(Abstract) With several candidate dengue vaccines under development, this is an important time to help stakeholders (e.g., policy makers, scientists, clinicians, and manufacturers) better understand the potential economic value (costeffectiveness) of a dengue vaccine, especially while vaccine characteristics and strategies might be readily altered. We developed a decision analytic Markov simulation model to evaluate the potential health and economic value of administering a dengue vaccine to an individual (≤ 1 year of age) in Thailand from the societal perspective. Sensitivity analyses evaluated the effects of ranging various vaccine (e.g., cost, efficacy, side effect), epidemiological (dengue risk), and disease (treatment-seeking behavior) characteristics. A ≥ 50% efficacious vaccine was highly cost-effective [< 1× per capita gross domestic product (GDP) ($4,289)] up to a total vaccination cost of $60 and cost-effective [< 3× per capita GDP ($12,868)] up to a total vaccination cost of $200. When the total vaccine series was $1.50, many scenarios were cost saving.

(Abstract) The growing burden of dengue in endemic countries and outbreaks in previously unaffected countries stress the need to assess the economic impact of this disease. This paper synthesizes existing studies to calculate the economic burden of dengue illness in the Americas from a societal perspective. Major data sources include national case reporting data from 2000 to 2007, prospective cost of illness studies, and analyses quantifying underreporting in national routine surveillance systems. Dengue illness in the Americas was estimated to cost $2.1 billion per year on average (in 2010 US dollars), with a range of $1–4 billion in sensitivity analyses and substantial year to year variation. The results highlight the substantial economic burden from dengue in the Americas. The burden for dengue exceeds that from other viral illnesses, such as human papillomavirus (HPV) or rotavirus. Because this study does not include some components (e.g., vector control), it may still underestimate total economic consequences of dengue.

(Abstract) An estimated 2·5 billion people are at risk of dengue. Incidence of dengue is especially high in resourceconstrained countries, where control relies mainly on insecticides targeted at larval or adult mosquitoes. We did epidemiological and economic assessments of diff erent vector control strategies. Six high-effi cacy adult vector control applications per year has a cost-eff ectiveness ratio that will probably meet WHO’s standard for a cost-eff ective or very cost-eff ective intervention. Year-round larval control can be counterproductive, exacerbating epidemics in later years because of evolution of insecticide resistance and loss of herd immunity. We suggest the reassessment of vector control policies that are based on larval control only.

(Abstract) Every year, there are several hundred thousand cases of dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) resulting in thousands of deaths. The only method currently available to prevent dengue infections is the control of Aedes aegypti, the mosquito vector. This approach has proved expensive and mostly unworkable. Serial infection occurs in most areas of the world where multiple dengue viruses circulate. Dengue vaccines must provide solid and longlasting protection against all four dengue viruses or, in dengue-endemic countries, there is the risk of sensitising recipients to severe disease. Many candidate dengue vaccines are moving towards clinical trials in human beings. These vaccines include several based on the formation of live-attenuated chimeric viruses. Evidence that dengue vaccines should succeed comes from encouraging experience with attenuated vaccines against related viruses such as yellow fever (YF) and Japanese encephalitis (JE), and from a recent successful phase 1 trial of a chimera of these two viruses. This progress is timely, because global dengue morbidity achieved an all time high during 2001–02.

(Abstract) Dengue is endemic throughout large parts of the Americas and Asia, and is increasingly reported in Africa. More than 2.5 billion people are at high risk of infection in more than 100 endemic countries throughout the tropical and subtropical climate zones. Unplanned urbanization, population migration, and the breakdown of vector control efforts have contributed to the spread of the vector. There is an increase of dengue in its more severe forms, such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), for reasons that are not fully understood. The severe forms, when not properly treated, have become an increasing cause of morbidity and mortality, and are straining the health care systems of many endemic countries. Current treatment of severe disease essentially involves the restoration of fluid, colloid, and electrolyte balances. However, over the past few years, the continuing spread and increasing intensity of the disease, combined with new funding mechanisms for the development and use of vaccines for the developing world, have triggered renewed interest and investment in dengue vaccine research.

(Abstract) This document is addressed to national health and regulatory authorities in dengue-endemic countries interested in using vaccines to control the disease. It is also written for vaccine developers and research scientists interested in the development and field evaluation of such vaccines. The guidelines, which were developed with contributions and comments from many individuals from a variety of countries and institutions (see Annex 1), are designed to help identify the basic technical information required to design dengue vaccine field trials. The purposes of the field trials are firstly, to obtain sufficient data on vaccine safety and efficacy to support vaccine licensure, and secondly, to establish that, in post-licensure field studies, the vaccine proves to be safe and provides long-term protection.

(Abstract) In this review, we consider the issues impacting conduct and design of dengue vaccine trials with reference to the recently published World Health Organization “Guidelines for Conduct of Clinical Trials of Dengue Vaccines in Endemic Areas.” We discuss logistic, scientific and ethical challenges concerning evaluation and introduction of dengue vaccines; these range from randomized trials that establish “proof of concept” of vaccine efficacy, to post-“proof of concept” trials, particularly demonstration projects likely to be required for licensure or for the introduction of an already licensed vaccine into public use. We clarify and define the meaning of “proof of concept” in the clinical trial context and the meaning of terms “phase 2b”, “phase 3b” and “demonstration project”, which are commonly used but have not been defined well in the clinical literature.

(Abstract) A survey of policymakers and other influential professionals in four southeast Asian countries (Cambodia, Indonesia, Philippines and Vietnam) was conducted to determine policymakers' views on the public health importance of dengue fever and dengue haemorrhagic fever (DHF), the need for a vaccine and the determinants influencing its potential introduction. Research felt to be key to future decision-making regarding dengue vaccine introduction include: disease surveillance studies, in-country vaccine trials or pilot projects, and studies on the economic burden of dengue and the cost-effectiveness of dengue vaccines. The results suggest favourable conditions for public and private sector markets for dengue vaccines and the need for creative financing strategies to ensure their accessibility to poor children in dengue-endemic countries. 

(Abstract) Dengue has been reportable in Cambodia since 1980. Virological surveillance began in 2000 and sentinel surveillance was established at six hospitals in 2001. Currently, national surveillance comprises passive and active data collection and reporting on hospitalized children aged 0–15 years. This report summarizes surveillance data collected since 1980.

(Abstract) Dengue vaccines are now in late-stage development, and evaluation and robust estimates of dengue disease burden are needed to facilitate further development and introduction. In Cambodia, the national dengue case-definition only allows reporting of children less than 16 years of age, and little is known about dengue burden in rural areas and among older persons. To estimate the true burden of dengue in the largest province of Cambodia, Kampong Cham, we conducted community-based active dengue fever surveillance among the 0-to-19–year age group in rural villages and urban areas during 2006–2008. The large-scale active surveillance study for dengue fever in Cambodia found a higher disease incidence than reported to the national surveillance system, particularly in preschool children and that disease incidence was high in both rural and urban areas. It also confirmed the previously observed focal nature of dengue virus transmission.