Evidence map›Paper›PMID 26525783›Full record

ArticleAntimicrobial agents and chemotherapy2016

Expression of Plasmodium vivax crt-o Is Related to Parasite Stage but Not Ex Vivo Chloroquine Susceptibility.

Zuleima Pava, Irene Handayuni, Grennady Wirjanata, Sheren To, Leily Trianty, Rintis Noviyanti, Jeanne Rini Poespoprodjo, Sarah Auburn, Ric N Price, Jutta Marfurt

Open access · hybridAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.0field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. No Association between the Plasmodium vivaxAntimicrobial agents and chemotherapy · 2023
    Article
  3. Article
  4. Article
  5. High Proportion of Genome-Wide Homology and Increased PretreatmentAntimicrobial agents and chemotherapy · 2021
    Article
  6. Monitoring Plasmodium vivax resistance to antimalarials: Persisting challenges and future directions.International journal for parasitology. Drugs and drug resistance · 2021
    Review
  7. Molecular Surveillance andFrontiers in cellular and infection microbiology · 2021
    Article
  8. Article
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  15. Frontiers in cellular and infection microbiology · 2018
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 3 countries.

Zuleima PavaGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia.
Irene HandayuniGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia.
Grennady WirjanataGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia.
Sheren ToGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia.
Leily TriantyEijkman Institute for Molecular Biology, Jakarta, Indonesia.
Rintis NoviyantiEijkman Institute for Molecular Biology, Jakarta, Indonesia.
Jeanne Rini PoespoprodjoPapuan Health and Community Development Foundation (PHCDF), Timika, Papua, Indonesia Department of Paediatrics, Faculty of Medicine, Gadjah Mada University, Yogyakarta, Indonesia.
Sarah AuburnGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia.
Ric N PriceGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
Jutta MarfurtGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia jutta.marfurt@menzies.edu.au.
Charles Darwin University · AUEijkman Institute for Molecular Biology · IDMenzies School of Health Research · AUUniversitas Gadjah Mada · ID

Funding

Wellcome Trust 091625
6 · The paper itself

Abstract

Chloroquine (CQ)-resistant Plasmodium vivax is present in most countries where P. vivax infection is endemic, but the underlying molecular mechanisms responsible remain unknown. Increased expression of P. vivax crt-o (pvcrt-o) has been correlated with in vivo CQ resistance in an area with low-grade resistance. We assessed pvcrt-o expression in isolates from Papua (Indonesia), where P. vivax is highly CQ resistant. Ex vivo drug susceptibilities to CQ, amodiaquine, piperaquine, mefloquine, and artesunate were determined using a modified schizont maturation assay. Expression levels of pvcrt-o were measured using a novel real-time quantitative reverse transcription-PCR method. Large variations in pvcrt-o expression were observed across the 51 isolates evaluated, with the fold change in expression level ranging from 0.01 to 59 relative to that seen with the P. vivax β-tubulin gene and from 0.01 to 24 relative to that seen with the P. vivax aldolase gene. Expression was significantly higher in isolates with the majority of parasites at the ring stage of development (median fold change, 1.7) compared to those at the trophozoite stage (median fold change, 0.5; P < 0.001). Twenty-nine isolates fulfilled the criteria for ex vivo drug susceptibility testing and showed high variability in CQ responses (median, 107.9 [range, 6.5 to 345.7] nM). After controlling for the parasite stage, we found that pvcrt-o expression levels did not correlate with the ex vivo response to CQ or with that to any of the other antimalarials tested. Our results highlight the importance of development-stage composition for measuring pvcrt-o expression and suggest that pvcrt-o transcription is not a primary determinant of ex vivo drug susceptibility. A comprehensive transcriptomic approach is warranted for an in-depth investigation of the role of gene expression levels and P. vivax drug resistance.

Indexed as

AmodiaquineAntimalarialsArtemisininsArtesunateChloroquineDrug Resistance, MultipleErythrocytesFructose-Bisphosphate AldolaseGene Expression RegulationHumansInhibitory Concentration 50Life Cycle StagesMalaria, VivaxMefloquineMembrane Transport ProteinsPiperazinesAmodiaquineAntimalarialsArtemisininsArtesunateChloroquineCrt-o protein, Plasmodium vivaxFructose-Bisphosphate AldolaseMefloquineMembrane Transport ProteinspiperaquinePiperazinesProtozoan ProteinsQuinolinesTubulin

Identifiers

PMID26525783
PMCPMC4704153
OpenAlexW1906493634

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.