Summary of study ST001384

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000948. The data can be accessed directly via it's Project DOI: 10.21228/M8540T This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST001384
Study TitlePlasmodium falciparum increased time in circulation underlies persistent asymptomatic infection in the dry season
Study SummaryThe dry season is a major challenge for Plasmodium falciparum parasites in many malaria endemic regions, where water availability limits mosquitoes to only part of the year. How P. falciparum bridges two transmission seasons months apart, without being cleared by the host or compromising host survival is poorly understood. Here we show that low levels of P. falciparum parasites persist in the blood of asymptomatic Malian individuals during the 5- to 6-month dry season, rarely causing symptoms and minimally affecting the host immune response. Parasites isolated during the dry season are transcriptionally distinct from those of subjects with febrile malaria in the transmission season, reflecting longer circulation within each replicative cycle, of parasitized erythrocytes without adhering to the vascular endothelium. Low parasite levels during the dry season are not due to impaired replication, but rather increased splenic clearance of longer-circulating infected erythrocytes. We propose that P. falciparum virulence in areas of seasonal malaria transmission is regulated so that the parasite decreases its endothelial binding capacity, allowing increased splenic clearance and enabling several months of subclinical parasite persistence.
Institute
Pennsylvania State University
Last NameLlinas
First NameManuel
AddressW126 Millennium Science Complex, University Park, PENNSYLVANIA, 16802, USA
Emailmanuel@psu.edu
Phone(814) 867-3527
Submit Date2020-05-25
Raw Data AvailableYes
Raw Data File Type(s).wiff
Analysis Type DetailLC-MS
Release Date2020-08-20
Release Version1
Manuel Llinas Manuel Llinas
https://dx.doi.org/10.21228/M8540T
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000948
Project DOI:doi: 10.21228/M8540T
Project Title:Plasmodium falciparum increased time in circulation underlies persistent asymptomatic infection in the dry season
Project Summary:The dry season is a major challenge for Plasmodium falciparum parasites in many malaria endemic regions, where water availability limits mosquitoes to only part of the year. How P. falciparum bridges two transmission seasons months apart, without being cleared by the host or compromising host survival is poorly understood. Here we show that low levels of P. falciparum parasites persist in the blood of asymptomatic Malian individuals during the 5- to 6-month dry season, rarely causing symptoms and minimally affecting the host immune response. Parasites isolated during the dry season are transcriptionally distinct from those of subjects with febrile malaria in the transmission season, reflecting longer circulation within each replicative cycle, of parasitized erythrocytes without adhering to the vascular endothelium. Low parasite levels during the dry season are not due to impaired replication, but rather increased splenic clearance of longer-circulating infected erythrocytes. We propose that P. falciparum virulence in areas of seasonal malaria transmission is regulated so that the parasite decreases its endothelial binding capacity, allowing increased splenic clearance and enabling several months of subclinical parasite persistence.
Institute:Pennsylvania State University
Last Name:Llinas
First Name:Manuel
Address:W126 Millennium Science Complex, University Park, PENNSYLVANIA, 16802, USA
Email:manuel@psu.edu
Phone:(814) 867-3527

Subject:

Subject ID:SU001458
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Genotype
SA101065blank1Blank
SA101066blank3Blank
SA101067blank2Blank
SA101068blank4Blank
SA101069b332MAL
SA101070b322MAL
SA101071b262MAL
SA101072b385MAL
SA101073b459MAL
SA101074b224MAL
SA101075b443MAL
SA101076b400MAL
SA101077b391MAL
SA101078b371MAL
SA101079b170MAL
SA101080b161MAL
SA101081poolb1MAL Pool
SA101082poolb2MAL Pool
SA101083poolb3MAL Pool
SA101084a320May
SA101085a326May
SA101086a325May
SA101087a308May
SA101088a351May
SA101089a244May
SA101090a448May
SA101091a388May
SA101092a373May
SA101093a355May
SA101094a357May
SA101095a334May
SA101096poola3May Pool
SA101097poola1May Pool
SA101098poola2May Pool
SA101099qc1Pool
SA101100qc2Pool
SA101101qc3Pool
Showing results 1 to 37 of 37

Collection:

Collection ID:CO001453
Collection Summary:2 mL venous blood was drawn of RDT+ individuals tested at the end of the dry season (May 2012) cross-sectional, and at the first malaria episode of the ensuing transmission season, into EDTA tubes (Vacutainer K3EDTA Tubes, BD) and processed directly at the field site. Plasma (used for metabolomic analysis) was separated by centrifugation and immediately frozen in liquid N2. Buffy coat was discarded and the RBC pellet was further removed of leucocytes in a two-step procedure; first by density gradient on Lymphoprep solution (Fresenius Kabi), followed by Plasmodipur (EuroProxima) filtration.
Sample Type:Blood (plasma)

Treatment:

Treatment ID:TR001473
Treatment Summary:None, samples were collected at 2 natural timepoints. RDT+ individuals tested at the end of the dry season (May 2012) cross-sectional, and at the first malaria episode of the ensuing transmission season.

Sample Preparation:

Sampleprep ID:SP001466
Sampleprep Summary:Each plasma sample was split into two independent samples for metabolite extraction. For hydrophilic metabolites, 50µL of plasma was extracted by the addition of 9X volumes of ice cold methanol. Samples were briefly vortexed before centrifuging for 10 minutes to remove precipitated protein. The clarified supernatants were dried under nitrogen gas and resuspended in 100µL (1:2 dilution final). For hydrophobic metabolites, 25µL of plasma was extracted by the addition of 3X volumes of isopropanol. Samples were briefly vortexed and allowed to sit at room temperature for 10 minutes. Samples were then placed at -20 °C to precipitate overnight. Precipitated samples were centrifuged for 20 minutes and the clarified supernatant was diluted to 50% water in a glass LCMS sample vial (1:6 dilution final). Sample groups were pooled to create a group QA and all samples were pooled to create a batch QC, which were injected periodically throughout each run.

Combined analysis:

Analysis ID AN002308 AN002309 AN002310 AN002311
Analysis type MS MS MS MS
Chromatography type Reversed phase Reversed phase Reversed phase Reversed phase
Chromatography system Shimadzu Prominence 20 UFLCXR Thermo Dionex Ultimate 3000 Shimadzu Prominence 20 UFLCXR Shimadzu Prominence 20 UFLCXR
Column Waters BEH C18 (100mm x 2.1mm; 1.7 µm) Waters XSelect HSS T3 column (2.1 x 100mm; 2.5 µm) Waters Acquity CSH C18 (100 x 2.1mm, 1.7um) Waters Acquity CSH C18 (100 x 2.1mm, 1.7um)
MS Type ESI ESI ESI ESI
MS instrument type QTOF Orbitrap QTOF QTOF
MS instrument name ABI Sciex 5600 TripleTOF Thermo Exactive Plus Orbitrap ABI Sciex 5600 TripleTOF ABI Sciex 5600 TripleTOF
Ion Mode POSITIVE NEGATIVE POSITIVE NEGATIVE
Units Area Area Area

Chromatography:

Chromatography ID:CH001695
Instrument Name:Shimadzu Prominence 20 UFLCXR
Column Name:Waters BEH C18 (100mm x 2.1mm; 1.7 µm)
Chromatography Type:Reversed phase
  
Chromatography ID:CH001696
Instrument Name:Thermo Dionex Ultimate 3000
Column Name:Waters XSelect HSS T3 column (2.1 x 100mm; 2.5 µm)
Chromatography Type:Reversed phase
  
Chromatography ID:CH001697
Instrument Name:Shimadzu Prominence 20 UFLCXR
Column Name:Waters Acquity CSH C18 (100 x 2.1mm, 1.7um)
Chromatography Type:Reversed phase
  
Chromatography ID:CH001698
Instrument Name:Shimadzu Prominence 20 UFLCXR
Column Name:Waters Acquity CSH C18 (100 x 2.1mm, 1.7um)
Chromatography Type:Reversed phase

MS:

MS ID:MS002151
Analysis ID:AN002308
Instrument Name:ABI Sciex 5600 TripleTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:The capillary voltage was set at 4.5 kV in negative ion mode, with a declustering potential of 80V. The mass spectrometer was operated in IDA (Information Dependent Acquisition) mode with a 100 ms survey scan from 100 to 1200 m/z, and up to 20 MS/MS product ion scans (100 ms) per duty cycle using a collision energy of 50V with a 20V spread. Data processing was performed using MS-DIAL and annotated using the built-in public library. Blank subtraction and analysis was performed in excel.
Ion Mode:POSITIVE
  
MS ID:MS002152
Analysis ID:AN002309
Instrument Name:Thermo Exactive Plus Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Aquired in MS1 mode only. Data processing and annotation performed using MAVEN and an in-house targeted list. Blank subtraction and analysis was performed in excel.
Ion Mode:NEGATIVE
  
MS ID:MS002153
Analysis ID:AN002310
Instrument Name:ABI Sciex 5600 TripleTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:IDA MS2 method. Ammonium formate and formic acid were added to the positive ESI solvents. Data processing performed using MS-DIAL and annotated using the in silico library. Blank subtraction and analysis was performed in excel.
Ion Mode:POSITIVE
  
MS ID:MS002154
Analysis ID:AN002311
Instrument Name:ABI Sciex 5600 TripleTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:IDA MS2 method. Ammonium acetate was used for negative ESI solvents. Data processing performed using MS-DIAL and annotated using the in silico library. Blank subtraction and analysis was performed in excel.
Ion Mode:NEGATIVE
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