WHO Updates Recommendations for Dengue Vaccine

Overview of Dengue Fever

Dengue fever is caused by four closely related viruses transmitted by the Aedes mosquito. This disease represents the most prevalent mosquito-borne viral infection, with an estimated 390 million infections annually, primarily in tropical regions. Although many dengue infections are asymptomatic, the disease leads to approximately 60 million symptomatic cases and 10,000 fatalities each year. Common symptoms include high fever, headaches, pain behind the eyes, rashes, and severe muscle and joint pain, often referred to as “bone-break” fever. Treatment typically involves supportive care, and symptoms generally resolve within ten days. However, a small percentage of cases can escalate to severe hemorrhagic fever, which may be fatal.

Increased Risk of Severe Symptoms

Severe symptoms may arise after an initial dengue infection, particularly in individuals who have previously been infected and later contract a different strain of the virus. This phenomenon appears linked to the body’s immune response during the second infection. The complexity of dengue infections has complicated the development of safe and effective vaccines.

Dengvaxia: The First Commercially Available Dengue Vaccine

Dengvaxia, developed by Sanofi Pasteur, is the first dengue vaccine to be commercially available. Clinical trials demonstrated its efficacy in reducing severe dengue cases and hospitalizations among individuals aged 9 to 45, leading to its approval in 19 dengue-endemic countries. Mass vaccination campaigns were conducted in the Philippines and Brazil during 2016-2017. However, the vaccine was not approved for younger children due to less favorable trial outcomes. The uncertainty surrounding these results was attributed either to the age of the participants or their seronegative status, indicating a lack of dengue antibodies.

Sanofi’s Warning and WHO Recommendations

In November 2017, following a long-term clinical study reassessment, Sanofi Pasteur cautioned that the vaccine could heighten the risk of severe dengue symptoms in seronegative individuals, regardless of age. The World Health Organization’s Strategic Advisory Group of Experts (SAGE) reviewed the data and, in April 2018, recommended that Dengvaxia should only be administered to individuals with a prior dengue infection, or those who are seropositive.

Implementation Challenges and Diagnostic Testing

The implications of Sanofi’s warning and the SAGE recommendations have been discussed in various publications, including the journal Science. A significant challenge remains the lack of reliable rapid testing methods to determine past dengue infections, complicating vaccination efforts. Consequently, the Philippines halted its vaccination program in December 2017, raising concerns about similar initiatives elsewhere.

Future Directions for Dengvaxia

Sanofi Pasteur remains confident in the safety and efficacy of Dengvaxia and is committed to developing a rapid diagnostic test to determine an individual’s dengue infection status (seropositive or seronegative) to facilitate vaccination efforts. The SAGE group has also acknowledged the public health value of Dengvaxia and its potential to alleviate the dengue burden in highly endemic regions.

References

1. Vogel G. A new dengue vaccine should only be used in people who were previously infected, WHO says. Science, April 19, 2018. Doi:10.1126/science.aat9362.
2. Editorial. The dengue vaccine dilemma. The Lancet Infectious Diseases Vol 18 Feb 2018, p123. Doi: 10.1016/S1473-3099(18)30023-9.
3. Sanofi Pasteur communication on SAGE recommendation about Dengvaxia dengue vaccine. April 19, 2018. http://mediaroom.sanofi.com/sanofi-pasteur-communication-on-sage-recommendation-about-dengvaxia-dengue-vaccine/