A recent experiment tests whether the gene-editing technology CRISPR can stop the virus from replicating, which would ultimately wipe out the HIV infection. In July, an HIV-positive man became the first volunteer in a clinical trial aimed at using the CRISPR gene editing technology to snip the HIV virus out of his cells. For an hour, he was hooked up to an IV-bag that pumped the experimental treatment directly into his bloodstream. The one-time infusion is designed to carry the gene-editing tools to the man’s infected cells to clear the virus.
Later this month, the volunteer will stop taking the anti-retroviral drugs he’s been on to keep the virus at undetectable levels. Then, investigators will wait 12 weeks to see if the virus rebounds and becomes detectable again. If not, they’ll consider the experiment a success.
“What we’re trying to do is return the cell to a near-normal state,” says Daniel Dornbusch, CEO of Excision BioTherapeutics, the San Francisco-based biotech company that’s running the trial. HIV attacks CD4-positive immune cells in the body and hijacks their machinery to make copies of itself. But some HIV-infected cells can go dormant—sometimes for years—and not actively produce new copies of the virus. These so-called reservoirs are a major barrier to curing HIV.
“HIV is a tough foe to fight because it’s able to insert itself into our own DNA, and it’s also able to become silent and reactivate at different points in a person’s life,” says Jonathan Li, a physician at Brigham and Women’s Hospital and HIV researcher at Harvard University who’s not involved with the CRISPR trial. Figuring out how to target these reservoirs—and doing it without harming vital CD4 cells—has proven challenging, Li says. While antiretroviral drugs can halt viral replication and clear the virus from the blood, they can’t reach these hide-out reservoirs, so people have to take medication every day for the rest of their lives. But Excision BioTherapeutics is hoping that this CRISPR-based approach will remove HIV for good.
CRISPR is being used in several other studies to treat a handful of conditions that arise from various genetic mutations. In those cases, scientists are using CRISPR to edit peoples’ own cells. But for the HIV trial, Excision researchers are turning the gene-editing tool against the virus. The CRISPR infusion contains gene-editing molecules that target two regions in the HIV genome important for viral replication. The virus can only reproduce if it’s fully intact, so CRISPR disrupts that process by cutting out chunks of the genome. In 2019, researchers at Temple University and the University of Nebraska found that using CRISPR to delete those regions eliminated HIV from the genomes of rats and mice. A year later, the Temple group also showed that the approach safely removed viral DNA from macaques with SIV, the monkey version of HIV. That was an important step toward testing the treatment in people, says Kamel Khalili, a professor of microbiology at Temple University who led the work and is a cofounder of Excision Biotherapeutics.
“You don’t want to eliminate the viral genome but at the same time cause any disruption in another part of the human genome and then create another set of problems for the patients,” he says. “We had to make sure that we identified a region within HIV that did not overlap with the human genome.” Dornbusch thinks this strategy will spare patients from serious side effects and “off-target” edits—unintentional cuts elsewhere in the genome that could cause problems such as cancer.
The regions targeted by the company’s CRISPR therapy are also in a part of the genome that tends to stay the same even when HIV evolves. That’s important because the virus mutates rapidly, and the researchers don’t want a moving target. This isn’t the first time scientists have tried to use gene editing in the hope of curing people with HIV, but other efforts have focused on a protective mutation in a gene called CCR5. In the 1990s, scientists found that people with this naturally occurring mutation didn’t get HIV even when exposed to it. The mutation—known as delta 32—thwarts the virus’s ability to get inside immune cells. In 2009, California-based Sangamo Therapeutics used an older editing technology involving zinc finger nucleases to add that protective mutation into patients’ T cells—an important part of the immune system. Those trials have had only limited success.
In 2017, Chinese scientists combined CRISPR with a bone marrow transplant in an attempt to cure a patient with HIV and leukemia. In a typical transplant, donor stem cells are transferred to a recipient to replace their cancerous blood cells. These cells go on to form new, healthy blood cells. To also address the patient’s HIV, researchers edited the donor stem cells with CRISPR to disable CCR5. But after the transplant, only a small percentage of the patient’s bone marrow cells ended up with the desired edit. Then in 2018, Chinese scientist He Jiankui used CRISPR to edit the CCR5 mutation into the genomes of twin baby girls to make them resistant to HIV during their lives. Fraught with ethical violations, the experiment was widely condemned by scientists. He’s research was suspended by the Chinese government, and he served a three-year prison sentence. While the twins were born healthy, only some of their cells were successfully edited, meaning the girls might in fact not be immune to HIV. As of 2022, two people have now been cured of HIV after receiving bone marrow transplants from donors with the CCR5. Known as the Berlin patient and the London patient, both had cancer and received transplants to treat their disease. But these transplants aren’t a viable option for most people—they’re highly risky, and donors with the delta 32 mutation are scarce. But a third person was declared cured of HIV earlier this year after she received a new type of transplant involving umbilical cord blood.
The Excision trial will eventually enroll nine participants and test three dosage amounts to determine which is most effective. Investigators will measure each person’s viral load and CD4 count before receiving the therapy and after they stop taking anti-retroviral drugs. The ultimate goal is to get viral loads down to an undetectable level—that is, less than 200 copies of HIV per milliliter of blood. At this level, HIV can’t be passed on through sex anymore. The challenge for Excision will be getting CRISPR to enough cells to bring HIV down to undetectable levels. The company is using an engineered virus to shuttle the gene-editing components to patients’ HIV-infected CD4 cells. But so far, there’s little human data on how well CRISPR works when it’s delivered directly to the body. “It’s possible that you get the virus to such low levels that if a person’s immune system were intact, they might be able to keep the virus at bay such that they don’t have to take antiretroviral therapy anymore,” says Rowena Johnston, vice president and director of research for amfAR, the Foundation for AIDS Research.
And even though these drugs are very effective, Johnston says, many people would rather be completely free of the virus. A single CRISPR infusion—if it works—would eliminate the need for daily pills. “People with HIV still live with a lot of stigma and internalized shame,” she says. “I think a cure is something that addresses that much better than lifelong therapy, regardless of how easy that therapy becomes.”
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The Nobel Assembly at the Karolinska Institutet has today decided to award the 2022 Nobel Prize in Physiology or Medicine to Svante Pääbo “for his discoveries concerning the genomes of extinct hominins and human evolution.”
Humanity has always been intrigued by its origins. Where do we come from, and how are we related to those who came before us? What makes us, Homo sapiens, different from other hominins?
Through his pioneering research, Svante Pääbo accomplished something seemingly impossible: sequencing the genome of the Neanderthal, an extinct relative of present-day humans. He also made the sensational discovery of a previously unknown hominin, Denisova. Importantly, Pääbo also found that gene transfer had occurred from these now extinct hominins to Homo sapiens following the migration out of Africa around 70,000 years ago. This ancient flow of genes to present-day humans has physiological relevance today, for example affecting how our immune system reacts to infections.
Pääbo’s seminal research gave rise to an entirely new scientific discipline; paleogenomics. By revealing genetic differences that distinguish all living humans from extinct hominins, his discoveries provide the basis for exploring what makes us uniquely human.
Reports of myocarditis, penile necrosis, and atypical/persistent rash requiring amputation. Be alert for potentially severe manifestations of monkeypox in patients who are immunocompromised or co-infected with HIV, the CDC told healthcare workers on Thursday.
"People who are immunocompromised due to HIV or other conditions are at higher risk for severe manifestations of monkeypox than people who are immunocompetent," the agency said in a health advisory to its Health Alert Network, adding that "the HIV status of all sexually active adults and adolescents with suspected or confirmed monkeypox should be determined."
Of the patients with severe manifestations "for whom CDC has been consulted," the majority had HIV with CD4 counts below 200 cells/mL, indicating "substantial immunosuppression," the agency noted. These severe manifestations have included cases involving atypical or persistent rash requiring amputation of an extremity; secondary bacterial or fungal infections; lesions in sensitive areas resulting in severe pain or urethral or bowel strictures; and co-morbidities involving organ systems, including myocarditis, transverse myelitis, bowel lesions, penile necrosis, and others. The news arrives as the U.S. records its third known monkeypox-associated death in Ohio. To date, over 25,000 monkeypox cases have been reported in the U.S., 38% of which involved patients co-infected with HIV. Researchers have highlighted monkeypox severity and outcomes in people with HIV before.
A recent study published in The Lancet about a 2017-2018 monkeypox outbreak in Nigeria reported seven deaths in a population of 122 patients, with four of the seven co-infected with HIV. More recently, papers on the current outbreak have reported conflicting results about the association between monkeypox severity and HIV co-infection. CDC data involving more than 1,300 monkeypox patients showed a higher rate of hospitalizations for those with HIV (8% vs 3% for those without HIV), with higher rates for those whose HIV was not virally suppressed. Conversely, German researchers reported that the clinical characteristics in HIV-infected versus non-infected monkeypox patients were largely similar. The new CDC advisory recommends that monkeypox treatment include optimization of immune function for people with immunocompromising conditions, such as limiting the use of immunosuppressive medications when "not otherwise clinically indicated," and offering antiretroviral therapy for those living with HIV.
Severe immunocompromising conditions can including those with autoimmune disease where immunodeficiency is a clinical component; leukemia or lymphoma, transplant recipients; and those treated with high-dose steroids, alkylating agents, antimetabolites, radiation, or tumor necrosis factor (TNF) inhibitors. On a case-by-case basis, medications such as oral and intravenous tecovirimat (Tpoxx), cidofovir or brincidofovir, and vaccinia immune globulin intravenous should be considered, "although there are no data on effectiveness in treating human monkeypox with these medical countermeasures," according to the CDC. Clinicians should gather repeat lesion swabs in patients with persistent monkeypox DNA, and continue tecovirimat beyond 14 days (but not more than 90 days), "until there is clinical improvement," the advisory stated. Modifications to the dose, frequency, and duration of tecovirimat may be necessary, depending on the patient's clinical condition, disease progression, or therapeutic response. The advisory encouraged clinicians to consult with the CDC Monkeypox Response Clinical Escalations team when appropriate. The following severe manifestations seen in monkeypox patients were reported to the CDC, although the advisory did not include information about HIV status:
Atypical or persistent rash with coalescing or necrotic lesions, or both, some of which have required extensive surgical debridement or amputation of an affected extremity
Lesions on a significant proportion of the total body surface area, which may be associated with edema and secondary bacterial or fungal infections among other complications
Lesions in sensitive areas (including mucosal surfaces such as the oropharynx, urethra, rectum, and vagina) resulting in severe pain that interferes with activities of daily living
Bowel lesions that are exudative or cause significant tissue edema, leading to obstruction
Severe lymphadenopathy that can be necrotizing or obstructing (such as in airways)
Lesions leading to stricture and scar formation resulting in significant morbidity such as urethral and bowel strictures, phimosis, and facial scarring
The flare-up of one of the world’s most infectious diseases has taken hold among church congregations that have rejected vaccinations. A measles outbreak in Zimbabwe, Africa, has now killed nearly 700 children, in a rapidly accelerating and “deeply concerning” flare-up of the highly contagious disease. Health officials are alarmed by both the speed of the spread and the high fatality rate of the outbreak, which has seen the recent death toll jump by dozens each day. The flare-up of one of the world’s most infectious diseases has taken hold among church congregations that have rejected vaccinations for religious reasons.
Deaths had reached 698 by September 4, 2022, according to the nation’s health ministry, up from less than a quarter of that a two weeks earlier. Officials reported that 37 children died on September 1 alone. The outbreak is thought to be the worst for some time in the southern African nation of 15 million. The last outbreak 11 years ago was far less severe. Unicef said that in the worst affected eastern province of Manicaland, nearly one-in-10 of those getting the disease were dying. That rate is higher than in other recent African outbreaks. The UN body said it was “deeply concerned with the numbers of cases and deaths among children due to a measles outbreak in Zimbabwe”.
Faith healers and anti-vaxxers
Dr Johannes Marisa, the president of the Medical and Dental Private Practitioners of Zimbabwe, told The Associated Press that the government may need to force children to be vaccinated. He said: “Because of the resistance, education may not be enough so the government should also consider using coercive measures to ensure that no one is allowed to refuse vaccination for their children.” He urged the government to “consider enacting legislation that makes vaccination against killer diseases such as measles mandatory”.
Zimbabwe’s government has already invoked a law used to respond to disasters to deal with the outbreak and has launched a mass vaccination campaign, which will target two million children under five years. Nationwide, the vaccination rate was around 85 per cent in 2020, having fallen back on previous years when it at times touched 95 per cent. The country’s Apostolic churches or sects are thought to be followed by around one-in-five of the population. Their teachings regularly include a potent mix of opposition towards Western medicine and belief in faith healing and prayer, meaning the congregations have become a stronghold of anti-vaccination sentiment. As the outbreak has worsened and pressure has mounted, some church leaders have in recent weeks appeared to change their stance and called on followers to get their children vaccinated. The virus causes fever, coughing and a tell-tale rash, but in some cases it causes complications that can be fatal.
Complications of measles include blindness, brain swelling, severe diarrhea and dehydration, ear infections, or severe respiratory infections such as pneumonia. It is one of the world’s most contagious diseases, with a reproduction rate as high as 18 – compared to an R rate of between 2 and 3 for the original strain of Covid19. Before mass vaccinations began in the 1960s, the disease flared up in occasional epidemics, killing an estimated 2.6m children each year. More than 140,000 people died from measles in 2018 – mostly children under the age of five years, despite the availability of a safe and effective vaccine, according to the World Health Organization. The virus is so contagious that more than 90 per cent of the population needs to be immunized to prevent outbreaks.
Human monkeypox virus is spreading in Europe and the USA among individuals who have not travelled to endemic areas. On July 23, 2022, monkeypox was declared a Public Health Emergency of International Concern by WHO Director-General Tedros Adhanom Ghebreyesus.
Human-to-human transmission of monkeypox virus usually occurs through close contact with the lesions, body fluids, and respiratory droplets of infected people or animals. The possibility of sexual transmission is being investigated, as the current outbreak appears to be concentrated in men who have sex with men and has been associated with unexpected anal and genital lesions. Whether domesticated cats and dogs could be a vector for monkeypox virus is unknown. Here we describe the first case of a dog with confirmed monkeypox virus infection that might have been acquired through human transmission.
Two men who have sex with men attended Pitié-Salpêtrière Hospital, Paris, France, on June 10, 2022 (appendix). One man (referred to as patient 1 going forward) is Latino, aged 44 years, and lives with HIV with undetectable viral loads on antiretrovirals; the second man (patient 2) is White, aged 27 years, and HIV-negative. The men are non-exclusive partners living in the same household. They each signed a consent form for the use of their clinical and biological data, and for the publication of anonymised photographs. The men had presented with anal ulceration 6 days after sex with other partners. In patient 1, anal ulceration was followed by a vesiculopustular rash on the face, ears, and legs; in patient 2, on the legs and back. In both cases, rash was associated with asthenia, headaches, and fever 4 days later.
12 days after symptom onset, their male Italian greyhound, aged 4 years and with no previous medical disorders, presented with mucocutaneous lesions, including abdomen pustules and a thin anal ulceration (figure C, D; appendix). The dog tested positive for monkeypox virus by use of a PCR protocol adapted from Li and colleagues that involved scraping skin lesions and swabbing the anus and oral cavity. Monkeypox virus DNA sequences from the dog and patient 1 were compared by next-generation sequencing (MinION; Oxford Nanopore Technologies, Oxford, UK). Both samples contained virus of the hMPXV-1 clade, lineage B.1, which has been spreading in non-endemic countries since April, 2022, and, as of Aug 4, 2022, has infected more than 1700 people in France, mostly concentrated in Paris, where the dog first developed symptoms. Moreover, the virus that infected patient 1 and the virus that infected the dog showed 100% sequence homology on the 19·5 kilobase pairs sequenced.
The men reported co-sleeping with their dog. They had been careful to prevent their dog from contact with other pets or humans from the onset of their own symptoms (ie, 13 days before the dog started to present cutaneous manifestations). In endemic countries, only wild animals (rodents and primates) have been found to carry monkeypox virus. However, transmission of monkeypox virus in prairie dogs has been described in the USA and in captive primates in Europe that were in contact with imported infected animals. Infection among domesticated animals, such as dogs and cats, has never been reported.
Vaccines introduce a harmless version of a pathogen to your body. The idea is that they train your immune system to fight off the real germ if you ever encounter it. The oral polio vaccine, originally developed by Albert Sabin, uses a live but weakened poliovirus that one swallows in a sugar cube or droplet. Scientists weaken – or attenuate – the virus so it can no longer cause disease. The other kind of polio vaccine was originally developed by Jonas Salk. It contains inactivated, dead virus. It is administered by an injection. In the U.S., children receive the inactivated polio vaccine at 2, 4 and 6 months of age. It provides nearly complete protection from paralytic polio.
How can the live vaccine lead to a case of polio?
The weakened form of the live virus in the oral vaccine cannot cause disease. However, because the vaccine is given orally, the weakened virus is excreted in the feces and can spread from someone who is vaccinated to their close contacts. If the weakened virus circulates person to person for long enough, it can mutate and regain its ability to cause paralysis. The mutated virus can then infect people in communities with poor sanitation and low vaccination rates, causing disease and even paralysis. This is an exceedingly rare occurrence. With more than 10 billion doses of the oral polio vaccine administered since 2000, there have been fewer than 800 cases of vaccine-derived polio reported. Apparently, the current patient in New York was somehow exposed to a mutated poliovirus that had been transmitted after vaccination overseas. Earlier this summer, routine surveillance spotted vaccine-derived poliovirus in London’s sewage system, but no cases have been reported there.
Why use the oral vaccine anywhere if it comes with this risk?
There’s a positive aspect to the fact that the weakened live virus can circulate in the community once oral vaccine recipients shed it in their feces. Traveling a feces-to-oral route, it can help induce immunity even in people who weren’t directly vaccinated. The oral polio vaccine is also cheaper and easier to administer than inactivated polio vaccines. Most importantly, the live-virus vaccine stops transmission of wild poliovirus in a way that the inactivated-virus vaccine does not. The eradication of polio in the Americas, Europe and Africa has been accomplished solely through the use of the live oral vaccine. Once polio has been wiped from a continent, then it is safe to stop using the oral live vaccine and use only the inactivated vaccine, which does prevent disease in recipients and does not pose the rare risk of vaccine-derived paralytic polio. A new and safer oral polio vaccine that has been engineered not to mutate is now replacing the earlier live-virus vaccine. Thus, even this extremely rare complication of polio vaccination should soon become a thing of the past.
How close is the world to eradicating polio?
Thanks to tremendous global effort, two of the three viruses that cause polio have been eradicated. The world is now on the verge of eradicating the final one, wild poliovirus 1 (WPV1). Today endemic polio is found only in Pakistan, with 12 cases of paralytic polio so far in 2022, and Afghanistan, with just one case this year. Africa has two cases, imported from overseas, which are being contained by additional vaccination campaigns. Once wild poliovirus has been eradicated from the planet, vaccination efforts may be able to switch to the inactivated polio vaccine, eliminating the risk of any future vaccine-derived cases.
Spain reported last Saturday a second death from monkeypox. These are believed to be the first confirmed fatalities from the disease in Europe since its recent spread beyond Africa. The ministry based in Madrid said both fatalities were young men. It reported its first death on Friday, the same day that Brazil also reported its first death from monkeypox.
The global monkeypox outbreak has seen more than 22,000 cases in nearly 80 countries since May. There have been 75 suspected deaths in Africa, mostly in Nigeria and Congo, where a more lethal form of monkeypox is spreading than in the West. In the U.S. and Europe, the vast majority of monkeypox infections have happened in men who have sex with men, though health officials have stressed that anyone can catch the virus. The deaths outside Africa come one week after the World Health Organization declared the monkeypox outbreak a global health emergency.
“The notification of deaths due to monkeypox does not change our assessment of the outbreak in Europe. We know that although the disease is self-limiting in most cases, monkeypox can cause severe complications,” said Catherine Smallwood, Senior Emergency Officer at WHO Europe. “With the continued spread of monkeypox in Europe, we will expect to see more deaths. Our goal needs to be on interrupting transmission quickly in Europe and stopping this outbreak,” she said.
On Friday, Spain’s health ministry reported 4,298 people were infected with the virus, making it the leading European country for monkeypox cases. Of that total, some 3,500 cases were of men who had had sex with other men. Only 64 were women. The ministry said 120 have needed hospital attention. Smallwood said around 8% of the monkeypox cases in Europe have required hospitalization.
Monkeypox has been endemic to parts of Africa for decades. Its leap to Europe and North America was linked by experts to two raves in Belgium and Spain. Spanish health authorities are administering 5,300 vaccines that Spain received from the joint EU vaccine purchase scheme. Health workers say that’s far fewer than the number needed to cover the at-risk groups. But the rush to buy limited vaccines by richer Western countries is putting Africa in danger of being left out. Monkeypox spreads mainly through skin-to-skin contact, but it can also be transmitted through bed sheets used by someone with monkeypox. Symptoms include fever, body aches, chills, fatigue and hives. The illness has been relatively mild in many men. But people can be contagious for weeks, and the lesions can be extremely painful.
AP Medical Writer Maria Cheng contributed to this report from London.
Ghana has announced the country’s first outbreak of Marburg virus disease, after a World Health Organization (WHO) Collaborating Centre Laboratory confirmed earlier results. The Institut Pasteur in Dakar, Senegal, received samples from each of the two patients from the southern Ashanti region of Ghana – both deceased and unrelated – who showed symptoms including diarrhea, fever, nausea and vomiting. The laboratory corroborated the results from the Noguchi Memorial Institute for Medical Research, which suggested their illness was due to a new occurrence of the Marburg virus.
One case was a 26-year-old male who checked into a hospital on 26 June 2022 and died just one day later. The second case was a 51 -year-old male who reported to the hospital on 28 June and died on the same day. WHO has been supporting a joint national investigative team in the Ashanti Region as well as Ghana’s health authorities by deploying experts, making available personal protective equipment, bolstering disease surveillance, testing, tracing contacts and working with communities to alert and educate them about the risks and dangers of the disease, and to collaborate with the emergency response teams.
“Health authorities have responded swiftly, getting a head start preparing for a possible outbreak. This is good because without immediate and decisive action, Marburg can easily get out of hand. WHO is on the ground supporting health authorities and now that the outbreak is declared, we are marshaling more resources for the response,” said Dr Matshidiso Moeti, WHO Regional Director for Africa. More than 90 contacts, including health workers and community members, have been identified and are currently being monitored.
Marburg virus is causing a highly infectious viral hemorrhagic fever and is in the same family as the more well-known Ebola virus. It is only the second time the zoonotic disease has been detected in West Africa. Guinea confirmed a single case in an outbreak that was declared over on 16 September 2021, five weeks after the initial case was detected.
Previous outbreaks and sporadic cases of Marburg in Africa have been reported in Angola, the Democratic Republic of the Congo, Kenya, South Africa and Uganda. WHO has reached out to neighboring high-risk countries and they are on alert. Marburg virus is transmitted to people from fruit bats and spreads among humans through direct contact with the bodily fluids of infected people, surfaces and materials. Illness begins abruptly, with high fever, severe headache and malaise. Many patients develop severe hemorrhagic signs within seven days. Case fatality rates have varied from 24% to 88% in past outbreaks depending on virus strain and the quality of case management. Although there are no vaccines or antiviral treatments approved to treat the virus, supportive care – rehydration with oral or intravenous fluids – and treatment of specific symptoms, improves survival. A range of potential treatments, including blood products, immune therapies and drug therapies, as well as candidate vaccines with phase I data are being evaluated.
The lineages’ rise seems to stem from their ability to infect people who were immune to earlier forms of Omicron and other variants. Like a Hollywood franchise that churns out sequel after mind-numbing sequel, Omicron is back. Mere weeks after the variant’s BA.2 lineage caused surges globally, two more Omicron spin-offs are now on the rise worldwide. First spotted by scientists in South Africa in April and linked to a subsequent rise in cases there, BA.4 and BA.5 are the newest members of Omicron’s growing family of coronavirus subvariants. They have recently been detected in dozens of countries worldwide. The BA.4 and BA.5 subvariants are spiking globally because they can spread faster than other circulating variants — mostly BA.2, which caused a surge in cases at the beginning of the year. But so far, the latest Omicron variants seem to be causing fewer deaths and hospitalizations than their older cousins — a sign that growing population immunity is tempering the immediate consequences of COVID-19 surges. Nature magazine explores what the rise of BA.4 and BA.5 means for the pandemic.
What are BA.4 and BA.5?
The two variants are more similar to BA.2 than to the BA.1 strain that kicked off most countries’ Omicron waves late last year. But BA.4 and BA.5 carry their own unique mutations, including changes called L452R and F486V in the viral spike protein that might tweak its ability to latch onto host cells and skirt some immune responses. A recent study found that BA.4 and BA.5 share an origin with earlier Omicron strains. But an unpublished analysis led by evolutionary geneticists Bette Korber and William Fischer at Los Alamos National Laboratory in New Mexico suggests that the variants are probably offshoots of BA.2 instead.
Korber and Fischer also found that many genome sequences that are classified as BA.2 in public databases are actually BA.4 or BA.5. As a result, researchers could be underestimating the variants’ ongoing rise, as well as the diversity of mutations carried by them. “It is important in this particular moment in the pandemic to get these calls right,” Korber and Fischer wrote in an e-mail to Nature.
Why are the variants on the rise globally?
Variants’ transmission advantages can result from biological changes that speed infection, for instance, allowing the virus to infect more people, more quickly. But the rise of BA.4 and BA.5 seems to stem, instead, from their capacity to infect people who were immune to earlier forms of Omicron and other variants, says Christian Althaus, a computational epidemiologist at the University of Bern. With most of the world outside Asia doing little to control SARS-CoV-2, the rise — and inevitable fall — of BA.4 and BA.5 will be driven almost entirely by population immunity, Althaus adds, with cases increasing when protection lulls and falling only when enough people have been infected. On the basis of the rise of BA.5 in Switzerland — where BA.4 prevalence is low — Althaus estimates that about 15% of people there will get infected. But countries are now likely to have distinct immune profiles because their histories of COVID-19 waves and vaccination rates differ, Althaus adds. As a result, the sizes of BA.4 and BA.5 waves will vary from place to place. “It might be 5% in some countries and 30% in others. It all depends on their immunity profile,” he says.
What impact will BA.4 and BA.5 have on society?
This, too, is likely to vary by country. Despite high case numbers, South Africa experienced only a small rise in hospitalizations and deaths during its BA.4 and BA.5 wave, says Waasila Jassat, a public-health specialist at the country’s National Institute for Communicable Diseases in Johannesburg. In a study that will soon be posted to the medRxiv preprint server, Jassat and her colleagues found that South Africa’s BA.4 and BA.5 wave led to similar rate of hospitalization but slightly lower death rate when compared with the country’s earlier Omicron wave. Both Omicron surges proved much milder, in terms of hospitalizations and deaths, than the country’s ferocious Delta wave. Outside South Africa, other countries are seeing more significant impacts from BA.4 and BA.5. In Portugal — where COVID-19 vaccination and boosting rates are very high — the levels of death and hospitalization associated with the latest wave are similar to those in the first Omicron wave (although still nothing like the impact caused by earlier variants). One explanation for the difference could be Portugal’s demographics, says Althaus. “The more elderly people you have, the more severe disease.” Jassat thinks that the nature of a country’s immunity can also explain varying outcomes. About half of adult South Africans have been vaccinated, and just 5% have taken up a booster. But this, combined with sky-high infection rates from earlier COVID-19 waves, has erected a wall of ‘hybrid immunity’ that offers strong protection against severe disease, particularly in older people, who are the most likely to have been vaccinated, she adds.
How well do vaccines work against the variants?
Lab studies consistently suggest that antibodies triggered by vaccination are less effective at blocking BA.4 and BA.5 than they are at blocking earlier Omicron strains, including BA.1 and BA.2 [2–6]. This could leave even vaccinated and boosted people vulnerable to multiple Omicron infections, scientists say. Even people with hybrid immunity, stemming from vaccination and previous infection with Omicron BA.1, produce antibodies that struggle to incapacitate BA.4 and BA.5. Research teams have attributed that to the variants’ L452R and F486V spike mutations. One explanation for this is the observation that BA.1 infection after vaccination seems to trigger infection-blocking ‘neutralizing’ antibodies that recognize the ancestral strain of SARS-CoV-2 (the one that vaccines are based on) better than they recognize Omicron variants [2,7]. “Infection with BA.1 does induce a neutralizing antibody response, but it appears to be a little bit narrower than one would expect,” leaving people susceptible to immune-escaping variants such BA.4 and BA.5, says Ravindra Gupta, a virologist at the University of Cambridge, UK.
What comes next?
That’s anybody’s guess. The parade of Omicron subvariants could continue, with new variants picking further holes in existing immunity. “Nobody can say BA.4/5 is the final variant. It is highly probable that additional Omicron variants will emerge,” says Kei Sato, a virologist at the University of Tokyo. Researchers have identified several spots on the spike protein that are currently recognized by the antibodies that are triggered by vaccination and previous infection, but that could mutate in future Omicron strains2. Another possibility is the emergence of a variant from a branch of the SARS-CoV-2 family tree different from the one that bore Omicron. Repeat Omicron infections could build broad immunity against successive lineages, creating an opening for a totally different SARS-CoV-2 variant that is unfamiliar to people’s immune responses, says Gupta. “The bar is getting higher and higher for a virus to take over.” Increasingly, scientists think that variants including Omicron and Alpha probably originated from months-long chronic SARS-CoV-2 infections, in which sets of immune-evading and transmissibility-boosting mutations can build up.
But the longer Omicron and its offshoots continue to dominate, the less likely it is that a totally new variant will emerge from a chronic infection, says Mahan Ghafari, who researches viral evolution at the University of Oxford, UK. To succeed, future variants will have to evade immunity. But they could come with other worrying properties. Sato’s team found that BA.4 and BA.5 were deadlier in hamsters than was BA.2, and better able to infect cultured lung cells6. Epidemiology studies, such as the one led by Jassat, suggest that successive COVID-19 waves are getting milder. But this trend should not be taken for granted, Sato cautions. Viruses don’t necessarily evolve to become less deadly.
It’s also unclear when the next variant will appear. BA.4 and BA.5 started emerging in South Africa only a few months after BA.1 and BA.2, a pattern now being repeated in places including the United Kingdom and United States. But as global immunity from repeated vaccination and infection builds, Althaus expects the frequency of SARS-CoV-2 waves to slow down. One possible future for SARS-CoV-2 is that it will become like the other four seasonal coronaviruses, the levels of which ebb and flow with the seasons, usually peaking in winter and typically reinfecting people every three years or so, Althaus says. “The big question is whether symptoms will become milder and milder and whether issues with long COVID will slowly disappear,” he says. “If it stays like it is now, then it will be a serious public-health problem.”
Researchers at Duke University are developing an artificial intelligence tool for toilets that would help providers improve care management for patients with gastrointestinal issues through remote patient monitoring. The tool, which can be installed in the pipes of a toilet and analyzes stool samples, has the potential to improve treatment of chronic gastrointestinal issues like inflammatory bowel disease or irritable bowel syndrome, according to a press release. When a patient flushes the toilet, the mHealth platform photographs the stool as it moves through the pipes. That data is sent to a gastroenterologist, who can analyze the data for evidence of chronic issues.
A study conducted by Duke University researchers found that the platform had an 85.1 percent accuracy rate on stool form classification and a 76.3 percent accuracy rate on detection of gross blood. “Typically, gastroenterologists have to rely on patient self-reported information about their stool to help determine the cause of their gastrointestinal health issues, which can be very unreliable,” Deborah Fisher, MD, an associate professor of medicine at Duke and one of the study’s lead authors, said in the press release.
“Patients often can’t remember what their stool looks like or how often they have a bowel movement, which is part of the standard monitoring process,” she said. “The smart toilet technology will allow us to gather the long-term information needed to make a more accurate and timely diagnosis of chronic gastrointestinal problems.”
This remote patient monitoring platform has the potential to benefit both patients and healthcare providers. Patients won’t need to do anything out of the ordinary, and gastroenterologists won’t have to try and diagnose based on a patient’s description or recollection. “An IBD flare-up could be diagnosed using the smart toilet and the patient’s response to treatment could be monitored with the technology,” Sonia Grego, PhD, a lead researcher on the study and founding director of the Duke Smart Toilet Lab, said in the release. “This could be especially useful for patients who live in long-term care facilities who may not be able to report their conditions and could help improve initial diagnosis of acute conditions,” The program makes use of something that nearly every American has at home.
It’s not the first study to target the toilet. Back in 2019, researchers at the Rochester Institute of Technology developed a sensor-embedded toilet seat. The toilet seat was designed to allow care providers to remotely monitor a patient’s weight, heart rate, blood pressure, blood oxygenation levels, and stroke volume. Similar to the AI tool for toilet pipes, RIT’s smart toilet seat presents the ability to catch patients’ symptoms early enough before they could lead to something more severe.
With gastroenterology appearing on Doximity’s list of specialties that are least engaged in telehealth, this artificial intelligence software, once available to the public, could change minds. Gastroenterology usually requires in-person and hands-on interaction but using remote monitoring in this way might prove to be even more beneficial.
Fast, high-throughput methods for measuring the level and duration of protective immune responses to SARS-CoV-2 are needed to anticipate the risk of breakthrough infections. A research team now reports the development of two quantitative PCR assays for SARS-CoV-2-specific T cell activation. The assays are rapid, internally normalized and probe-based: qTACT requires RNA extraction and dqTACT avoids sample preparation steps. Both assays rely on the quantification of CXCL10 messenger RNA, a chemokine whose expression is strongly correlated with activation of antigen-specific T cells. On re-stimulation of whole-blood cells with SARS-CoV-2 viral antigens, viral-specific T cells secrete IFN-γ, which stimulates monocytes to produce CXCL10. CXCL10 mRNA can thus serve as a proxy to quantify cellular immunity. These types of assays may allow large-scale monitoring of the magnitude and duration of functional T cell immunity to SARS-CoV-2, thus helping to prioritize revaccination strategies in vulnerable populations. The T cell response to SARS-CoV-2 is detected using a PCR assay on whole blood.
The origins of the deadly Black Death have been discovered more than 600 years after it entered the human population, scientists have said. The medieval, bubonic plague was first recorded in the 14th century and was the start of a near 500-year-long wave of killer diseases termed the Second Plague Pandemic. The Black Death killed millions and was considered one of the largest infectious disease catastrophes in human history. Despite years of research, the geographic and chronological origin of the disease remained a mystery. But now researchers believe the Black Death first originated in North Kyrgyzstan in the late 1330s. The team, from Scotland’s University of Stirling and Germany’s Max Planck Institute and University of Tubingen, analysed ancient DNA (aDNA) taken from the teeth of skeletons discovered in cemeteries near Lake Issyk Kul in the Tian Shan region of Kyrgyzstan.
They were drawn to these sites after identifying a huge spike in the number of burials there in 1338 and 1339, according to University of Stirling historian Dr Philip Slavin, who helped make the discovery. The team found the cemeteries, at Kara-Djigach and Burana, had already been excavated in the late 1880s, with about 30 skeletons taken from the graves, but were able to trace them and analyse DNA taken from the teeth of seven individuals.
The sequencing, which determines the DNA structure, showed three individuals carried Yersinia pestis, a bacterium which is linked to the beginning of the Black Death outbreak before it arrived in Europe. ‘Our study puts to rest one of the biggest and most fascinating questions in history and determines when and where the single most notorious and infamous killer of humans began,’ Dr Slavin said.
Monkeypox, a less-lethal relative of smallpox that’s normally found in Africa, has recently been spreading in some western countries, largely among gay men, and is mainly transmitted through intimate contact when people are symptomatic. More than 700 cases have been seen globally, said Jennifer McQuiston, deputy director of the CDC’s division of high-consequence pathogens and pathology. Supplies available in the Strategic National Stockpile are sufficient to combat the current outbreak, the agency said. Vaccines available for use against monkeypox are Jynneos from Bavarian Nordic A/S and Emergent BioSolutions Inc.’s ACAM2000. Both are prioritized for use in high-risk contacts of patients. Through contact-tracing efforts, officials have identified hundreds of people who may have been exposed to the virus in the US, but so far only 20 were determined to be high-risk.
The rapidly spreading monkeypox outbreak constitutes a global health emergency, the World Health Organization's highest alert level, WHO director-general Tedros Adhanom Ghebreyesus declared just recently. First identified in monkeys, the virus is transmitted chiefly through close contact with an infected person. Until this year, the viral disease has rarely spread outside Africa where it is endemic. But reports of a handful of cases in the United Kingdom in early May signalled that the outbreak had moved into Europe. Cases have since ballooned to more than 16,000 from than 75 countries. Five deaths, all of which occurred in Africa, have been reported so far.
HOW DANGEROUS ARE MONKEYPOX?
The monkeypox virus typically causes mild symptoms including fever, aches and pus-filled skin lesions. People tend to recover within two to four weeks, according to the WHO. Anyone can spread the virus, but the current outbreak outside of Africa is concentrated almost exclusively among men who have sex with men. Monkeypox spreads primarily via intimate skin-to-skin contact, usually with someone who has an active rash, as well as via contact with contaminated clothes or bedding. It is not as easily transmitted as the SARS-CoV-2 virus that spurred the COVID-19 pandemic. "COVID is spread by respiratory route and is highly infectious. This doesn't appear to be the case with the monkeypox," said Dr. Martin Hirsch of Massachusetts General Hospital. The risk of monkeypox is moderate globally, except in the Europe, where the WHO has deemed the risk as high.
Health officials from several countries had urged the WHO to label monkeypox a public health emergency of international concern due to the quick escalation of cases and concerns it may become endemic in more countries. The emergency declaration aims to spur global action and collaboration on everything from testing to the production and distribution of vaccines and treatments. The fatality rate in preceding monkeypox outbreaks in Africa of the strain currently spreading has been around 1%, but so far this outbreak appears to be less lethal in the non-endemic countries, many of which have stronger healthcare infrastructure. Scientists are trying to determine what caused the initial spate of cases and whether anything about the virus has changed. Increased global travel as well as climate change have generally accelerated the emergence and spread of viruses, experts say. Infectious disease experts say that years of financial neglect has left sexual health clinics - who are on the frontline of the current monkeypox response - ill-prepared to curb further spread.
PROTECTIVE MEASURES
Health officials say that people should avoid close personal contact with someone who has a illness presenting with a distinctive rash or who is otherwise unwell. People who suspect they have monkeypox should isolate and seek medical care.
Health officials have also been offering monkeypox vaccines to high-risk individuals and those that have recently been in close contact with an infected person.
An older vaccine, currently made by Emergent Biosolutions (EBS) , is called ACAM2000, but its uptake has been limited due to a severe side-effect warning. Bavarian Nordic (BVNKF) says it can produce 30 million doses of its vaccines - including the monkeypox one - each year, and has tapped a U.S.-based contract manufacturer to increase monkeypox vaccine capacity.
TREATMENT
Monkeypox symptoms often resolve on their own within weeks. Patients may receive extra fluids and additional treatment for secondary bacterial infections. An antiviral agent called tecovirimat - branded as TPOXX and made by SIGA Technologies (SIGA) - has U.S. and EU approval for smallpox, while its European approval also includes monkeypox and cowpox.
(Reporting by Natalie Grover in London and Michael Erman in New Jersey; Editing by Michele Gershberg, William Maclean)
New research shows that people with extreme look-alike faces share common genotypes, but differ in their DNA methylation and microbiome landscapes.
“For decades, the existence of individuals who resemble each other without having any family ties has been described as a proven fact, but only in anecdotal terms and without any scientific justification,” said senior author Dr. Manel Esteller, a researcher at the Josep Carreras Leukaemia Research Institute. “The widespread use of the Internet and social networks for image-sharing has meant that we are now able to identify and study such people.”
In their study, Dr. Esteller and his colleagues set out to characterize a set of look-alike humans on a molecular level. To do so, they recruited human doubles from the photographic work of François Brunelle, a Canadian artist who has been obtaining worldwide pictures of look-alikes since 1999. They obtained headshot pictures of 32 look-alike pairs. They determined an objective measure of likeness for the pairs using three different facial recognition algorithms. In addition, the participants completed a comprehensive biometric and lifestyle questionnaire and provided saliva DNA for multiomics analysis. “This unique set of samples has allowed us to study how genomics, epigenomics, and microbiomics can contribute to human resemblance,” Dr. Esteller said.
Overall, the results revealed that these individuals share similar genotypes, but differ in their DNA methylation and microbiome landscapes. Half of the look-alike pairs were clustered together by all three algorithms. Genetic analysis revealed that 9 of these 16 pairs clustered together, based on 19,277 common single-nucleotide polymorphisms. Moreover, physical traits such as weight and height, as well as behavioral traits such as smoking and education, were correlated in look-alike pairs.
Taken together, the results suggest that shared genetic variation not only relates to similar physical appearance, but may also influence common habits and behavior. “Our findings provide a molecular basis for future applications in fields such as biomedicine, evolution, and forensics,” Dr. Esteller said. “It would be very interesting to follow up the potential application in forensics, using the genome of unknown people to prepare bioinformatic strategies to reconstruct the face from DNA. And in medicine, we may be able to deduce the genome of a person from facial analysis and hence use this as a pre-screening tool to detect the presence of genetic mutations associated with disease and apply preventive strategies at an early stage. Some previous studies have compared the genome of individuals with face traits, but in the general population,” he added.
At the moment of fertilization, the genes in the fertilizing sperm and egg are switched off. For a new embryo to develop, they must be switched on—but how?
The answer is unknown, which seems remarkable for such a fundamental event at the beginning of embryonic life, and for decades, it was thought that genes in human embryos were silent for several days after fertilization. Recent findings, however, show they are switched on almost immediately.
Now that this is recognized, scientists have produced perhaps the first model of how the switch works to initiate embryonic development.
The model has been developed by Professor Tony Perry from the Department of Life Sciences at the University of Bath, with colleagues Dr. Maki Asami, also at Bath, and Dr. Brian Lam and Professor Giles Yeo at the University of Cambridge. Their work is published in this month's Trends in Cell Biology.
The model suggests that the myriad events that accompany fertilization act synergistically to switch on embryo gene expression. To emphasize that the switch occurs at the start of development, the piece borrows from "Under Milk Wood," by Dylan Thomas: "To begin at the beginning."
Professor Perry and colleagues have extended the model to predict something quite startling: that the switch that begins embryo formation may also initiate cancer.
The start of cancer and embryonic life
Often, by the time cancer is diagnosed, the disease is already advanced and in some cases, time is running out. We know little about how many cancers begin. It may be like lighting the blue touch paper of a firework, which is long gone when by the time see the sparkling array of colors. How can we discover the nature of this fuse, so that as soon as it is lit, we can detect it and put it out before cancer develops?
This is where a better understanding of the beginning of embryonic life fits in. The genes in an embryo need a switch to get going after fertilization, like the touch paper in cancer.
Professor Perry and his team have previously found that the switch in embryos involves genes, called oncogenes, that play key roles in cancer.
The immune system is highly complex and distributed throughout an organism, with hundreds to thousands of cell states existing in parallel with diverse molecular pathways interacting in a highly dynamic and coordinated fashion. Although the characterization of individual genes and molecules is of the utmost importance for understanding immune-system function, high-throughput, high-resolution omics technologies combined with sophisticated computational modeling and machine-learning approaches are creating opportunities to complement standard immunological methods with new insights into immune-system dynamics. Like systems immunology itself, immunology researchers must take advantage of these technologies and form their own diverse networks, connecting with researchers from other disciplines.
This Review is an introduction and ‘how-to guide’ for immunologists with no particular experience in the field of omics but with the intention to learn about and apply these systems-level approaches, and for immunologists who want to make the most of interdisciplinary networks. The explosion of single-cell and systems approaches in immunology risks leaving the uninitiated behind. This guide to systems immunology is designed for immunologists who want an introduction to the area.
Systems immunology provides a holistic understanding of the immune system, spanning single immunological components and pathways to form cross-scale networks. Unlike reductionist approaches aimed at understanding individual parts, systems immunology aims to understand properties of individual parts working together—a challenge requiring specialized methodologies1,2.
During the past century, many successful experimental strategies have been developed that were instrumental in defining cell types and cellular states within the immune system to reveal major molecular and functional components of the immune system and to establish causal relationships for transcriptional and functional cascades that drive immune activation (see Figure). For two decades, high-throughput, high-resolution technologies from the omics field have revolutionized our understanding of immunology and enabled the simultaneous assessment of hundreds to thousands of cellular, functional and molecular parameters with continuously increasing throughput and decreasing turn-around times.
Sequencing-based technologies are used to assess genomic, transcriptomic and epigenomic information, and sophisticated technologies in proteomics, metabolomics, microbiomics and lipidomics have been introduced to immunological research. In the past decade, single-cell sequencing technologies have emerged, with single-cell transcriptomics leading the way3.
In this how-to guide, the authors provide a brief introduction in the use and integration of omics technologies in systems immunology and explain how current single-cell-level omics technologies can be applied to immunological questions in model systems and increasingly in human immunology and clinical trials for immune-mediated diseases. They focus on the use of transcriptomic technologies in systems immunology, particularly on single-cell assays, as mRNA constitutes the first functional and relatively easily accessible readout of the genome; as such, it can serve as a surrogate to bridge genomic and functional phenotypes to enable the description and prediction of causal relationships and effectors of immune-cell function.
The human oral cavity is a hotspot of numerous, mostly unexplored, viruses that are important for maintaining oral health and microbiome homeostasis. A research team now analyzed 2,792 publicly available oral metagenomes and proposed the Oral Virus Database (OVD) comprising 48,425 non-redundant viral genomes (≥5 kbp). The OVD catalog substantially expands the known phylogenetic diversity and host specificity of oral viruses, allowing for enhanced delineation of some underrepresented groups such as the predicted Saccharibacteria phages and jumbo viruses.
Comparisons of the viral diversity and abundance of different oral cavity habitats suggests strong niche specialization of viromes within individuals. The virome variations in relation to host geography and properties is of high importance, especially the age-dependent viral compositional signatures in saliva. Overall, the viral genome catalog describes the architecture and variability of the human oral virome, while offering new resources and insights for current and future studies.
While the threat of COVID-19 still lingers two years on from the start of the pandemic and the outbreak of monkeypox is far from being contained, a new virus is looming over the horizon. Again coming from China. Researchers are monitoring the spread of the novel Langya henipavirus (LayV) in China, where dozens of cases have already been reported. The virus was first detected in 2018 in the northeastern provinces of Shandong and Henan but was only officially identified last week after China experienced a sudden surge in cases, now up to a total of 35.
According to a new study by the Beijing Institute of Microbiology and Epidemiology published last week, the Langya virus cases were identified after several patients experiencing a fever and reporting a history of animal exposure in eastern China were examined by health officials as part of a health surveillance project. After identifying the Langya virus in one of the patient’s throat swabs, the researchers found the presence of the virus in 35 people - mostly farmers - in the Shandong and Henan provinces.
What is the Langya virus?
The Langya virus belongs to the same family as the deadly Nipah and Hendra viruses, the henipavirus family. According to the World Health Organization (WHO), this family of viruses is highly dangerous, with Nipah being estimated to have a fatality rate between 40 to 75 per cent - much higher than the death rate reported for COVID-19. It’s unclear how dangerous the Langya virus could be to humanity, as all the patients who contracted the virus in China so far experienced mild flu-like symptoms, and there were no related fatalities reported.
The henipavirus viruses are naturally harboured by pteropid fruit bats (flying foxes) and microbats of several species, according to a Chinese study from 2008, but other studies have found other henipaviruses in bats, rodents, and shrews.
What are its symptoms of Langya virus?
The most common symptom of the Langya virus appears to be a fever (experienced by all patients), but those infected with the virus also reported fatigue (54 per cent of patients), loss of appetite (50 per cent), muscle pain (46 per cent), cough (50 per cent), nausea (38 per cent), headache and vomiting (35 per cent) after contracting the virus. Several also developed blood cell abnormalities and signs of liver and kidney damage, but none of the infected patients died.
How does Langya virus get transmitted?
The Langya virus is a zoonotic infection - meaning the virus is spread from animals to humans. But as none of the patients in China had close contact with each other, experts believe that the transmission of the virus from animal to human is still sporadic. Researchers in China are still trying to find exactly what animals were involved in the virus transmission, but they suspect shrews might be involved.
Scientists at the Beijing Institute of Microbiology and Epidemiology found that among 25 species of wild small animals surveyed, the genome of the virus was predominantly detected in shrews, with 27 per cent of 262 shrews examined found to be harbouring the virus. This could potentially mean that the tiny animal may be a natural reservoir of the Langya virus.
While it’s certain that the virus was transmitted from an animal to a human, researchers are still unsure about whether human-to-human transmission is possible at all. According to the Chinese scientists, contact tracing of 9 patients with 15 close-contact family members revealed no transmission of the virus. But the same researchers believe the sample analysed is too small to determine whether human-to-human transmission is possible.
Is there a vaccine or treatment?
There are currently no vaccines for humans for henipaviruses, though one against Hendra virus exists for horses. No effective anti-viral treatment is known either other than treating the symptoms.
Ultrasound is a convenient, noninvasive tool for doctors to look inside the human body and check out a person’s liver, heart and other internal structures, as well as the developing fetus of a pregnant patient. But today’s ultrasound imaging technology is large and technical, so it’s only available in healthcare facilities and must be operated by highly trained technicians. Plus, patients, who take time out of their schedules to go to an appointment, have to be covered in a sticky gel.
Now, researchers say they’ve developed an innovative solution to some of these challenges. Engineers at the Massachusetts Institute of Technology have unveiled a new adhesive ultrasound patch that’s about the size of a postage stamp and can provide continuous imaging of the body’s inner workings for up to 48 hours. The scientists shared their new technology in a paper published last week in the journal Science.
“We believe we’ve opened a new era of wearable imaging,” says Xuanhe Zhao, a mechanical engineer at MIT and one of the study’s authors, in a statement. “With a few patches on your body, you could see your internal organs.” In the past, engineers developing wearable ultrasound technologies have run into issues with image quality and flexibility, but the new MIT stickers seem to have struck the right balance. To create the small devices, which are about three millimeters thick and two square centimeters in size, engineers combined rigid transducers with a stretchy, sticky layer that encapsulates a layer of water-based hydrogel.
Moves by rich countries to buy large quantities of monkeypox vaccine, while declining to share doses with Africa, could leave millions of people unprotected against a more dangerous version of the disease and risk continued spillovers of the virus into humans, public health officials are warning. Critics fear a repeat of the catastrophic inequity problems seen during the coronavirus pandemic.
“The mistakes we saw during the COVID-19 pandemic are already being repeated,” said Dr. Boghuma Kabisen Titanji, an assistant professor of medicine at Emory University. While rich countries have ordered millions of vaccines to stop monkeypox within their borders, none have announced plans to share doses with Africa, where a more lethal form of monkeypox is spreading than in the West.
To date, there have been more than 22,000 monkeypox cases reported in nearly 80 countries since May, with about 75 suspected deaths in Africa, mostly in Nigeria and Congo. On Friday, Brazil and Spain reported deaths linked to monkeypox, the first reported outside Africa. Spain reported a second monkeypox death Saturday. “The African countries dealing with monkeypox outbreaks for decades have been relegated to a footnote in conversations about the global response,” Titanji said.
Scientists say that, unlike campaigns to stop COVID-19, mass vaccinations against monkeypox won’t be necessary. They think targeted use of the available doses, along with other measures, could shut down the expanding epidemics that were recently designated by the World Health Organization as a global health emergency. Yet while monkeypox is much harder to spread than COVID-19, experts warn if the disease spills over into general populations — currently in Europe and North America it is circulating almost exclusively among gay and bisexual men — the need for vaccines could intensify, especially if the virus becomes entrenched in new regions.
Recently, the Africa Centers for Disease Control and Prevention called for the continent to be prioritized for vaccines, saying it was again being left behind. “If we’re not safe, the rest of the world is not safe,” said Africa CDC’s acting director, Ahmed Ogwell. Although monkeypox has been endemic in parts of Africa for decades, it mostly jumps into people from infected wild animals and has not typically spread very far beyond the continent. Experts suspect the monkeypox outbreaks in North America and Europe may have originated in Africa long before the disease started spreading via sex at two raves in Spain and Belgium. Currently, more than 70% of the world’s monkeypox cases are in Europe, and 98% are in men who have sex with men.
The hallmarks of cancer conceptualization is a heuristic tool for distilling the vast complexity of cancer phenotypes and genotypes into a provisional set of underlying principles. As knowledge of cancer mechanisms has progressed over the years, other facets of the disease have emerged as potential refinements. Herein, the prospect is raised that phenotypic plasticity and disrupted differentiation is a discrete hallmark capability, and that non-mutational epigenetic reprogramming and polymorphic microbiomes both constitute distinctive enabling characteristics that facilitate the acquisition of hallmark capabilities. Additionally, senescent cells, of varying origins, may be added to the roster of functionally important cell types in the tumor microenvironment.
Cancer is daunting in the breadth and scope of its diversity, spanning genetics, cell and tissue biology, pathology, and response to therapy. Ever more powerful experimental and computational tools and technologies are providing an avalanche of “big data” about the myriad manifestations of the diseases that cancer encompasses. The integrative concept embodied in the hallmarks of cancer is helping to distill this complexity into an increasingly logical science, and the provisional new dimensions presented in this perspective may add value to that endeavor, to more fully understand mechanisms of cancer development and malignant progression, and apply that knowledge to cancer medicine.
The first COVID-19 vaccine outside a clinical trial setting was administered on Dec 8, 2020. To ensure global vaccine equity, vaccine targets were set by the COVID-19 Vaccines Global Access (COVAX) Facility and WHO. However, due to vaccine shortfalls, these targets were not achieved by the end of 2021. We aimed to quantify the global impact of the first year of COVID-19 vaccination programs.
A mathematical model of COVID-19 transmission and vaccination was separately fit to reported COVID-19 mortality and all-cause excess mortality in 185 countries and territories. The impact of thr COVID-19 vaccination initiative was determined by estimating the additional lives lost if no vaccines had been distributed. We also estimated the additional deaths that would have been averted had the vaccination coverage targets of 20% set by COVAX and 40% set by WHO been achieved by the end of 2021.
Findings
Based on official reported COVID-19 deaths, we estimated that vaccinations prevented 14·4 million (95% credible interval [Crl] 13·7–15·9) deaths from COVID-19 in 185 countries and territories between Dec 8, 2020, and Dec 8, 2021. This estimate rose to 19·8 million (95% Crl 19·1–20·4) deaths from COVID-19 averted when we used excess deaths as an estimate of the true extent of the pandemic, representing a global reduction of 63% in total deaths (19·8 million of 31·4 million) during the first year of COVID-19 vaccination. In COVAX Advance Market Commitment countries, we estimated that 41% of excess mortality (7·4 million [95% Crl 6·8–7·7] of 17·9 million deaths) was averted. In low-income countries, we estimated that an additional 45% (95% CrI 42–49) of deaths could have been averted had the 20% vaccination coverage target set by COVAX been met by each country, and that an additional 111% (105–118) of deaths could have been averted had the 40% target set by WHO been met by each country by the end of 2021.
Interpretation
COVID-19 vaccination has substantially altered the course of the pandemic, saving tens of millions of lives globally. However, inadequate access to vaccines in low-income countries has limited the impact in these settings, reinforcing the need for global vaccine equity and coverage.
Published in The Lancet Infectious Diseases (June 23, 2022):
Researchers at Baylor College of Medicine, Stanford School of Medicine and collaborating institutions report today in the journal Nature that they have identified a molecule in the blood that is produced during exercise and can effectively reduce food intake and obesity in mice. The findings improve our understanding of the physiological processes that underlie the interplay between exercise and hunger.
"Regular exercise has been proven to help weight loss, regulate appetite and improve the metabolic profile, especially for people who are overweight and obese," said co-corresponding author Dr. Yong Xu, professor of pediatrics- nutrition and molecular and cellular biology at Baylor. "If we can understand the mechanism by which exercise triggers these benefits, then we are closer to helping many people improve their health."
"We wanted to understand how exercise works at the molecular level to be able to capture some of its benefits," said co-corresponding author Jonathan Long, MD, assistant professor of pathology at Stanford Medicine and an Institute Scholar of Stanford ChEM-H (Chemistry, Engineering & Medicine for Human Health). "For example, older or frail people who cannot exercise enough, may one day benefit from taking a medication that can help slow down osteoporosis, heart disease or other conditions."
Xu, Long and their colleagues conducted comprehensive analyses of blood plasma compounds from mice following intense treadmill running. The most significantly induced molecule was a modified amino acid called Lac-Phe. It is synthesized from lactate (a byproduct of strenuous exercise that is responsible for the burning sensation in muscles) and phenylalanine, an amino acid that is one of the regular building blocks of proteins.
In mice with diet-induced obesity (fed a high-fat diet), a high dose of Lac-Phe suppressed food intake by about 50% compared to control mice over a period of 12 hours without affecting their movement or energy expenditure. When administered to the mice for 10 days, Lac-Phe reduced cumulative food intake and body weight (owing to loss of body fat) and improved glucose tolerance. The researchers also identified an enzyme called CNDP2 that is involved in the production of Lac-Phe and showed that mice lacking this enzyme did not lose as much weight on an exercise regime as a control group on the same exercise plan.
Interestingly, the team also found robust elevations in plasma Lac-Phe levels following physical activity in racehorses and humans. Data from a human exercise cohort showed that sprint exercise induced the most dramatic increase in plasma Lac-Phe, followed by resistance training and then endurance training. "This suggests that Lac-Phe is an ancient and conserved system that regulates feeding and is associated with physical activity in many animal species," Long said.
Rabies virus kills a shocking 59,000 people each year, many of them children. Some victims, especially kids, don’t realize they’ve been exposed until it is too late. For others, the intense rabies treatment regimen is out of the question: treatment is not widely available and the average $3,800 expense poses unthinkable economic burden for most people around the world.
Rabies vaccines, rather than treatments, are much more affordable and easier to administer. But those vaccines also come with a massive downside: “Rabies vaccines don’t provide lifelong protection. You have to get your pets boosted every year to three years,” says LJI Professor Erica Ollmann Saphire, Ph.D.. “Right now, rabies vaccines for humans and domestic animals are made from killed virus. But this inactivation process can cause the molecules to become misshapen—so these vaccines aren’t showing the right form to the immune system. If we made a better shaped, better structured vaccine, would immunity last longer?”
Saphire and her team, in collaboration with a team led by Institut Pasteur Professor Hervé Bourhy, DVM, PhD., may have discovered the path to better vaccine design. In a new study, published in Science Advances, the researchers share one of the first high-resolution looks at the rabies virus glycoprotein in its vulnerable “trimeric” form.
“The rabies glycoprotein is the only protein that rabies expresses on its surface, which means it is going to be the major target of neutralizing antibodies during an infection,” says LJI Postdoctoral Fellow Heather Callaway, Ph.D., who serves as the study’s first author.
“Rabies is the most lethal virus we know. It is so much a part of our history—we’ve lived with its specter for hundreds of years,” adds Saphire, who also serves as LJI’s President and CEO. “Yet scientists have never observed the organization of its surface molecule. It is important to understand that structure to make more effective vaccines and treatments—and to understand how rabies and other viruses like it enter cells.”
“This understanding is crucial for designing better vaccines and for developing treatments to cure rabid patients,” says Bourhy.
The number of reported cases using viruses to treat deadly Mycobacteriuminfections just went up by a factor of five. In a new study, a team led by researchers from the University of Pittsburgh and the University of California San Diego report 20 new case studies on the use of the experimental treatment, showing the therapy’s success in more than half of the patients. The number of reported cases using viruses to treat deadly Mycobacteriuminfections just went up by a factor of five. In a new study, a team led by researchers from the University of Pittsburgh and the University of California San Diego report 20 new case studies on the use of the experimental treatment, showing the therapy’s success in more than half of the patients. It’s the largest ever set of published case studies for therapy using bacteria-killing viruses known as bacteriophages, providing unprecedented detail on their use to treat dire infections while laying the groundwork for a future clinical trial. “Some of those are spectacular outcomes, and others are complicated,” said Graham Hatfull, the Eberly Family Professor of Biotechnology in the Kenneth P. Dietrich School of Arts and Sciences at the University of Pittsburgh. “But when we do 20 cases, it becomes much more compelling that the phages are contributing to favorable outcomes — and in patients who have no other alternatives.” Each patient treated in the study was infected with one or more strains of Mycobacterium, a group of bacteria that can cause deadly, treatment-resistant infections in those with compromised immune systems or with the lung disorder cystic fibrosis.
In 2019, Hatfull led a team showing the first successful use of phages to treat one of these infections. “For clinicians, these are really a nightmare: They’re not as common as some other types of infections, but they’re amongst some of the most difficult to treat with antibiotics,” said Hatfull. “And especially when you take these antibiotics over extended periods of time, they’re toxic or not very well-tolerated.” Last month, the University of Pittsburgh researchers were involved in two new case studies successfully treating patients in collaboration with colleagues at National Jewish Health and Harvard University. But those reports represent only a fraction of the cases the team has been involved in behind the scenes. Since 2019, Hatfull and his lab have fielded requests from more than 200 clinicians looking for treatments for their patients, working with them to find phages that could be effective against the particular strain of bacteria infecting each patient. The newest paper, published today in the journal Clinical Infectious Diseases alongside collaborators from 20 institutions, dramatically scales up the body of published evidence on the effectiveness of the therapy. “These are incredibly brave physicians, jumping off the ledge to do an experimental therapy to try to help patients who have no other options,” said Hatfull. “And each of these collaborations represents a marker that can move the field forward.” Looking at measures of patient health and whether samples from the patient still showed signs of Mycobacterium infections, the team found that the therapy was successful in 11 out of 20 cases. No patients showed any adverse reactions to the treatment. In another five patients the results of the therapy were inconclusive, and four patients showed no improvement. According to Hatfull, even these apparent failures are key to making the therapy available to more patients. “In some ways, those are the most interesting cases,” he said. “Understanding why they didn’t work is going to be important.” Several unexpected patterns emerged from the case studies. In 11 cases, researchers were unable to find more than one kind of phage that could kill the patient’s infection, even though standard practice would be to inject a cocktail of different viruses so the bacteria would be less likely to evolve resistance.
“If you’d asked me whether that was a good idea three years ago, I would have had a fit,” Hatfull said. “But we just didn’t observe resistance, and we didn’t see a failure of treatment from resistance even when using only a single phage.” In addition, the team saw that some patients’ immune systems attacked the viruses, but only in a few cases did their immune systems render the virus ineffective. And in some instances, the treatment was still successful despite such an immune reaction. The study paints an encouraging picture for the therapy, said Hatfull, and one that opens the possibility for new phage regimens that clinicians could use to maximize the treatment’s chance of success. Along with the study’s significance to patients facing Mycobacterium infections, it also represents a substantial advance for the wider field of phage therapy. A concern in some corners is that researchers may be only publishing case studies in which phage therapy is successful. “A series of consecutive case studies, where we’re not cherry-picking, is a much more transparent way of looking to see what works and what doesn’t,” said Hatfull. “This adds considerable weight to the sense that the therapy is safe.” The lab continues to provide phages for more patients — while at the same time conducting research to widen the funnel that narrowed an initial group of 200 patients down to 20, in the hopes of providing treatment to more people with no other options. “We’ve not yet figured out how to find or engineer phages that will get every strain of bacteria in these patients,” said Hatfull. “That represents one of the major challenges ahead.”
Research cited published in Clinical Infectious Diseases (June 9, 2022):
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