Dengue is a miserable illness caused by infection with any of the four dengue viruses (dengue-1, -2, -3 and -4). Infections have increased dramatically over the past two years while, at the same time, developers of anti-dengue drugs and vaccines have abandoned their research and development efforts. As a result, public health officials and clinicians are becoming increasingly concerned about their limited options to keep their populations and patients safe.
The Dengue Problem is Worsening
The dengue viruses primarily circulate in the tropics and subtropics and are transmitted to people by infected mosquitoes. There are an estimated 400 million infections every year making about 100 million people ill. Many recovering patients have told me dengue made them feel so sick they thought they were going to die. Annual dengue fatalities range between 8,000 and 40,000 people per year, with many deaths occurring in children.
Once infected with a specific dengue virus, the individual will develop immunity against that virus and be protected from future illnesses for years. However, a person can always be infected a second time with a different dengue virus. It is these second infections where the risk of severe dengue and death is highest. Third or fourth infections usually do not make people very ill because of the immunity developed from the first two infections.
Beginning in 2023, the global dengue problem started to significantly worsen. Dengue cases skyrocketed around the world not only in locations known to be endemic for the viruses like Central and South America and Southeast Asia, but also in new locations such as Nepal and Bangladesh. Infections this year alone are more than 300% higher in the Caribbean and Americas compared to the average of the last five years. Cases have also started popping up in more temperate climates. France had more locally acquired dengue virus infections in 2024 than any year prior.
In 2023 and 2024, the U.S. experienced an increase in the number of people becoming infected while traveling (4,730). There was also a rise in locally acquired dengue infections in places like Florida (249), Texas (2) and California (17). Puerto Rico frequently has dengue outbreaks and experienced a rise in infections with 6,452 reported cases.
Where Are the Anti-Dengue Vaccines and Drugs?
At the same time infections are surging, vaccine and drug developers have started calling it quits in the fight against dengue. Sanofi had one of only two licensed dengue vaccines, Dengvaxia, and the only vaccine licensed in the United States. The company recently announced it will stop manufacturing Dengvaxia, and existing supplies will fade away by August 2026. The company cited low global demand as the reason for discontinuing a vaccine, which took over two decades and cost more than $1.5 billion dollars to develop.
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The other licensed dengue vaccine, TAK-003, is made by the Japanese vaccine developer Takeda. Although TAK-003 is a modest improvement over Sanofi’s vaccine, it, too, has significant limitations. The vaccine has a better safety profile than Dengvaxia, but it does not seem to work against the dengue-3 virus, only the dengue-1 and dengue-2 viruses. It is unclear if works against dengue-4.
Millions of TAK-003 vaccine doses were provided to countries in Latin America during the recent dengue surge, and observations on safety and effectiveness from real world use will be available in the coming years. The U.S. may or may not benefit from this data because the company pulled out of the Food and Drug Administration review process required for vaccine licensure. It remains to be seen whether Takeda will reengage with the FDA and if TAK-003 will ever be available in the United States.
Janssen, a company of Johnson & Johnson, has also recently thrown in the towel in the fight against dengue. The company announced that it will cease development of Mosnodenvir, a drug candidate designed to be the first anti-viral treatment for dengue. It is unclear if another developer will license the drug and continue its development. As with Dengvaxia, Janssen’s decision represents years of lost effort and millions of dollars. (Disclosure: Throughout my career I have consulted with anti-dengue vaccine and drug developers including Sanofi, Takeda, Janssen and Merck.)
Are We Losing the Dengue War?
There are plenty of reasons to be pessimistic about our ability to confront the global dengue problem and prevent its further expansion into the United States.
Changing temperature and rainfall patterns have allowed the mosquito species that transmit dengue to flourish in the U.S. and extend to areas where they were not seen previously. This is a similar trend to what is being observed for diseases transmitted by ticks.
A second reason for concern is that every year more than 15 million travelers enter the U.S. from areas where dengue viruses circulate. More than 30 million Americans travel to and return from similar areas. Every traveler has the potential to introduce a dengue virus into the country.
More dengue viruses and more mosquitoes capable of transmitting them does not bode well for populations like the U.S., where most people lack immunity to any of the four dengue viruses.
Air-conditioning, indoor plumbing and window screens can limit high intensity human and mosquito interactions lowering the likelihood the U.S. will experience major dengue epidemics similar to those in Latin America and Southeast Asia. However, smaller local outbreaks like those in Key West, Florida (2009-2010), and Hawaii (2015-2016) remain possible and would stress local health care systems and cost millions of dollars to manage.
Another potential bright spot is that some scientists continue to develop anti-dengue vaccine and drug candidates. There is also interest in using newer antibody infusion technologies, like what was used to treat COVID-19 patients, to prevent or treat dengue virus infections. Antibody preparations could provide short-term protection from dengue during outbreaks or as a treatment for people already infected.
The Serum Institute of India is field testing an antibody preparation designed to treat dengue virus-infected patients. The antibodies are supposed to interrupt the virus’ multiplication in the body, thereby reducing the severity of illness patients experience. Academic groups and U.S. government agencies are also exploring the use of manufactured anti-dengue antibodies.
On the vaccine front, the Instituto Butantan (Brazil) licensed dengue vaccine technology from the U.S. National Institutes of Health and have completed a large (~16,000 people) field trial testing their vaccine formulation (Butantan-DV). The vaccine appears well tolerated and prevents a significant proportion of dengue-1 and dengue-2 illnesses. The company announced it has provided Brazilian regulators (Anvisa) all the final documentation required for them make a determination on whether the vaccine can be registered and made available in Brazil.
Panacea Biotech in India licensed the same NIH materials and started a large-scale vaccine field trial in 2024. Merck (MSD) is another licensee and is also expected to launch field trials. If the vaccine is successful and MSD pursues a license in the U.S., access remains years away.
What About the Future of Dengue Research?
Even though academic, government and industry groups are working on developing dengue prevention and treatment options now, there is a real risk that the resources supporting this work could soon dry up.
For over a century, the U.S. government has played an important role in advancing dengue research through work in the Department of Defense, Centers for Disease Control and Prevention and the NIH. The government has also influenced scientific advancement through its various external funding mechanisms. These activities have incentivized industry to take on the financial and scientific risk associated with developing vaccines and drug candidates where the market for the final products is unpredictable. The shared risk approach has been productive.
Depending on who Congress confirms to lead the U.S. Health and Human Services and its family of subordinate agencies, infectious diseases research could be significantly de-prioritized and underresourced in both money and human capital. This would certainly limit the U.S. government’s footprint in the dengue research landscape, but also dissuade other entities from starting or continuing their dengue work. All of this would be bad news for countries like the U.S., which are almost certainly going to confront a worsening dengue problem but currently have few tools at their disposal to prevent or manage the infections.
Contributor
I’m an infectious diseases physician, scientist, leader, and entrepreneur.
I’m the Director of the Global Health Institute and Frank E. Young, MD ’56 and Leanne Young Endowed Chair of