Record-breaking outbreak, fueled by an unusually hot rainy season, is disproportionally affecting poor people
When dengue started to circulate in his small town in the state of Rio Grande do Sul in Brazil, Fabio Vilella's first thought was that he should get his 13-year-old son vaccinated. Children are especially vulnerable, and his son had dengue before, which increases the risk of severe disease. But Vilella, an environmental biologist, soon made a startling discovery: Not a single private clinic or pharmacy in the country had any vaccine left. “I'm really worried,” he says.
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 fueled 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.
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.
Dengue is notoriously hard to control. A. aegypti thrives in cities, where water-filled flower pots, buckets, or discarded tires make ideal breeding spots. “The mosquito loves a water tank in the shade,” says Rafael Mello Galliez, an infectious diseases researcher at the Federal University of Rio de Janeiro. Poor populations lacking running water and proper waste disposal bear the brunt of the disease.
Regularly removing water reservoirs can help control dengue—along with Zika and chikungunya, two other viral diseases transmitted by A. aegypti —but is hard to sustain. Insecticide spraying is not very effective either, in part because mosquitoes are becoming insecticide-resistant. The use of larvicides—which female mosquitoes themselves help spread as tiny clumps of the powder stick to their body—has not stopped the epidemic either.
New technologies to control A. aegypti are on the way. One is the release of mosquitoes infected with the Wolbachia bacterium, which reduces their ability to transmit viruses. The nonprofit World Mosquito Program has deployed the mosquitoes in five localities in Brazil so far, and the results are encouraging. Niterói, a city of half a million where the mosquitoes have been deployed since 2015, has seen only 58 confirmed cases so far this year, compared with 9355 in nearby Rio de Janeiro, with almost 7 million inhabitants. The mosquitoes will soon be deployed at more sites, but scaling up the strategy nationwide is a tall order.
The same is true for the release of sterile male mosquitoes, which mate with females but don't produce offspring, causing the population to crash. One group of Brazilian researchers has created such insects not with radiation, the usual practice, but with a cheaper treatment consisting of a chemical and a bit of double-stranded RNA that silences a gene involved in male fertility. An experiment in the city of Ortigueira, in Paraná state, between 2020 and 2022 resulted in 97% fewer dengue cases when compared with control cities, the research team reported last year
Vaccination is the other promising new strategy. 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.
But all four weakened serotypes in the vaccine replicated in more than 50% of vaccinated individuals who never had dengue, notes Andre Siqueira of the Oswaldo Cruz Foundation. That suggests the Butantan vaccine will provide sustained protection for all serotypes, he says. It is expected to be cheaper than Qdenga as well. “Once Butantan-DV is approved and available, the Qdenga vaccine will be history,” Mello Galliez predicts.
Butantan hopes to apply for approval to ANVISA, Brazil's regulatory agency, by September, Kallas says. Vaccinating the target population nationwide—those between 2 and 60 years old—would take some 140 million doses, Kallas says, but he declines to speculate how long that would take: “I don't want to create expectations.”
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.
“Controlling dengue is very hard,” Paz-Bailey says. But she believes vaccination, new mosquito control strategies, and continued education will eventually help counter the disease's surge. “I'm optimistic about the future,” she says.
Marcia Triunfol