#16,788
Normally summer brings with it a drop in infectious disease reports, or at least a change more to vector-borne illnesses (like Dengue, CHKV, Zika, etc.), but this year seems destined to defy those norms.
Along with the evolution and spread of COVID, sporadic (and likely under-reported) spillover of avian H5N6 and H3N8 viruses into humans in China, arguably the worst (and most widespread) avian epizootic (HPAI H5N1) on record, and the unprecedented global spread of Monkeypox, the world is also dealing with the as-yet unidentified cause of acute hepatitis in hundreds of children being reported by nearly 3 dozen countries.
We are now 7 weeks into this investigation (see UK HSA: Investigating An Unusual Increase In Hepatitis In Children), and while a number of causes have been ruled out, the reason(s) behind this clustering of cases remains unknown.
Today the WHO has released a lengthy DON update, which lists 650 known cases across 33 countries, and provides an updated risk assessment and advice. According to this update:
Out of the 650 probable cases, at least 38 (6%) children have required transplants, and nine (1%) deaths have been reported to WHO.
Due to its length, I've only posted some excerpts, so follow the link to read it in its entirety.
Acute hepatitis of unknown aetiology in children - Multi-country
27 May 2022
Outbreak at a glance
Six hundred and fifty probable cases of acute hepatitis of unknown aetiology in children have been reported to WHO from 33 countries in five WHO Regions between 5 April and 26 May 2022. The aetiology of this severe acute hepatitis remains unknown and under investigation; the cases are more clinically severe and a higher proportion develops acute liver failure compared with previous reports of acute hepatitis of unknown aetiology in children. It remains to be established whether and where the detected cases are above-expected baseline levels. WHO assesses the risk at the global level as moderate.
Outbreak description:
Following the WHO Multicountry Disease Outbreak News on Acute hepatitis of unknown aetiology published on 23 April 2022, there have been continuing reports of cases of acute hepatitis of unknown cause among young children.
As of 26 May 2022, 650 probable cases fitting the WHO case definition1 have been reported to WHO from 33 countries in five WHO Regions, with 99 additional cases pending classification. The majority of reported cases (n=374; 58%) are from the WHO European Region (22 countries), with 222 (34%) cases from the United Kingdom of Great Britiain and Northern Ireland alone. Probable cases and cases pending classification have also been reported from the Region of the Americas (n=240, including 216 cases in the United States of America), Western Pacific Region (n=34), the South-East Asia Region (n=14) and Eastern Mediterranean Region (n=5) (Figure 1, Table 1).
WHO working case definition:
Confirmed: N/A at presentProbable: A person presenting with an acute hepatitis (non hep A-E*) with serum transaminase >500 IU/L (AST or ALT), who is 16 years and younger, since 1 October 2021Epi-linked: A person presenting with an acute hepatitis (non hep A-E*) of any age who is a close contact of a probable case, since 1 October 2021*If hepatitis A-E serology results are awaited, but other criteria met, these can be reported and will be classified as “pending classification”. Cases with other explanations for their clinical presentation are discarded.**Delta testing is not required, as it is only undertaken in persons who are HBsAg positive to establish presence of co-infection.
(SNIP)
WHO risk assessment
WHO assesses the risk at the global level as moderate considering that:The aetiology of this severe acute hepatitis remains unknown and under investigation; the cases are more clinically severe and a higher proportion develops acute liver failure compared with previous reports of acute hepatitis of unknown aetiology in children;
- Limited epidemiological, laboratory, histopathological and clinical information is currently available to WHO;
- The actual number of cases may be underestimated in some settings, in part due to the limited surveillance capacity in place;
- The source and mode of transmission of the potential aetiologic agent(s) has not yet been determined, and so the likelihood of further spread cannot be fully assessed;
- Although there are no available reports of healthcare-associated infections, human-to-human transmission cannot be ruled out as there have been a few reports of epidemiologically linked cases.
Adenovirus has been found in 75% of the cases tested in the United Kingdom, but the data for other countries are incomplete. Of the small number of samples that have so far been typed, a majority have been confirmed for Type 41 adenovirus (in the United Kingdom, in 27 of 35 cases with an available result). Adenovirus associated virus 2 (AAV-2) has also been detected in a small number of cases in the United Kingdom using meta-genomics in liver and blood samples. However, many of the remaining cases did not have appropriate samples taken, highlighting the importance of appropriate sampling (whole blood) to further characterize the type of adenovirus detected. Additionally, Type 41 adenovirus infection has not previously been linked to such a clinical presentation in otherwise healthy children.
While adenovirus is a plausible hypothesis as part of the pathogenesis mechanism, further investigations are ongoing for the causative agent; adenovirus infection (which generally causes mild self-limiting gastrointestinal or respiratory infections in young children) does not fully explain the more severe clinical picture observed with these cases. Factors such as increased susceptibility amongst young children following a lower level of circulation of adenovirus during the COVID-19 pandemic, the potential emergence of a novel adenovirus, SARS-CoV-2 co-infection or a complication of previous SARS-CoV-2 infection, leading to superantigen-mediated immune cell activation, proposed a causal mechanism of multisystem inflammatory syndrome in children need to be further investigated. Hypotheses related to side effects from COVID-19 vaccines are currently not supported as most of the affected children did not receive these vaccines. Other infectious and non-infectious explanations as independent or contributory factors need to be excluded to fully assess and manage the risk. It is important to note that the current apparent association identified with adenovirus could be an incidental finding due to enhanced laboratory testing in association with increased levels of community transmission of adenovirus. This will be further clarified with the expansion of adenovirus testing to other cases beyond Europe and the United States, and reporting of the findings from the UKHSA case-control study currently underway.
The absence of a confirmed aetiology poses additional challenges in some countries, including implementation of WHO’s case definition and further diagnostic exclusion, due to limited testing capacity, including for Hepatitis A-E viruses and adenovirus. The presence of cases of acute hepatitis in children cannot be ruled out in countries where cases have not been detected or reported yet, but it is unlikely that symptomatic and severely ill case patients requiring hospitalization would remain undetected.
