Diagnosis and Prognosis of Severe Dengue

Dengue has a broad spectrum of clinical symptoms, ranging from asymptomatic infection, undifferentiated fever and dengue fever (DF) to dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). DHF and DSS are the most severe forms of the disease, as they involve bleeding and hypovolemic shock and may lead to death if they are not diagnosed early and treated correctly. Every year, about 36 million cases of DF, of which about 2.1 million cases are DHF/DSS resulting in 21,000 deaths among children and young adults, are reported. Dengue not only has negative effects on public health worldwide but also poses significant economic burden. However, no licensed vaccines or (specific) anti-viral therapies for prevention or treatment of dengue are available. Thus, timely diagnosis and an accurate prognosis of severe dengue in the first few days of illness for clinical triage, treatment management, disease surveillance and research activities are vital and very helpful. We conducted three studies aiming to identify early markers of dengue, especially severe dengue and identify prognostic markers of severe dengue in Vietnamese children with clinically suspected dengue within the first few days of the illness. The results firstly showed that plasma collected within the first week of the illness could be used for dengue diagnosis as well as differentiation between primary and secondary dengue virus infections. Secondly, the research showed that plasma concentration of NS1 correlated with plasma viraemia and associated with DSS. NS1 concentrations in enrolment plasma of patients within the first four days of illness could be used for predicting DSS in patients with DENV-1 or DENV-2 infections. Thirdly, in the first three days of illness, we observed differences in clinical and haematological profiles between patients with DHF and those with DF or other febrile illnesses. Logistic models were then generated using the early clinical characteristics and/or haematological profiles to predict patients who will develop DHF. Our findings also showed that a greater virus burden leads to an augmented cascade of plasma concentrations of IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-13, IFNγ and TNFα in DHF patients compared to DF patients. This thesis shows the results and also points out predictive models that may be used to prognosticate of severe dengue among patients with clinically suspected dengue who are admitted to hospital within the first few days of the illness