PMID- 24324686
OWN - NLM
STAT- MEDLINE
DCOM- 20140911
LR  - 20231104
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 12
DP  - 2013
TI  - Tumor necrosis factor -alpha, interleukin-10, intercellular and vascular adhesion 
      molecules are possible biomarkers of disease severity in complicated Plasmodium 
      vivax isolates from Pakistan.
PG  - e81363
LID - 10.1371/journal.pone.0081363 [doi]
LID - e81363
AB  - BACKGROUND: Cytokine-mediated endothelial activation pathway is a known mechanism 
      of pathogenesis employed by Plasmodium falciparum to induce severe disease 
      symptoms in human host. Though considered benign, complicated cases of Plasmodium 
      vivax are being reported worldwide and from Pakistan. It has been hypothesized 
      that P.vivax utilizes similar mechanism of pathogenesis, as that of P.falciparum 
      for manifestations of severe malaria. Therefore, the main objective of this study 
      was to characterize the role of cytokines and endothelial activation markers in 
      complicated Plasmodium vivax isolates from Pakistan. METHODS AND PRINCIPLE 
      FINDINGS: A case control study using plasma samples from well-characterized 
      groups suffering from P.vivax infection including uncomplicated cases (n=100), 
      complicated cases (n=82) and healthy controls (n=100) were investigated. Base 
      line levels of Tumor necrosis factor-alpha (TNF-alpha), Interleukin-6 (IL-6), 
      Interleukin-10 (IL-10), Intercellular adhesion molecule-1 (ICAM-1), Vascular 
      adhesion molecule-1(VCAM-1) and E-selectin were measured by ELISA. Correlation of 
      cytokines and endothelial activation markers was done using Spearman's 
      correlation analysis. Furthermore, significance of these biomarkers as indicators 
      of disease severity was also analyzed. The results showed that TNF-alpha, IL-10, 
      ICAM-1and VCAM-1 were 3-fold, 3.7 fold and 2 fold increased between uncomplicated 
      and complicated cases. Comparison of healthy controls with uncomplicated cases 
      showed no significant difference in TNF-alpha concentrations while IL-6, IL-10, 
      ICAM-1, VCAM-1 and E-selectin were found to be elevated respectively. In 
      addition, significant positive correlation was observed between TNF-alpha and IL-10/ 
      ICAM-1, IL-6 and IL-10, ICAM-1 and VCAM-1.A Receiver operating curve (ROC) was 
      generated which showed that TNF-alpha, IL-10, ICAM-1 and VCAM-1 were the best 
      individual predictors of complicated P.vivax malaria. CONCLUSION: The results 
      suggest that though endothelial adhesion molecules are inducible by 
      pro-inflammatory cytokine TNF-alpha, however, cytokine-mediated endothelial 
      activation pathway is not clearly demonstrated as a mechanism of pathogenesis in 
      complicated P.vivax malaria cases from Pakistan.
FAU - Raza, Afsheen
AU  - Raza A
AD  - Department of Pathology and Microbiology, Aga Khan University, Karachi, Sindh, 
      Pakistan.
FAU - Ghanchi, Najia K
AU  - Ghanchi NK
FAU - Sarwar Zubairi, Ali bin
AU  - Sarwar Zubairi Ab
FAU - Raheem, Ahmed
AU  - Raheem A
FAU - Nizami, Sobia
AU  - Nizami S
FAU - Beg, Mohammad Asim
AU  - Beg MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131204
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers)
RN  - 0 (E-Selectin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Adult
MH  - Biomarkers/blood
MH  - Demography
MH  - E-Selectin
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/*blood
MH  - Interleukin-10/*blood
MH  - Malaria, Vivax/*blood/complications/*parasitology
MH  - Middle Aged
MH  - Pakistan
MH  - Plasmodium vivax/*isolation & purification
MH  - ROC Curve
MH  - Severity of Illness Index
MH  - Solubility
MH  - Tumor Necrosis Factor-alpha/*blood
MH  - Vascular Cell Adhesion Molecule-1/*blood
PMC - PMC3852525
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/12/11 06:00
MHDA- 2014/09/12 06:00
PMCR- 2013/12/04
CRDT- 2013/12/11 06:00
PHST- 2013/06/29 00:00 [received]
PHST- 2013/10/11 00:00 [accepted]
PHST- 2013/12/11 06:00 [entrez]
PHST- 2013/12/11 06:00 [pubmed]
PHST- 2014/09/12 06:00 [medline]
PHST- 2013/12/04 00:00 [pmc-release]
AID - PONE-D-13-27192 [pii]
AID - 10.1371/journal.pone.0081363 [doi]
PST - epublish
SO  - PLoS One. 2013 Dec 4;8(12):e81363. doi: 10.1371/journal.pone.0081363. eCollection 
      2013.