A prospective seroepidemiologic study on dengue in children four to nine years of age in Yogyakarta, Indonesia I. Studies in 1995-1996

A prospective study on dengue (DEN) viruses was initiated in October 1995 i n Gondokusuman kecamatan, Yogyakarta, Indonesia. This report presents data from the first year of the study. The studied cohort included all children 4-9 years of age living in the kecamatan. Blood samples for serology were c ollected from 1,837 children in October 1995 and again in October 1996. Blo od samples for virus isolation and serology were collected from cohort chil dren who were seen in municipal heath clinics with febrile syndromes or adm itted to hospitals with a provisional diagnosis of dengue hemorrhagic fever . Dengue serotype antibody prevalence and 1995-1996 infection rates were ca lculated using a single dilution (1:60) 70% plaque reduction endpoint neutr alization test. Prevalence of dengue antibody at the beginning of the study was DEN 1 = 12%, DEN 2 = 16%, DEN 3 = 2%, DEN 4 = 4%, and two or more deng ue infections = 22%. Total dengue antibody prevalence increased from 38% in 4-year-old children to 69% in 9-year-old children. During the observation period, primary dengue infection rates were DEN 1 = 4.8%, DEN 2 = 7.7%, DEN 3 = 4.2%, and DEN 4 = 3.4%, while two or more dengue infections occurred i n 6.7% of the study population. The secondary dengue infection rate was 19. 0%. From febrile cases, all four dengue viruses were isolated with DEN 3 pr edominating. Seven children were hospitalized, including one fatal case wit h a hospital diagnosis of dengue shock syndrome. Based upon presence of ant ibody in the initial cohort bleeding and the serologic response both weeks and several months following illness, all had secondary dengue infections. Neutralizing antibody patterns in the initial cohort bleeding and in late c onvalescent serum samples permitted recognition of dengue infection sequenc e in five patients: DEN 2-DEN 1 (3), DEN 2-DEN 4 (1), DEN 1- DEN 3 (1), and none in the sequence DEN 1-DEN 2. In the total cohort 6.5% of the observed secondary infections were of the sequence DEN 2-DEN 1, while 4.9% were DEN 1-DEN 2, a highly pathogenic sequence in previous studies. Reduced pathoge nic expression of secondary DEN 2 with enhanced pathogenic expression of se condary DEN 1 infections was an unexpected finding. Further studies will be required to understand the respective contributions to pathogenicity of an tibody from initial dengue infections versus the biological attributes of t he second infecting dengue viruses.