Health authorities around the world are investigating reports of an increase in severe and unexplained hepatitis cases among previously healthy children.
The World Health Organization (WHO) is probing cases of "severe, acute hepatitis of unknown origin in young children" that were first reported in the United Kingdom last month.
It has received reports of at least 228 probable cases with dozens more under investigation, a spokesperson said on Tuesday.
"As of 1 May, at least 228 probable cases were reported to WHO from 20 countries with over 50 additional cases under investigation," the WHO's Tarik Jasarevic told a Geneva press briefing.
Most of the cases are from Europe but there are others in the Americas, the Western Pacific and Southeast Asia, he said. No cases have been detected in Australia to date.
In an earlier update on 23 April, the WHO said cases were in those aged one month to 16 years old.
"It is not yet clear if there has been an increase in hepatitis cases, or an increase in awareness of hepatitis cases that occur at the expected rate but go undetected," it said.
What is hepatitis?
Hepatitis is inflammation of the liver and can have a variety of causes, including viral infections.
Peter White, an infectious diseases professor at the UNSW, said there are five known hepatitis viruses.
"We've known a lot about them since the 1970s through to the discovery of hepatitis C in 1989," he said.
"Other viruses which affect the whole body can also cause hepatitis, including some herpes virus infections and even measles, but the five main human hepatitis viruses A, B, C, D and E are well known, and well characterised," he said.
"So if we get a hepatitis causing virus that is not one of those, then that's something new that we haven't seen for 30 years."
The WHO says these common hepatitis viruses have not been detected in any of the recent cases, while investigations are ongoing.
What else do we know about the recent cases?
Relatively little, says Professor Andrew Lloyd, an infectious diseases physician and hepatitis researcher at UNSW's Kirby Institute.
"The illness was first recognised in England, Europe and most recently in the US, and is sometimes causing serious liver disease requiring hospitalisation and even liver transplantation," he said.
The WHO was first notified of 10 cases in children under the age of 10 across central Scotland on 5 April. More than 100 cases have now been recorded in Britain.
Mild paediatric hepatitis is not unheard of, but the cases attracted attention because children were very sick. Many cases reported jaundice, and gastrointestinal symptoms including abdominal pain, diarrhoea and vomiting. In its most recent update, the WHO said 17 children have required liver transplantation, and at least one death had been reported.
What might be causing them?
Professor Lloyd said all the known causes of hepatitis are being considered, but that information to date suggests a strain of adenovirus is a "possible cause".
The likely candidate is a type of adenovirus called F type 41, known for causing gastroenteritis in children. The WHO says adenovirus has been detected in at least 74 cases. Of those, 18 have been identified as F41.
"There are many different strains of adenoviruses which are a common cause of generally minor infections in children, causing illnesses ranging from gastroenteritis to common colds and conjunctivitis, with most adenovirus infections occurring in healthy children causing no symptoms at all," he said.
"This particular strain is a well-recognised cause of diarrhoea in children."
Professor White said the F41 type causes around 70 per cent of the adenovirus gastroenteritis that is seen clinically in Australia, which normally only results in mild symptoms in children.
"I'd be looking at sequencing the whole virus to get the full genome," he said. "That is probably what is rapidly taking place now, sequencing to look for recombination or mutation that enables this change to allow it to affect the liver cells."
Professor Robert Booy, an infectious diseases expert at the University of Sydney, said a minority of cases were co-infected with COVID-19, but few now think COVID-19 is part of the cause. He said other toxins and co-infections are also being carefully investigated.
"There's no evidence that vaccination is, in any way, associated with the problem," he said.
The WHO has said the vast majority of affected children were not vaccinated against COVID-19.
"We've never been able to test as thoroughly or as accurately as we can now. So, there's every possibility that we'll find the likely cause of this quite quickly," Professor Booy said.
"The samples are being tested for all known infections and even unknown ones because you can do that with clever genetic testing. As well, toxins, poisons and other pollutants are being looked for and whether this might be a combination of two things is also being considered."
What about Australia?
Professor Lloyd said it is not yet possible to predict whether the illness will occur in Australia until the cause and pattern of spread are confirmed.
"The fact that it has occurred initially in England and then in Europe suggests that it can spread between countries," he said.
In a statement on 29 April, the Gastroenterological Society of Australia (GESA) said there had not been an unusual spike of cases in Australia but that ongoing surveillance was occurring.
“In Australia, each year we see a small number of children with unexplained hepatitis, some of whom are sick enough to require a liver transplant," GESA paediatric hepatologist Professor Winita Hardikar said.
"We have not seen an unusual spike in cases here but are undertaking surveillance."
How can we protect our kids?
Professor Hardikar said parents or careers should be alert to symptoms - including nausea, vomiting, abdominal pain, loss of appetite or fever (above 38C) - and to contact a healthcare professional if they are concerned.
Patients might also develop jaundice along with dark urine or pale-coloured faeces.
Professor Lloyd said with transmission of adenovirus 41 as a possible cause, it looks to be a "traditional route for gastro" that is managed by handwashing and disinfectant.
"That approach should be something every mum and dad should be thinking of."
With AFP/Reuters.
