Lipopolysaccharide levels are elevated in dengue virus infected patients and correlate with disease severity.
BACKGROUND
Although in the majority of cases dengue virus (DENV) infection results in a self-limiting febrile disease, it can cause severe plasma leakage in a minority of patients. The appearance of plasma leakage indicates an increased permeability of the vascular wall. In this study we investigated if DENV infection can lead to leakage of lipopolysaccharide (LPS) from the intestine into the blood of the patient, indicative of an increased permeability of the intestinal mucosal barrier.


OBJECTIVE
The aim of this study was to investigate if LPS levels were elevated in DENV infected patients and if these levels correlated with disease severity.


METHODS
LPS levels in the blood of DENV infected children were determined using the Limulus Amebocyte Lysate assay. To determine disease severity we used the 1997-WHO criteria, the expert physician's judgement and a score that focused on plasma leakage in particular. Furthermore, the modulatory factors LPS binding protein (LBP) and sCD14, as well as the immune activation marker neopterin were determined.


RESULTS
We showed significantly elevated LPS levels in plasma of DENV infected children compared to healthy controls. The plasma leakage severity score had the strongest correlation with levels of LPS. LBP, sCD14 and neopterin were elevated compared to healthy controls.


CONCLUSIONS
In this study we show evidence of elevated LPS levels during DENV infection. Moreover, a correlation between LPS levels and disease severity was found, especially when disease severity was determined in terms of plasma leakage.
Department of Virology, Erasmus Medical Center, Dr. Molewaterplein 50, Rotterdam, The Netherlands.
Cornelia A M
CA
van de Weg
Penelope
P
Koraka
Eric C M
EC
van Gorp
Albert T A
AT
Mairuhu
Mohamad
M
Supriatna
Augustinus
A
Soemantri
David A M C
DA
van de Vijver
Albert D M E
AD
Osterhaus
Byron E E
BE
Martina
D000209:Acute-Phase Proteins; D000293:Adolescent; D002352:Carrier Proteins / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003715:Dengue / Q000097:blood* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D003716:Dengue Virus / Q000276:immunology / Q000472:pathogenicity*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008070:Lipopolysaccharides / Q000097:blood* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D019798:Neopterin / Q000097:blood; D012720:Severity of Illness Index; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D019798:Neopterin; D000099231:Lipopolysaccharide-Binding Protein