Dengue is surging in the Americas

By READDI, June 17, 2024 — Dengue, a mosquito-borne virus in the flavivirus family, is surging at unprecedented rates in the Americas.

During the first five months of 2024, the number of reported cases — more than 8.8 million — is up by 425% compared to the same period averaged over the past five years. Brazil alone registered 5.5 million cases before June.

Why the spike?

The leading reason is a warming planet — supercharged by recent El Niño effects — that’s extending the range of the Aedes genus of mosquitoes, which carry the virus. Also, dengue thrives in dense urban areas, and many of the world’s cities are exploding in growth.

Dengue will likely soon become endemic in the United States, according to World Health Organization chief scientist Jeremy Farrar.

“The thought of dengue establishing a permanent foothold in the United States is terrifying,” says virologist and READDI co-founder Dr. Nat Moorman. “Once you start that cycle, it’s incredibly hard to break.”

There are no approved drugs for treating dengue, but Moorman says he is hopeful growing awareness about dengue will spur increased investment into antiviral drug research and development.

Like wildfire

Dengue, now endemic in more than 100 countries, is the fastest-spreading mosquito-borne virus in the world. The largest number of dengue cases reported in recent years was in the WHO Region of the Americas, which includes Brazil, Argentina, Peru and Puerto Rico.

“Dengue is certainly even more widespread than we recognize,” Moorman says. “It’s unclear how widely testing is being performed. Where testing is unavailable, what’s the spread and the prevalence there?”

A 2019 modelling study estimates there are actually 100 million symptomatic cases of dengue per year worldwide, with more than half the world’s population, nearly 4 billion people, at risk of infection with dengue viruses.

Because dengue can spread asymptomatically, an unknown number of inapparent cases go unreported.

Once infected with dengue, an Aedes mosquito can transmit the virus to multiple people for the rest of its life, generally three or four weeks.

In the Americas, four dengue serotypes — DENV-1, DENV-2, DENV-3 and DENV-4 — circulate, simultaneously in some countries. Only Canada and continental Chile are free from dengue and Aedes mosquitoes.

One study put the total economic impact in the Americas at more than $3 billion per year, but that was well before the recent surge of cases.

There is one vaccine for dengue, but it is problematic, since it puts those who have never had dengue at greater risk of severe illness if they get it. Therefore, the vaccine is limited to children ages 9 to 16 who had dengue before and live in places where the virus is common.

The agony of breakbone fever

Dengue causes a febrile illness that affects infants, children and adults. It often presents as a mild fever and headache, but dengue can progress into severe dengue, characterized by shock, severe bleeding, organ complications and death. By June 5, 2024, reported dengue deaths in the Americas surpassed 4,100.

More and more, travelers from the U.S. are discovering the agony of dengue, also known as breakbone fever. On a March snorkeling trip to the island of Curaçao, Dr. Deborah Heaney, a Michigan physician, was caught off-guard by dengue-carrying mosquitoes that swarmed months before the typical mosquito season.

“My ribs felt broken, as if I’d been smashed against large boulders in the sea. Later that day came intense fever, alternating with shaking chills,” she wrote in a guest essay for the New York Times. “Back in Michigan — weak, nauseated and dehydrated from explosive diarrhea — I ended up in the emergency department.”

Heaney had no treatment options other than fluids and over-the-counter pain relievers, like acetaminophen. Ibuprophen and aspirin were off the table, since dengue can cause leaky blood vessels and hemorrhaging, and those medications can make bleeding worse.

“There are no approved antiviral drugs for treating dengue — or infections caused by any other member of the flavivirus family, including Zika, Yellow Fever and West Nile,” Moorman says.

“When we talk about the number of people each year who get sick and are negatively impacted by dengue, it seems a travesty,” he says. “The world has turned a blind eye to dengue.”

Why?

The WHO lists dengue as a neglected tropical disease, prevalent among some of the world’s most impoverished communities and lacking funding for research and development.

“The places where dengue is endemic typically don’t have incomes as high as Europe and the United States,” says Moorman. That means drug companies can’t charge as much for each course of drug. The bulk of the R&D funding that exists for dengue comes from governments and philanthropies. “Academic researchers find promising inhibitors but don’t have the resources to bring them through the innovation valley of death.”

A shifting market outlook

Moorman wants to test the hypothesis that there is no commercially viable market for dengue drugs. Several factors may be turning the tide, he says.

First, there is the rise in cases and a change in how outbreaks occur. Historically, outbreaks, especially in the Americas, happened every few years, but now they are occurring yearly. “If outbreaks are happening with regular frequency, does that mean there’s a market?” Moorman asks.

Then there is where the outbreaks are occurring. Along with dengue cases brought into the U.S. by international travelers, locally spread cases have been reported in Florida, Louisiana, Texas and other states. In October 2023, public health experts were especially concerned by the first-ever case of locally transmitted dengue in Los Angeles County, the most populous county in the U.S.

Locally spread dengue has been reported in Paris, which is expecting more than 15 million tourists this summer for the Olympics.

“If, or more likely when, dengue becomes endemic in the U.S. and Europe, drug companies may be able to charge a premium for antiviral drugs that reduce the misery of this disease,” he says.

Broad-spectrum approach

Dengue is just one of the debilitating diseases caused by viruses in the flavivirus family. The family also hosts viruses causing other febrile and neurological illnesses, such as Zika and Yellow Fever.

What if there were an antiviral drug that worked broadly across multiple viruses in the flavivirus family? Incentives for R&D investment might multiply if a drug under development could treat multiple existing diseases while also preparing the world for “Disease X,” an as-yet-unknown emerging infectious disease.

“There’s real concern for a brand-new virus coming out of the flavivirus family, similar to the recent emergence of Zika virus,” Moorman says.

READDI’s approach — developing broad-spectrum small molecule drugs in advance of the next highly contagious viral threat — could reduce disease, hospitalization and death caused by dengue.

“A drug that shows breadth against the flavivirus family will presumably work against all four strains of dengue,” Moorman says. “It will have the potential to also work against cases of Yellow Fever and Zika — and to be ready for efficacy testing when the next Disease X emerges.”

But the R&D must happen now, he says. “With viral disease, there’s often no commercially viable market until it’s a really big problem, but then it’s too late to find a solution.”