Reconstructing Historical Changes in the Force of Infection of Dengue Fever in Singapore: Implications for Surveillance and control/Reconstitution Des Variations Historiques a Singapour De la Virulence De la Dengue : Implications Pour la Surveillance et la Lutte Contre Cette maladie/Reconstruccion De la Evolucion De la Virulencia del Dengue En Singapur: Implicaciones Para la Vigilancia Y El Control

Introduction Dengue fever is a viral infection transmitted by Aedes mosquitoes that has recently re-emerged globally as the most important arboviral disease. (1) There are four antigenically distinct dengue virus serotypes (DEN 1-4) that induce permanent serotype-specific, IgG antibody-mediated protective immunity following first infection. (2) Dengue fever presents as a spectrum of increasingly severe clinical manifestations ranging from classic dengue fever to dengue haemorrhagic fever to dengue shock syndrome, (2) although the distinction between these conditions is often blurred. (3) In an endemic situation, the majority of dengue infections are subclinical and the risk factors for severity of clinical outcome include age, viral strain, host genetics and time between heterotypic infection. (4-6) Classic dengue fever is most commonly associated with primary viral infection, and in fully naive individuals the probability of developing clinical disease increases with age. (5) Early studies in the Philippines demonstrated that the risk of classic disease was very high in young adults following primary infection, (7,8) while more recent findings in Indonesia and Thailand indicate that most classic illness in children is the result of secondary infection. (9,10) Due to the complex set of factors that contribute to risk of dengue haemorrhagic fever, as well as the extremely low incidence of dengue haemorrhagic fever in Singapore, this analysis has limited its scope to classic dengue illness. Ae. aegypti, the primary vector for dengue fever, is well adapted to breeding in human-made breeding sites in urban and periurban environments. (11) Dengue is now endemic in over 100 countries, with a dramatic increase in incidence and geographical range recorded in recent years. Reasons for this increase include growing levels of urbanization, international trade and travel disseminating both the vector and viruses, and the inadequacies of current methods to reduce dengue transmission. (12) Singapore is one of the few settings that have recorded sustained suppression of the vector population. The dengue control programme combines ali WHO-recommended control activities, including public health education and community participation, active breeding site detection, environmental management, reactive insecticide fogging, and geo-referenced entomologic and clinical surveillance systems. (13) Since the first legislation to enforce vector control was introduced in 1966, Singapore has seen the Aedes household index (the percentage of ali properties with breeding sites of Aedes mosquitoes) reduced from over 50% to less than 1% (Fig. 1). (14) However, a contradictory phenomenon is occurring in Singapore, whereby the incidence of dengue fever has recently increased despite the success of the vector control programme. Notably, the overwhelming majority of cases in recent years have been as classic dengue fever, with dengue haemorrhagic fever representing less than 1% of the 21 000 officially reported cases between 2000 and 2004. (15,16) Intuitively, it would be expected that a decrease in the mosquito population would lower the force of infection (the per capita rate at which susceptible individuals acquire infection) and consequently decrease disease incidence. While the Aedes household index and the observed increases in average age of clinical dengue (17) (Fig. 2) are consistent with a decrease in the force of infection, the disease incidence continues to climb. The number of confirmed dengue cases climbed from a record level of 9292 in 2004 to a new high of over 13 800 in 2005 (Fig. 1). (18) Determining the temporal pattern of force of infection is essential to understanding the extent to which vector control in Singapore has reduced the intensity of dengue transmission, thus helping to clarify the unprecedented rise in disease incidence. Force of infection has been used widely to understand the intensity of disease transmission within a community. …