Evidence map›Paper›PMID 35659882›Full record

ArticleThe Lancet. Microbe2022

CRISPR detection of circulating cell-free Mycobacterium tuberculosis DNA in adults and children, including children with HIV: a molecular diagnostics study.

Zhen Huang, Sylvia M LaCourse, Alexander W Kay, Joshua Stern, Jaclyn N Escudero, Brady M Youngquist, Wenshu Zheng, Debrah Vambe, Muyalo Dlamini, Godwin Mtetwa and 11 more

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

Article in The Lancet. Microbe, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 2 pooled it
14.6field-weighted citation impact, top 1% 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

61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 103 citations in OpenAlex.

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  20. PlasmaInfectious diseases (London, England) · 2025
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1 more citing papers are in PubMed but not listed here.

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

21 authors at 7 institutions in 5 countries.

Zhen HuangCenter for Cellular and Molecular Diagnostics, Tulane University School of Medicine, New Orleans, LA, USA; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA, USA; State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, China.
Sylvia M LaCourseDepartment of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA.
Alexander W KayGlobal TB Program, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; Baylor Children's Foundation-Eswatini, Mbabane, Eswatini.
Joshua SternDepartment of Global Health, University of Washington, Seattle, WA, USA.
Jaclyn N EscuderoDepartment of Global Health, University of Washington, Seattle, WA, USA.
Brady M YoungquistCenter for Cellular and Molecular Diagnostics, Tulane University School of Medicine, New Orleans, LA, USA; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA, USA.
Wenshu ZhengCenter for Cellular and Molecular Diagnostics, Tulane University School of Medicine, New Orleans, LA, USA; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA, USA.
Debrah VambeEswatini National Tuberculosis Control Programme, Ministry of Health, Manzini, Eswatini.
Muyalo DlaminiNational TB Reference Laboratory, Eswatini Health Laboratory Services, Ministry of Health, Mbabane, Eswatini.
Godwin MtetwaGlobal TB Program, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; Baylor Children's Foundation-Eswatini, Mbabane, Eswatini.
Lisa M CranmerDepartment of Pediatrics, Division of Infectious Diseases, Emory University, Atlanta, GA, USA; Children's Healthcare of Atlanta, Atlanta, GA, USA; Department of Epidemiology, Emory Rollins School of Public Health, Atlanta, GA, USA.
Irene NjugunaDepartment of Global Health, University of Washington, Seattle, WA, USA; Research and Programmes, Kenyatta National Hospital, Nairobi, Kenya.
Dalton C WamalwaCenter for Cellular and Molecular Diagnostics, Tulane University School of Medicine, New Orleans, LA, USA; Department of Paediatrics and Child Health, University of Nairobi, Nairobi, Kenya.
Elizabeth Maleche-ObimboDepartment of Global Health, University of Washington, Seattle, WA, USA; Department of Paediatrics and Child Health, University of Nairobi, Nairobi, Kenya.
Donald G CatanzaroDepartment of Biological Sciences, University of Arkansas, Fayetteville, AR, USA.
Christopher J LyonCenter for Cellular and Molecular Diagnostics, Tulane University School of Medicine, New Orleans, LA, USA; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA, USA.
Grace John-StewartDepartment of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA.
Andrew DiNardoGlobal TB Program, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Anna M MandalakasGlobal TB Program, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Bo NingCenter for Cellular and Molecular Diagnostics, Tulane University School of Medicine, New Orleans, LA, USA; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA, USA.
Tony Y HuCenter for Cellular and Molecular Diagnostics, Tulane University School of Medicine, New Orleans, LA, USA; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA, USA. Electronic address: tonyhu@tulane.edu.
Tulane University · USUniversity of Washington · USBaylor College of Medicine · USMinistry of Health · SZEmory University · USUniversity of Arkansas at Fayetteville · USUniversity of Nairobi · KE

Funding

University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI EDWIN ROBERTO ORELLANA · 1988 to 2026
$104.9M
Urgent Versus Post-Stabilization ART in HIV+ Children with Severe Co-infectionsR01HD023412 · NICHD · UNIVERSITY OF WASHINGTON · PI Grace C. John-Stewart, DALTON CHEKOKO WAMALWA · 1987 to 2026
$12.2M
Direct quantitation of the circulating Mtb-peptidome for pediatric TB managementR01HD090927 · NICHD · TULANE UNIVERSITY OF LOUISIANA · PI Christopher J Lyon, Charles DeBeaux Mitchell · 2017 to 2026
$4.5M
Mtb and HIV/SIV antigen peptide signatures as blood biomarkers to detect early infection to active disease in young children and NHPR01HD103511 · NICHD · TULANE UNIVERSITY OF LOUISIANA · PI LYON, CHRISTOPHER J · 2021 to 2025
$3.7M
M. tuberculosis exosome detection for pediatric TB diagnosisR01AI162152 · NIAID · UNIVERSITY OF WASHINGTON · PI LACOURSE, SYLVIA · 2021 to 2025
$3.3M
Health-Professional Education Partnership Initiative (HEPI) - KenyaR25TW011212 · FIC · UNIVERSITY OF NAIROBI · PI NDUATI, RUTH WANJIRU, WAMALWA, DALTON CHEKOKO · 2018 to 2022
$3.2M
Digital Nanoplasmonic Quantification of Tumor-derived Extracellular Vesicles in Plasma MicrosamplesU01CA252965 · NCI · TULANE UNIVERSITY OF LOUISIANA · PI HU, TONY Y., LU, HUA · 2020 to 2024
$3.0M
A nanopore biosensor for leveling Mtb antigens in bloodR01AI144168 · NIAID · TULANE UNIVERSITY OF LOUISIANA · PI Christopher J Lyon · 2022 to 2026
$3.0M
Multiplexed detection of cell-free M. Tuberculosis DNA and its drug-resistant variants in bloodR01AI175618 · NIAID · TULANE UNIVERSITY OF LOUISIANA · PI Zhen Huang, Jeffrey Tornheim · 2023 to 2026
$2.9M
Quantification of Circulating Antigens for Pediatric TB Diagnosis andTreatment MonitoringR01AI122932 · NIAID · METHODIST HOSPITAL RESEARCH INSTITUTE · PI HU, TONY Y. · 2016 to 2019
$1.8M
Real-time Detection of Active TB in HIV Exposed Children on CustomizedNanotrapR01AI113725 · NIAID · METHODIST HOSPITAL RESEARCH INSTITUTE · PI LABAER, JOSHUA · 2015 to 2018
$1.6M
The role of antibodies in infant TB preventionK23AI143479 · NIAID · EMORY UNIVERSITY · PI CRANMER, LISA M · 2019 to 2023
$950k
FIC NIH HHS K01 TW011482FIC NIH HHS R25 TW011212NCI NIH HHS U01 CA252965NIAID NIH HHS K23 AI120793NIAID NIH HHS K23 AI141681NIAID NIH HHS K23 AI143479NIAID NIH HHS P30 AI027757NIAID NIH HHS R01 AI113725NIAID NIH HHS R01 AI122932NIAID NIH HHS R01 AI144168NIAID NIH HHS R01 AI162152NIAID NIH HHS R01 AI175618NIAID NIH HHS R21 AI143341NICHD NIH HHS R01 HD023412NICHD NIH HHS R01 HD090927NICHD NIH HHS R01 HD103511
6 · The paper itself

Abstract

backgroundTuberculosis remains a leading cause of global mortality, especially for adults and children living with HIV (CLHIV) underdiagnosed by sputum-based assays. Non-sputum-based assays are needed to improve tuberculosis diagnosis and tuberculosis treatment monitoring. Our aim in this study was to determine whether ultrasensitive detection of Mycobacterium tuberculosis cell-free DNA (Mtb-cfDNA) in blood can diagnose tuberculosis and evaluate tuberculosis treatment responses.

methodsIn this molecular diagnostics study we analysed archived serum from two patient populations evaluated for tuberculosis in Eswatini and Kenya to detect Mtb-cfDNA, analysing serum from all individuals who had both sufficient serum volumes and clear diagnostic results. An optimised CRISPR-mediated tuberculosis (CRISPR-TB) assay was used to detect Mtb-cfDNA in serum at enrolment from adults and children with presumptive tuberculosis and their asymptomatic household contacts, and at enrolment and during tuberculosis treatment from a cohort of symptomatic CLHIV at high risk for tuberculosis, who provided longitudinal serum at enrolment and during tuberculosis treatment.

findingsCRISPR-TB identified microbiologically and clinically confirmed tuberculosis cases in the predominantly HIV-negative Eswatini adult cohort with 96% sensitivity (27 [96%] of 28, 95% CI 80-100) and 94% specificity (16 [94%] of 17, 71-100), and with 83% sensitivity (5 [83%] of 6, 36-100) and 95% specificity (21 [95%] of 22, 77-100) in the paediatric cohort, including all six cases of extrapulmonary tuberculosis. In the Kenyan CLHIV cohort, CRISPR-TB detected all (13 [100%] of 13, 75-100) confirmed tuberculosis cases and 85% (39 [85%] of 46, 71-94) of unconfirmed tuberculosis cases diagnosed by non-microbiological clinical findings. CLHIV who were CRISPR-TB positive at enrolment had a 2·4-times higher risk of mortality by 6 months after enrolment. Mtb-cfDNA signal decreased after tuberculosis treatment initiation, with near or complete Mtb-cfDNA clearance by 6 months after tuberculosis treatment initiation.

interpretationCRISPR-mediated detection of circulating Mtb-cfDNA shows promise to increase the identification of paediatric tuberculosis and HIV-associated tuberculosis, and potential for early diagnosis and rapid monitoring of tuberculosis treatment responses.

fundingUS Department of Defense, National Institute of Child Health and Human Development, National Institute of Allergy and Infectious Diseases, University of Washington Center for AIDS Research, and the Weatherhead Presidential Endowment fund.

Indexed as

Cell-Free Nucleic AcidsHIV InfectionsMycobacterium tuberculosisTuberculosis, Lymph NodeAdultChildClustered Regularly Interspaced Short Palindromic RepeatsHumansKenyaPathology, MolecularSensitivity and SpecificityUnited StatesCell-Free Nucleic Acids

Identifiers

PMID35659882
PMCPMC9300929
OpenAlexW4281757796

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.