Unexplained Severe Acute Hepatitis
The initial report on 5 April was followed by another on 23 April by WHO, which revealed that at least 169 cases were found in 12 countries across the world.
Several countries have recently reported hundreds of cases of severe acute hepatitis in children, with the pathogens as yet unexplained. We must be vigilant, but there is no need to panic.
The findings were reported on the World Health Organization (WHO)'s Disease Outbreak News (DONs) on 15 April, which stated that on 5 April, WHO received notification of 10 cases of severe acute hepatitis with unknown causes.
The United Kingdom reported 74 cases as of 8 April. Oddly, the laboratory examinations failed to detect the viruses that would commonly be found in hepatitis A, B, C and E, or D.
The initial report on 5 April was followed by another on 23 April by WHO, which revealed that at least 169 cases were found in 12 countries across the world.
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On 28 April, the European Center for Disease Prevention and Control (ECDC) said 12 countries in Europe had reported the cases. There were also cases in Israel and Japan, which means the disease has spread across continents.
The disease has been found in 20 countries worldwide, with more than 200 cases reported, according to the Pan American Health Organization (PAHO) on 3 May. We have also learned that a few days before Idul Fitri, Singapore reported a case of infection in a 10-month-old baby, whose tests for hepatitis -- types A, B, C and E -- were all negative.
On 1 May, the Health Ministry cautioned the public to be vigilant after three pediatric patients with acute hepatitis died in Jakarta.
Although the news provokes health concerns, the fact that the number of new cases is still only around 200 people worldwide allows space for the gathering of scientific evidence to answer basic questions about the magnitude of cases, severity, transmission, causes of the disease and possible links with COVID-19.
Magnitude, severity, transmission
The first question is whether the number of cases is significant enough to cause worries. WHO said on 15 April that it was also possible that more cases might be reported from other countries.
The BMJ International Medical Journal stated on 26 April that there had been very rare cases of severe hepatitis in children with no hepatitis viruses being found (A to E). An expert from the UK says the number of hepatitis cases with no A to E hepatitis viruses has increased by five to 10 times at the university where he or she works. So there is evidently an increase in cases.
The second question is how severe the disease is and how it is transmitted. According to the data collected by WHO, the cases can generally be cured. However, around 10 percent of cases, i.e. 17 of the 170 cases in the initial report, required a liver transplant. WHO has reported one fatality.
Regarding the three death cases in Jakarta, as reported by the Health Ministry, it is necessary to take a deeper look at the laboratory and clinical records. The news did not elaborate the results of the hepatitis virus examination in the three cases. It would also be important to provide clearer information about the results of the examination for other viruses and, if possible, a liver biopsy in accordance with WHO recommendations, as well as the results of the sequencing examinations.
Regarding the transmission, preliminary epidemiological research data have not clearly demonstrated the existence of a major source of infection. In general, such an infection is rare. Neither is it clear whether there is a possibility of human-to-human transmission. Still being sporadic, the cases need further research.
Causes of disease
The third concern, and this is the most talked-about, is what actually causes the disease. It is intriguing especially because the hepatitis virus cannot be found. In most cases, the examinations have so far pointed toward a link to infection with an adenovirus, a family of common viruses that can cause flu-like or gastrointestinal symptoms.
In the UK, 75.5 percent of cases tested positive for adenovirus and subtype testing showed 11 cases revealed adenovirus 41F type.
The cases showed symptoms of vomiting and diarrhea, with some indicating upper respiratory-tract infections.
Meanwhile, the United States CDC reported late April that of the nine cases in Alabama, all were positive for adenovirus. Two infected children had to undergo a liver transplant. The cases showed symptoms of vomiting and diarrhea, with some indicating upper respiratory-tract infections.
Of course, from these findings, we cannot conclude as yet that adenovirus is the cause of this worrisome hepatitis. We know adenovirus as a virus that can cause respiratory problems, as well as vomiting and diarrhea, but it is usually mild and is not associated with hepatitis, except in very rare cases.
The UK Health Security Agency's report on 25 April mentioned several factors as the likely causes, but they were subject to further investigation for validation. These factors include the possibility of a new variant of the adenovirus as well as toxins, drugs, environment and potential exposure to other viruses as co-factors.
Fourth, which is also no less crucial, is whether there is a link between the infection of such a hepatitis and COVID-19. So far, there is no such evidence. It is clearly unrelated to the COVID-19 vaccination, because many of those infected children are still under the age of five or 10 years, and are therefore not required to have the COVID-19 vaccination.
Given the ongoing COVID-19 pandemic, there may be cases of hepatitis patients testing positive for COVID-19, such as the case in Singapore, in which the patient happened to have contracted COVID-19 last December. However, there has been no clear scientific evidence linking acute hepatitis and COVID-19 infection.
Journal of Hepatology, on 21 April, published an article entitled "SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis". However, scientific proof is as yet lacking for this hypothesis, as well as many others.
No need to panic
As stated above, on 5 April, WHO first received notification of the cases from the UK. The information was disclosed on the WHO Disease Outbreak News (DONs) on 15 April, and various news publications referred to the findings as a WHO-declared disease outbreak.
This handout image provided by the World Health Organization (WHO) on May 19, 2020, shows World Health Organization Director-General Tedros Adhanom Ghebreyesus reacting at the closing session of the World Health Assembly virtual meeting from the WHO headquarters in Geneva, amid the COVID-19 pandemic, caused by the novel coronavirus.
We need to understand that an unusual case of any disease will be included in DONs. It is a routine procedure for WHO to provide the world with information about important, or potentially crucial, public health developments. In April 2022 alone, there were 10 reported diseases in WHO's DONs.
In addition to the acute hepatitis, which was first reported in the UK and Ireland on 15 April and in several other countries on 23 April, there was Ebola in the Congo, Japanese encephalitis in Australia, salmoneum thypimurium in various countries, cholera in Malawi, malaria in Somalia, yellow fever in Uganda, vaccine derived polio virus (VDPV) type 3 in Israel and MERS CoV in Saudi Arabia. Clearly, there were many diseases other than hepatitis recorded in April 2022.
The placement of certain diseases in DONs is meant to provide the world with an initial heads-up and is expected to become a common concern. However, it does not necessarily mean the informed disease will become a worldwide epidemic.
On the other hand, the state certainly needs to take the necessary anticipatory steps, and the community should take precautions for their respective families.
Strictly speaking, we definitely need to be vigilant, but there is no need to panic excessively. On the other hand, the state certainly needs to take the necessary anticipatory steps, and the community should take precautions for their respective families.
Several things that can be done by the community include maintaining cleanliness, consuming cooked food and drinks, disposing of feces and/or diapers properly, sticking to their own eating utensils, diligently washing hands and maintaining health protocols.
In addition, if children have the symptoms of jaundice, nausea/vomiting, diarrhea, abdominal pain and others, early detection is important. They should immediately be taken to the nearest health-care facility.
Of course, the government also needs to increase early vigilance, enhance the capability of detailed and in-depth laboratory examinations, heighten epidemiological and laboratory surveillance and be prepared for emergency treatment of patients. In the meantime, we need to keep abreast of the scientific evidence that we hope to become available in the near future.
Tjandra Yoga Aditama
Tjandra Yoga Aditama, Postgraduate Director of YARSI University; WHO’s Former Director of Infectious Diseases for Southeast Asia; Former Director General of Disease Control/Head of Health Research and Development Agency (Balitbangkes)
(This article was translated by Musthofid)
