Diagnostic Performance of Conventional and Ultrasensitive Rapid Diagnostic Tests for Malaria in Febrile Outpatients in Tanzania.
Adolescent
Adult
Aged
Aged, 80 and over
Antigens, Protozoan
/ blood
Biomarkers
/ blood
Child, Preschool
Cross-Sectional Studies
False Negative Reactions
False Positive Reactions
Fever
/ blood
Humans
Infant
Limit of Detection
Malaria, Falciparum
/ blood
Middle Aged
Parasitemia
/ blood
Protozoan Proteins
/ blood
Reagent Kits, Diagnostic
Retrospective Studies
Sensitivity and Specificity
Tanzania
Time Factors
Young Adult
HRP2
Malaria
PCR
RDT
Tanzania
diagnosis
fever
quantitative
ultrasensitive
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:
16 04 2019
16 04 2019
Historique:
received:
05
10
2018
accepted:
21
11
2018
pubmed:
27
11
2018
medline:
10
1
2020
entrez:
27
11
2018
Statut:
ppublish
Résumé
A novel ultrasensitive malaria rapid diagnostic test (us-RDT) has been developed for improved active Plasmodium falciparum infection detection. The usefulness of this us-RDT in clinical diagnosis and fever management has not been evaluated. Diagnostic performance of us-RDT was compared retrospectively to that of conventional RDT (co-RDT) in 3000 children and 515 adults presenting with fever to Tanzanian outpatient clinics. The parasite density was measured by an ultrasensitive qPCR (us-qPCR), and the HRP2 concentration was measured by an enzyme-linked immunosorbent assay. us-RDT identified few additional P. falciparum-positive patients as compared to co-RDT (276 vs 265 parasite-positive patients detected), with only a marginally greater sensitivity (75% vs 73%), using us-qPCR as the gold standard (357 parasite-positive patients detected). The specificity of both RDTs was >99%. Five of 11 additional patients testing positive by us-RDT had negative results by us-qPCR. The HRP2 concentration was above the limit of detection for co-RDT (>3653 pg of HRP2 per mL of blood) in almost all infections (99% [236 of 239]) with a parasite density >100 parasites per µL of blood. At parasite densities <100 parasites/µL, the HRP2 concentration was above the limits of detection of us-RDT (>793 pg/mL) and co-RDT in 29 (25%) and 24 (20%) of 118 patients, respectively. There is neither an advantage nor a risk of using us-RDT, rather than co-RDT, for clinical malaria diagnosis. In febrile patients, only a small proportion of infections are characterized by a parasite density or an HRP2 concentration in the range where use of us-RDT would confer a meaningful advantage over co-RDT.
Sections du résumé
BACKGROUND
A novel ultrasensitive malaria rapid diagnostic test (us-RDT) has been developed for improved active Plasmodium falciparum infection detection. The usefulness of this us-RDT in clinical diagnosis and fever management has not been evaluated.
METHODS
Diagnostic performance of us-RDT was compared retrospectively to that of conventional RDT (co-RDT) in 3000 children and 515 adults presenting with fever to Tanzanian outpatient clinics. The parasite density was measured by an ultrasensitive qPCR (us-qPCR), and the HRP2 concentration was measured by an enzyme-linked immunosorbent assay.
RESULTS
us-RDT identified few additional P. falciparum-positive patients as compared to co-RDT (276 vs 265 parasite-positive patients detected), with only a marginally greater sensitivity (75% vs 73%), using us-qPCR as the gold standard (357 parasite-positive patients detected). The specificity of both RDTs was >99%. Five of 11 additional patients testing positive by us-RDT had negative results by us-qPCR. The HRP2 concentration was above the limit of detection for co-RDT (>3653 pg of HRP2 per mL of blood) in almost all infections (99% [236 of 239]) with a parasite density >100 parasites per µL of blood. At parasite densities <100 parasites/µL, the HRP2 concentration was above the limits of detection of us-RDT (>793 pg/mL) and co-RDT in 29 (25%) and 24 (20%) of 118 patients, respectively.
CONCLUSION
There is neither an advantage nor a risk of using us-RDT, rather than co-RDT, for clinical malaria diagnosis. In febrile patients, only a small proportion of infections are characterized by a parasite density or an HRP2 concentration in the range where use of us-RDT would confer a meaningful advantage over co-RDT.
Identifiants
pubmed: 30476111
pii: 5205808
doi: 10.1093/infdis/jiy676
pmc: PMC6467194
doi:
Substances chimiques
Antigens, Protozoan
0
Biomarkers
0
HRP-2 antigen, Plasmodium falciparum
0
Protozoan Proteins
0
Reagent Kits, Diagnostic
0
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1490-1498Informations de copyright
© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.
Références
Malar J. 2018 Mar 17;17(1):118
pubmed: 29549888
PLoS Med. 2015 Mar 03;12(3):e1001788
pubmed: 25734259
Lancet Infect Dis. 2018 Oct;18(10):1108-1116
pubmed: 30170986
Malar J. 2017 Mar 24;16(1):128
pubmed: 28340585
Nat Rev Microbiol. 2006 Sep;4(9 Suppl):S34-8
pubmed: 17034070
Stat Med. 1994 Nov 30;13(22):2345-58
pubmed: 7855468
Clin Vaccine Immunol. 2008 Jun;15(6):1012-8
pubmed: 18367583
Malar J. 2016 Oct 4;15(1):496
pubmed: 27716244
PLoS Med. 2017 Oct 23;14(10):e1002411
pubmed: 29059253
Malar J. 2012 Sep 13;11:325
pubmed: 22974086
Malar J. 2011 Apr 29;10:107
pubmed: 21529365
Malar J. 2012 Nov 16;11:377
pubmed: 23158019
Clin Infect Dis. 2010 Sep 1;51(5):506-11
pubmed: 20642354
Trans R Soc Trop Med Hyg. 2001 Mar-Apr;95(2):179-82
pubmed: 11355555
Am J Trop Med Hyg. 2017 Oct;97(4):1159-1162
pubmed: 28722629
Am J Trop Med Hyg. 2017 Nov;97(5):1540-1550
pubmed: 28820709
PLoS One. 2018 Jun 14;13(6):e0197982
pubmed: 29902174
Malar J. 2018 Jun 8;17(1):228
pubmed: 29884184
Clin Microbiol Rev. 2009 Jan;22(1):13-36, Table of Contents
pubmed: 19136431
J Clin Microbiol. 2018 Jul 26;56(8):
pubmed: 29898998
PLoS One. 2018 Aug 2;13(8):e0201769
pubmed: 30071004
J Infect Dis. 2018 Feb 14;217(5):685-692
pubmed: 29220497
J Infect Dis. 2009 Nov 15;200(10):1509-17
pubmed: 19848588
Am J Trop Med Hyg. 1997 May;56(5):538-47
pubmed: 9180605