The Centers for Disease Control and Prevention (CDC) issued the health advisory below today. The full CDC Health Advisory is below and online . Request for Notification of Possible Cases CDC is requesting notification from clinicians or state public health authorities of children 500 U/L) who have an unknown etiology for their hepatitis (with or without any adenovirus testing results, independent of the results) since October 1, 2021. Please email CDC at firstname.lastname@example.org to notify of any cases meeting the above criteria or with any related questions. For cases in LA County residents, please also email email@example.com to notify LA County Public Health. If patients are still under medical care or have residual specimens available, please save and freeze them for possible additional testing and contact CDC at firstname.lastname@example.org for additional instructions. This is an official CDC Health Advisory Distributed via the CDC Health Alert Network April 21, 2022, 11:00 AM ET CDCHAN-00462 Recommendations for Adenovirus Testing and Reporting of Children with Acute Hepatitis of Unknown Etiology 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 US 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 [5, 6]. 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 CDC is requesting notification from clinicians or state public health authorities of children 500 U/L) who have an unknown etiology for their hepatitis (with or without any adenovirus testing results, independent of the results) since October 1, 2021. Please email CDC at email@example.com to notify of any cases meeting the above criteria or with any related questions. If patients are still under medical care or have residual specimens available, please save and freeze them for possible additional testing and contact CDC at firstname.lastname@example.org for additional instructions. For More Information Division of Viral Hepatitis | CDC Adenovirus | CDC References World Health Organization. Acute hepatitis of unknown aetiology - the United Kingdom of Great Britain and Northern Ireland. Disease Outbreak News [Internet]. 2022 Apr 15; Available from: https://www.who.int/emergencies/disease-outbreak-news/item/acute-hepatitis-of-unknown-aetiology---the- united-kingdom-of-great-britain-and-northern-ireland Hepatitis Webpage. Centers for Disease Control and Prevention. Available from: https://www.cdc.gov/hepatitis/abc/index.htm Adenoviruses Webpage. Centers for Disease Control and Prevention. Available from: http://www.cdc.gov/adenovirus/index.html Kang G. Viral Diarrhea. International Encyclopedia of Public Health [Internet]. Elsevier; 2017. P. 260-7. Available from https://www.sciencedirect.com/referencework/9780128037089/international-encyclopedia- of-public-health Munoz FM, Piedra PA, Demmler GJ. Disseminated Adenovirus Disease in Immunocompromised and Immunocompetent Children. CLIN INFECT DIS. 1998. Nov;27(5):1194-200. https://doi.org/10.1086/514978 Peled N, Nakar C, Huberman H, Scherf E, Samra Z, Finkelstein Y, et al. Adenovirus Infection in Hospitalized Immunocompetent Children. Clin Pediatr (Phila). 2004 Apr;43(3):223–9. https://doi.org/10.1177/000992280404300303 The Centers for Disease Control and Prevention (CDC) protects people's health and safety by preventing and controlling diseases and injuries; enhances health decisions by providing credible information on critical health issues; and promotes healthy living through strong partnerships with local, national, and international organizations. Categories of Health Alert Network messages : Health Alert Requires immediate action or attention; highest level of importance Health Advisory May not require immediate action; provides important information for a specific incident or situation Health Update Unlikely to require immediate action; provides updated information regarding an incident or situation HAN Info Service Does not require immediate action; provides general public health information ##This message was distributed to state and local health officers, state and local epidemiologists, state and local laboratory directors, public information officers, epidemiologists, HAN coordinators, and clinician organizations## To view a printable PDF of this communication and other LAHAN communications, please visit publichealth.lacounty.gov/lahan . If this message was forwarded to you, please join LAHAN here .