Dengue is a systemic viral infection transmitted between humans by Aedes mosquitoes^[1]. For some patients, dengue is a life-threatening illness^[2]. There are currently no licensed vaccines or specific therapeutics, and substantial vector control efforts have not stopped its rapid emergence and global spread^[3]. The contemporary worldwide distribution of the risk of dengue virus infection^[4] and its public health burden are poorly known^{[2, 5]}. Here we undertake an exhaustive assembly of known records of dengue occurrence worldwide, and use a formal modelling framework to map the global distribution of dengue risk. We then pair the resulting risk map with detailed longitudinal information from dengue cohort studies and population surfaces to infer the public health burden of dengue in 2010. We predict dengue to be ubiquitous throughout the tropics, with local spatial variations in risk influenced strongly by rainfall, temperature and the degree of urbanization. Using cartographic approaches, we estimate there to be 390 million (95% credible interval 284–528) dengue infections per year, of which 96 million (67–136) manifest apparently (any level of clinical or subclinical severity). This infection total is more than three times the dengue burden estimate of the World Health Organization^[2]. Stratification of our estimates by country allows comparison with national dengue reporting, after taking into account the probability of an apparent infection being formally reported. The most notable differences are discussed. These new risk maps and infection estimates provide novel insights into the global, regional and national public health burden imposed by dengue. We anticipate that they will provide a starting point for a wider discussion about the global impact of this disease and will help to guide improvements in disease control strategies using vaccine, drug and vector control methods, and in their economic evaluation. [Abstract from Nature]

Author Summary from PLoS: Information gleaned from surveys of country-level policymakers and other opinion leaders can assist in planning the development, production and introduction of new or upcoming vaccines into public sector immunization programs. In the case of dengue vaccines, prevailing views among these leaders about the importance of the disease, their expressed level of interest in the government's use of the vaccine, and preferred strategies for vaccine introduction (e.g., geographically-targeted vs. nation-wide vaccination, specific age groups to target) can help to identify “early adopter” countries and indicate the level of demand for the vaccine. This information can be critical to current producers of the vaccine in planning their production capacity and to potential future producers in deciding whether to pursue development of the vaccine. This information also helps donors and international technical agencies, such as WHO and UNICEF, in setting their priorities and determining their level of technical and financial support to countries for the introduction of dengue vaccines. In addition, these surveys can provide crucial information to national governments and the above stakeholders about potential barriers to introducing dengue vaccines into national immunization programs, and what additional studies and data countries will require in order to make decisions about use of the vaccines in the public sector.

(Abstract) After 3 dengue cases were acquired in Key West, Florida, we conducted a serosurvey to determine the scope of the outbreak. Thirteen residents showed recent infection (infection rate 5%; 90% CI 2%-8%), demonstrating the reemergence of dengue in Florida. Increased awareness of dengue among health care providers is needed.

(Abstract) Conditions that facilitate sustained dengue transmission exist in the United States, and outbreaks have occurred during the past decade in Texas, Hawaii, and Florida. More outbreaks can also be expected in years to come. To combat dengue, medical and public health practitioners in areas with mosquito vectors that are competent to transmit the virus must be aware of the threat of reemergent dengue, and the need for early reporting and control to reduce the impact of dengue outbreaks. Comprehensive dengue control includes human and vector surveillance, vector management programs, and community engagement efforts. Public health, medical, and vector-control communities must collaborate to prevent and control disease spread. Policy makers should understand the role of mosquito abatement and community engagement in the prevention and control of the disease.

(Abstract) Dengue represents a major public health problem of growing global importance. In the absence of specific dengue therapeutics, strategies for disease control have increasingly focused on the development of dengue vaccines. While a licensed dengue vaccine is not yet available, several vaccine candidates are currently being evaluated in clinical trials and are described in detail in accompanying articles. In addition, there are a large variety of candidates in preclinical development, which are based on diverse technologies, ensuring a continued influx of innovation into the development pipeline. Potentially, some of the current preclinical candidates may become next generation dengue vaccines with superior product profiles. This review provides an overview of the various technological approaches to dengue vaccine development and specifically focuses on candidates in preclinical development.

(Abstract) PURPOSE OF REVIEW: Dengue is currently an expanding global health problem. Development of an effective tetravalent dengue vaccine is considered a high public health priority. The uniqueness of the dengue viruses (DENVs) and the spectrum of disease resulting from infection has made dengue vaccine development difficult. This review focuses on the current critical issues in dengue vaccine development. RECENT FINDINGS: DENVs are arboviral flaviviruses transmitted by Aedes mosquitoes causing a spectrum of clinical disease. DENV infections are a significant global health problem; the WHO estimates that more than 120 countries have endemic DENV transmission resulting in 70-500 million infections, 2.1 million clinically severe cases, and 21 000 deaths annually. There are currently no licensed antivirals or vaccines to treat or prevent dengue. The DENV-host interaction of infection is unique with severe disease a consequence of sequential dengue infection, viral immune evasion, host antibody enhancement, host immune activation, and genetic predisposition. This unique pathogen-host interaction complicates dengue vaccine development and creates provocative questions in vaccine development such as identifying markers of protective immunogenicity, the potential role of antibody in vaccine failures, and the possible impact of large-scale vaccination on the evolution of wild-type DENV. SUMMARY: Dengue is a unique and complex disease; developing a dengue vaccine has proven equally complex. In this review, the authors discuss issues that will prove to be critical to the success or failure of the dengue vaccine development effort.

(Abstract) Infection with dengue virus is a major public health problem in the Asia-Pacific region and throughout tropical and sub-tropical regions of the world. Vaccination represents a major opportunity to control dengue and several candidate vaccines are in development. Experts in dengue and in vaccine introduction gathered for a two day meeting during which they examined the challenges inherent to the introduction of a dengue vaccine into the national immunisation programmes of countries of the Asia-Pacific. The aim was to develop a series of recommendations to reduce the delay between vaccine licensure and vaccine introduction. Major recommendations arising from the meeting included: ascertaining and publicising the full burden and cost of dengue; changing the perception of dengue in non-endemic countries to help generate global support for dengue vaccination; ensuring high quality active surveillance systems and diagnostics; and identifying sustainable sources of funding, both to support vaccine introduction and to maintain the vaccination programme. The attendees at the meeting were in agreement that with the introduction of an effective vaccine, dengue is a disease that could be controlled, and that in order to ensure a vaccine is introduced as rapidly as possible, there is a need to start preparing now.

(Abstract) BACKGROUND: A vaccine to prevent dengue disease is urgently needed. Fortunately, a few tetravalent candidate vaccines are in the later stages of development and show promise. But, if the cost of these candidates is too high, their beneficial potential will not be realized. The price of a vaccine is one of the most important factors affecting its ultimate application in developing countries. In recent years, new vaccines such as those for human papilloma virus and pneumococcal disease (conjugate vaccine) have been introduced with prices in developed countries exceeding $50 per dose. These prices are above the level affordable by developing countries. In contrast, other vaccines such as those against Japanese encephalitis (SA14-14-2 strain vaccine) and meningitis type A have prices in developing countries below one dollar per dose, and it is expected that their introduction and use will proceed more rapidly. Because dengue disease is caused by four related viruses, vaccines must be able to protect against all four. Although there are several live attenuated dengue vaccine candidates under clinical evaluation, there remains uncertainty about the cost of production of these tetravalent vaccines, and this uncertainty is an impediment to rapid progress in planning for the introduction and distribution of dengue vaccines once they are licensed. METHOD: We have undertaken a detailed economic analysis, using standard industrial methodologies and applying generally accepted accounting practices, of the cost of production of a live attenuated vaccine, originally developed at the US National Institutes of Health (National Institute of Allergy and Infectious Diseases), to be produced at the Instituto Butantan in Sao Paulo, Brazil. We determined direct costs of materials, direct costs of personnel and labor, indirect costs, and depreciation. These were analyzed assuming a steady-state production of 60 million doses per year. RESULTS: Although this study does not seek to compute the price of the final licensed vaccine, the cost of production estimate produced here leads to the conclusion that the vaccine can be made available at a price that most ministries of health in developing countries could afford. This conclusion provides strong encouragement for supporting the development of the vaccine so that, if it proves to be safe and effective, licensure can be achieved soon and the burden of dengue disease can be reduced.

In 2012, dengue is the most important vector-borne viral disease of humans and likely more important than malaria globally in terms of morbidity and economic impact.

(Abstract) Dengue infection is a significant and escalating public health problem in Latin America. Its re-emergence and subsequent rise in the region over the past 50 years has largely been caused by a combination of a lack of political will, the radical growth of urban populations, migration flow and insufficient financial resources. Its increased incidence has been compounded by climate change, poor sanitation and extreme poverty, which lead to more breeding sites of the mosquito vector Aedes aegypti. In order to control dengue effectively, an integrated approach incorporating vector management and environmental and social solutions is required. To achieve success, these programmes require commitment and responses at both national and community level. The development of a vaccine is a vital tool in the fight against dengue. For successful introduction, those implementing vaccination need to be educated on the value of such a strategy. Effective political leadership, innovative financial mechanisms and co-operation across all disciplines, sectors and national borders are essential to eradication of the disease.