Evidence map›Paper›PMID 38383417›Full record

ArticleMalaria journal2024

Correlative light-electron microscopy methods to characterize the ultrastructural features of the replicative and dormant liver stages of Plasmodium parasites.

Gabriel Mitchell, Laura Torres, Matthew E Fishbaugher, Melanie Lam, Vorada Chuenchob, Reena Zalpuri, Shreya Ramasubban, Caitlin N Baxter, Erika L Flannery, Anke Harupa and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Malaria journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
2.2field-weighted citation impact, top 14% 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

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
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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

12 authors at 2 institutions in 1 country.

Gabriel MitchellOpen Innovation at Global Health Disease Area, Biomedical Research, Novartis, Emeryville, CA, USA. gabriel.mitchell@novartis.com.
Laura TorresOpen Innovation at Global Health Disease Area, Biomedical Research, Novartis, Emeryville, CA, USA.
Matthew E FishbaugherGlobal Health Disease Area, Biomedical Research, Novartis, Emeryville, CA, USA.
Melanie LamOpen Innovation at Global Health Disease Area, Biomedical Research, Novartis, Emeryville, CA, USA.
Vorada ChuenchobGlobal Health Disease Area, Biomedical Research, Novartis, Emeryville, CA, USA.
Reena ZalpuriElectron Microscope Laboratory, University of California, Berkeley, CA, USA.
Shreya RamasubbanElectron Microscope Laboratory, University of California, Berkeley, CA, USA.
Caitlin N BaxterElectron Microscope Laboratory, University of California, Berkeley, CA, USA.
Erika L FlanneryGlobal Health Disease Area, Biomedical Research, Novartis, Emeryville, CA, USA.
Anke HarupaGlobal Health Disease Area, Biomedical Research, Novartis, Emeryville, CA, USA.
Sebastian A MikolajczakGlobal Health Disease Area, Biomedical Research, Novartis, Emeryville, CA, USA.
Danielle M JorgensElectron Microscope Laboratory, University of California, Berkeley, CA, USA.
Novartis (United States) · USUniversity of California, Berkeley · US

Funding

Bill and Melinda Gates Foundation INV010720Gates Foundation INV-010720
6 · The paper itself

Abstract

backgroundThe infection of the liver by Plasmodium parasites is an obligatory step leading to malaria disease. Following hepatocyte invasion, parasites differentiate into replicative liver stage schizonts and, in the case of Plasmodium species causing relapsing malaria, into hypnozoites that can lie dormant for extended periods of time before activating. The liver stages of Plasmodium remain elusive because of technical challenges, including low infection rate. This has been hindering experimentations with well-established technologies, such as electron microscopy. A deeper understanding of hypnozoite biology could prove essential in the development of radical cure therapeutics against malaria.

resultsThe liver stages of the rodent parasite Plasmodium berghei, causing non-relapsing malaria, and the simian parasite Plasmodium cynomolgi, causing relapsing malaria, were characterized in human Huh7 cells or primary non-human primate hepatocytes using Correlative Light-Electron Microscopy (CLEM). Specifically, CLEM approaches that rely on GFP-expressing parasites (GFP-CLEM) or on an immunofluorescence assay (IFA-CLEM) were used for imaging liver stages. The results from P. berghei showed that host and parasite organelles can be identified and imaged at high resolution using both CLEM approaches. While IFA-CLEM was associated with more pronounced extraction of cellular content, samples' features were generally well preserved. Using IFA-CLEM, a collection of micrographs was acquired for P. cynomolgi liver stage schizonts and hypnozoites, demonstrating the potential of this approach for characterizing the liver stages of Plasmodium species causing relapsing malaria.

conclusionsA CLEM approach that does not rely on parasites expressing genetically encoded tags was developed, therefore suitable for imaging the liver stages of Plasmodium species that lack established protocols to perform genetic engineering. This study also provides a dataset that characterizes the ultrastructural features of liver stage schizonts and hypnozoites from the simian parasite species P. cynomolgi.

Indexed as

MalariaParasitesAnimalsHumansLiverMicroscopy, ElectronPlasmodium bergheiCLEMHepatocytesHypnozoitesMitochondriaPlasmodium bergheiPlasmodium cynomolgiRelapsing malariaSchizontsTEMTransmission electron microscopy

Identifiers

PMID38383417
PMCPMC10882739
OpenAlexW4392014877

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.