The World Health Organization reported Friday that there are at least 650 cases of sudden and unexplained hepatitis in young children under investigation in 33 countries, an increase of about 36 cases over the last international update, about a week ago. Another 99 cases are awaiting classification.
Last week, the European Centre for Disease Prevention and Control reported a total of 614 cases under investigation in 30 countries.
About one-third of the cases, 222, are in the UK, and another 216 have been reported in the US, WHO reported Friday.
Most of the children in the international investigation got sick in March and April, according to the update.
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Before this outbreak, about half of cases of sudden hepatitis - or inflammation of the liver -- in young children could not be tied to a known cause. But WHO says the cases being investigated now seem to be different from anything doctors have seen before. The hepatitis comes on quickly and appears to be more clinically severe, with a higher proportion of children developing liver failure.
Of a subset of 156 cases with data on hospital admission, about 14% required intensive care, and 12% needed a liver transplant.
WHO says it's not clear whether these are a greater number of cases of sudden hepatitis than doctors would normally expect to see over the same period of time.
Most of the affected children -- 75% -- are young, under the age of 5. Most were healthy before they fell ill.
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Common viruses known to cause hepatitis, such as hepatitis A, B, C, D and E, have been ruled out in these kids. The strongest connection between the cases seems to be a virus called adenovirus 41, which is known to cause stomach upset like diarrhea and vomiting; many of the affected kids reported those symptoms before becoming jaundiced, when the whites of their eyes and perhaps their skin developed a yellowish tinge that's a sign of liver problems.
But adenovirus 41 isn't an obvious culprit, experts say, because it has never been known to cause hepatitis in children who are don't have weakened immune systems.
The UK Health Security Agency has launched a case-control study to try to determine whether adenovirus 41 is detected more often in children with hepatitis than in others. UK scientists say they have found an increase in adenovirus activity, which is co-circulating with SARS-CoV-2, the virus that causes COVID-19.
WHO says SARS-CoV-2 has been detected in a number of the cases, although the data it has is incomplete.
Researchers are also looking into other possible causes, including environmental exposures, toxins and perhaps co-infections with another virus.
Investigators in the UK have ruled out exposure to dogs as a possibility in these cases, and because most of the children are too young to be vaccinated against COVID-19, they say the COVID vaccines are not playing any role.
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