The Centers for Disease Control and Prevention released a nationwide public health advisory on Thursday about an unusual group of children ages 1 to 6 diagnosed with severe hepatitis and an adenovirus infection. Although no deaths were reported, two of the pediatric patients required liver transplants.
The first US cluster was detected in Alabama where nine pediatric patients were admitted to hospital between October 2021 and February 2022 with significant liver injury – including three with acute liver failure – with no known cause. They all tested positive for adenovirus, with lab tests showing some of the children had adenovirus type 41, which usually causes pediatric gastroenteritis marked by diarrhoea, nausea and vomiting. Although there are over 100 known adenoviruses, with about 50 known to infect humans, most are common and cause only minor illness.
All children were previously healthy and none reported recent SARS-CoV-2 infection. Additionally, the children lived statewide and no known epidemiological links or common exposures were found.
Also on Thursday, the North Carolina Department of Health and Human Services told STAT it was investigating two cases of hepatitis in young children. Both cases involved school-aged children under the age of 10. Neither required a liver transplant and both made full recoveries. SARS-CoV-2 infections also played no role in North Carolina patients.
These cases in the United States come after the World Health Organization (WHO) reported a worrying number of acute hepatitis of unknown origin in several places across Europe.
The WHO on April 15 issued a public health notice similar to that of the CDC, detailing 74 cases that had been identified in the UK. Additional cases have since been detected, 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 had liver transplants.
Elsewhere in Europe, Spain has confirmed three cases in children aged 1 to 13, while Ireland is investigating “less than five” cases. The country’s health authorities have also reported cases in Denmark and the Netherlands.
Hepatitis, adenovirus and SARS-CoV-2
Unlike the US cases, the WHO has not ruled out the possible role that SARS-CoV-2 may play in these recent illnesses, particularly in the UK.
“Laboratory tests excluded hepatitis virus types A, B, C and E (and D where applicable) in these cases (UK), while SARS-CoV-2 and/or l Adenoviruses have been detected in several cases,” the international health agency said. says the organization. “The UK has recently observed an increase in the activity of adenoviruses, which co-circulates with SARS-CoV-2, although 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 Alabama pediatric patients, while all tested positive for adenovirus infection, with some positive for adenovirus type 41, in particular. Adenovirus was confirmed in most (~75%) European cases, but not all.
Adenovirus type 41 usually presents as diarrhea, vomiting, and fever, and is often accompanied by respiratory symptoms. According to the CDC, adenovirus type 41 is not known to cause hepatitis in otherwise healthy children, making this situation all the more rare.
“At this time, we believe that adenovirus may be the cause of these reported cases, but investigators are learning even 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.
Scottish health authorities agree.
“Although our investigations increasingly suggest a link to adenovirus infection, we continue to investigate other potential causes and will post further updates as the situation evolves 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 the CDC and state public health authorities. . The federal health agency suggests testing whole blood by PCR because plasma samples from two Alabama patients tested negative for adenovirus by qPCR, but both were positive when retested with whole blood.
WHO says laboratory testing for additional infections, chemicals and toxins is underway for cases already identified, and further investigations by national authorities will include more detailed exposure history, testing toxicological and additional virological/microbiological tests.