A mosquito-borne virus that infects as many as 400 million people every year, dengue can cause a wide range of symptoms. One in four cases can produce high fever, severe headache, and/or nausea—as well as the acute joint and muscle pain that give the illness its colloquial name: “breakbone fever.” (Infection with dengue feels “as if every inch of you has been smashed by a hammer,” the travel journalist Paul Theroux has written.) In about 5 percent of cases, shock, internal bleeding, and even death can ensue.
Dengue is the world’s fastest-spreading mosquito-borne disease, and climate change, urbanization, and globalization continue to expand its range. In 2019, the WHO identified dengue as one of the ten most urgent global health threats. Accounts of dengue epidemics go back five centuries, but science’s ability to mitigate or prevent illness has been limited—until now. We discussed an important breakthrough with Ramona Sequeira, President of the Global Portfolio Division of Takeda, developers of an investigational dengue vaccine candidate that has been approved for use in the European Union, the United Kingdom, Indonesia, and Brazil, and is currently under review by the U.S. Food and Drug Administration.
If Americans have heard of dengue, they know it as a disease that affects people in faraway places. To what degree has that changed in recent years?
There’s limited awareness of dengue in the U.S., but for many around the world, it is part of a very real day-to-day experience. Fifty years ago, there were only nine countries where dengue was endemic. Today, there are more than 125. About half of the world’s population, nearly four billion of us, live in dengue-endemic regions, and could be at risk. But many people travel to these areas as well, whether for business, vacation, or to visit loved ones. If you travel to one of these areas and you’re bitten by a species of mosquito infected with the virus, you may get dengue. To a lesser degree, it’s also possible for you to get dengue traveling abroad, return home, and—if the same kind of mosquito bites you—spread the disease to others. But global warming has expanded the habitat of mosquitoes. We’ve seen local cases in Florida, Texas, and other warm areas of the U.S. Many efforts around the world have focused on reducing the incidence of dengue by removing standing water, which can breed mosquitoes; using insecticides; and promoting hygiene, sanitation, and awareness.
How did Takeda develop its dengue vaccine candidate?
We’ve been working on it for the past 10 years. It has been evaluated in the largest dengue vaccine clinical program that’s ever been done—19 completed or ongoing clinical trials involving 28,000 participants ranging in age from eighteen months to 60.
In a randomized, placebo-controlled Phase III trial, a two-dose regimen was tested in children from 4 to 16 years old living in dengue-endemic countries. A long-term follow-up to establish the regimen’s efficacy and safety was done for 54 months following the second dose.
We think that the vaccine could have a substantial public-health impact in the countries where it has been approved, and in the U.S. should it be approved after the FDA completes its review.
We are proud that our dengue vaccine has been approved in the EU, UK, Indonesia, and Brazil. The approval is for broad use—meaning that someone can use it regardless of whether or not they’ve had dengue before. This could be a game changer for those countries.
Dengue, because it’s not transmitted person to person, seems to present a challenge that’s different from, say, COVID-19. What are the implications of dengue as a public-health issue?
There are four types of dengue, and they circulate at different times and at different rates. So if you have an infection from one particular type of dengue, that doesn’t stop you from getting infected with another one. There’s also evidence that if you have an infection from one type of dengue, then are bitten by a mosquito carrying a different type, the second infection could potentially be more severe.
When there’s an epidemic of dengue sweeping through a community, you get the same system overload we saw during COVID at its height. You get overwhelmed hospitals, overtaxed health care workers, an effect on the ability to treat other types of diseases. With COVID, everyone from pregnant women to people with broken limbs had trouble finding hospital beds. Dengue also has an economic impact in the sense that many people in developing countries are paying out of pocket for their hospital visits while possibly missing work. Losing a paycheck can be devastating for households that disproportionately rely on single-income earners. An epidemic of dengue can really take a toll on a country’s economy and health care infrastructures.
How will Takeda meet anticipated demand from a market of four billion people?
This is not a vaccine candidate geared only to individual impact. Rather, it’s geared to really making an impact on society—on both public health and health care. We expect to build our manufacturing capacity to approximately 100 million doses per year through our state-of-the-art vaccine manufacturing facility in Singen, Germany, along with our global manufacturing partners and partnerships in endemic countries.
We can’t do this on our own. We need to work very closely with local governments and NGOs to tailor our approaches to provide equitable access. In countries that implement very strong vector control, people don’t tend to get dengue until they’re older. In other countries, you see a lot of infections in children. For instance, we’re working with UNICEF to look at underrepresented communities, like the Amazônia region in Brazil. We’re partnering with them to help increase education, sanitation, and access to clean water. It’s not just about vaccination per se; it’s about the whole ecosystem around reducing the incidence of mosquito-borne illnesses. That could be dengue, it could be Zika or malaria, it could be chikungunya.
In this era of prevalent misinformation about vaccines, how can we assist people in determining whether or not they should take this one?
Getting vaccines to people is important – and that includes building not only a strong distribution network but also a high level of trust and awareness. We want to make sure we’re partnering with communities, including travel providers, to ensure we’re reaching trusted advisors and leaders. Beyond Latin America and Southeast Asia, which are the primary regions where it is endemic, dengue has reached the United States. It is endemic in Puerto Rico. We’ve seen some local transmission by mosquitoes in Florida. It is growing. The whole idea here is to make travelers aware of the risk in the locations they’re visiting, as well as of the vaccine candidate’s safety and efficacy profiles. Most importantly, it is our role to work with local authorities to make this vaccine, if it is approved, available to benefit as many people as possible to help address this global public-health threat.
