The Push for a Better Dengue Vaccine Grows More Urgent

The outbreak of dengue fever that has unfolded in Latin America over the past three months is staggering in its scale — a million cases in Brazil in a matter of weeks, a huge spike in Argentina, a state of emergency declared in Peru and now another in Puerto Rico.It forewarns of a changing landscape for the disease. The mosquitoes that spread dengue thrive in densely populated cities with weak infrastructure, and in warmer and wetter environments — the type of habitat that is expanding quickly with climate change.More than 3.5 million cases of dengue have been confirmed by governments in Latin America in the first three months of 2024, compared with 4.5 million in all of 2023. There have been more than 1,000 deaths so far this year. The Pan-American Health Organization is warning that this may be the worst year for dengue ever recorded.The rapidly shifting disease landscape needs new solutions, and researchers in Brazil delivered the lone shred of good news in this story with the recent announcement that a clinical trial of a new dengue vaccine, delivered in a single shot, had provided strong protection against the disease.There are two existing vaccines for dengue, but one is an expensive two-shot regimen, while the other can be given only to people who have already had a dengue infection.The new one-shot vaccine uses live, weakened forms of all four strains of the dengue virus. It was created by scientists at the National Institutes of Health in the United States and licensed for development by the Instituto Butantan, a huge public research institute in São Paulo.Butantan will make the vaccine. It already produces most of the immunizations used in Brazil, and has the capacity to make tens of millions of doses of this new one. The institute plans to submit the dengue vaccine to Brazil’s regulatory agency for approval in the next few months and could begin producing it next year.But that won’t help with this outbreak and, by the time the production gears up and a national rollout gets started, it may not be enough to help with the next one, either; dengue typically surges in three- or four-year cycles.And it won’t necessarily be of help to the rest of Latin America: Butantan will only make the vaccine for Brazil. The multinational drug company Merck & Co., which also licensed the NIH technology, is developing a related vaccine which will be sold in the rest of the world; the efficacy of that vaccine has not yet been tested in a clinical trial.And there is, of course, demand for a dengue vaccine beyond the Americas: Mosquitoes are spreading the disease to Croatia, Italy, California and other regions that haven’t seen it before. Places used to handling mild outbreaks now face record-breaking ones: Bangladesh had 300,000 cases last year.Dengue is commonly known by the name breakbone fever, after the excruciating joint pain it causes. Not everybody experiences that pain: Three-quarters of people infected with dengue don’t have any symptoms at all, and among those who do, most cases resemble only a mild flu.But about 5 percent of people who become sick will progress to what’s called severe dengue. Plasma, the protein-rich fluid component of blood, can start to leak out of blood vessels, causing patients to go into shock or have organ failure.When patients with severe dengue are treated with blood transfusions and intravenous fluids, the mortality rate tends to be between 2 and 5 percent. But when they don’t get treatment — because they don’t realize it’s dengue and don’t seek treatment quickly enough, or because health centers are overwhelmed — the mortality rate is 15 percent.In Brazil, the current dengue outbreak is hitting children hardest; those under 5 have the highest mortality rate of any age group, followed by those age 5 to 9. Adolescents between 10 and 14 have the highest number of confirmed cases, according to the Instituto Oswaldo Cruz, a national public health research center.As clinics began to be overwhelmed with dengue patients in January, the Brazilian government bought the entire global stock of a Japanese-made vaccine for dengue called Qdenga. Public health nurses are delivering it to children ages 6 to 16, but there will be enough vaccine to fully vaccinate only 3.3 million of Brazil’s 220 million people this year.This big national effort will protect a few million children, but it won’t contribute anything to its herd immunity.Qdenga is not cheap: It’s about $115 per dose in Europe and $40 in Indonesia. Brazil is paying $19 per dose, having negotiated a lower price for its huge purchase.Takeda Pharmaceuticals, which makes Qdenga, announced a deal last month with Biological E, a large Indian generic drug maker, to license and produce up to 50 million doses a year, part of a race to accelerate production. The Indian vaccine should cost considerably less. But Biological E is unlikely to have regulatory approval to market it before 2030; it’s a slow process that involves transferring technology, setting up a production line and getting a new version of even a well-known product approved by regulators.Dengue costs Brazil at least $1 billion a year in health care treatment and lost productivity. And that figure doesn’t take into account the human suffering involved.The fact that there are four different strains of the dengue virus complicates more than the process of making a vaccine: The potentially fatal form of the disease is more common when patients have a second infection, with a different strain than they had the first time. Qdenga protects against all four strains of dengue, and the hope is that the new Butantan vaccine does, too, although the data released so far shows it tested against only the two types that were circulating during the first part of the trial; more results are expected in June.Millions more people will have been exposed to dengue when this outbreak finally passes. But they’re going to need that new vaccine more urgently than ever.

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