Dengue Infection in Children in Ratchaburi, Thailand: A Cohort Study. I. Epidemiology of Symptomatic Acute Dengue Infection in Children, 2006–2009

Abstract
There is an urgent need to field test dengue vaccines to determine their role in the control of the disease. Our aims were to study dengue epidemiology and prepare the site for a dengue vaccine efficacy trial. We performed a prospective cohort study of children in primary schools in central Thailand from 2006 through 2009. We assessed the epidemiology of dengue by active fever surveillance for acute febrile illness as detected by school absenteeism and telephone contact of parents, and dengue diagnostic testing. Dengue accounted for 394 (6.74%) of the 5,842 febrile cases identified in 2882, 3104, 2717 and 2312 student person-years over the four years, respectively. Dengue incidence was 1.77% in 2006, 3.58% in 2007, 5.74% in 2008 and 3.29% in 2009. Mean dengue incidence over the 4 years was 3.6%. Dengue virus (DENV) types were determined in 333 (84.5%) of positive specimens; DENV serotype 1 (DENV-1) was the most common (43%), followed by DENV-2 (29%), DENV-3 (20%) and DENV-4 (8%). Disease severity ranged from dengue hemorrhagic fever (DHF) in 42 (10.5%) cases, dengue fever (DF) in 142 (35.5%) cases and undifferentiated fever (UF) in 210 (52.5%) cases. All four DENV serotypes were involved in all disease severity. A majority of cases had secondary DENV infection, 95% in DHF, 88.7% in DF and 81.9% in UF. Two DHF (0.5%) cases had primary DENV-3 infection. The results illustrate the high incidence of dengue with all four DENV serotypes in primary school children, with approximately 50% of disease manifesting as mild clinical symptoms of UF, not meeting the 1997 WHO criteria for dengue. Severe disease (DHF) occurred in one tenth of cases. Data of this type are required for clinical trials to evaluate the efficacy of dengue vaccines in large scale clinical trials. There is an urgent need to field test dengue vaccine. Efficacy trials need to be conducted in study sites with sufficiently high dengue incidence to make a robust estimate of vaccine efficacy and where all dengue virustypes circulate frequently. In this paper, we report on dengue disease surveillance on approximately 3000 primary-school children in seven schools in Muang district of Ratchaburi province, central Thailand, from 2006 through 2009. We report on the characteristics of children in this cohort who fell ill with laboratory confirmed dengue disease. The study showed that approximately four percent of the children had laboratory confirmed dengue per year. All four dengue virus types were found to be the causes of illness in children in all seven schools. This study has shown Muang district of Ratchaburi province to be suitable for dengue vaccine testing and the site has been selected for the world’s first dengue vaccine safety and efficacy study, being conducted from 2009–2014 in children aged 4–11 years.