Evidence map›Paper›PMID 33651824›Full record

ArticlePLoS neglected tropical diseases2021

Detection of toxoplasmic encephalitis in HIV positive patients in urine with hydrogel nanoparticles.

Hannah E Steinberg, Natalie M Bowman, Andrea Diestra, Cusi Ferradas, Paul Russo, Daniel E Clark, Deanna Zhu, Ruben Magni, Edith Malaga, Monica Diaz and 8 more

Open access · goldAbstract read
In one paragraph

Article in PLoS neglected tropical diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
0.7field-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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.

  1. Pooled it
  2. Seroprevalence of IgG Antibodies AgainstPathogens (Basel, Switzerland) · 2026
    Article
  3. Characterization ofMicroorganisms · 2026
    Article
  4. Review
  5. Article
  6. Article
  7. Tropical medicine and infectious disease · 2024
    Article
  8. Review
  9. Article
  10. 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

18 authors at 8 institutions in 2 countries.

Hannah E SteinbergDepartment of Microbiology and Immunology, University of Illinois Chicago, Chicago, Illinois, United States of America.ORCID 0000-0002-3841-6154
Natalie M BowmanDivision of Infectious Disease, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.ORCID 0000-0003-4260-8009
Andrea DiestraLaboratorio de Investigación en Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, Lima, Peru.ORCID 0000-0001-9391-8555
Cusi FerradasLaboratorio de Investigación en Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, Lima, Peru.
Paul RussoCenter for Applied Proteomics and Molecular Medicine, George Mason University, Virginia, United States of America.ORCID 0000-0002-6842-7815
Daniel E ClarkVanderbilt University Medical Center, Division of Cardiovascular Medicine, Nashville, Tennessee, United States of America.ORCID 0000-0002-8054-0642
Deanna ZhuDepartment of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, United States of America.ORCID 0000-0003-1339-9375
Ruben MagniCenter for Applied Proteomics and Molecular Medicine, George Mason University, Virginia, United States of America.ORCID 0000-0001-5012-6478
Edith MalagaLaboratorio de Investigación en Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, Lima, Peru.ORCID 0000-0002-0075-6655
Monica DiazDepartment of Neurology, University of North Carolina, Chapel Hill, North Carolina, United States of America.ORCID 0000-0001-9663-5948
Viviana Pinedo-CancinoLaboratorio de Investigación de Productos Naturales Antiparasitarios de la Amazonía, Facultad de Medicina Humana, Universidad Nacional de la Amazonía Peruana, Iquitos, Peru.
Cesar Ramal AsayagUniversidad Nacional de la Amazonía Peruana, Iquitos, Peru.
Maritza CalderónLaboratorio de Investigación en Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, Lima, Peru.ORCID 0000-0001-6582-7306
Vern B CarruthersDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.ORCID 0000-0001-6859-8895
Lance A LiottaCenter for Applied Proteomics and Molecular Medicine, George Mason University, Virginia, United States of America.
Robert H GilmanDepartment of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.ORCID 0000-0002-9037-0712
Alessandra LuchiniCenter for Applied Proteomics and Molecular Medicine, George Mason University, Virginia, United States of America.ORCID 0000-0003-1599-0214
Toxoplasmosis working group in Peru and Bolivia
George Mason University · USUniversidad Peruana Cayetano Heredia · PEUniversity of North Carolina at Chapel Hill · USUniversidad Nacional de la Amazonía Peruana · PEJohns Hopkins University · USUniversity of Illinois Chicago · USUniversity of Michigan · USVanderbilt University Medical Center · US

Funding

Virology, Immunology, and Microbiology CoreP30AI050410 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2001 to 2026
$76.9M
UJMT – ORWH – Gazzetta, Issa-BoubeD43TW009340 · FIC · UNIV OF NORTH CAROLINA CHAPEL HILL · PI William Checkley, Benjamin H. Chi · 2017 to 2026
$14.8M
University of California Launching Future Leaders in Global Health Research Training ProgramD43TW009343 · FIC · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CRAIG R COHEN, Sung-Jae Lee · 2017 to 2026
$14.7M
San Diego Resource Center for advancing Alzheimer's Research in Minority Seniors (ARMS)P30AG059299 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JOHN P. ELDER, PAUL E GILBERT · 2018 to 2026
$7.4M
Fogarty Global Health Fellows Coordinating CenterR25TW009340 · FIC · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CHI, BENJAMIN H. · 2012 to 2016
$6.9M
Infectious Diseases Training program in Bolivia: South-South Training with PeruD43TW010074 · FIC · JOHNS HOPKINS UNIVERSITY · PI ROBERT H GILMAN, Jeffrey Tornheim · 2015 to 2026
$3.5M
Novel nanoparticular diagnostics for cerebral toxoplasmosis and Chagas in HIV patients living in Latin AmericaR01AI136722 · NIAID · JOHNS HOPKINS UNIVERSITY · PI GILMAN, ROBERT H · 2018 to 2022
$3.3M
The pathogenesis of T. cruzi in HIV-infected persons in BoliviaK23AI113197 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BOWMAN, NATALIE MCCARTER · 2014 to 2018
$878k
High sensitivity multiplex detection of tick borne infection peptidesR21AI138135 · NIAID · GEORGE MASON UNIVERSITY · PI LUCHINI, ALESSANDRA · 2019 to 2020
$503k
Sensitive transrenal Mycobacterium tuberculosis nucleic acid detectionR21AI154295 · NIAID · GEORGE MASON UNIVERSITY · PI LUCHINI, ALESSANDRA · 2020 to 2021
$432k
FIC NIH HHS D43 TW009340FIC NIH HHS D43 TW009343FIC NIH HHS D43 TW010074FIC NIH HHS R25 TW009340Medical Research Council MR/P019978/1Medical Research Council MR/P019978/2NIAID NIH HHS K23 AI113197NIAID NIH HHS P30 AI050410NIAID NIH HHS R01 AI136722NIAID NIH HHS R21 AI138135NIAID NIH HHS R21 AI154295NIA NIH HHS P30 AG059299
6 · The paper itself

Abstract

backgroundDiagnosis of toxoplasmic encephalitis (TE) is challenging under the best clinical circumstances. The poor clinical sensitivity of quantitative polymerase chain reaction (qPCR) for Toxoplasma in blood and CSF and the limited availability of molecular diagnostics and imaging technology leaves clinicians in resource-limited settings with few options other than empiric treatment. METHOLOGY/PRINCIPLE

findingsHere we describe proof of concept for a novel urine diagnostics for TE using Poly-N-Isopropylacrylamide nanoparticles dyed with Reactive Blue-221 to concentrate antigens, substantially increasing the limit of detection. After nanoparticle-concentration, a standard western blotting technique with a monoclonal antibody was used for antigen detection. Limit of detection was 7.8pg/ml and 31.3pg/ml of T. gondii antigens GRA1 and SAG1, respectively. To characterize this diagnostic approach, 164 hospitalized HIV-infected patients with neurological symptoms compatible with TE were tested for 1) T. gondii serology (121/147, positive samples/total samples tested), 2) qPCR in cerebrospinal fluid (11/41), 3) qPCR in blood (10/112), and 4) urinary GRA1 (30/164) and SAG1 (12/164). GRA1 appears to be superior to SAG1 for detection of TE antigens in urine. Fifty-one HIV-infected, T. gondii seropositive but asymptomatic persons all tested negative by nanoparticle western blot and blood qPCR, suggesting the test has good specificity for TE for both GRA1 and SAG1. In a subgroup of 44 patients, urine samples were assayed with mass spectrometry parallel-reaction-monitoring (PRM) for the presence of T. gondii antigens. PRM identified antigens in 8 samples, 6 of which were concordant with the urine diagnostic. CONCLUSION/SIGNIFICANCES: Our results demonstrate nanoparticle technology's potential for a noninvasive diagnostic test for TE. Moving forward, GRA1 is a promising target for antigen based diagnostics for TE.

Indexed as

HydrogelsNanoparticlesAdultAntigens, ProtozoanEncephalitisFemaleHIV InfectionsHumansMaleMiddle AgedSensitivity and SpecificityToxoplasmaToxoplasmosisAntigens, ProtozoanHydrogels

Identifiers

PMID33651824
PMCPMC7954332
OpenAlexW3134408522

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.