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Collective Measles Virus Mutations Linked to Fatal Encephalitis

Researchers in Japan have uncovered the mechanism for how accumulated mutations in a key measles virus protein can allow the virus to infect the brain…

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Researchers in Japan have uncovered the mechanism for how the measles virus (MeV) can cause subacute sclerosing panencephalitis, or SSPE, a rare but fatal neurological disorder that can occur several years after a measles infection.

Although the normal form of the measles virus cannot infect the nervous system, the team found that viruses that persist in the body can develop mutations in a key protein that controls how they infect cells. The mutated proteins can interact with its normal form, making it capable of infecting the brain. The team, headed by Yuta Shirogane, MD, PhD, Assistant Professor at Kyushu University’s Faculty of Medical Sciences, hopes that the results will help scientists develop therapeutics for SSPE, as well as elucidate the evolutionary mechanisms common to viruses—such as novel coronaviruses, and herpesviruses—that have similar infection mechanisms to measles.

Shirogane and colleagues reported their findings in Science Advances, in a paper titled “Collective fusion activity determines neurotropism of an en bloc transmitted enveloped virus.”

Although people born after the 1970s may have received a measles vaccine as a child, World Health Organization estimates suggest that nearly nine million people worldwide were infected with measles in 2021, with the number of deaths reaching 128,000. Measles is caused by an enveloped RNA virus of the Morbillivirus genus, and remains one of the most contagious pathogens. MeV may persist in the brain, causing a fatal progressive neurological disorder SSPE several years after acute infection. The incidence of SSPE is estimated to be approximately four to 11 cases per 100,000 cases of measles. “Despite its availability, the recent COVID-19 pandemic has set back vaccinations, especially in the Global South,” commented Shirogane. “SSPE is a rare but fatal condition caused by the measles virus. However, the normal measles virus does not have the ability to propagate in the brain, and thus it is unclear how it causes encephalitis.”

A virus infects cells through a series of proteins that protrude from its surface. Usually, one protein will first facilitate the virus to attach to a cell’s surface, then another surface protein will cause a reaction that lets the virus into the cell, leading to an infection. So, what a virus can or cannot infect can depend heavily on the type of cell. “Usually, the measles virus only infects your immune and epithelial cells, causing the fever and rash,” pointed out Shirogane. “Therefore, in patients with SSPE, the measles virus must have remained in their body and mutated, then gained the ability to infect nerve cells. RNA viruses like measles mutate and evolve at very high rates, but the mechanism of how it evolved to infect neurons has been a mystery.” As the scientists further noted, “RNA virus populations generally evolve rapidly under selection pressures, because of the high error rates of viral RNA polymerase. This viral evolvability is known to cause some of the difficulties in controlling RNA virus infections, such as drug resistance, immune evasion, and expansion of the tropism and host range.”

The key player in allowing the measles virus to infect a cell is its fusion protein, or F protein.  “MeV has two kinds of glycoproteins on its envelope, the hemagglutinin (H) and the fusion (F) proteins,” the authors noted. “The H protein binds to receptors on the human cells and subsequently triggers the conformational changes of the trimeric F protein from the prefusion form to the post fusion form, leading to virus-to-cell or cell-to-cell membrane fusion.”

The team’s previous studies had shown that certain mutations in the F protein put it in a ‘hyperfusongenic’ state, allowing it to fuse onto neural synapses and infect the brain. For their newly reported study, the team analyzed the genome of the measles virus from SSPE patients and found that various mutations had accumulated in their F protein. Interestingly, certain mutations would increase infection activity while others actually decreased it.

“This was surprising to see, but we found an explanation,” continued Shirogane. “When the virus infects a neuron, it infects it through ‘en bloc transmission,’ where multiple copies of the viral genome enter the cell. In this case, the genome encoding the mutant F protein is transmitted simultaneously with the genome of the normal F protein, and both proteins are likely to coexist in the infected cell.”

Mutation in the F protein is key for the measles virus to fuse and infect neurons. Two primary strategies exist for such infection. Initially, fusion activity of a mutant F protein is suppressed due to interference from the normal F proteins (black box). That interference is overcome by accumulation of mutations and increased fusogenecity (orange box). In another case, a different mutation in the F protein acts oppositely and reduces fusion activity, but conversely cooperates with normal F proteins that increase the fusion activity (blue box). Thus, even mutant F proteins that appear to be unable to infect neurons can still infect the brain. [Kyushu University/Hidetaka Harada/Yuta Shirogane]
Based on their hypothesis, the team analyzed the fusion activity of mutant F proteins when normal (wild type; WT) F proteins were present. Their results showed that fusion activity of a mutant F protein is suppressed due to interference from the normal F proteins, but that interference is overcome by the accumulation of mutations in the F protein.

In another case, the team found that a different set of mutations in the F protein results in a completely opposite result: a reduction in fusion activity. However, to their surprise, this mutation can actually cooperate with normal F proteins to increase fusion activity. “In this study, we show that mutations accumulated in SSPE derived MeV F genes dynamically change the F protein fusogenicity,” they stated.

Thus, even mutant F proteins that appear to be unable to infect neurons can still infect the brain.  “A mutant F protein having SSPE-derived substitutions exhibits lower fusogenicity than the hyperfusogenic F protein containing some of those substitutions, but by the wild-type F protein coexpression, the fusogenicity of the former F protein is enhanced, while that of the latter is nearly abolished.”

Shirogane stated, “It is almost counter to the ‘survival of the fittest’ model for viral propagation. In fact, this phenomenon where mutations interfere and/or cooperate with each other is called ‘Sociovirology.’ It’s still a new concept, but viruses have been observed to interact with each other like a group. It’s an exciting prospect.”

The authors further commented, “ … this study provides important insights into the evolutionary process of MeV neuropathogenicity and genotype-phenotype relationships of oligomeric viral fusion proteins in viral evolution …” They acknowledged that further studies will be needed to further understand the mechanisms. “The concept of en bloc transmission could unveil positive and negative interactions among different fusion proteins in other enveloped viruses … we suggest that the interpretation of mutations found in en bloc transmitted viruses requires careful evaluations, because the effects of mutations depend on interactions between different viral genomes … Whether mutations in the H gene also contribute to the MeV neurotropism is not known.”

“There are many mysteries in the mechanisms by which viruses cause diseases,” Shirogane stated. “Since I was a medical student, I was interested in how the measles virus caused SSPE. I am happy that we were able to elucidate the mechanism of this disease.”

The post Collective Measles Virus Mutations Linked to Fatal Encephalitis appeared first on GEN - Genetic Engineering and Biotechnology News.

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Economic Death Spiral

Economic Death Spiral

Authored by Robert Stark via Substack,

Fed Trap: Financial Collapse or Hyper Inflation?

With this banking crisis,…

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Economic Death Spiral

Authored by Robert Stark via Substack,

Fed Trap: Financial Collapse or Hyper Inflation?

With this banking crisis, which has serious Lehman vibes, it is a good time to revisit my article, Is This The End of The End of History, from March of last year. The article dealt with the theme of collapse vs stagnation, and historical cycles, in light of the Ukraine war, the post-pandemic climate, the onset of inflation, and speculation about economic collapse. A point of mine, that has especially been vindicated, is that “a delay in the Fed raising interest rates, could cause a short term rally in stocks, further expanding the bubble. The bigger the bubble, the worse inflation gets, and the longer the Fed keeps delaying raising rates, the worse the crash will be down the road.” For the most part, most of my geopolitical and economic forecasts have come true, though I actually predicted an economic collapse to occur sooner, which actually vindicates that point, that kicking the can down the road will just create a much worse crisis.

Despite countless signs of economic volatility, the recent bank failures, with shockwaves to the entire financial system, are a turning point, where it is clear that there is going to be a severe economic downturn. For instance, Elon Musk recently said, lot of current year similarities to 1929, and Moody’s cut the outlook on the entire U.S. banking system to negative from stable, citing a "rapidly deteriorating operating environment." Even the perma bulls, mainstream media, and financial “experts,” can no longer deny the obvious signs of economic peril. However, the bullish propaganda was still strong as recently as January, which was really the bulls’ last gasp, with the monkey rally, in response to the Fed only raising interest rates by .25 points, plus economic data showing record low unemployment plus a dip in inflation.

It is important to emphasize that the same figures in media, banking, and government, who were recently shilling a soft landing or mild recession, were previously saying that inflation is transitory. It is especially laughable to think that there are people who take someone like CNBC’s, Jim Cramer, seriously, who in 2008 told his audience don’t be silly on Bear Stearns, right before it crashed, and more recently shilled for Silicon Valley Bank, and is still predicting a soft landing. A lot of the recent propaganda is practically identical to right before the 08 crash, as well as during stagflation in the 70s, and even before the Great Depression, as the media has vested economic and political interests in propping up the markets. The financial YouTuber, Maverick of Wall Street, brilliantly uses this “self-love” gif of  Jack Nicholson, from the film, One Flew Over the Cuckoo’s Nest, as a metaphor for whenever perma-bulls see any data that may signify a Fed pivot, causing stocks to rally. As the desperation really kicks in, expect further talk of a soft landing, as well as more rallies in stocks, as we saw in response to the bailouts, as well as desperate investors switching back and forth between the NASDAQ and S&P500, which happened in 08. So any return to bullish sentiment is actually a sign of greater economic catastrophe. The stock market rallying over bad economy news, as a sign of a potential pivot, just further shows that the markets are not a good metric for the health of the economy. Not to mention that the top 1% own over half of all stocks.

It has always been the case with bubbles, that the greater the size of the bubble, the more copes to deny reality, and the more vested interests there are in preventing the inevitable crash. Certainly many corporations and banks have made economic decisions based upon an assumption of a soft landing or Fed pivot. This also explains the gaslighting to justify that the 2010s economic boom, especially in tech, was based upon productivity and innovation, when it was primary due to Fed monetary policy, plus data mining in the case of Big Tech. While it is silly for conservatives to blame wokeness as the primary culprit of bank failures, wokeness and bullshit DEI jobs, are a symptom of the corruption that Fed policy enabled. 

Fed Balance Sheet: Return to QE

Source

The current banking crisis is triggering more stock buybacks, and a return to Quantitative Easing with the bank bailouts, including plans to inject another $2 Trillion into the banking system, on top of the $300 billion increase in the Fed’s Balance Sheet, in just the last week. This seems counter intuitive, as QE caused inflation, but the economy is so addicted to the “Cocaine,” that is  cheap money. So basically quantitative tightening is being implemented and interest rates raised  to stop inflation, but as soon as the first major economic disruption of raising rates is felt, then a return to financial policies to further prop up the bubble, causing more inflation. Now the Fed is trapped with two bad options, raise rates or pivot, both of which will lead to inevitable economic doom.

Populists can talk about nationalizing the banks into public debt free banking, and Austrian School libertarians can call for ending the Fed, and returning to a gold standard. While it is true that the Federal Reserve is a corrupt system, that is quasi private in how private banks own shares, the reality is that we are stuck with this system of relying upon the Fed’s interest rates, for the incoming economic crisis. If the Fed continues raising rates, there will be a liquidity crisis, with more bank failures. While interest rates were close to zero, banks used uninsured deposits to both invest in securities and purchase bonds, and thanks to fractional reserve banking, banks are only required to hold a fraction of deposits. So when rates rose, bonds fell in value and unrealized losses surged, so the banks were not able to pay off their depositors.

source  

Regional banks make up about half of all US banking, so any contagion in the banking system, as people and businesses move their deposits to mega banks, deemed “too big to fail,” could trigger a Depression. One of the main reasons that the economy has not crashed sooner is because more people have been tapping into their savings and maxing out their credit cards. However, high interest rates will cause many people to default on their credit card debt, which will exacerbate the banking crisis. Not to mention Auto loans defaults wiping out credit unions, and the potential for another mortgage crisis, due to rising mortgage rates. There is a ripple effect, as far as rising interest rates being felt by debt holders, and now is just the tip of the iceberg. This could end up being a multifaceted debt crisis, in banking, corporate debt, personal debt, and government debt.

Besides the Fed likely pivoting soon due to the banking crisis, higher rates will make interest payments on the National Debt too expensive to pay off, risking a default on government debt. Overall levels of debt, both public and private, are much worse than when Fed Chair, Volcker, raised rates very high to successfully quell inflation. Any freeze in Federal spending or a default on the national debt, in response to the debt ceiling, will crash the economy, and any major extension in the debt ceiling will accelerate inflation. There is a good chance that inflation will be tolerated, with the dollar greatly devalued, to make government debt cheaper so that creditors eat the costs.

Source: Peter G. Peterson Foundation

A tight labor market is the main case that the bulls make to prove a strong economy. However, the official BLS jobs numbers are “baked” to exclude those who have given up on seeking employment, as well as counting 2nd or 3rd jobs. Not to mention that the BLS numbers were exposed by the Fed as overstating 1 million jobs during 2022. Even if one accepts the “baked” numbers, layoffs have a lagging effect on unemployment, including by industry (eg. tech layoffs before service sector). Now new jobless claims have grown at the fastest pace since Lehman'. It is also noteworthy that just about every recession has been preceded by low unemployment numbers. The increase in layoffs will put further pressure on the Fed to pivot, which on top of increased unemployment benefits, will cause inflation to surge again. This creates another doom loop, as inflation leads to more unemployment, as consumers are forced to cut back on spending.

Source: ZeroHedge

While bulls can say that this time is different from past crashes, all of the signs are pointing to this crisis being much worse than previous crashes. For instance, the economic recovery, after Volcker was done raising rates to fight inflation, was possible because of lower levels of debt, but the US has never entered a recession with debt/GDP at 125% and deficit/GDP at 7% in at least 85 years. Also the fallout of the 2008 crash was mitigated by a strong dollar, which also minimized the effects of inflation last year, but inflation will surge if the dollar is weakened. Despite signs of a pivot, the Fed has been moving much faster to fight inflation, then in the past, even with Volker. This crisis is also unique in that rates are being raised while entering a severe recession, and inflation could coincide mass layoffs. While the general assumption is that severe economic downturns are deflationary, financial commentator, Peter Schiff, makes a compelling case as for why an Inflationary Depression is a likelihood. Under this nightmare scenario, which would be much worse than even the Great Depression, inflation will negate any of the remedies that ended past crises, such as the New Deal, quantitative easing in 08, and the covid stimulus. Other signs of economic peril include, the steepest yield curve inversion since the early 80s recession, which is a barometer that has predicted just about every single recession, a major decline in ISM manufacturing sales, a big decline in savings rates, and Americans’ credit card debt approaching a record $1 Trillion.

source

This is the perfect storm with inflation, stagflation, recession, a potential debt crisis, as well as energy and supply chain issues. With this bubble to end all bubbles or too big to fail on steroids, the Fed has two choices, cause a liquidity crisis by shrinking the money supply, or letting inflation rip. While raising rates appears to be the least bad of these two options, further rate hikes are futile with the return of QE. A combo of QE plus interest rates having to remain high, is what could lead to that scenario of inflationary financial collapse, that Peter Schiff warned about. Though most likely it will either be long term stagflation or a deflationary Depression. This is not a hyperbole, nor clickbait, but a Depression is a very real possibility, especially if policy makers continue to kick the can down the road, to prop up the bubble.

*  *  *

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Tyler Durden Tue, 03/21/2023 - 17:25

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Three Years To Slow The Spread: COVID Hysteria & The Creation Of A Never-Ending Crisis

Three Years To Slow The Spread: COVID Hysteria & The Creation Of A Never-Ending Crisis

Authored by Jordan Schachtel via ‘The Dossier’…

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Three Years To Slow The Spread: COVID Hysteria & The Creation Of A Never-Ending Crisis

Authored by Jordan Schachtel via 'The Dossier' Substack,

Last Thursday marked the three year anniversary of the infamous “15 Days To Slow The Spread” campaign.

By March 16, yours truly was already pretty fed up with both the governmental and societal “response” to what was being baselessly categorized as the worst pandemic in 100 years, despite zero statistical data supporting such a serious claim.

I was living in the Washington, D.C. Beltway at the time, and it was pretty much impossible to find a like-minded person within 50 miles who also wasn’t taking the bait. After I read about the news coming out of Wuhan in January, I spent much of the next couple weeks catching up to speed and reading about what a modern pandemic response was supposed to look like.

What surprised me most was that none of “the measures” were mentioned, and that these designated “experts” were nothing more than failed mathematicians, government doctors, and college professors who were more interested in policy via shoddy academic forecasting than observing reality.

Within days of continually hearing their yapping at White House pressers, It quickly became clear that the Deborah Birx’s and Anthony Fauci’s of the world were engaging in nothing more than a giant experiment. There was no an evidence-based approach to managing Covid whatsoever. These figures were leaning into the collective hysteria, and brandishing their credentials as Public Health Experts to demand top-down approaches to stamping out the WuFlu.

To put it bluntly, these longtime government bureaucrats had no idea what the f—k they were doing. Fauci and his cohorts were not established or reputable scientists, but authoritarians, charlatans, who had a decades-long track record of hackery and corruption. This Coronavirus Task Force did not have the collective intellect nor the wisdom to be making these broad brush decisions.

Back then, there were only literally a handful of people who attempted to raise awareness about the wave of tyranny, hysteria, and anti-science policies that were coming our way. There were so few of us back in March in 2020 that it was impossible to form any kind of significant structured resistance to the madness that was unfolding before us. These structures would later form, but not until the infrastructure for the highway to Covid hysteria hell had already been cemented.

Making matters worse was the reality that the vast majority of the population — friends, colleagues, peers and family included — agreed that dissenters were nothing more than reckless extremists, bioterrorists, Covid deniers, anti-science rabble rousers, and the like.

Yet we were right, and we had the evidence and data to prove it. There was no evidence to ever support such a heavy-handed series of government initiatives to “slow the spread.”

By March 16, 2020, data had already accumulated indicating that this contagion would be no more lethal than an influenza outbreak.

The February, 2020 outbreak on the Diamond Princess cruise ship provided a clear signal that the hysteria models provided by Bill Gates-funded and managed organizations were incredibly off base. Of the 3,711 people aboard the Diamond Princess, about 20% tested positive with Covid. The majority of those who tested positive had zero symptoms. By the time all passengers had disembarked from the vessel, there were 7 reported deaths on the ship, with the average age of this cohort being in the mid 80s, and it wasn’t even clear if these passengers died from or with Covid.

Despite the strange photos and videos coming out of Wuhan, China, there was no objective evidence of a once in a century disease approaching America’s shores, and the Diamond Princess outbreak made that clear.

Of course, it wasn’t the viral contagion that became the problem.

It was the hysteria contagion that brought out the worst qualities of much of the global ruling class, letting world leaders take off their proverbial masks in unison and reveal their true nature as power drunk madmen.

And even the more decent world leaders were swept up in the fear and mayhem, turning over the keys of government control to the supposed all-knowing Public Health Experts.

They quickly shuttered billions of lives and livelihoods, wreaking exponentially more havoc than a novel coronavirus ever could.

In the United States, 15 Days to Slow The Spread quickly became 30 Days To Slow The Spread. Somewhere along the way, the end date for “the measures” was removed from the equation entirely.

3 years later, there still isn’t an end date…

Anthony Fauci appeared on MSNBC Thursday morning and declared that Americans would need annual Covid boosters to compliment their Flu shots.

So much of the Covid hysteria era was driven by pseudoscience and outright nonsense, and yet, very few if any world leaders took it upon themselves to restore sanity in their domains. Now, unsurprisingly, so many elected officials who were complicit in this multi-billion person human tragedy won’t dare to reflect upon it.

In a 1775 letter from John Adams to his wife, Abigail, the American Founding Father wrote:

“Liberty once lost is lost forever. When the People once surrender their share in the Legislature, and their Right of defending the Limitations upon the Government, and of resisting every Encroachment upon them, they can never regain it.”

Covid hysteria and the 3 year anniversary of 15 Days To Slow The Spread serves as the beginning period of a permanent scar resulting from government power grabs and federal overreach.

While life is back to normal in most of the country, the Overton window of acceptable policy has slid even further in the direction of push-button tyranny. Hopefully, much of the world has awakened to the reality that most of the people in charge aren’t actually doing what’s best for their respective populations.

Tyler Durden Tue, 03/21/2023 - 18:05

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From the bed sheets to the TV remote, a microbiologist reveals the shocking truth about dirt and germs in hotel rooms

The filthy secrets of hotel rooms and why you might want to pack disinfectant on your next trip.

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Relaxing in filth? Pexels/Cottonbro studio

For most of us, staying in a hotel room is either something of a necessity – think business travel – or something to look forward to as part of a holiday or wider excursion.

But what if I told you there’s a large chance your hotel room, despite how it might appear to the naked eye, isn’t that clean. And even if it’s an expensive room, that doesn’t necessarily mean it’s any less dirty.

Indeed, whoever has stayed in your room prior to you will have deposited bacteria, fungi and viruses all over the furniture, carpets, curtains and surfaces. What remains of these germ deposits depends on how efficiently your room is cleaned by hotel staff. And let’s face it, what is considered clean by a hotel might be different to what you consider clean.

Typically, assessment of hotel room cleanliness is based on sight and smell observations –- not on the invisible microbiology of the space, which is where the infection risks reside. So let’s take a deep dive into the world of germs, bugs and viruses to find out what might be lurking where.

It starts at the lift

Before you even enter your room, think of the hotel lift buttons as germ hotspots. They are being pressed all the time by many different people, which can transfer microorganisms onto the button surface, as well back onto the presser’s fingers.

Communal door handles can be similar in terms of germ presence unless sanitised regularly. Wash your hands or use a hand sanitiser after using a handle before you next touch your face or eat or drink.

The most common infections people pick up from hotel rooms are tummy bugs – diarrhoea and vomiting – along with respiratory viruses, such as colds and pneumonia, as well as COVID-19, of course.

Hotel door opening.
Welcome to germ paradise. Pexels/Pixabay

Toilets and bathrooms tend to be cleaned more thoroughly than the rest of a hotel room and are often the least bacteriologically colonised environments.

Though if the drinking glass in the bathroom is not disposable, wash it before use (body wash or shampoo are effective dishwashers), as you can never be sure if they’ve been cleaned properly. Bathroom door handles may also be colonised by pathogens from unwashed hands or dirty washcloths.

Beware the remote

The bed, sheets and pillows can also be home to some unwanted visitors. A 2020 study found that after a pre-symptomatic COVID-19 patient occupied a hotel room there was significant viral contamination of many surfaces, with levels being particularly high within the sheets, pillow case and quilt cover.

While sheets and pillowcases may be more likely to be changed between occupants, bedspreads may not, meaning these fabrics may become invisible reservoirs for pathogens – as much as a toilet seat. Though in some cases sheets aren’t always changed between guests, so it may be better to just bring your own.

Less thought about is what lives on the hotel room desk, bedside table, telephone, kettle, coffee machine, light switch or TV remote – as these surfaces aren’t always sanitised between occupancies.

TV remote lying on pink bedding.
Handle with care: the TV remote is often one of the dirtiest items in a hotel room. Pexels/Karolina grabowska

Viruses such as the norovirus can live in an infectious form for days on hard surfaces, as can COVID-19 – and the typical time interval between room changeovers is often less than 12 hours.

Soft fabric furnishings such as cushions, chairs, curtains and blinds are also difficult to clean and may not be sanitised other than to remove stains between guests, so washing your hands after touching them might be a good idea.

Uninvited guests

If all those germs and dirty surfaces aren’t enough to contend with, there are also bedbugs to think about. These bloodsucking insects are experts at secreting themselves into narrow, small spaces, remaining dormant without feeding for months.

Small spaces include the cracks and crevices of luggage, mattresses and bedding. Bed bugs are widespread throughout Europe, Africa, the US and Asia – and are often found in hotels. And just because a room looks and smells clean, doesn’t mean there may not be bed bugs lurking.

Woman making bed in hoteroom.
Get those cushions off the bed straightaway. Pexels/Cottonbro studio

Fortunately, bed bug bites are unlikely to give you a transmissible disease, but the bite areas can become inflamed and infected. For the detection of bedbugs, reddish skin bites and blood spots on sheets are signs of an active infestation (use an antiseptic cream on the bites).

Other signs can be found on your mattress, behind the headboard and inside drawers and the wardrobe: brown spots could be remains of faeces, bed bug skins are brownish-silvery looking and live bed bugs are brown coloured and typically one to seven millimetres in length.

Inform the hotel if you think there are bed bugs in your room. And to avoid taking them with you when you checkout, carefully clean your luggage and clothes before opening them at home.

As higher-status hotels tend to have more frequent room usage, a more expensive room at a five-star hotel does not necessarily mean greater cleanliness, as room cleaning costs reduce profit margins. So wherever you’re staying, take with you a pack of antiseptic wipes and use them on the hard surfaces in your hotel room.

Also, wash or sanitise your hands often – especially before you eat or drink anything. And take slippers or thick socks with you so you can avoid walking barefoot on hotel carpets – known to be another dirt hotspot. And after all that, enjoy your stay.

Primrose Freestone does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

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