In May 2019, the U.S. Food and Drug Administration (FDA) approved Dengvaxia, the first vaccine authorized for the prevention of dengue disease caused by all four dengue virus serotypes (1, 2, 3, and 4). This approval applies to individuals aged 9 through 16 with laboratory-confirmed prior dengue infection who reside in areas where dengue is endemic. Dengue is endemic in U.S. territories such as American Samoa, Guam, Puerto Rico, and the U.S. Virgin Islands.
Global Burden and Severity of Dengue
Dengue disease is the most common mosquito-borne viral disease in the world, and its global incidence has significantly increased in recent decades. According to the U.S. Centers for Disease Control and Prevention (CDC), over one-third of the global population lives in regions at risk of dengue infection. The disease is a major cause of illness in tropical and subtropical areas. Initial infection with the dengue virus may cause no symptoms or mild illness, often mistaken for the flu. However, subsequent infections may lead to severe dengue, including dengue hemorrhagic fever (DHF), a more dangerous form of the disease that can be fatal. Symptoms of severe dengue can include stomach pain, persistent vomiting, bleeding, confusion, and difficulty breathing. Most severe or hospitalized cases are associated with a second dengue virus infection. There are currently no specific antiviral treatments approved for dengue disease, and care is limited to symptom management.
Each year, approximately 400 million dengue virus infections occur globally. Around 500,000 of these develop into DHF, resulting in about 20,000 deaths annually, primarily among children. While dengue cases are rare in the continental U.S., the disease remains prevalent in U.S. territories and regions such as Latin America, Southeast Asia, and the Pacific islands.
Importance of Protection for Previously Infected Individuals
Infection with one type of dengue virus generally provides immunity to that specific serotype. However, a subsequent infection with another serotype increases the risk of severe disease, which can require hospitalization or become fatal. Because the second infection tends to be more dangerous than the first, the approval of a vaccine that protects previously infected individuals is considered an important step in reducing the disease’s impact.
Clinical Studies and Effectiveness
The safety and effectiveness of Dengvaxia were evaluated through three randomized, placebo-controlled clinical trials involving about 35,000 participants from dengue-endemic areas, including Puerto Rico, Latin America, and the Asia Pacific region. Results showed the vaccine was approximately 76 percent effective in preventing symptomatic, laboratory-confirmed dengue disease among individuals aged 9 to 16 who had previously been infected.
Side Effects and Usage Limitations
Reported side effects among those who received the vaccine included headache, muscle pain, joint pain, fatigue, injection site pain, and low-grade fever. These side effects occurred at similar rates between the Dengvaxia and placebo groups and tended to decrease with subsequent doses.
Dengvaxia is not approved for individuals who have not been previously infected with dengue or whose infection history is unknown. In these individuals, the vaccine can simulate a first infection, thereby increasing the risk of severe disease during a future infection. Health care professionals are advised to confirm prior dengue infection using medical records or serological testing before administering the vaccine.
Dosage Schedule and Regulatory Review
This live, attenuated vaccine is delivered in three doses, with the first injection followed by two more doses at six- and twelve-month intervals. The FDA granted Dengvaxia Priority Review and awarded a Tropical Disease Priority Review Voucher, encouraging the development of medical products targeting neglected tropical diseases. Approval of the vaccine was granted to its manufacturer.
Role of the FDA
The FDA is responsible for ensuring the safety, effectiveness, and security of human and veterinary drugs, vaccines, biological products, and medical devices, along with overseeing food safety, radiation-emitting products, dietary supplements, cosmetics, and tobacco regulation.