Journal article

Meta-analysis of Plasmodium falciparum var Signatures Contributing to Severe Malaria in African Children and Indian Adults

Fergal Duffy, Maria Bernabeu, Prasad H Babar, Anne Kessler, Christian W Wang, Marina Vaz, Laura Chery, Wilson L Mandala, Stephen J Rogerson, Terrie E Taylor, Karl B Seydel, Thomas Lavstsen, Edwin Gomes, Kami Kim, John Lusingu, Pradipsinh K Rathod, John D Aitchison, Joseph D Smith

mBio | AMER SOC MICROBIOLOGY | Published : 2019

Abstract

The clinical presentation of severe Plasmodium falciparum malaria differs between children and adults, but the mechanistic basis for this remains unclear. Contributing factors to disease severity include total parasite biomass and the diverse cytoadhesive properties mediated by the polymorphic var gene parasite ligand family displayed on infected erythrocytes. To explore these factors, we performed a multicohort analysis of the contribution of var expression and parasite biomass to severe malaria in two previously published pediatric cohorts in Tanzania and Malawi and an adult cohort in India. Machine learning analysis revealed independent and complementary roles for var adhesion types and p..

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Grants

Awarded by NIH


Awarded by NIH National Center for Advancing Translational Science (NCATS) Einstein-Montefiore


Awarded by National Center for Dynamic Interactome Research


Awarded by American Heart Association


Awarded by National Health and Medical Research Council of Australia


Funding Acknowledgements

This study was made possible by NIH grant U19AI089688 (J.D.S., J.D.A., and P.R.), R01AI034969 (T.E.T.), NIH National Center for Advancing Translational Science (NCATS) Einstein-Montefiore CTSA TL1TR001072 (A.K.), National Center for Dynamic Interactome Research P41 GM109824 (F.D. and J.D.A.), American Heart Association Grant 17POST33670672 (M.B.), the Burroughs Wellcome Fund (A.K.), and Program Grant APP1092789 and Project Grant APP1061993 from the National Health and Medical Research Council of Australia (S.J.R.). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.