Throughout the month of April, a new global alert has emerged: an unusual uptick in rare hepatitis of unknown origin in children.

International organizations are working to find out what is causing it since the United Kingdom sounded the alarm.

How many cases are there in the world?

In Europe, the European Center for Disease Prevention and Control (ECDC) has published on April 28, 2022, the cases detected in EU countries and the United Kingdom in children under 16 years of age: the United Kingdom reported 111 cases (81 in England). , 14 in Scotland, 11 in Wales and 5 in Northern Ireland).

In addition, 11 countries have reported cases: Austria (2), Belgium (2), Denmark (6), France (2), Ireland (5), Italy (17), Germany (1), the Netherlands (4), Norway (2), Poland (1), Romania (1).

In total, 166 cases have been reported, of which (50) have been positive for adenovirus and (15) have required liver transplantation.

In addition,

the World Health Organization (WHO) has pointed out a total in the world of about 190.

Sporadic cases have been registered in other countries of the world, such as Canada, Israel, Japan and the United States.

How many are the cases in Spain and what is the patient profile?

In Spain there are officially 22 cases registered since December 2021, according to the latest Health report.

Ages range from 18 months to 16 years.

One has needed a transplant.

Of the initially notified cases (report of April 22), 3 cases have been ruled out.

In 4 cases out of 8 analyzed in which results are available, a positive result has been given for adenovirus.

It has been possible to determine at the National Microbiology Center through genomic sequencing that the Adenovirus is type 2 and the rest are pending results.

The Spanish epidemiology services apply an exhaustive questionnaire to all the cases identified to date, without a common cause having been found so far.

What characteristics do cases have to meet to be registered as such?

The definition adopted by Spain at this time is:

  • Case under investigation: Person with severe acute hepatitis (with admission criteria) and in whom determinations against hepatitis A, B, D, C and E have been negative, with elevated GOT or GPT >500 U/L, aged between 0 and 16 years and with a date of onset of symptoms from January 1, 2022.

  • Case with epidemiological link: Person with severe acute hepatitis (with admission criteria) and in whom determinations against hepatitis A, B, D, C and E have been negative, with elevated GOT or GPT >500 U/L of any age who has had close contact with a symptomatic case under investigation since January 1, 2022.

  • Discarded case: Person with severe acute hepatitis (with admission criteria) and acute hepatitis AE or a cause of non-infectious origin that justifies the clinical picture.

What has been ruled out so far?

The ECDC and the WHO insist that the exact cause of hepatitis in these children is still "unknown".

Laboratory tests have excluded viral hepatitis types A, B, C, D, and E in all cases.

What is known about the origins of childhood hepatitis?

In the United Kingdom, a possible cause linked to a high percentage of cases has been established:

adenovirus, specifically AF41

.

Meera Chand, director of clinical and emerging infections at the Health Security Agency, pointed out that, although no hypothesis is ruled out, "in the United Kingdom, adenovirus infection has been identified in 75% of affected patients."

Adenoviruses 40-41 are

one of the most common causes of viral gastroenteritis

in children.

Hepatitis can be a rare complication in these cases, especially in immunosuppressed patients.

The ECDC reminds that fecal-oral exposure to viruses such as adenovirus is more likely in young children.

Therefore, they advise reinforcing general good hygiene practices (including careful hand hygiene and cleaning and disinfection of surfaces) in settings where young children attend.

There is also the possibility, as Chan has pointed out, that "new variants of adenoviruses" or other pathogens of interest are currently circulating.

The head of the Infectious Diseases service at the Virgen Macarena University Hospital in Seville and former president of ECCMID, Jesús Rodríguez-Baño, believes that "the hypothesis of an adenovirus is the most plausible."

Despite this, the specialist agrees with Chan and it would be a new variant with a more hepatotropic profile, that is, with a greater capacity to cause liver damage.

In Spain, the impact of the adenovirus has been studied.

In three of the four Autonomous Communities with available information on adenoviruses in the Microbiological Information System, there is no evidence of any increase in these cases in 2022 compared to the year before the pandemic.

In one of them, between February 1 and April 29, there are 603 cases of adenovirus compared to 419 for the same period of 2019. Information from the National Epidemiological Surveillance Network (RENAVE) does not contain any outbreak of adenovirus in 2022 , taking into account that there is a delay in the notification of the information.

Why is adenovirus not the definitive answer?

Because this theory is only adapted to a profile of patients in the United Kingdom, not globally.

Antonio Rivero-Juárez, a researcher at CiberINFEC and at the Infectious Diseases Unit of the Reina Sofía University Hospital and Maimónides Institute for Biomedical Research of Córdoba (Imibic), believes that "this is not enough", because there are "older minors up to the age of 16.

At the Congress of the European Society for Clinical Microbiology and Infectious Diseases (ECCMID), recently held in Lisbon, the main theories were presented: from a cofactor that makes adenovirus infections more serious;

a new variant of adenovirus;

a drug, toxin, or environmental exposure;

a new pathogen;

or even a new variant of SARS-CoV-2.

At this time, in any case, the ECDC sets as a priority "to determine the underlying etiological factor, the pathogenesis of the disease and the risk factors for the severity of cases of severe acute hepatitis among children".

"The current hypothesis is that a human adenovirus infection or co-infection is the most likely causative agent. However, other etiologies are still being studied and have not yet been excluded," they emphasize.

Is there any relationship with covid or vaccination against SARS-CoV-2 infection?

Artificial anti-Covid immunization has been categorically ruled out, because most children are minors without access to vaccine administration.

And regarding the possibility of its natural infection, Rivero-Juárez explained to this newspaper that "only a small percentage of children with Covid reinfections have been found."

What symptoms have been reported in the cases?

Patients present with acute hepatitis, with a high level of transaminases (more than 500 IU/L).

Many of the children suffer from jaundice and gastrointestinal symptoms, such as abdominal pain, vomiting and diarrhoea.

How many serious cases have there been?

To date, 10% of reported cases have required a liver transplant.

This supposes a strong impact given the affected pediatric population, according to the European center.

In addition, one death has been recorded so far.

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  • Hepatitis

  • Infectious diseases

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