If someone asked you what the most deadly animal in the world is, you might first think of lions or crocodiles.
But—perhaps surprisingly—it’s the mosquito: These tiny insects are responsible for killing over 1 million people each year.
Mosquitoes can spread serious diseases, including Zika, malaria, West Nile and dengue, the last of which the World Health Organization (WHO) named a top 10 global health threat in 2019. Worldwide, dengue causes up to 400 million infections and 20,000 to 25,000 deaths are attributed to dengue each year, making it the most common viral infection caused by mosquitoes. The virus can cause fever, headaches, pain—and in severe cases, serious illness and death. Outbreaks can further strain healthcare systems that are facing existing challenges in capacity and resources.
Alarmingly, the number of dengue cases reported to the WHO increased more than eight-fold in the past two decades, and nearly 4 billion people in over 129 countries are currently at risk for infection.
For more than a decade, Johnson & Johnson has been committed to fighting neglected tropical diseases (NTDs) like dengue; in 2012, the company joined leading global health organizations to sign the landmark London Declaration on Neglected Tropical Diseases, which has helped drive meaningful progress in the control, elimination and eradication of NTDs. And Johnson & Johnson is continuing to push this work forward. This month, the company announced a new commitment to the Kigali Declaration on neglected tropical diseases, which aims to put commitments to achieve the United Nations Sustainable Development Goal 3 target on NTDs into action. Johnson & Johnson’s commitment will include—among other efforts to fight NTDs—expanded research into dengue.
For World Neglected Tropical Disease Day, we spoke to two Johnson & Johnson experts to learn more about this NTD and the work underway that may help curb its spread.
1.
You can get dengue more than once.
The dengue virus is primarily transmitted by the bite of the infected Aedes species of mosquito, which also transmits Zika, chikungunya and other viruses. When a mosquito feeds on blood, it ingests any viruses or parasites living there—which are then transmitted via saliva to the next person the mosquito bites. Once infected with dengue, mosquitoes can transmit it during their life span.
Right now, more than 50% of the human population is living in dengue virus endemic areas, and that percentage is expected to rise worldwide.
“The mosquitoes that transmit dengue are really adjusted to the human environment and love areas with an increased population density,” says Tine De Marez, Ph.D., Compound Development Team Leader, Dengue, Johnson & Johnson. This may be because after the rainy season, the mosquitoes must survive a long, dry spell but need water to breed—and humans are a good source for it, since they often have outdoor items that collect standing water.
This may also be why Aedes mosquitoes have adapted to bite humans, rather than animals; they also tend to bite more than one person during a feeding, which further drives the rapid spread of dengue.
There are four serotypes (or strains) of the dengue virus: DENV-1, DENV-2, DENV-3 and DENV-4. “It’s possible to get infected by each serotype, so a person can get dengue up to four times,” says Olivia Goethals, Ph.D., Associate Director, Janssen Pharmaceutical Companies of Johnson & Johnson and Project Leader for Johnson & Johnson’s Dengue Compound Discovery Program. During a second infection with another serotype, you may experience what’s called antibody-dependent enhancement, which can lead to more severe disease, she explains.
2.
Infections range from asymptomatic to deadly.
Many people infected with the dengue virus don’t experience any signs or symptoms, but asymptomatic dengue still contributes to the transmission and further spread of the disease. And symptomatic dengue can be serious, and sometimes fatal.
When symptoms occur, they usually begin three to eight days after the bite by the infected mosquito, and can include a high fever along with severe headache, nausea, vomiting, swollen glands, rash, pain behind the eyes and muscle, joint or bone pain. The fact that these symptoms can be mistaken for other illnesses such as flu, along with the existence of asymptomatic dengue infections, means incidence is likely under-reported.
“In some cases, people develop severe dengue, which is also known as dengue hemorrhagic fever,” says Goethals. It can cause extreme abdominal pain, fatigue, persistent vomiting, bleeding from the nose or gums, blood in the stool and vomit. Severe dengue is a medical emergency and can lead to internal bleeding, shock and death.
3.
Dengue incidence is on the rise.
Dengue is commonly found in tropical and subtropical climates—mainly in Southeast Asia, Latin America and the Pacific Islands. But local transmissions have been reported in the U.S. and its territories, as well as in parts of Europe. They typically rise during the rainy season but infections can happen anytime.
“Right now, more than 50% of the human population is living in dengue virus endemic areas, and that percentage is expected to rise worldwide,” says Goethals.
Global warming is the biggest driving force for the increase. “Mosquitoes, especially the ones that transmit dengue, love warm temperatures and humidity, and with the warming climate they’re now able to travel farther north than they could before,” says De Marez.
In addition to climate change, Goethals also cites urbanization and intercontinental travel as contributors to the growing dengue problem.
As dengue cases increase, so too will their impact on the healthcare system. “Major dengue outbreaks burden healthcare systems because all at once you get large numbers of hospitalizations, similar to what happened with COVID-19,” says De Marez. This can be especially difficult for resource-limited settings, she adds.
4.
The virus presents several challenges to researchers.
This month, Johnson & Johnson launched the J&J Satellite Center for Global Health Discovery at Duke-NUS in Singapore. The Satellite Center will focus on researching flaviviruses, including dengue fever.
Currently, there is only one approved vaccine for dengue, but there are strict restrictions for its usage.
There’s also no cure; only the symptoms can be managed.
The reasons for so few preventive and treatment methods are myriad. With dengue—as with other NTDs, which tend to occur mainly in resource-limited settings—research and development tends to be underfunded, says De Marez (hence why they’re called “neglected”).
Another complication, she notes, is that for preventives and therapeutic treatments to really make a difference, they must work against all four serotypes of dengue.
5.
New ways to prevent and treat dengue are on the horizon.
Janssen’s Dengue Compound Discovery Program, in collaboration with KU Leuven Rega Institute and the Centre for Drug Design and Discovery, both in Belgium, has developed a compound with a novel mechanism of action that could potentially protect against and treat all dengue serotypes.
The molecule works by blocking the interaction between two viral proteins that are necessary for the replication of the virus, Goethals explains.
“We’ve completed a first-in-human Phase 1 double-blind, randomized, placebo-controlled study,” says De Marez. Results showed that the compound, when administered orally as single or multiple doses, was safe and well-tolerated and had no serious adverse events reported. Currently, Janssen is evaluating the antiviral in Phase 2 clinical studies.
This month, Janssen scientists presented research at the Asia Dengue Summit in Singapore and discussed the potential role of antivirals in the prevention and treatment of dengue. “So far the dengue research world is dominated mostly by potential vaccines, and our compound is really the first small-molecule antiviral that is moving forward and being developed for prevention as well as treatment,” De Marez says.
Also this month, Johnson & Johnson launched the J&J Satellite Center for Global Health Discovery (Satellite Center) at Duke-NUS in Singapore. The Satellite Center will focus on researching flaviviruses, which refer to single-stranded RNA viruses, including dengue, West Nile virus, Zika and others.
Collaborations like this, with Duke-NUS’ expertise in flaviviruses and Johnson & Johnson’s legacy in drug discovery and development, can only be beneficial for the quest to combat diseases like dengue, says Goethals.
De Marez agrees. With dengue cases increasing even more in already endemic areas and spreading farther north, it’s more important than ever to accelerate research, she says. For its part, “Johnson & Johnson is well-placed to play a role in developing a compound that can be one of the tools used to successfully fight dengue globally.”
