The push for a better dengue vaccine becomes increasingly urgent

The dengue fever epidemic that has swept through Latin America over the past three months is staggering in 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 a more in Puerto Rico.

It warns of a changing landscape for the disease. The mosquitoes that spread dengue thrive in densely populated cities with weak infrastructure and in warmer, wetter environments, the type of habitat that is expanding rapidly with climate change.

More than 3.5 million cases of dengue were confirmed by Latin American governments in the first three months of 2024, compared to 4.5 million in all of 2023. There have been more than 1,000 deaths this year. The Pan American Health Organization warns that this could be the worst year on record for dengue.

The rapidly changing disease landscape requires new solutions, and Brazilian researchers provided the only good news in this story with the recent announcement that a clinical trial of a new dengue vaccine, administered in a single dose, provided a strong protection against disease. .

There are two dengue vaccines, but one is an expensive two-dose regimen, while the other can only be given to people who have already had a dengue infection.

The new single-use vaccine uses live and 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 Sao Paulo.

Butantan will produce the vaccine. It already produces most of the vaccinations used in Brazil and has the capacity to produce tens of millions of doses of this new vaccination. The institute plans to submit the dengue vaccine to Brazil's regulatory agency for approval in the coming months and could begin producing it next year.

But that won't help with this outbreak, and by the time production gets underway and nationwide rollout begins, it may not even be enough to help with the next one; dengue typically occurs in three- or four-year cycles.

And it won't necessarily help the rest of Latin America: Butantan will produce the vaccine only for Brazil. Multinational pharmaceutical company Merck & Co., which also licensed the NIH technology, is developing a related vaccine that will be sold to the rest of the world; that vaccine's effectiveness has not yet been tested in a late-stage clinical trial.

And there is, of course, demand for a dengue vaccine beyond the Americas: Mosquitoes are spreading the disease in Croatia, Italy, California and other regions where they've never seen it before. Places used to dealing with mild outbreaks are now facing record-breaking cases: Bangladesh had 300,000 cases last year.

Dengue is commonly known as bone-breaking fever, due to the excruciating joint pain it causes. Not everyone feels this pain: three-quarters of people infected with dengue have no symptoms, and among those who do, most cases only feel like a mild flu.

But about 5% of people who get sick will progress to what's called severe dengue. Plasma, the protein-rich fluid component of blood, can begin to leak from blood vessels, causing shock or organ failure in patients.

When severe dengue patients are treated with blood transfusions and intravenous fluids, the mortality rate tends to be between 2 and 5%. 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%.

In Brazil, the current dengue epidemic is hitting children hardest; those under 5 have the highest mortality rate of any age group, followed by those aged 5 to 9. Adolescents between 10 and 14 years old have the highest number of confirmed cases, according to the Instituto Oswaldo Cruz, a national public health research center.

When clinics began to be overwhelmed with dengue patients in January, the Brazilian government purchased the entire global stock of a Japanese-made dengue vaccine called Qdenga. Public health nurses are delivering it to children ages 6 to 16, but this year there will be enough vaccine to fully vaccinate only 3.3 million of Brazil's 220 million people.

This great national effort will protect a few million children, but will not contribute anything to its herd immunity.

Qdenga isn't cheap: It costs about $115 a dose in Europe and $40 in Indonesia. Brazil pays $19 a dose, after negotiating a lower price for its huge purchase.

Takeda Pharmaceuticals, which makes Qdenga, announced last month a deal with Biological E, a large Indian generic drug maker, to license and produce up to 50 million doses a year, as part of a rush to accelerate production. The Indian vaccine is expected to cost much less. But organic E is unlikely to get regulatory approval to market before 2030; it is a slow process that involves transferring technology, setting up a production line, and getting regulatory approval of a new version, even of a well-known product.

Dengue costs Brazil at least $1 billion a year in healthcare 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 the first time. Qdenga protects against all four strains of dengue, and the hope is that the new Butantan vaccine will do so too, although data released so far shows that it has only been tested against the two strains that were circulating during the first part of the trial; further results are expected in June.

Millions more people will have been exposed to dengue when this epidemic finally passes. But they will need that new vaccine more urgently than ever.

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