The Centers for Disease Control and Prevention issued a nationwide public health advisory Thursday regarding an unusual cluster of children aged 1 to 6 diagnosed with severe hepatitis and adenovirus infection. While no deaths have been reported, two of the pediatric patients required a liver transplant.
The first U.S. cluster was detected in Alabama where nine pediatric patients were admitted to the hospital between October 2021 and February 2022 with significant liver injury—including three with acute liver failure—without known cause. They all tested positive for adenovirus, with laboratory tests showing some of the children had adenovirus type 41, which commonly causes pediatric gastroenteritis marked by diarrhea, nausea and vomiting. While there are more than 100 known adenoviruses, with about 50 known to infect humans, most are common and cause only minor illnesses.
All of the children were previously healthy, and none reported recent SARS-CoV-2 infection. Additionally, the children lived throughout the state and no known epidemiological link or common exposures were found.
Also on Thursday, North Carolina’s Department of Health and Human Services told STAT they are investigating two cases of hepatitis in young children. Both cases were in school-aged children under 10. Neither required a liver transplant and both have fully recovered. SARS-CoV-2 infections also did not play a role in either North Carolina patient.
These U.S. cases come after the World Health Organization (WHO) reported concerningly high numbers of acute hepatitis of unknown origin in multiple locations throughout Europe.
WHO released a public health notice similar to the CDC’s on April 15, detailing 74 cases that had been identified in the UK. Additional cases have been detected since, bringing the total to 108 cases in the UK—79 in England, 14 in Scotland and 15 in Wales and Northern Ireland, the most of any country. No deaths have been reported in the UK, but eight children have undergone liver transplants.
Elsewhere in Europe, Spain has confirmed three cases in children ranging from 1 to 13-years-old, while Ireland is investigating “less than five” cases. Country health authorities have also reported cases in Denmark and the Netherlands.
Hepatitis, adenovirus and SARS-CoV-2
Unlike the U.S. cases, WHO has not ruled out the possible role SARS-CoV-2 may be playing in these recent illnesses, especially in the UK.
“Laboratory testing has excluded hepatitis type A, B, C, and E viruses (and D where applicable) in these (UK) cases, while SARS-CoV-2 and/or adenovirus have been detected in several cases,” the international health organization said. “The United Kingdom has recently observed an increase in adenovirus activity, which is co-circulating with SARS-CoV-2, though the role of these viruses in the pathogenesis is not yet clear.”
Hepatitis A, hepatitis B and hepatitis C viruses were ruled out for all the Alabama pediatric patients, while all tested positive for adenovirus infection, with some positive for adenovirus type 41, specifically. Adenovirus has been confirmed in most (~75%) of the European cases, but not all.
Adenovirus type 41 typically presents as diarrhea, vomiting and fever, and is often accompanied by respiratory symptoms. According to the CDC, adenovirus type 41 is not known to be a cause of hepatitis in otherwise healthy children—which makes this situation all the more rare.
“At this time, we believe adenovirus may be the cause for these reported cases, but investigators are still learning more—including ruling out other possible causes and identifying other possible contributing factors. So far, other common causes of viral hepatitis, such as Hepatitis A, B, and C have been ruled out,” the CDC said in a statement.
Health authorities in Scotland agree.
“Although our investigations increasingly suggest that there is a link to adenovirus infection, we are continuing to look into other potential causes and will issue further updates as the situation develops and we have more information,” said Jim McMenamin, Head of Health Protection, Public Health Scotland in a statement on Thursday.
The CDC is asking physicians to consider adenovirus testing for pediatric patients with hepatitis of unknown etiology, and to report any possible cases of hepatitis of unknown origin to CDC and state public health authorities. The federal health agency suggests testing whole blood by PCR, as plasma samples from two Alabama patients tested negative for adenovirus by qPCR but both were positive when retested using whole blood.
WHO says laboratory testing for additional infections, chemicals and toxins is underway for the already identified cases, and further investigations by national authorities will include more detailed exposure history, toxicology testing and additional virological/microbiological tests.