Comparison of dengue case classification schemes and evaluation of biological changes in different dengue clinical patterns in a longitudinal follow-up of hospitalized children in Cambodia

Background The World Health Organization (WHO) proposed guidelines on dengue clinical classification in 1997 and more recently in 2009 for the clinical management of patients. The WHO 1997 classification defines three categories of dengue infection according to severity: dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). Alternative WHO 2009 guidelines provide a cross-sectional classification aiming to discriminate dengue fever from dengue with warning signs (DWWS) and severe dengue (SD). The primary objective of this study was to perform a comparison of two dengue classifications. The secondary objective was to describe the changes of hematological and biochemical parameters occurring in patients presenting with different degrees of severity during the course of the disease, since progression to more severe clinical forms is unpredictable. Methodology/Principal findings We performed a prospective, monocentric, cross-sectional study of hospitalized children in Cambodia, aged from 2 to 15 years old with severe and non-severe dengue. We enrolled 243 patients with acute dengue-like illness: 71.2% were dengue infections confirmed using quantitative reverse transcription PCR or NS1 antigen capture ELISA, of which 87.2% and 9.0% of DF cases were respectively classified DWWS and SD, and 35.9% of DHF were designated SD using an adapted WHO 2009 classification for SD case definition. Systematic use of ultrasound at patient admission was crucial for detecting plasma leakage. No difference was observed in the concentration of secreted NS1 protein between different dengue severity groups. Lipid profiles were different between DWWS and SD at admission, characterized by a decrease in total cholesterol, HDL cholesterol, and LDL cholesterol, in SD. Conclusions/Significance Our results show discrepancies between the two classifications, including misclassification of severe dengue cases as mild cases by the WHO 1997 classification. Using an adapted WHO 2009 classification, SD more precisely defines the group of patients requiring careful clinical care at a given time during hospitalization.
Author summary Dengue is a viral disease that results in various health conditions, ranging from strictly asymptomatic infections to life-threatening severe dengue. Here we have compared the two World Health Organization (WHO) dengue classification schemes from 1997 and 2009, which define different categories of dengue fever and have been at the root of much debate in the dengue research community. We enrolled a Cambodian pediatric cohort of hospitalized dengue-confirmed patients, with clinical and biological follow-up. Our findings demonstrate that (i) the WHO 1997 classification is a longitudinal dengue-case classification which uses strict prerequisite clinical and/or biological signs to move from one level of severity to another, and (ii) the WHO 2009 classification, being a transversal dengue-case classifier, is more flexible and when adapted with systematic use of ultrasound is more accurate in identifying severe dengue case for timely and appropriate clinical management of hospitalized patients. Our laboratory results found that lipid profiles exhibited changes and differences between different dengue severity groups at hospital.