Metabolomics

Dataset Information

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MaHPIC Experiment HuC - Metabolomics of plasma samples from human volunteers infected with Plasmodium vivax


ABSTRACT: Project Description:
The Malaria Host-Pathogen Interaction Center (MaHPIC) is 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.

MaHPIC Experiment Description:
Sixteen healthy volunteers, 7 malaria naïve and 9 semi-immune, aged 18-45 years, were enrolled in this study during October 2012 to November 2013. Malaria-naive volunteers were recruited in Cali, Colombia, a non-endemic city; those with previous malaria experience were recruited in Buenaventura, a malaria-endemic area on the Colombian Pacific Coast. The study was approved by Institutional Review Boards (IRB) of the Malaria Vaccine and Drug Development Center–MVDC (CECIV, Cali) and Centro Médico Imbanaco (Cali). All protocols and documentation were reviewed and samples shipments approved by the Emory IRB. Male and female patients were eligible for inclusion, which included two steps: 1) age between 15-60 years, hemoglobin levels > 9g/dL, presence of current Plasmodium vivax infection, absence of other Plasmodium species determined by thick blood smear and PCR, blood parasite count of 0.1% or more, absence of other acute or chronic diseases, being able to sign an informed consent form; 2) healthy 18 to 45 years old man or non-pregnant women, capacity to sign an informed consent in a free and voluntary way, acceptable understanding of the clinical trial through the approval of a questionnaire regarding the information given in the consent process, obligatory use of adequate contraceptive method from beginning of recruitment and screening time up to three months after last immunization, do not have chronic or acute diseases, accept not traveling to malaria endemic areas during the clinical trial, have telephone at home or mobile phone that permit permanent contact for follow up, being willing to participated during both steps of the clinical trial. Exclusion criteria included pregnancy, abnormal laboratory test values, hemoglobin pathology, glucose-6-phosphate dehydrogenase (G6PDH) deficiency, positive for blood bank infectious diseases (syphilis, HIV, Chagas disease, HTLV 1–2, and hepatitis B and hepatitis C), or have any condition that would increase the risk of an adverse outcome. Volunteers were infected with P. vivax via sporozoite challenge by exposing volunteers to bites of 2–4 mosquitoes (Anopheles albimanus) of the same infected batch. Plasma samples were collected at 4 time points: Baseline, 1 month pre-inoculation; Diagnosis; 3 weeks post-treatment; 4 months post-treatment. As soon as parasites were detected by thick blood smears, participants were treated orally with curative doses of chloroquine (1500 mg chloroquine provided in three doses: 600 mg initially then 450 mg doses at 24 and 48 hours) and primaquine (30 mg dose given once per day for 14 days). Clinical trial registration: NCT01585077. Samples were analyzed with liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS), evaluated in a time course and between naïve and semi-immune volunteers. Within the MaHPIC, this project is known as ‘Experiment HuC’. Samples were obtained in collaboration with Socrates Herrera from the Malaria Vaccine and Drug Development Center, Colombia. Metabolomics results were produced by Dean Jones at Emory University. To access other publicly available results from HuC and other MaHPIC Experiments visit http://plasmodb.org/plasmo/mahpic.jsp . This page will be updated as datasets are released to the public.

The following contributed to the creation of this dataset: The MaHPIC Consortium, Jeremy D. DeBarry, Mary R. Galinski, Luiz G. Gardinassi, Socrates Herrera, Myriam Arévalo-Herrera, Dean P. Jones, Jessica C. Kissinger, Shuzhao Li, Regina Joice Cordy, Esmeralda VS Meyer, Mustafa V. Nural, Suman B. Pakala, ViLinh Tran, Karan Uppal

Linked Studies: Malaria Host-Pathogen Interaction Center (MaHPIC)

INSTRUMENT(S): Exactive (Thermo Scientific)

SUBMITTER: Jessica Kissinger 

PROVIDER: MTBLS665 | MetaboLights | 2018-06-19

REPOSITORIES: MetaboLights

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Publications

Integrative metabolomics and transcriptomics signatures of clinical tolerance to Plasmodium vivax reveal activation of innate cell immunity and T cell signaling.

Gardinassi Luiz G LG   Arévalo-Herrera Myriam M   Herrera Sócrates S   Cordy Regina J RJ   Tran ViLinh V   Smith Matthew R MR   Johnson Michelle S MS   Chacko Balu B   Liu Ken H KH   Darley-Usmar Victor M VM   Go Young-Mi YM   Jones Dean P DP   Galinski Mary R MR   Li Shuzhao S  

Redox biology 20180411


Almost invariably, humans become ill during primary infections with malaria parasites which is a pathology associated with oxidative stress and perturbations in metabolism. Importantly, repetitive exposure to Plasmodium results in asymptomatic infections, which is a condition defined as clinical tolerance. Integration of transcriptomics and metabolomics data provides a powerful way to investigate complex disease processes involving oxidative stress, energy metabolism and immune cell activation.  ...[more]

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