title: Serotype-specific differences in the risk of dengue hemorrhagic fever: an analysis of data collected in Bangkok, Thailand from 1994 to 2006.
abstract: BACKGROUND
  It is unclear whether dengue serotypes differ in their propensity to cause severe disease. We analyzed differences in serotype-specific disease severity in children presenting for medical attention in Bangkok, Thailand.
  
  
  RESULTS
  Prospective studies were conducted from 1994 to 2006. Univariate and multivariate logistic and multinomial logistic regressions were used to determine if dengue hemorrhagic fever (DHF) and signs of severe clinical disease (pleural effusion, ascites, thrombocytopenia, hemoconcentration) were associated with serotype. Crude and adjusted odds ratios were calculated. There were 162 (36%) cases with DENV-1, 102 (23%) with DENV-2, 123 (27%) with DENV-3, and 64 (14%) with DENV-4. There was no significant difference in the rates of DHF by serotype: DENV-2 (43%), DENV-3 (39%), DENV-1 (34%), DENV-4 (31%). DENV-2 was significantly associated with increased odds of DHF grade I compared to DF (OR 2.9 95% CI 1.1, 8.0), when using DENV-1 as the reference. Though not statistically significant, DENV-2 had an increased odds of total DHF and DHF grades II, III, and IV. Secondary serologic response was significantly associated with DHF (OR 6.2) and increased when considering more severe grades of DHF. DENV-2 (9%) and -4 (3%) were significantly less often associated with primary disease than DENV-1 (28%) and -3 (33%). Restricting analysis to secondary cases, we found DENV-2 and DENV-3 to be twice as likely to result in DHF as DEN-4 (p = 0.05). Comparing study years, we found the rate of DHF to be significantly less in 1999, 2000, 2004, and 2005 than in 1994, the study year with the highest percentage of DHF cases, even when controlling for other variables.
  
  
  CONCLUSIONS
  As in other studies, we find secondary disease to be strongly associated with DHF and with more severe grades of DHF. DENV-2 appears to be marginally associated with more severe dengue disease as evidenced by a significant association with DHF grade I when compared to DENV-1. In addition, we found non-significant trends with other grades of DHF. Restricting the analysis to secondary disease we found DENV-2 and -3 to be twice as likely to result in DHF as DEN-4. Differences in severity by study year may suggest that other factors besides serotype play a role in disease severity.
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. jessica@tropmedres.ac
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Fried
authors.forename: Robert V
authors.initials: RV
authors.lastname: Gibbons
authors.forename: Siripen
authors.initials: S
authors.lastname: Kalayanarooj
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Thomas
authors.forename: Anon
authors.initials: A
authors.lastname: Srikiatkhachorn
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Yoon
authors.forename: Richard G
authors.initials: RG
authors.lastname: Jarman
authors.forename: Sharone
authors.initials: S
authors.lastname: Green
authors.forename: Alan L
authors.initials: AL
authors.lastname: Rothman
authors.forename: Derek A T
authors.initials: DA
authors.lastname: Cummings
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003716:Dengue Virus / Q000145:classification* / Q000302:isolation & purification*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D011446:Prospective Studies; D012703:Serotyping; D019595:Severe Dengue / Q000473:pathology* / Q000821:virology*; D012720:Severity of Illness Index; D013785:Thailand