Langya virus infection since 3 August 2022

The newly-discovered Langya virus is related to the Nipah virus [The Star Online, 29 Aug 2022]

By DR MILTON LUM

Researchers from China, Singapore and Australia reported on Aug 4 (2022) the identification of the Langya henipavirus (LayV) in a throat swab sample from a 53- year-old woman in the town of Langya in Shandong, China.

Their finding was published in a letter in the New England Journal of Medicine.

The genome of the LayV is most closely related to the Mojiang henipavirus, which was first isolated from rats in an abandoned Yunnan mine in south China.

Henipaviruses belong to the Paramyxoviridae family of viruses, which includes measles, mumps and many respiratory viruses that infect humans.

Several other henipaviruses have been discovered in bats, rats and shrews, from Australia to South Korea and China, but only the Hendra, Nipah, and now LayV, viruses are known to infect people.

Langya virus
The researchers that identified LayV had been monitoring patients with fever at three hospitals in Shandong and Henan between April 2018 and August 2021.

They identified 35 patients – mostly farmers – with acute LayV, of whom 26 were infected with only LayV (and no other pathogens).
These 26 patients had:
• Fever (100% of the patients)
• Fatigue (54%)
• Cough (50%)
• Anorexia, or loss of appetite (50%)
• Myalgia, or muscle pain (46%)
• Nausea (38%)
• Headache (35%), and
• Vomiting (35%).

These symptoms were accompanied by:
• Thrombocytopenia, or low platelets (35%)
• Leukopenia, or low white blood cells (54%),
• Impaired liver function (35%), and
• Impaired kidney function (8%).

The symptoms ranged from severe pneumonia to a cough.

Most stated in a questionnaire that they had been exposed to an animal within a month of their symptoms appearing.

According to the researchers, findings from the patients with acute LayV infection suggest that it was the cause of febrile illness based on the following factors:
• LayV was the only potential pathogen detected in 26 of the 35 patients (74%).
• In paired serum samples that were obtained from 14 patients during the acute and convalescent phases of infection, the IgG (immunoglobulin G, a type of antibody) titres in 86% of the convalescent phase samples were four times as high as those in the acute phase samples.
• Viraemia (presence of viruses in the bloodstream) was associated with acute LayV infection.
• Patients with pneumonia had higher viral loads than those without pneumonia.

The researchers did not find strong evidence of LayV spreading between people as there was no obvious association between the cases either in location or time.

There was also no close contact or common exposure history among the patients, which suggests that the infection in the human population may be sporadic.

But retrospective contact-tracing was only done on 15 family members of nine patients.

The researchers said that it “revealed no close-contact LayV transmission, but the sample size was too small to determine the status of human-to-human transmission for LayV”.

To determine the potential animal origin of LayV, tests were done on goats, pigs and cattle in the villages of the infected patients.

Antibodies against LayV were found in goats (three out of 168, or 2%) and dogs (four out of 79, or 5%).

Tissue and urine samples were taken from 25 species of small wild animals to ascertain the presence of LayV RNA (ribonucleic acid).

LayV RNA was predominantly detected in shrews (71 out of 262, or 27%), a finding that suggests the shrew may be a natural reservoir of LayV, infecting themselves and infecting people by chance.

It was unclear how people were infected in the first place, whether directly from shrews or an intermediate animal.

The researchers conclude that a lot of work is needed to ascertain how LayV is spreading in shrews and how people get infected.

They stressed the need for a global surveillance system to detect viral spread from animals to humans, and rapid communication to avoid more pandemics like Covid-19.

Hendra and Nipah viruses
The Hendra virus (HeV) was first isolated in 1994, during an outbreak of respiratory and neurologic disease in horses and humans in the Brisbane suburb of Hendra, Australia.

The outbreak involved 21 stabled racehorses and two humans who died.

To date, seven humans have contracted HeV following exposure to the body fluids, tissues or excretions of infected horses, with four dying – a death rate of 57%.

HeV has not been reported outside of northeast Australia.

A commercial HeV vaccine for horses has recently been licensed in Australia.

Malaysia was the first country in the world to encounter the Nipah virus (NiV), which sparked an outbreak here in 1998-1999.

It resulted in the near decimation of the local pig-rearing industry, which was then the largest in Asean, with about a million pigs culled.

Many of the humans who survived the infection have been left with residual complications.
The initial NiV cases were reported near Ipoh in September 1998.

Four of these 28 cases tested positive for IgM (immunoglobulin M) antibodies against Japanese Encephalitis (JE) and a JE outbreak was declared by the Health Ministry.

The pigs were sold and transferred out of Perak.

By the end of 1998, more cases were reported in Bukit Pelandok in Port Dickson, Negri Sembilan.

In March 1999, Dr Chua Kaw Bing, then attached to Universiti Malaya’s Department of Medical Microbiology, isolated NiV from a patient being treated at the university’s hospital, who was from Sungai Nipah village.

The outbreak eventually caused 283 cases and 109 deaths with a death rate of 38.5%.

An NiV outbreak (11 cases, one death) was also reported in Singapore among slaughterhouse workers in March 1999.

Since then, there have been annual outbreaks in Bangladesh starting from 2001, as well as outbreaks in eastern India.

The death rate of NIV ranges from about 40% to 75% depending on the local clinical management capability.

Most human NiV infections in Malaysia resulted from unprotected exposure to secretions of sick pigs or their contaminated tissues.

Subsequent outbreaks in Bangladesh and India, however, were most likely due to consumption of fruits or fruit products that had contact with infected fruit bats.

These bats, which are the natural reservoir of NiV, have been found in Indonesia, Philippines, Thailand, Cambodia, Ghana and Madagascar.

Human-to-human NiV transmission have been reported among family and caregivers of the infected through close contact with their secretions and excretions.

Similarly, healthcare workers in Bangladesh and India have been reported to be infected due to providing care.

NiV outbreaks have also been reported in domestic animals like pigs, horses, goats, sheep, cats and dogs.

An infected pig can be asymptomatic (have no symptoms), but some develop fever, difficulty breathing and neurological symptoms like trembling, twitching and muscle spasms.

The death rate in pigs is usually low, except in young piglets.

There is no treatment or vaccine available for NiV in either humans or animals.

A need for surveillance
Only three henipaviruses – HeV, NiV, and now LayV – are known to infect humans.

Although there has been no NiV outbreak in Malaysia since about two decades ago, only the very brave can vouch that it will not recur.

Could LayV occur in Malaysia?
Only time will tell.

As such, it is very important for the Health and Agriculture ministries to provide the public updated information about its surveillance of both NiV and LayV in humans and animals.

Dr Milton Lum is a past president of the Federation of Private Medical Practitioners Associations and the Malaysian Medical Association. For more information, email [e-mail]. The views expressed do not represent that of organisations that the writer is associated with. The information provided is for educational and communication purposes only, and it should not be construed as personal medical advice. Information published in this article is not intended to replace, supplant or augment a consultation with a health professional regarding the reader’s own medical care. The Star disclaims all responsibility for any losses, damage to property or personal injury suffered directly or indirectly from reliance on such information.

New Langya virus discovered in China may only be ‘the tip of the iceberg’ for zoonotic cases globally, scienitsts say [PennLive, 12 Aug 2022]

By Deron Dalton

Scientists have suggested more surveillance of a new Langya virus found in dozens of people in China and hence, are now studying how easy it is for viruses to spread from animals to humans, and how these outbreak of diseases have gone undetected for so long.

The new virus is called Langya henipavirus. Nearly three dozen farmers and residents have been infected in eastern China. It is believed the virus has spread directly and/or indirectly from mole-like mammals called shrews.

While no deaths were reported, the pathogens were reported in 35 unrelated cases of fevers in hospitals in Henan and Shandong provinces between 2018 and 2021, according to CNN. The findings are aligned with long-standing warning animal viruses are spreading to humans and are left undetected on a global scale.

Leo Poon, a professor at the University of Hong Kong’s School of Public Health, wasn’t involved in the study, but called the virus “the tip of the iceberg.”

“We are hugely underestimating the number of these zoonotic cases in the world, and this (Langya virus) is just the tip of the iceberg,” said Poon.

Researchers published a study on the matter in the New England Journal of Medicine just last week. The issue has received global attention due to the concern over disease outbreaks and pandemics.

What Is the New Langya Virus, and Should We Be Worried? [Scientific American, 11 Aug 2022]

By Allen Cheng

The Langya virus, which is related to the Nipah and Hendra viruses, has infected at least 35 people in China in the two years before 2021

The following essay is reprinted with permission from The Conversation, an online publication covering the latest research.

A new virus, Langya henipavirus, is suspected to have caused infections in 35 people in China’s Shandong and Henan provinces over roughly a two-year period to 2021.

It’s related to Hendra and Nipah viruses, which cause disease in humans. However, there’s much we don’t know about the new virus – known as LayV for short – including whether it spreads from human to human.

Here’s what we know so far.

HOW SICK ARE PEOPLE GETTING?
Researchers in China first detected this new virus as part of routine surveillance in people with a fever who had reported recent contact with animals. Once the virus was identified, the researchers looked for the virus in other people.

Symptoms reported appeared to be mostly mild – fever, fatigue, cough, loss of appetite, muscle aches, nausea and headache – although we don’t know how long the patients were unwell.

A smaller proportion had potentially more serious complications, including pneumonia, and abnormalities in liver and kidney function. However, the severity of these abnormalities, the need for hospitalisation, and whether any cases were fatal were not reported.

WHERE DID THIS VIRUS COME FROM?
The authors also investigated whether domestic or wild animals may have been the source of the virus. Although they found a small number of goats and dogs that may have been infected with the virus in the past, there was more direct evidence a significant proportion of wild shrews were harbouring the virus.

This suggests humans may have caught the virus from wild shrews.

DOES THIS VIRUS ACTUALLY CAUSE THIS DISEASE?
The researchers used a modern technique known as metagenomic analysis to find this new virus. Researchers sequence all genetic material then discard the “known” sequences (for example, human DNA) to look for “unknown” sequences that might represent a new virus.

This raises the question about how scientists can tell whether a particular virus causes the disease.

We have traditionally used “Koch’s postulates” to determine whether a particular micro-organism causes disease:
• it must be found in people with the disease and not in well people
• it must be able to be isolated from people with the disease
• the isolate from people with the disease must cause the disease if given to a healthy person (or animal)
• it must be able to be re-isolated from the healthy person after they become ill.

The authors acknowledge this new virus doesn’t yet meet these criteria, and the relevance of these criteria in the modern era has been questioned.

However, the authors say they didn’t find any other cause of the illness in 26 people, there was evidence 14 people’s immune systems had responded to the virus, and people who were more unwell had more virus.

WHAT CAN WE LEARN FROM RELATED VIRUSES?
This new virus appears to be a close cousin of two other viruses that are significant in humans: Nipah virus and Hendra virus. This family of viruses was the inspiration for the fictional MEV-1 virus in the film Contagion.

Hendra virus was first reported in Queensland in 1994, when it caused the deaths of 14 horses and the trainer Vic Rail.

Many outbreaks in horses have been reported in Queensland and northern New South Wales since, and are generally thought to be due to “spillover” infections from flying foxes.

In total, seven human cases of Hendra virus have been reported in Australia (mostly veterinarians working with sick horses), including four deaths.

Nipah virus is more significant globally, with outbreaks frequently reported in Bangladesh.

The severity of infection can range from very mild to fatal encephalitis (inflammation of the brain).

The first outbreak in Malaysia and Singapore was reported in people who had close contact with pigs. However, it is thought more recent outbreaks have been due to food contaminated with the urine or saliva of infected bats.

Significantly, Nipah virus appears to be transmitted from person to person, mostly among household contacts.

WHAT DO WE NEED TO FIND OUT NEXT?
Little is known about this new virus, and the currently reported cases are likely to be the tip of the iceberg.

At this stage, there is no indication the virus can spread from human to human.

Further work is required to determine how severe the infection can be, how it spreads, and how widespread it might be in China and the region.

New ‘Langya’ virus identified in China: what scientists know so far [Nature.com, 11 Aug 2022]

By Smriti Mallapaty

The henipavirus can cause respiratory symptoms and is related to Nipah and Hendra viruses, but cannot spread easily in people.

A new animal virus that can infect people has been identified in eastern China. But scientists say they are not overly concerned because the virus doesn’t seem to spread easily between people, nor is it fatal.

The virus, named Langya henipavirus (LayV), can cause respiratory symptoms such as fever, cough and fatigue, and is closely related to two other henipaviruses known to infect people — Hendra virus and Nipah virus. These also cause respiratory infections, and can be fatal. Researchers think LayV is carried by shrews, which might have infected people directly or through an intermediate animal. The virus was described in the New England Journal of Medicine1 on 4 August.

Researchers say LayV has infected only 35 people since 2018, and none of the cases seems to be linked. “There is no particular need to worry about this, but ongoing surveillance is critical,” says Edward Holmes, an evolutionary virologist at the University of Sydney in Australia. Regularly testing people and animals for emerging viruses is important to understand the risk of zoonotic diseases — those that can be transmitted from other animals to humans, he says.

Large outbreaks of infectious diseases typically take off after a lot of false starts, says Emily Gurley, an infectious-diseases epidemiologist at Johns Hopkins University in Baltimore, Maryland. “If we are actively looking for those sparks, then we are in a much better position to stop or to find something early.”

Hospital surveillance
The research team that identified LayV did so while monitoring patients at three hospitals in the eastern Chinese provinces of Shandong and Henan between April 2018 and August 2021. Participants were recruited into the study if they had a fever.

The team sequenced the LayV genome from a throat swab taken from the first patient identified with the disease, a 53-year-old woman. The virus was named after a town called Langya, in Shandong, where she was from, says co-author Linfa Wang, a virologist at Duke–National University of Singapore Medical School in Singapore.

Throughout the study period, the researchers found 35 people who were infected with LayV, mostly farmers, with symptoms ranging from severe pneumonia to a cough. Most patients said in a questionnaire that they had been exposed to an animal within a month of their symptoms appearing.

The LayV genome shows that the virus is most closely related to Mojiang henipavirus, which was first isolated in rats in an abandoned mine in the southern Chinese province of Yunnan in 2012. Henipaviruses belong to the Paramyxoviridae family of viruses, which includes measles, mumps and many respiratory viruses that infect people. Several other henipaviruses have been discovered in bats, rats and shrews, from Australia to South Korea and China, but only Hendra, Nipah and now LayV are known to infect people.

The researchers did not find strong evidence of LayV spreading between people — there were no clusters of cases in the same family, within a short time span or in close geographical proximity. “Of the 35 cases, not a single one is linked,” says Wang. Gurley says that this is good news, but the study did retrospective contact tracing on only 15 family members of 9 infected individuals, which makes it difficult to determine how exactly the individuals were exposed. Still, she notes that she didn’t see anything in the data to “cause alarm from a pandemic-threat perspective”.

Animal origin
To determine the potential animal origin of the virus, the researchers tested goats, dogs, pigs and cattle living in the villages of infected patients for antibodies against LayV, and took tissue and urine samples from 25 species of wild small animals to look for the presence of LayV RNA. They found LayV antibodies in a handful of goats and dogs, and identified LayV viral RNA in 27% of the 262 sampled shrews. This suggested that shrews are a reservoir for the virus, passing LayV between themselves “and somehow infecting people here and there by chance”, says Gurley.

But it is not clear how people were infected in the first place — whether directly from shrews or an intermediate animal, says Gurley. A lot of research still needs to be done to work out how the virus is spreading in shrews and how people are getting infected, she says.

Holmes says there is an urgent need for a global surveillance system to detect virus spillovers and rapidly communicate those results to avoid more pandemics, such as the one sparked by COVID-19. “These sorts of zoonotic spillover events happen all the time,” he says. “The world needs to wake up.”

References
1. Zhang, X.-A. et al. N. Engl. J. Med. 387, 470–472 (2022).

Langya vs. Nipah: China's New Virus Spread by Shrews Has a Deadly Relative [Newsweek, 10 Aug 2022]

BY JESS THOMSON

Langya henipavirus (LayV), a virus that spreads by shrews which has been identified in 35 people in China, has an extremely deadly relative: Nipah virus

The latest Langya cases were announced in a letter published in the New England Journal of Medicine. In it, Xiao-Ai Zhang, from the Beijing Institute of Microbiology and Epidemiology, and colleagues said cases had been found in two provinces: Shandong and Henan.

As reported by Focus Taiwan, the Taiwan Centers for Disease Control (CDC) said it is starting to develop ways to track the Langya virus and that methods of sequencing its genome will be ready within a week.

Nipah virus outbreaks and symptoms

This new virus is a close relative of a previously reported, extremely deadly, Nipah virus. Both Nipah and Langya belong to the henipavirus family, which according to the World Health Organization (WHO) are classed as biosafety Level 4 viruses.

The Nipah virus is zoonotic, having evolved in fruit bats. It is able to be transmitted to humans via animals like bats or pigs, contaminated foods, and between humans.

It is fatal in between 40 to 75 percent of cases. The fatality rate, however, varies on local capabilities.

Nipah was first discovered during an outbreak among pig farmers in Malaysia in 1999. Two years later, cases were found in Bangladesh. There have been an outbreaks almost every year in India ever since.

Other regions known to be at risk include Cambodia, Ghana, Indonesia, Thailand, Madagascar and the Philippines, as natural reservoirs of the virus exist in bats in these regions.

Symptoms of Nipah virus are known to include fever, headaches, myalgia (muscle pain), vomiting and sore throat, as well as dizziness, drowsiness, and acute encephalitis. In serious cases, the patient may fall into a coma within 48 hours.

How does Langyna virus compare?
The NEJM letter describes the symptoms of the 35 Langya patients. It said that of the 26 patients who were infected with Langya alone, had a fever, 54 percent were experiencing fatigue, 50 percent had a cough, 46 percent had muscle aches and pain, 38 percent had nausea, and 35 percent had a headache. The same number reported vomiting.

Half of the patients had anorexia, while 35 percent developed thrombocytopenia—a condition where the platelet count in the blood drops too low. Over half developed leukopenia, where a person's white blood cell count drops. Thirty five percent developed impaired liver function, and eight percent had impaired kidney function.

The fatality rates of this new strain are not yet known, as nobody infected with the virus has yet died.