Brazil is seeing an unprecedented surge in dengue, a viral disease that can cause excruciating pains and is sometimes fatal. An unusually hot rainy season, along with rapid, unplanned urbanization, have fuelled its spread this year. Health officials have reported more than 1 million suspected cases in January and February, four times as many as in the same period in 2023, and hundreds have died. But the country has far too little vaccine to protect its population. The government cut a deal last year with the Japanese manufacturer Takeda Pharmaceuticals, but it will receive doses to fully vaccinate only 3.3 million people this year, in a country of more than 220 million. www.science.org/content/article/dengue-raging-brazil-promising-local-vaccine-least-year-away?
A locally produced vaccine could prove to be better and cheaper, but it will be available in 2025 at the earliest. “We are frenetically working against time,” says Esper Kallas, director of the Butantan Institute, which is developing the shot. Brazil has embraced new control strategies for the Aedes aegypti mosquitoes that transmit dengue, but scaling them up will take time as well.
The dengue virus, which comes in four different varieties, or serotypes, can cause high fevers, headaches, painful joints and muscles, and rash. In some cases it can lead to severe abdominal pain, bleeding, and death. This typically occurs when a person is infected for the second time with a different serotype, in a phenomenon called antibody-dependent enhancement. Brazil’s Ministry of Health expects more than 4 million dengue cases this year, which would be a record. Other South American countries are seeing an uptick in cases as well.
Takeda’s two-dose vaccine, named Qdenga and designed to protect against all four serotypes, contains an attenuated, or weakened, strain of one serotype as a “backbone” with genes from the other three added to it. In trials, the vaccine had an overall efficacy of 64.2% in people who had dengue before and 53.5% in those who were never exposed to the virus.
In February, Brazil’s public health service (SUS) started a campaign to vaccinate 10- and 11-year-old children, the group most at risk of hospitalization from dengue. But because Brazil is only expecting 6.6 million Qdenga doses this year, SUS is only targeting 521 of Brazil’s municipalities, fewer than 10% of the total. Vaccine uptake has been modest: Only 32% of eligible children in the Federal District, and only 18% in Rio de Janeiro, have received their first shot.
The vaccine made in Brazil, named Butantan-DV, might reach more people. Originally developed by the U.S. National Institutes of Health, it contains live strains of all four dengue serotypes, attenuated by the removal of a small genome fragment. It’s a single-dose vaccine, which is “always preferred,” says Gabriela Paz-Bailey, a dengue researcher at the U.S. Centers for Disease Control and Prevention, because some people never get their second dose.
In a trial in Brazil among 16,235 people between ages 2 and 59, published last month by The New England Journal of Medicine, the vaccine offered 89.5% and 69.6% protection, respectively, against two serotypes, DEN-1 and DEN-2, during the first 2 years after immunization. There are no efficacy data on DEN-3 and DEN-4 because no cases were seen in the study, which is continuing.
Even after its introduction, the vaccine will be watched closely. The first approved dengue vaccine, produced by Sanofi, did appear to trigger antibody dependent enhancement, like the virus itself, in children in the Philippines who never had dengue before and became infected after vaccination. The country has since banned the vaccine. So far, there are no clear signs of the phenomenon with either the Takeda and Butantan shots, but it will take more follow-up to be sure.
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Every year, millions of tissue and organ samples from animal experiments go to waste, left forgotten in the back of lab freezers or destroyed to free up space. Scientists in Spain are hoping a new online tool could help. Called aRukon and set to launch globally this year, the virtual marketplace will allow researchers to sell unused animal samples to other labs, potentially cutting waste and saving animal lives. https://www.science.org/content/article/online-marketplace-animal-samples-could-cut-waste-and-save-lives?
aRukon is the brainchild of Javier Burgos, a biomedical researcher at Jaume I University. He says 20 years of researching neurogenerative diseases taught him just how “tedious, complicated, and expensive” animal experiments can be. And a lot of his hard work is ultimately tossed out, even though, Burgos says, it could be of use to other researchers studying the same devastating diseases. “I have often found myself in front of an open freezer, faced with the challenging decision of determining which samples to discard,” he says. “Panic sets in when the freezer reaches full capacity.”
Burgos believes the platform will help drastically reduce the costs of animal work and open up access to samples for labs that don’t normally conduct such experiments. It can cost thousands of euros to run a single animal experiment, he notes, and it takes months to obtain ethical approval. “Why expend that sum when I can acquire a sample within days and at a significantly lower cost?”
He also hopes sharing unwanted samples will reduce overall animal use, particularly if the platform gains traction around Europe: “Each match between researchers on our platform is a life saved for an animal.” aRukon’s approach is consistent with both Spanish and European legislation that requires researchers to minimize the number of animals they use, Montoliu notes.
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A non-profit that seeks to repurpose approved drugs for new indications will receive more than $48 million from the U.S. Advanced Research Projects Agency for Health to supercharge its work, the agency said on 28 February. Every Cure plans to use Artificial Intelligence to predict the power of more than 3,000 approved drugs against more than 10,000 rare diseases, most without effective treatments. www.science.org/content/article/news-glance-methane-hunting-satellite-elsevier-s-earnings-and-protecting-kinsey?
The Philadelphia-based non-profit was cofounded by University of Pennsylvania immunologist David Fajgenbaum, who a decade ago identified a treatment—sirolimus, which prevents organ rejection—for his own rare, life-threatening immune condition, Castleman disease.
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In a study reported on 25 February in The New England Journal of Medicine, researchers tested a drug called omalizumab in 3 adults and 177 children aged between one and 17 who were severely allergic to peanuts and at least two other foods. After about four months of treatment, 67% of those who received the drug were able to ingest the equivalent of two or three peanuts without it causing a significant reaction, compared with just 7% of those who received a placebo. Omalizumab seemed to be similarly effective at raising participants’ tolerance to other foods they were allergic to, including cashews, milk and eggs. https://www.nature.com/articles/d41586-024-00586-8?
On the basis of this evidence, the US Food and Drug Administration (FDA) approved omalizumab as a treatment for food allergies earlier this month.
Omalizumab, known commercially as Xolair, isn’t a new drug: the FDA approved it for the treatment of asthma in 2003 and, later, for chronic hives and for nasal polyps that occur with certain breathing conditions.
The drug is a monoclonal antibody designed to attack a specific type of human antibody known as IgE. Like other antibodies, IgE is produced by immune cells when the body perceives a specific protein to be a threat. But if that protein is an allergen, such as peanut protein or cat dander, IgE causes unnecessary inflammation that can prompt the body to go into anaphylactic shock. Omalizumab recognizes all kinds of IgE antibody — including those that attack air pollutants in asthma and those that attack food proteins. Researchers have long suspected that the drug could also be useful for treating food allergies.
The drug must be injected once every two to four weeks, depending on the allergic person’s weight and the severity of their reaction, and can cost more than US$1,400 per injection.
The FDA has approved only one other treatment for a food allergy — a peanut-protein powder called Palforzia. Approved in 2020 for children aged four years and over, Palforzia works by allowing the immune system to build up a tolerance to peanuts over time. This is done by gradually increasing the dosage over the course of about six months. Conversely, omalizumab starts to work immediately and has been shown to be safe in children as young as one year old.
Moreover, because the monoclonal antibody attacks all kinds of IgE antibody, it can be used for allergies to foods other than peanuts. “It theoretically should work as well for any different food allergy that that person has,” says the study’s lead author Robert Wood, a paediatric allergy specialist at Johns Hopkins University School of Medicine in Baltimore, Maryland. He says omalizumab might also work for other autoimmune conditions that people taking it have, such as pollen allergies and eczema.
Perhaps the drug’s most important limitation is that it doesn’t eliminate allergies — it only raises the threshold for the amount of food a person can eat before it triggers a reaction. In the FDA’s statement approving omalizumab, the agency said that people taking the drug “must continue to avoid foods they are allergic to”.
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Last November, a clinical trial offered a glimmer of hope in the often gloomy fight against antimicrobial resistance. An oral antibiotic, called zoliflodacin, was shown to be effective against the bacterium that causes the sexually transmitted disease gonorrhoea. And because it is the first of a new class of antibiotics, the drug also offers hope of stopping the spread of ‘super gonorrhoea’,which is resistant to most standard treatments. https://www.nature.com/articles/d41586-024-00543-5?
That month brought good news on another front, too. An international research team reported that a new antifungal drug, fosravuconazole, was safe and effective at treating a devastating disease called fungal mycetoma, which scars and damages the skin and can lead to amputation if left untreated. Antifungal drugs are difficult to develop and are scarce. The only existing mycetoma treatment requires taking expensive pills for a long time: two pills per dose, twice per day, for several months. The new drug requires only taking two pills once a week, which could reduce stress and expense for tens of thousands of people in South Asia and sub-Saharan Africa.
What is especially notable about the success of these two drugs, however, is that they followed a new path to get this far. Both trials were conducted by non-profit organizations that were founded specifically to bring new drugs to the market: zoliflodacin by the Global Antibiotic Research and Development Partnership (GARDP) based in Geneva, Switzerland, and fosravuconazole by the Drugs for Neglected Diseases Initiative (DNDi), also based in Geneva.
These organizations hope to fill a big gap in the development and testing of drugs at a time when most legacy pharmaceutical firms have withdrawn from antimicrobial drug discovery, and many of the small biotechnology companies that picked up the torch have gone bankrupt (see ‘Stagnant investment’). These two latest achievements suggest that non-profits could help to solve the problem of drug access, while fending off the rise of drug-resistant microbes, which contribute to almost five million deaths per year.
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Lalita Panicker is Consulting Editor, Views and Editor, Insight, Hindustan Times, New Delhi
