pfhrp2 and pfhrp3 Gene Deletions That Affect Malaria Rapid Diagnostic Tests for Plasmodium falciparum: Analysis of Archived Blood Samples From 3 African Countries.


Journal

The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675

Informations de publication

Date de publication:
26 09 2019
Historique:
received: 10 03 2019
accepted: 27 06 2019
pubmed: 30 6 2019
medline: 20 5 2020
entrez: 29 6 2019
Statut: ppublish

Résumé

Malaria rapid diagnostic tests (mRDTs) that target histidine-rich protein 2 (HRP2) are important tools for Plasmodium falciparum diagnosis. Parasites with pfhrp2/3 gene deletions threaten the use of these mRDTs and have been reported in Africa, Asia, and South America. We studied blood samples from 3 African countries to determine if these gene deletions were present. We analyzed 911 dried blood spots from Ghana (n = 165), Tanzania (n = 176), and Uganda (n = 570). Plasmodium falciparum infection was confirmed by 18S rDNA polymerase chain reaction (PCR), and pfhrp2/3 genes were genotyped. True pfhrp2/3 gene deletions were confirmed if samples were (1) microscopy positive; (2) 18S rDNA PCR positive; (3) positive for merozoite surface protein genes by PCR or positive by loop-mediated isothermal amplification; or (4) quantitative PCR positive with >5 parasites/µL. No pfhrp2/3 deletions were detected in samples from Ghana, but deletions were identified in Tanzania (3 pfhrp2; 2 pfhrp3) and Uganda (7 pfhrp2; 2 pfhrp3). Of the 10 samples with pfhrp2 deletions, 9 tested negative by HRP2-based mRDT. The presence of pfhrp2/3 deletions in Tanzania and Uganda, along with reports of pfhrp2/3-deleted parasites in neighboring countries, reinforces the need for systematic surveillance to monitor the reliability of mRDTs in malaria-endemic countries.

Sections du résumé

BACKGROUND
Malaria rapid diagnostic tests (mRDTs) that target histidine-rich protein 2 (HRP2) are important tools for Plasmodium falciparum diagnosis. Parasites with pfhrp2/3 gene deletions threaten the use of these mRDTs and have been reported in Africa, Asia, and South America. We studied blood samples from 3 African countries to determine if these gene deletions were present.
METHODS
We analyzed 911 dried blood spots from Ghana (n = 165), Tanzania (n = 176), and Uganda (n = 570). Plasmodium falciparum infection was confirmed by 18S rDNA polymerase chain reaction (PCR), and pfhrp2/3 genes were genotyped. True pfhrp2/3 gene deletions were confirmed if samples were (1) microscopy positive; (2) 18S rDNA PCR positive; (3) positive for merozoite surface protein genes by PCR or positive by loop-mediated isothermal amplification; or (4) quantitative PCR positive with >5 parasites/µL.
RESULTS
No pfhrp2/3 deletions were detected in samples from Ghana, but deletions were identified in Tanzania (3 pfhrp2; 2 pfhrp3) and Uganda (7 pfhrp2; 2 pfhrp3). Of the 10 samples with pfhrp2 deletions, 9 tested negative by HRP2-based mRDT.
CONCLUSIONS
The presence of pfhrp2/3 deletions in Tanzania and Uganda, along with reports of pfhrp2/3-deleted parasites in neighboring countries, reinforces the need for systematic surveillance to monitor the reliability of mRDTs in malaria-endemic countries.

Identifiants

pubmed: 31249999
pii: 5524476
doi: 10.1093/infdis/jiz335
pmc: PMC6761929
doi:

Substances chimiques

Antigens, Protozoan 0
DNA, Protozoan 0
DNA, Ribosomal 0
HRP-2 antigen, Plasmodium falciparum 0
HRP3 protein, Plasmodium falciparum 0
Protozoan Proteins 0
RNA, Ribosomal, 18S 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1444-1452

Subventions

Organisme : World Health Organization
ID : 001
Pays : International
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K00736X/1
Pays : United Kingdom

Informations de copyright

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

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Auteurs

Rebecca Thomson (R)

London School of Hygiene and Tropical Medicine, London, United Kingdom.

Khalid B Beshir (KB)

London School of Hygiene and Tropical Medicine, London, United Kingdom.

Jane Cunningham (J)

World Health Organization, Geneva, Switzerland.

Frank Baiden (F)

London School of Hygiene and Tropical Medicine, London, United Kingdom.

Jameel Bharmal (J)

London School of Hygiene and Tropical Medicine, London, United Kingdom.

Katia J Bruxvoort (KJ)

London School of Hygiene and Tropical Medicine, London, United Kingdom.
Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena.

Catherine Maiteki-Sebuguzi (C)

Infectious Disease Research Collaboration, Kampala, Uganda.

Seth Owusu-Agyei (S)

London School of Hygiene and Tropical Medicine, London, United Kingdom.
University or Health and Allied Sciences, Kintampo Health Research Centre, Ghana.

Sarah G Staedke (SG)

London School of Hygiene and Tropical Medicine, London, United Kingdom.

Heidi Hopkins (H)

London School of Hygiene and Tropical Medicine, London, United Kingdom.

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Classifications MeSH