Prediction of plasma leakage phase of dengue in resource limited settings

Abstract

The pathophysiology of severe dengue is related to increased capillary permeability and plasma leakage into extracellular space. A simple, low cost risk prediction tool for plasma leakage will be useful for clinicians practicing in rural areas without imaging facilities. Study design: A prospective observational study was carried out over 12 months at the National Hospital, Sri Lanka enrolling patients with confirmed diagnosis (via NS1 antigen testing) of early dengue infection. Clinical features on admission and investigation results on D3, D5 and D7 of the illness were recorded. Evidence of plasma leakage was confirmed by ultrasonography. Results: A total of 179 patients met the inclusion criteria (males; 91, 50.8%, mean age: 31.6 years, SD ± 14.7). Sixty seven patients (67/173, 38.7%) had ultrasonographic evidence of plasma leakage. Several clinical features (severe vomiting, severe diarrhoea, abdominal pain and liver tenderness) as well as mean differences of some investigations were significantly associated with progression to plasma leakage. However, only liver tenderness on day 3 emerged as independent significant predictors of critical phase in the adjusted analysis (specificity: 93%, sensitivity: 44%). Conclusions: Having liver tenderness by day 3 of the illness is helpful to identify a subgroup of patients at risk of plasma leakage.

Risk prediction for severe disease and better diagnostic accuracy in early dengue infection; the Colombo dengue study

“…A similar study carried out in the same hospital showed an association of liver tenderness in early infection and plasma leakage. Therefore, presence of early hepatitis in this subgroup cannot be ruled out [25].…”

Direct costs of managing in-ward dengue patients in Sri Lanka: A prospective study

“…CDS aims to record natural history of dengue fever and build a comprehensive predictive model to identify people at risk of plasma leakage, early in the infection. The details of this collaborative project led by investigators of University of Colombo, Sri Lanka and University of New South Wales, Australia has been published previously [9,22]. In brief, CDS recruits' adults clinically suspected of having dengue fever (as evaluated by two independent medical officers to meet the clinical case definition of dengue [13]) admitted to NHSL within the first three days of fever.…”

“…The sample size calculation for CDS has been published previously [9,22] and this costing study includes all patients recruited to CDS by February 2020 (Phase 1 of CDS). All costs are indicated in United States dollars (USD) in the main manuscript and in Sri Lankan Rupees (LKR) in the S1-S5 Tables, using the average exchange rate of one United States dollar to 185.43 LKR in 2020.…”

“…Some people experience complications (e.g., severe bleeding [6], pulmonary involvement [7]) resulting in a protracted course of illness [8]. Approximately 20-40% of symptomatic dengue patients have a stage of illness characterized by increased vascular permeability and extravasation of plasma, around day 5-7 since the onset of fever [9][10][11]. This phase, also known as the critical phase, is short lasting (48-72 hours), but if undiagnosed and mismanaged can result in shock and organ dysfunction leading to severe dengue and associated fatalities [12,13].…”

“…We have been conducting a prospective cohort study (the Colombo Dengue Study-CDS) on natural history of clinically suspected dengue patients admitted to the National Hospital of Sri Lanka (Colombo) since 2017 and have built up a comprehensive database of records of clinical management [9,22]. In all patients recruited to CDS a dengue diagnosis is confirmed by RT-PCR, but this is done retrospectively.…”