Dated May 6, 2022, an official document prepared by the Directorate of Epidemiology and Disease Control of the Ministry of Health looks at the global alert for cases of acute hepatitis of unknown etiology in children .
According to a recent publication by Dr. Mourad Merabetcoordinator of the National Public Health Emergency Operations Center at the Ministry of Health, no case of acute hepatitis of unknown etiology in children has been recorded in Morocco.
The document from the Ministry of Health goes back to the epidemiological data and the preliminary results of investigations carried out at UKto the UNITED STATES and in Europewhere several cases have been detected, including some progressed to acute liver failure requiring a liver transplant.
According to the document, the number of cases of acute hepatitis of unknown etiology in children worldwide is 227including 145 in the United Kingdom, 57 in the European Union and the European Economic Area, 12 in the United States, 12 in Israel and 1 case in Japan, knowing thatone death is to be deplored.
UK, no link with the Covid-19 vaccine has been established
In the UK, the initial alert was given on April 5, 2022. That said, the increase in cases was noticed as early as February 2022. Most of the identified cases showed symptoms from March 2022.
The clinical picture shows “acute hepatitis with increased liver enzyme levels”. Some cases progressed to acute liver failure; 10 children who required a liver transplantalthough no deaths were reported andno link with the Covid-19 vaccine has been establishedsincenone of the confirmed cases in the UK had been vaccinated. These are 145 cases, including 108 in England. The majority of them are children between the ages of 3 and 5 (65.4%), and more than half are female (54.3%).
The clinical signs observed are as follows: jaundice (jaundice) in more than 74% of cases, vomiting (72.8%), discolored stools (58%), diarrhea (49.4%), nausea (39.5 %), lethargy (55.6%), fever (29.6%) and, less frequently, respiratory signs (19.8%). It should be noted that 53.1% of cases were declared cured, including 3 transplanted.
40 of 53 cases tested for adenovirus tested positive
Although no epidemiological link has been established, the preliminary results of the English surveys show that 40 of 53 cases tested for adenovirus tested positivewith more frequent detection in blood/serum specimens, followed by stool or respiratory specimens.
Adenoviruses form a “diverse group” that affects the “upper respiratory tract and gastrointestinal systems”. They are “very resistant in the environment and therefore easily transmissible between individuals”. They can affect humans of any age, “but most commonly the pediatric population, especially young children and infants.”
“By the age of 10, most children have had at least one episode of adenovirus infection,” reads the Health Ministry document, which says “respiratory infections” are the “most common form.” more common” in children.
These infections are “most often trivial in the immunocompetent”, but “serious in the immunocompromised patient and responsible for hepatitis, pancreatitis, hemorrhagic cystitis, myocarditis, cardiomyopathy and meningoencephalitis with a very poor prognosis”.
Furthermore, adenoviruses are also “considered excellent vectors for vaccine development” and can “efficiently deliver target antigens to mammalian hosts”.
According to the preliminary results of the English surveys, SARS-CoV-2 was detected in 10 of 61 children tested, without revealing the presence of a new variant. Nevertheless, “the new variant” is one of the five hypotheses explaining this acute hepatitis of unknown etiology.
Indeed, the English surveys have made it possible to detect the following five hypotheses:
– and cofactor affecting young children that makes adenovirus infections more severe or causes them to trigger immunopathology. This may be increased susceptibility from lack of previous exposure during the pandemic, or previous infection with SARS-CoV-2 or other infection, including restricted effect of Omicron, or co-infection with Sras-CoV-2 or another infection, or even toxin, drug or environmental exposure;
– and new adenovirus variant ;
– a dopea toxins or a environmental exposure ;
– and new pathogen acting alone or as a co-infection;
– and new variant of Sars-CoV-2.
Alabama: 9 cases of hepatitis of unknown etiology and concomitant adenovirus infection
According to the Department of Health document, clinicians at a pediatric hospital in Alabama, USA, notified five children with severe hepatitis as well as adenovirus viremia. A retrospective epidemiological investigation of clinical records since October 1, 2021, as well as active hospital surveillance for cases of hepatitis of unknown origin and adenovirus infection, have identified four other children. .
There are a total of 9 children with hepatitis of unknown etiology and concomitant adenovirus infection between October 2021 and February 2022, including 7 females. All were immunocompetent with no comorbidities and, as in the UK, no epidemiological link has been detected.
Again, all of the children tested negative for hepatitis A, B, and C viruses, and for SARS-CoV-2 infection as well as other causes of pediatric hepatitis and infections. None of the children had a documented history of previous SARS CoV-2 infection.
Adenovirus was detected in whole blood samples from all patients by real-time PCR testing, and sequencing performed on samples from five patients revealed adenovirus type 41. Seven patients were co-infected with d other viral pathogens.
According to the same document, three patients developed acute liver failure, two of whom were treated with Cidofovir (off-label use: marketing authorization) and steroids, and transferred for liver transplantation. To note that all patients have recovered or are on the mend, including the two transplant recipients.
The potential impact for the affected pediatric population is high
The Directorate of Epidemiology and Disease Control of the Ministry of Health also presents the risk assessment, compiled by the European Center for Disease Prevention and Control (ECDC). “The incidence in the European Union/European Economic Area is overall very low, although no systematic monitoring is undertaken,” it says.
It indicates that the “evidence concerning human-to-human transmission remains unclear”, but also that the “risk for the European pediatric population cannot currently be assessed with precision”, knowing that the “probability of observing an increase in severe acute hepatitis d unknown origin in children cannot be quantified”.
That said, “given that some of the reported cases required liver transplantation, the potential impact for the affected pediatric population is considered high”.
For the ECDC, the main hypothesis is the “cofactor affecting young children with adenovirus infectionwhich would be mild under normal circumstances” and which “triggers more serious infection or immune-mediated liver damage”.
In the same document, the Department of Epidemiology and Disease Control of the Ministry of Health presents the case definitions respectively established by Santé publique-France and by the World Health Organization (WHO).
In France, a cas possible is defined as:
– of a child under the age of 18, having presented severe acute hepatitis since January 1, 2022, defined by: cytolysis (ASAT and/or ALAT) > 500 IU/L and a prothrombin level (PT) < 50%;
– or with a negative first-line etiological assessment. Namely a negative toxicological assessment: paracetamol, halothane, phalloid syndromes, sodium valproate, isoniazid, rifampicin, phenobarbital, sulfonamides. But also no known or very strongly suspected chronic liver disease (a1AT deficiency, Wilson’s disease, autoimmune hepatitis, progressive familial intrahepatic cholestasis), no known or very strongly suspected metabolic cause, nor acute leukaemia. And having detected no virus detected among the following: HAV, HBV, HCV, HEV, HSV, HHV6/8, EBV, CMV, VZV, parvovirus, echovirus, cocksakie, Sars-CoV2, influenza virus;
– or with positive adenovirus, with or without infectious agent detected, with or without chronic liver disease, with or without metabolic cause.
Le cas sous investigationin France, is that of a “child aged 0 to 16 who has had severe acute hepatitis since January 1, 2022 with GOT or GPT > 500 U/L, and in whom the analyzes for hepatitis A, B, D , C and E are negative”.
Le cases with an epidemiological link is, meanwhile, that of a “person of any age who presents with severe acute hepatitis with GOT or GPT > 500 U/L, in whom the analyzes for hepatitis A, B, D, C and E are negative, and who has been in close contact with a symptomatic case under investigation since January 1, 2022”.
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