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Abstract Correlating aberrant miRNA levels with imported malaria during the blood stage is required to better understand the in vivo biological and molecular processes that are involved in the response to Plasmodium falciparum infection and to find new biomarkers and diagnosis tools. We used a parallel microarray-based approach to investigate an integrated view of how the host miRNA expression profile changes in response to P. falciparum infection in whole blood obtained from six subjects with adult imported falciparum malaria (AIFM) and six normal subjects. We first investigated the functions of 1007 significantly differentially expressed genes from microarrays and predicted 56 putative pathways participating in malaria pathogenesis, which reflected systemic changes in the host under falciparum infection. Then, we validated the in silico -predicted targets of 50 differentially modulated miRNAs (7 upregulated and 43 downregulated) by examining the actual mRNA expression of these particular genes in our gene expression profile database; putative target gene sets were grouped into functional categories to investigate the roles of differentially expressed miRNAs. We considered 36 intersecting putative pathways, most of which were involved in multiple immune response processes, such as cell defense response, immune response, TNF signaling pathway, and T cell receptor signaling pathway, which may actually be regulated by differentially expressed miRNAs. Additionally, we identified five enriched upregulated miRNA sets (miR-3135b, miR-6780b-5p, miR-1246, miR-6126, and miR-3613-5p) as potential blood biomarkers of immunopathological status and prediction of early host responses, disease prognosis, and severe outcomes in AIFM. Highlights • A parallel microarray-based method studies host miRNA expression profile changes under malaria. • Most of putative pathways are involved in immune response processes during falciparum malaria. • Five miRNAs were identified as potential blood biomarkers for falciparum malaria. [ABSTRACT FROM AUTHOR]