Alarm bells rang in the global public health community this week when Indonesia confirmed that three children had experienced fever, nausea, and convulsions before passing away from severe acute hepatitis last month.
Concern only grew on Thursday, when the country’s Ministry of Health announced that there are four more similar cases undergoing intensive treatment in a Jakarta hospital after exhibiting symptoms such as yellow marks on the skin, acute diarrhea, vomiting, and seizures.
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The announcements come amid growing attention surrounding a mysterious liver disease that has infected more than 200 children across the globe, from the U.S. to the U.K., Israel and Singapore. While unconfirmed, the Indonesian cases are strongly suspected to be part of this global trend, placing public health officials on high alert.
According to Indonesian health ministry spokesperson Siti Nadia Tarmizi, the three unrelated fatal cases—children aged two, eight, and 11—were transferred to Jakarta’s Cipto Mangunkusumo General Hospital from smaller hospitals in the city in April.
Hanifah Oswari, a representative of the Indonesian Pediatrician Association involved in the Ministry of Health’s investigation into the cases, told VICE World News that the three children experienced symptoms similar to the recent unexplained hepatitis cases seen in other parts of the world. Hanifah added, however, that more research is needed to confirm that they are suffering from the same liver disease flagged by the World Health Organization.
“By next week we [should] have the result,” he said. “We also have reports from areas in Jakarta and from outside Jakarta reporting the same problem, but we still need to investigate that too.”
The paediatrician said the symptoms exhibited by the three children were unusually severe compared to other hepatitis cases he typically sees.
“Sometimes we get [paediatric] patients coming from other hospitals that are very severe, but that’s only one or two in a year,” he said. “But [in this case] we got three patients around the same time, in about one month. It’s very unusual.”
As Indonesian authorities continue to study the three deaths, their investigation forms a crucial part of a global hunt for answers surrounding an unidentified liver disease that has spread among children across 20 countries. Since it was first detected in the U.K. in early April, some 228 previously healthy children—the youngest just a month old and the oldest 16—have fallen sick to severe acute hepatitis of unknown origin.
“We are taking these reports very seriously, and working with countries to better understand what is happening,” a WHO representative told VICE World News in an email response. “WHO has activated its emergency response infrastructure and is working closely across regional offices and with partners to coordinate data collection and exchange information.”
At least one child has died—four if the three Indonesian cases are confirmed to be connected—while around 18 have undergone liver transplants after coming down with acute hepatitis, the WHO confirmed at a press briefing on Wednesday.
Children falling ill to hepatitis due to unknown origins is relatively rare, with the spread sparking concern among public health officials. So far, health experts are yet to identify a cause, with the viruses most commonly associated with acute viral hepatitis (hepatitis A, B, C, D, and E) not detected in any cases.
“It is important to be aware that reports of unexplained hepatitis in children do occur every year, but it is usually only a few cases in a year,” said the WHO.
“At this point in time, we do not know for certain why only children seem to be affected by this [hepatitis outbreak]. One likely explanation is that most adults have been exposed to this virus while they were children and have developed immunity against it.”
Philippa Easterbrook, a senior scientist at the WHO Global Hepatitis Programme, said at a press briefing that “there is no link to one geographic area or common exposure to particular foods or animals, travel or to toxins.” But she added that “considerable progress” has been made over the past week to explore potential explanations, “particularly about whether adenovirus really is a cause of the hepatitis and not just an incidental finding.”
Adenoviruses have been listed as a common denominator in 74 of the worldwide cases; in particular, the adenovirus strain F type 41 was identified in 18 cases, the WHO said in a statement on April 23. Adenovirus type 41 is typically known to result in stomach flu and respiratory symptoms among children. But despite some reports of adenovirus type 41 causing hepatitis in immunocompromised children, the virus hasn’t been known to cause hepatitis in healthy children.
“While adenovirus is currently one hypothesis as the underlying cause, it does not fully explain the severity of the clinical picture,” said the WHO.
Markus Buchfellner, a paediatric infectious diseases expert at the University of Alabama at Birmingham, told VICE World News that adenoviruses are quite common among children, but he said the “overwhelming majority recover well with no long-term complications and require no specific treatments.”
“At this point in time, we do not know for certain why only children seem to be affected by this [hepatitis outbreak],” said Buchfellner. “One likely explanation is that most adults have been exposed to this virus while they were children and have developed immunity against it.”
Back in Indonesia, a crucial node in unraveling the mystery, Hanifah and his team of medical experts have excluded hepatitis A, B, and C in their search for the cause of hepatitis among the three deceased children. They are now looking into other pathogens, such as adenovirus type 41.
The need for answers to prevent further cases is growing, and on Thursday an Indonesian health minister urged extensive mapping of suspected severe acute hepatitis cases.
“The Ministry of Health is very concerned about this. We’re trying to do the investigation very thoroughly,” said Hanifah.
Indonesian authorities have urged parents and guardians to have their children admitted for medical treatment if they exhibit symptoms of hepatitis such as jaundice, abdominal pain, sudden vomiting and diarrhea, dark tea-colored urine, pale stools, seizures, and loss of consciousness.
Tjandra Yoga Aditama, a professor in the faculty of medicine at the University of Indonesia and the former director of communicable diseases at the World Health Organisation’s Southeast Asia office, said “people should be anticipating the situation and be ready.”
“The [Indonesian] government should increase their surveillance capability and their laboratory capacity to detect if there are cases,” he told VICE World News. “For the community, while we are still waiting for a scientific explanation of this particular disease, please keep hygiene and sanitation as a priority for children.”
But as disturbing as the cases of unexplained hepatitis may be—especially to parents with young children—Tjandra urges caution against premature catastrophizing. In April alone, there were nine diseases identified in the WHO’s Disease Outbreak News, as well as four each in March and February.
“In Indonesia I keep telling people, putting a disease in the WHO Disease Outbreak News doesn’t mean it will become an outbreak later on,” he said.