New Coronavirus News from 23 Mar 2023

China's only now revealed crucial COVID-19 origins data. Earlier disclosure may have saved us 3 years of political argy-bargy [The Conversation、 23 Mar 2023]

By Dominic Dwyer

Once more, we’re talking about the origins of SARS-CoV-2, the virus that causes COVID-19.
First the US Department of Energy’s review gave more emphasis to the laboratory leak hypothesis than previously, although the confidence for this conclusion was low.

Second, and more importantly, is the release and analysis this week of viral and animal genetic material collected from the Huanan wet market in Wuhan, the place forever associated with the beginning of the pandemic.

It’s a subject close to me. I was the Australian representative on the international World Health Organization (WHO) investigation into the origins of SARS-CoV-2. I went to Wuhan on a fact-finding mission in early 2021. I visited the now-closed market.

Now we have stronger evidence that places raccoon dogs at the market as a possible animal reservoir of SARS-CoV-2, potentially infecting humans.

If we’d had this evidence three years ago, we need to ask ourselves how different recent history would have been. We would have reduced the enormous energy, media frenzy and political argy-bargy about less likely hypotheses of the pandemic’s origins. We might have better focused our research attention.

Read more: COVID origins debate: what to make of new findings linking the virus to raccoon dogs

The twists, turns and puzzles
Samples were taken from various places in the market, in January 2020, within weeks of the early COVID-19 cases in Wuhan. SARS-CoV-2 RNA and human DNA were identified in these environmental samples, although no animal swabs were positive for the virus.

This was presented to the WHO team investigating the origins of the pandemic in January 2021, of which I was part.

The work was published as a preprint (posted online, before being independently verified) in February 2022.

The underlying “metagenomic” data to support the conclusions in the preprint – that SARS-CoV-2 and human (but not animal) sequences were present – needed to be provided to allow further analyses. This is something that is generally required by journals and regarded as appropriate in the spirit of scientific openness and collaboration.

However, it wasn’t until early March 2023 that the international community had access to the data.

That’s when there was a “drop” of these environmental metagenomic sequences into the GISAID database, the international open access repository of viral sequences.

This allowed an independent team of international experts to analyse them. In a startling revelation, they identified large amounts of raccoon dog and other animal DNA in conjunction with SARS-CoV-2. Raccoon dogs can be readily infected with SARS-CoV-2 and can transmit it. The international team published their observations as a preprint earlier this week.

Of note was the physical co-location of these virus and animal sequences in the corner of what is a very large market, the corner associated with early human cases. It is now known (but initially rejected by Chinese authorities) that wild and farmed animals were sold in this area of the market.

After the sequences were analysed by the international team, the Chinese scientists who had performed the market testing were contacted for comment and discussion – especially around the important observation that mixed in among the SARS-CoV-2 sequences were a large proportion of raccoon dog and other animal DNA.

The sequences were then withdrawn from the GISAID database within a few hours of the study authors being approached. This is perhaps unusual for an open database such as GISAID, and clarity could be sought why this occurred.

Why is this work important?
This latest work does not prove raccoon dogs were definitely the source of SARS-CoV-2. Presumably, they are likely to have been an intermediate host between bats and humans. Bats harbour many coronaviruses, including ones related to SARS-CoV-2.

However, the data fits the narrative of the animal/human connections of SARS-CoV-2.

This, along with other examination of animal links to SARS-CoV-2, should be taken in the context of the lack of robust data to support the other SARS-CoV-2 origins hypotheses, such as a laboratory leak, contaminated frozen food, and acquisition outside China. Bit by bit, the evidence supports animal origins of the outbreak, centred on the Huanan market in Wuhan.

The length of time taken for this early work to surface and the difficulty in accessing the raw data are unfortunate, points made recently by the WHO.

Sympathetically, one might say, the wrong analysis of the original data collected in early 2020 was undertaken and the researchers missed the animal links.

Cynically, (and without evidence) one might say that the significance of the data was recognised, but not made readily available. This is a question for the Chinese researchers at the Chinese Center for Disease Control to answer.

What are the implications of this delay?
If this had been identified in early 2020 then further studies to understand the viral origins in animals could have been undertaken.

Three years on, it is very difficult to do such studies, tracking backwards from the now closed market to the animal sources and the people who handled these animals.

Clearer answers would have taken some of the heat out of the debate around the possible viral origins. Of course, all hypotheses should remain on the table, but some of these could have been much better explored with earlier data.

Would it have changed the course of the pandemic? Probably not. The virus had already spread worldwide and adapted very well to human-to-human transmission by the time this work was available. However, it would have driven research in better directions and improved future pandemic planning.

What now?
Lessons for the future are obvious. Open disclosure of sequence data is the best way to undertake scientific investigation, especially for something of such international significance.

Making data unavailable, or not reaching out for assistance in complicated analyses, only slows the process.

The resulting political to and fro by all countries, particularly the US and China, has meant that suspicion has deepened, and progress slowed even further.

Although WHO has been criticised for errors in how it managed the pandemic, and in collating data to understand the origins and progress future research, it remains the best international agency to foster open sharing of data.

Scientists, for the most part, want to do the right thing and find the answers to important questions. Facilitating this is crucial.

China’s huge quarantine camps standing months after ‘zero COVID’ [Al Jazeera English, 23 Mar 2023]

Satellite imagery shows facilities are still intact nearly four months after the end of Beijing’s draconian pandemic policy.
Taipei, Taiwan – Nearly four months after China abruptly scrapped its tough “zero-COVID” policies following rare mass protests, authorities have yet to dismantle sprawling quarantine facilities designed for isolating hundreds of thousands of people, an Al Jazeera investigation based on satellite imagery shows.

Mass quarantine facilities in three Chinese provinces appear fully intact with no visible changes to their structure, an analysis of the satellite images shows, raising questions about the Chinese government’s post-pandemic plans for the now-defunct structures.

China’s quarantine facilities, which were previously used to isolate, and at times treat, positive COVID-19 cases and close contacts, became a symbol of the human cost of Beijing’s “zero-COVID” policy, which was dropped in December amid mounting public frustration with the draconian measures.

Beiijng’s overarching plan for its now-defunct quarantine centres, if there is one, is not clear.
Provincial authorities in Guangdong, Shandong and Sichuan did not reply to Al Jazeera’s requests for comment. Efforts to reach the National Health Commission (NHC) were unsuccessful.

In December, however, the NHC called on local governments to “upgrade” quarantine centres into hospitals with facilities including intensive care. The NHC said local authorities should carry out the upgrades with local needs in mind but did not specify the ratio or number of facilities that should be refurbished.

Meanwhile, some local governments have announced plans for a variety of other uses for the centres – from temporary housing to elderly care.

The satellite images obtained and analysed by Al Jazeera’s Sanad investigation unit cover six quarantine centres: three in northern China’s Shandong province, two in Guangdong province on the southern coast, and one in Sichuan in the centre of the country.

The facilities include Guangzhou’s 80,000-person capacity Nansha Health Centre, which was only completed in November. The furthest distance between locations – from the outskirts of Jining in Shandong to Guangzhou in Guangdong – is more than 1,700km (1,056 miles).

Sanad geolocated the quarantine centres using drone footage circulated on social media and analysed satellite images of the facilities taken within the last few days.

The images of quarantine centres analysed by Al Jazeera do not show any structural changes or construction to suggest significant upgrades.

For China, upgrading defunct quarantine centres en masse could potentially be a potentially difficult and costly task.

“Quarantine hospitals are designed in a very different way from acute care hospitals because for quarantine, the main purpose of the facility is to quarantine, not treatment,” Chi Chunhuei, director of the centre for global health at Oregon State University, told Al Jazeera.

While the Chinese government has not published official figures, news reports and official statements suggest that a large number of makeshift structures were erected across the country during the pandemic.

As early as January and February 2020, the National Development and Reform Commission allocated 530 million yuan ($77m) to quickly build two prefabricated COVID-19 hospitals in Wuhan, the then epicentre of the pandemic. China State Construction allocated another 500 million yuan (72.6m) to the project, which was modelled after a makeshift hospital built during the SARS pandemic in 2003.

The two facilities were dismantled in April 2020 as China began to contain the first COVID wave but the model would be widely adapted again two years later in the midst of an even larger infection wave in the spring of 2022.

As authorities struggled to contain the virus once again, local and city governments got to work to flatten the curve and ultimately achieve zero cases.

Chinese health official Jiao Yahui said there were 33 prefabricated hospitals completed or under construction in March 2022 alone. In May, the director of the NHC, Ma Xiaowei, called for more quarantine facilities in an op-ed for the Communist Party’s Qiushi Magazine.

China’s “zero-Covid” is gone, but quarantine facilities remain

Shanghai, a large COVID hotspot in 2022, by itself allocated at least 16.77 billion yuan ($2.4bn) for COVID-19 infrastructure, services, staff salaries and other needs in its 2022 budget. Like those of other local governments, the budget did not break down how much was spent on quarantine facilities specifically.

“The funding for the COVID infrastructure is a little bit opaque but it seems to come from a variety of sources, including SPB [special purpose bonds], central government budget and municipal/provincial budgets,” Arendse Huld, an editor at the business-intelligence website and magazine China Briefing, told Al Jazeera.

In August 2022, an NHC directive called for more reserve quarantine facilities, while stipulating they should be built with normal day-to-day functions in mind. Construction continued across China, including in Guangzhou, where authorities announced plans to build 36 facilities with a total capacity of 110,000 beds as late as November 2022.

Discussions on the costs and future of the quarantine facilities are difficult to find in China’s heavily-censored media.

A critical article on the news platform 163.com, which questioned who would pay for Shandong to dismantle quarantine camps built at a cost of 23 billion yuan ($3.3bn), had its contents deleted, although its title remains visible online.Much of the cost of China’s quarantine centres was funded by debt.

Chinese financial news site Yicai reported that more than 100 local governments issued special purpose bonds, racking up debts of up to 440 million yuan ($63.9m).

Many of the local authorities said they planned to rent out the facilities after the pandemic to generate income and fund the debt.

Huld, the editor, said authorities may find it difficult to make the centres economically viable if converted to other uses, which could include hotels, office buildings, shopfronts, warehouses, expo centres and even parking lots.

“I think it’s reasonable to be sceptical of the viability of these facilities for long-term use and of whether they can really generate income in the future,” Huld said.

“These facilities were not made to be permanent and so it seems unlikely that they will really have much longevity. This sentiment is also being felt in China, as we can see from various social media posts [and] web articles.”

In Jinan, the capital of Shandong province, a 650-cabin quarantine camp – that spans more than 20,000 square metres (215,000 sq feet) – was converted into temporary housing for “skilled talent” to resolve a housing shortage for people working at a nearby tech complex, an official statement said. In Shandong, at least one quarantine facility has been designated to become an elderly care home.

Government authorities in remote Qinghai on the Tibetan Plateau said 29 quarantine camps with more than 10,000 beds in total would be kept open to provide reserve beds.

The NHC also recommended that some quarantine centres could be upgraded to medical facilities but Jin Dong-yan, a professor of medicine at the University of Hong Kong, questioned their suitability.

He said the facilities are typically in less-than-ideal locations, far from urban centres, while the buildings themselves would not meet medical standards.

“Even if you build a new hospital from the ground up, there may not be manpower to run it,” Jin told Al Jazeera.

China’s rural areas have just 2.4 practising physicians and 2.6 registered nurses per 1,000 people, according to data compiled by China Briefing, far fewer than urban areas, where the ratio is 3.7 practising physicians and 4.6 nurses.

Jin said authorities might try to save face by repurposing the centres regardless of their long-term viability or suitability.

“The money has already been spent, the best they can do is try to recycle the waste,” he said.
Despite the unresolved questions, Beijing has cast its handling of the pandemic as an unqualified success.

During China’s National People’s Congress earlier this month, newly-appointed Premier Li Qiang said China’s COVID-19 policies were “completely right” and “delivered highly effective outcomes”.

After praising China’s “remarkable” transition from “zero-COVID”, Li said China would continue to “strengthen medical and health services at all levels” and improve its early warning system for epidemics.

China’s official death toll is just 120,576, according to World Health Organization statistics. Health experts widely agree that figure greatly underestimates the actual toll, with some academic studies estimating 1-1.5 million deaths.

While some quarantine facilities may find other uses, others are likely to be consigned to the ash heap of history, said Chi, from Oregan State University, particularly if they are built on highly-sought urban land.

“If they are built in a more suburban area, the land value is not so high, they will probably not tear them down and they can convert them into other use,” he said. “But if some of the quarantine hospitals were built on high-value city land, there’s a high likelihood they will tear it down or modify them into commercial buildings because they desperately need to boost [economic] growth.”

For some Chinese, the centres stand as reminders of the draconian policies that upended the economy and their personal lives for the quixotic goal of zero infections.

For Guangzhou local Jenny, who asked not to be identified by her name, even the sight of kiosks built for PCR testing still haunts her.

“They remind me of painful memories, what else can there be?” Jenny told Al Jazeera.

Jenny, who vividly recalls images of police deploying batons, water cannons and tear gas against protesters during last year’s anti-lockdown protests, is not worried about what happens to the quarantine centres.

Like many Chinese, she just wants to move on from the pandemic.

“The average person does not care,” Jenny said.

Zoonotic Bird Flu News since 11 Mar 2023

BIRD SHOTS [Science, 6 Apr 2023]

By JON COHEN

As an avian influenza virus devastates the poultry industry, the United States considers an unprecedented step: vaccinating its flocks

LAKESIDE, CALIFORNIA—Hilliker’s Ranch Fresh Eggs in this San Diego suburb has 30,000 chickens in three “cage-free,” open-air barns, where birds crowd the floor like rush-hour riders on a big city subway. “A cage-free aviary is a very interesting science experiment,” says Frank Hilliker, who runs the farm his grandfather started in 1942. He worries mightily about infections spreading through the massed birds. On his iPhone, he pulls up a list of the vaccines his chickens get: against Newcastle disease, infectious laryngotracheitis, coryza, colibacillosis, salmonella, infectious bronchitis, and fowlpox.

There is one disease for which his chickens have not been vaccinated: a highly pathogenic avian influenza (HPAI) that’s now racing around the world, killing 90% or more of the poultry it infects. Endemic in migratory birds, this HPAI emerged in U.S. poultry in February 2022, and to date has killed or required the culling of a record 58 million chickens, turkeys, and ducks in commercial and backyard flocks.

Hilliker, who despite the unusually chilly February morning is wearing cargo shorts and a zip-up sweatshirt—this is San Diego—has a no-nonsense demeanor mixed with a tinge of superstition from years of worrying about his chickens. His farm has never detected an HPAI, he says, knocking on a wood wall. “We’re pretty isolated here,” he says, giving another rap. But he might well use an HPAI vaccine to protect his birds, he says, if it was priced right—and allowed.

The goal of vaccination is not just to protect poultry. Well before COVID-19, epidemiologists were nervously watching two kinds of highly pathogenic influenza viruses, H5 and H7, fearing they could erupt into a human pandemic reminiscent of the 1918 flu. HPAI can infect mammals, and the current, massive outbreak has killed seals, bears, and farmed mink and infected at least seven people, killing one. Thankfully, there is no evidence the virus can spread from mammal to mammal, let alone person to person—so far. But fears are growing that the more mammals it infects, the higher the odds that it will adapt to humans.

Slowing the spread among birds could reduce the risk. “I think it is time to give serious consideration to vaccinating commercial poultry in the United States,” says Robert Webster, an emeritus influenza researcher at St. Jude Children’s Research Hospital. But despite strong evidence that HPAI vaccine programs can work—mainly from China, which has aggressively vaccinated poultry over the past 2 decades—the U.S. Department of Agriculture (USDA) does not give farmers like Hilliker the option. Instead, the country has fought HPAI by combining intensive surveillance, strict biosecurity at farms, and culling.

Skeptics of poultry vaccination say that’s the right approach. Immunizing flocks, they argue, could allow the virus to spread silently—not reducing the threat of an avian flu pandemic but simply making it more difficult to detect. And the current practice of “stamping out” outbreaks has worked: Before the current HPAI strain surfaced in U.S. flocks in February 2022, no HPAI had swept through since 2015. But in the face of the largest HPAI outbreak on record, both the United States and Europe are rethinking their hesitancy.

Many questions remain about how, exactly, to use a vaccine in countries that have relied on culling. And because of the uncertain U.S. market, companies are reluctant to invest in moving beyond the initial steps of making vaccines against the current variant and embarking on the rigorous and costly process of seeking regulatory approval. “There’s no incentive at all,” says microbiologist Mahesh Kumar, who heads global biologics R&D for Zoetis, which makes vaccines for pets and livestock and sells an HPAI vaccine outside the United States. “It’s very, very difficult for anybody to continue to invest in that space.”

And something else has kept the brakes on HPAI vaccination in both the United States and Europe: trade. Some countries—including the United States—won’t allow imports of meat or eggs from vaccinated birds.

Scientific evidence doesn’t support those bans. But as Nancy Reimer, a poultry veterinarian who provides care for Hilliker’s birds, puts it, “Some of this is political science, not poultry science.”

THE FIRST GLIMPSE of the HPAI strain now wreaking havoc came in 2010 in China’s Jiangsu province, when researchers from Yangzhou University isolated a new variant of a known subtype, H5N8, from a duck sold in a market. (The H and N refer to two viral surface proteins, hemagglutinin and neuraminidase.) Three years later, a similar virus was spotted in another duck, about 300 kilometers south in Zhejiang. When relatives surfaced a third time, in Korean breeder ducks the next year, a new clade was christened: 2.3.4.4b.

The march of 2.3.4.4b took an ominous turn at an island in Qinghai Lake on the Tibetan Plateau. The lake, the largest in China, provides a temporary home to some 150,000 migratory birds each year flying between Russia and India or Australia. On 1 May 2016, researchers discovered the carcass of a brown-headed gull, the first of some 150 gulls and geese at the lake found to have been infected with variants of 2.3.4.4b. The virus was evidently headed north.

That summer and fall some of the same variants turned up near the Ural mountains in Russia, and then the virus took hold in Western Europe. The resulting HPAI epidemic in poultry, researchers wrote in the Proceedings of the National Academy of Sciences, was “the largest and most widespread … ever recorded in Europe.”

By October 2020, the virus had undergone a significant genetic change, swapping N8 for N1, but the new H5N1 2.3.4.4b proved just as transmissible as its predecessor. It spread to Africa and back to Asia. Then, in November 2020, came evidence it had jumped the Atlantic Ocean: Researchers documented a sick great black-backed gull on Newfoundland. In the following weeks and months it established multiple beachheadsin North America.

By now, 2.3.4.4b has evolved a niche unlike any HPAI ever seen. Usually HPAI infections die out in a season, but the 2.3.4.4b clade is present year-round in migratory birds. It infects so many species in so many locales that no country’s poultry flocks are ever safe.

Despite their name, HPAIs can cause mild or no disease in some avian species, including ducks. But their arrival on an unvaccinated chicken farm can be devastating. Birds may become weak and listless, stop laying eggs, develop severe diarrhea, stumble, and struggle to breathe. An entire flock can die within 2 days. By USDA regulations, just a single bird infected with HPAI requires stamping out a flock, a gruesome procedure that entails cutting off ventilation in barns or suffocating the birds with carbon dioxide or fire-fighting foam. USDA has a program that compensates producers who are forced to cull, but rebuilding the business can still mean a major financial hit.

Globally the toll is enormous. The intergovernmental World Organisation for Animal Health has tracked stamp-outs triggered by H5 and H7 infections. Between January 2005 and 2022, more than 8500 H5 outbreaks led to the culling of nearly 400 million birds, with another 30 million sacrificed to fight more than 100 outbreaks of H7s.

IN 1995, MEXICO PIONEERED an alternative approach to combating HPAI, becoming the first country to use a vaccine as well as culling to stop a virus designated H5N2. The vaccine, which cost pennies per dose, was made like the human one, by growing the virus in eggs and then inactivating it with chemicals. The campaign eliminated the virus from Mexico’s flocks in short order.

China in November 2005 upped the ante in the face of a frightening H5N1 strain that spilled over to nearly 100 humans in Asia that year. In addition to culling, it set out to vaccinate all 14 billion chicken, geese, and ducks then consumed in the country each year—the largest single vaccination effort ever for any species, according to the Food and Agriculture Organization of the United Nations. The government provided the vaccine at no cost to farmers, who were required to use it. Thirteen other countries also used H5 vaccines in poultry by 2010, but China alone accounted for 91% of the total shots given to birds—nearly 100 billion doses.

Later, China faced a new threat: an H7N9 strain that spread through flocks in multiple waves starting in 2013. People caught it, too, mainly from farming or live poultry sold at markets, and by 2017 it had sickened 1500, killing 39% of them. The human tragedy and the economic loss led China in 2017 to introduce a bivalent H5/H7 vaccine for poultry.

This Iowa farm had to cull 56,000 birds in 2015 because of highly pathogenic avian influenza.

Culling flocks is a standard way to control the virus in the United States.SCOTT MORGAN/THE NEW YORK TIMES/REDUX

China’s HPAI vaccines have had limitations, says virologist Chen Hualan at the Harbin Veterinary Research Institute, who with her colleagues studied the country’s vaccination campaign. The evolution of new variants, which immune pressure from vaccines helped to speed up, forced repeated vaccine updates. And domestic ducks—which often did not get vaccinated—provided a haven for the virus.

China’s farmers rear about 4 billion ducks each year, mostly in open fields where they mingle with wild birds and are regularly exposed to flu and other viruses. But because ducks rarely become ill from HPAI, only about 30% of duck farmers vaccinated their birds. “This explains why even though the H5 vaccine has been used in poultry in China for over 10 years, H5 virus can still be detected in the live poultry markets, mainly from ducks,” Chen and her colleagues wrote in 2018.

Some Chinese farmers shunned HPAI vaccination because of worries that it could allow infections to spread without being detected by surveillance. Farms that raise chickens for their meat (the “broilers” that are slaughtered when they are about 6 to 8 weeks old) also had less financial incentive to vaccinate than farms with egg layers, which typically produce for a year or longer.

Still, Chen’s group found that about 70% of the chickens they sampled had antibodies from the H5N1 or the H5/H7 bivalent vaccines. As a result, she and her colleagues wrote in Emerging Microbes & Infections on 2 December 2022, “even though the globally circulating H5 viruses have been detected in many species of wild birds and occasionally in ducks or geese in recent years, they have never caused problems on routinely vaccinated poultry farms in China.”

China’s success in vaccinating against H7N9 is even more compelling. The Chen team sampled more than 50,000 poultry at some 1500 markets and farms before and after the H7N9 vaccine campaign began. They found the prevalence of the virus dropped by 93.3%, and the spread of H7N9 to humans stopped altogether. No human case of H7N9 has been reported since 2019.

The effort benefits both poultry and farmers, Chen told Science, because the government does not require culling an entire farm if the virus is found in one bird. “If it is in a farm with several barns, just birds in that barn will be destroyed,” she says.

Given that success, “We recommend that any unnecessary obstacles to vaccination strategies should be removed immediately and forever,” she and her colleagues wrote in a review paper this year.

Webster also sees lessons in China’s vaccination effort, which not only tamped down HPAI in China but likely kept H7N9 influenza viruses from spreading worldwide. “It is remarkable,” he says. “I believe that Chen is justified in believing that vaccination played an important role.”

The European Union in May 2022 conceded that vaccinating might make sense and is now testing candidates against 2.3.4.4b. At an October 2022 meeting in Paris, organized under the aegis of the International Alliance for Biological Standardization, participants called for “removing unnecessary barriers” for vaccination to control HPAI.

“We cannot keep doing the same thing over and over again,” said David Swayne, a veterinarian who for 28 years ran USDA’s main HPAI research group and co-organized the meeting, which brought together academic scientists, vaccinemakers, and representatives of European governments. “The virus has changed. We’ve got to change.”

IN THE UNITED STATES, the National Chicken Council is not convinced. The organization, which represents broiler farmers, has long argued that using HPAI vaccines would lead to trade restrictions, based in part on fears of silent infections that could contaminate chicken products.

Swayne dismisses that concern, which his own group’s experiments may have helped fuel.

They gave vaccinated birds extraordinarily high “challenge” doses of virus to see how well the vaccine prevented death and reduced viral shedding. The high doses meant that vaccinated birds sometimes got infected but showed no signs of illness. But the silent infection concern is “a misinterpretation of that data,” Swayne says. Vaccinated birds exposed to more realistic, real-world virus doses, he says, are unlikely to become infected.

Even if farms missed infections, the main U.S. export is meat, usually frozen—not live birds. No evidence exists that frozen meat can transmit influenza viruses. “When you look at risk analyses, they would say the chances of that happening are low or negligible,” Swayne says.

The bottom line is that business worries often trump science, says James Sumner, who served as president of the USA Poultry and Egg Export Council from 1990 to 2022 and remains a consultant there. “Many countries look for excuses to restrict trade,” he says—and many already have grievances against the United States. “The products that we export the most are the leg quarters, and we export those at a pretty low price because our industry makes its money on the upper half of the chicken, on the breast and the wings,” which Americans prefer, Sumner explains. Farmers in foreign countries “consider that unfair trade, and it is often classified as dumping,” he says. Refusing to import chicken meat from the United States if it vaccinates is a tempting retaliatory measure.

On the flip side, farmers who raise turkeys, another big branch of the U.S. poultry meat market, are more pro-vaccine because their birds are particularly susceptible to HPAI and they live for up to 6 months. “There are these divided camps,” Sumner says.

Still, the unprecedented H5N1 outbreak in the United States has altered the conversation.

Vaccination “is discussed much more widely now, and there are some people who are pushing for it,” Sumner says. “We all recognize that there are situations where vaccination would be beneficial.”

Poultry vaccinemakers say they stand ready to develop products if the market exists. Kumar says it would be wise for the government to at least order doses for USDA’s National Veterinary Stockpile now, as it did in 2016 to prepare for a variant of an H5N1 strain that had devastated poultry flocks the year before. (In response to a Freedom of Information Act request, USDA told Science that the stockpile currently contains no HPAI vaccines.)

Zoetis has produced what’s known as a master seed to make vaccine against 2.3.4.4b, Kumar says, and done initial safety and efficacy studies. Boehringer Ingelheim told Science that it, too, had “completed efficacy tests against clade 2.3.4.4b.” But both companies are waiting for a signal from USDA that it will allow use of the vaccines. “It’s not like you just turn on the button, and you have vaccine ready, right? It takes time to get it done,” Kumar says.

In March, USDA began to test four different HPAI vaccines made by agency scientists, Zoetis, and Merck. Erica Spackman, acting director of USDA’s Exotic and Emerging Avian Viral Diseases unit, says her team will challenge vaccinated chickens to see how well they’re protected against the 2.3.4.4b strain. The commercial vaccines target earlier H5 strains, but Spackman says a mismatch between a genome used to make a vaccine and the virus in circulation sometimes doesn’t matter. “Some strains are very immunogenic and that overcomes the mismatches,” she says. Spackman has little concern about vaccines creating silent infections. “Within the context of a population monitored by a surveillance program, as would be the case here, infection is not silent,” she says.

In a statement to Science, USDA said if the vaccines work, which the agency should know by June, it will look for manufacturers to produce them. (It will also consider data from European labs now testing vaccines against 2.3.4.4b, Spackman says.) Then, “there are 20 discrete stages to complete” before companies can submit data for regulatory approval, the statement says. It typically takes 2.5 to 3 years to complete that process, the agency said, but “in emergency situations manufacturers may expedite development, resulting in a shortened timeframe to licensure.”

Reimer, the veterinarian who cares for the birds at Hilliker’s farm, does not expect to be vaccinating chickens soon enough to protect them from the current HPAI wave. “I’ve had these discussions before,” Reimer says. “With this particular outbreak, I’m guessing we won’t resolve anything.” But by the time the next HPAI outbreak hits, she says, her charges may not have to face the virus unprotected.

BIRD FLU, HUMAN CASES AND THE RISK TO AUSTRALIA [ealth & Medicine, 20 Mar 2023]

By Dr Michelle Wille and Professor Ian Barr

Avian flu is continuing to spread throughout the world, infecting some mammals as it goes – but what’s the risk to Australia? Avian flu is continuing to spread throughout the world, killing wild birds and poultry en masse across the northern hemisphere, Africa and South America.

Not only is this strain of bird flu wreaking havoc on wild birds and poultry, it is responsible for numerous cases in mammals, including humans.

But what is the threat to Australia?

WHAT IS BIRD FLU?
Bird flu is a form of avian influenza that’s highly pathogenic for poultry and many wild birds.

Since 2021, we have seen the unfolding of an enormous panzootic of a particular strain of this highly pathogenic avian influenza, known as HPAI clade 2.3.4.4b H5N1.


There are current outbreaks on all continents except, for now, the Antarctic and Australia.

These outbreaks have been responsible for the deaths of more than half a billion poultry as of 28 Feb 2023, either due to the virus itself or in attempts to stop the virus spread through culling.

The number of wild bird deaths is unknown, but the scale is potentially in the millions across a great diversity of birds. So far, deaths have been recorded in some 303 different bird species.

For example, a recent outbreak in Peru reported more than 50,000 dead wild birdsacross the country’s protected areas. These outbreaks are of substantial conservation concern for wild birds, with potential population effects and, in some cases, a risk of extinction.

Of note, is that while HPAI viruses usually cause very high mortality in chickens and other poultry, with varying mortality in wild birds, there is an enormous diversity of avian influenza strains that cause no disease and circulate naturally in wild birds. These are called low pathogenic avian influenza (or LPAI) viruses.

WHAT IS THE RISK FOR HUMANS?
In addition to the avian outbreaks, numerous cases have been detected in mammals. These include outbreaks in a large Spanish mink farm, in sea lions in South Americaand a variety of human cases, most recently, a child in Cambodia.

These outbreaks have caused global concern about any potential mammal-to-mammal transmission.

Currently, this virus is still a bird adapted virus – meaning there are no confirmed cases of mammal-to-mammal transmission. The vast majority of cases reported in mammals have been in predators and scavengers that have been infected by the dead or dying birds that they’ve eaten.

So, perhaps it’s not surprising to see an increase in the number of mainly carnivorous mammalian cases given the scale of wild-bird outbreaks.

From experimental studies, we have a good idea which mutations are required for mammal-to-mammal transmission.

One of these mutations is currently widely detected in mammalian cases and occurs at lower mammalian body temperatures instead of the hotter avian body temperatures.

The other mutations of concern, which could make avian influenza viruses more transmissible in mammals, have not yet been found in the wild, but continued genomic surveillance and mutation mapping is critical to track the ongoing evolution of this virus.

To date, all human cases have been in people exposed to sick or dead birds (mainly poultry) infected with HPAI and there have been no confirmed instances of human-to-human transmission.

HPAI H5Nx has caused around 900 human infections since 2003, with an overall case fatality rate of approximately 60 per cent.

Given the large number of avian outbreaks, it’s reassuring that the number of human cases is very few. Even some of the human cases that have been initially recorded as infections with the 2.3.4.4b H5N1 viruses may have been due to carriage of the virus in the nose rather than a true infection.

This is often referred to as “environmental contamination”, resulting in a positive test for H5N1 virus in nasal swabs but the person shows no symptoms of a true infection, as has been suggested in two recent cases in Spain.

The World Health Organization (WHO) states that the risk for humans remains low, but is elevated for people occupationally exposed to infected birds. However, the WHO also indicates that the zoonotic risk is elevated.

Importantly, there are a number of therapeutics, like specific influenza antiviral drugs, which work well against all avian influenza viruses including H5N1 if taken early enough.

The WHO also evaluates avian influenza viruses at its bi-annual vaccine strain meeting in preparation for a potential pandemic and prepares seed viruses that could be used to produce vaccines if required.

GLOBAL RESPONSE AND RISK TO AUSTRALIA
Avian influenza is clearly a OneHealth disease – that is it affects wildlife, domestic animals and humans. So a multi-pronged OneHealth response is critical; we cannot wait until signs of human-to-human transmission occur.

Strong biosecurity is key to preventing viral incursion into poultry production and subsequent spill-over into wild birds – there’s certainly capacity for continued improvements.

More recently, vaccination has been considered as an additional tool to control spread.

Some countries, like Mexico, Vietnam and China have been vaccinating flocks for some time to try to control HPAI.

The US, UK, European Union (EU) and Australia do not vaccinate, however EU legislation has recently been changed to accommodate vaccination, but strict conditions must be met to ensure that vaccination efforts are effective and do not further drive virus evolution or cause “silent spread” (diminishes disease but does not stop infection).

These measures include making sure the vaccine is well matched to the circulating HPAI and that vaccination actually prevents infection with HPAI.

While not a silver bullet, vaccination has the potential to alleviate the burden of HPAI H5Nx on poultry when done appropriately and in combination with other exisiting approaches.

This will likely help prevent human spillover infections and would also hopefully reduce the impact on wild birds by lowering the overall environmental viral load.

Currently, Australia remains free from HPAI H5N1.

While avian influenza outbreaks have occurred here previously, they have always been caused by domestic strains that have evolved to become highly pathogenic rather than an incursion from globally circulating HPAI strains.

However, just because it hasn’t happened before, doesn’t mean this particular virus (that has become increasingly capable to also infect wild birds) will not arrive in Australia.

Millions of wild birds migrate between Asia and Australia each year, arriving from their northern hemisphere breeding grounds between September and November.

The main reason why this virus has not yet reached Australia is likely because there are no migratory duck species, which are the main movers of influenza viruses, migrating between East Asia and Australia.

However, we do know that shorebirds and seabirds are hosts for influenza, so if HPAI H5N1 were to arrive in Australia, it would most likely arrive with them.

In response to this risk, our team has performed enhanced surveillance on wild migratory birds as they arrived in Australia between September and December last year.

Thankfully all birds tested negative and there have been no indications of outbreaks in Australia since.

We will again enter a risk period of viral introduction when the migratory birds return in the second half of this year, and our teams will again be on the front lines to provide state and federal agencies rapid information to help them respond to any outbreaks – if they occur.

HPAI looks like it will continue to circulate for many years to come, so we need to maintain our long-term vigilance in Australia and work with others to try and eradicate or control this global threat.

Two dolphins die from bird flu in UK waters for the first time [inews, 16 Mar 2023]

The highly infectious H5N1 variant has previously been found in otters, foxes and grey seals in the UK
Two dolphins have died from bird flu in UK waters for the first time, the government has announced.

The sea mammals were found in separate locations, on beaches in Devon and in Pembrokeshire, last month.

Both dolphins were confirmed to have been infected with the highly infectious H5N1 variant of avian influenza which has spread around the globe during the past 18 months.

Millions of birds have died from bird flu in the latest outbreak, either from the virus itself or from culling, but scientists are concerned that it is spreading to mammals.

The virus has now been confirmed in 23 mammals in the UK. Bird flu has been discovered in dolphins in other parts of the world but these are the first cases in the UK. It has previously been found in foxes, otters and grey seals around the British Isles.

There has not so far been confirmation that the virus can spread between mammals in the wild, and most wildlife who contract avian flu are believed to have caught it from scavenging infected birds.

However there are concerns that H5N1 could potentially be spreading between mammals after the mass deaths of seals and sea lions elsewhere in the world.

The findings have been passed to the World Organisation for Animal Health.

The risk to humans from avian flu is classed as very low and the only cases have been in people who came into close contact with infected birds. There is no evidence of human to human transmission.

A spokesperson for the Animal and Plant Health Agency said: “Samples taken as part of routine wildlife surveillance have detected the presence of influenza of avian origin in two dolphins and one porpoise.

“The animals were found dead, and it is very likely they had predated on infected wild birds.

“The presence of influenza of avian origin in mammals is not new, although it is uncommon, and the risk of the H5N1 strain to non-avian UK wildlife remains low.”

The government says there is no evidence of an increased risk to non-avian wildlife following the deaths of the dolphins.

People are advised not to touch any sick or dead wild animals or birds and to wash hands thoroughly with soap after contact with any animal.

Bird flu: Nigeria is on major migratory bird routes, new strains keep appearing [The Conversation Indonesia, 16 Mar 2023]

Avian influenza is a highly contagious viral infection of birds, commonly called “bird flu”, which has been recurring in Nigeria since 2006. It has resulted in the loss of millions of birds and income for people who rely on the poultry industry. Nigeria is currently grappling with another outbreak which started in 2021.

The Conversation Africa asked Clement Meseko, a virologist and expert on animal influenza, to explain the disease’s re-occurrences.

What is bird flu? How does it spread? Is it dangerous to humans?

Bird flu is scientifically known as avian influenza and the pathogenic form as highly pathogenic avian influenza. It is a disease in birds (specifically poultry) caused by an influenza virus. It is highly pathogenic, meaning it causes tissue and organ damage in the host, and can kill more than 75% of the infected flock.

Waterfowls like ducks are natural reservoirs of the disease. They can harbour avian flu without showing any symptoms. Many waterfowls and other wild birds are migratory, moving across and between continents – this brings them into contact with resident birds and domestic poultry. Their body secretions and excretions may contain virus that can then infect other birds and poultry.

The symptoms in infected poultry include sudden death, respiratory distress, cough and haemorrhages in tissue and organs. Other animals, including pigs, horses and dogs can also be infected – and so can humans. In fact, it is zoonotic and therefore can be fatal for humans too.

Highly pathogenic avian influenza H5N1 virus infections have infected more than 880 people with about 50% case fatality globally.

The virus also has the capacity to cause a pandemic: an influenza virus of avian origin, but not the currently circulating strain, caused the 1918 pandemic that ultimately killed about 50 million people – worse than the current COVID-19 pandemic .

How many outbreaks have there been in Nigeria since 2006?
Nigeria’s first outbreak of bird flu was confirmed in January 2006, the first epidemic in poultry in Africa. It killed millions of birds and millions more were culled to contain its spread. The economic and livelihood loss was huge as the disease spread all over the country with 100% mortality in many cases. The estimate of the economic cost of bird flu outbreak in Nigeria was over nine billion Nigerian naira (about US$32 million) – with people losing investment, livelihood and jobs.

The disease was brought under control by 2008 thanks to stringent biosecurity measures like depopulation (culling), decontamination and control of poultry movement. In 2015 another strain emerged in Nigeria. Since then, new strains keep appearing.

Live bird markets, common across Nigeria, are the main points of spread of bird flu while wetlands are the points of initial transmissions. Local waterfowls and other birds that may harbour avian flu come into contact with other bird species and with people. In 2006, 312 cases and in 2015, 256 outbreaks of highly pathogenic avian influenza were recorded.

What should Nigeria be doing differently?
The disease may become endemic in Nigeria if circulation continuous and detection of the same strain is established. If a disease is constantly circulating in reservoir hosts it will lead to spill over to poultry and humans.

If that’s the case, biosecurity measures must be stepped up. For instance, the government may consider other measures in addition to biosecurity. This may include controlled and regulated vaccination. There are vaccines. They have been used in Egypt, China, Indonesia with a mixture of failure and success. Vaccines only reduce the impact of the disease but do not prevent infection or re-infection.

Those in the agricultural sector also need to introduce effective control measures at live bird markets and in the way poultry is traded more broadly. Measures would include restructuring the live bird markets, discouraging the mixing of species, the introduction of plastic cages and crates that can be easily cleaned and disinfected. Frequent cleaning, disinfection and decontamination of live bird market environments is very important for disease containment.

You’ve described as Nigeria was an “ecological sink” for such viruses. Please explain
In the research that examined the outbreak of the 2015-2016 bird flu, we found that west Africa was the epicentre of the virus that was later found in other sub-Saharan African regions – the central, eastern and southern African countries. In particular, within west Africa, Nigeria was the most important point of virus introduction and a central hub in the virus spread.

Bird flu is mostly introduced into Nigeria through the presence and activities of wild birds. For instance, in the 2015-2016 outbreak we identified four virus introductions into Nigeria likely from east Europe.

These birds travel across continents and countries through multiple international migratory routes, in much the same way that airlines move across the world on designated routes. Three major wild bird migratory routes from Asia and Europe transverse Nigeria. That’s good news for biodiversity but bad news for disease control.

Bird watchers and ornithologists have found that migratory birds from Europe move into Nigeria every year during the cold harmattan season (November - February). This is the peak time for avian flu outbreaks.

Nigeria is the most affected African country in terms of the frequency and burden of avian flu.

This makes it the destination “sink” of the strains that may be circulating in Europe at any given time.

Because we can’t change birds’ routes or habits, it would be up to Nigerian authorities to make sure it keeps its local birds and people as safe as possible. This would include surveillance of wild birds at wetlands and the monitoring of viral infections. Early detection is vital for early warning, risk analysis and control of infection.

'Like no outbreak we've seen': Will spring migration spike often-deadly bird flu cases? [Star Tribune, 16 Mar 2023]

By Bob Timmons

A year after a new outbreak took a toll on wild birds, wildlife health specialists are remaining cautious.

Minnesota wildlife health specialists have learned something from a year ago when a deadly bird flu outbreak began killing wild birds like bald eagles, hawks and owls: the virus remains a serious threat even if signs of its presence ebbs at times.

Now, with spring migration ahead and reports of new cases in Central and South America, attention is heightened. Migratory waterfowl, which naturally host some form of the virus, are known drivers of transmission.

"This outbreak continues to unfold like no other outbreak we have ever seen," said Victoria Hall, executive director of the Raptor Center at the University of Minnesota. Each year the center treats upward of 1,000 sick and injured birds.

The three most common species treated are great horned owls, bald eagles and red-tailed hawks. All were seen exponentially more in 2022, said Hall, attributed to an outbreak that originated in Europe. As of March 6, the center has tested 1,051 birds, with 215 positive cases. All but one raptor with bird flu died.

Great horned owls especially have been hard-hit by several factors, Hall said. They are cagey hunters and more likely to eat an infected waterfowl, or hunt in areas where geese and ducks live and are shedding the virus through bodily secretions and feces. The virus is endemic to swans, ducks and geese, some of which show no signs of illness. Plus, Minnesota has a significant waterfowl population that overwinters.

The owls in some cases were bringing the virus back to their nests — and their young, which already had hatched when the outbreak was peaking last spring.

"Entire family units would come in sick at one time, which we did not see with other species," said Hall, recalling a case of four or five owls together. Since last March, 92 of 215 positive cases have been great horned owls. Only one survived and was released back into the wild.

"Any time you are taking out breeding pairs, you have to think about population impact," she added.

As the virus shifts, specialists have shifted tactics, too, Hall said.

The center is working with the Center for Disease Control and wildlife managers with the Department of Agriculture, in addition to the Minnesota Department of Natural Resources, dialing in on how to respond and sharing knowledge.

The Raptor Center is testing for antibody levels in birds arriving at the center for reasons other than the flu to learn if raptors are surviving infection in the wild, Hall said.

"There is so much about wildife we are learning in real time, how this virus is working its way through," Hall said. "We can generate some of the science and tell the community what we are seeing."

For its part, the DNR partners with federal wildlife officials to test waterfowl seasonally for HPAI and has for several years. DNR staff were out last week in the south metro capturing dabbling ducks like mallards, with a goal of 110 swab samples this winter, said Wildlife Health Program Supervisor Erik Hildebrand.

The agency also investigates when there are reports of five or more sick or dead birds over a short period of time in a localized area. Carcasses are collected for testing at the University of Minnesota Veterinary Diagnostic Laboratory. Bird flu was confirmed in the deaths of American crows found in Hennepin County in mid-to-late January.

The Wildlife Health Program has to be mindful of all wildlife. Last May, DNR specialists investigated and confirmed the first case of bird flu in a mammal in Minnesota, when a sick fox kit was found in Anoka County. Sporadic infections have been reported, too, in foxes, skunks, bears and sea lions in the United States, Canada and other countries. Most recently, the World Organization for Animal Health reported six more U.S. cases, including a river otter in Wisconsin.

Hildebrand said people who see dead or dying birds or other wildlife should call the DNR's hotline at 888-646-6367.

"I hope we don't see what we saw last spring," he added.

Bird flu associated with hundreds of seal deaths in New England in 2022 [Science Daily, 15 Mar 2023]

Highly pathogenic avian influenza connected to a large scale mortality event in wild mammals
Summary:
Researchers have found that an outbreak of highly pathogenic avian influenza (HPAI) was associated with the deaths of more than 330 New England harbor and gray seals along the North Atlantic coast in June and July 2022, and the outbreak was connected to a wave of avian influenza in birds in the region.

Researchers at Cummings School of Veterinary Medicine at Tufts University found that an outbreak of highly pathogenic avian influenza (HPAI) was associated with the deaths of more than 330 New England harbor and gray seals along the North Atlantic coast in June and July 2022, and the outbreak was connected to a wave of avian influenza in birds in the region.

HPAI is more commonly known as bird flu, and the H5N1 strain has been responsible for about 60 million poultry deaths in the U.S. since October 2020, with similar numbers in Europe. The virus was known to have spilled over from birds into mammals, such as mink, foxes, skunk, and bears, but those were mostly small, localized events. This study is among the first to directly connect HPAI to a larger scale mortality event in wild mammals.

The co-first authors on the paper -- virologist and senior scientist Wendy Puryear and post-doctoral researcher Kaitlin Sawatzki, who both work in the Runstadler Lab at Cummings School -- have been researching viruses in seals for years. They credit their findings in the new study to a unique and robust data set made possible by a collaboration with wildlife clinics and rehabilitation and response organizations in the region, in particular with Tufts Wildlife Clinic and director Maureen Murray, V03, associate clinical professor at Cummings School, and an author on the paper.

"We have a better resolution and greater depth of detail on this virus than before because we were able to sequence it and detect changes almost in real time," said Puryear. "And we have pairings of samples, sometimes literally from a bird and a seal on the same beach."

The clinic has been conducting avian influenza surveillance on birds and some mammals since January 2022, shortly after this strain of avian influenza took a trans-Atlantic journey from Europe into the U.S. Through this testing, the team found a wide range of flu viruses, including at least three strains that crossed the Atlantic, and they witnessed consistent waves of infection in birds.

At the same time, in collaboration with NOAA's Greater Atlantic Region Marine Mammal Stranding Network, they were able to screen nearly all seals that came through the network, whether or not the animal appeared sick. The stranding network is composed of experts from state and federal wildlife and fisheries agencies, non-profit rehabilitation and response facilities, aquariums, and academic institutions who respond to strandings.

"Because of the genetic data that we gathered, we were the first to see a strain of the virus that's unique to New England. The data set will allow us to more meaningfully address questions of which animals are passing the virus to which animals and how the virus is changing," said Sawatzki.

How HPAI Is Transmitted
In addition to poultry, H5N1 also has had a huge impact on wild birds, especially sea birds. Multiple locations around the globe have experienced large die-offs, such as recently in Peru, where the virus killed 60,000 pelicans, penguins, and gulls.

At the time of the seal mortality event in New England, the virus was hitting gulls particularly hard, the researchers found. There are lots of ways gulls and other birds may transmit the virus to seals, they said. Seals and sea birds are coastal animals living in the same areas that have environmental contact, if not direct contact, since they share the same water and shoreline. A seal may contract the virus if it comes in contact with a sick bird's excrement or water contaminated by that excrement, or if it preys upon an infected bird.

The accepted knowledge is that H5N1 is nearly 100% fatal for domestic and wild birds other than waterfowl, and the same is proving true when it comes to spillover in wild mammals. All the seals that tested positive for HPAI were deceased at the time of sampling or succumbed shortly after. None of the animals that tested positive recovered. However, it's possible some asymptomatic or recovered cases never came into the stranding networks.

In addition to the seal mortality event in New England, which was the first time H5N1 was detected in marine mammals in the wild, other locations have lost marine mammals to the virus. Peru announced about 3,500 sea lions died from the virus, Canada reported a seal mortality event along the St. Lawrence Estuary, and there was a similar event with seals in the Caspian Sea, according to news reports from Russia.

A hotly debated topic among scientists is whether there has been mammal-to-mammal transmission of HPAI between seals.

"It's not surprising that you might have transmission between the seals, because it has happened with low pathogenic avian influenza," said Puryear. "However, we can't say definitively whether or not there has been mammal-to-mammal transmission of HPAI."

"To get strong evidence of mammal-to-mammal transmission, you need two things: lots of infected animals and time," explained Sawatzki. "Time for the virus to mutate, and time for the mutated virus to be transmitted to another seal. As the virus acquires mutations, we can see shared mutations in the sequences that are specific only to mammals and that haven't been seen in a bird before. We had the numbers, but this outbreak didn't last long enough to provide evidence for seal-to-seal transmission."

The research team found evidence that the virus mutated in a small number of seals. But fortunately, they have not seen a case of bird flu in seals along the Atlantic coast since the end of last summer. However, stranding season is about to start for harbor seals and gray seals, so they are bracing themselves for what might happen.

Prevention and Risk to Humans
The risk to the public remains low, according to the Centers for Disease Control and Prevention. Since December 2021, less than 10 human cases of H5N1 have been reported globally, and those cases occurred in people with direct exposure to infected poultry. There are no documented cases of human transmission for this variant.

However, there is the possibility it could become a larger issue for human health. Avian influenza emerged in 1996, and since 2003, 868 cases of human infection with H5N1 have been reported worldwide, according to the World Health Organization. Of those, 457 were fatal, roughly a 50% fatality rate.

"And that's why people get nervous about it," Puryear said.

There is a single-dose vaccine available for poultry, but it's not currently administered on a large scale -- in part because of cost and logistics, and in part because there's some concern it may make future surveillance of the virus more difficult. There's not much that can be done in terms of responding to the virus for wildlife, particularly given the scale at which infection is occurring.

Biosecurity is important in limiting the ways in which the virus can spread between and within species, the researchers said. For example, wild birds should be kept separate from domestic birds, such as backyard chickens. In addition, thorough and timely surveillance of domestic animals and wildlife is key to understanding how the virus is evolving to prepare the best possible vaccines and treatments.

Citation: Research reported in this article was supported by the National Institutes of Health's National Institute of Allergy and Infectious Disease under award 75N93021C00014. Complete information on authors, funders, and conflicts of interest is available in the published paper.

Story Source:
Materials provided by Tufts University. Original written by Angela Nelson. Note: Content may be edited for style and length.

Journal Reference:
1. Puryear W, Sawatzki K, Hill N, Foss A, Stone JJ, Doughty L, et al. Highly pathogenic avian influenza A(H5N1) virus outbreak in New England seals, United States. Emerg Infect Dis., 2023 DOI: 10.3201/eid2904.221538

Scientists Investigate a Bird Flu Outbreak in Seals [The New York Times, 15 Mar 2023]

By Emily Anthes

Wild birds passed the virus to seals in New England at least twice last summer, a new study suggests.

Last summer, the highly contagious strain of avian influenza that had been spreading through North American birds made its way into marine mammals, causing a spike in seal strandings along the coast of Maine. In June and July, more than 150 dead or ailing seals washed ashore.

Now, a study provides new insight into the outbreak. Of the 41 stranded seals tested for the virus, nearly half were infected with it, scientists reported on Wednesday in the journal Emerging Infectious Diseases. It is likely that wild birds introduced the virus to seals at least twice, the researchers concluded. In several seals, the virus had mutations that are associated with adaptation to mammals.

The risk to humans remains low, and the seal outbreak waned quickly, the scientists said.

“It was a dead-end event, as far as we can tell,” said Kaitlin Sawatzki, a postdoctoral researcher at the Cummings School of Veterinary Medicine at Tufts University and an author of the new paper. “The virus that entered into those seals has not persisted.”

But the report comes amid growing concerns that the virus, which has already caused the largest bird flu outbreak in the nation’s history, could adapt to spread more efficiently among mammals, potentially sparking a new pandemic.

It remains unclear whether the seals were spreading the virus to one another or primarily picking it up from birds. But the number of affected seals suggests that either the virus spreads easily among the marine mammals or that the barrier for bird-to-seal transmission is low.

“We truly don’t know if it’s transmitting from bird to seal, bird to seal, bird to seal 100 times over or if it’s going into a couple of seals and then spreading,” said Wendy Puryear, a virologist at the Tufts veterinary school and an author of the new paper. “Both are possible,” she added. “Neither are great.”

Either scenario calls for closer monitoring of seals, said David Stallknecht, an expert on wildlife diseases and influenza at the University of Georgia, who was not involved in the research.

“We need to just keep our eyes on them,” he said. “The easiest way to tell if this persists in seals is to keep testing them.”

The current version of H5N1 has become unusually widespread in wild birds and has spilled over repeatedly into mammals, including bobcats, raccoons and foxes. Scientists believe that most wild mammals are contracting the virus directly from birds.

But a bird flu outbreak on a Spanish mink farm last fall suggested that the virus could spread efficiently among some mammalian species. And a mass die-off of sea lions in Peru has raised concerns that marine mammals might be spreading the virus to one another, too.

Seals are known to be susceptible to avian influenza, and other versions of the virus have previously caused outbreaks in the animals.

The new study is a collaboration between researchers at several academic institutions and wildlife organizations, including Marine Mammals of Maine and New England Wildlife Centers, as well as federal scientists.

The researchers collected samples from 1,079 wild birds and 132 gray seals and harbor seals stranded along the North Atlantic coast from Jan. 20 to July 31, 2022. “That gave us a really powerful ability to see what is happening in the birds and the seals in the same time in the same region,” Dr. Puryear said.

There were two waves of flu in wild birds, the researchers found. The first, which peaked in March 2022, primarily affected raptors, while the second, which began in June, hit gulls and sea ducks known as eiders.

No seals tested positive for avian influenza during the first wave of bird infections. But during the summer stranding event, 19 of 41 seals tested positive.

The researchers found two slightly different versions of the virus in the seals. One matched what was circulating in terns, while the other resembled what was circulating in a broader array of birds, including gulls and eiders. The finding suggests that the virus spilled over at least twice.

Because these seals do not typically eat birds, the scientists suspect that the animals are picking up the virus from the environment, perhaps through contact with bird droppings.
Viral samples from the seals also had mutations that were rare or absent in birds. Three seal samples had mutations that have been shown to improve viral replication or increase virulence in mammals.

Such mutations are not unique. In another recent study, a team of Canadian scientists found the same mutations in some viral samples taken from bird-flu-infected foxes. “When there’s a bird-to-mammalian spillover event, they seem to be acquired to pretty quickly,” Dr. Sawatzki said.

The presence of these mutations is not, in and of itself, a reason to “sound the alarm,” Dr. Stallknecht said. But continued surveillance is necessary not only to safeguard human health but also to protect wild animals from a virus that has already proved devastating.

“These emerging diseases need to be looked at on a bigger scale than just ‘pandemic potential,’” he said, “because they affect a lot of other species on the globe.”

Europe's Bird Flu Outbreak Raises Concerns [Precision Vaccinations, 14 Mar 2023]

by Robert Carlson

Avian influenza is spreading in birds, mammals, and infecting people.

Since late 2021, a global shift has occurred in the ecology of highly pathogenic avian influenza (HPAI) of the H5 subtype. The continual spread of H5 HPAI (bird flu) is cause for concern, given the high mortality in birds, mammals, and some humans.

'Because past influenza pandemics originated from animal reservoirs, we argue that it is crucial to step up actions both to prevent H5 HPAI from becoming a future pandemic,' wrote Marion P G Koopmans. Viroscience Department, Erasmus University Medical Centre, Netherlands and colleagues in The Lancet Infectious Diseases on March 7, 2023.

To visualize the current impact across Europe, the European Food Safety Agency, the European Centre for Disease Prevention and Control (ECDC), and the European Union published an assessment of bird flu data collected from December 2022 to March 1, 2023.

This analysis found HAPI clade 2.3.4.4b was reported in domestic (522) and wild (1,138) birds in 24 countries.

An unexpected number of HPAI virus detections in sea birds were observed, mainly in gull species, particularly in black-headed gulls in France, Belgium, the Netherlands, and Italy.

The close genetic relationship among viruses collected from black-headed gulls suggests a southward spread of the HAPI virus.

Moreover, the genetic analyses indicate that the virus persisted in Europe in residential wild birds during and after the summer months.

And might increase during the coming months as breeding bird colonies move inland with possible overlap with poultry production areas.

Worldwide, the bird flu virus continued to spread southward in the Americas, from Mexico to southern Chile.

The Peruvian pelican was the most frequently reported infected species, with thousands of deaths reported.

The reporting of bird flu in mammals (sea lions) also continued, probably linked to feeding on infected wild birds.

Since October 2022, six A(H5N1) detections in humans were reported from Cambodia (a family cluster with two people, clade 2.3.2.1c), China (2, clade 2.3.4.4b), Ecuador (1, clade 2.3.4.4b), and Vietnam (1, clade 2.3.4.4b), as well as two A(H5N6) human infections from China.

This 43-page ECDC report says the risk of bird flu infection in Europe is assessed as low for the general population and low to moderate for occupationally or otherwise exposed people.
However, the number of mammals infected with A(H5N1) viruses and the detection of viruses carrying markers for mammalian adaptation in other genes, such as the PB2 that correlated with increased replication and virulence in mammals in Canada, South America, and the U.S. is of concern for humans.

Currently, the U.S. Food and Drug Administration, and other agencies, have approved bird flu vaccines for people.

In the U.S., the Audenza vaccine was approved in 2020 and would become available during an outbreak.

Furthermore, the U.S. government has funded initiatives to develop new bird flu vaccines.

Over 10% of Japan's Chickens to be Killed This Season as Avian Influenza Rages, Chicken Farmers [Mainichi Shimbun, 13 Mar 2023]

by Toru Morinaga

Since October 2022, highly pathogenic avian influenza has been raging across Japan, killing a record number of chickens and other animals. The price of chicken eggs is also at an all-time high. Koichi Tanaka, 78, who has supported the Tokyo metropolitan area for half a century in Ibaraki, the "chicken and egg kingdom," had his chicken coop emptied after the first round of culls.

The poultry farm he had spent half a century building was...
It was around 10:00 a.m. on December 20, 2010. The employee reported that 170 adult chickens had died in one of the six chicken coops at Tanaka Egg Farm, an egg-laying and poultry farm in Kasama City, Ibaraki Prefecture. The thought crossed my mind, "Could it be ......? In the afternoon, another 80 birds died, and on the following day, the simple test confirmed that they were positive. There was nothing Mr. Tanaka could do while prefectural officials in protective clothing spent two days disposing of all 106,000 birds on the farm with carbon dioxide gas.

Born and raised on a poultry farm, he started his own business around 1970 with 2,000 birds. Over the course of half a century, he has grown to employ nine employees and ship 90,000 to 100,000 eggs per day.

As a veteran poultry farmer, he also served as vice president of the Prefectural Poultry Farmers Association, and thought he had taken sufficient measures to prevent infection. He drew curtains over the skylights of his chicken coops to keep out wild birds and their droppings, and changed his boots when entering the coop. Vehicles entering and leaving the premises were disinfected, and rodents were regularly exterminated and slaked lime was sprayed to prevent small animals from entering. The Ministry of Agriculture, Forestry, and Fisheries is currently analyzing the cause of the outbreak. I thought we had prevented the outbreak because of the measures we had taken, but it may have just been a coincidence that there were no outbreaks," he muses. He has not been attending meetings of the association for some time because he feels uncomfortable.

A chicken coop where an outbreak of avian influenza was confirmed. A curtain was drawn over the skylight at Tanaka Egg in Ikenobe, Kasama City, Ibaraki Prefecture, at 0:09 p.m. on February 16, 2023.

A chicken coop where an outbreak of avian influenza was confirmed. A curtain was drawn over the skylight at Tanaka Chicken Egg in Ikenobe, Kasama City, Ibaraki Prefecture, at 0:09 p.m. on February 16, 2023 (photo by Toru Morinaga).

In mid-February, employees at Tanaka Chicken Egg were busy disinfecting chicken coops. All buildings had been disinfected three times, with several more scheduled. For a while, they were in a state of despair, but encouraged by their eldest son, who serves as managing director, they changed their mind, saying, "We intend to resume operations once we pass an inspection (by the Livestock Health and Sanitation Department) to see if the virus is detected in the walls and other parts of the poultry house.

With the advice of the Livestock Health Center, the company has set up "front rooms" in all the buildings where the poultry are changed before entering the coops in preparation for the reopening, which is expected in April. The plan is to install pipes to spray disinfectant on the roofs of the chicken coops by the fall, when migratory birds are expected to fly in.

Invisible root cause of the outbreak
The reason why the fear of another outbreak of avian influenza persists is that no fundamental solution is in sight, even though it has been nearly 20 years since 2004, when the first outbreak of avian influenza occurred in Japan in 79 years.

The number of birds killed this season has exceeded 15 million nationwide, a record high. The majority of these were egg-laying hens, which accounted for more than 10% of the approximately 137.29 million hens kept nationwide (as of February 2010). In Ibaraki alone, which had the largest number of egg-laying hens in Japan at approximately 15.14 million (as of February 2010), approximately 4.28 million, or nearly 30%, have already been disposed of. In March, the wholesale price of eggs, which had been kept low for many years, reached an average of 337 yen per kilogram of medium-size eggs (Tokyo area, as of March 9), the highest price since 1993, when statistics were first published.

The stable supply of "price superiority" is wavering. Mr. Tanaka says, "I hope they will allow the use of vaccines," but according to the Animal Health Division of the Ministry of Agriculture, Forestry and Fisheries, there is still no vaccine that can prevent the infection itself. Although four types of vaccines that are effective in suppressing the onset of the disease have been approved, the quarantine guidelines do not permit their use because "if symptoms are suppressed, detection may be delayed, and the infection may spread.

The Japan Poultry Farmers Association, a group of poultry farmers from across the country, has begun to request that the government take the lead in conducting research and studies on vaccines. In fact, calls for vaccination and development of a vaccine were also raised in 2004, mainly by the industry. The association sought approval for the use of a vaccine on the grounds that it could significantly reduce the amount of virus produced by infected people and could be effective in preventing the spread of infectious diseases. However, nearly 20 years have passed without any progress in the debate.

We have been making efforts to ensure a stable supply of safe eggs, but there are still concerns. We want consumers to know what is going on. The soil on the site where the hens and eggs were buried remains heaped up like a tomb.

Bird Flu Continues Decimating Mammals [Precision Vaccinations, 12 Mar 2023]

By Karen McClorey Hackett

The U.K. National History Museum recently reported sea lions in Peru are among the latest victims of a version of the highly pathogenic avian influenza (HPAI) known as bird flu.

The HAPI virus has killed about 3,500 South American sea lions in Peru as of March 9, 2023.
The Peruvian government has reported that since November 2022, around 3% of the country's sea lions have died due to HPAI infections.

Peru, like many South American countries, believes HAPI was brought south by pelicans before jumping into the marine mammals.

In the Northern Hemisphere, Canada and the United States have reported multiple mammalian fatalities related to bird flu infections.

The United States Department of Agriculture and the World Animal Health Information System reported during March 2023, over 131 HAPI H5N1 detections of wild striped skunks, black bears, raccoons, and red foxes.

? The California Department of Fish and Wildlife received confirmation on February 15, 2023, that an adult bobcat died from the Eurasian strain of HPAI H5N1.
? The Colorado Parks and Wildlife confirmed on February 9, 2023, several cases of HPAI in free-ranging wildlife (black bear, skunk, mountain lion).
? The Montana Department of Fish, Wildlife, and Parks confirmed on January 17, 2023, three juvenile grizzly bears tested positive for HAPI.

While there are no vaccines that protect birds or mammals from H5N1 infections, there are bird flu vaccines for humans.

In the U.S., the Food and Drug Administration authorized CSL Seqirus' Audenz vaccine on January 31, 2020, and RAPIVAB in 2022.

And the U.S. government has financially supported the development of newer bird flu vaccines for people.

Furthermore, the government reminds everyone that annual flu shots are effective against certain types of influenza, but they are not effective against bord flu viruses.

Tainai City Poultry Farm Confirmed Infected with Avian Influenza by Simple Inspection [NHK, 11 Mar 2023]

It has been confirmed that dead chickens at a poultry farm in Tainai City, Niigata Prefecture, were infected with avian influenza.

The prefectural government plans to begin the disposal of approximately 330,000 chickens being raised if the highly pathogenic virus, which has a high fatality rate, is detected.

On the morning of the 11th, a poultry farm in Tainai City reported to the prefectural government that it had noticed an increase in the number of dead chickens and other abnormalities, and as a result of a simple test, it was confirmed that the dead chickens were infected with avian influenza.

As a result, the prefectural government ordered the poultry farm to restrict the movement of the chickens and to thoroughly disinfect them.

If the highly pathogenic avian influenza virus, which has a high mortality rate, is detected in the ongoing genetic testing, the prefecture plans to begin the disposal of approximately 330,000 chickens raised for egg production at this poultry farm.

The prefectural government held a task force meeting at 5:00 p.m. on November 11, attended by Governor Hanazumi, to discuss future measures.

In Tainai City, highly pathogenic avian influenza virus was detected at another poultry farm this month, and the disposal of approximately 680,000 chickens was completed on November 11.

The prefectural government is calling for a calm response, saying that there have been no confirmed cases of avian influenza infection in Japan from eating chicken meat or eggs.

According to the prefectural government, if the highly pathogenic avian influenza virus is confirmed by genetic testing, this will be the fifth case of avian influenza at poultry farms and other facilities in the prefecture this season, following 13 cases in Kagoshima, 6 in Ibaraki, Chiba, and Hiroshima prefectures.

In response to the successive confirmations of avian influenza, the prefectural government has requested poultry farm operators to take extra precautions by thoroughly changing their boots when entering farms, and by checking again for holes where small animals can enter, such as ventilation fans and air vents, and other out-of-sight areas.

(translated by M.Y.)

New Coronavirus News from 1 Mar 2023

Long COVID Now Looks like a Neurological Disease, Helping Doctors to Focus Treatments [Scientific American, 1 Mar 2023]

By Stephani Sutherland

Tara Ghormley has always been an overachiever. She finished at the top of her class in high school, graduated summa cum laude from college and earned top honors in veterinary school. She went on to complete a rigorous training program and build a successful career as a veterinary internal medicine specialist. But in March 2020 she got infected with the SARS-CoV-2 virus—just the 24th case in the small, coastal central California town she lived in at the time, near the site of an early outbreak in the COVID pandemic. “I could have done without being first at this,” she says.

Almost three years after apparently clearing the virus from her body, Ghormley is still suffering. She gets exhausted quickly, her heartbeat suddenly races, and she goes through periods where she can't concentrate or think clearly. Ghormley and her husband, who have relocated to a Los Angeles suburb, once spent their free time visiting their “happiest place on Earth”—Disneyland—but her health prevented that for more than a year. She still spends most of her days off resting in the dark or going to her many doctors' appointments. Her early infection and ongoing symptoms make her one of the first people in the country with “long COVID,” a condition where symptoms persist for at least three months after the infection and can last for years. The syndrome is known by medical professionals as postacute sequelae of COVID-19, or PASC.

People with long COVID have symptoms such as pain, extreme fatigue and “brain fog,” or difficulty concentrating or remembering things. As of February 2022, the syndrome was estimated to affect about 16 million adults in the U.S. and had forced between two million and four million Americans out of the workforce, many of whom have yet to return. Long COVID often arises in otherwise healthy young people, and it can follow even a mild initial infection.

The risk appears at least slightly higher in people who were hospitalized for COVID and in older adults (who end up in the hospital more often). Women and those at socioeconomic disadvantage also face higher risk, as do people who smoke, are obese, or have any of an array of health conditions, particularly autoimmune disease. Vaccination appears to reduce the danger but does not entirely prevent long COVID.

The most common, persistent and disabling symptoms of long COVID are neurological. Some are easily recognized as brain- or nerve-related: many people experience cognitive dysfunction in the form of difficulty with memory, attention, sleep and mood. Others may seem rooted more in the body than the brain, such as pain and postexertional malaise (PEM), a kind of “energy crash” that people experience after even mild exercise. But those, too, result from nerve dysfunction, often in the autonomic nervous system, which directs our bodies to breathe and digest food and generally runs our organs on autopilot. This so-called dysautonomia can lead to dizziness, a racing heart, high or low blood pressure, and gut disturbances, sometimes leaving people unable to work or even function independently.

The SARS-CoV-2 virus is new, but postviral syndromes are not. Research on other viruses, and on neurological damage from the human immunodeficiency virus (HIV) in particular, is guiding work on long COVID. And the recognition that the syndrome may cause its many effects through the brain and the nervous system is beginning to shape approaches to medical treatment. “I now think of COVID as a neurological disease as much as I think of it as a pulmonary disease, and that's definitely true in long COVID,” says William Pittman, a physician at UCLA Health in Los Angeles, who treats Ghormley and many similar patients.

Although 16 million U.S. sufferers is a reasonable estimate of the condition's toll, there are other, more dire assessments. A meta-analysis of 41 studies conducted in 2021 concluded that worldwide, 43 percent of people infected with SARS-CoV-2 may develop long COVID, with about 30 percent—translating to approximately 30 million people—affected in the U.S. Some studies have offered more conservative numbers. A June 2022 survey reported by the U.S. National Center for Health Statistics found that among adults who had had COVID, one in five was experiencing long COVID three months later; the U.K. Office for National Statistics put the estimate at one in 10. Even if only a small share of infections result in long COVID, experts say, they will add up to millions more people affected—and potentially disabled.

Most of the first recognized cases of long COVID were in patients who needed extended respiratory therapy or who had obvious organ damage that caused lasting symptoms. People reporting neurological symptoms were often overlooked or dismissed as traumatized by their initial illness and hospitalization. But as 2020 came to an end, says Helen Lavretsky, a psychiatrist at the University of California, Los Angeles, “we started getting to a place of sorting through what was really going on ... and it became very evident at that time that neuropsychiatric symptoms were quite prevalent,” most commonly fatigue, malaise, brain fog, smell loss and post-traumatic stress disorder, as well as cognitive problems and even psychosis.

Ghormley was in her late 30s and relatively healthy when she caught the virus, but she had underlying conditions—including rheumatoid arthritis and asthma—that put her at risk for severe COVID. She spent several days at home, struggling to breathe, and then she went to the hospital, where her blood pressure soared and her blood glucose dropped precipitously. She mostly recovered from this acute phase within a few weeks, but, she says, “I never really got better.”

Soon after coming home from the hospital, Ghormley developed what her husband called “goldfish brain.” “I'd put something down and have no idea where I put it,” she recalls. “It kept happening over and over. I was thinking, ‘This is getting weird.’ My husband said I was not remembering anything. I'd try to talk, and I knew what I wanted to say, but I couldn't think of the word.”

“Everything fell apart for me,” says Tara Ghormley, who has been struggling with long COVID since 2020. Credit: Ewan Burns

She also experienced tremors, dramatic mood swings and painful hypersensitivity to sounds. “My husband opening a paper bag felt like knives stabbing me in the ear,” she recounts. Any exertion—physical or mental—left her exhausted and in pain. The changes were jarring to Ghormley, who prided herself on her sharp mind. “The thing that bothered me the most was that I was really having trouble thinking, speaking, remembering—trying to complete a task and having no idea what it was. Suddenly I had quite profound neurological deficits. Everything fell apart for me at that time. That was horribly traumatic ... it kind of broke me. I didn't feel like me.”

ROOTS OF DYSFUNCTION
As a veterinary internist, Ghormley says, it's her job to problem solve when mysterious symptoms arise, including her own. “I was actively trying to find reasons and find what I could do.” She theorized that some of her neurological symptoms might be the result of thrombotic events, blood clots that can cause ministrokes. Several early studies showed that COVID attacks endothelial cells, which line blood vessels. That can lead to clotting and oxygen deprivation in multiple organs, including the brain. Even subtle disruption of endothelial cells in the brain could contribute to cognitive dysfunction.

One study found that in people with neurological COVID symptoms, the immune system seems to be activated specifically in the central nervous system, creating inflammation. But brain inflammation is probably not caused by the virus infecting that organ directly. Avindra Nath, who has long studied postviral neurological syndromes at the National Institutes of Health, found something similar in an autopsy study of people who died of COVID. “When you look at the COVID brain, you don't actually find [huge amounts of virus, but] we found a lot of immune activation,” he says, particularly around blood vessels. The examinations suggested that immune cells called macrophages had been stirred up. “Macrophages are not that precise in their attack,” Nath says. “They come and start chewing things up; they produce all kinds of free radicals, cytokines. It's almost like blanket bombing—it ends up causing a lot of damage.

And they're very hard to shut down, so they persist for a long time. These are the unwelcome guests” that may be causing persistent inflammation in the brain.

Determining which patients have ongoing inflammation could help inform treatments. Early research identified markers that often are elevated in people with the condition, says Troy Torgerson, an immunologist at the Allen Institute in Seattle. Three cell-signaling molecules—tumor necrosis factor alpha, interleukin 6 and interferon beta—stood out in long COVID patients. But this pattern wasn't found in absolutely everyone. “We're trying to sort through long COVID patients and say, ‘This would be a good group to take to trials of an anti-inflammatory drug, whereas this group may need to focus more on rehabilitation,’” Torgerson says. He led a study (currently released as a preprint, without formal scientific review by a journal) in which his team measured proteins from the blood of 55 patients. The researchers found that a subset had persistent inflammation. Among those people, they saw a distinct immune pathway linked to a lasting response to infection. “One subset of patients does appear to have an ongoing response to some virus,” Torgerson says.

Isolated pockets of SARS-CoV-2 or even pieces of viral proteins may remain in the body well after the initial infection and continue to elicit an immune attack. The first solid evidence for “viral persistence” outside the lungs came in 2021 from researchers in Singapore who found viral proteins throughout the gut in five patients who had recovered from COVID as much as six months earlier. A study conducted at the University of California, San Francisco, found evidence for viral particles in the brains of people with long COVID. Scientists collected exosomes, or tiny packets of cellular material, released specifically from cells of the central nervous system. The exosomes contained pieces of viral proteins as well as mitochondrial proteins, which may indicate an immune attack on those vital cellular organelles. Amounts of such suspicious proteins were higher in patients with neuropsychiatric symptoms than in those without them.

The virus could linger in the brain for months, according to research conducted at the NIH and reported in Nature in December 2022. The autopsy study of 44 people who died of COVID found rampant inflammation mainly in the respiratory tract, but viral RNA was detected throughout the body, even in the brain, as long as 230 days after infection. Two other studies, both published last year in the Proceedings of the National Academy of Sciences USA, showed evidence that SARS-CoV-2 may infect astrocytes, a type of neural support cell, gaining entrance via neurons in the skin lining the nose.

Researchers are examining inflammatory signals in patients with long COVID in increasingly fine detail. A small study led by Joanna Hellmuth, a neurologist at U.C.S.F., found that patients with cognitive symptoms had immune-related abnormalities in their cerebrospinal fluid, whereas none of the patients without cognitive symptoms did. At the 2022 meeting of the Society for Neuroscience, Hellmuth reported that she had looked at more specific immune markers in people with cognitive symptoms and found that some patients had an elevated level of VEGF-C, a marker of endothelial dysfunction. Higher VEGF-C concentrations are associated with higher levels of immune cells getting into the brain, she says, and “they're not doing their normal function of maintaining the blood-brain barrier; they're distracted and perhaps activated.” Although the studies are small, Hellmuth adds, they reveal “real biological distinctions and inflammation in the brain. This is not a psychological or psychosomatic disorder; this is a neuroimmune disorder.”

What keeps the immune system in attack mode? According to Torgerson, “one option is that you've developed autoimmunity,” in which antibodies produced by the immune system to fight the virus also mark a person's own cells for immune attack. The response to the virus “turns the autoimmunity on, and that doesn't get better even when the virus goes away,” he says. Several studies have found evidence of autoimmune components called autoantibodies that interact with nerve cells in people with long COVID.

Clues about the inflammatory processes at work could point toward treatments for neurological symptoms. “If it's a macrophage-mediated inflammatory process ... intravenous immunoglobulin could make a difference [to] dampen the macrophages,” Nath says. The treatment, referred to as IVIg, contains a cocktail of proteins and antibodies that can mitigate an overactive immune response.

IVIg can also be used to block autoantibodies. And a therapy called rituximab that targets antibody-producing B cells provides “a time-tested therapy for a lot of autoantibody-mediated syndromes,” Nath says. Another strategy is to use corticosteroids to dampen immune activity altogether, although those drugs can be used for only a limited time. “That's a sledgehammer approach, and you can see if it makes a difference. At least it gives you an idea that, yes, it's an immune-mediated phenomenon, and now we need to find a better way to target it,” Nath says.

If the virus does hang around in some form, antiviral medications could potentially clear it, which might help resolve neurological symptoms. That's the hope of scientists running a clinical trial of Paxlovid, Pfizer's antiviral drug for acute COVID.

A CHRONIC FATIGUE CONNECTION?
Postviral syndromes have been documented for more than a century, arising after infection with viruses from HIV to the flu. Epstein-Barr virus, which causes mononucleosis, is one of several viruses linked to a condition called myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which is estimated to affect at least one and a half million people in the U.S. ME/CFS bears striking resemblances to long COVID, with symptoms such as immune system dysregulation, fatigue and cognitive dysfunction. “One of the patterns we see is patients who definitely meet the criteria for ME/CFS. This is something we are seeing and treating all the time” in long COVID patients, Pittman says. ME/CFS can be severe, with some people losing mobility and becoming bedbound.

Nath, who also studies ME/CFS, says that “we think mechanistically they are going to be related.” Researchers suspect that ME/CFS, like some cases of long COVID, could be autoimmune in nature, with autoantibodies keeping the immune system activated. ME/CFS has been difficult to study because it often arises long after a mild infection, making it hard to identify a viral trigger. But with long COVID, Nath says, “the advantage is that we know exactly what started the process, and you can catch cases early in the [development of] ME/CFS-like symptoms.” In people who have had ME/CFS for years, “it's done damage, and it's hard to reverse that.” Nath speculates that for long COVID, if doctors could study people early in the illness, they would have a better chance of reversing the process.

Torgerson hopes that researchers will ultimately come to better understand ME/CFS because of COVID. “COVID has been more carefully studied with better technology in the time we've had it than any other infectious disease ever. I think we'll learn things that will be applicable to other inflammatory diseases driven by infection followed by an autoimmune process.”

TEAM TREATMENT
Ghormley, after months of illness, sought care at UCLA Health's long COVID clinic, among the country's few comprehensive, multidisciplinary programs for people with this syndrome. Even though her symptoms are rooted in nervous system dysfunction, she needed an array of medical specialists to treat them. The clinic grew out of a program aimed at coordinating care for medically complex COVID patients, says its director Nisha Viswanathan, an internist and primary care physician. In following up with COVID patients after several months, she realized that “we had a group of patients who still had symptoms. There was no understanding around the condition; we were just trying to see what we could offer them.” Viswanathan and others convened a biweekly meeting of UCLA Health doctors in pulmonology, cardiology, neurology, psychiatry and other specialties to discuss individual cases and overall trends.

At UCLA Health, Pittman coordinates Ghormley's treatment. He says the interdisciplinary team is crucial to getting patients the best possible care. “Oftentimes there are so many symptoms,” and some patients have seen multiple specialists before arriving, but not necessarily the right ones. As long COVID primary care providers, he says, “we do the initial testing and get them to the right person.” For Ghormley, that list of providers includes Pittman, along with a neurologist, a pulmonologist, a cardiologist, a psychiatrist, a trauma counselor, a rheumatologist and a gynecologist.

The team approach has also been critical for doctors trying to understand a brand-new disease, Pittman says. “It's been a very interesting journey from knowing almost nothing to knowing a little bit now, and we're learning more every day, every week, every month,” he says.

The term “long COVID” “is an umbrella, and I think there are multiple diseases under that umbrella.” Although each long COVID patient is unique, Pittman says, “we start to see patterns developing. And with Ghormley, we saw a pattern of dysautonomia, which we see frequently.”

Dysautonomia impairs the autonomic nervous system, a network of nerves that branch out from the brain or spinal cord and extend through the body, controlling unconscious functions such as heartbeat, breathing, sweating and blood vessel dilation. For Ghormley, like many people with long COVID, dysautonomia takes the form of postural orthostatic tachycardia syndrome, or POTS. The syndrome encompasses a collection of symptoms that include a racing heart rate—particularly on standing—and fatigue, and it can cause bowel and bladder irregularities. POTS can also be a component of the exhaustion that comes with PEM. Although the symptoms may seem to affect the body, they stem from nervous system dysfunction.
Ghormley's dysautonomia led her to see cardiologist Megha Agarwal at a UCLA clinic near her home. Many physicians are not familiar with POTS, but Agarwal is particularly attuned to it, having seen it in some of her patients before COVID hit. “There's dysregulation of the nervous system, and so many things can cause it: some cancer therapies, viruses, autoimmune conditions.” Agarwal recognized POTS in Ghormley in the fall of 2020, when very little was known about long COVID. Now she believes “POTS is really what long-haul COVID is causing” in many patients. Luckily, Agarwal says, there are medical interventions that can help.

Tachycardia—the T in POTS—causes the heartbeat to speed up, contributing to exhaustion and fatigue in addition to stressing the heart itself. Drugs called beta-blockers (for the beta-adrenergic receptors they shut off in the heart) can lower the heart rate and improve symptoms. “When heart rate is controlled, not only does the pump improve,” Agarwal says, “[but people's] energy improves, their fatigue is gone, and sometimes there's better mental clarity.” For some patients like Ghormley, beta-blockers are not enough, so Agarwal adds a medication called ivabradine. “It's a bit off-label, but it's currently being aggressively studied” for POTS. For Ghormley, the combination led to real improvements, “so now she doesn't feel like she ran the Boston Marathon when all she did was sit down and stand up at work or take a shower,” Agarwal says.

Among Ghormley's toughest symptoms is her brain fog, a catchall term for a slew of cognitive problems that make it hard for her to function. For days when Ghormley works, her psychiatrist prescribes Adderall, a stimulant used to treat attention deficit hyperactivity disorder that helps her concentrate and stay focused. That has “helped immensely,” Ghormley says.

Ghormley credits her doctors and Agarwal in particular with doing the detective work to dig into her symptoms. “Nobody knew anything about it, but everyone listened to me,” Ghormley says. Perhaps because she was a professional from a medical field, no one “brushed me aside.”

That's unusual for people with long COVID, many of them women, who are often dismissed by physicians who doubt their complaints are real. “Patients just don't feel heard,” Viswanathan says. “I had a patient who told me everything, and after, I just said, ‘This must be so hard for you. I want you to know that everything you're feeling is real, and I've seen so many patients like you.’ And she started crying. She said, ‘No one has told me that. I can't tell you the number of times I was told it was in my head.’”

Credit: Now Medical Studio; Sources: “Postural Orthostatic Tachycardia Syndrome as a Sequela of COVID-19,” by Cameron K. Ormiston et al., in Heart Rhythm, Vol. 19; November 2022; “Long COVID-19 and Postural Orthostatic Tachycardia Syndrome—Is Dysautonomia to Be Blamed?” by Karan R. Chadda et al., in Frontiers in Cardiovascular Medicine; March 2022 (references)
In addition to drugs, other types of therapies, including physical therapy, can help improve some symptoms. But people who experience PEM face a particular challenge when using movement therapies. Pittman says the exertion can make these patients feel worse. “We don't want patients to go to not moving at all, but sometimes the type of movement they're doing may be flaring their symptoms.” He notes that often PEM strikes young, previously healthy people who will say, “‘I need to push myself,’ and then they go way too far and get worse. Our job is to try to find that middle ground and then make that consistent over time, so they're not getting further deconditioned but they don't have the PEM, which has been shown to set them back.”

THE LONG HAUL
Some patients, Pittman says, “have the expectation that they're going to come in, and within a month they're going to be back to normal. And resetting those expectations can be really challenging. You have to be really empathetic because people's lives have completely changed.”

But sometimes patients' quality of life can improve noticeably when they are able to adjust to a new normal. Still, he says, “patients have so many questions, and I can't lead them down a physiological pathway. I can tell them there's neuroinflammation, maybe there's autoimmunity, but we still don't have the answers. Sometimes it's really tough for us to accept and for the patient to accept that we just have to try our best.”

A number of people, Viswanathan says, benefit from reducing various treatments they have accumulated. Some people become so desperate that they will try anything from supplements to off-label medications to untested potions from the Internet. Stopping those sometimes leads to improved symptoms, she says.

Psychological care and support groups can help. Lavretsky adds that “lifestyle choices can play a huge role in improvement,” particularly better sleep habits and the use of breathing exercises to control anxiety. She tells people their bodies can heal themselves if the patients and clinicians find the right tools.

Whether that's true for everyone remains to be seen, Viswanathan says. “We see many patients who have gotten better with time. I have patients whose symptoms have disappeared in the course of a year, or they disappear and occasionally flare up again.” But for some, she says, “it could last many years.”

“We're going to be addressing this for probably decades,” Viswanathan says. “COVID is not going to go away so much as we're just going to get used to living with it, but part of [that] means that people will continue to develop long COVID.”

Vaccination appears to reduce the risk of long COVID. But a study published in May 2022 in Nature Medicine suggests the protection, though real, is not as good as one might hope. The survey of electronic health records from the U.S. Department of Veterans Affairs looked at the relatively small portion of vaccinated people who subsequently became infected. They developed long COVID only 15 percent less often than unvaccinated people. “These patients can have symptoms for one to two years or longer, and so every month you're racking up more patients. Even if it's 15 percent less, the total population of patients is still growing and exploding,” Pittman says. The best way to avoid getting long COVID, experts all agree, is to avoid getting COVID at all.

The syndrome is still mired in a lot of medical uncertainty. Patients might have one or a combination of the problems investigated so far: Long COVID might be caused by viral particles that persist in the brain or other parts of the nervous system. Or it might be an autoimmune disorder that lasts long after the virus has disappeared. Maybe overactive immune cells continue to perturb the nervous system and nearby blood vessels. Fortunately, the increasing ability to recognize specific problems is helping clinicians hone treatments that give patients the best chance of recovery.

Although Ghormley says her care has dramatically improved her symptoms and allowed her to “do some normal things again,” she continues to experience flare-ups that make it impossible for her to work for weeks at a time. One day last year she skipped a dose of her heart medication and made a Target run in the southern California heat. “I got home and basically collapsed in the hallway. Since then, everything has been out of whack. If I try to move around, my legs give out.” Most frustrating—and scary—to Ghormley is the unpredictability of her symptoms. “They have changed so much; some are manageable, some debilitating. One thing will get better, and another thing comes back. I'm always hopeful that it's going to get better, but I just don't know.”

New Coronavirus News from 4 Mar 2023

WHO calls on US to share information on Covid-19 origins after China lab claims [The Guardian, 4 Mar 2023]

World Health Organization’s director general says the politicisation of research into Covid’s origins was making the scientific work harder

The World Health Organization has urged all countries to reveal what they know about the origins of Covid-19, after claims from several US government agencies that a Chinese lab leak was behind the disease were furiously denied by Beijing.

“If any country has information about the origins of the pandemic, it’s essential for that information to be shared with WHO and the international scientific community,” the WHO director general, Tedros Adhanom Ghebreyesus, said on Friday.

The FBI director, Christopher Wray, told Fox News on Tuesday that his agency had now assessed the source of the Covid-19 pandemic was “most likely a potential lab incident in Wuhan”.

The first infections from coronavirus were recorded in late 2019 in the Chinese city, which hosts a virus research laboratory. Chinese officials have denied the FBI claim, calling it a smear campaign against Beijing.

Tedros stressed that the WHO did not wish to apportion blame, but wanted to “advance our understanding of how this pandemic started so we can prevent, prepare for and respond to future epidemics and pandemics”.

He said the politicisation of the origins research was making the scientific work harder and the world less safe as a result.

In 2021, the UN’s health agency set up the Scientific Advisory Group for the Origins of Novel Pathogens (Sago) to look into the origins of the pandemic.

“WHO continues to call for China to be transparent in sharing data and to conduct the necessary investigations and share the results,” said Tedros, adding that he had written and spoken to top Chinese leaders on multiple occasions.

“Until then, all hypotheses on the origins of the virus remain on the table.”

The comments from Wray came after a report earlier this week said the US Department of Energy had determined that a Chinese lab leak was the most likely cause of the Covid-19 outbreak. However, this assessment was made with “low confidence”.

Other agencies within the US intelligence community believe the virus emerged naturally.

Maria Van Kerkhove, the WHO’s Covid-19 technical lead, said the organisation had reached out to the US mission in Geneva for more information.

So far, however, they did not have access to the data on which the US reports were based, said Van Kerkhove.

“It remains vital that that information is shared”, to help move the scientific studies forward, she added.

Tedros said there was a moral imperative to find out how the pandemic started, for the sake of the millions who lost their lives to Covid-19 and those living with long Covid.

More than 6.8m Covid-19 deaths and more than 758m confirmed cases have been recorded by the WHO. The organisation acknowledges that the true toll is far higher.

New Coronavirus News from 6 Mar 2023

Bulgaria scraps large quantities of expired COVID vaccines [ABC News, 6 Mar 2023]

Bulgarian health authorities say that 2.8 million of expired COVID-19 doses will be destroyed this year in addition to 2.3 million doses that have already been scrapped

SOFIA, Bulgaria -- Bulgarian health authorities said Monday that 2.8 million of expired COVID-19 doses will be destroyed this year in addition to the 2.3 million doses that have already been scrapped in the country with the lowest vaccination rate in the European Union.
According to Health Minister Assen Medzhidiev there is an excessive number of vaccines, low vaccination coverage, and a lack of people who want a shot. Only 30% of the country’s 6.5 million population has basic immunization.
Medzhidiev said Bulgaria has called on the European Commission to end a contract with BioNTech/Pfizer under which his country is obliged to buy coronavirus vaccines until 2025. He said Bulgaria's position is supported by Poland, the Czech Republic and Lithuania.
The minister called it “irrational” for Bulgaria to buy more vaccines that the country will end up destroying.
Official figures show that Bulgaria will scrap more anti-COVID doses than it has administered.
A total of 4,6 million doses have been administered in Bulgaria. Some 2 million people have completed a two-shot vaccination course, while nearly 1 million have received a booster dose. There have been some 1.3 million confirmed cases of COVID-19 in Bulgaria, and a confirmed death toll of 38,211.

Zoonotic Bird Flu News since 24 Feb till 10 Mar 2023

Bird Flu" from dead crows in Fukuoka City: Positive in simple test, confirming whether it is highly pathogenic [TV Nishinippon, 10 Mar 2023]

Fukuoka Prefecture announced that a dead crow suspected of being infected with highly pathogenic avian influenza was recovered in Fukuoka City.

According to the prefecture, on the morning of March 9, the carcass of a raven was found in Fukuoka City, and as a result of a simple test, it was confirmed positive for avian influenza.

A genetic test is currently being conducted at the National Institute for Environmental Studies to confirm whether or not it is highly pathogenic avian influenza, and the results are expected to be known within a few days.

The Ministry of the Environment has designated the area within a 10-kilometer radius of where the carcass was recovered as a priority wild bird monitoring area, and the prefecture is continuing to strengthen its monitoring of wild birds and calling for the attention of poultry farms and others in the prefecture.

A total of 10 cases of highly pathogenic avian influenza have already been confirmed in the prefecture this season, the highest number ever recorded.

(translated by M.Y.)

Avoiding the Culling of All Birds Due to Bird Flu by Split Control of Poultry Houses...A Poultry Farmer in Aomori Takes the Lead [Yomiuri Shimbun, 4 Mar 2023]

The highly pathogenic avian influenza raging in Japan has prompted an egg-laying poultry farmer in Aomori Prefecture to introduce a "split management" system for sanitary control on farms, whereby each group of poultry houses is managed separately. Normally, if any part of a farm is infected, all the birds in the farm will be subject to culling, but by treating the chicken coop groups as "separate farms," the number of birds subject to culling can be reduced. The Ministry of Agriculture, Forestry and Fisheries plans to promote the introduction of this system to large-scale farms nationwide through prefectural governments.

This season's outbreak of highly pathogenic avian influenza has occurred at 55 egg-laying farms nationwide since last October. As of the 3rd of this month, a record 13.79 million hens, or 10% of all egg-laying hens, had been culled. Of these, five farms had more than 1 million chickens, accounting for 5.97 million. The shortage of eggs is spreading and prices continue to soar.

Under the split management, large farms with over 1 million eggs are divided into multiple groups of poultry houses, each with separate personnel, vehicles, equipment, egg sorting and packaging facilities, and other facilities. By eliminating back and forth traffic, the spread of the virus can be prevented, and in the event of an outbreak, the killing of infected chickens can be limited to the same group of poultry houses as the infected chickens. This is also called "block management" or "separate farm management (translated by M. Y.).

Cambodia Child Dies of Bird Flu "No Mutation to Spread to Humans" [nhk.or.jp, ３ Mar 2023]

In response to the death of an 11-year-old child infected with bird flu in Cambodia last month, the U.S. Centers for Disease Control and Prevention (CDC) has released its latest analysis of the virus found in the country, which found no genetic mutations that could spread the disease from human to human or weaken the effectiveness of drugs against the virus.

In Cambodia, an 11-year-old girl and her father were infected with H5N1 avian influenza, and the girl died last month.

The CDC had been analyzing the virus found in the dead girl, and announced on April 2 that no genetic mutation had been identified in the virus that could spread the virus from human to human or weaken the effectiveness of drugs against the virus.

Since the two infected individuals had the opportunity to come in contact with infected birds in an environment where birds are raised, the CDC now believes that the case is not human-to-human, but bird-to-human transmission.

According to the World Health Organization (WHO), the H5N1 avian influenza virus has been reported to infect birds in many parts of the world, and cases of infection in mammals have also been found one after another, prompting health authorities in various countries to increase their vigilance. (translated by M.Y.)

A Record Number of 240,000 Cattle Killed in Fukuoka; Japan Self-Defense Forces Requested to Dispatch Dispatchers - Avian Influenza "Confirmed" at Large Poultry Farm [rkb.jp, 2 Mar 2023]

Chickens found dead at a large-scale poultry farm in Fukuoka City have been "confirmed" positive for avian influenza by genetic testing. Fukuoka Prefecture announced the news on the morning of March 2. This is the fourth case this season at a farm in Fukuoka Prefecture. A record number of more than 240,000 chickens will be killed. Disinfection points will be set up at various locations. Due to the large scale of the disaster, Fukuoka Prefecture has requested the Self-Defense Forces to be dispatched to the disaster site.

"Positive" Even with Highly Accurate Genetic Tests
A large poultry farm in Fukuoka City was newly confirmed "positive" in a genetic test for avian influenza. The prefecture will not disclose the specific location or name of the facility.

According to the prefectural government, about 90 chickens died on February 28 and about 100 on March 1 at the poultry farm, and since a simple test on the morning of the 1st tested "positive," a more accurate genetic test was conducted.

The Self-Defense Forces were requested to be dispatched to the disaster site.

All chickens, numbering over 240,000, are to be destroyed. The prefecture has requested the Self-Defense Forces to be dispatched to the disaster site. The period of time will be from the 2nd to the end of the operation. In addition, based on national guidelines, quarantine measures will be taken, including the establishment of restricted movement zones and disinfection points at various locations. This is the fourth case of avian influenza this season at a farm in Fukuoka Prefecture.

Not contagious to humans.
The government has stated that there is no possibility that the avian influenza virus can be transmitted to humans by eating chicken or chicken eggs.

How the fourth case was "confirmed" by genetic testing
March 1, 8:10 a.m. The farm notifies Fukuoka Prefecture
March 1, 11:15 a.m. 12 out of 13 birds test positive in relation tests.
March 2, 9:00 a.m. Genetic testing (PCR test) confirms the H5 subtype gene, and the animals are determined to be highly pathogenic avian influenza pseudo-affected.

This is the first to third highly pathogenic avian influenza cases in Fukuoka Prefecture.
December 19, 2022: Confirmed at a poultry farm in Itoshima City
December 26, 2022: confirmed at a poultry farm in Itoshima City
January 3, 2023: Confirmed at a poultry farm in Koga City

(translated by M. Yamage)

Falcon Found in Komatsu City, Identified as Highly Pathogenic Avian Influenza [NHK, 2 Mar 2023]

In February, a wild falcon was found dead in Komatsu City, infected with avian influenza.

The prefectural government will continue to conduct a focused survey of the surrounding area until late March.

On February 27, a dead wild falcon was found in Komatsu City and was found to be infected with the avian influenza virus.

Detailed examination of the specimen has been conducted at a laboratory in Ibaraki Prefecture, and as a result, the avian influenza virus that infected the falcon was identified as the highly pathogenic "H5 subtype," which is highly infectious.

The Ministry of the Environment has designated a 10-kilometer radius around the area where the dead birds were found as a priority area, and the prefectural government is continuing to investigate whether there are any dead or weakened birds in reservoirs, riverbeds, etc. within this area.

The prefectural government has also called on poultry farms to disinfect their premises and prohibit unauthorized entry.

In the prefecture, the same H5 subtype was detected in two wild birds found in Kanazawa in January of this year, making this the third highly pathogenic virus confirmed in the prefecture this year. (translated by M. Yamage)

Bird flu kills 1.52 million egg-laying hens, more than 10% of all hens raised in Japan [Asahi Shimbun, 2 Mar 2023]

On March 2, the Ministry of Agriculture, Forestry, and Fisheries (MAFF) announced that Fukuoka Prefecture will begin culling 243,000 egg-laying hens following the confirmation of a suspected highly pathogenic outbreak of avian influenza at a poultry farm in Fukuoka City. This brings the total number of egg-laying hens targeted for culling nationwide to 13.85 million, more than 10% of the 137.29 million hens kept nationwide (as of last February).

The bird flu has spread at a record pace this season (last fall through this spring), with 77 cases reported in 25 prefectures as of the morning of February 2. A total of 15.02 million birds, including meat chickens and ducks, have been targeted for culling.

The spread of the disease has also affected the supply of eggs, with some supermarkets experiencing a shortage. According to a survey of price trends conducted by the Ministry of Agriculture, Forestry and Fisheries at 470 stores nationwide, the price of eggs in February was 262 yen per pack (mixed size, 10 pieces). The price has remained high, at 108% of the previous month's level and 125% of the normal level. At a press conference on February 28, Minister of Agriculture, Forestry and Fisheries Tetsuro Nomura explained, "This is not a story of an immediate solution, so it will take six months or nearly a year (for normalization).

Bird Flu Detected in Jay Carcass in Moka City (Tochigi TV) [Yahoo News, 1 Mar 2023]

Regarding the bird flu virus detected in the carcass of a wild jay found in Mooka City on February 21, Tochigi Prefecture announced on March 28 that a national genetic test showed that the virus was highly virulent and highly pathogenic. 　This is the sixth case this season in the prefecture. According to the prefectural government, no abnormality has been confirmed at poultry farms in the area. (translated by M. Yamage)

Wholesale Egg Prices Hit New Highs in February Due to Spread of Avian Influenza [N H K, 28 Feb 2023]

This month's wholesale price of eggs reached its highest level since 1993, when statistics were first published, due to soaring feed prices and the spread of bird flu.

The average price per kilogram of medium-size eggs in the Tokyo area of JA Zen-Noh Eggs　（ ja.z-tamago.Co.,Ltd）, the standard for wholesale egg prices, was 327 yen this month, up 152 yen, or 86%, compared to the same month last year.

The price in December last year was 284 yen, the highest price since 1993, when statistics were first published, and this month's price was 43 yen higher.

According to the Ministry of Agriculture, Forestry and Fisheries, egg prices usually peak in December, when demand for Christmas cakes and Osechi dishes is high, and then tend to fall.
This season, however, the high prices are due to soaring prices for corn and other feedstuffs as a result of Russia's invasion of Ukraine and the continued spread of avian influenza since the beginning of the year, which has led to a decrease in the number of shipments.

Because of the decline in egg shipments, poultry farmers are prioritizing the supply of eggs for households, and convenience stores and restaurants have been unable to offer some of their products using eggs.

Regarding the outlook for the future, the Ministry of Agriculture, Forestry and Fisheries states, "Since the number of bird flu outbreaks in Japan usually tends to decrease after March, we will continue to monitor the situation closely.

We asked Seiji Nobuoka, a former professor at Tokyo University of Agriculture and executive advisor to the "Japan Poultry Farmers Association," about the outlook for egg prices.

In Japan, approximately 14.78 million chickens have been destroyed so far this season due to the avian influenza.

Of these, approximately 10% of the chickens raised in Japan for egg production have been destroyed.

Mr. Nobuoka commented, "It is not easy to immediately put new birds into poultry farms after killing the chickens. It takes more than a year to bring a poultry farm up to full operation. The price of corn, the raw material for feed, remains high, so there is concern that the impact will be prolonged," he said.

Nobuoka then points out that egg prices are higher in rural areas than in the Tokyo metropolitan area.

According to JA Zen-Noh Eggs, the average wholesale price per kilogram of M-size eggs this month was 341 yen in the Nagoya area, 332 yen in Osaka, and 337 yen in Fukuoka, all higher than the 327 yen in Tokyo.

Mr. Nobuoka commented on this, "Outside of the Tokyo metropolitan area, major production areas such as Kyushu, Chugoku, and Shikoku were severely affected by bird flu, so egg prices are higher in western Japan. Also, Nagoya ships not only locally but also to Osaka and Tokyo, so demand has increased and prices have risen," he said.

(translated by M. Yamage)

How concerning is bird flu? [The Financial Express, 27 Feb 2023]

A recent report published in the British multidisciplinary science journal, Nature, says that a variant of bird flu virus, H5N1, that can spread from mammal to mammal also poses risk to both humans and wild animals. At an American mink farm in Spain, the outbreak of H5N1 occurred in October 2022. Scientists through genetic sequencing found that the bird flu virus that infected the minks was a new variant of the H5N1. The genetic material included a strain from gulls and it also bore the mark of a genetic change that increases some bird flu virus's ability to reproduce in mammals. In fact, this change in the genetic makeup of the avian flu makes it unpredictable. The virus found in the American mink farm in Spain should be under closer scrutiny so that it may not infect people, scientists warned. What is worrying is that the H5N1 seems to be gaining its capacity for jumping from birds to mammals. So far as the American experience goes, about a dozen species including racoon fox, seal and grizzly bear have been found to be infected by the avian flu virus.

According to the US Centers for Disease Control and Prevention (CDC), the ancestors of the H5N1 bird flu that were infecting wild birds and poultry since 2021, first emerged in southern China in 1996. That was followed by widespread infection in the poultry population in Hong Kong in 1997. However, the outbreak could finally be controlled. Later the bird flu (H5N1) reappeared in 2003 and broke out among birds throughout Asia. Then it spread to Africa, Europe and the Middle East infecting poultry birds. But there were also some sporadic reports of human infection by the avian flu virus. In 2014 and 2015, it again appeared in the wild birds and poultry in the USA and Canada leading to massive outbreak of the avian flu among the poultry population of those two countries.

However, as the records of the World Health Organization (WHO) goes, since 2003 reports of human infections with avian flu H5N1 have been few and far between. Meanwhile, through comparing the properties of H5N1 viruses responsible for earlier outbreaks of avian flu with those of 2021and 2022, the US national public health agency, CDC, also found some differences (in properties of H5N1 of 2021-22). And the CDC views the observed changes in the H5N1 virus to be benign in nature since some elements of the past bird flu that were responsible for infections among humans are absent in latest version of bird flu (H5N1).Even so, the recent devastating impact of the avian flu on poultry population with some 15 million birds dead and 193 million culled, its fast spread across the continents, the changes found in the genetic make up of H5N1 that enabled it to jump from birds to mammals. The occasional reports, though rare, of human infections by the virus give reasons to be concerned. As recently as in January, a WHO report said that a young girl was infected by the avian flu in Ecuador. This is first such report from South America. Al Jazeera reports that last year there were only five cases of human infection by the bird flu. In the past, according WHO, the mortality rate of the humans infected by bird flu was 53 per cent. Actually, between 2003 and 2009, 468 people, mostly poultry workers, were reported to have been infected by the bird flu.

And 282 of those infected died of the disease. In the last two decade, 457 cases of people dying after the bird flu infection could be confirmed. Though epidemiologists are seeing no cause for alarm, still the general public with their recent experience with covid-19 pandemic want to be reassured. The recent history of the H5N1 variant's ability to kill birds and mammals like the American minks on an unprecedented scale is obviously concerning.

Against this backdrop, it would be worthwhile to see under what conditions the bird flu virus infected people leading to their deaths. The illness caused by the avian flu among people was both mild and severe. In milder cases, from eye infection to upper respiratory infections occurred. In the severer cases, it turned into pneumonia causing the deaths. Those who got infected by the bird flu were in close contact with the infected birds for long without taking any precautionary measures such as wearing of gloves, masks or other protective gears to safeguard their lungs and eyes from the virus. The victims touched or even breathed in from air polluted with droplets of the sick birds' saliva, mucous, faeces, etc. Such long exposure of the unprotected human subjects to the bird flu can cause mild to severe respiratory conditions and may ultimately prove deadly for some. Scientists have discovered five subtypes of the bird flu viruses that can spread to people causing respiratory illness. Those include H5, H6, H7, H9 and H10. And the subtypes causing most of the infections are H5N1, as we already know and the H7N9 variants. However, reports of the bird flu-infected people spreading the disease among other people by contagion are indeed rare. Until now, the avian flu is still an animal health issue, says the US national public health agency, CDC.

But that does not mean that precautionary measures are not necessary. The behavioural interventions including social distancing and other health protocols, even resorting to lockdowns in extreme cases as were practised during the covid-19 pandemic is the proven deterrents against any new pandemic. If the bird flu virus by any accident of natural origin turns into a deadly virus infecting humans on a massive scale, then behavioural interventions should be the first weapon to fight it. That is, until, of course, an effective vaccine is developed against the new pandemic.

Viruses in Cambodian bird flu cases identified as endemic clade [Reuters.com, 27 Feb 2023]

Feb 26 (Reuters) - The viruses that infected two people in Cambodia with H5N1 avian influenza have been identified as an endemic clade of bird flu circulating in the country, the U.S. Centers for Disease Control and Prevention (CDC) said.

The cases reported last week had raised concerns they were caused by a new strain of H5N1, clade 2.3.4.4b, which emerged in 2020 and has caused record numbers of deaths among wild birds and domestic poultry in recent months.

But work so far suggests this is not the case.

Preliminary genetic sequencing carried out in Cambodia led its health ministry to identify the viruses as H5 clade 2.3.2.1c, which has circulated in Cambodia among birds and poultry for many years and has sporadically caused infections in people, the CDC said in a statement on Saturday.

"Yes, this is an older clade of avian influenza that had been circulating around the region for a number of years and while it has caused human infections in the past, it has not been seen to cause human-to-human transmission. However, that doesn't mean that the threat is any less," said Erik Karlsson, director of the National Influenza Center of Cambodia and acting head of virology at the Institut Pasteur du Cambodge, which sequenced the virus.

He added that the response needed to be coordinated and swift to prevent any further spread and to limit exposure to any common source.

An investigation into the source and to detect any additional cases is ongoing, the CDC said, adding that so far there had been no indication of person-to-person spread.

Cambodia tested at least 12 people for the H5N1 strain last week, after an 11-year-old girl died from the virus in the first known transmission to humans in the country in nearly a decade.

The victim's father, who was part of a group the girl had been in contact with in a province east of the capital Phnom Penh, tested positive for the virus but did not exhibit any symptoms, Cambodia's Health Minister Mam Bunheng had said in a statement on Friday.

Only the girl's case has been sequenced and the father's case is still being worked on, Karlsson said.

The World Health Organization said it is working with Cambodian authorities following the cases, describing the situation as worrying due to the recent rise in cases in birds and mammals.

Lateral flow tests being prepared for UK outbreaks of avian flu [The Guardian, 26 Feb 2023]

By　Robin McKie

People are being warned to be careful when in contact with wild birds. Photograph: Maureen McLean/REX/Shutterstock

British health officials are preparing plans to deploy lateral flow tests if signs emerge that avian flu has begun to spread from one person to another.

The programme would provide rapid information about the dangers posed by the disease.

The UK Health Security Agency (UKHSA) is also working on blood tests to detect antibodies against the virus and officials will analyse the disease’s genetic mutations to reveal data about the increased risk to human health from avian flu.

The moves follow last week’s news that an 11-year-old girl in Cambodia has died from H5N1, the flu strain that is being spread around the globe by migrating birds and is infecting poultry farms.

Investigators are now trying to establish if infected birds were the cause of the Cambodian case, rather than human-to-human transmission.

At present, evidence suggests the H5N1 virus does not pass easily to people although scientists have urged care and caution.

“Viruses constantly evolve, and we remain vigilant for any evidence of changing risk to the population,” said Dr Meera Chand, incident director for avian influenza at the UKHSA .

This point was backed by Professor Ian Brown of the Animal and Plant Health Agency (APHA). “There have been over 850 cases in humans across the globe since 1996 with a high case- fatality rate.

“Almost all cases to date have not resulted in human-to-human transmission but vigilance is required.”

Scientists also warned last week that although direct risks of infection were low, people should avoid contact with sick or dead wild birds in public areas such as parks or waterways and should wash their hands after feeding wild birds.

Last week, the UKHSA confirmed it had found avian flu cases in poultry at 145 premises and in 656 wild birds in England, a rise of 15 new premises and 209 detections in wild birds since December 2022.

In addition, 14 out of 134 wild mammals collected since October 2021 were found to have avian flu: four in foxes in England and one in Wales. In Scotland, there were four cases in otters, four in seals and one in a fox.

“This virus keeps cropping up in various mammals and this could increase the possibility of further human infections,” said Prof Jonathan Ball, of Nottingham University. “The risk to humans is still very low, but it’s important that we continue to monitor circulation of flu in both bird and mammal populations.”

The human Spanish flu pandemic of 1918 ? which killed an estimated 50 million people ? is believed to have been triggered by a successful transmission of an avian flu virus to humans.

“The initial strain then adapted and became endemic in the human population, giving rise to the seasonal flu viruses,” said Professor Massimo Palmarini, director of the Centre for Virus Research, Glasgow University.

“This is why it is important to detect human cases of avian influenza as quickly as possible and make sure that we give as little opportunity as possible to the virus to be transmitted further and mutate.”

Cambodia reports H5N1 avian influenza clade is 2.3.2.1c - Outbreak News Today [Outbreak News Today, 25 Feb 2023]

In a follow-up on the H5N1 avian influenza cases reported in Cambodia this week, the Cambodian CDC announced on their Facebook page today that the clade identified is 2.3.2.1c.

Here’s what they wrote (computer translated):
Bird flu virus H5N1, which is the cause of death of girls living in Rolang village, Khlach commune, Central Sitha district, is a virus that has been studied among local birds, wild birds in Cambodia during the last few years.


Bird flu H5N1 (clade 2.3.2.1c): Different from H5N1 bird flu in other countries around the world.

Monitoring of the disease is ongoing, while the population in contact with the patient remains monitored.

As of today, there has not been any clear evidence of transmitting H5N1 bird flu from person to person.

Request all citizens to avoid direct harm with sick or dead birds. Let’s protect and prevent together for our health.

From the World Health Organization:
A(H5) viruses from birds and non-human mammals characterized from September 2022 to February 2023 belonged to the following clades:
Clade 2.3.2.1a viruses were detected in poultry in Bangladesh. There were up to 10 amino acid substitutions in the HA of recent viruses compared to the HA of A/duck/Bangladesh/17D1012/2018, from which a candidate vaccine viruses (CVV) has been developed. Some of the recent viruses did not react well to a post-infection ferret antiserum raised against the A/duck/Bangladesh/17D1012/2018 CVV but instead reacted well with a post-infection ferret antiserum raised against the A/duck/Bangladesh/19097/2013 CVV.

Clade 2.3.2.1c viruses were detected in birds in Viet Nam and Lao People’s Democratic Republic. Viruses from Viet Nam reacted well with a post-infection ferret antiserum raised against the A/duck/Vietnam/NCVD1584/2012 CVV, despite recent strains having up to 9 amino acid substitutions in the HA.

Clade 2.3.2.1e viruses were detected in Timor-Leste. The HAs of these viruses were most closely related to viruses previously detected in Indonesia. There are no CVVs representative of this HA clade and the viruses from Timor-Leste reacted poorly with post-infection ferret antisera raised against clade 2.3.2.1a and 2.3.2.1c CVVs. No human infections have been associated with viruses of this clade and the extent of their circulation is uncertain.

Clade 2.3.4.4b viruses were detected in birds in many countries in Africa, Asia, Europe, North America and, for the first time, in Central and South America. An increasing number of infections in wild and captive mammals has been reported, with mink-to-mink transmission suspected on a farm in Spain. Viruses from this clade have been associated with several different NA subtypes with N1 now predominating. The high levels of infection in birds with these viruses and increased geographic distribution have been accompanied by genetic diversification. Some A(H5N1) viruses from Europe, the United States of America (USA) and Viet Nam show reduced reactivity with post-infection ferret antisera raised against the A/Astrakhan/3212/2020 CVV. All viruses from Europe reacted well with post-infection ferret antiserum raised against A/chicken/Ghana/AVL763_21VIR7050-39/2021; a representative CVV is being developed. Many viruses from the USA that had reduced reactivity with antisera raised against the A/Astrakhan/3212/2020 CVV showed better reactivity with post-infection ferret antisera raised against A/American wigeon/South Carolina/22-000345-001/2021.

The US Centers for Disease Control and Prevention writes: HPAI A(H5N1) virus infections have been reported in more than 880 people with approximately 50% case fatality proportion since 1997, including 20 cases and 7 deaths in Hong Kong during 1997-2003, and more than 860 cases reported in 21 countries since November 2003. Mild upper respiratory tract symptoms, lower respiratory tract disease, severe pneumonia with respiratory failure, encephalitis, and multi-organ failure have been reported. One case of asymptomatic infection was reported in Vietnam in 2011, and another asymptomatic case was reported in the United Kingdom that occurred in late 2021. The spectrum of illness caused by human infection with current H5N1 bird flu viruses is unknown. Since 2016, a small number of sporadic infections have been reported each year globally. Illness in humans from all bird flu virus infections has ranged in severity from no symptoms or mild illness to severe disease that resulted in death.

Bird flu: UK health officials make contingency plans [BBC, 24 Feb 2023]

By Michelle Roberts

UK health experts are sharing details of their Covid-style plans against bird flu, including modelling for the unlikely scenario that it could mutate and cause a pandemic in people.

The UK Health Security Agency (UKHSA) says there is no evidence H5N1 virus is an imminent threat or can spread between people, despite some getting sick after contact with infected birds.

But there is no room for complacency.

One expert told the BBC "we must prepare for the worst" just in case.

The World Health Organization (WHO) is urging heightened vigilance from all countries, following the death of an 11-year-old girl in Cambodia from H5N1.

The girl's father has also tested positive, according to Cambodia's health minister.

Investigators are working to establish if infected birds were the cause, rather than a case of human-to-human transmission.

Humans rarely get bird flu, but when they do it is usually from coming into direct contact with infected birds.

Since late 2021, the world has been experiencing one of the worst global avian influenza outbreaks on record, with tens of millions of poultry culled and mass wild bird die-offs.

And there have been a few infections in some mammals, including foxes and otters in the UK.
Dr Meera Chand, from the UKHSA, said all of the latest evidence suggested H5N1 could not currently spread easily to people.

"However, viruses constantly evolve, and we remain vigilant for any evidence of changing risk to the population, as well as working with partners to address gaps in the scientific evidence."
In preparation for a worst-case scenario of human-to-human spread, the UKHSA is modelling:
? How many might become infected and get very sick
? Whether lateral flow tests and blood tests would be helpful
? What genetic mutations might signal an increased risk to human health

When the Covid pandemic hit, there were no suitable vaccines available to fight that virus. But for bird flu, there are already several good candidates that might help.

WHO-affiliated labs already hold two flu virus strains that are closely related to the circulating H5N1 virus, that manufacturers can use to develop new shots if needed, experts said at a meeting on Friday.

Prof Peter Openshaw, from Imperial College London, is a member of Nervtag - the group that advises the British government on new and emerging threats from respiratory viruses.

He told the BBC that the fact that we are still in a Covid pandemic in no way lessened the possibility of another pandemic coming from elsewhere.

"We absolutely need to watch this one," he said.

"The good news at the moment is that there's no evidence of human-to-human spread.
"We need to prepare for the worst but obviously hope for the best, to use the old phrase."

"Not another pandemic" might well be the exasperated response of many to talk of the risks from bird flu.

Covid fatigue is understandable but the H5N1 virus is a real concern to many scientists who monitor global disease threats.

Thankfully, the virus does not spread easily from birds to humans, requiring close contact.

That would need to change if the threat of a human pandemic was to be realised, which would require the virus to mutate.

Since 2003 the WHO has recorded 868 cases in humans, of which 457 were fatal, so the mortality rate is more than 50%.

Scientists want to see better surveillance, more investment in vaccines and antivirals - so that should the worst ever happen, the world will be better prepared than it was when Covid emerged.

Bird Flu pandemic plan drawn up by scientists as they prepare for 'biggest threat' [GB News, 24 Feb 2023]

By Carl Bennett

It comes following the death of an 11-year-old girl in Cambodia
The brains behind Britain’s Covid lockdown measures have met to prepare for the latest global pandemic threat amid growing fears the Bird Flu outbreak could transfer to humans.

The group of experts meets twice a year to decide which strain of seasonal flu to include in the vaccine for the upcoming winter season, with the H5N1 avian flu being considered following a record number of bird deaths worldwide in recent months.

Officials from the UK Health Security Agency (UKHSA) are said to be developing “scenarios of early human transmission” in order to “facilitate preparedness.”

Since the latest outbreak of Bird Flu only one Briton has caught the disease, and the World Health Organization (WHO) say the threat to humans is low.

But experts are concerned amid recent reports of mass deaths in infected mammals, from seals to bears, as well as potential mammal-to-mammal transmission on a Spanish mink farm last year.

It also follows Cambodia reporting the death of an 11-year-old girl after she was infected by the H5N1 strain of Bird Flu, the Southeast Asian country’s first known human infection with the strain since 2014.

Health workers have since disinfected the property in Prey Veng province, east of the capital Phnom Penh, where the girl lived.

Speaking ahead of the meeting, Sylvie Briand, WHO director of global infectious hazard preparedness, said “"we are more prepared (than for Covid), but even if we are more prepared, we are not yet prepared enough," adding “We need to really continue the efforts for a flu pandemic."

Those working on the models in the UK include Professor Neil Ferguson, whose Covid projections led to the UK Government to force the first lockdown.

Experts are already discussing potential vaccines.

WHO-affiliated labs have two flu virus strains which are closely related to the H5N1 virus, which could be used by manufacturers to create a human vaccine if needed.

One of them was added following the previous WHO flu meeting in September 2022, with labs globally testing how closely both subtypes match the strain spreading among animals to determine whether any more updates are necessary.

A number of companies that produce season flu vaccines could also make pandemic flu vaccines.

Having the strains ready and prepared could save two months in vaccine development, according to Briand. The problem, however, would be producing enough vaccine quickly, experts warn.

Whilst extremely rare, human-to-human transmission of H5N1 can happen.

In 1997, 18 cases were discovered in Hong Kong, but these were maintained and ultimately did not lead to a global viral spread.

The World Health Organization warns that of the 868 human H5N1 cases reported to it over the last two decades, 456 were fatal.

Bird flu spreading from mammals to humans 'increasingly worrying,' experts warn [Daily Star, 24 Feb 2023]

BY Adam Cailler

Bird flu experts fear we are sleepwalking into disaster with more than half of folk dying after catching the disease.

Of the 860 known human cases of avian flu since 2003, 53% have died, a British Medical Journalstudy found.

Dr Quinton Fivelman, of London Medical Lab, fears we are becoming “used to outbreaks on poultry farms” while the rising virus spread from bird to mammals was incredibly worrying.

Dr Fivelman said: “The fact that it is now spreading to mammals shows we cannot let our guard down against this virus. The higher number of cases mean a greater chance of mutation. It’s concerning there is no vaccine as yet.”

The first human cases were recorded in Hong Kong and China in 1997.

It comes as we reported a a girl had died from bird flu, confirming the worst fears of scientists who predicted it could jump from mammals to humans just last month.

The sad death of the 11-year-old was reported in Cambodia earlier today (Thursday, February 23).

The girl first became ill just six days before her death, and suffered from a fever, cough and sore throat.

Her death was confirmed by the country's Communicable Disease Control Department, who said that the girl from the Prey Veng province “tested positive for H5N1”.

As a result, the World Health Organization has said: "The recent spillover to mammals needs to be monitored closely."

The news comes just a weeks after we reported that it was found that a deadly strain of the avian bird flu had mutated and can now impact mammals.

Scientists had found that the avian flu had been transmitted from wild birds to a group of mink on a farm in the Spanish city of La Coruna.

The study, published on top infectious disease surveillance website Euro Surveillance, stated that the outbreak happened in Spain in October 2022.

Explainer: H5N1 Bird Flu in Mammals Sparks Fears of Virus Spreading Among Humans [Bloomberg, 24 Feb 2023]

By Michelle Fay Cortez

An avian influenza ? bird flu ? outbreak with the H5N1 strain that began in 2020 has hit record levels, affecting millions of animals. As the virus mutates genetically and spreads geographically, the normal ebb and flow of infection has given way to a persistently elevated level in wild birds. They are spreading the highly contagious pathogen to domesticated poultry and a rising number of mammals, including badgers, bears, ferrets, pigs and raccoons ? as well as a handful of people. Though the virus has been around for decades, there are no signs of it having made the jump to human-to-human transmission. Still, the possibility exists that it could further evolve to cause catastrophic outbreaks in people ? just as the world is moving beyond the worst of the Covid-19 pandemic.

Avian influenza in the US alone has affected nearly 60 million birds ? including wildlife, commercial poultry and backyard flocks ? since January 2022, according to the Centers for Disease Control and Prevention. That’s on top of the 50 million birds destroyed in 36 European countries between October 2021 and September 2022. And it’s not just birds. In the UK, there have been 10 reports of infections in non-avian wildlife since the start of 2022, including in red foxes, Eurasian otters and harbor seals.

Bird flu death: What will happen next and is there a vaccine? [New Scientist, 24 Feb 2023]

By Clare Wilson

An 11-year-old girl in Cambodia has died in hospital after catching bird flu. Her father has tested positive for the virus responsible, but it is unclear whether he caught the infection from her or the family's poultry collection

A girl has died from bird flu in Cambodia after possibly catching it from her family’s small flock of chickens and ducks. At least one of her close contacts has also tested positive, but authorities are still waiting on the results of testing her wider circle.

How many people have died from bird flu in the latest cluster of cases?
An 11-year-old girl from Cambodia has died from a subtype of the bird flu virus called H5N1 in the rural Prey Veng province, a region close to the capital Phnom Penh. She developed flu-like symptoms on 16 February and after her condition deteriorated, she was sent to hospital, where she died. Out of 12 of her close contacts who have been tested, only her father has so far been found to be positive for the virus.

How did she catch it?
It could have been from her family’s small collection of ducks and chickens, as all the animals at her home ? 22 chickens and three ducks ? had recently died, according to BNO News, but the cause of their deaths is unknown. There have also been a number of fatalities among wild birds in the area.

Is bird flu now spreading between people?
Even if more of the girl’s 12 contacts test positive, this doesn’t mean the virus has evolved to spread easily between people. Her father and any other cases could have caught the virus directly from infected birds, says Wendy Barclay at Imperial College London. “If she’s had contact with backyard poultry, there’s a chance that friends she played with have also had contact [with the birds],” she says.

Should we expect more cases?
Since 2021, bird flu has been surging in wild bird populations and spreading to domestic poultry flocks and occasionally other animals, such as foxes and seals, which eat birds. That raises the likelihood of the virus crossing over to people, says James Wood at the University of Cambridge. “We expect there to be some cases of [human] disease with such a widespread infection,” Wood said in a statement to the Science Media Centre in the UK.

How deadly is bird flu in people?
Over the past 20 years, there have been about 900 known cases of human infection with various strains of H5N1, of which about half were fatal. But the death rate may appear higher than it really is because there are likely to be many cases where people didn’t develop symptoms or weren’t tested for the virus, says Barclay. There is now thought to be about 30 different genetic variants of H5N1 viruses circulating in birds, which probably differ in their ability to make people sick.

Has vaccine production begun?
Mass production of a bird flu vaccine cannot begin because we don’t yet know which variant, if any, could make the jump to start freely spreading between people. The effectiveness of flu vaccines hinges on making them from viruses that are as close a match as possible to the one that people eventually catch.

Manufacturers are about to start making the usual seasonal vaccines ahead of the northern hemisphere’s winter. If they were to switch to making H5N1 vaccines prematurely, that would risk not enough seasonal flu vaccines being available later this year. “Seasonal vaccine is very important in saving lives,” Sylvie Briand at the World Health Organization (WHO) said at a press conference this week. “You need to balance the risks and benefits when you talk about switching vaccines.”

But manufacturers routinely carry out preparatory work using “candidate vaccine viruses” and the WHO has asked them to do this using a selection of the H5N1 viruses, the organisation announced this week.

Are there any treatments?
There are several antiviral treatments for seasonal flu, such as oseltamivir (Tamiflu), which has been used as a treatment as well as a preventative medicine among the close contacts of people known to have bird flu.

In a few cases, the H5N1 virus evolved resistance to oseltamivir, although this seemed to be linked with the virus also becoming less virulent and less transmissible. At the press conference, the WHO said it has been in talks with manufacturers of antivirals about how quickly they could scale up production.

What happens if bird flu does start spreading between people?
Briand has said that if human-to-human transmission were discovered, health authorities would try to prevent further crossover events from animals to people, as well as aiming to stop the virus’s spread between people. This would be “by treating cases, isolating cases so that they don’t further transmit the virus and also identifying contacts”, she said. “We can use antivirals to treat contacts for post-exposure prophylaxis and reduce the likelihood of further human transmission.”

The WHO would also try to prepare neighbouring areas for further spread using intense surveillance of viruses, informing communities about how to reduce their risk of infection and helping healthcare workers avoid infection with protective equipment.

How concerned should we be about bird flu? [The Hub at Johns Hopkins, 24 Feb 2023]

By Katie Pearce

Johns Hopkins epidemiologist and environmental microbiologist Meghan Frost Davis discusses the current state of the H5N1 outbreak and its global reverberations

Now two years in, the global avian flu outbreak has devastated wild and domestic bird populations, leapt into various species of mammals, and cost governments and farmers billions as consumers feel the pain in their grocery bills. Despite containment efforts, the record-breaking outbreak?caused by a highly contagious new variant of H5N1?shows no signs of slowing as migration season looms.

While the virus so far has not posed significant threats to humans, many unknowns remain as it continues to evolve, according to Johns Hopkins epidemiologist and environmental microbiologist Meghan Frost Davis. "What we know about flu strains is that they're constantly changing. Our influenzas have the potential to become epidemics or pandemics," she says. "So that's what we keep at the back of our minds."

"RIGHT NOW, THERE'S NO REASON TO BELIEVE THAT THESE AVIAN INFLUENZA STRAINS WILL RISE TO THE NEED TO BE INCLUDED IN OUR DECISION-MAKING OVER HUMAN VACCINES. WE'LL SEE IF THAT CHANGES."

In particular, the jump from birds to mammals?including foxes, bears, mink, whales, and seals?is "significant and something to pay attention to," says Davis, an associate professor in environmental health and engineering at Johns Hopkins University's Bloomberg School of Public Health. "What people may not remember from high school biology is that there are larger differences between birds and mammals than there are among mammals, so finding the virus in mammals indicates an expanded host range."

Davis recently spoke with the Hub about the current state of the outbreak and its global reverberations.

What can you tell us about the extent of this outbreak?
What we're seeing is an epizootic?the term we use for an epidemic, but with animals?happening in wild birds in many parts of the world, which has caused a record-breaking outbreak of avian flu in domestic poultry, including chickens and turkey raised for meat and eggs, as well as backyard poultry kept for the household or as pets. So the outbreak is of great concern for animal health, starting with the poultry especially. But now we've also seen it detected in a number of other animals, including mammals. And it's shown up in a very small number of people globally.

What makes this avian flu outbreak stand out from other similar ones of the past?
What we more typically see with outbreaks in animals is that they'll surface and then go away, usually within the space of a season. What's unusual about this one is that it's been going on for some time, starting sometime in 2021, with various sub-strains developing. It's been persistent and widespread, and now has affected an estimated 58 million birds in the United States and more globally.

What usually happens to prevent these outbreaks from spreading further is going to commercial flocks to depopulate them. So remove the animals, then wait out the viability of the virus in the local environment. They'll do a good cleaning to make sure everything's good, then repopulate the flock.

These control measures aren't enough to contain the current outbreak. That's pretty significant because we're not just talking about the loss of animal lives, which is tragic, but we're talking about widespread impacts to our food systems and our ecosystem, not to mention the commercial and psychosocial impacts on people raising the animals. This can all be quite devastating.

Why is it significant that the avian influenza has shown up in mammals?
From a public health perspective, we're perennially concerned about any infectious agent that has potential to move from one species to another species, and in particular from an animal species into a human. And if thatbecomes the kind of virus that can transmit human-to-human, that's where we see outbreaks, epidemics, or even pandemics. Of course the SARS-CoV-2 virus that caused the COVID-19 pandemic is one example of this, and we're still struggling with it.

"THERE HAVE BEEN RARE CASES WHERE AVIAN FLU HAS BEEN FOUND IN PET ANIMALS SUCH AS CATS AND DOGS. THE BASIC ADVICE IS TO PREVENT CONTACT WITH WILD BIRDS … I WORRY MORE ABOUT PET BIRDS, INCLUDING THOSE THAT ARE INDOORS BUT MIGHT HAVE INDIRECT CONTACT WITH WILD BIRDS THROUGH A SCREENED WINDOW OR DOOR."

What level of concern is there that this could spread more widely among humans?
Thankfully with the current outbreak we've seen fewer than 10 human cases documented, one of those in the United States. And we've been doing targeted surveillance of people who have been in contact with positive birds, which was the case for the individual in the U.S., who experienced mild symptoms for a few days. Surveillance is key to catching these groups with potential exposure, who could help us identify and track new strains.

With the current strains circulating, we haven't seen high risk to humans?so that's reassuring, right? However, what we know about flu strains is that they're constantly changing. This is why our seasonal influenzas have the potential for epidemics or pandemic strains. Those are the worst-case scenarios we imagine.

Even though the number of cases in humans from this outbreak is small, the recent death of a girl in Cambodia shows how severe the disease can be.

You mentioned depopulation as a control method. What are other methods to limit the spread of bird flu?
With the wild bird population, clearly it's not really possible to control it. But as far as what individuals can do, you'll hear advisories for people to disinfect bird feeders, or to not use bird feeders or bird baths at all because you don't want congregations of birds. For people who deal closely with birds, wear N95 masks, and if you suspect an animal might be sick?maybe they're not eating or drinking well, maybe you see discharge around the eyes, or unkempt feathers?it's time to call your veterinarian or potentially also contact appropriate state agencies.

With domestic poultry, some of these flocks are hundreds of thousands of birds, so once the virus gets into the flock, it can spread quickly. In these facilities, prevention focuses on biosecurity and biocontainment. Basically, you stop any new elements from coming into a large farm, for example. You disinfect, you limit visitors, you try to enclose the facilities. Even with backyard flocks these principles can be used?you isolate chickens in coops.

Different states may have different agencies or groups handling this kind of thing; for example in Maryland we have an extension service through the University of Maryland as well as the state Department of Agriculture monitoring this situation and taking action. It's something that's on the radar and a high priority for the poultry industry as well as for animal health professionals.

What about vaccines? What role could they play here?
With human vaccinations, we have expert groups come together to decide which strains to include in our seasonal flu vaccines. Right now, there's no reason to believe that these avian influenza strains will rise to the need to be included in our decision-making over human vaccines. We'll see if that changes.

With animal vaccination, there are two different considerations: How effective is it in preventing disease, and is it economically feasible? We tried this with COVID-19 vaccines for animals and found that the cost-benefit ratio wasn't really where it should be. With the bird flu, I'm not certain these questions have been fully addressed to the point where an effective vaccine could be brought to market. To my knowledge, there is no widespread deployment right now of vaccines for poultry.

Should we be concerned about impacts to our pets, i.e. cats that interact with birds?
There have been rare cases where avian flu has been found in pet animals such as cats and dogs. The basic advice is to prevent contact with wild birds. Since outdoor cats can sometimes hunt wild birds, this could lead to exposure, so you'd want to keep them indoors to decrease risks. I worry more about pet birds, including those that are indoors but might have indirect contact with wild birds through a screened window or door.

What misunderstandings do you think may exist about the bird flu?
The biggest thing I've been hearing is how upset and horrified people are about the price of eggs going up?which, yes, is an economic issue related to this avian influenza outbreak. But I think many general consumers aren't fully comprehending or appreciating just how complex our food systems are and how something like this can impact supplies coming into the market and their price points. To me this really illustrates how vulnerable our food system is and the value of investing in animal health?research and resources that look at the entirety of the food system and try to build as resilient a structure as possible.

The challenges we face with animal health diseases aren't limited to avian flu. For example, almost a decade ago, porcine epidemic diarrhea (PED, a coronavirus) caused a major outbreak that impacted pork production. Right now we're seeing African Swine Fever causing disease in pigs around the world, though it hasn't yet been identified in the U.S. There are major efforts underway to try to prevent introduction of this virus and to protect animal health and the food supply.

How closely is human health connected to animal health and well-being?
I think the bird flu gives us a window into how animal diseases broadly impact human health and all the different pathways for that to occur. After COVID-19 we're all sensitized to the possibility of a virus in animals spilling over into humans. That's not something we want to happen, but it's something that we now understand occurs more frequently than we once thought.

But when we think about these animal diseases, we shouldn't limit our concerns just to the possibility of human infection. There can be major global impacts regardless?affecting our food systems, our livelihoods, and causing major disruptions to our ecosystems. Healthy ecosystems can support cleaner air and cleaner water and also can help mitigate impacts from flooding or extreme weather events. If we can't understand and respect the way all of this works together, we'll lose many of these benefits and human populations will certainly feel impacts in one way or another.