Outbreak at a glance

As of 22 June 2022, 33 countries in five WHO Regions have reported 920 probable cases of severe acute hepatitis of unknown aetiology in children which fulfill the WHO case definition. Since the previous Disease Outbreak News published on 27 May 2022, 270 new probable cases have been reported to WHO, including from four new countries. This Disease Outbreak News includes updates on the epidemiology of the outbreak, the publication of the new interim guidance on laboratory testing, and the launch of the clinical case report form on the WHO Global Clinical Platform. The detection of severe acute hepatitis of unknown aetiology in children across five WHO Regions is unusual, and the severe clinical sequelae of some cases warrant detailed investigation.

Description of the outbreak

This outbreak was initially detected on 5 April 2022 when the United Kingdom of Great Britain and Northern Ireland (the United Kingdom) notified WHO of ten cases of severe acute hepatitis of unknown aetiology in previously healthy young children aged under 10 years in the central belt of Scotland.

As of 22 June 2022, 33 countries in five WHO Regions have reported 920 probable cases (Figure 1). These include new and retrospectively identified cases since 1 October 2021, which fit the WHO case definition as stated below. There are four additional countries that have reported cases which are pending classification and are not included in the cumulative probable case count. Of the probable cases, 45 (5%) children have required transplants, and 18 (2%) deaths have been reported to WHO.

Half of the probable reported cases have been reported from the WHO European Region (20 countries reporting 460 cases), including 267 cases (29% of global cases) from the United Kingdom (Table 1, Figure 2). The second highest number of probable cases have been reported from the Region of the Americas (n=383, including 305 cases from the United States of America), followed by the Western Pacific Region (n=61), the South-East Asia Region (n=14) and Eastern Mediterranean Region (n=2). Seventeen countries are reporting more than five probable cases. The actual number of cases may be underestimated, in part due to the limited enhanced surveillance schemes in place. The case count is expected to change as more information and verified data become available.

Figure 1. Distribution of probable cases of severe acute hepatitis of unknown aetiology in children by country, as of 22 June 2022 (n=920)

Table 1. Distribution of reported probable cases of severe acute hepatitis of unknown aetiologyby WHO Region since 1 October 2021, as of 22 June 2022

WHO Region Probable cases Cases requiring liver transplants SARS-CoV-2 positive by PCR (number of positive cases) Adenovirus positive by PCR⸸ (number of positive cases) Adenovirus type 41 (number of positive cases) Deaths Americas 383 23 11 118 14 12 Eastern Mediterranean 2 0 Not available 1 Not available 1 Europe 460 22 47 203 30 1 Southeast-Asia 14 0 Not available Not available Not available 4 Western Pacific 61 0 6 5 0 0 Cumulative* 920 45 64 327 44 18

*The information included in this table contains data notified under IHR (2005), including from The European Surveillance System (TESSY) and official sources detected through event-based surveillance activities within the Public Health Intelligence process. Further information is presented in the Annex table.

⸸ Adenovirus positive in any specimen type (respiratory, urine, stool, whole blood, serum, other, or unknown specimen type)

Laboratory testing of cases

Based on the working case definition for probable cases (Box 1), laboratory testing has excluded hepatitis A-E viruses in these children. Other pathogens were detected in a number of the cases, although the data reported to WHO are incomplete.

Adenovirus continues to be the most frequently detected pathogen among cases with available data. In the European region, adenovirus was detected by PCR in 55% of cases (203/371) with available results (see Annex). Preliminary reports from the United States indicate that adenovirus was detected in 45% of cases (113/252) with available results.

SARS-CoV-2 has been detected in a number of cases, however, data on serology results for are limited. In the European region, SARS-CoV-2 was detected by PCR in 15% of cases (47/307) with available results (see Annex). Preliminary reports from the United States indicate that SARS-CoV-2 was detected in 10% of cases (8/83) with available results.

Most reported cases did not appear to be epidemiologically linked; however, epidemiologically linked cases have been reported in Scotland, and the Netherlands.

Box 1. WHO Working case definition of acute hepatitis of unknown aetiology

Epidemiological characteristics of cases