Evaluation of the Traditional and Revised WHO Classifications of Dengue Disease Severity

Abstract

Dengue is a major public health problem worldwide and continues to increase in incidence. Dengue virus (DENV) infection leads to a range of outcomes, including subclinical infection, undifferentiated febrile illness, Dengue Fever (DF), life-threatening syndromes with fluid loss and hypotensive shock, or other severe manifestations such as bleeding and organ failure. The long-standing World Health Organization (WHO) dengue classification and management scheme was recently revised, replacing DF, Dengue Hemorrhagic Fever (DHF), and Dengue Shock Syndrome (DSS) with Dengue without Warning Signs, Dengue with Warning Signs (abdominal pain, persistent vomiting, fluid accumulation, mucosal bleeding, lethargy, liver enlargement, increasing hematocrit with decreasing platelets) and Severe Dengue (SD; dengue with severe plasma leakage, severe bleeding, or organ failure). We evaluated the traditional and revised classification schemes against clinical intervention levels to determine how each captures disease severity using data from five years (2005–2010) of a hospital-based study of pediatric dengue in Managua, Nicaragua. Laboratory-confirmed dengue cases (n = 544) were categorized using both classification schemes and by level of care (I–III). Category I was out-patient care, Category II was in-patient care that did not meet criteria for Category III, which included ICU admission, ventilation, administration of inotropic drugs, or organ failure. Sensitivity and specificity to capture Category III care for DHF/DSS were 39.0% and 75.5%, respectively; sensitivity and specificity for SD were 92.1% and 78.5%, respectively. In this data set, DENV-2 was found to be significantly associated with DHF/DSS; however, this association was not observed with the revised classification. Among dengue-confirmed cases, the revised WHO classification for severe dengue appears to have higher sensitivity and specificity to identify cases in need of heightened care, although it is no longer as specific for a particular pathogenic entity as was the traditional schema.

An evaluation of the World Health Organization’s 1997 and 2009 dengue classifications in hospitalized dengue patients in Malaysia

“…Several studies [10,13,14] reported that the revised WHO classification is more sensitive as well as more or comparably specific in identifying severe cases. In contrast, some still indicate that WHO 1997 is more sensitive -though less specific -in capturing severe cases [15].…”

Markers of dengue severity: a systematic review of cytokines and chemokines

“…The WHO (1986) and WHO (1997) case definition guidelines were grouped together during analysis, but were analysed separately from the WHO (2009) case definition guidelines due to reported differences Narvaez et al, 2011;Tsai et al, 2013a Odds ratios or statistical mean/median values could not be identified in most studies. No pooling was done given the extra sources of methodological diversity (types of prognostic factors being measured) and bias.…”

Single-Cell Analysis of B Cell/Antibody Cross-Reactivity Using a Novel Multicolor FluoroSpot Assay

“…We next sought to assess whether the QCF could be used to detect MBC and PB/PC responses in primary human PBMCs from DENV-infected individuals during either acute-or convalescentphase time points in participants in our Hospital-based Dengue Study in Nicaragua (11,23). PBMCs from a DENV-positive patient (secondary DENV3) were plated directly ex vivo and assessed via QCF to determine the PB/PC response.…”