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Nowhere to hide: interrogating different metabolic parameters of Plasmodium falciparum gametocytes in a transmission blocking drug discovery pipeline towards malaria elimination

Overview of attention for article published in Malaria Journal, May 2015
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About this Attention Score

  • Good Attention Score compared to outputs of the same age (69th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (57th percentile)

Mentioned by

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6 tweeters
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1 Facebook page

Citations

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79 Dimensions

Readers on

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119 Mendeley
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Title
Nowhere to hide: interrogating different metabolic parameters of Plasmodium falciparum gametocytes in a transmission blocking drug discovery pipeline towards malaria elimination
Published in
Malaria Journal, May 2015
DOI 10.1186/s12936-015-0718-z
Pubmed ID
Authors

Janette Reader, Mariëtte Botha, Anjo Theron, Sonja B Lauterbach, Claire Rossouw, Dewaldt Engelbrecht, Melanie Wepener, Annél Smit, Didier Leroy, Dalu Mancama, Theresa L Coetzer, Lyn-Marie Birkholtz

Abstract

The discovery of malaria transmission-blocking compounds is seen as key to malaria elimination strategies and gametocyte-screening platforms are critical filters to identify active molecules. However, unlike asexual parasite assays measuring parasite proliferation, greater variability in end-point readout exists between different gametocytocidal assays. This is compounded by difficulties in routinely producing viable, functional and stage-specific gametocyte populations. Here, a parallel evaluation of four assay platforms on the same gametocyte populations was performed for the first time. This allowed the direct comparison of the ability of different assay platforms to detect compounds with gametocytocidal activity and revealed caveats in some assay readouts that interrogate different parasite biological functions. Gametocytogenesis from Plasmodium falciparum (NF54) was optimized with a robust and standardized protocol. ATP, pLDH, luciferase reporter and PrestoBlue(®) assays were compared in context of a set of 10 reference compounds. The assays were performed in parallel on the same gametocyte preparation (except for luciferase reporter lines) using the same drug preparations (48 h). The remaining parameters for each assay were all comparable. A highly robust method for generating viable and functional gametocytes was developed and comprehensively validated resulting in an average gametocytaemia of 4 %. Subsequent parallel assays for gametocytocidal activity indicated that different assay platforms were not able to screen compounds with variant chemical scaffolds similarly. Luciferase reporter assays revealed that synchronized stage-specific gametocyte production is essential for drug discovery, as differential susceptibility in various gametocyte developmental populations is evident. With this study, the key parameters for assays aiming at testing the gametocytocidal activity of potential transmission blocking molecules against Plasmodium gametocytes were accurately dissected. This first and uniquely comparative study emphasizes differential effects seen with the use of different assay platforms interrogating variant biological systems. Whilst this data is informative from a biological perspective and may provide indications of the drug mode of action, it does highlight the care that must be taken when screening broad-diversity chemotypes with a single assay platform against gametocytes for which the biology is not clearly understood.

Twitter Demographics

The data shown below were collected from the profiles of 6 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 119 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 <1%
Tanzania, United Republic of 1 <1%
Unknown 117 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 28 24%
Student > Ph. D. Student 24 20%
Student > Master 20 17%
Student > Bachelor 8 7%
Student > Postgraduate 8 7%
Other 12 10%
Unknown 19 16%
Readers by discipline Count As %
Agricultural and Biological Sciences 31 26%
Chemistry 24 20%
Biochemistry, Genetics and Molecular Biology 18 15%
Medicine and Dentistry 10 8%
Pharmacology, Toxicology and Pharmaceutical Science 7 6%
Other 4 3%
Unknown 25 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 February 2016.
All research outputs
#6,851,787
of 22,805,349 outputs
Outputs from Malaria Journal
#2,048
of 5,563 outputs
Outputs of similar age
#81,814
of 267,780 outputs
Outputs of similar age from Malaria Journal
#47
of 112 outputs
Altmetric has tracked 22,805,349 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 5,563 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.8. This one has gotten more attention than average, scoring higher than 62% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 267,780 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 69% of its contemporaries.
We're also able to compare this research output to 112 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 57% of its contemporaries.