Evidence map›Paper›PMID 22514702›Full record

ArticlePloS one2012

Activity of clinically relevant antimalarial drugs on Plasmodium falciparum mature gametocytes in an ATP bioluminescence "transmission blocking" assay.

Joël Lelièvre, Maria Jesus Almela, Sonia Lozano, Celia Miguel, Virginia Franco, Didier Leroy, Esperanza Herreros

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 1 pooled it
22.3field-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

93 citing papers in PubMed, 1 synthesis or guideline pooled it, 217 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Efficacy, Safety and Tolerability of Pyronaridine-artesunate in Asymptomatic Malaria-infected Individuals: a Randomized Controlled Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022
    Trial
  4. Trial
  5. Trial
  6. Trial
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Real-time measurements of ATP dynamics via ATeams inAntimicrobial agents and chemotherapy · 2024
    Article
  18. Prevalence ofParasite epidemiology and control · 2023
    Article
  19. Article
  20. Review

33 more citing papers are in PubMed but not listed here.

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

7 authors at 2 institutions in 2 countries.

Joël LelièvreGlaxoSmithKline R&D, Tres Cantos Medicine Development Campus, Malaria Discovery Performance Unit, Madrid, Spain. Joel.l.lelievre@gsk.com
Maria Jesus Almela
Sonia Lozano
Celia Miguel
Virginia Franco
Didier Leroy
Esperanza Herreros
GlaxoSmithKline (Spain) · ESMedicines for Malaria Venture · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCurrent anti-malarial drugs have been selected on the basis of their activity against the symptom-causing asexual blood stage of the parasite. Which of these drugs also target gametocytes, in the sexual stage responsible for disease transmission, remains unknown. Blocking transmission is one of the main strategies in the eradication agenda and requires the identification of new molecules that are active against gametocytes. However, to date, the main limitation for measuring the effect of molecules against mature gametocytes on a large scale is the lack of a standardized and reliable method. Here we provide an efficient method to produce and purify mature gametocytes in vitro. Based on this new procedure, we developed a robust, affordable, and sensitive ATP bioluminescence-based assay. We then assessed the activity of 17 gold-standard anti-malarial drugs on Plasmodium late stage gametocytes. METHODS AND

findingsDifficulties in producing large amounts of gametocytes have limited progress in the development of malaria transmission blocking assays. We improved the method established by Ifediba and Vanderberg to obtain viable, mature gametocytes en masse, whatever the strain used. We designed an assay to determine the activity of antimalarial drugs based on the intracellular ATP content of purified stage IV-V gametocytes after 48 h of drug exposure in 96/384-well microplates. Measurements of drug activity on asexual stages and cytotoxicity on HepG2 cells were also obtained to estimate the specificity of the active drugs.

conclusionsThe work described here represents another significant step towards determination of the activity of new molecules on mature gametocytes of any strain with an automated assay suitable for medium/high-throughput screening. Considering that the biology of the forms involved in the sexual and asexual stages is very different, a screen of our 2 million-compound library may allow us to discover novel anti-malarial drugs to target gametocyte-specific metabolic pathways.

Indexed as

Adenosine TriphosphateAnimalsAntimalarialsGerm CellsLuminescent MeasurementsParasitic Sensitivity TestsPlasmodium falciparumAdenosine TriphosphateAntimalarials

Identifiers

PMID22514702
PMCPMC3325938
OpenAlexW2163816642

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.