Passive surveillance is based on the reporting of confirmed or suspected cases encountered by health care workers. However, as most dengue cases are ambulatory, and not always seen by health care workers, this system results in significant under-reporting. Under-reporting also results from the lack of a universally Veliparib applicable or uniformly applied case definition [16]. Improving the availability and reliability of diagnostics for dengue is a major priority. Recent recommendations from the Asia-Pacific and Americas Dengue Prevention Boards (organised by the Dengue Vaccine

Initiative Consortium) include: making the reporting of dengue mandatory, use of electronic reporting systems, application of minimum reporting requirements and sharing of expertise and data [15]. To obtain support from governments and global decision-makers, a dengue vaccine must be shown to be cost-effective. This requires accurate data on the economic costs of dengue. Dengue is responsible for an annual

estimated global burden of 750,000 disability-adjusted life years (DALY) SNS-032 clinical trial [6], [17] and [18]. A study across eight countries in Asia and Latin America estimated that the mean cost per hospitalised case of dengue is US$571, of which 76% was direct costs and 24% indirect costs [19]. For ambulatory cases the mean cost per case was US$248, of which 28% was direct costs and 72% indirect costs [19]. Another study estimated the total cost of dengue illness across the Americas (based on data from 2000 to 2007) at US$2149.8

million per year, with a total of 72,772 DALY lost [17]. Ambulatory cases accounted for 73% of the costs, hospitalised cases 24%, from and deaths 3% [17]. A comprehensive review of health economic studies of dengue burden has recently been published [20]. Such cost studies face two main challenges: (i) it is difficult to incorporate all of the costs of a case of dengue, and (ii) incidence of dengue is considerably under-estimated. Expansion factors are used to adjust for the under-reporting of cases and provide estimates of the true extent of the dengue burden [21]. Expansion factors of 10–27 in Puerto Rico [22], 6 in Panama [23] and 21.3 in Nicaragua [24] have been reported. While different expansion factors for different countries might be expected given differences in surveillance systems, the wide variation observed calls for a systematic and comprehensive analysis of dengue under-reporting. Indeed, reliable expansion factors will be essential to calculate the full cost of dengue. The threshold for vaccine cost-effectiveness recommended by the WHO is a cost per DALY saved of three times the annual per capita gross domestic product (GDP) [25]. For dengue-endemic countries in the Asia-Pacific region this threshold is approximately US$3000. The cost-effectiveness of a dengue vaccine in Southeast Asia was calculated assuming a two-dose schedule and different potential prices per dose [26] and [27].