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Consider adenovirus testing for hepatitis cases of unknown etiology: CDC alert

April 21, 2022

A possible association between pediatric hepatitis and adenovirus infection is under investigation after a cluster of children with these conditions was identified. The Centers for Disease Control and Prevention (CDC) issued a Health Alert Network advisory Thursday for clinicians and public health officials.

 Cases in Alabama, Europe

In November 2021, clinicians at an Alabama children’s hospital notified the CDC of five previously healthy children with significant liver injury. Three had acute liver failure and also tested positive for adenovirus. None had COVID-19. Two patients required a liver transplant and none died.

Case-finding efforts at the hospital identified four additional children with hepatitis and adenovirus for a total of nine patients admitted from October 2021 through February 2022.

All five that were sequenced had adenovirus type 41 infection. In two patients, plasma samples were negative for adenovirus by quantitative polymerase chain reaction (qPCR), but both patients tested positive when retested using whole blood.

In addition, cases of pediatric hepatitis in children who tested negative for hepatitis viruses A,B, C, D and E — including some with adenovirus infection — were reported earlier this month in the United Kingdom.

 Testing, reporting

Clinicians who encounter patients with hepatitis of unknown etiology should consider adenovirus testing and report cases to state public health authorities and the CDC. Nucleic acid amplification testing (e.g., PCR) is preferred for adenovirus detection. This may be performed on respiratory specimens, stool or rectal swabs, or blood.

The CDC is requesting notification of cases of children younger than 10 years with elevated aspartate aminotransferase or alanine aminotransferase (over 500 units per liter) who have unknown etiology for hepatitis — with or without adenovirus testing results, independent of the results, since October 2021.

 Background

In the U.S., the most common causes of viral hepatitis are hepatitis A, B and C viruses. Signs and symptoms of hepatitis include fever, fatigue, loss of appetite, nausea, vomiting, abdominal pain, dark urine, light-colored stools, joint pain and jaundice. Treatment depends on the underlying etiology.

Adenoviruses are double-stranded DNA viruses that spread by close personal contact, respiratory droplets and fomites. More than 50 types can cause infection in humans. While adenoviruses most commonly cause respiratory illness, depending on the type, they also can cause illnesses such as gastroenteritis, conjunctivitis, cystitis and, occasionally, neurological disease.

There is no specific treatment for adenovirus infections.

Adenovirus type 41 usually causes pediatric acute gastroenteritis, typically presenting as diarrhea, vomiting and fever, and sometimes accompanied by respiratory symptoms.

While hepatitis has been reported in immunocompromised children with adenovirus type 41 infection, this type is not known to be a cause of hepatitis in otherwise healthy children, according to the health advisory.

 Contact CDC

Email the CDC at ncirddvdgast@cdc.gov to notify the agency of cases meeting the criteria or with questions. If patients still are under medical care or have residual specimens available, save and freeze them for possible additional testing and contact the CDC for instructions.

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