Research Article: Serotype-Specific Differences in the Risk of Dengue Hemorrhagic Fever: An Analysis of Data Collected in Bangkok, Thailand from 1994 to 2006

Date Published: March 2, 2010

Publisher: Public Library of Science

Author(s): Jessica R. Fried, Robert V. Gibbons, Siripen Kalayanarooj, Stephen J. Thomas, Anon Srikiatkhachorn, In-Kyu Yoon, Richard G. Jarman, Sharone Green, Alan L. Rothman, Derek A. T. Cummings, Scott B. Halstead

Abstract: BackgroundIt 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.Methodology/Principal FindingsProspective 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/SignificanceAs 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.

Partial Text: Dengue virus (DENV) is an increasing problem in tropical and sub-tropical countries, where Aedes spp mosquitoes transmit the virus primarily in urban or semi-urban settings. Infection with DENV may result in a sub-clinical infection, undifferentiated fever, dengue fever (DF), dengue hemorrhagic fever (DHF), or dengue shock syndrome (DSS) [1]. Clinical manifestations of DF commonly include fever, rash, hemorrhagic symptoms, headache, ocular pain, arthralgia, myalgia, nausea, and vomiting [2]–[4]. DHF is difficult to differentiate from DF in the early stages of infection and illness [4],[5]. The criteria that differentiate DHF from DF are plasma leakage confirmed by pleural effusion, ascites, and/or hemoconcentration (>20% above patient’s baseline), and thrombocytopenia (<100,000/mm3) [2]. The results of this prospective observational, single-site study of pediatric dengue showed a significant association between DENV-2 and DHF grade I and nonsignificant associations with other grades of DHF. DENV-2 was also associated with the presence of ascites and larger pleural effusions index. Additionally, we confirmed the previously reported associations between secondary serologic response and DHF as well as a more severe grade of DHF. Source: http://doi.org/10.1371/journal.pntd.0000617