Evidence map›Paper›PMID 34580442›Full record

ArticleNature microbiology2021

Plasmodium falciparum is evolving to escape malaria rapid diagnostic tests in Ethiopia.

Sindew M Feleke, Emily N Reichert, Hussein Mohammed, Bokretsion G Brhane, Kalkidan Mekete, Hassen Mamo, Beyene Petros, Hiwot Solomon, Ebba Abate, Chris Hennelly and 9 more

Open access · hybridAbstract read
In one paragraph

Article in Nature microbiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed, 1 pooled it
28.4field-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

113 citing papers in PubMed, 1 synthesis or guideline pooled it, 185 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
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  11. Review
  12. Malaria control and the unexpected spread of diagnostic-resistantbioRxiv : the preprint server for biology · 2026
    Article
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  14. Article
  15. Molecular, Transcriptomic, and Proteomic Characterization ofmedRxiv : the preprint server for health sciences · 2026
    Article
  16. Low prevalence ofFrontiers in epidemiology · 2026
    Article
  17. Article
  18. Local variability inMalariaWorld journal · 2026
    Article
  19. Article
  20. Evaluation ofiScience · 2025
    Article

53 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

19 authors at 7 institutions in 3 countries.

Sindew M Feleke *Ethiopian Public Health Institute, Addis Ababa, Ethiopia. sindewm@gmail.com.ORCID http://orcid.org/0000-0002-5778-653X
Emily N Reichert *Institute for Global Health and Infectious Diseases, Department of Medicine, Division of Infectious Diseases and Department of Geography, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-4424-8908
Hussein MohammedEthiopian Public Health Institute, Addis Ababa, Ethiopia.ORCID http://orcid.org/0000-0002-5677-9522
Bokretsion G BrhaneEthiopian Public Health Institute, Addis Ababa, Ethiopia.
Kalkidan MeketeEthiopian Public Health Institute, Addis Ababa, Ethiopia.
Hassen MamoDepartment of Microbial, Cellular and Molecular Biology, College of Natural and Computational Sciences, Addis Ababa University, Addis Ababa, Ethiopia.ORCID http://orcid.org/0000-0001-9541-8976
Beyene PetrosDepartment of Microbial, Cellular and Molecular Biology, College of Natural and Computational Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
Hiwot SolomonMinistry of Health, Addis Ababa, Ethiopia.
Ebba AbateEthiopian Public Health Institute, Addis Ababa, Ethiopia.
Chris HennellyInstitute for Global Health and Infectious Diseases, Department of Medicine, Division of Infectious Diseases and Department of Geography, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Madeline DentonInstitute for Global Health and Infectious Diseases, Department of Medicine, Division of Infectious Diseases and Department of Geography, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Corinna KeelerInstitute for Global Health and Infectious Diseases, Department of Medicine, Division of Infectious Diseases and Department of Geography, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-3445-6589
Nicholas J HathawayDepartment of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Jonathan J JulianoInstitute for Global Health and Infectious Diseases, Department of Medicine, Division of Infectious Diseases and Department of Geography, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jeffrey A BaileyDepartment of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, USA.
Eric RogierDivision of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Jane CunninghamGlobal Malaria Programme, World Health Organization, Geneva, Switzerland. cunninghamj@who.int.
Ozkan AydemirDepartment of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, USA.
Jonathan B ParrInstitute for Global Health and Infectious Diseases, Department of Medicine, Division of Infectious Diseases and Department of Geography, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. jonathan_parr@med.unc.edu.ORCID http://orcid.org/0000-0002-4465-9830
University of North Carolina at Chapel Hill · USEthiopian Public Health Institute · ETAddis Ababa University · ETBrown University · USCenters for Disease Control and Prevention · USUniversity of Massachusetts Chan Medical School · USWorld Health Organization · CH

Funding

POPULATION STUDIEST32HD007168 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ELIZABETH A FRANKENBERG · 1985 to 2026
$13.8M
RDT-undetectable Malaria in the DR Congo: Epidemiology and Development of AlternativesR01AI132547 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DINGLASAN, RHOEL DAVID RAMOS, JULIANO, JONATHAN J · 2018 to 2022
$3.6M
Mentoring in Translational Malaria GenomicsK24AI134990 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Jonathan J Juliano · 2018 to 2026
$1.6M
Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund) EPHI5405NIAID NIH HHS K24 AI134990NIAID NIH HHS R01 AI132547NICHD NIH HHS T32 HD007168World Health Organization 001
6 · The paper itself

Abstract

In Africa, most rapid diagnostic tests (RDTs) for falciparum malaria recognize histidine-rich protein 2 antigen. Plasmodium falciparum parasites lacking histidine-rich protein 2 (pfhrp2) and 3 (pfhrp3) genes escape detection by these RDTs, but it is not known whether these deletions confer sufficient selective advantage to drive rapid population expansion. By studying blood samples from a cohort of 12,572 participants enroled in a prospective, cross-sectional survey along Ethiopia's borders with Eritrea, Sudan and South Sudan using RDTs, PCR, an ultrasensitive bead-based immunoassay for antigen detection and next-generation sequencing, we estimate that histidine-rich protein 2-based RDTs would miss 9.7% (95% confidence interval 8.5-11.1) of P. falciparum malaria cases owing to pfhrp2 deletion. We applied a molecular inversion probe-targeted deep sequencing approach to identify distinct subtelomeric deletion patterns and well-established pfhrp3 deletions and to uncover recent expansion of a singular pfhrp2 deletion in all regions sampled. We propose a model in which pfhrp3 deletions have arisen independently multiple times, followed by strong positive selection for pfhrp2 deletion owing to RDT-based test-and-treatment. Existing diagnostic strategies need to be urgently reconsidered in Ethiopia, and improved surveillance for pfhrp2 deletion is needed throughout the Horn of Africa.

Indexed as

Evolution, MolecularAdolescentAdultAntigens, ProtozoanChildCross-Sectional StudiesDiagnostic Tests, RoutineEthiopiaFemaleGene DeletionGenotypeGeographyHumansMalaria, FalciparumMalePlasmodium falciparumAntigens, ProtozoanHRP-2 antigen, Plasmodium falciparumHRP3 protein, Plasmodium falciparumProtozoan Proteins

Identifiers

PMID34580442
PMCPMC8478644
OpenAlexW3203392215

What OpenQuestion holds

Textmetadata
LicenceTDM
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.