Adenovirus and Acute Hepatitis Advisory for Healthcare Providers

Recommendations for Adenovirus Testing and Reporting of Children with Acute Hepatitis of Unknown Etiology

Posted April 27, 2022. Past health advisories and alerts are archived for historical purposes and are not maintained or updated.


Summary

The Centers for Disease Control and Prevention (CDC) is issuing this Health Alert Network (HAN) Health Advisory to notify clinicians and public health authorities of a cluster of children identified with hepatitis and adenovirus infection. In November 2021, clinicians at a large children’s hospital in Alabama notified 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; all five that were sequenced had adenovirus type 41 infection identified. In two patients, plasma samples were negative for adenovirus by quantitative polymerase chain reaction (qPCR), but both patients were positive when retested using whole blood. Two patients required liver transplant; no patients died. A possible association between pediatric hepatitis and adenovirus infection is currently under investigation. 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 infection.

This Health Advisory serves to notify U.S. clinicians who may 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 CDC. Nucleic acid amplification testing (NAAT, e.g. PCR) is preferred for adenovirus detection and may be performed on respiratory specimens, stool or rectal swabs, or blood.

Background

Hepatitis is inflammation of the liver that can be caused by viral infections, alcohol use, toxins, medications, and certain other medical conditions. In the United States, the most common causes of viral hepatitis are hepatitis A, hepatitis B, and hepatitis 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 of hepatitis depends on the underlying etiology.

Adenoviruses are doubled-stranded DNA viruses that spread by close personal contact, respiratory droplets, and fomites. There are more than 50 types of immunologically distinct adenoviruses that can cause infections in humans. Adenoviruses most commonly cause respiratory illness but depending on the adenovirus type they can cause other illnesses such as gastroenteritis, conjunctivitis, cystitis, and, less commonly, neurological disease. There is no specific treatment for adenovirus infections.

Adenovirus type 41 commonly causes pediatric acute gastroenteritis, which typically presents as diarrhea, vomiting, and fever; it can often be accompanied by respiratory symptoms. While there have been case reports of hepatitis in immunocompromised children with adenovirus type 41 infection, adenovirus type 41 is not known to be a cause of hepatitis in otherwise healthy children.

Recommendations
  • Clinicians should consider adenovirus testing in pediatric patients with hepatitis of unknown etiology. NAAT (e.g. PCR) is preferable and may be done on respiratory specimens, stool or rectal swabs, or blood.
  • Anecdotal reports suggest that testing whole blood by PCR may 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.
Request for Notification of Possible Cases

Please notify SRHD of any children who have an unknown etiology for their hepatitis (with or without any adenovirus testing results, independent of the results) since October 1, 2021 by encrypted email at CDEpi@srhd.org, by fax at 509-324-3623, or phone at 509-324-1449.

If patients are still under medical care or have residual specimens available, please save and freeze them for possible additional testing and contact SRHD for additional instructions.

For More Information

Centers for Disease Control and Prevention Hepatitis

Centers for Disease Control and Prevention Adenovirus