Is it time to rollback dengue? - Mini Review

The past 40 years have seen a dramatic increase in the frequency, magnitude and geographic expansion of epidemic dengue, making it the most important vector-borne viral disease in the world. Mosquito control, the only option available for dengue control, has failed. New and innovative tools in the pipeline, however, may provide the opportunity to rollback this disease. The past 40 years have seen a dramatic increase in the frequency, magnitude and geographic expansion of epidemic dengue, closely tied to the unprecedented human population growth, urbanization and globalization that have occurred during the same time period. These global trends, combined with lack of effective mosquito control, have facilitated the expansion of both the viruses and the mosquito vectors that transmit the disease, to most urban centres of the tropics. Dengue, the most important vector-borne viral disease in the world, is primarily an urban disease, with an estimated 3.6 billion people living in areas of risk and 400 million infections annually. The economic and social costs of epidemic dengue make it a devastating public health problem in the resource poor countries of the tropics [1–4]. There is neither approved vaccine nor specific drugs available for dengue, mosquito control being the only option available for disease prevention and control. Unfortunately, conventional mosquito control methods have failed in sustainable prevention of epidemic dengue [5]. The reasons for this failure are complex and beyond the scope of this paper, but include the lack of effective mosquito control tools, resources and commitment to control the disease in dengue endemic countries. That is the bad news! The good news is that the outlook for dengue control going forward is very positive. Recent dengue research has led to the development of a number of new and innovative dengue control tools, including vaccines, antiviral drugs, therapeutic antibodies, insecticides and other mosquito control tools. The insecticides include new classes of chemicals that will provide residual activity for 6 months to a year, a characteristic that is critical to control adult mosquitoes emerging from cryptic or hidden larval habitats. Other new insecticides can be formulated as spatial repellents to prevent mosquitoes from entering selected areas or to treat both natural and artificial oviposition sites. These new insecticides have the potential to provide costeffective adult mosquito control. Other new and promising mosquito control tools include both genetic and biological approaches [6, 7]. The most promising genetic approach is the release of sterile male mosquitoes into a natural population to mate with wild female mosquitoes. If the sterile males are released in high enough numbers, the wild population will decrease. Sterile males can be produced by the millions and released as eggs into natural populations. Field trials have been or are being conducted in Malaysia, Cayman Islands, Brazil and Panama, all with promising results. A promising biological control tool is the infection of Aedes aegypti mosquitoes with a common bacterium, Wolbachia that naturally infects over 70% of all insects in nature, but for reasons that are unknown, not Ae. aegypti. Several strains of Wolbachia have been adapted to infect Ae. aegypti, causing decreased survival and decreased susceptibility to infection with dengue viruses. Field trials have been carried out in Australia showing effective spread of Wolbachia into the natural Ae. aegypti populations. Other trials in Vietnam, Indonesia, China, Colombia and Brazil are in progress. Also exciting is the progress in dengue vaccine development [8]. There are currently six candidate dengue vaccines in the clinical trial pipeline, one in phase III, two in phase II and three in phase I (Table 1). In addition, there are numerous third-generation vaccines under development using new molecular technology. The candidate in phase III is a tetravalent chimeric vaccine constructed on the 17D yellow fever vaccine backbone manufactured by Sanofi Pasteur. The yellow fever PrM and envelope genes have been replaced with the respective genes from DENV 71, 72, 73 and 74. A phase IIB trial of this vaccine in Thailand raised concern because efficacy was low for DENV-2; however, it was safe [9]. The first phase III efficacy trial involving 10,275 children aged 2–14 years in five Asian countries has just been published, with more promising results [10]. Although the DENV-2 efficacy was still relatively low, the vaccine performed well against the other serotypes and in protecting against severe disease. The overall efficacy was 56.5%. Results from a second phase III trial in five dengue endemic countries in the Americas will be available in late 2014. Expectations are that the Sanofi vaccine will be licensed by 2017 if all goes as expected. The two vaccines in phase II trials are the Takeda (Inviragen) dengue chimeric vaccine that uses the http://www.cabi.org/cabreviews CAB Reviews 2014 9, No. 029