New malaria vaccine works well in infants, offers adults layered protection

An African girl holding a sign with

Even after 140 years of its discovery, malaria remains one of the deadliest infections humans have ever encountered. It affected 247 million individuals and was responsible for over 600,000 deaths in 2022, according to the World Health Organization. What’s more shocking is that 95 percent of malaria cases and deaths are reported in Africa alone, and 80 percent of the people who die in various African countries due to malaria are children under 5.

Currently, there exists only one malaria vaccine called RTS,S, and it only offers partial protection in children. However, a newly developed vaccine elicits a much stronger immune response in children, and it could offer layered protection to everyone by targeting a different stage of the malarial parasite’s life cycle.

The RH5 vaccine

A team of researchers from the University of Oxford recently tested a new malaria vaccine on 63 participants ranging in age from 6 months to 35 years in Bagamoyo, a town in Tanzania. The vaccine is technically ChAd63-MVA RH5, but generally called the RH5 vaccine. It exclusively targets RH5, a protein that Plasmodium falciparum (malaria parasite) employs to penetrate human red blood cells.

“RH5 is essential for the parasite to invade red blood cells and survive. Without it, the parasite will die. An RH5 vaccine stimulates the body to produce antibodies against the RH5 protein. These antibodies will bind to RH5 and if there are enough antibodies that bind, they will prevent the parasite from invading the red blood cells and causing the disease,” Dr. Angela Minassian, chief research investigator and a clinician scientist at Oxford, told Ars Technica.

Before testing the vaccine, the participants were divided into different groups based on their age (infants, teenagers, and adults). The researchers then conducted a double-blind trial in which neither the participants nor the health care workers who administered the doses didn’t know who received the malaria vaccine and who received a rabies vaccine that acted as the control.

Those who were administered the malaria vaccine developed antibodies targeting RH5. When these antibodies were tested against P. falciparum in lab settings, they prevented the growth of the pathogen, limiting it to levels that should protect against the disease.

Apart from mild fever and injection pain, none of the participants experienced any side effects from the vaccine during or after the trial period. The people who ran the trial note, “There were no serious adverse events (SAEs), adverse events (AEs) of special interest (AESIs), or unexpected reactions and no safety concerns during the course of the trial.”

In contrast to the RTS,S vaccine, RH5 triggered the most robust immune response in the group comprising infants 11 months old or younger. The next best malaria immunity was observed in 1- to 6-year-old children. The study authors said, “Higher anti-RH5 serum immunoglobulin (Ig) G responses were observed post-boost in young children and infants compared to adults.” They added, “Why the infants and young children vaccinated with ChAd63-MVA RH5 induced such high levels of antibody remains to be fully understood.”

Layered protection?

In the last two years, the RTS,S vaccine, which is currently being used in Malawi, Ghana, and Kenya, has prevented thousands of malaria deaths. The UN recently announced that nine more African countries will soon receive their first batch of RTS,S, and it plans to allocate 18 million RTS,S vaccine doses this year. WHO is reviewing another vaccine called R21 that showed 80 percent efficacy during its initial trials.

Both RTS,S and R21 are anti-sporozoite vaccines, which means they can prevent the malaria parasite’s spores from infesting the liver (plasmodium first enters the liver, then invades the blood, and from there, the infection spreads throughout the body). If somehow the pathogen makes it to the bloodstream despite these vaccines, they won’t offer any protection.

The RH5 protein, in contrast, is essential for the spread of the parasite to the blood. So the new vaccine should provide blood-stage protection that can work as a “second line of defense” against malaria. Even if some P. falciparum spores evade the RTS,S response, the antibodies produced by the new vaccine will still limit the parasite’s ability to enter red blood cells.

Med, 2023. DOI: http://dx.doi.org/10.1016/j.medj.2023.07.003 (About DOIs)

Rupendra Brahambhatt is an experienced journalist and filmmaker. He covers science and culture news, and for the last five years, he has been actively working with some of the most innovative news agencies, magazines, and media brands operating in different parts of the globe.

https://arstechnica.com/?p=1961792




The one-shot drug that keeps on dosing

Close up of needle with microparticles
Brandon Martin/Rice University

On average, patients with chronic illnesses follow their prescribed treatments about 50 percent of the time. That’s a problem. If drugs aren’t taken regularly, on time, and in the right doses, the treatment may not work, and the person’s condition can worsen.

The issue isn’t that people are unwilling to take their prescriptions. It’s that some drugs, like HIV medications, require unwavering commitment. And essential medicines, like insulin, can be brutally expensive. Plus, the Covid pandemic illustrated the difficulties of delivering perishable follow-up vaccine shots to regions with no cold chain. “Are we really squeezing all the utility out of those drugs and vaccines?” asks Kevin McHugh, a bioengineer at Rice University. “The answer is, in general, no. And sometimes we’re missing out on a lot.”

For example, the injectable drug bevacizumab can be used to treat macular degeneration, a leading cause of blindness. But even though it’s effective, dosing adherence is notoriously low. “People hate getting injections into their eyes,” McHugh says. “And I don’t blame them at all—that’s terrible.”

McHugh’s lab is in the drug delivery business. The goal is to give patients what they want—less hassle—while also giving them what they need: consistent dosing. The lab’s answer is an injection of drug-delivering microparticles that release their contents in timed delays that can span days or even weeks. “We’re trying to engineer these delivery systems to work in the real world, as opposed to in this idealized version of the world,” McHugh says.

In the June issue of Advanced Materials, McHugh’s team described how their system works. It starts with an injection containing hundreds of tiny microplastic particles, each encapsulating a small dose of a drug. These minuscule capsules are made of the polymer PLGA, which our bodies break down safely. By adjusting the molecular weight of the polymer used for each capsule, the scientists can control how fast they erode and release medication. In this study, the team demonstrated a single shot containing four groups of microparticles that released their contents at 10, 15, 17, and 36 days after injection.

“Having long-acting delivery strategies is a great unmet need,” says SriniVas Sadda, an ophthalmologist with UCLA and the Doheny Eye Institute who was not involved in the study. The patients Sadda sees are elderly. They are often dependent on family members for transportation and may skip appointments because of other health problems. “Maybe they’ve fallen and broke their hip and they end up not coming in,” he says. “Missed visits can be a big problem because you miss treatment and the disease could get worse. And it’s not always possible to recover.”

It’s hard to have delicate control over the levels of a drug in your body, in part because most medications operate like sledgehammers. Pop an ibuprofen or an antidepressant, and those levels will spike as the drug quickly passes through your gastrointestinal tract. Extended release pills prolong a drug’s effect but still taper off from a peak. And you can’t simply front-load a steep dose to delay the next one, since some drugs, like insulin, have a narrow “therapeutic window” between being helpful and dangerous.

Ironically, new and more advanced kinds of drugs have only made this problem more daunting. In 2021, seven of the 10 best-selling drugs in the United States were biologics, a class that includes proteins, hormones, and gene therapies. Biologics are more finicky than small molecules like ibuprofen, and rarely work orally. But they’re effective. “The potency and the specificity provided by protein drugs like antibodies is so great,” McHugh says. “Now the question would be how to make them last for long.”

During a postdoctoral fellowship at MIT about six years ago, McHugh experimented with manipulating polymers to encase drugs. His team invented a type of microparticle that encapsulated a drug using PLGA because the polymer has been used clinically in FDA-approved treatments since 1989. It was clear that changing the polymer’s molecular weight would delay its degradation—and the drug’s release—but the technique was expensive and hard to scale up. And some of the most important applications, like for vaccines, need to be extremely low-cost. “If we’re trying to develop and deliver vaccines in low- and middle-income countries, maybe these technologies have to cost a couple of pennies,” he says. “How do we make a billion of these?”

So when McHugh started his own lab at Rice, his team put his original process under the microscope. His previous method entailed casting a microscopic PLGA “bucket” to fill with a drug, then adding a flat “lid” of the polymer. They’d line the bucket and lid up under a specialized microscope, smush them together, and heat them to form a seal. Too many steps, McHugh thought.

https://arstechnica.com/?p=1950191




Ultra low-cost smartphone attachment measures blood pressure at home

Image of a hand pressing its thumb into a black plastic cell phone attachment.
Enlarge / The BPClip in action.
Yinan Xuan et al.

Given that 47 percent of adults in the US alone have hypertension, keeping on top of your blood pressure readings is a smart thing to do. And doing so could become much more convenient, requiring nothing more than your phone and an $0.80 piece of plastic, thanks to new research from the University of California, San Diego.

The school’s device, called BPClip, gives broadly comparable readings to those taken with a traditional cuff but functions as a simple cell phone attachment. It relies on the flashlight and the smartphone’s camera—along with some simple physics.

BPClip consists of a plastic clip with a spring mechanism that lets the user squeeze the device and two light channels: one to direct a flashlight to your finger and the other to direct the reflected light to the camera for image processing. A custom-made Android app handles the data processing and guides users through the measurement.

“The main motivation of this work lies in the low-cost aspect, and the main reason that we want to go in this direction is because currently there aren’t really any truly low-cost blood pressure measuring devices out there,” Yinan Xuan, lead author of the paper, told Ars. “All the off-the-shelf ones you can get from convenience stores or drug stores are cuff devices and cost around $20 or $30, even for the cheapest ones.”

For lower-income individuals, this can act as a financial barrier to having their blood pressure measured. “Worldwide, just over one-third of patients with hypertension are diagnosed and treated,” said Dr. Harriette Van Spall, associate professor at the McMaster University Division of Cardiology, who was not involved with the work. “Those in marginalized populations, including women, people of color, and socioeconomically deprived people are particularly susceptible to underdiagnosis and undertreatment and could benefit from such patient-centered technologies,” she added.

Xuan and his co-workers hope that if the device enters large-scale production, BPClip could eventually be handed out by doctors or nonprofit organizations just as dentists hand out floss and toothbrushes. To this end, they have already created a startup company, Billion Labs Inc., to further refine their design.

Light at the end of the tunnel

BPClip relies on a simple principle to take readings: blood absorbs light. If you cover your phone’s flashlight with your finger in a dark room, you may see pulsing in your glowing finger. This is from your actual pulse, which sends blood flowing through the veins and arteries in your finger—more blood (more light absorbed) when your heart contracts and less blood (less light absorbed) when your heart relaxes.

BPClip records these pulses of light using the phone’s camera. By simply averaging the brightness of each captured frame, the app can read how much blood is flowing through your finger in real time.

This information alone, however, isn’t enough to calculate a blood pressure reading: BPClip also needs to know how this blood flow changes as pressure is applied to the finger—essentially the same process that cuff-based devices use to take their measurements.

This is where the BPClip’s spring comes in. By gradually compressing the spring from 0 to 100 percent, a range of different pressures can be applied to the blood vessels in the finger. These pressures affect the flow of blood, which can be used to calculate blood pressure readings.

Consider when the user has pressed the spring all the way down: the pressure forces vessels in the finger to close, and no blood can flow, so there’s no light pulse for the camera to see. If the user releases the spring gradually, they reach a point where the blood can flow again, restoring a pulsing of light that the camera can detect. This corresponds to the maximum blood pressure during a heartbeat (the systolic pressure).

As the user continues to decrease pressure on the spring, blood can flow more and more freely through the finger, changing how much light is reflected. Eventually, the pressure on the finger will no longer be sufficient to impede the flow of blood, and the reflected light becomes a steady pulse. We are now at the minimum pressure during a heartbeat: the diastolic pressure.

By looking at blood flow at different compression levels and matching those measurements to the force exerted on the finger, BPClip can calculate the user’s systolic and diastolic blood pressures. This raises the question: How does the system tell how much force the BPClip is applying?

https://arstechnica.com/?p=1948581




mRNA technology for vaccines and more: An Ars Frontiers recap

Ars' John Timmer (left) with Karin Bok (center) and Nathaniel Wang (right).
Enlarge / On May 22, John Timmer (left) moderated a panel featuring Karin Bok (center) and Nathaniel Wang (right) for the Ars Frontiers 2023 session titled, “Beyond COVID: What Does mRNA Technology Mean for Disease Treatment?”
Ars Technica

The world of biomedicine has developed a lot of technology that seems a small step removed from science fiction, but the public isn’t aware of much of it. mRNA-based vaccines, though, were a big exception as a lot of the public tracked the technology’s development as a key step toward emerging from the worst of the pandemic and then received the vaccines in droves.

mRNA technology has a lot of potential applications beyond COVID, and we talked a bit about those during the “Beyond COVID: What Does mRNA Technology Mean for Disease Treatment?” panel at last week’s Ars Frontiers event. We’ve archived the panel on YouTube; if you want to focus on the discussion about mRNA therapies, you can start at the 1-hour, 55-minute mark.

[embedded content]

mRNA is a nucleic acid molecule that instructs the cell to make specific proteins. When used as vaccines, the instructions call for a protein produced by a pathogen, such as a virus. “It helps put up a wanted poster for the immune system,” was how Nathaniel Wang, co-founder and CEO of Replicate Bioscience put it.

The production of a wanted poster is no different from other vaccines. “mRNAs is just the vessel, it’s the delivery vehicle,” said Karin Bok of the National Institutes of Health. “So let’s say you have your sandwich for lunch—mRNA is the bread that you choose to deliver that sandwich.” Where RNA differs is in how easy it is to work with. Bok said that since the mRNA is synthetic, it avoids many of the potential safety precautions that need to be taken when the vaccine is produced in cells. (Bok is the director of Pandemic Preparedness and Emergency Response at NIH’s Vaccine Research Center.) This means that we can get a vaccine into safety tests quickly and potentially test alternate vaccines in parallel.

That ease of use affects manufacturing, as well. “You don’t need to recreate a manufacturing process for flu versus COVID-19 versus Epstein-Barr virus,” Wang said. “You just change the sequence that’s in the RNA itself, but the way you manufacture and purify that material is the same, and that’s why it’s so much faster.”

Beyond speed

Speed of development has some additional benefits. Bok named seasonal vaccines, such as the flu (and potentially COVID in the future), as a big beneficiary. Because the testing and manufacturing process go faster, we can wait a few extra months to gather additional data before committing to a specific formulation for the year’s vaccine. Beyond that, Bok suggested we’ll use mRNAs for additional diseases, but which ones will depend on an analysis of the specific disease and whether mRNA can provide what’s needed to generate lasting immunity.

Wang, for his part, is excited by technologies that are in development (he termed them “mRNA 2.0”) that could produce more protein from each RNA molecule and include signals that stimulate the immune response. This, he suggested, could lower the required vaccine dose by as much as 1,000-fold, making manufacturing even easier.

That could be good news for uses beyond vaccines. Therapies such as those for autoimmune disorders and diabetes may be based on protein injections, often done daily. But with mRNAs, we can get our cells to produce the therapies themselves. Wang said there is work toward developing mRNA-like molecules that can drive expression for weeks or even months, potentially eliminating the need for daily injections.

Further into the future, Wang said people are working on so-called “cancer vaccines,” where proteins are used to restore the immune response to cancerous cells. mRNA, he suggested, was an obvious candidate for use in this work.

All of these uses, however, depend on the public being comfortable with the continued use of mRNA, which caused a lot of suspicion in some circles after the COVID vaccine rollout. Bok partially attributed that to the speed aspect of Project Warp Speed, though she emphasized that “we only bet money; we didn’t bet safety.” But she also acknowledged that there has been long-term mistrust of vaccines in many societies.

“I think our R&D excitement needs to come hand-in-hand with how do we instill trust in vaccines, but also in mRNA vaccines, which is a fantastic new technology that we can use for many, many infectious diseases that we don’t have vaccines for,” Bok said. She and Wang emphasized that transparency and authenticity will be key to instilling trust.

Still, the fact that we need to restore trust is a sign of just how successful this technology has been compared to where it was before COVID. “I think it’s hard to remember anything before the pandemic sometimes, but people were ready to take RNA technologies behind the shed and shoot it,” Wang said. “There were real questions on whether it could ever scale, whether it was ever going to be commercially deployable, whether there were going to be fundamental safety questions, and I think what the past few years have done is really answer all of those questions with a resounding yes, it is a scalable technology, it can be manufactured, it can be safe and deployable.”

https://arstechnica.com/?p=1943062




Neuralink says it has the FDA’s OK to start clinical trials

Cartoon of a brain made of electronics, with the neuralink company logo superimposed

In December 2022, founder Elon Musk gave an update on his other, other company, the brain implant startup Neuralink. As early as 2020, the company had been saying it was close to starting clinical trials of the implants, but the December update suggested those were still six months away. This time, it seems that the company was correct, as it now claims that the Food and Drug Administration (FDA) has given its approval for the start of human testing.

Neuralink is not ready to start recruiting test subjects, and there are no details about what the trials will entail. Searching the ClinicalTrials.gov database for “Neuralink” also turns up nothing. Typically, the initial trials are small and focused entirely on safety rather than effectiveness. Given that Neuralink is developing both brain implants and a surgical robot to do the implanting, there will be a lot that needs testing.

It’s likely that these will focus on the implants first, given that other implants have already been tested in humans, whereas an equivalent surgical robot has not.

The news is undoubtedly a relief for both the staff of the company and its owner Musk, given that Neuralink has had several negative interactions with federal regulators of late. It’s a bad sign when having an earlier bid to start clinical trials rejected by the FDA was the least of the company’s problems. The company has also been accused of being abusive toward its research animals and violating transportation rules by shipping implants contaminated with monkey tissue and pathogens.

Typically, when the FDA rejects an application for clinical trials, it is willing to communicate in detail why it found the plan for trials insufficient. It’s a positive sign for Neuralink that the company was able to address the concerns of federal regulators in a relatively short period.

https://arstechnica.com/?p=1942466




How an early-warning radar could prevent future pandemics

Multi-pipettes

On December 18, 2019, Wuhan Central Hospital admitted a patient with symptoms common for the winter flu season: a 65-year-old man with fever and pneumonia. Ai Fen, director of the emergency department, oversaw a typical treatment plan, including antibiotics and anti-influenza drugs.

Six days later, the patient was still sick, and Ai was puzzled, according to news reports and a detailed reconstruction of this period by evolutionary biologist Michael Worobey. The respiratory department decided to try to identify the guilty pathogen by reading its genetic code, a process called sequencing. They rinsed part of the patient’s lungs with saline, collected the liquid, and sent the sample to a biotech company. On December 27, the hospital got the results: The man had contracted a new coronavirus closely related to the one that caused the SARS outbreak that began 17 years before.

The original SARS virus was sequenced five months after the first cases were recorded. This type of traditional sequencing reads the full genetic code, or genome, of just one organism at a time, which first needs to be carefully isolated from a sample. The researchers hired by Wuhan Central Hospital were able to map the new virus so quickly using a more demanding technique called metagenomic sequencing, which reads the genomes of every organism in a sample at once — without such time-intensive preparation. If the traditional approach is like locating a single book on a shelf and copying it, metagenomic sequencing is like grabbing all of the books off the shelf and scanning them all at once.

This ability to quickly read a range of genomes has proven useful in fields from ecology to cancer treatment. And the COVID-19 pandemic has pushed some researchers to use metagenomics to try to spot new diseases and respond to them earlier — before they become epidemics, and potentially before they even infect people. Some of these experts say the early spread of COVID-19 in the United States could have been curbed more quickly if the medical community had applied this technology.

“If metagenomic sequencing was done more routinely, maybe we would’ve known what it was when there were only 20 infections,” in the US, said Joe DeRisi, a professor of biochemistry and biophysics at the University of California San Francisco and president of the Chan Zuckerberg Biohub, a nonprofit research center.

But while the raw power of metagenomics is clear, there are challenges to using it to squelch potential pandemics. The technique requires intensive computer processing, making it costlier than some others, and calls for greater expertise to interpret the results. Using the copious data metagenomics produce to guide treatment also raises quandaries about medical decision-making when, for instance, it’s not clear whether a certain pathogen is causing a certain illness.

Still, advocates say the costs are worth it. “Metagenomics plays a critical role in pandemic preparedness, by looking for the things we don’t know to look for,” said Jessica Manning, an infectious disease researcher at the National Institute of Allergy and Infectious Diseases.

The rise of metagenomics over the past couple of decades is due in part to advances in genome sequencing. To read the contents of the genome, researchers first isolate the molecules that store genetic information, DNA and RNA, which are long chains of nucleotides, the letters of the genetic library. Then they cut the long molecules into shorter chunks and read the order of letters in each chunk. Finally, they combine the shorter “reads” to reconstruct the full genome.

Over the past 40 years, innovation, especially automation, dramatically improved every part of this process. The Human Genome Project, launched in 1990, took more than a decade of work coordinated between 20 research groups and cost around a billion dollars. Today a human genome can be sequenced more accurately, for less than one-millionth the cost, by one scientist in one day.

As the technology got better, researchers started trying to sequence many organisms at once, a complex task that requires figuring out how millions of short reads fit together to make any number of genomes. Eventually researchers wrote sophisticated software that can sort out the sequences using networks of powerful computers.

https://arstechnica.com/?p=1920075




Bonkers Republican bill in Idaho would make mRNA-based vaccination a crime

The Comirnaty (Pfizer/BioNTech) and Moderna COVID-19 vaccines.
Enlarge / The Comirnaty (Pfizer/BioNTech) and Moderna COVID-19 vaccines.

Two Republican lawmakers in Idaho have introduced a bill that would make it a misdemeanor for anyone in the state to administer mRNA-based vaccines—namely the lifesaving and remarkably safe COVID-19 vaccines made by Pfizer-BioNTech and Moderna. If passed as written, it would also preemptively ban the use of countless other mRNA vaccines that are now in development, such as shots for RSV, a variety of cancers, HIV, flu, Nipah virus, and cystic fibrosis, among others.

The bill is sponsored by Sen. Tammy Nichols of Middleton and Rep. Judy Boyle of Midvale, both staunch conservatives who say they stand for freedom and the right to life. But their bill, HB 154, proposes that “a person may not provide or administer a vaccine developed using messenger ribonucleic acid [mRNA] technology for use in an individual or any other mammal in this state.” If passed into law, anyone administering lifesaving mRNA-based vaccines would be guilty of a misdemeanor, which could result in jail time and/or a fine.

While presenting the bill to the House Health & Welfare Committee last week, Nichols said their anti-mRNA stance stems from the fact that the COVID-19 vaccines were initially allowed under emergency use authorizations (EUAs) from the Food and Drug Administration, not the agency’s full regulatory approval. “We have issues that this was fast-tracked,” she told fellow lawmakers, according to reporting from local news outlet KXLY.com.

The EUAs for the two mRNA-based COVID-19 vaccines were issued in December 2020, and the FDA has subsequently granted full approval to both (Pfizer-BioNTech’s in August 2021 and Moderna’s in January 2022). This was pointed out to Nichols in the hearing last week.

Safe, effective

“They ultimately were approved under the ordinary approval process and did ultimately, you know, survive the scrutiny of being subjected to all the normal tests,” Rep. Ilana Rubel, a democrat from Boise, said.

Nichols seemed unswayed by the point, however, with KTVB7 reporting that she responded that the FDA’s approval “may not have been done like we thought it should’ve been done.”

It’s unclear what Nichols meant by that statement or why any potential questions about the regulatory review of two specific vaccines would justify criminalizing the use of all vaccines using a similar platform.

To date, more than 269 million people in the US have received at least one COVID-19 vaccine, and over 700 million doses of mRNA-based vaccines have gone into American arms, according to data from the Centers for Disease Control and Prevention. The agency keeps close tabs on safety through various national surveillance systems. Although the shots do carry some risk (as is the case for any medical intervention), they have proven remarkably safe amid widespread use of hundreds of millions of doses in the US and worldwide. A study released late last year found that COVID-19 vaccination in the US alone averted more than 18 million additional hospitalizations and more than 3 million additional deaths from the pandemic coronavirus, SARS-CoV-2.

There have been rare reports of adverse events, including blood clots and inflammation of the heart muscle and lining (myocarditis and pericarditis). However, these problems are very rare, and, in the case of myocarditis and pericarditis, they tend to be mild. Independent health experts who advise the FDA and CDC have consistently determined that the risk of developing these conditions does not outweigh the benefits of vaccination.

mRNA plans

mRNA-based vaccines made their public debut amid the COVID-19 pandemic, but researchers at the National Institutes of Health and pharmaceutical companies had been working toward these vaccines for decades beforehand. In fact, by 2016, Moderna began working with the NIH to come up with a general design for mRNA-based vaccines. One of their first targets for such a vaccine was a relative of SARS-CoV-2, the Middle East respiratory syndrome (MERS) coronavirus. By 2019, Moderna and the NIH set out plans for a clinical trial of an mRNA vaccine against the Nipah virus.

Generally, the vaccines work by delivering to our cells a snippet of artificially stabilized genetic code—in the form of messenger RNA—which is packaged in a fatty coating. In the case of COVID-19 vaccines, the bit of genetic code is for making a critical protein from SARS-CoV-2 called the spike protein, which typically juts out from the surface of the virus and helps it invade human cells. Once the vaccine’s fatty package is delivered, our cells translate the mRNA code into a protein—the spike protein, in this case—which can then be used to train immune cells to identify and attack invaders with the same protein—in this case, SARS-CoV-2.

With the massive success of mRNA-based COVID-19 vaccines, expectations are high that the platform can be used to target a wide variety of other infectious and non-infectious diseases. Moderna, for instance, has a wide pipeline of mRNA-based vaccines in the works. Already this year, the company reported findings from a late-stage clinical trial indicating their mRNA-based vaccine against RSV (respiratory syncytial (sin-SISH-uhl) virus) was highly effective. RSV is a common respiratory virus that can be deadly to older adults and young children.

In Idaho, it’s unclear if Nichols and Boyle’s bill will make it through the committee and, further, into law. However, its introduction fits into a worrying trend by conservative lawmakers for attacking lifesaving vaccination and evidence-based medicine, generally.

https://arstechnica.com/?p=1918936




Controlled experiments show MDs dismissing evidence due to ideology

Image of a group of people wearing lab coats, scrubs, and carrying stethoscopes.
Enlarge / Those lab coats aren’t going to protect you from your own biases.

It’s no secret that ideology is one of the factors that influences which evidence people will accept. But it was a bit of a surprise that ideology could dominate decision-making in the face of a pandemic that has killed over a million people in the US. Yet a large number of studies have shown that stances on COVID vaccination and death rates, among other things, show a clear partisan divide.

And it’s not just the general public having issues. We’d like to think people like doctors would carefully evaluate evidence before making treatment decisions, yet a correlation between voting patterns and ivermectin prescriptions suggests that they don’t.

Of course, a correlation at that sort of population level leaves a lot of unanswered questions about what’s going on. A study this week tries to fill in some of those blanks by performing controlled experiments with a set of MDs. The work clearly shows how ideology clouds professional judgments even when it comes to reading the results of a scientific study.

Call a doctor

The work primarily focuses on a panel of about 600 critical care physicians—the people who are most likely to be the first source of treatment for those who develop severe COVID-19. It also involved a panel of 900 people who aren’t involved in medicine to provide a comparison population. While some initial surveys were done earlier, most of the data comes from the spring of 2022, long after COVID-19 vaccines had established their effectiveness in limiting severe symptoms of the disease. By then, a couple of widely hyped “cures”—hydroxychloroquine and ivermectin—had been definitively ruled out as therapeutic.

All the participants were asked to self-rate on a seven-point scale, from very liberal to very conservative. For most studies, the answers from the liberal and conservative participants were evaluated in terms of how greatly they differed from those of the moderate participants.

When asked about the effectiveness of treatments, the non-MDs showed exactly the sort of behavior you’d expect from politically polarized subjects. Liberal participants were more likely than moderates to say vaccines worked and less likely to ascribe effectiveness to ivermectin and hydroxychloroquine. Conservatives showed the converse behavior, being enthusiastic about ivermectin and hydroxychloroquine and less likely to think vaccines worked. If you plot these results across a liberal-to-conservative axis, the result is a nearly straight line with a slope that represents the liberal-conservative difference of opinion.

In these graphs, purple represents physicians, green the general public. For these medicines, liberals and moderates evaluate their effectiveness similarly, while conservative MDs evaluate them like the public does.
In these graphs, purple represents physicians, green the general public. For these medicines, liberals and moderates evaluate their effectiveness similarly, while conservative MDs evaluate them like the public does.
Levin, et. al.

For physicians, things were considerably different. Here, the lines were largely straight and flat from very liberal to moderates, indicating that these physicians all had similar opinions on the value of these three medicines. But then the graph changed moving from moderates to the conservative end of the spectrum. This indicates that, among experts, the political polarization is one-sided. In other words, the opinions of liberal MDs look like those of moderate MDs, while the opinions of conservative MDs are difficult to distinguish from those of non-experts.

https://arstechnica.com/?p=1916505




Gonorrhea is becoming unstoppable; highly resistant cases found in US

Colorized scanning electron micrograph of Neisseria gonorrhoeae bacteria, which causes gonorrhea.
Colorized scanning electron micrograph of Neisseria gonorrhoeae bacteria, which causes gonorrhea.

The most highly drug-resistant cases of gonorrhea detected in the US to date appeared in two unrelated people in Massachusetts, state health officials announced Thursday.

The cases mark the first time that US isolates of the gonorrhea-causing bacterium, Neisseria gonorrhoeae, have shown complete resistance or reduced susceptibility to all drugs that are recommended for treatment.

Fortunately, both cases were successfully cured with potent injections of the antibiotic ceftriaxone, despite the bacterial isolates demonstrating reduced susceptibility to the drug. Ceftriaxone is currently the frontline recommended treatment for the sexually transmitted infection.

But health officials said the cases are a warning. “N. gonorrhoeae is becoming less responsive to a limited arsenal of antibiotics,” they said.

Brewing resistance

For years, global surveillance data collected by the World Health Organization has shown that gonorrhea is becoming more and more resistant to our entire lineup of drugs, including frontline drugs like ceftriaxone. Though surveillance is spotty globally, a study of WHO’s 2017–2018 data published in 2021 found N. gonorrhoeae isolates with decreased susceptibility or resistance to ceftriaxone have turned up in 21 of the 68 reporting countries, or 31 percent.

Resistance against alternative antibiotics was even higher. Among the 61 countries reporting data on an alternative antibiotic, azithromycin, 51 countries (84 percent) reported resistance. And of 51 countries reporting data on the alternative antibiotic treatment, cefixime, 24 countries (47 percent) reported resistance. For ciprofloxacin, an antibiotic largely abandoned as a gonorrhea treatment due to resistance, all 70 reporting countries found resistance.

“In many countries, ciprofloxacin resistance is extremely high, azithromycin resistance is rapidly increasing, and resistance or decreased susceptibility to ceftriaxone and cefixime continue to emerge,” the WHO said in 2021. “Without new gonorrhoea treatments, there will be people with gonorrhoea infections that will be difficult to treat and cure.”

The agency wasn’t exaggerating. Last year, WHO added that reports of gonorrhea treatment failure are stacking up. “In the past decade, confirmed failure to cure gonorrhoea with ceftriaxone alone or combined with azithromycin or doxycyline was reported in Australia, France, Japan, Slovenia, Sweden, and the United Kingdom of Great Britain and Northern Ireland,” WHO reported.

One of the isolates reported in Massachusetts yesterday demonstrated reduced susceptibility to ceftriaxone, cefixime, and azithromycin and resistance to ciprofloxacin, penicillin, and tetracycline in lab tests. The second isolate appeared to have a similar profile based on genetic data, Massachusetts’ public health department reported. This strain of N. gonorrhoeae has been seen circulating in Asia-Pacific countries and has been detected in recent cases in the UK.

High cases

Alongside the worrying trend of increased resistance is the fact that gonorrhea cases are high worldwide and are on the rise in the US. In 2020, WHO estimated that there were 82.4 million new cases of gonorrhea worldwide. In the US, there were nearly 700,000 cases in 2021, up more than 25 percent from 2017, according to preliminary estimates from the Centers for Disease Control and Prevention.

In many people, gonorrhea has no symptoms. In others, it’s so mild that it may be mistaken as a minor bladder infection or yeast infection. Over time, however, it can lead to pelvic inflammatory disease, severe pain, and fertility problems. Health officials stress the need for screening and surveillance to treat infections early before they become severe and have a chance to spread.

For the two Massachusetts cases, health officials are now working on contact tracing. Without a clear link between the two cases, officials say it’s likely it’s more widespread than currently known.

“The discovery of this strain of gonorrhea is a serious public health concern which DPH, the CDC, and other health departments have been vigilant about detecting in the US,” Massachusetts Public Health Commissioner Margret Cooke said in a statement. “We urge all sexually active people to be regularly tested for sexually transmitted infections and to consider reducing the number of their sexual partners and increasing their use of condoms when having sex. Clinicians are advised to review the clinical alert and assist with our expanded surveillance efforts.”

https://arstechnica.com/?p=1911508




US acceptance of COVID vaccines rises, now like other Western democracies

A medical professional administers a shot to the arm of a seated individual.

COVID vaccines remain the safest way to reduce the chance that SARS-CoV-2 can put you in the hospital and are a critical component of the public health campaign against the pandemic. Yet, in the US, there has been lots of controversy and outright anger about attempts to expand vaccine use, and a substantial portion of the population appears to be avoiding the shots for political reasons.

The extreme polarization of US politics hasn’t gone away, and the controversy seems fresh in some politicians’ minds, so it’s easy to expect that vaccine hesitancy isn’t going away. But an international survey on COVID vaccine attitudes suggests that the US has seen a large boost in COVID vaccine acceptance and now has attitudes similar to other Westernized democracies. Elsewhere in the world, the survey reveals clear regional patterns in vaccine acceptance, although there are oddities everywhere.

Becoming typical

The survey started in 2020 as a series of questions about whether people intended to get vaccines once they became available. In the intervening years, the people performing the survey have added several nations (now up to 23) and shifted the questions to account for the availability of vaccines, addition of boosters, and development of treatments for COVID-19. In all 23 countries, the survey involved a pool of 1,000 participants who were generally reflective of the country’s population.

The survey focuses on what it calls vaccine hesitancy, which it defines as not having gotten a dose if it’s available or don’t intend to get one once it is. Questions about the boosters took the same form but were specific to those who have already had vaccines.

Overall, the news is good. Globally, the average vaccine hesitancy has dropped in each survey edition and is now just over 20 percent. That’s right about where the US now finds itself, with just under 20 percent indicating they have not received a first shot. (That appears to be similar to the percentage having had at least one shot, calculated from CDC data.)

That also makes the US fairly typical of its peer group of Westernized democracies, which tend to be in the 15–20 percent vaccine-hesitancy range. Spain is on the low side, at 10 percent hesitancy, but rates rise as you move east across Europe, with Sweden and Germany above 20 percent. Poland has the highest rate of hesitancy among European democracies, at 36 percent, perhaps influenced by neighboring Russia, where hesitancy nears 40 percent. The US is now typical among this group primarily due to a rise of about 20 percent in people having reported getting vaccinated over the last year alone.

There’s no clear pattern when it comes to boosters. France, where vaccine hesitancy was under 20 percent, saw booster hesitancy of over 25 percent, and Germany saw booster hesitancy of only 11 percent. So, while local factors seem to matter most here, it’s clear that we can’t expect that any messaging that worked for vaccines will automatically carry over to boosters.

Spanning the globe

The rest of the globe is sparsely represented by comparison, and the countries included mostly highlight the exceptions. For example, South American countries (Brazil, Ecuador, and Peru) tended to have vaccine hesitancy of about 10 percent, while just north of there in Mexico, hesitancy was more than double at over 26 percent. Acceptance in East and South Asia was very high (from 11 percent hesitancy in South Korea to under 2 percent in India), whereas it was much lower in African countries, where the best results, in Nigeria, were nearly 30 percent hesitancy.

Notably, South Africa saw a 20 percent drop in vaccine acceptance—the largest in the survey—and over half of its population now expresses vaccine hesitancy. South Korea is also unusual, in that, despite its high level of vaccine acceptance, 27 percent of the participants there report being hesitant about boosters, which is second only to Russia.

It’s important to note that, for many of the countries with lower GDPs, people are still answering the question without really having the option of getting vaccinated. More equitable vaccine access may allow more people in these countries to get vaccinated despite their hesitancy. Elsewhere, other research has identified vaccine misinformation, lower education levels, and mistrust of science and government as factors driving hesitancy.

Medical education appears to be especially effective at driving vaccine acceptance, with only 4.6 percent of those employed as health care workers expressing hesitancy—a number that’s still falling.

Another thing that’s trending upward with familiarity is the willingness of parents to have their children vaccinated. Globally, that rose slightly and is now at roughly 70 percent.

https://arstechnica.com/?p=1908714