Fatal Dengue Hemorrhagic Fever in Adults: Emphasizing the Evolutionary Pre-fatal Clinical and Laboratory Manifestations

Ing-Kit Lee,Kuender D Yang,Jien-Wei Liu,Scott B Halstead

doi:10.1371/journal.pntd.0001532

Abstract

BackgroundA better description of the clinical and laboratory manifestations of fatal patients with dengue hemorrhagic fever (DHF) is important in alerting clinicians of severe dengue and improving management.Methods and FindingsOf 309 adults with DHF, 10 fatal patients and 299 survivors (controls) were retrospectively analyzed. Regarding causes of fatality, massive gastrointestinal (GI) bleeding was found in 4 patients, dengue shock syndrome (DSS) alone in 2; DSS/subarachnoid hemorrhage, Klebsiella pneumoniae meningitis/bacteremia, ventilator associated pneumonia, and massive GI bleeding/Enterococcus faecalis bacteremia each in one. Fatal patients were found to have significantly higher frequencies of early altered consciousness (≤24 h after hospitalization), hypothermia, GI bleeding/massive GI bleeding, DSS, concurrent bacteremia with/without shock, pulmonary edema, renal/hepatic failure, and subarachnoid hemorrhage. Among those experienced early altered consciousness, massive GI bleeding alone/with uremia/with E. faecalis bacteremia, and K. pneumoniae meningitis/bacteremia were each found in one patient. Significantly higher proportion of bandemia from initial (arrival) laboratory data in fatal patients as compared to controls, and higher proportion of pre-fatal leukocytosis and lower pre-fatal platelet count as compared to initial laboratory data of fatal patients were found. Massive GI bleeding (33.3%) and bacteremia (25%) were the major causes of pre-fatal leukocytosis in the deceased patients; 33.3% of the patients with pre-fatal profound thrombocytopenia (<20000/µL), and 50% of the patients with pre-fatal prothrombin time (PT) prolongation experienced massive GI bleeding.ConclusionsOur report highlights causes of fatality other than DSS in patients with severe dengue, and suggested hypothermia, leukocytosis and bandemia may be warning signs of severe dengue. Clinicians should be alert to the potential development of massive GI bleeding, particularly in patients with early altered consciousness, profound thrombocytopenia, prolonged PT and/or leukocytosis. Antibiotic(s) should be empirically used for patients at risk for bacteremia until it is proven otherwise, especially in those with early altered consciousness and leukocytosis.

Highlights

Dengue is the most prevalent mosquito-borne viral infection in the world [1]
Clinicians should be alert to the potential development of massive GI bleeding, in patients with early altered consciousness, profound thrombocytopenia, prolonged prothrombin time (PT) and/or leukocytosis
In a retrospective analysis of 10 adults who died of and 299 survived dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) alone was found in only 20% of dengue-related death, while intractable massive gastrointestinal (GI) bleeding was found in 40%, and DSS with concurrent subarachnoid hemorrhage, intractable massive GI bleeding with concurrent bacteremia, bacterial sepsis/meningitis, and sepsis due to ventilator associated pneumonia each were found in 10%

Summary

Introduction

Dengue is the most prevalent mosquito-borne viral infection in the world [1]. Clinically, dengue ranges from asymptomatic, nonspecific febrile illness, classic dengue, to dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) [1]. Only a small number of dengue-attributed mortality cases were included for analysis in each of these series [2,8,10,11,12]. A better description of the clinical and laboratory presentations of cases with fatal outcome may lead clinicians to an earlier recognition of the warning signs of severe dengue resulting in timely and improved management. The importance of continuous analysis of relevant findings in fatal patients from dengue-affected populations cannot be overemphasized. A better description of the clinical and laboratory manifestations of fatal patients with dengue hemorrhagic fever (DHF) is important in alerting clinicians of severe dengue and improving management

Methods

Results

Discussion

Conclusion