Wed. Dec 7th, 2022
Common brown rat (Rattus norvegicus).
enlarge / Common brown rat (Rattus norvegicus).

The first known case of hepatitis in rats jumping to a human patient has reopened a long-standing mystery about how the cryptic viruses spread and bounce between human and animal reservoirs.

Last Friday, Sept. 28, researchers from the University of Hong Kong revealed that a 56-year-old man had contracted a strain of hepatitis E previously thought to infect only rats. Hepatitis E viruses generally cause liver inflammation in humans that is usually self-limiting but can become serious or even fatal for some, including organ transplant patients and pregnant women.

Investigators spotted the man’s infection as early as September last year, after he had a liver transplant in May. They reported that the man’s infection had been treated and cleared by March this year, after which they verified the presence of the unexpected virus and tried to track down its source.

In the course of their work, the researchers ruled out the possibility that the man was infected from his organ or blood donors. Instead, the researchers noticed evidence of a rodent infestation near the man’s home with conspicuous collections of droppings from an adjacent garbage chute. Testing at least one rat collected nearby in recent years had shown positive for hepatitis E in rats, the researchers reported.

Infectious disease expert and microbiologist Yuen Kwok-yung, of the University of Hong Kong, described the case as “a wake-up call” in a news conference. He said some rats in the city had grown larger than cats and urged officials to improve sanitation to avoid public health risks from the looming rodents.

While the suggestion may not be a bad idea, there is no need to panic, however, according to hepatitis E expert XJ Meng of the VA-MD College of Veterinary Medicine at Virginia Tech. “This has never happened before,” Meng noted of the virus jumping from a rat to a human. It’s “unprecedented,” he continued in an interview with Ars. Anyway, I personally don’t like this [case] is a major public health problem.”

Still, the news sheds light on the lingering mystery surrounding the little-known form of hepatitis.

Enigmatic infections

Meng notes that in recent years, researchers have made several attempts to see if hepatitis E from rats could spread to humans — it’s one piece of the long-standing puzzle surrounding how the virus spreads. In general, the transmission tests were done by looking at whether the virus could pass from rats in labs to non-human primates or pigs. So far all attempts have failed. And, explains Meng, we know that hepatitis E in rats, like the rest of its species, spreads through a fecal-oral route, which works exactly as it sounds. Essentially, for the rat virus to become a major public health crisis, there would have to be a situation such as a significant amount of rat feces contaminating a source of drinking water, he speculated.

In the case of the 56-year-old man in Hong Kong, Meng speculates that it was just an unfortunate twist of fate that he was given the title of “first infected”. His immune system was probably suppressed after the liver transplant (to help his body accept the new organ), making him much more susceptible. And it seems that he happened to have a high probability of exposure from his environment.

Still, the rare case of rats gnaws at the lingering questions of hepatitis E that Meng and other infectious disease trackers have agonized over for decades.

Researchers have long documented that human versions of the virus cause outbreaks of acute liver inflammation in developing countries, usually in cases where fecal contamination seeps into water sources. The human viruses cause an estimated 20 million infections each year around the world, leading to tens of thousands of deaths, according to the World Health Organization.

But in the late 1990s, researchers began to notice that surprisingly many blood donors in the US and other developed countries showed up with anti-hepatitis E antibodies in their blood (which is typical evidence of a previous infection). The researchers were unable to figure out why or how these donors were exposed to the viruses, without international travel.

The findings indicated that people somehow got subclinical infections that went away on their own, Meng said. But if they had the infection, we probably wouldn’t have been able to figure it out. When doctors treat liver inflammation or other viral illnesses, they tend to think of the other hepatitis viruses first, A, B, C, but not E, he said. “This disease is grossly underdiagnosed in many countries” and “we don’t have an FDA-approved diagnostic test for it,” he added. If we did, “I’m sure you’ll see more cases reported in the clinics.”

The lack of diagnostics is part of a bigger problem, Meng notes. “This is a very important public health pathogen, but it has been extremely little studied. There are very few labs studying this virus.”

germ mess

However, the few researchers have found that there are at least four types of hepatitis E that infect humans, also known as HEVs. They are HEV genotypes 1, 2, 3, and 4. Researchers have gathered genetic evidence that these HEVs can also infect a variety of animals, including pigs, wild boars, deer, rabbits, mongooses, chickens, camels, ferrets, greater bandicoots, Asian musk shrew, mink, moose and fish. HEV G3 and G4 in particular were found to spread directly from pigs and wild boars to humans.

There are other strains (HEV-like strains) that infect rats and ferrets. These are genetically different from the HEVs, Meng points out, and there is no evidence (except for the new case) that hepatitis E in rats can spread from rats to humans. The genetic analysis of the strain infecting the patient in Hong Kong has not yet been published, but researchers reported it was “very different” from the strains that infect humans.

Still, in recent years there have been numerous but controversial reports of rats catching and potentially spreading the HEVs themselves. This would be a neat explanation of how people, particularly in urban areas of developed countries, might be exposed to HEVs.

In 2010, researchers reported molecular evidence of HEV infections in wild rats in Hamburg, Germany. In the following years, researchers found further evidence of HEV in wild rats in Los Angeles and, more specifically, HEV G3 in wild rats from various places in the US. Still, researchers’ efforts to infect rats with HEV in labs have hit the mark. And — except for the new case in Hong Kong — no one has caught viruses jumping from rats to humans.

In a 2016 article, Meng noted that we probably don’t know enough about hepatitis E viruses to figure out what’s going on. We may only have glimpses of their genetic diversity in the wild, and we still don’t understand their life cycles or the full range of animals they can infect. “Significant progress has been made in HEV research over the past decade,” Meng concluded, “but many important questions remain.”

By akfire1

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