The 56-year-old man, who had undergone a liver transplant, showed abnormal liver function without any obvious cause.
Tests found that his immune system was responding to hepatitis E – but in fact they couldn't find the human strain of the hepatitis E virus (HEV) in his blood.
Hepatitis E is a liver disease that can also cause fever, jaundice and an enlarged liver. The virus comes in four species, which circulate in different animals; At that time, only one of these four was known to infect humans.
With tests for the human load of HEV negative, researchers researched the diagnostic test, ran it again – and for the first time in history found rat hepatitis E in a human.
But then it happened again. And again.
But the rat tribe represents a new mystery: No one knows exactly how these people are infected. In the two years since its discovery, scientists have not yet identified the exact transmission pathway from rats to humans. They have theories – maybe the patients drank contaminated water like the usual human strain, or handled contaminated objects – but nothing is definitely proven.
The 61-year-old patients who have recently gained authority are particularly blunt; there were no rats or rat cramps in his home, no one else in his household has shown symptoms, and he has no recent travel history.
"Based on available epidemiological information, the source and route of infection could not be determined," the Hong Kong Center for Health Protection (CHP) said in a statement April 30. The man is still in the hospital, and CHP's investigation is ongoing.
What we know and don't know
The research team and city authorities have been trying to better understand this new health threat since 2018.
They have made some progress. Diagnostic tests have been refined and improved. They have spread awareness among the health care system so that doctors know how to test for HEV for rats, and launched public awareness campaigns.
Researchers are testing rat populations across the country to try to identify clusters before they can jump to humans, which has provided data on how many rodents in the city have rat HEV and which areas have the most rats.
But there is still much that remains unknown. They do not know how long the incubation period for this virus is – meaning how long it takes for patients to become ill after exposure. They are still trying to find a treatment, as the drugs used to treat the human variant of hepatitis E have had mixed results in patients with HEV from rats.
And of course, the biggest unknown that continues to displace scientists is how.
Not knowing how the virus jumps from rats to humans makes it very difficult to prevent further infections – or even to make sense of all the data scientists have collected. For example, people living in rat-infested areas should theoretically be at greater risk, but still some infected patients come from neighborhoods with low rat numbers.
"What we know is the rats in Hong Kong that carry the virus, and we test the humans and find the virus. But how exactly it jumps between them – whether the rats contaminate our food, or there's another animal involved, we don't know," said Sridhar. "That's the missing link."
One solution might be to just get rid of all the rats in Hong Kong, but eradicating rats is a long, complicated feat that is not very feasible. It will require reducing places they can remember as well as their access to food, with measures that prevent food from being thrown into the back alley.
For now, all authorities can encourage people to take preventative measures, such as washing their hands before eating, storing food properly or in the refrigerator, and keeping the household clean and disinfected with minimal rodent nesting places.
This can happen anywhere
This is probably not just a Hong Kong problem, or even a recent one, experts say. Rat HEV can infect people in New York or Paris, and we just don't know – because no one tests for it.
"My feeling is that this has been going on for a long time," Sridhar said. "2017, 2018 is definitely not the first time it's happening in the world."
In Hong Kong, the 11 confirmed cases are probably just the tip of the iceberg, he added. Doctors could test them for HEV from the rat because they sought medical help for symptoms, or were given controls due to existing conditions or transplants.
But there may be hundreds of infected cases in the community, which do not fall into these categories and have not been diagnosed, he said.
Many people with hepatitis E experience only mild symptoms, and in some cases they do not even know that they are infected or go to the hospital.
However, the virus can have serious health consequences, especially for patients with impaired immunity. Young, healthy people without pre-existing conditions may be able to recover on their own – but for vulnerable populations it can cause chronic hepatitis that patients cannot shake off, as well as long-term liver damage and scar tissue.
Apart from the 11 cases in Hong Kong, only one other case is confirmed globally – a man in Canada, who had previously traveled to Africa. He went to the hospital after experiencing hives, nausea, severe jaundice and an inflamed liver, and tested positive for HEV from rats, according to a report in February 2019.
This is the problem – most countries do not test for rat HEV, so there is a good chance that they are just missing diagnoses, Sridhar said.
It takes a specialized test, like the one that HKU designed to specifically look for rat HEV in humans. It is not a difficult test to perform, but it has not been widely adopted because no one until recently believed that rat HEV was even a threat to humans.
Just last year, ECDC finally developed guidelines for collecting data and reporting information on hepatitis E, the letter states – but these new guidelines focused on the human variant and do not include rat HEV, leaving what Sridhar calls "a blind spot in our diagnostics."
This blind spot, and the possibility of the virus infecting people globally without control measures, endanger some of society's most vulnerable people – the elderly, HIV-affected communities, those with pre-existing conditions and more.
"This should not happen," Sridhar said. "We need constant vigilance in the public to control this unusual infection. I really hope that public health authorities take the first step and look at how much their population is actually exposed to rat hepatitis E."