Dengue vaccine no silver bullet but worth a shot for those who need it most

Stefan Flasche, Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine

‘Dengue fever kills 20 in Burkina Faso’ reports the BBC. ‘Dengue claims 26 lives in Maharashtra’ leads the Times of India. Deaths from dengue are actually rare but these recent headlines are a reminder of the dangers the virus poses and the need for a concerted global effort to tackle it.Spread by the Aedes aeygypti mosquito, which is also the main vector for Zika virus, it is the burden of dengue which gives cause for most concern. Dengue cases are dramatically increasing and about half of the world’s population is at risk.

Most cases are reported from South-East Asia and Latin America but Africa also sees devastating outbreaks. Although dengue virus is not currently present in the UK, a warming climate, which Aedes aegypti needs to survive, means dengue could yet arrive here. So what is being done to combat the dengue threat?

Fortunately, a potent vaccine has become available. Clinical trials of CYD-TDV in over 30,000 individuals among Latin America and South East Asia concluded that it has the potential to protect against all four serotypes of dengue, leading to the vaccine being rolled out in certain areas of that part of the world.

CYD-TDV, however, has an unprecedented catch: it provides the best protection to those who have already had one dengue infection before. This is due to a characteristic unique to dengue – a first infection with the virus is usually mild but if the person is infected again it can lead to severe disease including high fever, bleeding and the potentially fatal dengue shock syndrome.

The vaccine acts like an asymptomatic infection, so if given to someone who has never had dengue, a more severe outcome could occur when next infected. This disqualifies the vaccine for use in individuals who are unlikely to have been exposed to dengue before, such as travellers or people in settings with low dengue burden.

A study (link) published earlier this year showed CYD-TDV may increase the risk for hospitalisation if used in young children who have not previously been exposed to dengue. So what now for CYD-TDV? Vaccines are expensive and with concerns over safety, is it time to pull the plug? Absolutely not.

A new London School of Hygiene & Tropical Medicine-led study published in the journal PLOS Medicine, initiated by the World Health Organization and conducted with a team of international experts, offers a new, important perspective. Using mathematical models to combine evidence on the vaccine’s effectiveness and existing knowledge of dengue, we predicted the impact of rolling out CYD-TDV in a variety of settings.

Our study showed that giving CYD-TDV only to those populations with a high burden of disease has the potential to prevent about 1 out of 5 dengue hospitalisations. It predicts that a substantial positive impact of vaccination can be achieved if targeted at individuals who most likely had an infection before and, if priced competitively, a cost-effectiveness profile that is similar to that of other vaccines currently in use.

This situation presents many challenges to local authorities: identifying specific areas within countries that would benefit from vaccination, communicating the benefits and risks of this vaccine to the public in order to avoid both vaccine hesitancy and inappropriate use, and designing and implementing studies that measure the impact of vaccination.

These are tough challenges, but they must be overcome. The global health community must ensure that we are in a position to make best use of this dengue vaccine until other, more effective means of prevention become available.

CYD-TDV is no silver bullet, but if targeted accurately it will bring help to those who need it most.

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Stefan Flasche, Mark Jit, Isabel RodrõÂguez-Barraque, Laurent Coudeville, Mario Recker, Katia Koelle, George Milne, Thomas J. Hladish, T. Alex Perkins, Derek A. T. Cummings, Ilaria Dorigatti, Daniel J. Laydon, Guido España, Joel Kelso, Ira Longini, Jose Lourenco, Carl A. B. Pearson, Robert C. Reiner, Luis Mier-y-TeraÂn-Romero, Kirsten Vannice, Neil Ferguson. The Long-Term Safety, Public Health Impact, and Cost-Effectiveness of Routine Vaccination with a Recombinant, Live-Attenuated Dengue Vaccine (Dengvaxia): A Model Comparison Study. PLOS Medicine. DOI:10.1371/journal.pmed.1002181