At least one child has died of unexplained liver inflammation amid a growing international outbreak of mysterious cases of hepatitis in children, according to the World Health Organization.
The number of outbreaks has reached more than 170 cases in 12 countries and is expected to continue to increase. At least 17 children — 10 percent of the cases — required a liver transplant. Affected children range in age from one month to 16 years, although the majority are children under the age of 10 and many under the age of 5.
Over the weekend, the WHO reported 114 cases in the UK, 13 in Spain, 12 in Israel, six in Denmark, fewer than five in Ireland, four in the Netherlands, four in Italy, two in Norway, two in France, and one in Romania one in Belgium. The WHO also found nine cases in the US, all in Alabama. But two more cases were reported in North Carolina last week, bringing the total number of cases in the US to at least 11. Two of the US cases resulted in transplants.
The WHO has not reported the age or nationality of the deceased child, but no deaths have been reported in the US.
Medical mystery
Although the number of cases worldwide may seem low, severe liver inflammation (also known as hepatitis) is uncommon in young children. Health officials in Scotland – who first sounded the alarm about the unexplained cases – realized something was wrong when they saw 13 cases of severe childhood hepatitis in March and April alone. Typically, Scotland records fewer than four such cases over a full year.
Health experts around the world are working to understand what causes the severe liver damage. Affected children have consistently tested negative for viruses that attack the liver, namely hepatitis viruses A, B, C, D and E. To date, there has been no clear association between the cases, nor an association with travel, nor a clear association with an environmental , drug or food exposure. The vast majority of cases had not received COVID-19 vaccines, ruling out that possibility.
The prime suspect remains an adenovirus, although the common family of viruses is not known to cause hepatitis in healthy children. Of the approximately 170 reported cases, at least 74 tested positive for an adenovirus, with 18 testing specifically positive for adenovirus type 41.
More than 50 different adenoviruses are known to infect humans, but they are typically associated with respiratory, ocular, and sometimes gastrointestinal and disseminated infections. Some adenoviruses have occasionally been associated with hepatitis, but generally only in immunocompromised children.
Adenovirus type 41, which has not been linked to hepatitis, typically causes diarrhea, vomiting, fever and difficulty breathing, the WHO notes. Based on data from cases in the UK, the most common symptoms of children affected by the outbreak are: jaundice, vomiting and abdominal painand most cases had no fever.
working hypotheses
The international outbreak comes as the UK and the Netherlands have documented a surge in adenovirus infections in the community, as people resume normal activities that have been curtailed during the pandemic. As such, some experts have hypothesized that the hepatitis cases may simply be a rare outcome that has always been possible with common adenovirus – but the rare outcome now appears to be more common as many post-pandemic immunologically naïve children get adenoviruses at the same time . However, there is also a possibility that a new type of adenovirus has emerged and is explaining the hepatitis cases.
It is also possible that it is not due to an adenovirus at all. Some data suggests that many children who test positive for an adenovirus have low levels of the virus in their bodies. These data raised the possibility that the presence of adenoviruses is simply fortuitous – reflecting high community transmission, not the cause of hepatitis.
In addition, it is also possible that an adenovirus is only part of the story and co-infection may explain the unusual cases. One possibility is that a co-infection of SARS-CoV-2 and an adenovirus is behind the cases. WHO noted that 20 children tested positive for SARS-CoV-2 and another 19 were found to be co-infected with SARS-CoV-2 and adenovirus. However, the researchers also do not rule out that the liver damage is a rare consequence of an Omicron infection alone or an infection with a SARS-CoV-2 variant that has not yet been identified.
The WHO and other experts are calling for more awareness, testing and data sharing around the world to solve the mystery.
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