{
  "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.\n\nMethodsWe 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.\n\nResultsMedian 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.\n\nConclusionsMost 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.\n\nShort 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.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Global Health, University of Geneva, Geneva, Switzerland"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "C. B. G. Bionda Valera"
    },
    {
      "name": "C. Alvarez"
    },
    {
      "name": "A. Dighe"
    },
    {
      "name": "I. Ciglenecki"
    },
    {
      "name": "I. Eckerle"
    },
    {
      "name": "R. C. Nesbitt"
    },
    {
      "name": "Y. Sarmiento"
    },
    {
      "name": "E. Gignoux"
    },
    {
      "name": "J. Rumunu"
    },
    {
      "name": "V. K. Asilaz"
    },
    {
      "name": "B. Meyer"
    },
    {
      "affs": [
        0
      ],
      "name": "A. S. Azman"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5fhjqj0brb7j7.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.03.26362164",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.03.26362164v1.full",
  "id": "5fhjqj0brb7j7",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.03.26362164v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "infectious diseases"
    ],
    [
      "openalex",
      "2721|Hepatitis Viruses Studies and Epidemiology"
    ]
  ],
  "openalex": "W7211936412",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.03.26362164v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5fhjqj0brb7j7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:58Z",
      "native_id": "10.64898/2026.09.03.26362164",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.03.26362164v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:infectious diseases",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Avidity as a marker of protection against hepatitis E during a genotype 1 outbreak in South Sudan",
  "title_text": "Avidity as a marker of protection against hepatitis E during a genotype 1 outbreak in South Sudan",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:58Z",
  "url": "https://research.draconitic.com/paper/5fhjqj0brb7j7",
  "venue": "medRxiv",
  "versions": []
}