Malaria Host Pathogen Interaction Center Experiment 23R: Host and parasite gene transcript abundances, from whole blood, of Macaca mulatta infected Plasmodium cynomolgi B strain treated with artemether over 7 time points in a 100 day study

This project is part of the Malaria Host-Pathogen Interaction Center (MaHPIC) - a transdisciplinary malaria systems biology research program initially supported by an NIH/NIAID contract (# HHSN272201200031C, 2012-2017; see http://www.systemsbiology.emory.edu). The MaHPIC continues with ongoing support from the Defense Advanced Research Project Agency (DARPA) and others. The MaHPIC generates many data types (e.g., clinical, hematological, parasitological, metabolomics, functional genomics, lipidomics, proteomics, immune response, telemetry) and mathematical models, to iteratively test and develop hypotheses related to the complex host-parasite dynamics in the course of malaria in non-human primates (NHPs), and metabolomics data via collaborations with investigators conducting clinical studies in malaria endemic countries, with the overarching goal of better understanding human disease, pathogenesis, and immunity. Curation and maintenance of all data and metadata are the responsibility of the MaHPIC:  Mary Galinski [e-mail] (MaHPIC Program Director), Jessica Kissinger [e-mail] (MaHPIC Co-Program Director), and Alberto Moreno [e-mail] (MaHPIC Co-Program Director). Malaria-naive male rhesus macaques (Macaca mulatta), approximately four years of age, were inoculated intravenously with salivary gland sporozoites produced and isolated at the Centers for Disease Control and Prevention from multiple Anopheles species (An. dirus, An. gambiae, and An. stephensi) and then profiled for clinical, hematological, parasitological, immunological, functional genomic, lipidomic, proteomic, and metabolomic measurements. The experiment was designed for about 100 days, with pre- and post-100 day periods to prepare subjects and administer curative treatments respectively. During the 100-day period subjects experienced periods of patent and sub-patent infection. The anti-malarial drug artemether was subcuratively administered to subjects after the initial peak of infection, if subjects were not able to self-resolve. Blood-stage curative artemether was administered to all subjects following peak infection, and following a period of relapse infection. All peaks were clinically determined for each subject. The anti-malarial drugs primaquine and chloroquine were administered to all subjects at the end of the study for curative treatment of the liver and blood-stage infections, respectively. Capillary blood samples were collected daily for the measurement of CBCs, reticulocytes, and parasitemias. Capillary blood samples were collected every other day to obtain plasma for metabolomic analysis. Venous blood and bone marrow samples were collected at seven time points for functional genomic, proteomic, lipidomic, and immunological analyses. E23 is an iteration of Experiment 04 with the same parasite-host combination. E23 is the first in a series of experiments that includes subsequent homologous (Experiment 24, P. cynomolgi B strain) and heterologous (Experiment 25, P. cynomolgi strain ceylonensis) challenges of individuals from the E23 cohort. Note that one E23 subject was not included in subsequent experiments due to persistent behavioral issues that prevented sample collection. Within the MaHPIC, this project is known as ‘Experiment 23R’. E23R is a 'resequencing' of all samples from E23, processed with SOPs and technology consistent with that used for E04R, E24, and E25 so that results from these experiments could be reliably compared. Only E23R is intended for comparison with E04R, E24, and E25. This dataset was produced by Dr. Steven E. Bosinger, Nirav Patel, and Greg Tharp at the Emory University Yerkes Genomics Core. To access other publicly available results from E23R and other MaHPIC Experiments, including clinical results (specifics on drugs administered, diet, and veterinary interventions), and other omics, visit http://plasmodb.org/plasmo/mahpic.jsp. This page will be updated as datasets are released to the public. The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC).