MULTIPRONGED QUANTITATIVE PROTEOMICS ANALYSIS OF PLASMODIUM VIVAX INDUCED ALTERATIONS IN HUMAN SERUM FOR IDENTIFICATION OF POSSIBLE BIOMARKERS FOR SEVERE VIVAX MALARIA

Abstract 
Background & objectives
Recent incidences of involvement of Plasmodium vivax in severe malaria suggest a drastic shift in the clinical paradigm for vivax malaria. Mechanisms that trigger transition from non-severe (NSVM) to severe vivax malaria (SVM) are obscure. This multi-disciplinary study provides a comprehensive analysis of serum proteomics profile of NSVM and SVM to understand the itinerary during the ontogenetic advancement of the disease into severe forms and longitudinal analysis of the P.vivax infected children to identify surrogate markers of severity.  
Methods
This prospective cohort study was conducted on 126 children of P.vivax malaria admitted from January 2017 to December 2017. The species diagnosis was made with peripheral smear and rapid diagnostic test and confirmed with polymerase chain reaction analysis. Severe malaria was defined as per WHO guidelines. Serum samples from children with NSVM (n=30) and SVM (n=30) were analysed by iTRAQ-based quantitative proteomic approach in comparison to healthy controls (HC) (n=50) and dengue illness as febrile control (FC) (n=45). The results were validated by employing immunoassay-based techniques.
Results
Comparative proteomics analysis of NSVM, SVM, HC and FC revealed evidences for the modulation of diverse physiological pathways including oxidative stress, cytoskeletal regulation, lipid metabolism and complement cascades in P.vivax malaria. Proteins like complement C3, alpha-2-macroglobulin, complement C5, hemopexin, plasminogen, alpha-1-antichymotrypsin, apolipoprotein A-IV, prothrombin, antithrombin-III, inter-alpha-trypsin inhibitor heavy chain H3, gelsolin & apolipoprotein A-I showed similar trends of differential expression. Proteins like Superoxide dismutase, C-Reative Protein, Apolipoprotein E, Apolipoprotein A-1, Serum amyloid A, and Haptoglobin displayed significant (p≤.0001) correlation with the disease severity and therefore can be eventually used as powerful indicators for disease severity.

Conclusion
In this comprehensive multidisciplinary prospective study, 6 serum proteins were identified as potential predictive markers for P.vivax malaria severity.

MULTIPRONGED QUANTITATIVE PROTEOMICS ANALYSIS OF PLASMODIUM VIVAX INDUCED ALTERATIONS IN HUMAN SERUM FOR IDENTIFICATION OF POSSIBLE BIOMARKERS FOR SEVERE VIVAX MALARIA