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There's A Promising New Vaccine For One Of The World's Top Health Threats

Indonesians independently carry out fumigation in their neighborhood to eradicate the larvae of mosquitoes that cause dengue fever. A new vaccine to prevent dengue may be on the horizon.
Aditya Irawan
NurPhoto/Getty Images
Indonesians independently carry out fumigation in their neighborhood to eradicate the larvae of mosquitoes that cause dengue fever. A new vaccine to prevent dengue may be on the horizon.

A new vaccine to prevent dengue may be on the horizon. And health officials say it's desperately needed.

The World Health Organization this year listed dengue as one of the top 10 threats to global health.

The mosquito-borne disease is a growing threat for several reasons. First, the sheer number of dengue cases has been increasing dramatically in recent years. The WHO says there's been a 30-fold increase in infections since 1970. Last year nearly 100 million people came down with the disease, also known as breakbone fever.

Second, there's no specific treatment for the viral disease. When outbreaks occur, local clinics can get overwhelmed with patients experiencing severe flu-like symptoms. Third, the disease is moving in to new areas as the mosquitoes that carry the dengue virus expand their range. The Aedes aegypti mosquito basks in warm, wet, tropical areas, and shifting global temperatures have made more places to its liking.

So far this year Brazil has had more than 2 million cases.

The Philippines, Indonesia and Bangladesh are also dealing with major dengue epidemics. Guam has recorded its first outbreak in 75 years.

"This is the fastest-spreading mosquito-borne viral disease on the planet," says Derek Wallace, who leads the Takeda Pharmaceutical Company's global effort to develop a dengue vaccine.

"Dengue is a very important disease across a large part of the world. Nearly half the world's population is at risk of dengue," he says. "There are nearly 400 million infections annually, and about 100 million of those are symptomatic."

So 100 million people are getting sick with a disease that clinicians have no drugs to fight. All doctors and nurses can do is manage the patient's symptoms. Make sure they stay hydrated. Try to control the fever. Give them some painkillers to counter the intense discomfort in their joints.

Most patients fight through the disease. They get better in a week or so — but in severe cases, dengue can cause organ failure and even death.

Wallace and his team at Takeda think they're very close to having a marketable vaccine that could dramatically reduce the number of cases of the mosquito-borne disease.

"We're thrilled with the results," Wallace says, about a large-scale study of a vaccine they're calling TAK-003. Staring in 2016, Takeda enrolled 20,000 people between the ages of 4 and 16 in a study of TAK-003. The vaccinations occurred at 26 sites in seven dengue-endemic countries.

In results just published in the New England Journal of Medicine, Wallace and his colleagues found TAK-003 to be 80% effective in preventing participants from getting dengue and 95% effective in preventing cases of dengue-associated hospitalizations.

"A vaccine efficacy of 80% has the potential to have a massive impact on the significant public health burden of dengue," Wallace says.

Stephen Waterman, the head of the U.S. Centers for Disease Control and Prevention's Dengue Branch, who was not involved in the Takeda study, says a highly effective dengue vaccine could be a game-changer in controlling this expanding disease.

"We are not getting a better handle on [dengue] worldwide," he says. "There's been a steady trend of an increasing number of cases."

But developing dengue vaccines has been difficult, he says. There are four different strains of dengue, and the vaccine needs different elements to fight each one.

"Because of the four different viruses involved, you need to package four different viruses into one vaccine," he says. In the past, researchers have had trouble doing that effectively.

Asked what rate of efficacy he'd like to see in a new dengue vaccine, Waterman says with a laugh, "Well, everybody's shooting for 100%, but that's impossible." Still, anything above 50% could have an impact on public health, he says. The 80% being touted by Takeda he calls "excellent." But he adds that he still wants to see more data on TAK-003.

"Dengue is a tricky disease in terms of the antibodies that come from vaccines to protect against it," Waterman says. "So I think we would want to see the full trial data over a longer period of time to be convinced of the efficacy is that high."

The world's first dengue vaccine, Dengvaxia, was licensed in 2015. But it caused a major scandal two years ago in the Philippines. After nearly a million Filipino children had been vaccinated with Dengvaxia, the drug's manufacturer, Sanofi, announced that the inoculation might actually make dengue worse in some people. It was a public health and public relations fiasco that significantly undermined many Filipinos' confidence in vaccines in general.

Wallace says Takeda's new product is fundamentally different from Dengvaxia. TAK-003 is built around a live but weakened dengue virus, while Dengvaxia is based on a strain of the yellow fever virus.

"We have not seen any evidence of an increase in severe dengue as a result of vaccination in this study, but it is important that we continue to look at this over a longer period of time," Wallace says.

Takeda intends to continue to monitor the thousands of kids who were vaccinated with TAK-003 for several more years.

The Takeda dengue vaccine still needs to win regulatory approval before it's made available to the public. Company officials, however, are confident they'll get it. This week Takeda opened a 100 million-euro factory in Germany exclusively to manufacture TAK-003.

Copyright 2021 NPR. To see more, visit https://www.npr.org.

Corrected: November 20, 2019 at 12:00 AM EST
A previous version of this story stated that the Takeda vaccine was 95% effective in preventing cases of severe dengue. However, the study did not draw a conclusion about the efficacy of the vaccine against severe dengue. Rather, the vaccine was shown to cut by 95% dengue-associated hospitalizations, the majority of which were not confirmed cases of severe dengue.
Jason Beaubien is NPR's Global Health and Development Correspondent on the Science Desk.
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