Day 1102: vxCJD Paper Published

The mysterious disappearing vaxx-variant CJD preprint from last summer has finally been published, in the International Journal of Vaccine Theory, Practice, and Research (h/t the bad cat). The final paper is restricted to mainly the French cases from the preprint, including one who was still alive in August:

Creutzfeldt-Jakob Disease, the formerly rare but universally fatal prion disease in humans, normally progresses over several decades before it leads to death. In the Appendix to this paper, we highlight the presence of a prion region in the spike protein of the original SARS-CoV-2, and in all the “vaccine” variants built from the Wuhan virus. The prion region in the spike of SARS-CoV-2 has a density of mutations eight times greater than that of the rest of the spike, and, yet, strangely that entire prion region disappears completely in the Omicron variant. In the main body of our text, we present 26 cases of Creuzfeldt-Jacob Disease, all diagnosed in 2021 with the first symptoms appearing within an average of 11.38 days after a Pfizer, Moderna, or AstraZeneca COVID-19 injection. Because the causal progression, the etiopathogenesis, of these atypical and new cases of human prion disease — cases of what is apparently a totally new form of rapidly developing Creuzfeldt-Jacob Disease — we focus on the chronology of the symptomatic development. We consider it from an anamnestic point of view — one in which we compare the typical development of pre-COVID cases of Creuzfeldt-Jacob Disease to the extremely accelerated development of similar symptoms in the 26 cases under examination. By such an approach, we hope to work out the etiopathogenesis critical to understanding this new and much more rapidly developing human prion disease. By recalling the sequential pathway of that the formerly subacute and slowly developing disease followed in the past, and by comparing it with this new, extremely acute, rapidly developing prion disease — one following closely after one or more of the COVID-19 injections — we believe it is correct to infer that the injections caused the disease in these 26 cases. If so, they have probably also caused a many other cases that have gone undiagnosed because of their rapid progression to death. By late 2021, 20 had died within 4.76 months of the offending injection. Of those, 8 died suddenly within 2.5 months confirming the rapid progression of this accelerated form of Creuzfeldt-Jacob Disease. By June 2022, 5 more patients had died, and at the time of this current writing, only 1 remains still alive.

One of the authors has also died. Note that the VAERS search mentioned in the paper (for CJD from COVID vaccines) originally produced 20 cases, 19 of whom were already deceased. In our previous vxCJD post the search produced 33 deaths, and as of last week is was up to 79 cases, 42 of whom are marked deceased, and two of which involved J&J rather than the mRNA vaccines.

If you're feeling brave, the bad cat goes into the prospective mechanisms behind vaxx-induced CJD. Keep in mind that vxCJD onset appears to be sudden, usually within 15 days of vaccination, rather than a delayed side-effect of the vaccines.

Day 908: Prions Again

A French preprint came out in June documenting 26 out of over 50 sudden cases of Creutzfeld Jakob disease (CJD) after vaccination with COVID vaccines. The preprint has since been taken down, but you can get it from the Wayback Machine if you're interested.

The paper goes through the usual PLAAC analysis to detect a prion region in the older COVID spike protein used in the vaccines, and reassuringly documents that this region has disappeared from Omicron. It's perhaps more interesting for the 26 French case studies (out of over 50), along with another 16 cases from abroad. In a later edit they mention 19 CJD deaths recorded in VAERS through April, and link to a search that actually produces 33 CJD deaths out of VAERS when run on today's data. (If you're wondering whether health care workers have the time these days for differential diagnosis of CJD, there are more accurate, real-time tests now than the traditional "check the brain for holes on autopsy".)

Before you start worrying that you may already be a downer, the authors have more good news; the average time of onset in France was 11 days after vaccination, so you're probably in the clear as long as you avoid boosters. (Sadly there was no genetic analysis for the downer codon.)

CJD is a death sentence, and it took about five months for patients to die, though some died "sudden[ly]" after only 2.5 months. An addendum notes that they are all dead now; one unfortunate soul apparently lasted a year. The sudden onset and rapid death are enough to distinguish the cases from sporadic CJD (sCJD) or variant (mad cow) CJD (vCJD).

PlagueBlog pauses to suggest the abbreviation vxCJD.

Three of the French cases were associated with the AstraZeneca (non-mRNA) vaccine, though all the VAERS cases list mRNA vaccines. (This is not a result of high uptake of AstraZeneca, which is only about 5% of the doses given in France to date.) While COVID itself may have caused some rise in CJD cases pre-Omicron, PlagueBlog has found that case reports claiming so usually fail to note whether the patient had a spike-based vaccine about 11 days before onset of CJD symptoms, regardless of their COVID histories.

Note that this rash of vxCJD would not be the first vaccine disaster involving transmissible spongiform encephalopathies. A sheep vaccine caused a scrapie outbreak known as the 1935 Moredun Louping-ill Vaccine Disaster. Another contaminated vaccine caused a smaller scrapie outbreak in Italy in the 1990's.

Day 832: Scrapieing the Bottom of the Barrel

If you've heard the wild stories about experimental mRNA vaccines causing cancer and prion disease but brushed them off because the mechanism by which they might have such outrageous effects is unclear, the bad cat has some bad news for you:

a nasty ringer is the emergence of the GGGG quadruplex (made easier by adding more G’s) which can cause neurological disease and bind to prions.

this may actually be quite a lot worse in that it appears that you do not even need a full quadruplex for this to happen. duplexes will do if the protein can fold in such a way as to generate what is effectively a quadruplex binding site and thus based on THIS study, all of these sites can play this role: (i) d(TGGGGT), (ii) r(GGAGGAGGAGGA) and (iii) d(GGAGGAGGAGGA) can serve as a quad.

this appears to facilitate the transition of PrPc into its pathologic isoform.

that’s bad.

If you don't recognize PrPSc in the above, just keep in mind that now is not the time to take up cannibalism. And in the future, avoid new technologies that have gone down in flaming failure with horrific side-effects in every previous trial, but are allegedly working perfectly this time.

Speaking of the trials, Steve Kirsch, not content with breaking the news of all-cause mortality being up for the vaccinated in Britain by their own numbers, has also publicized evidence of what the internet cats call pfraud in the latest data dump: Pfizer fraud? Or just great execution? He waffles on whether what happened in Argentina was actual fraud, but of course there were yet more side effects that never made it onto the label:

Neither Augusto’s pericardial effusion, nor another volunteer’s penile vein thrombosis, appear to have found their way into the reported side effects of this trial.

P.S. Massachusetts cases were up a third of a percentage point today.

Interlude: Mad Squirrel Disease

PlagueBlog apologizes for missing this 2018 account of a death from mad squirrel disease in Rochester, New York circa 2015. Mad squirrel disease (not its official name) has apparently been known for at least 35 years.

The risk of contracting Creutzfeldt-Jakob disease by eating squirrel brains was documented in the Lancet in 1997. It seems the skilled roadkill chefs of rural Kentucky are able to extract brains from squirrels (which is perhaps the most impressive part of the whole story), which they then scramble with eggs or add to a stew named "burgoo".

The Lancet article is still paywalled after a quarter of a century, but the New York Times reported on it at the time, giving away a good deal of paywalled information:

In the last four years, 11 cases of a human form of transmissible spongiform encephalopathy, called Creutzfeldt-Jakob disease, have been diagnosed in rural western Kentucky, said Dr. Erick Weisman, clinical director of the Neurobehavioral Institute in Hartford, Ky., where the patients were treated.

''All of them were squirrel-brain eaters,'' Dr. Weisman said. Of the 11 patients, at least 6 have died.

Within the small population of western Kentucky, the natural incidence of this disease should be one person getting it every 10 years or so, Dr. Weisman said. The appearance of this rare brain disease in so many people in just four years has taken scientists by surprise.

While the patients could have contracted the disease from eating beef and not squirrels, there has not been a single confirmed case of mad cow disease in the United States, Dr. Weisman said. Since every one of the 11 people with the disease ate squirrel brains, it seems prudent for people to avoid this practice until more is known, he said.

The journalists are also more specific about squirrel prep:

Families that eat brains follow only certain rituals. ''Someone comes by the house with just the head of a squirrel,'' Dr. Weisman said, ''and gives it to the matriarch of the family. She shaves the fur off the top of the head and fries the head whole. The skull is cracked open at the dinner table and the brains are sucked out.'' It is a gift-giving ritual. The second most popular way to prepare squirrel brains is to scramble them in white gravy, he said, or to scramble them with eggs. In each case, the walnut-sized skull is cracked open and the brains are scooped out for cooking.

These practices are not a matter of poverty, Dr. Berger said. People of all income levels eat squirrel brains in rural Kentucky and in other parts of the South. Dr. Frank Bastian, a neuropathologist at the University of South Alabama in Mobile, said he knew of similar cases of Creutzfeldt-Jakob disease in Alabama, Mississippi and West Virginia.

The self-styled "Official Mad Cow Disease Home Page" seems to have covered this story as well, even including a recipe for burgoo. Significantly for the timeline, they also included several references from the paper. Among them was a 1984 article, Creutzfeldt-Jakob Disease. Possible Transmission to Humans by Consumption of Wild Animal Brains, in which the wild animals considered were wild goats and squirrels.

And that's the smoking squirrel that takes us back 36 years, to a time long before mad cow disease. Needless to say, PlagueBlog recommends you remove and dispose of the brain and spinal cord before eating any mammal, whether it has been reported to transmit TSEs yet or not.

New Prion Disease Discovered

Via ProMED-mail: last month ScienceDaily reported the publication of a journal article on a new spontaneous prion disease:

In 2008, Pierluigi Gambetti, MD, and Wen-Quan Zou, MD, PhD, with collaborators, reported the discovery of this novel disease, which affected patients who exhibit only one of the three types of the prion protein gene. In this follow-up study, they discovered that all three genetic groups can be affected also by this novel disease which now joins sCJD in displaying this feature. However, VPSPr is associated with an abnormal prion protein that exhibits characteristics very different from those of sCJD, as well as other prion diseases, suggesting that it may be caused by a different mechanism, perhaps more akin to other neurodegenerative diseases, such as Alzheimer's disease. This finding may exemplify, for the first time, the possibility that the prion protein affects the brain with different mechanisms.

Some claim there's a smoking cow behind this new variant.

Prion Evolution

Ed Yong discusses prion evolution in his blog at ScienceBlogs:

Jiali Li from the Scripps Institute in Florida has found that prions - the infectious proteins behind mad cow disease, CJD and kuru - are capable of Darwinian evolution, all without a single strand of DNA or its sister molecule RNA.
Prions are rogue version of a protein called PrP. Like all proteins, they are made up of chains of amino acids that fold into a complex three-dimensional structure. Prions are versions of PrP that have folded incorrectly and this misfolded form, called PrPSc, is social, evangelical and murderous. It converts normal prion proteins into a likeness of its abnormal self, and it rapidly gathers together in large clumps that damage and kill surrounding tissues.
Li has found that variation can creep into populations of initially identical prions. Their amino acid sequence stays the same but their already abnormal structures become increasingly twisted. These "mutant" forms have varying degrees of success in different environments. Some do well in brain tissue; others thrive in other types of cell. In each case, natural selection culls the least successful ones. The survivors pass on their structure to the "next generation", by altering the folds of normal prion proteins.

Microevolutionary Defenses against Kuru

Via Twitter: Razib at ScienceBlogs reports on cannibals, kuru, and microevolution.

127V is extremely efficacious against fatality due to kuru. Looking through the pedigrees in a region of very high kuru exposure the researchers found that of the individuals who carried 127V, only 1 out of 36 in the parent generation died of kuru. By contrast, 33 of 218 parents from those carrying 127G only (the modal allele) had died of kuru (some of these presumably would also have carried the protective variant of 129). When the researchers looked at the 127V haplotype, the nature of the variation around this mutation implied that a common ancestor existed ~10 generations ago, with a 95% confidence interval 7 to 15 generations. That means that all of the copies of 127V extant today in the Fore descend from one particular copy present on the order of 250 years in the past within the population.

Atypical Scrapie

Via ProMED-mail: the New Zealand Ministry of Agriculture and Forestry reports on a case of atypical scrapie.

MAFBNZ Principal International Adviser Dr Stuart MacDiarmid says global knowledge about atypical scrapie/Nor 98 is evolving. The widely accepted mainstream scientific view is that it occurs spontaneously or naturally in very small numbers of older sheep in all sheep populations around the world.
"This positive detection of atypical scrapie/Nor 98 in a sheep from New Zealand's national flock reinforces that view. Every country that has conducted sufficient surveillance for atypical scrapie/Nor 98 has found it in their flocks. This includes most Scandinavian and EU countries, the UK, the USA and Canada," he says.
The detection does not change New Zealand's status as free from scrapie.

Mad Elk and Mad Fish

Via ProMED-mail: last month, the New York Times reported on the spread of CWD among elk via fecal-oral transmission, due to preclinical shedding of prions.

Dr. Aiken said prions tended to bind to clay in soil and to persist indefinitely. When deer graze on infected dirt, prions that are tightly bound to clay will persist for long periods in their intestinal regions. So there is no chance chronic wasting disease will be eradicated, he said. Outside the laboratory, nothing can inactivate prions bound to soil. They are also impervious to radiation.

Also, Practical Fish Keeping reported last month on a study of mad cow and scrapie transmissibility to fish:

The authors found that while the bream never displayed clinical signs of spongiform encephelopathies during the study period, the brains of TSE-fed fish sampled two years after challenge showed signs of neurodegeneration and accumulation of deposits that reacted positively with antibodies raised against sea bream PrP. The control groups, fed with brains from uninfected animals, showed no such signs.

Prions are Forever

Via ProMED-mail: in June ScienceDaily reported on prions surviving waste water treatment.

Until now, scientists did not know whether prions entering sewers and septic tanks from slaughterhouses, meatpacking facilities, or private game dressing, could survive and pass through conventional sewage treatment plants.
Joel Pedersen and colleagues used laboratory experiments with simulated wastewater treatment to show that prions can be recovered from wastewater sludge after 20 days, remaining in the "biosolids," a byproduct of sewage treatment sometimes used to fertilize farm fields.

I suppose if you can get prions from squirrels, you can get them anywhere.

A New Non-variant CJD

Via an unnamed source: the BBC reports the discovery of a new type of sporadic CJD (Creutzfeldt-Jakob disease).

Dr Pierluigi Gambetti, director of the US National Prion Disease Pathology Surveillance Center, in Ohio, said that he believed the newly discovered type had probably "been around for years, unnoticed".
He suggested one interesting common factor was that the patients came from families with a history of dementia, suggesting a genetic cause, but did not carry the gene traditionally associated with a small number of sporadic CJD cases.

The Return of the Virion

Via ProMED-mail: Yale Daily News reports on research by Dr. Laura Manuelidis, the head of neuropathology at Yale's School of Medicine, into viral explanations for Creutzfeldt-Jakob and related diseases:

The research team’s goal was to try to identify viral particles in infected cells. They infected cell lines with either scrapie (a sheep disease related to mad cow) or CJD agents and found virus-like particles that did not contain prion protein. An abundance of these particles was related to high levels of infectivity, which was not true of the presence of prion proteins.
“People hypothesize that prion proteins are infectious, but they’re probably part of the disease, not the infectious agent itself,” Manuelidis said.
The virus-like particles had been found by other researchers but were largely ignored. They were first identified in 1968 in synaptic regions of scrapie-infected brain and later found in many other animals with different TSEs. But Manuelidis said that researchers apparently forgot about them once the prion hypothesis became dominant.

Kuru in the 21st Century

Via ProMED-mail: A paper in The Lancet [registration required even to see the abstract] establishes the incubation period for Kuru, the famous cannibal prion disease, and makes some ominous predictions about the future of mad cow disease:

We identified 11 patients with kuru from July 1996, to June 2004, all living in the South Fore. All patients were born before the cessation of cannibalism in the late 1950s. The minimum estimated incubation periods ranged from 34 to 41 years. However, likely incubation periods in men ranged from 39 to 56 years and could have been up to 7 years longer. PRNP [the prion protein gene] analysis showed that most patients with kuru were heterozygous at polymorphic codon 129, a genotype associated with extended incubation periods and resistance to prion disease.

Interpretation

Incubation periods of infection with human prions can exceed 50 years. In human infection with BSE prions, species-barrier effects, which are characteristic of cross-species transmission, would be expected to further increase the mean and range of incubation periods, compared with recycling of prions within species. These data should inform attempts to model variant CJD epidemiology.

Another paper in PNAS also indicates that many more people than the current victims may eventually come down with a new and unknown variant of mad cow disease:

All neuropathologically confirmed cases of variant Creutzfeldt-Jakob disease (vCJD), characterized by abundant florid plaques and type 4 disease-related prion protein (PrP^Sc) in the brain, have been homozygous for methionine at polymorphic residue 129 of PRNP. The distinctive neuropathological and molecular phenotype of vCJD can be faithfully recapitulated in Prnp-null transgenic mice homozygous for human PrP M129 but not V129, where a distinct prion strain is propagated. Here we model susceptibility of 129MV heterozygotes, the most common PRNP genotype, in transgenic mice and show that, remarkably, propagation of type 4 PrP^Sc was not associated with characteristic vCJD neuropathology. Depending on the source of the inoculum these mice can develop four distinct disease phenotypes after challenge with bovine spongiform encephalopathy (BSE) prions or vCJD (human-passaged BSE) prions. vCJD-challenged mice had higher attack rates of prion infection than BSE-challenged recipients. These data argue that human PRNP 129 heterozygotes will be more susceptible to infection with vCJD prions than to cattle BSE prions and may present with a neuropathological phenotype distinct from vCJD.

Third Transfusion-Related vCJD Case

Reuters reports on the third case of human-to-human transmission of mad cow disease via blood transfusion in Britain:

"The patient developed symptoms of vCJD about eight years after receiving a blood transfusion from a donor who developed symptoms of vCJD about 20 months after donating this blood. The patient is still alive and is under the care of doctors at the National Prion Clinic," the agency said in a statement.
Professor Peter Borriello, Director of the HPA's Center for Infections said: "The occurrence of a third case of vCJD infection in a small group of patients like this suggests that blood transfusion from an infected donor may be a relatively efficient mechanism for the transmission of vCJD, although much still remains unknown.

Cows Eating People

Via ProMED-mail: The BBC reports on a new theory of the origin of Bovine Spongiform Encephalopathy--cows eating human remains.

Some raw materials for fertiliser and feed imported from South Asia in the 60s and 70s contained human bones and soft tissue, the Lancet reports.
Bone collectors could have picked up the remains of corpses deposited in the Ganges river to sell for export.
If infected with prion diseases, they could have been the source for BSE.

Mad Cow News

Via ProMED-mail: Portugal reports its first case of variant Creutzfeldt-Jakob disease, not surprising for the country ranked third in mad cows. The United States thinks about reporting its second mad cow.

From the don't-eat-the-downers files

Via ProMED-mail: several NY sources report on at least 5 deer infected with Chronic Wasting Disease, a transmissible spongiform encephalopathy. One of the deer was served at a Verona Fire Department annual dinner (apparently while the brain was languishing at a lab someplace). This means that the state department of health has a few CWD exposures to track, to see whether CWD really poses no threat to humans.

Disease Roundup

Several new and/or interesting outbreaks via ProMED-mail:

• Agence France-Presse reports that the Marburg death toll in Angola has hit 155, not counting the suspected Marburg death of a South African who left Luanda about a week ago. The virus continues to rage uncontrolled.
• Reuters reports on two more suspected cases of bird flu (not counting the woman who drank duck blood from earlier this week) as well as a doctor who died of apparent SARS, all in Vietnam.
• Folha de S.Paulo reports [in Portuguese] on a Brazilian outbreak of the parasite Diphyllobothrium latum in patients who ate raw, smoked, or undercooked fish. Patients consumed their sushi and sashimi at several establishments across Sao Paulo.
• UPI reports on a French woman who may have had variant CJD 20 years before the mad cow epidemic began.
• The AP reports that North Korean birds are sick with a different strain of bird flu (H7) than the highly fatal one which has spread to humans in other parts of Southeast Asia (H5).
• Agence France-Presse reports on the continuing spread of the rare Chlamydia infection lymphogranuloma venereum (LGV) among homosexual European males.
• NYNewsday reports on a rash of E. coli infections acquired from petting-zoo animals. PlagueBlog recommends avoiding contact with animals before their internal temperature has reached 160°F. Use a meat thermometer if necessary.

And don't travel to Angola.

Mad Goat

I've gotten behind on reporting, but I did get a friendly tip on the mad goat [ProMED] last week.

Britain said on Tuesday [8 Feb 2005] that a goat confirmed as having the brain-wasting disease scrapie in 1990 may have had mad cow disease. [...]
In January 2005 mad cow disease, formally known as bovine spongiform encephalopathy (BSE), was found in a goat in France, the 1st time the brain-wasting affliction that ravaged European cattle herds and killed at least 100 people had been diagnosed in another animal.

Mad Cow II

More weekend news: a second Canadian mad cow leads to concern about the lifting of the US ban on Canadian cattle imports.