CDC Warns of Severe Hepatitis and Adenovirus Infections in Children

The US Centers for Disease Control and Prevention (CDC) issued a Health Alert Network Health Advisory to notify clinicians and public health authorities of a cluster of children identified with hepatitis and adenovirus infection.

The World Health Organization (WHO) has reported 169 cases in at least 11 countries, including 114 cases in the United Kingdom. Cases of pediatric hepatitis in children who tested negative for hepatitis viruses A, B, C, D, and E were reported earlier this month in the United Kingdom, including some with adenovirus type 41 infection. Cases have also been reported in Asia. About 10% of children have required liver transplants, and several have reportedly died.

In the United States there are now reports of at least 30 cases of the infection in 10 states. The first report came from Alabama. In November 2021 clinicians at a large children’s hospital in Alabama notified the CDC of five pediatric patients with significant liver injury, including three with acute liver failure, who also tested positive for adenovirus. All children were previously healthy. None had COVID-19. Case-finding efforts at this hospital identified four additional pediatric patients with hepatitis and adenovirus infection, for a total of nine patients admitted from October 2021 through February 2022. Five patients were sequenced and found to have adenovirus type 41 infection. In two patients, plasma samples were negative for adenovirus, but both patients were positive when retested using whole blood. Two patients required liver transplant; no patients died. Since then, other state health departments have reported cases, including four in Wisconsin and two in Minnesota, including one who died and one who required a liver transplant. Reported cases have occurred in patients between the ages of 1 month and 16 years.

The CDC notes that based on the Alabama data, the following causes have been ruled out:

  • Hepatitis viruses A, B, and C
  • SARS-CoV-2 infection
  • Autoimmune hepatitis
  • Wilson disease

There is no link between these cases and COVID-19 vaccination, according to the WHO, because most affected children have not been vaccinated.

CDC Recommendations and Requests for Reports
The CDC’s advisory notifies US clinicians who encounter pediatric patients with hepatitis of unknown etiology to consider adenovirus testing and to elicit reporting of such cases to state public health authorities and to the CDC. Nucleic acid amplification testing (eg, polymerase chain reaction, PCR) is preferred for adenovirus detection and can be performed on respiratory specimens, stool or rectal swabs, or blood. Anecdotal reports suggest that testing whole blood by PCR might be more sensitive than testing plasma by PCR; therefore, testing of whole blood could be considered in those without an etiology who tested negative for adenovirus in plasma samples.

The CDC requests notification from clinicians or state public health authorities of children younger than 10 years with elevated aspartate aminotransferase or alanine aminotransferase (>500 U/L) who have hepatitis of an unknown etiology (with or without any adenovirus testing results, independent of the results) since October 1, 2021. Email CDC at [email protected] to report any cases meeting these criteria or with any related questions. If patients are still under care or have residual specimens available, save and freeze them for possible additional testing and contact CDC for additional instructions at the designated email address.

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