Systemic host inflammatory and coagulation response in the Dengue virus primo-infection.
BACKGROUND
Dengue virus infection has been rising in tropical countries. Clinical manifestations range from fever and general malaise to hemorrhagic manifestations and death. The role of endothelial damage and cytokines has not been well established for dengue infection.


OBJECTIVE
Determine the profile of the pro-inflammatory cytokines and several markers of coagulopathy of dengue infection.


METHODS
Patients admitted between September 2000 and April 2001, who met the WHO dengue diagnosis criteria, were enrolled. Blood samples were collected at 0, 6, 12, 24, 48, 72 h and 5 and 7 days after hospitalization. Profile of pro-inflammatory cytokines, markers of coagulopathy, protein C, protein S, d-dimer, prothrombin time, activated partial thromboplastin time, fibrinogen and activated protein C levels were determined.


RESULTS
Thirty-three patients were enrolled. Median (range) age was 31 (13-70) years; 51.5% (17/33) were female. Ten of 33 (30%) presented with hemorrhagic manifestations. Patients were classified: Grade 1: 23/33 (70%), Grade II: 10/33 (30%). At study entry IL-6 was the most elevated, followed by IL-8 and TNF alpha. IL-10 was not elevated. No significant differences (P < 0.05) were demonstrated in the levels of any of the haemostatic or cytokine markers by disease severity (Grade I versus Grade II patients).


CONCLUSIONS
The systemic host inflammatory and coagulation activation response occurs early in patients with dengue viral infection in the absence of severe hemorrhagic manifestations, and provides the basis for considering future clinical study in the use of recombinant human activated protein C to treat patients with severe sepsis from dengue infection.
Avila-Aguero
María L
ML
Infectious Disease Division, Costa Rica's National Children's Hospital, San José, Costa Rica. maluvi@racsa.co.cr
Avila-Aguero
Claudio R
CR
Um
Suzane L
SL
Soriano-Fallas
Alejandra
A
Cañas-Coto
Alejandro
A
Yan
S Betty
SB
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers; D001777:Blood Coagulation / Q000502:physiology*; D016207:Cytokines / Q000097:blood*; D003715:Dengue / Q000097:blood* / Q000276:immunology* / Q000503:physiopathology; D003716:Dengue Virus / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation; D008875:Middle Aged; D011446:Prospective Studies
D015415:Biomarkers; D016207:Cytokines