WHO recommends that countries and regions remain vigilant and strengthen investigations.
Written by | Yan Xiaoliu
Source | "Medical Community" public account
"Europe and the United States are investigating dozens of puzzling and serious cases of acute hepatitis in children." BMJ recently posted.
According to BMJ, the United Kingdom has reported 74 cases of related children, mostly under the age of 10, who have been physically fit and have no underlying diseases in the past. After the onset of the disease, the child has a significant increase in transaminases, accompanied by jaundice, diarrhea, vomiting, abdominal pain and other symptoms, and a few will have fever. However, no hepatitis A, B, C, D, or E virus infection has been detected. This is often the main trigger for acute hepatitis.
Similar cases have been detected in four European countries, including Denmark, Ireland, the Netherlands and Spain, as well as in the United States. Investigations are under way in all the countries involved. On April 19, local time, the European Centre for Disease Prevention and Control (ECDC) said that the exact cause of acute hepatitis in children mentioned above was not known.
As of 12 April, no deaths have been reported in countries, but some of the children are in critical condition. Six children in the UK have received liver transplants due to acute liver failure. In addition, 1 Spanish child and 2 children in the United States are waiting for a liver source.
"Outbreaks of severe acute hepatitis in children are rare. There are fewer viral infections or potential health problems. Karen Landers, who has been a pediatrician for 45 years, told the STAT website that because of this, the above cases have attracted the attention of the global medical community.
The World Health Organization (WHO) issued a document on April 15 recommending that countries and regions remain vigilant and strengthen investigations. "Given the increase in the number of reports over the past month and the expansion of case searches, more cases are likely to be detected in the coming days."
Meets 3 definitions,
That is, "unexplained acute hepatitis in children"
"It's not clear when it all started." According to the National Broadcasting Corporation, according to the WHO, the first children were all located in the United Kingdom and were found while hospitalized, with the earliest case being in January this year.
The U.S. investigation set a new time record. Stat said nine cases of unexplained acute hepatitis in children have been identified in the United States, all reported by Alabama, with children ranging in age from 1 to 6 years. The earliest case was admitted to the hospital in the fall of 2021.
"In early February, the Alabama Department of Public Health issued a reminder to clinicians to pay attention to related cases." Karen Landers is a District Medical Officer at the Alabama Department of Public Health. She said that after investigation, no epidemiological association was found in the British and American cases.
The WHO said it strongly recommends that countries identify, investigate and report potential cases that meet the definition. The so-called "conformity to the definition" includes 3 aspects:
First, the confirmed case is defined as: after 1 January 2022, 10 years of age or younger, with acute hepatitis (not caused by A, B, C, D or E virus infection) and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 500U/L.
In the United Kingdom, where the number of cases is highest, researchers published the earliest clinical data on 13 children in Eurosurveillance on April 14. The results showed that most children had ALT levels of more than 2000 IU/L. The normal ALT value is 10-40 IU/L.
"Just 1 week before the onset of illness, these children were very healthy. They do not have any significant past medical history, such as underlying immunodeficiency or immunosuppressive therapy. The European Surveillance article reads.
Helena Gutierrez, medical director of the Pediatric Liver Transplant Program at the University of Alabama at Birmingham, told STAT that like the United Kingdom, nine children in the United States are very sick. "From severe hepatitis to acute liver failure, we've seen a full range of reports."
Photo caption: In March 2022, the number of confirmed cases of unexplained acute hepatitis in children in Scotland, UK, suddenly increased. /Eurosurveillance
Second, suspected cases, defined as: after 1 January 2022, aged 11-16 years, with acute hepatitis (not caused by A, B, C, D or E virus infection) and AST or ALT > 500U/L.
Third, epidemiologically related cases: after 1 January 2022, there was acute hepatitis (not caused by A, B, C, D or E virus infection) and had close contact with the confirmed case.
As the above information was made public, more and more countries and health departments began to search extensively.
As of 14 April, a total of 3 cases, ranging in age from 22 months to 13 years, were reported in Spain.
Agence France-Presse reported that two children under the age of 10 have been admitted to the University Hospital of Lyon in France, "suspected of rare unexplained acute hepatitis, which is under investigation." ”
A new type of virus has emerged?
"Puzzlingly, in nearly 100 cases, no evidence of hepatitis virus infection was found. No other epidemiological risk factors, such as international travel, were identified. Scientists and doctors are considering other possibilities, including viral infections such as COVID-19, as well as environmental factors. Europe News reported.
According to the European Monitor article, the earliest "disease trigger" speculation was directed at toxic substances in food, water or toys. However, after investigating and questioning the guardian, these possibilities were initially ruled out.
In addition, children were tested for the virus in the United Kingdom, the United States, and Spain to rule out hepatitis A, B, C, D, and E virus infection. Bacteriological tests also found no abnormalities.
Then, the researchers expanded the scope of viral screening to those viruses that are not within the scope of routine detection of acute hepatitis, including enteroviruses, varicella zoster virus, adenovirus and so on.
Eventually, they found a clue. Of the 13 children tracked by the Europe Surveillance article, 5 tested positive for adenovirus.
At the same time, all 9 children reported in the United States have reported positive for adenovirus. Five of them were confirmed positive for adenovirus-41.
STAT quoted Kristen Nordlund, a spokeswoman for the U.S. Centers for Disease Control and Prevention (CDC), as saying adenovirus could be "the culprit." "We're also investigating and learning more."
The UK Health Security Agency (UKHSA) has a similar argument. "One of the potential causes is adenovirus infection."
According to UpToDate, adenoviridaevirus is an important cause of febrile illness in young children, most commonly causing upper respiratory syndrome and can also cause pneumonia. Rarely, it can cause diseases of the digestive system, eyes, genitourinary system and nervous system.
Adenovirus-41 type detected in children in the United States can cause acute gastroenteritis in children.
Most adenoviral diseases are self-limiting. But for immunocompromised people, fatal infections can occur. This is occasionally the case in healthy children and adults.
As a seasonally transmitted virus, February to April is the peak of adenovirus epidemic. The WHO statement noted that an increase in adenovirus transmission activity was observed in the UK during the same period as the above-mentioned child cases were reported.
According to the European Surveillance article, if the above-mentioned acute hepatitis in children is indeed caused by adenovirus infection, it is either a new variant with a unique clinical syndrome or a routinely circulating adenovirus strain, but it has a more serious impact on immunocompromised children. The latter scenario may be the result of restricting social interaction during the COVID-19 pandemic.
"During the COVID-19 pandemic, children in isolation at home have had less contact with external pathogens and their immune function has been spared exercise. After the relaxation of the new crown epidemic prevention, children resumed classes and social activities, and the possibility of contracting the virus increased significantly. This includes adenovirus infection. Will Irving, a professor of virology at the University of Nottingham in the UNITED Kingdom, said.
The "European Monitoring" article also pointed out that all the children have not been vaccinated against the new crown, and some children have tested positive for the new crown, which is also worthy of attention. For example, could it be the result of Omiljung lineage BA.2 infection? Or is there a newer strain of COVID-19 that is more pathogenic?
"These are all hypotheses. Other infectious and non-communicable factors need to be thoroughly investigated first to properly assess and manage risk. "The WHO proposes that the priority now is to identify the cause to guide further clinical and public health actions and to identify risk factors.
Do you want to panic?
Amy Feldman, medical director of the Pediatric Liver Transplant Division at Colorado Children's Hospital, said that while the above cases are important, parents should not pay too much attention to it, "there is no need to think about insomnia." ”
"This week, my daughter threw up and pulled. But I definitely wouldn't worry about her liver failure. That's too rare. She said she had not seen similar cases of acute hepatitis in children as in Alabama.
Speaking as meera Chand, UKHSA's director of clinical and emerging infections, AFP said "normal hygiene measures", such as hand washing, have helped reduce the spread of many infectious diseases, including acute hepatitis in children mentioned above.
Source:
[1] Acute hepatitis of unknown aetiology–the United Kingdom of Great Britain and Northern Ireland.WHO
[2] Scientists search for cause of hepatitis cases in children. BMJ
[3] Children in more countries suffer mystery hepatitis. The Straits Times
[4] Investigation into cases of hepatitis of unknown aetiology among young children,Scotland,1 January 2022 to 12 April 2022.Eurosurveillance.Volume 27,Issue 15,14/Apr/2022
[5] UK,US health officials investigating cases of severe hepatitis with unknown causes in children. CNN
Pathogenesis, epidemiology and clinical manifestations of adenovirus infection. UpToDate
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