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

    Fingerprint

    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.",
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    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",
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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.

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    KW - fructose bisphosphate aldolase

    KW - histidine

    KW - histidine rich protein 2

    KW - lactate dehydrogenase

    KW - protozoal protein

    KW - unclassified drug

    KW - adolescent

    KW - adult

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    KW - diagnostic test

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    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

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    KW - Plasmodium vivax

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    KW - polymerase chain reaction

    KW - priority journal

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    KW - Adult

    KW - Aged

    KW - Aged, 80 and over

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    KW - Diagnostic Tests, Routine

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    KW - Fructose-Bisphosphate Aldolase

    KW - Humans

    KW - L-Lactate Dehydrogenase

    KW - Malaria

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    KW - Male

    KW - Middle Aged

    KW - Parasitology

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    DO - 10.1128/JCM.03285-12

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    JO - Journal of Clinical Microbiology

    JF - Journal of Clinical Microbiology

    SN - 0095-1137

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