The Centers for Disease Control and Prevention (CDC) issued a Health Alert Network Health Advisory regarding a possible link between a mysterious cluster of children with hepatitis, which is inflammation of the liver, and a virus known as adenovirus, according to a recent press release.
"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," the CDC said. "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."
A large children’s hospital in Alabama in November 2021 notified the agency of five previously healthy pediatric patients with significant liver injury, including three with acute liver failure who were also positive for adenovirus, but none had COVID-19.
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Adenovirus most commonly causes respiratory illness, but can cause a range of other illnesses, including conjunctivitis — otherwise known as pink eye — acute gastroenteritis, cystitis and rarely neurologic disease, but there is no treatment other than symptomatic care, according to the CDC.
The virus is spread by close personal contact, respiratory droplets and fomites with more than 50 distinct types that can cause infections in humans.
But the virus type sequenced in the five pediatric patients, adenovirus type 41, commonly causes acute gastroenteritis, which typically presents as diarrhea, vomiting and fever, but can be associated also with 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," per the health advisory.
Four additional pediatric patients with hepatitis and adenovirus infection were identified at the Alabama children’s hospital for a total of nine hospitalized patients from October 2021 through February 2022, with two patients requiring a liver transplant. But no patients died.
The United Kingdom Health Security Agency (UKHSA), Public Health Scotland, Public Health Wales and the Public Health Agency reported a total of 108 cases of "sudden onset hepatitis" in children under the age of 10 who tested negative for common viruses known to cause hepatitis, including hepatitis viruses A, B, C, D, and E between January 2022 and April 12, 2022, according to a U.K. Health Security Agency press release.
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U.K. authorities reported approximately 77% of their cases have tested positive for adenovirus infection.
"The United Kingdom has recently observed an increase in adenovirus activity, which is co-circulating with SARS-CoV-2, though the role of these viruses in the pathogenesis (mechanism by which disease develops) is not yet clear," the World Health Organization noted.
The release noted 79 of the confirmed cases are in England, 14 are in Scotland and the remainder are in Wales and Northern Ireland, with 8 children receiving a liver transplant. But none of the confirmed cases are known to be vaccinated against COVID-19.
"We are working with the NHS [National Health Service] and public health colleagues in Scotland, Wales and Northern Ireland to swiftly investigate a wide range of possible factors which may be causing children to be admitted to hospital with liver inflammation known as hepatitis," said Dr. Meera Chand, director of clinical and emerging infections at UKHSA.
"Information gathered through our investigations increasingly suggests that this is linked to adenovirus infection. However, we are thoroughly investigating other potential causes."
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Spain and Denmark have also reported cases of unusual hepatitis in children, while France is investigating two suspected cases in Lyon and Israel is looking into a dozen children with unexplained hepatitis over four months, two needing liver transplants, according to a Stat report.
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Hepatitis can be caused by viruses, alcohol, toxins, medications and other medical conditions. But, in the United States, the most common causes of viral hepatitis are hepatitis A, hepatitis B, and hepatitis C viruses, according to the CDC.
Signs and symptoms of hepatitis include nausea, vomiting, abdominal pain, turning yellow and dark urine, with treatment directed at underlying cause, per the agency.