic, anti-HEV IgG seroprevalence approaches saturation, yet how often disease occurs in previously infected individuals, and how protective natural genotype 1 immunity is, remains unmeasured. IgG concentration cannot answer this as levels rise within days of symptom onset masking any pre-existing levels; IgG avidity, maturing over months, may serve as a useful tool to understand reinfections.
MethodsWe enrolled 1007 suspected HEV patients and measured anti-HEV IgG avidity in IgG-positive confirmed cases and an age-stratified sample of IgG-positive test-negatives (n = 366) in enhanced surveillance around a 2022 vaccination campaign in Bentiu, South Sudan. Using high avidity (avidity index [≥]50%) as a marker of past infection, we estimated (i) the reinfection fraction, (ii) protection from prior infection using a test negative design and (iii) associations with viral load and infection severity.
ResultsMedian avidity index was 11% in cases versus 77% in test-negatives. Among unvaccinated cases, 11.6% (28/242) carried high-avidity IgG (indicative of mature immunity and therefore reinfection), rising with age (odds ratio 1.6 per decade, p=0.006). Mature immunity was associated with 95% lower odds of disease (adjusted OR 0.05, 95% CI 0.03-0.08), robust to threshold and case-definition. High-avidity cases were less often viremic (29% vs 78%) at matched time since onset, though we found no differences in liver function biomarkers between patients with high-avidity and low-avidity.
ConclusionsMost HEV disease occurred in previously uninfected individuals, and prior immunity was strongly protective against detected disease. Avidity provides a population-level tool to read the immune landscape where seroprevalence may be uninformative.
Short SummaryUsing IgG avidity to distinguish between past from recent hepatitis E infection in a highly endemic setting, we found most disease occurred in previously uninfected individuals. Prior infection was associated with 95% lower odds of disease, demonstrating strong natural immunity.
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BibTeX
@misc{valera2026avidity,
title = {{Avidity as a marker of protection against hepatitis E during a genotype 1 outbreak in South Sudan}},
author = {C. B. G. Bionda Valera and C. Alvarez and A. Dighe and I. Ciglenecki and I. Eckerle and R. C. Nesbitt and Y. Sarmiento and E. Gignoux and J. Rumunu and V. K. Asilaz and B. Meyer and A. S. Azman},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.03.26362164},
url = {https://www.medrxiv.org/content/10.64898/2026.09.03.26362164v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Avidity as a marker of protection against hepatitis E during a genotype 1 outbreak in South Sudan
AU - C. B. G. Bionda Valera
AU - C. Alvarez
AU - A. Dighe
AU - I. Ciglenecki
AU - I. Eckerle
AU - R. C. Nesbitt
AU - Y. Sarmiento
AU - E. Gignoux
AU - J. Rumunu
AU - V. K. Asilaz
AU - B. Meyer
AU - A. S. Azman
PY - 2026
DA - 2026/09/03
PB - medRxiv
DO - 10.64898/2026.09.03.26362164
UR - https://www.medrxiv.org/content/10.64898/2026.09.03.26362164v1
AB - BackgroundIn settings where hepatitis E virus (HEV) is highly endemic, anti-HEV IgG seroprevalence approaches saturation, yet how often disease occurs in previously infected individuals, and how protective natural genotype 1 immunity is, remains unmeasured. IgG concentration cannot answer this as levels rise within days of symptom onset masking any pre-existing levels; IgG avidity, maturing over months, may serve as a useful tool to understand reinfections. MethodsWe enrolled 1007 suspected HEV patients and measured anti-HEV IgG avidity in IgG-positive confirmed cases and an age-stratified sample of IgG-positive test-negatives (n = 366) in enhanced surveillance around a 2022 vaccination campaign in Bentiu, South Sudan. Using high avidity (avidity index [≥]50%) as a marker of past infection, we estimated (i) the reinfection fraction, (ii) protection from prior infection using a test negative design and (iii) associations with viral load and infection severity. ResultsMedian avidity index was 11% in cases versus 77% in test-negatives. Among unvaccinated cases, 11.6% (28/242) carried high-avidity IgG (indicative of mature immunity and therefore reinfection), rising with age (odds ratio 1.6 per decade, p=0.006). Mature immunity was associated with 95% lower odds of disease (adjusted OR 0.05, 95% CI 0.03-0.08), robust to threshold and case-definition. High-avidity cases were less often viremic (29% vs 78%) at matched time since onset, though we found no differences in liver function biomarkers between patients with high-avidity and low-avidity. ConclusionsMost HEV disease occurred in previously uninfected individuals, and prior immunity was strongly protective against detected disease. Avidity provides a population-level tool to read the immune landscape where seroprevalence may be uninformative. Short SummaryUsing IgG avidity to distinguish between past from recent hepatitis E infection in a highly endemic setting, we found most disease occurred in previously uninfected individuals. Prior infection was associated with 95% lower odds of disease, demonstrating strong natural immunity.
ER -