Derek Wallace, president, world vaccine enterprise unit, Takeda
Permission granted by Takeda
Derek Wallace was in a dengue-focused ICU in Thailand in 2009 when he first noticed the devastating, up-close influence of the illness, often known as the painful “breakbone fever.” Dealing with a scarcity of area, youngsters shared beds whereas dad and mom slept collectively on mattresses tucked beneath.
“That’s been the case for many years in some international locations,” mentioned Wallace, who was a scientific workforce chief for Sanofi’s dengue vaccine research on the time and is now president of Takeda Pharmaceutical’s world vaccine enterprise unit. “However what’s actually vital is that it’s getting worse. There’s 30 instances extra dengue than there was 50 years in the past, and there’s eight instances extra dengue now than there was 20 years in the past.”
The mosquito-transmitted virus is among the many high 10 world well being threats designated by the World Well being Group. There have been a document 6.43 million instances of dengue and almost 7,000 deaths worldwide in 2023 — the most important outbreak ever recorded. Dengue can be spreading quicker in locations the place it hasn’t earlier than because of elements like local weather change, urbanization and elevated world journey, based on the WHO.
“Dengue is shifting, and we’re beginning to get a ton of regionally acquired dengue fever instances within the U.S., particularly in Puerto Rico, Virgin Islands and Florida,” mentioned Katelyn Jetelina, an epidemiologist and information scientist recognized for a well-liked publication. “And we count on this to proceed growing over time.”
Regardless of the fast world unfold, there isn’t a particular remedy for dengue, and worldwide vaccine availability is restricted.
Sanofi’s Dengvaxia is presently the one FDA-approved dengue vaccine. However the firm is discontinuing the shot within the third quarter of 2026 “as a consequence of low world demand for this product,” a Sanofi spokesperson mentioned by way of electronic mail.
Takeda’s two-dose dengue vaccine, Qdenga, is accepted in 40 international locations excluding the U.S, and Takeda withdrew its U.S. utility in 2023.
“Some further information was requested that we could not present,” Wallace mentioned, however declined to supply particulars.
Though the U.S. IND continues to be open for Qdenga, “there are not any particular updates to share presently in regards to the timing of supplying further information or resubmission,” a Takeda spokesperson mentioned by way of electronic mail.
The vaccination problem
Contracting most viral ailments for the primary time will arm you with antibodies that fend off subsequent infections. However that’s not the case with dengue, because of antibody dependent enhancement that stems from dengue’s 4 intently associated however distinctly totally different viral serotypes.
“It’s difficult as a result of it is a very distinctive illness through which secondary infections are extra extreme than the primary infections,” mentioned Jetelina.
Sanofi’s vaccine has lengthy been mired in controversy because of this. Receiving Dengvaxia might act as a primary dengue an infection, leading to a extra extreme sickness after contracting the virus a second time. Because of this, Dengvaxia can solely be administered to individuals who’ve had dengue earlier than, and other people should be screened for a earlier an infection earlier than getting the shot.
“Dengue is spreading to areas the place it was not prevalent, and it’s affecting extra inclined populations that don’t have any immunity in any way.”
André Siqueira
Head, Dengue World Program, Medication for Uncared for Illnesses
However that’s not how Dengvaxia’s preliminary Philippines rollout went — a mass vaccination program didn’t take this screening step, resulting in extra extreme illness amongst some sufferers and doubtlessly some deaths.
The onerous double whammy of needing a pre-vaccine screening mixed with a three-dose routine — to not point out eroded public belief in vaccines — has meant that demand for Dengvaxia is so low, Sanofi is falling by the wayside.
“Whereas we have now made constant efforts to facilitate its entry and the implementation of the ‘Display & Vaccinate’ strategy as really useful by WHO in 2018, uptake and demand has remained low,” the Sanofi spokesperson mentioned. “Regardless of an elevated prevalence of dengue in numerous components of the world, there’s just one Dengvaxia immunization program in place as a result of complexity of implementing this product.”
Qdenga doesn’t have these limitations. In keeping with Takeda, the two-dose jab is “the one vaccine accepted to be used no matter earlier dengue publicity.” The WHO doesn’t advocate pre-vaccination screenings for Qdenga administration in settings with excessive dengue transmission, though native approvals might range. Qdenga has been proven to be 61% efficient towards symptomatic illness and 84% efficient in stopping hospitalization. Nonetheless, it’s not accepted within the U. S.
Different vaccines are in growth, together with the single-dose Butantan–Dengue vaccine that confirmed constructive section 3 outcomes.
Dengue’s unfold
These vaccination and remedy challenges solely make dengue’s unfold extra worrisome.
“Dengue is spreading to areas the place it was not prevalent, and it’s affecting extra inclined populations that don’t have any immunity in any way,” mentioned André Siqueira, head of the Dengue World Program on the nonprofit Medication for Uncared for Illnesses.
He factors to southern Brazil, the place dengue’s latest and fast unfold has overwhelmed well being methods in an space that beforehand didn’t have any infections.
“What has occurred the previous few years in Brazil might mirror what can occur in these locations the place dengue transmission continues to be choosing up,” Siqueira mentioned.
The U. S. is a kind of locations. In Puerto Rico, a record-high dengue surge sparked a public well being emergency in March, and within the Florida Keys, public well being officers issued an alert final summer season.
Dengue thrives in heat city areas, and the mosquitoes chargeable for its unfold can effectively reproduce even in small pockets of water. Due to this fact, a warming local weather with heavier rainfalls, together with elevated urbanization, are all fueling the unfold. Furthermore, these mosquitoes have developed resistance to pesticides and are adapting to totally different situations, together with extra temperate climates, Siqueira mentioned.
That’s why public well being organizations are taking motion. DNDi kick-started its Dengue Alliance in 2022; the WHO launched a world strategic plan towards dengue earlier this month; and Takeda partnered with the Indian pharma Organic E. Restricted earlier this yr to speed up entry to the vaccine in endemic areas.
However public well being officers and native well being methods are nonetheless racing towards the clock, calling for extra vaccines, dengue-specific remedies and improved diagnostics.
“There’s a notion that we’ll discover one answer for dengue,” Siqueira mentioned. “What we most likely want in essentially the most affected areas is an built-in strategy.”
