pfhrp2 and pfhrp3 Gene Deletions That Affect Malaria Rapid Diagnostic Tests for Plasmodium falciparum: Analysis of Archived Blood Samples From 3 African Countries.
Adolescent
Adult
Aged
Aged, 80 and over
Antigens, Protozoan
/ analysis
Child
Child, Preschool
DNA, Protozoan
/ chemistry
DNA, Ribosomal
/ chemistry
Diagnostic Tests, Routine
/ methods
False Negative Reactions
Female
Gene Deletion
Genotype
Genotyping Techniques
Ghana
Humans
Immunoassay
/ methods
Infant
Infant, Newborn
Malaria, Falciparum
/ diagnosis
Male
Microscopy
Middle Aged
Plasmodium falciparum
/ genetics
Protozoan Proteins
/ analysis
RNA, Ribosomal, 18S
/ genetics
Sensitivity and Specificity
Sequence Analysis, DNA
Tanzania
Uganda
Young Adult
pfhrp2
pfhrp3
Ghana
Tanzania
Uganda
deletion
histidine
malaria
mutation
rapid diagnostic test
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
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
1444-1452Subventions
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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