Due to the possible increased risk of severe symptoms in some cases, a WHO advisory group has updated recommendations for the use of a new dengue vaccine.
Dengue fever is caused by four closely related viruses carried by the Aedes mosquito. It is the most common mosquito-borne virus infection, with an estimated 390,000 million infections every year, mostly in tropical countries. The majority of dengue infections are “silent” with no symptoms, but it causes an estimated 60 million symptomatic cases and 10,000 deaths per year.
Dengue symptoms include high fever, headache, pain behind the eyes, rash and severe muscle and joint pain. It is sometimes called “bone-break” fever. Treatment for dengue involves supportive care to control the symptoms, which usually settle after about 10 days. However, a small proportion of cases develop a severe hemorrhagic fever with bleeding that may result in death.
Severe symptoms can appear after an episode of dengue infection, but the chances of severe disease seem to be greater in people who had a dengue infection in the past and are later re-infected by a different type of dengue virus. This is thought to be linked to the body’s immune response to the second infection. This complex pattern of dengue infections has made it difficult to develop safe and effective vaccines.
Dengue vaccine may increase the risk of severe symptoms in individuals who are seronegative
Dengvaxia, developed by Sanofi Pasteur, is the first commercially available dengue vaccine. Following clinical trials, where it was shown to reduce severe dengue cases and hospital admissions in those aged between 9-45 years, the vaccine was approved for use in 19 countries where dengue is highly endemic. Dengvaxia was used in mass vaccination programs in The Philippines and Brazil in 2016-2017.
The vaccine was not approved for use in younger children, because the trial results in this group were less favourable. It was unclear from the initial clinical trial data if this was due to the young age of the subjects, or because many of them had not yet had previous exposure to the dengue virus. This is known as being “seronegative”, indicating that the individual does not have dengue antibodies in their blood.
After a reassessment of long-term clinical study data, Sanofi Pasteur warned in November 2017 that the vaccine can increase the risk of severe dengue symptoms in subjects who are seronegative, regardless of age.
Recommendations to use Dengvaxia only in people who have had a previous dengue infection
The World Health Organization’s (WHO) Strategic Advisory Group of Experts (SAGE) further reviewed the clinical data, and in April 2018, they recommended that Dengvaxia should only be used in people who have had previous dengue infection and are therefore seropositive.
The implications of Sanofi’s warning and the subsequent SAGE recommendation were discussed in the journal Science, and elsewhere. Currently, there is no reliable rapid testing method for checking if someone has been previously infected with dengue. This causes practical difficulties for vaccination programs. The Philippines stopped its vaccination program in December 2017, and there are concerns about other programs.
Commitment to develop a rapid diagnostic test to assess the status of dengue infection
Sanofi Pasteur has expressed confidence in the safety and efficacy of Dengvaxia and their commitment to develop a rapid diagnostic test that can assess dengue infection status (seropositive or seronegative) as an aid to vaccination programs. They also comment that the SAGE group confirmed the public health value of Dengvaxia and its potential to reduce the burden of dengue infection in countries and populations where it is highly endemic.
Written by Julie McShane, Medical Writer
(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/