On December 13, 2017, following a consultation with the Global Advisory Committee on Vaccine Safety, the World Health Organization (WHO) determined that the dengue vaccine CYD-TDV, sold under the brand name Dengvaxia, prevents disease in majority of vaccine recipients but it should not be administered to people who have previously not been infected with dengue virus53.
This recommendation was based on new evidence communicated by the vaccine manufacturer (Sanofi Pasteur), indicating an increase in incidence of hospitalization and severe illness in vaccinated children never infected with dengue.
The WHO Global Advisory Committee on Vaccine Safety considered the company's new results from the analysis of clinical trial data, which indicate an increased risk of severe dengue disease, in people who have never been infected affects about 15% of the vaccinated individuals. The magnitude of risk is in the order of about 4 out of every 1000 seronegative patients vaccinated who developed severe dengue disease during the five years of observation; whereas the risk of developing severe dengue disease in non-vaccinated individuals has been calculated as 1.7 per 1000 over the same period of observation. By contrast, for the 85% who have had dengue disease before immunization, there is a reduction of 4 cases of severe dengue per 1 000 who are vaccinated.
To minimize illness for seronegative vaccinated people, WHO recommends enhancing measures that reduce exposure to dengue infection among populations where the vaccine has already been administered. For vaccine recipients who present with clinical symptoms compatible with dengue virus infection, access to medical care should be expedited to allow for proper evaluation, identification, and management of severe forms of the disease.
Background
Dengue is a mosquito-borne viral infection causing a severe flu-like illness and, sometimes causing a potentially lethal complication called severe dengue. The incidence of dengue has increased 30-fold over the last 50 years. Up to 50-100 million infections are now estimated to occur annually in over 100 endemic countries, putting almost half of the world's population at risk54. The dengue virus (DEN) comprises four distinct serotypes (DEN-1, DEN-2, DEN-3 and DEN-4) which belong to the genus Flavivirus, family Flaviviridae. Distinct genotypes have been identified within each serotype, highlighting the extensive genetic variability of the dengue serotypes. Among them, "Asian" genotypes of DEN-2 and DEN-3 are frequently associated with severe disease accompanying secondary dengue infections.
The disease is endemic in more than 100 countries in WHO's African, American, Eastern Mediterranean, South- East Asian and Western Pacific regions; wherein the Americas, South-East Asia and Western Pacific regions are the most seriously affected.
There is no specific dengue treatment and prevention is primarily limited to vector control measures. A safe and effective dengue vaccine would therefore, represent a major advance in the control of the disease.
Sanofi Pasteur, the vaccines division of Sanofi, was the first pharmaceutical company to develop and market a vaccine for Dengue known as Dengvaxia® (earlier known as CYD-TDV). It is the first vaccine to be licensed in the world for the prevention of dengue. It is a live attenuated tetravalent vaccine made using recombinant DNA technology and is administered in three phases separated by six-month intervals. It became commercially available in 2016 and is currently licensed in 19 countries (Argentina, Australia, Bangladesh, Bolivia, Brazil, Cambodia, Costa Rica, El Salvador, Guatemala, Honduras, Indonesia, Malaysia, Mexico, Paraguay, Peru, The Philippines, Singapore, Thailand and Venezuela)55.
New analysis evaluated long-term safety and efficacy
Earlier on November 29, 2017, Sanofi announced that it will ask health authorities to update information provided to physicians and patients on its dengue vaccine Dengvaxia® in countries where it is approved. The request was based on a new analysis of long-term clinical trial data, which found differences in vaccine performance based on prior dengue infection56.
Based on up to six years of clinical data, the new analysis evaluated long-term safety and efficacy of Dengvaxia in people who had been infected with dengue prior to vaccination and those who had not been infected. The analysis confirmed that Dengvaxia provides persistent protective benefit against dengue fever in those who had prior infection. For those not previously infected by dengue virus, however, the analysis also found that in the longer term, more virulent and severe form of disease could occur following vaccination upon a subsequent dengue infection.
Proposed Label Update
Based on the new analysis, Sanofi will propose that national regulatory agencies update the prescribing information, known as the label in many countries, requesting that healthcare professionals assess the likelihood of prior dengue infection in an individual before vaccinating. Vaccination should only be recommended when the potential benefits outweigh the potential risks (in countries with high burden of dengue disease). For individuals who have not been previously infected by dengue virus, vaccination should not be recommended.
Footnotes
54 http://www.who.int/denguecontrol/disease/en/
55 http://dengue.info/dengue-vaccine-registered-in-19-countries/
56 http://mediaroom.sanofi.com/sanofi-updates-information-on-dengue-vaccine/
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