Evaluation of the Sensitivity of a pLDH-Based and an Aldolase-Based Rapid Diagnostic Test for Diagnosis of Uncomplicated and Severe Malaria Caused by PCR-Confirmed Plasmodium knowlesi, Plasmodium falciparum, and Plasmodium vivax

Bridget Barber, Timothy William, Matthew Grigg, Kim Piera, Tsin Yeo, Nicholas Anstey

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Plasmodium knowlesi can cause severe and fatal human malaria in Southeast Asia. Rapid diagnosis of all Plasmodium species is essential for initiation of effective treatment. Rapid diagnostic tests (RDTs) are sensitive for detection of uncomplicated and severe falciparum malaria but have not been systematically evaluated in knowlesi malaria. At a tertiary referral hospital in Sabah, Malaysia, we prospectively evaluated the sensitivity of two combination RDTs for the diagnosis of uncomplicated and severe malaria from all three potentially fatal Plasmodium species, using a pan-Plasmodium lactate dehydrogenase (pLDH)-P. falciparum histidine-rich protein 2 (PfHRP2) RDT (First Response) and a pan-Plasmodium aldolase-PfHRP2 RDT (ParaHIT). Among 293 hospitalized adults with PCR-confirmed Plasmodium monoinfection, the sensitivity of the pLDH component of the pLDHPfHRP2 RDT was 74% (95/129; 95% confidence interval [CI], 65 to 80%), 91% (110/121; 95% CI, 84 to 95%), and 95% (41/43; 95% CI, 85 to 99%) for PCR-confirmed P. knowlesi, P. falciparum, and P. vivax infections, respectively, and 88% (30/34; 95% CI, 73 to 95%), 90% (38/42; 95% CI, 78 to 96%), and 100% (12/12; 95% CI, 76 to 100%) among patients tested before antimalarial treatment was begun. Sensitivity in severe malaria was 95% (36/38; 95% CI, 83 to 99), 100% (13/13; 95% CI, 77 to 100), and 100% (7/7; 95% CI, 65 to 100%), respectively. The aldolase component of the aldolase-PfHRP2 RDT performed poorly in all Plasmodium species. The pLDH-based RDT was highly sensitive for the diagnosis of severe malaria from all species; however, neither the pLDH- nor aldolase-based RDT demonstrated sufficiently high overall sensitivity for P. knowlesi. More sensitive RDTs are needed in regions of P. knowlesi endemicity. � 2013, American Society for Microbiology.
Original languageEnglish
Pages (from-to)1118-1123
Number of pages6
JournalJournal of Clinical Microbiology
Volume51
Issue number4
DOIs
Publication statusPublished - 2013

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Plasmodium knowlesi
Plasmodium vivax
Fructose-Bisphosphate Aldolase
Plasmodium
Plasmodium falciparum
L-Lactate Dehydrogenase
Routine Diagnostic Tests
Malaria
Confidence Intervals
Polymerase Chain Reaction
Malaysia
Southeastern Asia
Falciparum Malaria
Antimalarials
Microbiology
Tertiary Care Centers

Cite this

@article{403bd89120054135892892eba3eac9f8,
title = "Evaluation of the Sensitivity of a pLDH-Based and an Aldolase-Based Rapid Diagnostic Test for Diagnosis of Uncomplicated and Severe Malaria Caused by PCR-Confirmed Plasmodium knowlesi, Plasmodium falciparum, and Plasmodium vivax",
abstract = "Plasmodium knowlesi can cause severe and fatal human malaria in Southeast Asia. Rapid diagnosis of all Plasmodium species is essential for initiation of effective treatment. Rapid diagnostic tests (RDTs) are sensitive for detection of uncomplicated and severe falciparum malaria but have not been systematically evaluated in knowlesi malaria. At a tertiary referral hospital in Sabah, Malaysia, we prospectively evaluated the sensitivity of two combination RDTs for the diagnosis of uncomplicated and severe malaria from all three potentially fatal Plasmodium species, using a pan-Plasmodium lactate dehydrogenase (pLDH)-P. falciparum histidine-rich protein 2 (PfHRP2) RDT (First Response) and a pan-Plasmodium aldolase-PfHRP2 RDT (ParaHIT). Among 293 hospitalized adults with PCR-confirmed Plasmodium monoinfection, the sensitivity of the pLDH component of the pLDHPfHRP2 RDT was 74{\%} (95/129; 95{\%} confidence interval [CI], 65 to 80{\%}), 91{\%} (110/121; 95{\%} CI, 84 to 95{\%}), and 95{\%} (41/43; 95{\%} CI, 85 to 99{\%}) for PCR-confirmed P. knowlesi, P. falciparum, and P. vivax infections, respectively, and 88{\%} (30/34; 95{\%} CI, 73 to 95{\%}), 90{\%} (38/42; 95{\%} CI, 78 to 96{\%}), and 100{\%} (12/12; 95{\%} CI, 76 to 100{\%}) among patients tested before antimalarial treatment was begun. Sensitivity in severe malaria was 95{\%} (36/38; 95{\%} CI, 83 to 99), 100{\%} (13/13; 95{\%} CI, 77 to 100), and 100{\%} (7/7; 95{\%} CI, 65 to 100{\%}), respectively. The aldolase component of the aldolase-PfHRP2 RDT performed poorly in all Plasmodium species. The pLDH-based RDT was highly sensitive for the diagnosis of severe malaria from all species; however, neither the pLDH- nor aldolase-based RDT demonstrated sufficiently high overall sensitivity for P. knowlesi. More sensitive RDTs are needed in regions of P. knowlesi endemicity. � 2013, American Society for Microbiology.",
keywords = "antimalarial agent, fructose bisphosphate aldolase, histidine, histidine rich protein 2, lactate dehydrogenase, protozoal protein, unclassified drug, adolescent, adult, article, controlled study, diagnostic test, disease classification, disease severity, endemic disease, female, human, major clinical study, malaria falciparum, male, outcome assessment, Plasmodium falciparum, Plasmodium knowlesi, Plasmodium knowlesi malaria, Plasmodium vivax, Plasmodium vivax malaria, polymerase chain reaction, priority journal, prospective study, rapid diagnostic test, sensitivity analysis, Adolescent, Adult, Aged, Aged, 80 and over, Antigens, Protozoan, Diagnostic Tests, Routine, Female, Fructose-Bisphosphate Aldolase, Humans, L-Lactate Dehydrogenase, Malaria, Malaysia, Male, Middle Aged, Parasitology, Protozoan Proteins, Sensitivity and Specificity, Tertiary Care Centers, Young Adult",
author = "Bridget Barber and Timothy William and Matthew Grigg and Kim Piera and Tsin Yeo and Nicholas Anstey",
year = "2013",
doi = "10.1128/JCM.03285-12",
language = "English",
volume = "51",
pages = "1118--1123",
journal = "Journal of Clinical Microbiology",
issn = "0095-1137",
publisher = "American Society for Microbiology",
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TY - JOUR

T1 - Evaluation of the Sensitivity of a pLDH-Based and an Aldolase-Based Rapid Diagnostic Test for Diagnosis of Uncomplicated and Severe Malaria Caused by PCR-Confirmed Plasmodium knowlesi, Plasmodium falciparum, and Plasmodium vivax

AU - Barber, Bridget

AU - William, Timothy

AU - Grigg, Matthew

AU - Piera, Kim

AU - Yeo, Tsin

AU - Anstey, Nicholas

PY - 2013

Y1 - 2013

N2 - Plasmodium knowlesi can cause severe and fatal human malaria in Southeast Asia. Rapid diagnosis of all Plasmodium species is essential for initiation of effective treatment. Rapid diagnostic tests (RDTs) are sensitive for detection of uncomplicated and severe falciparum malaria but have not been systematically evaluated in knowlesi malaria. At a tertiary referral hospital in Sabah, Malaysia, we prospectively evaluated the sensitivity of two combination RDTs for the diagnosis of uncomplicated and severe malaria from all three potentially fatal Plasmodium species, using a pan-Plasmodium lactate dehydrogenase (pLDH)-P. falciparum histidine-rich protein 2 (PfHRP2) RDT (First Response) and a pan-Plasmodium aldolase-PfHRP2 RDT (ParaHIT). Among 293 hospitalized adults with PCR-confirmed Plasmodium monoinfection, the sensitivity of the pLDH component of the pLDHPfHRP2 RDT was 74% (95/129; 95% confidence interval [CI], 65 to 80%), 91% (110/121; 95% CI, 84 to 95%), and 95% (41/43; 95% CI, 85 to 99%) for PCR-confirmed P. knowlesi, P. falciparum, and P. vivax infections, respectively, and 88% (30/34; 95% CI, 73 to 95%), 90% (38/42; 95% CI, 78 to 96%), and 100% (12/12; 95% CI, 76 to 100%) among patients tested before antimalarial treatment was begun. Sensitivity in severe malaria was 95% (36/38; 95% CI, 83 to 99), 100% (13/13; 95% CI, 77 to 100), and 100% (7/7; 95% CI, 65 to 100%), respectively. The aldolase component of the aldolase-PfHRP2 RDT performed poorly in all Plasmodium species. The pLDH-based RDT was highly sensitive for the diagnosis of severe malaria from all species; however, neither the pLDH- nor aldolase-based RDT demonstrated sufficiently high overall sensitivity for P. knowlesi. More sensitive RDTs are needed in regions of P. knowlesi endemicity. � 2013, American Society for Microbiology.

AB - Plasmodium knowlesi can cause severe and fatal human malaria in Southeast Asia. Rapid diagnosis of all Plasmodium species is essential for initiation of effective treatment. Rapid diagnostic tests (RDTs) are sensitive for detection of uncomplicated and severe falciparum malaria but have not been systematically evaluated in knowlesi malaria. At a tertiary referral hospital in Sabah, Malaysia, we prospectively evaluated the sensitivity of two combination RDTs for the diagnosis of uncomplicated and severe malaria from all three potentially fatal Plasmodium species, using a pan-Plasmodium lactate dehydrogenase (pLDH)-P. falciparum histidine-rich protein 2 (PfHRP2) RDT (First Response) and a pan-Plasmodium aldolase-PfHRP2 RDT (ParaHIT). Among 293 hospitalized adults with PCR-confirmed Plasmodium monoinfection, the sensitivity of the pLDH component of the pLDHPfHRP2 RDT was 74% (95/129; 95% confidence interval [CI], 65 to 80%), 91% (110/121; 95% CI, 84 to 95%), and 95% (41/43; 95% CI, 85 to 99%) for PCR-confirmed P. knowlesi, P. falciparum, and P. vivax infections, respectively, and 88% (30/34; 95% CI, 73 to 95%), 90% (38/42; 95% CI, 78 to 96%), and 100% (12/12; 95% CI, 76 to 100%) among patients tested before antimalarial treatment was begun. Sensitivity in severe malaria was 95% (36/38; 95% CI, 83 to 99), 100% (13/13; 95% CI, 77 to 100), and 100% (7/7; 95% CI, 65 to 100%), respectively. The aldolase component of the aldolase-PfHRP2 RDT performed poorly in all Plasmodium species. The pLDH-based RDT was highly sensitive for the diagnosis of severe malaria from all species; however, neither the pLDH- nor aldolase-based RDT demonstrated sufficiently high overall sensitivity for P. knowlesi. More sensitive RDTs are needed in regions of P. knowlesi endemicity. � 2013, American Society for Microbiology.

KW - antimalarial agent

KW - fructose bisphosphate aldolase

KW - histidine

KW - histidine rich protein 2

KW - lactate dehydrogenase

KW - protozoal protein

KW - unclassified drug

KW - adolescent

KW - adult

KW - article

KW - controlled study

KW - diagnostic test

KW - disease classification

KW - disease severity

KW - endemic disease

KW - female

KW - human

KW - major clinical study

KW - malaria falciparum

KW - male

KW - outcome assessment

KW - Plasmodium falciparum

KW - Plasmodium knowlesi

KW - Plasmodium knowlesi malaria

KW - Plasmodium vivax

KW - Plasmodium vivax malaria

KW - polymerase chain reaction

KW - priority journal

KW - prospective study

KW - rapid diagnostic test

KW - sensitivity analysis

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antigens, Protozoan

KW - Diagnostic Tests, Routine

KW - Female

KW - Fructose-Bisphosphate Aldolase

KW - Humans

KW - L-Lactate Dehydrogenase

KW - Malaria

KW - Malaysia

KW - Male

KW - Middle Aged

KW - Parasitology

KW - Protozoan Proteins

KW - Sensitivity and Specificity

KW - Tertiary Care Centers

KW - Young Adult

UR - http://www.scopus.com/inward/record.url?scp=84875873760&partnerID=8YFLogxK

U2 - 10.1128/JCM.03285-12

DO - 10.1128/JCM.03285-12

M3 - Article

VL - 51

SP - 1118

EP - 1123

JO - Journal of Clinical Microbiology

JF - Journal of Clinical Microbiology

SN - 0095-1137

IS - 4

ER -