Evidence map›Paper›PMID 38093306›Full record

ArticleMalaria journal2023

Plasmodium knowlesi in pig-tailed macaques: a potential new model for malaria vaccine research.

Melanie J Shears, Rebekah A Reynolds, Caroline J Duncombe, Felicia N Watson, Weston J Staubus, Chris Chavtur, Annette M Seilie, Tuan M Tran, Sumana Chakravarty, Stephen L Hoffman and 1 more

Abstract read
In one paragraph

Article in Malaria journal, 2023. 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
–field-weighted citation impact
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.

  1. Review
  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

11 authors.

Melanie J ShearsDepartment of Laboratory Medicine and Pathology, University of Washington, 750 Republican Street, F870, Seattle, WA, 98109, USA.
Rebekah A ReynoldsDepartment of Laboratory Medicine and Pathology, University of Washington, 750 Republican Street, F870, Seattle, WA, 98109, USA.
Caroline J DuncombeDepartment of Laboratory Medicine and Pathology, University of Washington, 750 Republican Street, F870, Seattle, WA, 98109, USA.
Felicia N WatsonDepartment of Laboratory Medicine and Pathology, University of Washington, 750 Republican Street, F870, Seattle, WA, 98109, USA.
Weston J StaubusDepartment of Laboratory Medicine and Pathology, University of Washington, 750 Republican Street, F870, Seattle, WA, 98109, USA.
Chris ChavturDepartment of Laboratory Medicine and Pathology, University of Washington, 750 Republican Street, F870, Seattle, WA, 98109, USA.
Annette M SeilieDepartment of Laboratory Medicine and Pathology, University of Washington, 750 Republican Street, F870, Seattle, WA, 98109, USA.
Tuan M TranDivision of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Sumana ChakravartySanaria, Inc., 9800 Medical Center Drive, Suite A209, Rockville, MD, 20850, USA.
Stephen L HoffmanSanaria, Inc., 9800 Medical Center Drive, Suite A209, Rockville, MD, 20850, USA.
Sean C MurphyDepartment of Laboratory Medicine and Pathology, University of Washington, 750 Republican Street, F870, Seattle, WA, 98109, USA. murphysc@uw.edu.

Funding

Washington National Primate Research CenterP51OD010425 · OD · UNIVERSITY OF WASHINGTON · PI Mari Ostendorf · 2012 to 2026
$201.8M
NIH HHS P51 OD010425
6 · The paper itself

Abstract

backgroundPlasmodium knowlesi is an established experimental model for basic and pre-clinical malaria vaccine research. Historically, rhesus macaques have been the most common host for malaria vaccine studies with P. knowlesi parasites. However, rhesus are not natural hosts for P. knowlesi, and there is interest in identifying alternative hosts for vaccine research. The study team previously reported that pig-tailed macaques (PTM), a natural host for P. knowlesi, could be challenged with cryopreserved P. knowlesi sporozoites (PkSPZ), with time to blood stage infection equivalent to in rhesus. Here, additional exploratory studies were performed to evaluate PTM as potential hosts for malaria vaccine studies. The aim was to further characterize the parasitological and veterinary health outcomes after PkSPZ challenge in this macaque species.

methodsMalaria-naïve PTM were intravenously challenged with 2.5 × 10

resultsIn naïve animals, the kinetics of P. knowlesi blood stage replication was reproducible, with parasite burden rising linearly during an initial acute phase of infection from 6 to 11 days post-challenge, before plateauing and transitioning into a chronic low-grade infection. After re-challenge, infections were again reproducible, but with lower blood stage parasite densities. Clinical signs of disease were absent or mild and anti-malarial treatment was not needed until the pre-defined study day. Whole blood gene expression analysis identified immunological changes associated with acute and chronic phases of infection, and further differences between initial challenge versus re-challenge.

conclusionsThe ability to challenge PTM with PkSPZ and achieve reliable blood stage infections indicate this model has significant potential for malaria vaccine studies. Blood stage P. knowlesi infection in PTM is characterized by low parasite burdens and a benign disease course, in contrast with the virulent P. knowlesi disease course commonly reported in rhesus macaques. These findings identify new opportunities for malaria vaccine research using this natural host-parasite combination.

Indexed as

AntimalarialsMalariaMalaria VaccinesPlasmodium knowlesiAnimalsMacaca mulattaMacaca nemestrinaAntimalarialsMalaria VaccinesMacaca nemestrinaMalariaPig-tailed macaquePlasmodium knowlesiSporozoite

Identifiers

PMID38093306
PMCPMC10720125

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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.