Evidence map›Paper›PMID 30053881›Full record

ArticleMalaria journal2018

Plasmodium 18S rRNA of intravenously administered sporozoites does not persist in peripheral blood.

Sean C Murphy, Andrew S Ishizuka, Zachary P Billman, Tayla M Olsen, Annette M Seilie, Ming Chang, Nahum Smith, Vorada Chuenchob, Sumana Chakravarty, B Kim Lee Sim and 3 more

Open access · goldAbstract read
In one paragraph

Article in Malaria journal, 2018. 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
0.2field-weighted citation impact, top 36% 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
  2. Article
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

13 authors at 4 institutions in 1 country.

Sean C MurphyDepartments of Laboratory Medicine and Microbiology, University of Washington, 750 Republican St., E630, Seattle, WA, 98109, USA. murphysc@uw.edu.ORCID http://orcid.org/0000-0002-2048-0131
Andrew S IshizukaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 40, Room 3512, 40 Convent Drive, Bethesda, MD, 20814, USA.
Zachary P BillmanDepartments of Laboratory Medicine and Microbiology, University of Washington, 750 Republican St., E630, Seattle, WA, 98109, USA.
Tayla M OlsenDepartments of Laboratory Medicine and Microbiology, University of Washington, 750 Republican St., E630, Seattle, WA, 98109, USA.
Annette M SeilieDepartments of Laboratory Medicine and Microbiology, University of Washington, 750 Republican St., E630, Seattle, WA, 98109, USA.
Ming ChangDepartments of Laboratory Medicine and Microbiology, University of Washington, 750 Republican St., E630, Seattle, WA, 98109, USA.
Nahum SmithDepartments of Laboratory Medicine and Microbiology, University of Washington, 750 Republican St., E630, Seattle, WA, 98109, USA.
Vorada ChuenchobCenter for Infectious Disease Research, 307 Westlake Ave N #500, Seattle, WA, 98109, USA.
Sumana ChakravartySanaria, Inc., 9800 Medical Center Drive, Suite A209, Rockville, MD, 20850, USA.
B Kim Lee SimSanaria, Inc., 9800 Medical Center Drive, Suite A209, Rockville, MD, 20850, USA.
Stefan H I KappeCenter for Infectious Disease Research, 307 Westlake Ave N #500, Seattle, WA, 98109, USA.
Stephen L HoffmanSanaria, Inc., 9800 Medical Center Drive, Suite A209, Rockville, MD, 20850, USA.
Robert A SederVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 40, Room 3512, 40 Convent Drive, Bethesda, MD, 20814, USA.
University of Washington · USSanaria · USCenter for Infectious Disease Research · USNational Institutes of Health · US

Funding

WOMEN'S HEALTH AGENDAU01AI038858 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI BENSON, CONSTANCE ANN · 1996 to 2008
$157.5M
University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI EDWIN ROBERTO ORELLANA · 1988 to 2026
$104.9M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007171 · NIGMS · DUKE UNIVERSITY · PI KONTOS, CHRISTOPHER D · 1985 to 2021
$31.2M
Plasmodium Falciparum Whole Sporozoite Malaria VaccineR44AI055229 · NIAID · SANARIA, INC. · PI HOFFMAN, STEPHEN LEV · 2005 to 2015
$10.0M
IMPROVING MANUFACTURING AND POTENCY OF CRYOPRESERVED MALARIA SPOROZOITE VACCINER44AI058499 · NIAID · SANARIA, INC. · PI HOFFMAN, STEPHEN LEV · 2008 to 2014
$6.0M
Bill & Melinda Gates Foundation OPP1133622NIAID NIH HHS P30 AI027757NIAID NIH HHS R44 AI055229NIAID NIH HHS R44 AI058499NIAID NIH HHS U01 AI038858NIGMS NIH HHS T32 GM007171
6 · The paper itself

Abstract

backgroundPlasmodium 18S rRNA is a biomarker used to monitor blood-stage infections in malaria clinical trials. Plasmodium sporozoites also express this biomarker, and there is conflicting evidence about how long sporozoite-derived 18S rRNA persists in peripheral blood. If present in blood for an extended timeframe, sporozoite-derived 18S rRNA could complicate use as a blood-stage biomarker.

methodsBlood samples from Plasmodium yoelii infected mice were tested for Plasmodium 18S rRNA and their coding genes (rDNA) using sensitive quantitative reverse transcription PCR and quantitative PCR assays, respectively. Blood and tissues from Plasmodium falciparum sporozoite (PfSPZ)-infected rhesus macaques were similarly tested.

resultsIn mice, when P. yoelii sporozoite inoculation and blood collection were performed at the same site (tail vein), low level rDNA positivity persisted for 2 days post-infection. Compared to intact parasites with high rRNA-to-rDNA ratios, this low level positivity was accompanied by no increase in rRNA-to-rDNA, indicating detection of residual, non-viable parasite rDNA. When P. yoelii sporozoites were administered via the retro-orbital vein and blood sampled by cardiac puncture, neither P. yoelii 18S rRNA nor rDNA were detected 24 h post-infection. Similarly, there was no P. falciparum 18S rRNA detected in blood of rhesus macaques 3 days after intravenous injection with extremely high doses of PfSPZ. Plasmodium 18S rRNA in the rhesus livers increased by approximately 101-fold from 3 to 6 days post infection, indicating liver-stage proliferation.

conclusionsBeyond the first few hours after injection, sporozoite-derived Plasmodium 18S rRNA was not detected in peripheral blood. Diagnostics based on 18S rRNA are unlikely to be confounded by sporozoite inocula in human clinical trials.

Indexed as

Administration, IntravenousAnimalsFemaleMacaca mulattaMiceMice, Inbred BALB CPlasmodium yoeliiRNA, ProtozoanRNA, Ribosomal, 18SSporozoitesRNA, ProtozoanRNA, Ribosomal, 18S18S rRNAMolecular diagnosticPlasmodiumSmall subunit rRNASSU

Identifiers

PMID30053881
PMCPMC6062992
OpenAlexW2883574069

What OpenQuestion holds

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LicenceCC BY
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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.