Evidence map›Paper›PMID 34139428›Full record

ArticleEBioMedicine2021

A novel CRISPR-based malaria diagnostic capable of Plasmodium detection, species differentiation, and drug-resistance genotyping.

Clark H Cunningham, Christopher M Hennelly, Jessica T Lin, Ratawan Ubalee, Ross M Boyce, Edgar M Mulogo, Nicholas Hathaway, Kyaw L Thwai, Fernandine Phanzu, Albert Kalonji and 4 more

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 1 pooled it
6.2field-weighted citation impact, top 2% 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

48 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.

  1. Pooled it
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  8. Next-generation molecular tools in veterinary parasitology: advances, challenges, and perspectives in the diagnosis of emerging parasites.Revista brasileira de parasitologia veterinaria = Brazilian journal of veterinary parasitology : Orgao Oficial do Colegio Brasileiro de Parasitologia Veterinaria · 2026
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  14. Article
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  16. Applications of CRISPR in Parasitology.Current pharmaceutical biotechnology · 2025
    Review
  17. Article
  18. Advancements in AI-driven drug sensitivity testing research.Frontiers in cellular and infection microbiology · 2025
    Review
  19. Article
  20. 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

14 authors at 5 institutions in 4 countries.

Clark H CunninghamUniversity of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Christopher M HennellyUniversity of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Jessica T LinUniversity of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Ratawan UbaleeArmed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
Ross M BoyceUniversity of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Mbarara University of Science and Technology, Mbarara, Uganda.
Edgar M MulogoMbarara University of Science and Technology, Mbarara, Uganda.
Nicholas HathawayUniversity of Massachusetts School of Medicine, Worcester, MA, United States.
Kyaw L ThwaiUniversity of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Fernandine PhanzuSANRU ASBL (Global Fund), Kinshasa, Democratic Republic of the Congo.
Albert KalonjiSANRU ASBL (Global Fund), Kinshasa, Democratic Republic of the Congo.
Kashamuka MwandagalirwaKinshasa School of Public Health, Kinshasa, Democratic Republic of the Congo.
Antoinette TshefuKinshasa School of Public Health, Kinshasa, Democratic Republic of the Congo.
Jonathan J JulianoUniversity of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Jonathan B ParrUniversity of North Carolina at Chapel Hill, Chapel Hill, NC, United States. Electronic address: jonathan_parr@med.unc.edu.
University of North Carolina at Chapel Hill · USMbarara University of Science and Technology · UGMinistry of Public Health · CDArmed Forces Research Institute of Medical Science · THUniversity of Massachusetts Chan Medical School · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI David Darr · 1985 to 2026
$201.5M
Re-Entry Supplement: Investigation of Oral Microbial Enzymes for the Detection and Treatment of Periodontal DiseaseUL1TR002489 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BUSE, JOHN BERNARD, SHAHEEN, NICHOLAS J · 2018 to 2022
$48.6M
NRSA IN GENETICST32GM007092 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SEKELSKY, JEFF J. · 1985 to 2019
$5.9M
Variation in Resistance and Fitness to Artemisinins in African MalariaR01AI121558 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JULIANO, JONATHAN J · 2016 to 2020
$3.3M
Determinants of malaria transmission by submicroscopic gametocytemiaR01AI137395 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LIN, JESSICA · 2018 to 2022
$3.3M
Mentoring in Translational Malaria GenomicsK24AI134990 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Jonathan J Juliano · 2018 to 2026
$1.6M
Development of novel diagnostics for African non-falciparum malariaR21AI148579 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LIN, JESSICA, PARR, JONATHAN BOYD · 2020 to 2021
$420k
Plasmodium ovale hypnozoite development and relapse: a coordinated in vivo in vitro studyR21AI152260 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ADAMS, JOHN H, LIN, JESSICA · 2021 to 2022
$418k
NCATS NIH HHS UL1 TR002489NCI NIH HHS P30 CA016086NIAID NIH HHS K24 AI134990NIAID NIH HHS R01 AI121558NIAID NIH HHS R01 AI137395NIAID NIH HHS R21 AI148579NIAID NIH HHS R21 AI152260NIGMS NIH HHS T32 GM007092
6 · The paper itself

Abstract

backgroundCRISPR-based diagnostics are a new class of highly sensitive and specific assays with multiple applications in infectious disease diagnosis. SHERLOCK, or Specific High-Sensitivity Enzymatic Reporter UnLOCKing, is one such CRISPR-based diagnostic that combines recombinase polymerase pre-amplification, CRISPR-RNA base-pairing, and LwCas13a activity for nucleic acid detection.

methodsWe developed SHERLOCK assays capable of detecting all Plasmodium species known to cause human malaria and species-specific detection of P. vivax and P. falciparum, the species responsible for the majority of malaria cases worldwide. We further tested these assays using a diverse panel of clinical samples from the Democratic Republic of the Congo, Uganda, and Thailand and pools of Anopheles mosquitoes from Thailand. In addition, we developed a prototype SHERLOCK assay capable of detecting the dihydropteroate synthetase (dhps) single nucleotide variant A581G associated with P. falciparum sulfadoxine resistance.

findingsThe suite of Plasmodium assays achieved analytical sensitivities ranging from 2•5-18•8 parasites per reaction when tested against laboratory strain genomic DNA. When compared to real-time PCR, the P. falciparum assay achieved 94% sensitivity and 94% specificity during testing of 123 clinical samples. Compared to amplicon-based deep sequencing, the dhps SHERLOCK assay achieved 73% sensitivity and 100% specificity when applied to a panel of 43 clinical samples, with false-negative calls only at lower parasite densities.

interpretationThese novel SHERLOCK assays demonstrate the versatility of CRISPR-based diagnostics and their potential as a new generation of molecular tools for malaria diagnosis and surveillance.

fundingNational Institutes of Health (T32GM007092, R21AI148579, K24AI134990, R01AI121558, UL1TR002489, P30CA016086).

Indexed as

Drug ResistanceBase PairingClustered Regularly Interspaced Short Palindromic RepeatsCongoDemocratic Republic of the CongoDiagnostic Tests, RoutineDihydropteroate SynthaseDNA, ProtozoanEarly DiagnosisGenotyping TechniquesHumansMalariaPlasmodiumPolymorphism, Single NucleotidePopulation SurveillanceProof of Concept StudyDihydropteroate SynthaseDNA, ProtozoanSulfadoxineCas13aCRISPRDiagnosticMalariaSHERLOCK

Identifiers

PMID34139428
PMCPMC8213918
OpenAlexW3168409055

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.