A ProMED-mail post
ProMED-mail is a program of the
International Society for Infectious Diseases
In this update:
 USA (Wisconsin): alert
 USA (Wisconsin): alert
Date: Wed 27 Apr 2022 3:30 PM CDT
Source: Wisconsin Department of Health Services [edited]
Wisconsin DHS Health alert no. 42: Recommendations for adenovirus
testing and reporting of children with acute hepatitis of unknown
The Wisconsin Department of Health Services (DHS) is issuing this
Health Alert Network (HAN) Health Advisory to notify clinicians and
public health authorities of a recent increase in cases of acute
hepatitis and adenovirus infection in children.
From November 2021 to February 2022, clinicians at a large children's
hospital in Alabama identified 9 pediatric patients with significant
liver injury, including 3 with acute liver failure, who also tested
positive for adenovirus. All children were previously healthy. All 5
of the 9 specimens that were sequenced had adenovirus type 41
infection identified. 2 patients required liver transplant; no
patients died. Since being notified of this adenovirus-associated
hepatitis cluster, DHS is now investigating at least 4 similar cases
among children in Wisconsin. This includes 2 children who had severe
outcomes, 1 liver transplant, and 1 fatality.
A possible association between pediatric hepatitis and adenovirus
infection in children who tested negative for hepatitis viruses A, B,
C, D, and E is currently under investigation worldwide. This Health
Alert serves to notify American clinicians who may encounter pediatric
patients with hepatitis of unknown etiology to consider adenovirus
testing and to elicit reporting of such cases to state public health
authorities and to the CDC. Nucleic acid amplification testing (NAAT,
e.g., PCR) is preferred for adenovirus detection and may be performed
on respiratory specimens, stool, rectal swabs, or blood.
CDC issued an official Health Advisory describing a cluster of cases
in Alabama and provided recommendations for testing and reporting on
21 Apr 2022. The WHO has also published a Disease Outbreak News report
on 23 Apr 2022 describing 169 cases of acute hepatitis of unknown
etiology, of these, adenovirus had been detected in at least 74
Hepatitis is inflammation of the liver that can be caused by viral
infections, alcohol use, toxins, medications, and certain other
medical conditions. In the USA, the most common causes of viral
hepatitis are hepatitis A, hepatitis B, and hepatitis C viruses. Signs
and symptoms of hepatitis include fever, fatigue, loss of appetite,
nausea, vomiting, abdominal pain, dark urine, light-colored stools,
joint pain, and jaundice. Treatment of hepatitis depends on the
underlying etiology. Adenoviruses are double-stranded DNA viruses that
spread by close personal contact, respiratory droplets, and fomites.
There are more than 50 types of immunologically distinct adenoviruses
that can cause infections in humans. Adenoviruses most commonly cause
respiratory illness. However, some adenovirus types can cause other
illnesses, such as gastroenteritis, conjunctivitis, cystitis, and,
less commonly, neurological disease.
There is no specific treatment for adenovirus infections. Adenovirus
type 41 commonly causes pediatric acute gastroenteritis, which
typically presents as diarrhea, vomiting, and fever; it can often be
accompanied by respiratory symptoms. While there have been case
reports of hepatitis in immunocompromised children with adenovirus
type 41 infection, adenovirus type 41 is not known to be a cause of
hepatitis in otherwise healthy children.
Clinicians should consider adenovirus testing in pediatric patients
with hepatitis of unknown etiology. NAAT (e.g., PCR) is preferable and
may be done on respiratory specimens, stool or rectal swabs, or blood.
Anecdotal reports suggest that testing whole blood by PCR may be more
sensitive than testing plasma by PCR; therefore, testing of whole
blood could be considered in those without an etiology who tested
negative for adenovirus in plasma samples. If patients are still under
medical care or have residual specimens available, please save and
freeze specimens for possible additional testing and contact DHS at
Clinical criteria for case reporting
- Children under age 16, presenting with hepatitis of unknown etiology
(with or without any adenovirus testing results) since 1 Jan 2021, AND
elevated liver function tests (that is, aspartate aminotransferase
(AST) or alanine aminotransferase (ALT) >500 U/L).
- Suspect cases should be reported to public health electronically via
the Wisconsin Electronic Disease Surveillance System (WEDSS) and
selecting "hepatitis unknown" as the disease type, or by contacting
DHS at 608-267-9003.
Ryan Westergaard, MD, PhD, MPH
Chief Medical Officer and State Epidemiologist
Bureau of Communicable Diseases
Division of Public Health
Wisconsin Department of Health Services
[ProMED map of Wisconsin, United States:
Date: Thu 28 Apr 2022
Source: NHK [in Japanese, machine trans., edited]
Regarding hepatitis of unknown cause, which has been mainly in young
children in Europe and the USA, the Ministry of Health, Labor and
Welfare has revealed that 2 new children under the age of 16 have been
hospitalized with similar symptoms in Japan. There are now 3 patients
with unexplained severe hepatitis confirmed in Japan.
According to the WHO, there have been a series of reports of acute
hepatitis in 12 countries, including the UK and the USA, mainly in
children under the age of 10, with at least 169 cases reported as of
21 Apr 2022, one died.
The Ministry of Health, Labor and Welfare announced on 25 Apr 2022
that a patient with a possible cause of hepatitis of unknown cause was
confirmed for the 1st time, and the number of patients confirmed in
Japan is now 3. The relationship between these 3 children has not been
clarified. The Ministry of Health, Labor and Welfare is requesting
local governments nationwide to report any patients with similar
symptoms and is collecting information on the situation overseas.
Ryo Sumazaki, Honorary Director of Ibaraki Prefectural Children's
Hospital, a pediatric doctor who is familiar with liver diseases in
children, said, "Mild hepatitis generally occurs in children, but
cases requiring liver transplantation or liver failure are rare.
However, it is still unclear whether the same thing as in Europe and
the USA, which has been reported one after another, will occur in
Japan. In children, hepatitis A to E does not [generally] apply, and
acute hepatitis of unknown cause often occurs. It is necessary for the
country and experts to carefully investigate whether the number of
cases is increasing, but at this point, generally, parents do not have
to worry excessively.
Also, regarding the fact that adenovirus is detected in many children
with acute hepatitis in Europe and the USA, he said "Adenovirus itself
is a common virus, so even if it is detected in a patient, it cannot
be immediately determined that it is the cause. However, adenovirus
often spreads not only through the air but also by contact infection,
so I want you to wash your hands thoroughly."
[ProMED map of Japan:
Date: Thu 28 Apr 2022
Source: In-Cyprus [edited]
A case of acute hepatitis of unknown origin has to do with a girl 4.5
years old and has already been reported to the relevant European
bodies by the Makarios Children's Hospital.
The chief of the pediatrics division at Makarios hospital, Avraam
Elia, said that a young child was diagnosed back in February 
with acute hepatitis of unexplained origin, as cases emerge across the
world. He noted that the case had been reported as unexplained
hepatitis. "Lab work that was done on the child yielded no correlation
with a cause of hepatitis," Elia said.
[ProMED map of Cyprus:
More cases of severe hepatocellular injury in children are being
reported with many reported on a review of previous cases. Cases
apparently fitting the clinical case definition have come from at
least 12 European countries, the USA (now 5 states), Japan (now 3
cases), and Cyprus (1 case) to this point and are likely to increase.
Adenovirus serotype 41, one of the so-called enteric adenoviruses, has
been found in some of the cases, but the virus has not been known
previously to cause hepatitis in the immunologically normal host.
Whether the finding of adenovirus serotype 41 is an epiphenomenon or
the virus is etiologic here is not yet known. No information has yet
been forthcoming on evidence that the virus was found in liver tissue
or not, whether a whole genomic analysis of the virus has been
compared to older adenovirus serotype 41 and the specific pathology of
the affected liver has not been reported. If the virus is the cause,
has the agent acquired additional virulence factors, or is a cofactor
involved (virus or toxin)? Are certain children genetically more
susceptible for the more severe disease?
To this point, no evidence for household clusters has been reported,
which one might expect if a foodborne toxin or transmissible agent was
involved. Additionally, it would be interesting to know if any
asymptomatic aminotransferase elevations were looked for in household
contacts. The cases recognized as severe could be the "tip of the
iceberg," as we saw with paralytic poliomyelitis when only a small
percentage of infections resulted in the classical asymmetrical
flaccid paralysis of polio. Additionally, it is not clear whether all
these cases are related to the same cause. Also, most of the newer
reported cases do not specifically say that the case fits the proposed
case definition. - Mod.LL]
Hepatitis, undefined - Global: children, USA, Japan, Canada
Hepatitis, undefined - USA, Europe (07): children, aflatoxin
hypothesis, 2021-22 http://promedmail.org/post/20220426.8702860
Hepatitis, undefined - USA, Europe (06): USA, children, poss
adenovirus 2021-22 http://promedmail.org/post/20220426.8702848
Hepatitis, undefined - USA, Europe (05): UKHSA,children, poss
adenovirus 2021-22 http://promedmail.org/post/20220425.8702847
Hepatitis, undefined - USA, Europe (04): WHO, children, poss
adenovirus, 2021-22 http://promedmail.org/post/20220424.8702811
Hepatitis, undefined - USA, Europe (03): CDC, children, poss
adenovirus, 2021-22 http://promedmail.org/post/20220421.8702752
Hepatitis, undefined - USA, Europe (02): Israel, children, possible
adenovirus, 2021-22 http://promedmail.org/post/20220420.8702720
Hepatitis, undefined - USA, Europe: children, possible adenovirus, RFI
Hepatitis, undefined - UK: children, RFI
Non-viral hepatitis - USA (02): bottled water, fatal, recall
Non-viral hepatitis - USA: (NV) bottled water susp
ProMED makes every effort to verify the reports that are posted, but the accuracy
and completeness of the information, and of any statements or opinions based
thereon, are not guaranteed. The reader assumes all risks in using information
posted or archived by ProMED. ISID and its associated service providers shall not
be held responsible for errors or omissions or held liable for any damages incurred
as a result of use or reliance upon posted or archived material.
Donate to ProMED. Details available at: https://isid.networkforgood.com/projects/79924-invest-in-the-mission.
Visit ProMED's website at https://www.promedmail.org/.
Submit all items for posting via the ProMED website at https://promedmail.org/submitinfo/.
If you have any questions or need support, please contact us via the ProMED website at https://promedmail.org/support/.
You may subscribe/unsubscribe at https://isid.org/promedmail-subscribe/.