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Dengue vaccine estimated to reduce disease burden in dengue-affected areas

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The first available dengue vaccine, CYD-TDV (Dengvaxia), is estimated to reduce the burden of dengue and be potentially cost effective in settings where infections with dengue are common, according to a study published by Stefan Flasche from the London School of Hygiene & Tropical Medicine, UK and an international consortium of dengue experts, in PLOS Medicine.

The researchers used dynamical models informed by the results of efficacy trials combined with assumptions on vaccine mechanisms, to estimate the impact and cost-effectiveness of CYD-TDV over a 30-y post-vaccination period in a variety of epidemiological settings. In settings with moderate to high dengue transmission intensity, i.e. where at least 50% of children get infected with dengue before they are nine years old, they estimated that a routine vaccination policy involving a three-dose schedule in 9-y-old children at 80% coverage would reduce the burden of dengue disease for the population by 6%-25% and that vaccination would be potentially cost-effective if priced competitively. However, in settings where dengue infections are uncommon, they identified a risk of potential increase in hospitalizations for dengue disease.

These findings were an important contribution to the evidence base that led the WHO to recommend countries to consider the use of CYD-TDV only in settings with a high burden of dengue disease.

The authors say: "Our results can guide countries on the general suitability of Dengvaxia introduction; however, local factors related to treatment costs, intensity of dengue transmission and age groups particularly exposed to dengue will need to be considered."

In a linked Perspective, Jacqueline Deen from the University of the Philippines, Manila, discusses challenges in balancing the individual and population risks and benefits for CYD-TDV.

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Research Article

Funding:

SF and MJ received funding from WHO and Gavi, the Vaccine Alliance, to conduct this work. LC is a paid employee at Sanofi Pasteur. GM and JK were funded by the University of Western Australia, with computing resources provided by the Pawsey Supercomputing Centre, which is funded by the Australian Government and the Government of Western Australia. MR is funded by a Royal Society University Research Fellowship. NF, ID and DJL received research funding from the UK Medical Research Council, the UK NIHR under the Health Protection Research Unit initiative, NIGMS under the MIDAS initiative, and the Bill and Melinda Gates Foundation. IRB and DATC were funded by MIDAS Center Grant NIH/NIGMS U54-GM088491 and the Bill and Melinda Gates Foundation. DATC was also supported by NIH/NIAID R01-AI114703. TJH, IL, and CABP were funded by a Dengue Vaccine Initiative Grant to IL, NIH/NIAID R37 AI32042. THJ, IL, and KK were funded by MIDAS Center Grant NIH/NIGMS 1135 U54 GM111274. All other authors have received no specific funding to conduct this work. The funders had no role in the study design, data analyses, decision to publish or preparation of the manuscript.

Competing Interests:

I have read the journal's policy and the authors of this manuscript have the following competing interests: LC is employed by Sanofi Pasteur. KV is a staff member of the World Health Organization. TAP and GE receive support from GlaxoSmithKline for unrelated work on dengue vaccine modelling. IL, TJH, and CABP have received travel support from Sanofi Pasteur to present other work on dengue vaccine modelling. Sanofi Pasteur has not funded any of their research and was not involved in any research decisions related to their work presented. NF gave advice to Sanofi-Pasteur and the World Health Organization on the efficacy profile and potential public health impact of Dengvaxia. He is also collaborating with Sanofi-Pasteur on secondary analyses of Dengvaxia clinical trial data. He has received no remuneration, grant income, expense payments or in-kind benefit from Sanofi-Pasteur. DATC and IRB have advised WHO on the use of the Sanofi vaccine in a number of meetings and as part of a consortium of modelers who estimated the potential impact of the vaccine. On occasion they received travel expenses for visits to WHO. They have also advised Sanofi Pasteur Ltd. on the implications their work has for use of their vaccine. They have not received any financial or in-kind payment from Sanofi. All other authors have declared that no competing interests exist.

Citation:

Flasche S, Jit M, Rodríguez-Barraquer I, Coudeville L, Recker M, Koelle K, et al. (2016) 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 Med 13(11): e1002181. doi:10.1371/journal.pmed.1002181

Author Affiliations:

London School of Hygiene and Tropical Medicine, London, United Kingdom Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America Sanofi Pasteur, Brussels, Belgium University of Exeter, Exeter, United Kingdom Duke University, Durham, North Carolina, United States of America University of Western Australia, Crawley, Australia University of Florida, Gainesville, Gainesville, Florida, United States of America University of Notre Dame, Notre Dame, Indiana, United States of America Imperial College London, London, United Kingdom University of Oxford, Oxford, United Kingdom Indiana University, Bloomington, Indiana, United States of America World Health Organization, Geneva, Switzerland

IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER:http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002181

Perspective Article

Funding:

No funding was received for this work.

Competing Interests:

I have read the journal's policy and have the following conflicts: I was an unpaid external consultant in the "Extended Study Group for dengue vaccine effectiveness evaluation studies in Asia" from 6 April 2015 to 31 August 2015 convened by Sanofi Pasteur. I was a WHO temporary adviser in a meeting entitled "Targeting Vaccination and Post-licensure Studies for the Licensed Dengue Vaccine" in Geneva from 14 to 15 June 2016 convened by the WHO. I am an unpaid co-investigator of a study entitled "Effectiveness of the tetravalent dengue vaccine, CYD-TDV (Dengvaxia) in the Philippines" currently in preparation, sponsored by the University of the Philippines-Manila and funded by Sanofi Pasteur.

Citation:

Deen J (2016) The Dengue Vaccine Dilemma: Balancing the Individual and Population Risks and Benefits. PLoS Med 13(11): e1002182. doi:10.1371/journal.pmed.1002182

Author Affiliations:

Institute of Child Health and Human Development, National Institutes of Health, University of the Philippines, Manila, Philippines

IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER:http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002182

Media Contact

Stefan Flasche
[email protected]

http://www.plos.org

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