About half of these cases come from just two countries: the United States and the United Kingdom. On Thursday, investigators in those two countries said they were working diligently to get answers.
One of their first tasks was to try to determine whether these cases of sudden and often severe liver damage in children represent a real increase in recent years. The answer is that it depends on where you look.
The UK has better data on its hepatitis cases than many other countries, as it only sees children with liver disease in three national hospitals.
“The care for these children is highly centralized,” Diedre Kelly, professor of pediatric hepatology at the University of Birmingham, UK, said during a press call for reporters on Thursday, hosted by the independent non-profit organization Science Media Centre.
In an average year, Kelly says they would see about 20 children who suddenly develop hepatitis with no obvious cause for their liver inflammation. This year, they saw 176 such cases, an increase of almost 8 times.
This contrasts with European countries. Kelly said she was recently part of a study that counted cases of hepatitis in children at specialist liver centers across Europe, and “they saw absolutely no increase in the number of acute and severe hepatitis” or liver transplants compared to previous years.
Kelly says they’re still trying to figure out what that means. “Either Europe is behind us and still has to catch up, or this is something that is not happening in Europe,” she said.
In the United States, unexplained cases of hepatitis are not routinely reported to public health authorities, making it unclear whether the 180 cases under investigation here represent an increase over what doctors see normally.
During a CDC call to clinicians on Thursday, Amanda Ingram, an epidemiologist with the Alabama Department of Public Health, said state investigators have seen an increase in emergency room visits across the state for the children with hepatitis, jaundice, and liver failure for approximately one month between November 21 and December 25, 2021. Alabama was the first state to report a cluster of 9 unexplained cases of hepatitis in children.
Investigators have no irrefutable proof. But they were able to restrict some of the things they were considering.
So far, they say, based on questionnaires collected from cases, they have been able to rule out contact with dogs as a potential contributor to the diseases, said Dr. Calum Semple, a pediatrician and professor of child health. and Epidemic Medicine at the University. of Liverpool.
Many of the children in the study had pet dogs or reported recent contact with dogs, so this possibility was initially listed, but upon further study, the researchers say it was ruled out as a possibility. that postman.
“We looked very carefully at the case control data as well as those with severe disease and those without severe disease and there are no differences between these children with respect to contact with dogs,” said Simple.
Although Covid-19 has not been ruled out entirely, it seems increasingly less likely to play a role.
“I don’t think we’re completely ruling out Covid,” Semple said, “I’m saying I think Covid goes down that ‘possibilities under consideration’ list, and adenoviruses and adeno-associated viruses and other viruses like that are moving up the list,” he said.
That’s not to say, however, that the pandemic, with its social distancing, masks and other behavioral changes, might not have its part in all of this. It could very well be that after almost two years of minimal exposure to infections, our immune system behaves differently.
Investigators in the UK are looking at T-cell responses in affected children to see if there is unusual activation of these immune defenders in these otherwise commonplace infections.
About 70% of children in the UK and more than half of children in the US have tested positive for adenovirus 41F in their blood, making the association hard to ignore.
But the researchers aren’t sure if they tested children of the same age and gender who didn’t have hepatitis, if they would find as many with the adenovirus in their blood. It’s called a case-control study, and Will Irving, professor of virology at the University of Nottingham, UK, said the data could be coming shortly.
“Adenovirus is the main contender here, but we need more data to be convinced, at least I do,” Irving said.
Scientists are skeptical because adenovirus 41 is generally not a big player when it comes to viral infections. It’s not even in the top 10 for adenoviruses that make people sick every year, Ingram said.
“It’s very hard to know if that’s the cause, which we would instinctively feel isn’t the case, or if it’s a trigger in the child who was susceptible for some other reason. “, said Kelly.
In the Alabama cases, the sickest children — those who ultimately needed liver transplants — had the highest levels of adenovirus in their blood, suggesting a dose-response — which researchers research when they try to figure out whether two related things are related because one caused the other or by pure coincidence.
Curiously, however, while many children test positive for adenovirus in their blood, samples of their destroyed liver tissue usually find no virus.
Researchers say they don’t know what it means, but say it’s unusual. When adenovirus 5 attacks the liver, for example, and you look at liver cells under a microscope.
“Liver cells are absolutely full of new adenovirus particles, so there’s no doubt that the virus itself infects hepatocytes and kills them. We don’t have that link yet,” Irving said.
So there are a few factors to consider, Irving said. Maybe the virus doesn’t act alone. Or can it trigger a damaging immune reaction.
In Alabama, 75% of cases — nine out of 12 children currently identified as having sudden, unexplained hepatitis — had more than one virus detected at the time of their illness.
In addition to adenovirus 41, the children tested positive for viruses known to cause upper respiratory tract infections, including rhinovirus, enterovirus, respiratory syncytial virus (RSV), OC43-like coronavirus, human metapneumovirus and rotavirus, which usually causes diarrhea. None were positive for current Covid-19 infection.
What is clear from the detailed study of children in Alabama is that the children were very sick.
Almost all had vomited, more than half suffered from diarrhea and fever. Almost all had yellow in the whites of the eyes or a yellowish-orange tint to the skin, a symptom called jaundice.-
Reassuringly, at least in the UK, there do not appear to be any geographical or social links between the cases, meaning the children do not know each other or live in the same areas. “It’s really sporadic,” Kelly says.
If hepatitis is caused by an infection or infections, but it does not affect children in the same area, what does this mean?
Irving, the virologist, said he thinks this could mean that very many children and possibly also adults are infected, but for the most part these infections do not lead to serious liver problems.
“Which then begs the question, what is special about these young children?” who are diagnosed with liver problems, Irving said.
For that, researchers are turning to genetics to try to unravel the mystery behind these cases, with several projects already underway to study the genetic traits of affected children and their parents to see if they had any unrecognized risk factors. for their liver problems.
While the puzzle of these cases is fascinating, the researchers say they try to keep the families affected at the center of their work.
“We must not forget that there are 170 families [in the UK] who are very distressed by this mysterious disease that causes such problems in their children, and getting a liver transplant is a life-changing event,” Semple said.
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