Dengue is erupting in Brazil and around the world. Can new vaccines stop it?

March 14, 2024:

Dengue (pronounced DEN-gay), a mosquito-borne illness that has circulated to a limited degree for centuries, is now spreading with unprecedented speed around the world. It’s a worrying example of how a changing climate and 21st-century demographic trends can quickly turn a public health nuisance into a daunting global health crisis.

In 2000, there were about 500,000 reported dengue cases and 19,685 recorded dengue deaths around the world; by 2019, there were 5.2 million cases and 30,000 deaths, the most ever. Deaths are on pace to set another record in 2024.

The disease’s true reach is likely even higher, as dengue is sometimes asymptomatic or only mildly symptomatic, and its symptoms can be mistaken for other infections, such as yellow fever or the chikungunya virus.

In South and Southeast Asia, the Pacific Islands, and South America, which has long faced dengue epidemics every three to five years, the virus has turned into a chronic threat.

In January and February, Brazil reported more than 1 million cases and around 300 deaths from dengue — the fastest spread of the virus ever recorded in the country. In all of 2023, Brazil saw 1.6 million dengue cases, already an 18 percent increase over the previous year. Seven of Brazil’s 26 states have declared a state of emergency, and the country has been mobilizing an unprecedented vaccination campaign, the first-ever nationalized rollout of dengue vaccines.

Argentina has seen more than 74,000 cases since the beginning of this year, an astonishing 2,100-percent increase from the same period in 2023. Peru declared a state of emergency after more than 31,000 dengue cases were recorded in the first eight weeks of the year, and hospitals in the country’s north reported being overwhelmed by sick patients.

On the other side of the world, Bangladesh saw more than 300,000 dengue infections last year, a record high and three times the previous high in 2019. Between 2000 and 2022, fewer than 1,000 people in the country died of dengue. In 2023 alone, the disease killed 1,700.

And increasingly, dengue has been spreading in parts of the world where it has rarely if ever been reported previously, including the US. Last year, California discovered its first-ever local transmission of dengue. Over the last several years, cases have been reported for the first time in France, Croatia, subtropical parts of Africa, and Afghanistan.

Public health experts attribute the rise of dengue primarily to two factors: climate change and rapid urbanization in the developing world. Both trends are expected to intensify in the coming years — meaning today’s record-setting dengue outbreaks may only be a preview of the future.

Why dengue is suddenly everywhere

Humanity has lived with dengue for millennia: The first recorded case appeared in a Chinese medical encyclopedia from around 400 CE. In the 16th century, partly fueled by the global slave trade, the mosquito species responsible for spreading dengue — primarily Aedes aegypti, as well as Aedes albopictus — migrated around the world. Outbreaks were reported periodically in the following centuries until they started to occur with more frequency in the second half of the 20th century.

Many people who are infected with dengue experience no symptoms or only a mild fever and recover in around a week. But some patients become more seriously ill, with severe abdominal pain and vomiting. In a small number of cases, patients can experience organ failure and even death. Estimates of dengue’s fatality rates range widely, from 1 to 14 percent across various studies from around the world, likely in part a reflection of variation in the quality and timeliness of available treatments.

Since the 1950s, there’s been a marked increase in the number of severe dengue cases and fatalities. Increased awareness of dengue and improved diagnostics likely explain some of that increase, but the dramatic spikes in case numbers, especially in the last few years, suggest something bigger is at work.

Part of the dengue surge is likely due to the expansion of urban centers in tropical climates and the increased travel in those regions.

The World Health Organization has identified climate change as another primary cause of dengue’s aggressive expansion over the past 70 years.

Hotter temperatures and the attendant changes in weather patterns make it easier for the mosquitoes that carry dengue to proliferate. In Bangladesh, for example, where dengue has long thrived, the rainy season has extended by more than a month in recent years. Wet weather and humidity mean more standing water where mosquitoes flourish and easily reproduce.

Regions farther north are also becoming more hospitable to the Aedes mosquito. One estimate calculated that from 1950 to 2018, climate change had made the world 9 percent more susceptible to dengue transmission from Aedes aegypti and 15 percent more from Aedes albopictus. In Europe, where dengue has historically been rare, 2018 was the most suitable year for dengue transmission ever recorded, the study found, based on historical climate records that go back to 1900. Another climate model projected that an additional 2.2 billion people will be at risk of dengue exposure by 2080 compared to 2015 exposure levels.

Dengue-spreading mosquitoes thrive in dense cities, particularly in less developed countries that lack advanced water and sanitation systems. Things like water buckets, discarded tires, flower pots, and detritus from construction sites all allow standing water to accumulate, creating welcoming environs for mosquito reproduction.

“The mosquito loves a water tank in the shade,” Rafael Mello Galliez, an infectious diseases researcher at the Federal University of Rio de Janeiro, told Science this month.

Travelers to regions where dengue circulates can unknowingly bring the virus to new parts of the world — the likely explanation for isolated cases of local transmission, such as the cases in California last year.

What the world is doing to try to slow down dengue

Public health authorities have developed a playbook for combating dengue that resembles those of other mosquito-borne diseases like malaria and yellow fever: encouraging people in dengue-vulnerable regions to take precautions, such as wearing long-sleeved clothing, placing mosquito nets on beds, and applying bug repellent.

Countries currently battling acute outbreaks are taking more aggressive steps. In Brazil, government officials have been using fog machines to spray insecticides in an attempt to kill disease-carrying mosquitoes in urban centers with standing water. (There is some evidence that local mosquitoes are becoming resistant to certain insecticides, which may limit the strategy’s effectiveness.)

But the conventional playbook has been losing in the battle against climate change. We have more advanced countermeasures at our disposal — but the challenge is getting them into the field.

Brazil, which has already had to set up field hospitals as the number of infections grows, has been deploying the newest dengue vaccine, developed by Japanese firm Takeda Pharmaceuticals in 2022. In clinical trials, the shot was 80 percent effective at preventing symptomatic disease, a marked improvement over its predecessors (earlier vaccines have had an efficacy rate between 55 and 65 percent, depending on the particular strain of dengue).

But there aren’t enough vaccines available to stamp out Brazil’s outbreak anytime soon. The vaccine requires two doses, and this year, there are only 6 million doses available in a country of 214 million people. Over the next five years, just 50 million doses are expected to become available in Brazil. For now, the vaccine is available in only about 10 percent of Brazilian cities and eligibility is limited to prepubescent children, who are especially susceptible to serious illness (as are older adults).

Competition for the vaccines may increase in the years to come. For now, Argentina’s government has elected not to make the dengue vaccine available through the public health system, making it unaffordable to many people even as other modes of prevention, such as bug spray, are selling out. That could change if the outbreak gets worse.

Production may soon increase. Takeda is in talks with India to sell doses of the vaccine to the nation’s health care system and to contract with local manufacturers to boost its manufacturing capacity. The company has said it hopes to produce 100 million doses annually by 2030.

That would represent progress, but not nearly enough to cover everyone in regions vulnerable to dengue.

More vaccine candidates are in the works, including a potentially game-changing one-dose version being produced by Brazil’s Butantan Institute. In clinical trials, it has proven highly effective against multiple strains of dengue, which has long been a hurdle in vaccine development. But it’s still at least a year away from final approval, and even after that, manufacturing will take time to ramp up.

Other cutting-edge technologies are being rolled out. At least five Brazilian towns and cities have deployed genetically modified mosquitoes to slow the spread of dengue, with some encouraging results.

Niterói, a city of 500,000, has been seeding mosquitoes infected with bacteria that make it more difficult for them to transmit the virus since 2015. The city reported fewer than 60 dengue cases last year, while neighboring Rio de Janeiro had nearly 10,000. Another experiment involving sterile male mosquitoes in a small town led to a 97 percent reduction in dengue cases from 2020 to 2022.

Gene-editing mosquitoes comes with its own ethical quandaries. It could drive mosquito species to extinction, which could have unpredictable consequences for local ecosystems.

Other novel products, such as house paint formulated with insecticide, have shown promising preliminary results. Researchers are exploring whether a hepatitis C drug could be repurposed to treat people with dengue.

The best strategy is likely an all-of-the-above approach. That has been the lesson of the world’s battle against malaria, in which the combination of vaccines, insecticide-laden bed nets, and anti-malarial drugs has proven highly effective at reducing case numbers.

On a warming planet, the spread of tropical diseases like dengue is no longer a problem exclusively for the Global South. There is already some evidence that other mosquito-borne diseases, such as the chikungunya virus, are following a similar trajectory. The entire world will need to collaborate to find solutions lest the current dengue crisis foreshadow bigger outbreaks to come.

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