Therapy of Dengue Hemorrhagic Fever Based on Pathophysiology Involving Host and Pathogen Factors

In contrast to predominant children being affected, dengue fever (DF) and dengue hemorrhagic fever (DHF) in particular have been mostly found in adults, especially in elderly patients in Taiwan. Intravenous fluid (IVF) supplement recommended by WHO for patients with dengue illness was not developed based experimental evidence; instead, it was put forwarded based on the opinions of experts in the field. Marked clinical effects of IVF supplement have been reported in pediatric patients; however, IVF supplement might put elderly patients with a declining cardiopulmonary function at high risk for pulmonary edema, leading to respiratory failure. Another problem that was not infrequently encountered in clinical practice was that some clinically severe patients with dengue illness did not always fulfill the 1997 WHO criteria defining DHF. To improve this, WHO put forwarded new criteria for dengue illness in 2009, of which the applicability requires further supports by the not yet pooled enough clinical data. The aims of this study are (i) to compare responses in patients with dengue illness receiving IVF supplement vs. those receiving oral hydration, and (ii) to evaluate the applicability of 2009 WHO criteria for dengue illness. The study will be conducted at 3 medical centers in Kaohsiung, namely, Chang Gung Memorial Hospital, Kaohsiung Medical University Hospital and Kaohsiung Veterans General Hospital. Included patients are dengue-affected adults aged 20-60 years, non-pregnant women, with clear consciousness and stable vital signs and without warning signs for severe dengue such as nausea and vomiting. The included patient will be categorized into 2 groups (group 1, aged 20-40 years, and group 2, aged 4—60 years). Patients in each group are randomly treated with either IVF supplement or oral hydration. As for IVF supplement, normal saline will be given at 6cc/kg/h for the first one hour, followed by 3cc/kg/h for 2-4 hours, and then ＜2cc/kg/h till the third day. Patients receiving oral hydration will be given Nudrink (1 table in 120ml water; contains Na 56mmol/L, K 20mmol/L, Cl 46 mmol/L, citrate 30mmol/L, glucose 140mmol/L), and daily oral fluid ingestion will be at least 1500mL for a total of 3 days. The innate and adaptive immunologic responses, dengue viral load and clinical responses in the included patients will be measured. Findings in this study will provide valuable information for establishing guidelines for treatment of dengue illness with regard to determining IVF or oral fluid supplement based on patients’ ages, thus minimizing the complication of respiratory failure due to fluid overloading. If oral hydration is proved to be as effective as IVF supplement, a much larger number of dengue-affected patients can be treated on outpatient instead of hospitalization basis, thus markedly lowering medical financial burdens; this is particularly important in areas where medical resources are limited. Analysis of our data of the included patients with dengue illness respectively classified based on 1997 WHO criteria and 2009 WHO criteria will provide solid data for evaluating the applicability of latter in clinical practice. This study works with other studies in programmed proposals to understand the relationship among host genetic factors, age, serotype of dengue viruses, and fluid supplement in dengue-affected patients. The results of this study additionally provide information regarding therapeutic strategies for dengue-affected patients with the underlying diabetes mellitus and of different age in the other study in the programmed proposals.

Project ID:PC10007-0004
External Project ID:NSC100-2314-B182A-090-MY3