Challenges in reducing dengue burden; diagnostics, control measures and vaccines

Abstract

Dengue is a major public health concern worldwide, with the number of infections increasing globally. The illness imposes the greatest economic and human burden on developing countries that have limited resources to deal with the scale of the problem. No cure for dengue exists; treatment is limited to rehydration therapy, and with vector control strategies proving to be relatively ineffective, a vaccine is an urgent priority. Despite the numerous challenges encountered in the development of a dengue vaccine, several vaccine candidates have shown promise in clinical development and it is believed that a vaccination program would be at least as cost-effective as current vector control programs. The lead candidate vaccine is a tetravalent, live attenuated, recombinant vaccine, which is currently in Phase III clinical trials. Vaccine introduction is a complex process that requires consideration and is discussed here. This review discusses the epidemiology, burden and pathogenesis of dengue, as well as the vaccine candidates currently in clinical development.

Keywords::

• burden
• chimeric
• dengue
• DNA
• live attenuated
• non-replicating
• subunit
• tetravalent
• vaccine introduction
• vector control

Acknowledgements

The author would like to thank Rémy Teyssou (Sanofi Pasteur) for their helpful comments.

Financial & competing interests disclosure

SK Lam thanks the University of Malaya for its support in providing a grant (HIR J-00000-73554-B27110) for his involvement in dengue activities. SK Lam was the Chair of Dengue v2V, an advocacy initiative supported by an unrestricted educational grant from Sanofi Pasteur. Editorial support was provided by Interlace Global and funded by Sanofi Pasteur. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• • Dengue is a major public health concern worldwide, with 2.5 billion people at risk of transmission in over 100 endemic countries.

• • The illness imposes a significant human and economic burden in developing countries and the annual global burden of dengue is estimated to be 750,000 disability-adjusted life-years (DALYs).

• • There is no cure for dengue and, with vector control strategies providing minimal short-term benefit, there is an urgent need for a vaccine.

• • The development of an effective vaccine has been hindered by a number of challenges, including the need to ensure the absence of vaccine-induced sensitization and the lack of appropriate animal models of disease.

• • Several live attenuated and non-replicating vaccine candidates are showing promise in clinical development, with the lead candidate in Phase III clinical trials.

• • Vaccine introduction requires a variety of considerations, such as logistics, infrastructure, long-term efficacy and safety and planning of vaccine supply.

• • It is now necessary to raise dengue disease awareness and, in future, to integrate vector control measures with vaccination to increase the control of dengue.

Notes