Evaluation of the importance of fever with respect to dengue prognosis according to the 2009 WHO classification: a retrospective study

BACKGROUND The 2009 revised World Health Organization (WHO) guidelines for dengue describe fever as the core symptom. Accordingly, the diagnosis of non-febrile patients is complicated. The aim of this study was to evaluate the importance of fever in patients with dengue according to the 2009 revised WHO classification. METHODS In this study, we assessed 30,670 dengue cases using enzyme-linked immunosorbent assay, detection of the non-structural protein 1, or polymerase chain reaction for diagnostic confirmation. Fisher's exact test was used to evaluate associations between fever and related clinical manifestations. The Mann-Whitney U test was used to assess the association of dengue classification with fever and time to treatment. The effects of fever and time to treatment on the risk of progression were analyzed using an ordinal logistic regression to stereotype the model. RESULTS Disease classification was found to associate significantly with both fever and time to treatment (both P < 0.001). Non-febrile patients were nearly four-fold more likely to exhibit "dengue without warning signs" than "severe dengue" (odds ratio [OR] = 3.74; 95% confidence interval [CI]: 3.20-4.36). Patients who received treatment within 7 days were twice as likely to have "dengue without warning signs" as opposed to "severe dengue" when compared to those who waited >7 days (OR = 2.23; 95% CI: 1.78-2.80). However, this difference was negligible in the multivariate analysis (OR = 1.02; 95% CI: 0.98-1.07). CONCLUSIONS Fever is a risk factor for disease progression in patients with dengue. However, non-febrile patients should not be neglected because this may delay treatment and could lead to more severe disease.