Impact of sickle cell trait hemoglobin on the intraerythrocytic transcriptional program of Plasmodium falciparum

Purpose: The goals of this study are to compare parasite transcriptomes in sickle cell trait infected red blood cells during the intraerythrocytic developmental cycle (IDC) from in vitro time series and in vivo blood samples to identify new therapeutic targets in the treatment of malaria Methods: In vitro time series: Parasites were synchronized to early ring-stage parasites and sampled every three hours for 48 hours to capture every stage of the IDC, generating 16 RNA-seq libraries per replicate (128 total). In vivo blood samples: Samples were collected in an observational study of malaria in children in Kenieroba, Mali (ClinicalTrials.gov Identifier: NCT02645604). From children presenting with uncomplicated falciparum malaria, we selected all available samples from children with HbAS and matched each of these to a sample from a child with HbAA on: month of episode, parasite density, ethnic background, and, if possible, ABO blood type. mRNA profiles of P. falciparum in HbAS iRBCs compared to HbAA in vitro 3 hour time points 16 time points per replicate 8 replicates (4 HbAA, 4 HbAS) -------------------------------------- 128 RNA-seq libraries in vivo 16 HbAA 16 HbAS ------------------------- 32 RNA-seq libraries