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Mpox Discussion Forum: Latest News & Information Regarding the Clade 1b Mpox Virus

A new pandemic

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Dutch Josh 2 View Drop Down
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Dutch Josh 2 Quote  Post ReplyReply Direct Link To This Post Posted: Yesterday at 2:43am
https://flutrackers.com/forum/forum/welcome-to-the-scientific-library/vaccines/1003033-mol-ther-low-inflammatory-lipid-nanoparticle-based-mrna-vaccine-elicits-protective-immunity-against-h5n1-high-pathogenicity-avian-influenza-virus-with-reduced-adverse-reactions  or https://flutrackers.com/forum/forum/welcome-to-the-scientific-library/vaccines/1003033-mol-ther-low-inflammatory-lipid-nanoparticle-based-mrna-vaccine-elicits-protective-immunity-against-h5n1-high-pathogenicity-avian-influenza-virus-with-reduced-adverse-reactions ;

Mol Ther . Low-inflammatory lipid nanoparticle-based mRNA vaccine elicits protective immunity against H5N1 high-pathogenicity avian influenza virus with reduced adverse reactions

Mol Ther


. 2024 Dec 17:S1525-0016(24)00831-1.
doi: 10.1016/j.ymthe.2024.12.032. Online ahead of print. Low-inflammatory lipid nanoparticle-based mRNA vaccine elicits protective immunity against H5N1 high-pathogenicity avian influenza virus with reduced adverse reactions

Atsushi Kawai Taro Shimizu Hiroki Tanaka Shintaro Shichinohe Jessica Anindita Mika Hirose Eigo Kawahara Kota Senpuku Makoto Shimooka Le Thi Quynh Mai Ryo Suzuki Takuto Nogimori Takuya Yamamoto Toshiro Hirai 10 Takayuki Kato 11 Tokiko Watanabe 12 Hidetaka Akita Yasuo Yoshioka 13



AffiliationsAbstract

Messenger RNA vaccines based on lipid nanoparticles (mRNA-LNPs) are promising vaccine modalities. However, mRNA-LNP vaccines frequently cause adverse reactions such as swelling and fever in humans, partly due to the inflammatory nature of LNP. Modification of the ionizable lipids used in LNP is one approach to avoid these adverse reactions. Herein, we report the development of mRNA-LNP vaccines with better protective immunity and reduced adverse reactions using LNP, which contains a disulfide (SS)-cleavable bond and pH-activated lipid-like materials with oleic acid (ssPalmO) as an ionizable lipid (LNPssPalmO). We used mRNA expressing H5N1 subtype high-pathogenicity avian influenza virus-derived hemagglutinin or neuraminidase to generate mRNA-LNP vaccines against H5N1 influenza. Compared with conventional LNP, mRNA-LNPssPalmO induced comparable antigen-specific antibodies and better interferon-gamma (IFN-γ)-producing T-helper type-1 (Th1) responses in mice. Both mRNA-LNPssPalmO and conventional mRNA-LNP conferred strong protection against homologous H5N1 virus challenge. In addition, mRNA-LNPssPalmO showed better cross-protection against heterologous H5N1 virus challenge compared with conventional mRNA-LNPs. Furthermore, we observed that mRNA-LNPssPalmO induced less inflammatory responses (e.g., inflammatory cytokine production and vascular hyperpermeability) and fewer adverse reactions (e.g., weight loss and fever) compared with conventional mRNA-LNP. These results suggest that mRNA-LNPssPalmO would be a safe alternative to conventional vaccines to overcome mRNA-LNP vaccine hesitancy.

DJ, I did get 7 S E V E N !!!! CoViD vaccinations....I do believe it does limit damage when I catch(ed) CoViD. I do get a flu-vaccine every year...

However; vaccines can NOT be the solution to an unhealthy way of "living/running an economy"....
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Medical-historians very likely never agree for a 100% on what made the Spanish Flu into a pandemic...It did take 50 years to link the H1N1 flu-virus to some people who died from the flu, burried in frozen soil in Alaska. There are "limited" virus-indications...Some people who did survive the flu-pandemic may have seen blood samples taken...The peak of the Spanish Flu pandemic is now over 100 years ago...

Was the flu-virus itself "very high risk" or was it -mostly- the background. Concentrating lots of people in many places-resulting in very high spread. Some of those catching the Spanish Flu also already in bad shape...Very likely a mix of both...

Did the Spanish Flu spread into (other) mammals ? 

Can the Spanish flu infect animals?
Presented data support the hypothesis that the 1918 pandemic influenza virus was able to infect and replicate in swine, causing a respiratory disease, and that the virus was likely introduced into the pig population during the 1918 pandemic, resulting in the current lineage of the classical H1N1 swine influenza viruses ...

DJ, Some claims indicate swine did get the Spanish Flu from humans...Spread from swine into other swine/mammals may have been limited...
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DJ-The present global health situation may be far more complex compared to 1917-1918...We may not have much virus-info prior to the Spanish Flu...So the 1880, 1890 outbreaks in Russia are "open for speculation" (with some claims CoViD played a role). 

The https://en.wikipedia.org/wiki/Trans-Siberian_Railway#Construction or https://en.wikipedia.org/wiki/Trans-Siberian_Railway#Construction may have been a (spread) factor...

Travel (certainly long(er) distance)  was very limited in most of human history. 

Disease-transport-host did see animals spreading a lot of disease (flees spreading the plague). The Spanish Flu had a very high level of human-to-human spread (H2H).  Other diseases-in general-may have been a limited and more local factor-in a world with under 2 billion people often living in rural societies...

In 2024/25 the US has a "very major H5N1 problem".  Outside the US there may have been some cases-linked to the US (export of cattle, raw milk, farmworkers returning ill). 

SE Asia did see limited cases-linked to wild birds...with some-limited-indications in Vietnam H1N1 could have been seeing some mixing with H5N1 (???).
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Pandemic risk however is more then a high risk type of disease. CoViD may "open the door" to other diseases (like Mpox-types)...however the global situation is not yet seeing a H5N1 crisis. 

Christmas/New Year means schools are closed...There may be spread in gatherings. 

DJ-Again-I expected we would start 2024 with a major CoViD wave-I am glad I was wrong then ! 

Are we in an early pandemic phase for H5N1 ? Or will the main H5N1 problem-for now-remain a US problem ? 

Another aspect; If a pandemic would kill 0,5-1% of the global population in 4-6 months I may "change" the way people react to science. 

Denial of any problem is easy when you are not confronted with consequences...

A major aspect is we may miss -certainly in this time of year- a lot of info/testing/sequencing..."Going blind" for almost a month...both un-wise and un-welcome...



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https://afludiary.blogspot.com/2024/12/virus-evolution-recurring-incursions.html or https://afludiary.blogspot.com/2024/12/virus-evolution-recurring-incursions.html ;

Virus Evolution: Recurring Incursions & Dissemination of Novel Eurasian-origin H5Nx Avian Influenza Viruses in Atlantic Canada

Last August, in Something Winged This Way Comes, we discussed our `knowledge gap' of what evolutionary changes might have occurred over the summer among HPAI H5 viruses in the high latitude summer roosting areas for migratory waterfowl. 

I wrote:

Exactly what returns this fall is unknown, as the virus has had numerous opportunities to reassort or mutate over the summer. We could see something worse, or if we get very lucky, an attenuated threat (see Sci Repts.: Southward Autumn Migration Of Waterfowl Facilitates Transmission Of HPAI H5N1).

And true to form, this fall we've seen two new H5N1 genotypes (D1.1 and D1.2) join the fray, causing numerous outbreaks in poultry, more than a dozen human infections, and apparently causing significant die offs of wild birds across the country.  

These D1.x genotypes are genetically distinct from the B3.13 `Bovine' strain, and have been linked to at least 2 `severe' human infections.  A reminder that HPAI H5 is a constantly moving target. 

But at the same time, we've been tracking another viral interloper - HPAI H5N5 - making inroads both in Europe, and (repeatedly) crossing the Atlantic, and appearing in Eastern Canada (see The Continued Expansion of HPAI H5N5).

New subtypes or new genotypes of the HPAI H5 virus are a product of the H5 virus reassorting with other LPAI viruses - which can occur in both birds and mammals around the globe.  

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We've seen reports of H5N5 in European birds going back to 2016but it was first detected in dead raccoons on Prince Edward Island about 18 months ago (see CIDRAP Report).  Since last May, we've seen increasing reports of its western expansion (see WAHIS: More Reports of HPAI H5N5 in Canada).


Last July, in Cell Reports: Multiple Transatlantic Incursions of HPAI clade 2.3.4.4b A(H5N5) Virus into North America and Spillover to Mammalsresearchers reported finding the mammalian adaptive E627K mutation in a number of samples.

They wrote:

Thus, while A(H5N5) viruses are comparably uncommon, their high virulence and mortality potential demand global surveillance and further studies to untangle the molecular markers influencing virulence, transmission, adaptability, and host susceptibility.

While still a relatively minor player, we've seen increased H5N5 activity in both Europe and the UK in recent months.  To that we can also add the following journal article from Virus Evolution, which describes its repeated introductions into Canada and recent evolutionary changes. 
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Over the past decade we've seen the rise (and fall) of a highly successful H5N8 virus, followed by the surprise return of a far more capable clade 2.3.4.4b H5N1 virus. 

In the 3 years since H5N1 arrived in North America, the virus has evolved into more than 100 genotypes.  

Globally, H5's diversity is even greater.  Admittedly, most of these variants will fall by the wayside, unable to successfully compete against more biologically `fit' strains.   

Right now, it isn't clear how much of a player H5N5 will turn out to be. For now, however, it appears to be on the ascendant. 

The growing array of H5 viruses circulating globally arguably poses a much greater pandemic threat than it did just a few years ago.  Meaning - even if we somehow manage to suppress or eradicate `bovine H5N1' - there are a number of other H5Nx contenders out there to take its place.

There's an old joke about a tourist asking a NYC cabby, `What’s the best way to get to Carnegie Hall? and the cabby replies, “Practice, practice, practice”.

Unfortunately, our largely passive (`don't test, don't tell')  approach to HPAI over the past year has given HPAI nearly unfettered opportunities to practice; on cattle, humans, cats, and dozens of other peridomestic species. 

Whether or when the virus will ever be ready for Carnegie Hall remains unknown.

But the longer it circulates and the more opportunities it is given to evolve (or reassort), the greater the odds are that a viral prodigy will eventually emerge. 

DJ; https://en.wikipedia.org/wiki/Influenza_A_virus_subtype_H5N6 or https://en.wikipedia.org/wiki/Influenza_A_virus_subtype_H5N6 ;

Since 2014, at least 94 cases have occurred in humans.[1] 37 people have died. A spike in human cases was reported in 2021. There have been no confirmed cases of human-to-human transmission. Some infections have been identified where no direct contact with infected birds or contaminated surfaces has been known to had occurred. Only one infected woman has said that she never came into any contact with poultry

For a more global perspective. Asia may be most high-risk...somehow China does see (for centuries) new diseases starting a world tour from China...(South China rain forest animal link ?)

Also H7, H10 types of flu did show up in humans...(normal human flu is A-H1/H2/H3 types with some B-types of flu. C and D flu so far not more then a "cold" in humans...CoViD may change that...). 

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⚠️ BREAKING: China 🇨🇳 Faces Surge in Deadly Virus Outbreaks, Hospitals Overwhelmed as Fatalities Rise China is grappling with a significant rise in infections from multiple deadly viruses, including COVID-19 and Human Metapneumovirus (HMPV).
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In schools, outbreaks of Adenovirus and Norovirus have forced many to shift to online classes. Norovirus, which causes vomiting and stomach pain, has already infected 18 children at some schools.
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Health authorities have warned that Norovirus is resistant to common disinfectants and alcohol, complicating containment efforts. Also, Influenza, Mycoplasma pneumoniae, and other viruses are spreading quickly further overwhelming hospitals and increasing respiratory infections.

DJ, "Normal viruses creating abnormal symptoms due to CoViD ???"

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Dutch Josh 2 Quote  Post ReplyReply Direct Link To This Post Posted: 20 hours 26 minutes ago at 12:29pm
https://flutrackers.com/forum/forum/the-pandemic-discussion-forum/987828-discussion-thread-h5n1-avian-flu-in-us-dairy-cows-including-human-cases-poultry-dairy-workers-march-24-2024?view=stream  or https://flutrackers.com/forum/forum/the-pandemic-discussion-forum/987828-discussion-thread-h5n1-avian-flu-in-us-dairy-cows-including-human-cases-poultry-dairy-workers-march-24-2024?view=stream (latest);

Commonground
Commonground replied
December 22, 2024
NBC News
Key warning signs about bird flu are all going in the wrong direction

​Excerpt:

“The traffic light is changing from green to amber,” said Dr. Peter Chin-Hong, a professor of medicine at the University of California, San Francisco, who studies infectious diseases. “So many signs are going in the wrong direction.”

No bird flu transmission between humans has been documented, and the CDC maintains that the immediate risk to public health is low. But scientists are increasingly worried, based on four key signals.

For one, (1) the bird flu virus — known as H5N1 — has spread uncontrolled in animals, including cows frequently in contact with people. Additionally,  (2) detections in wastewater show the virus is leaving a wide-ranging imprint, and not just in farm animals.

Then there are  (3) several cases in humans where no source of infection has been identified, as well as research about the pathogen’s evolution, which has shown that the virus is (4)  evolving to better fit human receptors and that it will take fewer mutations to spread among people.

Together, experts say, these indicators suggest the virus has taken steps toward becoming the next pandemic.

“We’re in a very precarious situation right now,” said Scott Hensley, a professor of microbiology at the University of Pennsylvania.

...https://www.nbcnews.com/health/healt...gns-rcna185084

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https://www.wormsandgermsblog.com/2024/12/articles/animals/cats/h5n1-flu-in-cats-in-california-an-update/  or https://www.wormsandgermsblog.com/2024/12/articles/animals/cats/h5n1-flu-in-cats-in-california-an-update/ ;

I’m spending a lot of time talking to veterinarians about how to flag potential H5N1 flu cases in pets coming into the clinic, both to help make a quick diagnosis and to help ensure any risk of further transmission from infected pets is contained. Our lack of understanding of the disease in cats is a big challenge, including the potential scope of illness, how common it is, and what the main risk factors are. This report from California actually helps a lot, as it provides more information about a broader range of clinical signs in cats, and once again raises the concern about the potential for exposure via raw pet diets.

The LA County Department of Public Health is recommending that veterinarians ask owners of sick pets about raw milk and raw diet exposure.

  • That’s good advice all the time, and is particularly important now.
  • I’d add a need to query outdoor access as a potential risk factor for exposure as well (both intended outdoor access (i.e. indoor-outdoor cats) or unintended access (i.e. indoor cat sneaking out)).

They are also recommending the use of appropriate PPE “when in contact with animals suspected or confirmed of being infected with H5 bird flu; acutely sick animals that have history of exposure to raw milk or raw milk products, wild birds or raw or undercooked animal products.”

  • That’s good advice too. “Appropriate PPE” isn’t defined but I consider it to be a mask (ideally an N95 respirator or equivalent), gown and gloves, and eye / face protection (which often gets overlooked).

They don’t give a specific disease type to focus on in terms of screening cats for flu infection. That’s fair, because we just don’t know what to expect in all cases at this point. We know that flu sometimes kills cats showing signs of severe neurological and/or respiratory disease. We don’t know if some infected cats may have less severe signs, but we should approach it as if they can. So, cats with risk factors and non-specific disease should also be handled with care, at least for now.

They are also recommending flu vaccination of veterinary personnel. “Animal health staff are strongly recommended to receive their seasonal flu vaccine. Although this vaccine is not proven to prevent infection with H5 Bird Flu, it can help protect staff from seasonal human flu which is circulating right now.”

  • That’s a good idea too. Seasonal flu vaccination may not do anything to protect against H5N1 infection, but may help to to avoid people getting infected with H5N1 and human seasonal flu at the same time. That helps to decrease the risk of H5N1 flu mixing with a human flu strain to make a new (and potentially nastier) strain that is more easily transmitted to and between people.

I suspect we’re going to learn a lot more about H5N1 in cats in the next few months, especially from California, where a state of emergency has been declared because of their poorly contained dairy cattle H5N1 flu situation.


DJ, growing concerns...mammal-spread soon could jump to human spread on a larger scale. 

H5N1 in cats may be a global issue-outdoor cats may ear infected animals/droppings and may be more vulnerable then dogs...
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#H5N1 #AvianInfluenza updates - #Washington WFAC reports #HPAI has claimed the lives of over half their #wildfelids with rapid fatal pneumonia-like symptoms (likely D.1* genotype) Quarantine & other protective measures followed Hope they can protect the rest of their cats
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Canine Parvovirus Outbreak The highly contagious canine parvovirus outbreak in Windsor is escalating, with at least 18 dogs dead and 34 infected. Officials warn the real number is likely higher due to unreported cases. This outbreak is dynamic.
- https://windsorstar.com/news/local-news/dynamic-situation-why-death-toll-from-dog-virus-continues-climbing-in-windsor  or https://windsorstar.com/news/local-news/dynamic-situation-why-death-toll-from-dog-virus-continues-climbing-in-windsor 
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California: £7.04 for a dozen eggs
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DJ, I notice others making up their minds. Some include CoViD, food price, socio-economic unrest...By definition it is a complex matter...

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H5N1’s Mammalian Adaptation 🧵 PB2 E677K mutation in macaques is a warning we shouldn’t ignore. The last time the world ignored such signs, 50 million died in 1918. 1/

DJ, Underlining how difficult/complex history is...Some go for a wider timeline for Spanish Flu; 1917-1923. One of the outcomes is often a higher number of deaths-to 100 million people. Lowest numbers of Spanish Flu deaths still go between 15 and 20 million..global population at the time under 2 billion. So 1% to 5% of the population died...

In 2024 1% of the global population would mean 82 million deaths...5% 410 million...During the Spanish Flu 1-in-5 got infected (estimate)...today that would mean 1,5 to 2 billion people getting ill...The socio-economic impact would in itself be a disaster of unseen proportions...

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H5N1 B3.13 is a highly pathogenic strain of avian influenza that primarily infects birds but is now increasingly concerning due to its ability to spill over into mammals. In a recent experiment, researchers infected macaques (a close model for human biology) with this strain. They discovered a mutation in the virus (PB2 E677K) present in the animals’ lung tissue. 2/
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This is an evolutionary signal that the virus is adapting to mammalian hosts. Such adaptations can increase its potential to infect humans. Why is this a red flag? Mutations in the PB2 gene of influenza viruses are historically linked to the ability to replicate efficiently in mammalian cells. For example, the PB2 E627K mutation (often detected in mammalian-adapted influenza) has been shown to enhance replication at human body temperatures. The emergence of PB2 E677K suggests the virus is similarly evolving mechanisms to thrive in mammals, including humans. 3/
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The controlled infection of macaques models the potential mammalian adaptation of H5N1 B3.13. Lung samples revealed the same PB2 E677K mutation across multiple individuals: •A/macaque/Montana/60_LLL/2024 •A/macaque/Montana/59_RML/2024 •A/macaque/Montana/55_RLL/2024 And so on. 4/

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Dutch Josh 2 Quote  Post ReplyReply Direct Link To This Post Posted: 9 hours 38 minutes ago at 11:17pm
part 2, Outbreak Updates concentrating on H5N1...reality is ALWAYS for more complex...From H5/H7/H10 flu, CoViD to wars, climate as a background...

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This convergence isn’t random. PB2 mutations don’t appear unless there’s selective pressure The presence of E677K across multiple samples means a consistent adaptation to mammalian biology. 5/
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But why is this terrifying? Consider the broader context. H5N1 has already infected mammals outside the lab. Outbreaks in mink farms, cows, seals, and even domestic cats in Poland highlight the virus’s growing mammalian compatibility. PB2 E677K might be the molecular bridge it needs. 6/
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Historically, these bridges lead to pandemics. In 1918, the H1N1 virus underwent a series of unnoticed adaptations, ultimately enabling efficient human-to-human transmission. By the time it was detected, it had already seeded a global catastrophe. 7/
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Similarly, the 2009 H1N1 pandemic arose after years of reassortment in pigs. The warning signs, sporadic infections in humans. were ignored. By the time the virus became efficient at spreading, it was too late to contain. E677K could be today’s ignored warning. 8/
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PB2 mutations, including E677K, often affect how the polymerase complex interacts with host factors. While E627K facilitates replication in human-like cells, E677K might enhance polymerase stability or binding affinity in mammalian systems. 9/
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This could translate to: -More efficient replication in mammals -Improved immune evasion -Broader tissue tropism, meaning the virus could target more organs in mammals, including humans. Each of these increases the risk of zoonotic spillover and sustained human transmission. 10/

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Dutch Josh 2 Quote  Post ReplyReply Direct Link To This Post Posted: 9 hours 33 minutes ago at 11:22pm
part 3, DJ-A major mistake may be the idea "flu is respitory symptoms"...In a.o. cats, birds it did damage the brain. A virus may enter the host via a respitory traject-it does NOT have to stay there...

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And this isn’t happening in isolation. H5N1 B3.13 is just one branch of a virus that has been mutating in bird populations for decades. Global poultry outbreaks have created the perfect evolutionary incubator. And mammals are now in the virus’s sights. 11/
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We’ve seen this evolutionary pattern before. The 1957 and 1968 flu pandemics were preceded by years of unnoticed viral reassortment in avian reservoirs. When the virus finally crossed to humans, its machinery was already optimized for us. PB2 E677K suggests history could repeat itself. 12/
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Here’s where it gets brutal. The experiments that revealed E677K were conducted in a controlled lab setting. But what about the countless mutations happening in the wild? If E677K can emerge in macaques, there’s little stopping it from appearing in humans exposed to infected animals. 13/
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And humans are exposed. Infected birds, mink farms, and even domestic pets are all potential points of contact. Each exposure is an evolutionary roll of the dice. If PB2 E677K or a similar mutation appears in a transmissible human case, the game changes forever. 14/
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For context, SARS-CoV-2 showed us how single mutations (D614G or N501Y) can dramatically alter transmissibility. Influenza viruses are even more adaptable, thanks to their segmented genome. E677K might just be the opening act for a larger evolutionary drama. 15/
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What happens next? If PB2 E677K enables mammalian transmission, it could accelerate the virus’s path toward sustained human outbreaks. Vaccines and antivirals, already limited for H5N1, may prove insufficient against a strain adapted to mammals. 16/

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Dutch Josh 2 Quote  Post ReplyReply Direct Link To This Post Posted: 9 hours 21 minutes ago at 11:34pm
part 4;


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Let’s not sugarcoat this. Influenza viruses are evolutionary opportunists. The scientific community is sounding the alarm. Will policymakers listen? 17/
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History is a cruel teacher. In 1918, 1957, 1968, and even 2009, the world underestimated influenza. Today, with H5N1 and PB2 E677K, we’re at a similar crossroads. The choices we make now will determine whether this becomes another ignored warning. Or the start of meaningful action. 18/
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This isn’t “just another flu story” It represents a critical evolutionary step for a virus that already has a staggering 50–60% mortality rate in documented human cases. 19/19

DJ, Case Fatality Ratio (CFR) depends on a lot of issues. Very likely in lots of diseases lots of cases may be missed/misdiagnosed or not the "main reason". CoViD does do damage all over the body...so an increase of people dying from hearth, kidney, lung, brain damage may be linked to CoViD doing the damage...

Some forms of cancer seem to be virus-infection linked (most in younger people ?). 

In general education/income also is linked to CFR. Better educated often means higher income=better healthcare..., But also a willingness/understanding of steps one may take. 

Higher income/education=more vaccination.  But also understanding Personal Protection Equipment/PPE; masks/eye protection...

The most important tool in limiting/preventing pandemics is good information ! 

YOU can do a lot to limit chances of infection ! 

How many contacts/what kind of contacts/risks do you want ? 

DJ-I hate to see stories on how ill people catch infections in hospitals/care...

Maybe a basic point to make on limiting a multi-disease pandemic is we can still do a lot...Bad "politics" can be limited...trade unions can increase ventilation, UV-protection-safety...

INFORMATION/COMMUNICATION has to be the first step !

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