Estimates of dengue disease incidence

We used dengue incidence and case fatality rates as provided by Vong et al who conducted an active community-based surveillance (ACS) among individuals aged 0-19 years in Kampong Cham province, Cambodia from 2006 to 2008 [8]. Most of the population (~80%) lives in the southern and northwestern part of the country, mainly along the Mekong River. Kampong Cham is a central province and the most populated of Cambodia. Conditions of dengue's transmission are probably quiet representative of the whole country. A total of 42 villages were under active fever surveillance comprising a total study population of 14,354 participants. For groups of people aged above 20 years, it was assumed that incidences were constant. Since the vast majority of dengue cases in Cambodia occurred before age 20, assumptions made for adults appeared reasonable [9].

Cost of illness

Burden of disease

We used the base case recommended by Murray and Lopez with C = 0.1658, r = 0.03, K = 1 and β = 0.04 [20]. Other factors were calculated for 17 groups of age in 5 year increments (<5 years, 5-9 years and so on until >80 years). Specific incidence rate of dengue, hospitalization and mortality were used for the first four groups of age (from <5 to 15-19 years) as provided by Vong et al [8]. As for previous similar studies carried out in other countries, a disability weight of 0.81 [4, 21, 22] and a duration of disability of 5 days were chosen [17].

Cost of illness

Overall annual dengue costs ranged from US$3,327,284 in 2008 up to US$14,429,513 in 2007 with 2006 showing comparable amounts to 2008 (Table 3). In absence of a discount rate applied to future losses due to premature mortality, total costs doubled. On average the cost per dengue case was US$75 in 2006 and dropped to US$36 in 2007 and US$27 in 2008. Direct medical cost per case was $38 in 2006, $15 in 2007 and US$8 in 2008. When considering cases that sought care in both private and public sectors, these numbers rose to US$41 in 2006, US$29 in 2007 and US$21 in 2008 per case. Patients and their families support the highest share of costs with 65%, 80% and 80% of the total cost for 2006, 2007 and 2008 respectively (Fig. 1). When considering only direct medical costs, out-of-pocket payments represented 48%, 60% and 82% of the total for 2006, 2007 and 2008 respectively (Fig. 2). A sensitivity analysis was performed estimating costs in 2007 and 2008 with health seeking behaviors of 2006. Thus, costs in 2007 would be multiplied by 1.7 and costs of 2008 by 2.1.

	2006	2007	2008
Total costs	5,771,079	14,429,513	3,327,284
Direct costs	3,437,570	6,432,840	1,463,189
Medical costs	2,937,570	5,932,840	963,189
Public hospitals	2,132,224	2,846,950	208,633
Private clinics	743,397	2,470,746	688,489
Health centers	57,628	508,384	34,772
Pharmacies	4,322	106,761	31,295
Control costs	500,000	500,000	500,000
Productive costs	2,333,509	7,996,673	1,864,095
Morbidity	632,325	3,321,906	994,579
Mortality (3% discount rate)	1,701,183	4,674,767	869,516
(Mortality (no discount))	(4,592,640)	(12,354,240)	(2,197,920)

Burden of disease

On costs

Our analyses confirmed the high societal burden of dengue in Cambodia whose total costs represented between 0.03 and 0.17% of Cambodia's Gross Domestic Product. We feel that this analysis is a more accurate estimate of Cambodia's cost of illness due to dengue fever. These costs calculations were based upon robust estimates provided by the ACS of a large population. Unlike previous estimates, proportions of both hospitalized and ambulatory cases were accounted for [7]. Moreover, the study provided a longitudinal perspective of the burden of dengue through estimates from three years with differing epidemiological patterns. Indeed, the incidence data encompassed a regular seasonal epidemic year (2006), a large scale epidemic year (2007) and Year 2008 - a year following a major epidemic. This situation has been observed to be associated with a year of milder clinical presentation and lower incidence of dengue fever [23].

Nevertheless, these numbers still probably represent an underestimation of the real costs caused by endemic dengue. Mothers are well aware of the risks of potential severity during the dengue season. There is a local name for dengue "krun chheam" which translates into "hemorrhagic fever" in Khmer language. As such, during the rainy season fearing hemorrhagic dengue, it is thought that more mothers would seek hospital admission when their children present with febrile illnesses than that they would during the low dengue season. This phenomenon is likely to saturate hospitals capacities and to lower global health care quality because of an overwhelmed staff coping with commonly ill-equipped facilities. As defined by health economists, opportunity costs would occur when treatments for patients suffering from other diseases have to be postponed because of the dengue outbreak [11]. Our results underlined the importance of health seeking behavior on costs. The sensitivity analysis showed that changes in heath seeking behavior in 2007 decreased the medical costs.

COI aim at assessing the economic burden of a given disease to society. Since introduction of these studies, their utility in the decision-making process has often been disputed [10]. Some authors argue that COI merely identify diseases for which large amount of resources are already allocated [24]. COI could also fail in identifying diseases amenable by medical treatment or prevention [25]. Finally it is difficult to compare COI between countries of different health care capacity and access of individuals to adequate health care. Although incidence of dengue may be among the highest, COI may be proportionately lower compared with more developed neighboring countries as ill-equipped public and private hospitals would spend less on symptomatic treatment of dengue. Indeed, our results indicated that small amounts were devoted to dengue in Cambodia compared to other countries with an average cost per case around US$50 [7]. More importantly, despites recent effort by the Cambodian government to introduce safety nets (insurance) or health equity funds in hospitals, the burden of this cost is disproportionately born by the patients and their relatives. In 1997, Cambodia introduced user fees in order to increase hospital revenue, to limit under-the-table payments and eventually improve the quality of care [26, 27]. It was thought that the system could improve financial sustainability and increase heath services utilization, as a consequence of higher quality health services [28]. Hitherto, results from early studies suggest that overall health care utilization increased following user fees introduction [29]. However, utilization of the poorer members of the community is not well documented. In addition nearly half of district hospitals were not covered by equity funds in 2006 [26]. Fee-exemption rates in Cambodia are known to be relatively low compared to other developing countries [26]. Since a significant proportion of Cambodians have no access or cannot afford private health care, many families forgo healthcare. This would be supported by recent findings that suggested a lower hospitalization rate for dengue in Cambodia's poorest households [14]. For the poorest, healthcare access or hospital costs remained an insurmountable issue [24] because loans and high interest rates can impoverish them for many years [14].

On DALYs

Our results are consistent with previous studies. Sheppard et al. reported a DALY rate of 42 DALYs/100,000 in South East Asia [17] and the WHO estimated 54 DALYs/100,000 caused by dengue in Cambodia in 2004. However, Sheppard et al. found that 52% of DALYs were due to premature mortality whereas our results showed a higher share. Cambodia has a very young population with about 50% of the population under 20 years. Since duration of disability is very short and the vast majority of deaths occurred in the 0-20 age group, our estimate is probably more accurate. Some authors reproach age weighting in DALYs calculation to give more value to young adults than to other groups of age [30]. In the Cambodian demographic context, such assumption tends to underestimate the true burden of dengue. Compared to other DALYs estimates provided by the WHO, the burden of dengue appears similar to those of Japanese encephalitis (54 DALYs/100,000), trachoma (69 DALYs/100,000) or even malaria (143 DALYs/100,000). Regional comparisons suggest a burden equivalent in Thailand (60 DALYs/100,000) and Laos (93 DALYs/100,000).

Limitations

As mentioned previously, opportunity costs were not taken into account and are likely to have an important impact on overall costs. Unfortunately, such data were not available and further studies are needed to document these costs. Incidence rates for groups of age above 20 years old were based on assumptions. Average income estimates were based on macroeconomic indicators since accurate data on both salaries and unemployment rate were not available. Median income is likely to be inferior to mean income in Cambodia because of a minority of people with very high incomes. Moreover, all estimates are subject to inaccuracy since informal work represents the majority of employment in Cambodia [31]. However, conservative values were taken on purpose to avoid any overestimation (1 dengue case per 1000 pop. on average).

Implications for health policy

The question is to determine whether COI and DALYs are helpful in prioritizing resources allocation. At first glance, burden of dengue could appear as an issue little importance in Cambodia. DALYs caused by tuberculosis (1,712 DALYs/100,000) or meningitis (356 DALYs/100,000) are by far more considerable (WHO 2004 estimates). However, dengue strikes primarily children in Cambodia, resulting in a lesser impact on DALYs calculation. Regardless of costs underestimation, the share born by families clearly gives an indication of the true burden of dengue for Cambodians. Should a dengue vaccine be highly cost effective, its introduction in Cambodia would provide great benefits to the population [17] in terms of reduced incurrence of debt [14].