450 cases, 11 dead worldwide in growing mystery of childhood hepatitis

Enlarge / Adenoviruses remain the main suspect, although no cause has been identified.

The global tally of unexplained hepatitis cases in children has reached around 450, including 11 reported deaths, according to an update from the European Center for Disease Prevention and Control.

The cases come from more than two dozen countries around the world, with around 14 countries reporting more than five cases. The countries with the highest number of cases so far are the UK and the US.

In the UK, authorities have identified 163 cases in children under 16, 11 of whom required liver transplants. Last week, the US Centers for Disease Control reported 109 cases under investigation in children under 10 in 25 states. Of these cases, 14% required a liver transplant and five children died.

Fourteen countries in the European Union have reported about 106 cases collectively, with Italy (35) and Spain (22) reporting the highest counts of EU member countries. Outside the EU, officials have reported cases in Argentina (8), Brazil (16), Canada (7), Costa Rica (2), Indonesia (15), Israel (12), in Japan (7), Panama (1), Palestine (1), Serbia (1), Singapore (1) and South Korea (1).

The 11 deaths were reported in Indonesia (5), Palestine (1) and the United States (5).

The cause of severe hepatitis – inflammation of the liver – remains a mystery, despite the growing count. Some of the cases were identified retrospectively, dating back to October 1, 2021.

Health officials around the world are tracking cases of acute hepatitis in children that cannot be explained by common culprits, such as hepatitis A, B, C, D, and E viruses, which are known to damage the liver. Those with cases also have elevated levels of liver enzymes.

“Right now, the main hypotheses remain those involving the adenovirus,” Philippa Easterbrook, a senior scientist at the World Health Organization, said in a press briefing on Tuesday. “But,” she added, “I think [there’s] also always an important consideration on the role of COVID, either as a co-infection or as a past infection.

Easterbrook noted that about 70% of cases that have been tested for adenovirus have tested positive, and subtype testing continues to commonly reveal adenovirus type 41.

Data coming soon

Adenoviruses are not known to cause hepatitis in healthy children, although the large family of viruses have previously been linked to liver damage in children with weakened immune systems. Adenoviruses often cause common respiratory infections in healthy children, while type 41 is linked to gastrointestinal illnesses.

So far, liver biopsy data have not revealed adenovirus in the livers of affected children, raising further questions. Additionally, adenoviruses are quite common in children and some of the cases of hepatitis occurred when transmission of adenoviruses in the general population was high. This raises the possibility that the detection of adenovirus is merely accidental and not the cause of the liver damage.

At Tuesday’s press conference, Easterbrook noted the possibility, saying: “Hopefully within a week there will be data from the UK on [an] large case-control study comparing whether the detection rate of adeno in children with liver disease differs from that of other hospitalized children. This will really help determine if the adeno is just an accidental infection that was caught or if there is a causal or probable connection. »

Otherwise, authorities have reported that the cases are sporadic and unlinked, with no known common exposure to drugs, food, drink, toxic substances or travel. The US CDC has also ruled out bacterial infections, urinary tract infections, autoimmune hepatitis and a rare genetic condition called Wilson’s disease, based on data from cases in Alabama.

According to Easterbrook, tests have found that around 18% of cases are positive for SARS-CoV-2. However, the US CDC ruled out SARS-CoV-2 as a possible direct cause of the cases, noting that the first nine cases identified in Alabama were all negative for the virus. During a press briefing last week, CDC Deputy Director for Infectious Diseases Jay Butler said the agency is still keeping open the possibility that prior SARS-CoV-2 infections may play a role in cases. Studies looking at past SARS-CoV-2 infections in affected children are currently underway in the United States and elsewhere.

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