Summary of Study ST003117

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 PR001936. The data can be accessed directly via it's Project DOI: 10.21228/M8GB12 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 IDST003117
Study TitleMetabolomics of patients with Plasmodium vivax malaria
Study SummaryBackground: Malaria is the leading parasitic disease worldwide, with P. vivax being a major challenge for its control. Several studies have indicated metabolomics as a promising tool for combating the disease. Objective: The study evaluated plasma metabolomic profiles of patients with recurrent and non-recurrent P. vivax malaria in the Brazilian Amazon. Methods: Metabolites extracted from the plasma of P. vivax-infected patients were subjected to LC-MS analysis. Untargeted metabolomics was applied to investigate the metabolic profile of the plasma in the two groups. Results: Overall, 51 recurrent and 59 non-recurrent patients were included in the study. Longitudinal metabolomic analysis revealed 52 and 37 significant metabolite features from the recurrent and non-recurrent participants, respectively. Recurrence was associated with disturbances in eicosanoid metabolism. Comparison between groups suggest alterations in vitamin B6 (pyridoxine) metabolism, tyrosine metabolism, 3-oxo-10-octadecatrienoate β-oxidation, and alkaloid biosynthesis II. Integrative network analysis revealed enrichment of other metabolic pathways for the recurrent phenotype, including the butanoate metabolism, aspartate and asparagine metabolism, and N-glycan biosynthesis. Conclusion: The metabolites and metabolic pathways predicted in our study suggest potential biomarkers of recurrence and provide insights into targets for antimalarial development against P. vivax.
Institute
University of Sao Paulo
Last NameGardinassi
First NameLuiz Gustavo
AddressAv. dos Bandeirantes, 3900, Campus Universitário, Ribeirão Preto, SP, Brazil
Emailgardinassi@eerp.usp.br
Phone55 16 3315-3395
Submit Date2024-03-01
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2024-04-05
Release Version1
Luiz Gustavo Gardinassi Luiz Gustavo Gardinassi
https://dx.doi.org/10.21228/M8GB12
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR001936
Project DOI:doi: 10.21228/M8GB12
Project Title:Metabolomics of patients with Plasmodium vivax malaria
Project Summary:Background: Malaria is the leading parasitic disease worldwide, with P. vivax being a major challenge for its control. Several studies have indicated metabolomics as a promising tool for combating the disease. Objective: The study evaluated plasma metabolomic profiles of patients with recurrent and non-recurrent P. vivax malaria in the Brazilian Amazon. Methods: Metabolites extracted from the plasma of P. vivax-infected patients were subjected to LC-MS analysis. Untargeted metabolomics was applied to investigate the metabolic profile of the plasma in the two groups. Results: Overall, 51 recurrent and 59 non-recurrent patients were included in the study. Longitudinal metabolomic analysis revealed 52 and 37 significant metabolite features from the recurrent and non-recurrent participants, respectively. Recurrence was associated with disturbances in eicosanoid metabolism. Comparison between groups suggest alterations in vitamin B6 (pyridoxine) metabolism, tyrosine metabolism, 3-oxo-10-octadecatrienoate β-oxidation, and alkaloid biosynthesis II. Integrative network analysis revealed enrichment of other metabolic pathways for the recurrent phenotype, including the butanoate metabolism, aspartate and asparagine metabolism, and N-glycan biosynthesis. Conclusion: The metabolites and metabolic pathways predicted in our study suggest potential biomarkers of recurrence and provide insights into targets for antimalarial development against P. vivax.
Institute:University of Sao Paulo
Last Name:Gardinassi
First Name:Luiz Gustavo
Address:Av. dos Bandeirantes, 3900, Campus Unviversitário, Ribeirão Preto, SP, Brazil
Email:gardinassi@eerp.usp.br
Phone:55 16 3315-3395

Subject:

Subject ID:SU003273
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Gender:Male and female
Species Group:Mammals

Factors:

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

mb_sample_id local_sample_id Class Day Treatment
SA341215ID_47non-recurrence 0 CQ+PQ
SA341216ID_173non-recurrence 0 CQ+PQ
SA341217ID_120non-recurrence 0 CQ+PQ
SA341218ID_106non-recurrence 0 CQ+PQ
SA341219ID_99non-recurrence 0 CQ+PQ
SA341220ID_76non-recurrence 0 CQ+PQ
SA341221ID_56non-recurrence 0 CQ+PQ
SA341222ID_313non-recurrence 0 CQ+PQ
SA341223ID_275non-recurrence 0 CQ+PQ
SA341224ID_281non-recurrence 0 CQ+PQ
SA341187ID_22non-recurrence 0 CQ+PQDHA+PQ422
SA341188ID_295non-recurrence 0 CQ+PQDHA+PQ422
SA341189ID_298non-recurrence 0 CQ+PQDHA+PQ422
SA341190ID_82non-recurrence 0 CQ+PQDHA+PQ422
SA341191ID_40non-recurrence 0 CQ+PQDHA+PQ422
SA341192ID_179non-recurrence 0 CQ+PQDHA+PQ422
SA341193ID_300non-recurrence 0 CQ+PQDHA+PQ422
SA341194ID_25non-recurrence 0 CQ+PQDHA+PQ422
SA341195ID_224non-recurrence 0 CQ+PQDHA+PQ422
SA341196ID_61non-recurrence 0 CQ+PQDHA+PQ422
SA341197ID_216non-recurrence 0 CQ+PQDHA+PQ422
SA341198ID_212non-recurrence 0 CQ+PQDHA+PQ422
SA341199ID_250non-recurrence 0 CQ+PQDHA+PQ422
SA341200ID_164non-recurrence 0 CQ+PQDHA+PQ422
SA341201ID_95non-recurrence 0 CQ+PQDHA+PQ422
SA341202ID_278non-recurrence 0 CQ+PQDHA+PQ422
SA341203ID_110non-recurrence 0 CQ+PQDHA+PQ422
SA341204ID_318non-recurrence 0 CQ+PQDHA+PQ422
SA341205ID_5non-recurrence 0 CQ+PQDHA+PQ422
SA341206ID_118non-recurrence 0 CQ+PQDHA+PQ422
SA341207ID_112non-recurrence 0 CQ+PQDHA+PQ422
SA341208ID_266non-recurrence 0 CQ+PQDHA+PQ422
SA341209ID_103non-recurrence 0 CQ+PQDHA+PQ422
SA341210ID_230non-recurrence 0 CQ+PQDHA+PQ422
SA341211ID_145non-recurrence 0 CQ+PQDHA+PQ422
SA341212ID_138non-recurrence 0 CQ+PQDHA+PQ422
SA341213ID_130non-recurrence 0 CQ+PQDHA+PQ422
SA341214ID_151non-recurrence 0 CQ+PQDHA+PQ422
SA341237ID_161non-recurrence 0 DHA+PQ
SA341238ID_34non-recurrence 0 DHA+PQ
SA341239ID_301non-recurrence 0 DHA+PQ
SA341240ID_206non-recurrence 0 DHA+PQ
SA341241ID_310non-recurrence 0 DHA+PQ
SA341242ID_123non-recurrence 0 DHA+PQ
SA341243ID_243non-recurrence 0 DHA+PQ
SA341225ID_248non-recurrence 0 DHA+PQ42
SA341226ID_287non-recurrence 0 DHA+PQ42
SA341227ID_185non-recurrence 0 DHA+PQ42
SA341228ID_234non-recurrence 0 DHA+PQ42
SA341229ID_17non-recurrence 0 DHA+PQ42
SA341230ID_156non-recurrence 0 DHA+PQ42
SA341231ID_192non-recurrence 0 DHA+PQ42
SA341232ID_270non-recurrence 0 DHA+PQ42
SA341233ID_128non-recurrence 0 DHA+PQ42
SA341234ID_289non-recurrence 0 DHA+PQ42
SA341235ID_3non-recurrence 0 DHA+PQ42
SA341236ID_260non-recurrence 0 DHA+PQ42
SA341271ID_204non-recurrence 6 CQ+PQ
SA341272ID_207non-recurrence 6 CQ+PQ
SA341273ID_314non-recurrence 6 CQ+PQ
SA341274ID_309non-recurrence 6 CQ+PQ
SA341275ID_9non-recurrence 6 CQ+PQ
SA341276ID_38non-recurrence 6 CQ+PQ
SA341277ID_132non-recurrence 6 CQ+PQ
SA341278ID_229non-recurrence 6 CQ+PQ
SA341279ID_127non-recurrence 6 CQ+PQ
SA341280ID_321non-recurrence 6 CQ+PQ
SA341244ID_303non-recurrence 6 CQ+PQDHA+PQ422
SA341245ID_188non-recurrence 6 CQ+PQDHA+PQ422
SA341246ID_77non-recurrence 6 CQ+PQDHA+PQ422
SA341247ID_307non-recurrence 6 CQ+PQDHA+PQ422
SA341248ID_105non-recurrence 6 CQ+PQDHA+PQ422
SA341249ID_317non-recurrence 6 CQ+PQDHA+PQ422
SA341250ID_7non-recurrence 6 CQ+PQDHA+PQ422
SA341251ID_12non-recurrence 6 CQ+PQDHA+PQ422
SA341252ID_142non-recurrence 6 CQ+PQDHA+PQ422
SA341253ID_88non-recurrence 6 CQ+PQDHA+PQ422
SA341254ID_154non-recurrence 6 CQ+PQDHA+PQ422
SA341255ID_150non-recurrence 6 CQ+PQDHA+PQ422
SA341256ID_165non-recurrence 6 CQ+PQDHA+PQ422
SA341257ID_199non-recurrence 6 CQ+PQDHA+PQ422
SA341258ID_242non-recurrence 6 CQ+PQDHA+PQ422
SA341259ID_238non-recurrence 6 CQ+PQDHA+PQ422
SA341260ID_283non-recurrence 6 CQ+PQDHA+PQ422
SA341261ID_33non-recurrence 6 CQ+PQDHA+PQ422
SA341262ID_258non-recurrence 6 CQ+PQDHA+PQ422
SA341263ID_43non-recurrence 6 CQ+PQDHA+PQ422
SA341264ID_263non-recurrence 6 CQ+PQDHA+PQ422
SA341265ID_286non-recurrence 6 CQ+PQDHA+PQ422
SA341266ID_54non-recurrence 6 CQ+PQDHA+PQ422
SA341267ID_220non-recurrence 6 CQ+PQDHA+PQ422
SA341268ID_65non-recurrence 6 CQ+PQDHA+PQ422
SA341269ID_210non-recurrence 6 CQ+PQDHA+PQ422
SA341270ID_28non-recurrence 6 CQ+PQDHA+PQ422
SA341293ID_119non-recurrence 6 DHA+PQ
SA341294ID_293non-recurrence 6 DHA+PQ
SA341295ID_265non-recurrence 6 DHA+PQ
SA341296ID_116non-recurrence 6 DHA+PQ
SA341297ID_169non-recurrence 6 DHA+PQ
SA341298ID_162non-recurrence 6 DHA+PQ
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Collection:

Collection ID:CO003266
Collection Summary:Individuals with P. vivax were admitted at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), a reference center for infectious diseases located in Manaus, Western Brazilian Amazon. At inclusion into the CURAVIVAX study, patient socio-demographic data including sex, age, weight, body-mass index and ethnicity was captured. Laboratory analyses were done at pre-treatment through the treatment days and follow-up including the day of recurrence. Patients of both sexes, aged > 6 months, body weight ≥ 5 kg, with symptomatic P. vivax monoinfection, parasite density between 100 and 100,000 parasites/ µL were included. Exclusion criteria included the use of antimalarials in the last 60 days, mixed Plasmodium infections especially P. falciparum, pregnancy, or lactation and concomitant or underlying diseases. Patients with dengue and other febrile diseases were excluded during screening. After confirmation of malaria vivax by thick blood smears, whole blood and plasma samples were collected, aliquoted and stored at -80OC until needed for analysis. Plasma samples for day of inclusion and before treatment (D0), day six (D6), day ninety (D90) and recurrence day (DR) were used for this study.
Sample Type:Blood (plasma)
Storage Conditions:-80℃

Treatment:

Treatment ID:TR003282
Treatment Summary:Patients were randomly assigned to one of four treatment groups: Group1- chloroquine (CQ) for 3 days + primaquine (PQ) for 14 days (0.50mg/kg/day) concurrently. Group 2 - dihydroartemisinin/piperaquine (DHA/PPQ) for 3 days + PQ for 14 days (0.50mg/kg/day) concurrently, Group 3 - CQ for 3 days + PQ for 14 days (0.50mg/kg/day) starting on day 42 after the initial CQ, and Group 4 - DHA/PPQ for 3 days + PQ for 14 days (0.50mg/kg/day) starting on day 42 after the initial DHA/PPQ.

Sample Preparation:

Sampleprep ID:SP003280
Sampleprep Summary:Metabolites were extracted from 150 µL of sample (plasma EDTA), which was mixed with acetonitrile (2:1, v/v; -5 °C) and centrifuged at 15,000 rpm for 15 min to remove proteins. Stable isotopes caffeine-¹³C3, tyrosine-15N and progesterone-d9 were used as internal standards.

Chromatography:

Chromatography ID:CH003916
Chromatography Summary:The binary mobile phases were water 0.5% formic acid with 5 mM of ammonium formate (A), and acetonitrile (B). Their gradient elution started with 20% (B) for 5 min, then linearly increased to 100% (B) in 30 min and kept constant for 8 min in 100% (B). The eluent was restored to the initial conditions in 4 minutes to re-equilibrate the column and held for the remaining 8 minutes. The flow rate was kept at 0.5 mL min-1. The injection volume for analysis was 3 μL, and the column temperature was set at 35 °C.
Instrument Name:Agilent 1220 Infinity
Column Name:Agilent ZORBAX Eclipse Plus C18 (100 x 4.6mm,3.5um)
Column Temperature:35
Flow Gradient:gradient elution started with 20% (B) for 5 min, then linearly increased to 100% (B) in 30 min and kept constant for 8 min in 100% (B). The eluent was restored to the initial conditions in 4 minutes to re-equilibrate the column and held for the remaining 8 minutes.
Flow Rate:0.5 mL/min
Solvent A:100% water; 0.5% formic acid; 5 mM of ammonium formate
Solvent B:100% acetonitrile
Chromatography Type:Reversed phase

Analysis:

Analysis ID:AN005177
Analysis Type:MS
Chromatography ID:CH003916
Has Mz:1
Has Rt:1
Rt Units:Seconds
Results File:ST003117_AN005177_Results.txt
Units:normalized intensity
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