Evidence map›Paper›PMID 31324806›Full record

ArticleNature communications2019

Antimalarial activity of primaquine operates via a two-step biochemical relay.

Grazia Camarda, Piyaporn Jirawatcharadech, Richard S Priestley, Ahmed Saif, Sandra March, Michael H L Wong, Suet Leung, Alex B Miller, David A Baker, Pietro Alano and 5 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 2 pooled it
19.5field-weighted citation impact, top 1% 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

73 citing papers in PubMed, 2 syntheses or guidelines pooled it, 151 citations in OpenAlex.

  1. Pooled it
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  13. Humanization of Drug Metabolism in theACS infectious diseases · 2025
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13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 4 countries.

Grazia CamardaCentre for Drugs and Diagnostics Research, Tropical Disease Biology Department, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK.
Piyaporn JirawatcharadechCentre for Drugs and Diagnostics Research, Tropical Disease Biology Department, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK.
Richard S PriestleyCentre for Drugs and Diagnostics Research, Tropical Disease Biology Department, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK.ORCID http://orcid.org/0000-0002-5284-5326
Ahmed SaifCentre for Drugs and Diagnostics Research, Tropical Disease Biology Department, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK.
Sandra MarchHealth Sciences and Technology/Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Michael H L WongDepartment of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK.ORCID http://orcid.org/0000-0001-8110-0916
Suet LeungDepartment of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK.
Alex B MillerHealth Sciences and Technology/Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
David A BakerFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK.ORCID http://orcid.org/0000-0002-5490-8933
Pietro AlanoDipartimento di Malattie Infettive, Istituto Superiore di Sanità, Rome, 00161, Italy.
Mark J I PaineVector Biology Department, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK.ORCID http://orcid.org/0000-0003-2061-7713
Sangeeta N BhatiaHealth Sciences and Technology/Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Paul M O'NeillDepartment of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK.
Stephen A WardCentre for Drugs and Diagnostics Research, Tropical Disease Biology Department, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK.
Giancarlo A BiaginiCentre for Drugs and Diagnostics Research, Tropical Disease Biology Department, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK. Giancarlo.Biagini@lstmed.ac.uk.ORCID http://orcid.org/0000-0001-6356-6595
Liverpool School of Tropical Medicine · GBMassachusetts Institute of Technology · USUniversity of Liverpool · GBIstituto Superiore di Sanità · ITLondon School of Hygiene & Tropical Medicine · GB

Funding

Medical Research Council MC_PC_14111Medical Research Council MC_PC_16052Medical Research Council MR/L000644/1
6 · The paper itself

Abstract

Primaquine (PQ) is an essential antimalarial drug but despite being developed over 70 years ago, its mode of action is unclear. Here, we demonstrate that hydroxylated-PQ metabolites (OH-PQm) are responsible for efficacy against liver and sexual transmission stages of Plasmodium falciparum. The antimalarial activity of PQ against liver stages depends on host CYP2D6 status, whilst OH-PQm display direct, CYP2D6-independent, activity. PQ requires hepatic metabolism to exert activity against gametocyte stages. OH-PQm exert modest antimalarial efficacy against parasite gametocytes; however, potency is enhanced ca.1000 fold in the presence of cytochrome P450 NADPH:oxidoreductase (CPR) from the liver and bone marrow. Enhancement of OH-PQm efficacy is due to the direct reduction of quinoneimine metabolites by CPR with the concomitant and excessive generation of H

Indexed as

AminoquinolinesAntimalarialsBone MarrowCytochrome P-450 CYP2D6Cytochrome P-450 Enzyme SystemDose-Response Relationship, DrugHumansHydrogen PeroxideLiverMalaria, FalciparumNADPPharmacokineticsPlasmodium falciparumPrimaquine8-aminoquinolineAminoquinolinesAntimalarialsCytochrome P-450 CYP2D6Cytochrome P-450 Enzyme SystemHydrogen PeroxideNADPPrimaquine

Identifiers

PMID31324806
PMCPMC6642103
OpenAlexW2962967773

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.