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Accepted for/Published in: JMIR Public Health and Surveillance

Date Submitted: Dec 19, 2023
Date Accepted: May 29, 2024

The final, peer-reviewed published version of this preprint can be found here:

Using Laboratory Test Results for Surveillance During a New Outbreak of Acute Hepatitis in 3-Week- to 5-Year-Old Children in the United Kingdom, the Netherlands, Ireland, and Curaçao: Observational Cohort Study

Swets MC, Kerr SR, MacKenna B, Fisher L, van Wijnen M, Brandwagt D, Schenk PW, Fraaij P, Visser LG, Bacon S, Mehrkar A, Nichol A, Twomey P, Matthews PC, ISARIC4C Hepatitis Study Group , Semple MG, Groeneveld GH, Goldacre B, Jones I, Baillie JK

Using Laboratory Test Results for Surveillance During a New Outbreak of Acute Hepatitis in 3-Week- to 5-Year-Old Children in the United Kingdom, the Netherlands, Ireland, and Curaçao: Observational Cohort Study

JMIR Public Health Surveill 2024;10:e55376

DOI: 10.2196/55376

PMID: 39864403

PMCID: 11770233

Utilising laboratory test results for surveillance during a new outbreak of acute hepatitis in 3 week to 5 year old children in the UK, the Netherlands, Ireland and Curaçao: an observational cohort study

  • Maaike C Swets; 
  • Steven R Kerr; 
  • Brian MacKenna; 
  • Louis Fisher; 
  • Merel van Wijnen; 
  • Diederik Brandwagt; 
  • Paul W Schenk; 
  • Pieter Fraaij; 
  • Leonardus G Visser; 
  • Sebastian Bacon; 
  • Amir Mehrkar; 
  • Alistair Nichol; 
  • Patrick Twomey; 
  • Philippa C Matthews; 
  • ISARIC4C Hepatitis Study Group; 
  • Malcolm G Semple; 
  • Geert H Groeneveld; 
  • Ben Goldacre; 
  • Iain Jones; 
  • J Kenneth Baillie

ABSTRACT

Background:

In March 2022, a concerning rise in cases of unexplained paediatric hepatitis was reported in multiple countries. Cases were defined as acute hepatitis with serum transaminases >500 U/L (aspartate transaminase (AST) or alanine transaminase (ALT)) in children aged 16 or under. We explored a simple federated data analytics method to search for evidence of unreported cases using routinely held data. We conducted a pragmatic survey to analyse changes in the proportion of hospitalised children with elevated AST or ALT over time. In addition, we studied the feasibility of using routinely collected clinical laboratory results to detect or follow up an outbreak of an infectious disease.

Objective:

We explored a simple federated data analytics method to search for evidence of unreported cases using routinely held data.

Methods:

We provided hospitals with a simple computational tool to enable laboratories to share non-disclosive summary-level data. Summary statistics for aspartate transaminase (AST) and alanine transaminase (ALT) measurements were collected from the last 10 years across all age groups. Measurements were considered elevated if ALT and/or AST was >200 U/L. The rate of elevated AST and/or ALT tests for 3-week to 5-year-olds was compared between a period of interest in which cases of hepatitis were reported (01-12-2021 to 31-08-2022) and a pre-pandemic baseline period (01-01-2012 to 31-12-2019). We calculated a Z-score, which measures the extent to which the rate for elevated ALT and/or AST was higher or lower in the period of interest compared to a baseline period, for the 3-week to 5-year-olds.

Results:

Our approach of sharing a simple software tool for local use enabled rapid, federated data analysis. 34 hospitals in the UK, the Netherlands, Ireland and Curaçao were asked to contribute summary data, and 30 (88%) submitted their data. For all locations combined, the rate of elevated AST or ALT measurements in the period of interest was not elevated (Z-score -0.46; p 0.64). Results from individual regions were discordant, with a higher rate of elevated AST or ALT values in the Netherlands (Z-score 4.48; p<0.0001), driven by results from a single centre in Utrecht. We did not observe any clear indication of changes in primary care activity or test results in the same period.

Conclusions:

Hospital laboratories collect large amounts of data on a daily basis that can potentially be of use for disease surveillance, but these are currently not optimally utilised. Federated analytics using non-disclosive, summary-level laboratory data sharing was successful, safe and efficient. The approach holds potential as a tool for pandemic surveillance in future outbreaks. Our findings do not indicate the presence of a broader outbreak of mild hepatitis cases among young children, although there was an increase in elevated AST or ALT values locally in the Netherlands.


 Citation

Please cite as:

Swets MC, Kerr SR, MacKenna B, Fisher L, van Wijnen M, Brandwagt D, Schenk PW, Fraaij P, Visser LG, Bacon S, Mehrkar A, Nichol A, Twomey P, Matthews PC, ISARIC4C Hepatitis Study Group , Semple MG, Groeneveld GH, Goldacre B, Jones I, Baillie JK

Using Laboratory Test Results for Surveillance During a New Outbreak of Acute Hepatitis in 3-Week- to 5-Year-Old Children in the United Kingdom, the Netherlands, Ireland, and Curaçao: Observational Cohort Study

JMIR Public Health Surveill 2024;10:e55376

DOI: 10.2196/55376

PMID: 39864403

PMCID: 11770233

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