Health authorities in North Carolina say they are investigating two cases of hepatitis in young children, making the state the second to report cases that appear to be linked to an outbreak that is being seen in a growing number of countries.
Bailey Pennington, a spokesperson for the state’s Department of Health and Human Services, told STAT of the cases in an email on Thursday, saying the state is both conducting surveillance for other possible cases and working with its poison control center and epidemiologists to try to determine the cause of the illnesses.
“Both North Carolina cases were in school-aged children. Neither required a transplant and both have since recovered,” Pennington said.
The development came as health authorities in the United States and some European countries on Thursday cautioned doctors to be on the lookout for young children suffering from signs of hepatitis and urging parents to make sure their children wash their hands well and often as investigations continue into cases of unexplained hepatitis in kids. The leading hypothesis at present is that infection with an adenovirus, a virus normally associated with colds, may have triggered the liver inflammation in affected children.
The overall number of cases is small, but the outbreak is unusual. The affected children are mainly under the age of 10 — with many younger than 5. All were previously healthy. While most of the children have made full recoveries, some have required liver transplants, including two in Alabama, eight in the United Kingdom, and one in Spain. To date, there have been no reports of deaths.
The number of countries reporting these unusual cases of hepatitis continues to rise, with reports that France is investigating two suspected cases in Lyon and Israel is studying a dozen children who had unexplained cases of hepatitis over the past four months, two requiring liver transplants. The U.K., the U.S., Spain, Denmark, the Netherlands, and Ireland have all reported cases. To date the largest number has been reported by the U.K., which has now recorded 108 cases — 79 in England, 14 in Scotland, and 15 in Wales and Northern Ireland.
Most of the cases have been diagnosed this year, though Alabama first noticed a cluster of five cases last November and notified the Centers for Disease Control and Prevention, with which it has been working to try to determine the cause of the illnesses. Alabama has since recorded four more cases.
The CDC issued an advisory to clinicians Thursday over its health alert network urging them to consider testing children with signs of liver inflammation for adenoviruses. A variety of issues can cause hepatitis, including toxins and fungi, but the leading causes, the hepatitis viruses A, B, C, D, and E, have been ruled out in these children.
Authorities in the U.K. have reported 77% of their cases have tested positive for adenovirus infection and Alabama reported last week that five of its nine cases tested positive for adenovirus 41. Karen Landers, district medical officer for the Alabama Department of Public Health, told STAT on Thursday that not all of the cases had a high enough viral load to be able to conduct tests to home in on the type of adenovirus. There are more than 100 known adenoviruses, though roughly half that number is known to infect people.
The CDC’s alert said that adenovirus type 41 commonly causes acute gastroenteritis — inflammation of the stomach and intestines, which induces diarrhea and vomiting — as well as respiratory symptoms. There have been reports of hepatitis in immunocompromised children infected with adenovirus type 41, but it hasn’t previously been seen to cause liver disease in healthy children.
Public health officials in Scotland, which first alerted the broader world to the problem, said Thursday they haven’t closed the door on other possible causes.
“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,” Jim McMenamin, head of Public Health Scotland’s health protection unit, said in a statement.
The U.K. Health Security Agency said it too is actively pursuing other possible causes, as well as investigating whether the implicated adenovirus has undergone genetic changes that might explain the infections.
Rachel Tayler, a gastroenterologist at the Royal Hospital for Children, Glasgow, first sensed something was going on in late March, after seeing several cases in quick succession. Tayler, her department’s lead for pediatric hepatitis cases, said in the course of a normal year, the hospital would care for two children with unexplained hepatitis.
“To go from that to then suddenly have 13 is why we’ve recognized that there was something going on,” she told STAT late last week. Scotland has since reported another case. One of the children from Scotland required a liver transplant.
“The severity of the illness was one of the other things we were concerned about,” Tayler said. “Because children do present and will have mild evidence of liver inflammation with lots of common viral infections. But the degree of it was the thing that was concerning to us.”
Authorities have ruled out Covid vaccines as a source of the illness. “None of the currently confirmed cases in the U.K. is known to have been vaccinated,” the Health Security Agency’s statement said.