Limitations of microscopy to differentiate Plasmodium species in a region co-endemic for Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi

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

    Research output: Contribution to journalArticleResearchpeer-review

    3 Downloads (Pure)

    Abstract

    Background: In areas co-endemic for multiple Plasmodium species, correct diagnosis is crucial for appropriate treatment and surveillance. Species misidentification by microscopy has been reported in areas co-endemic for vivax and falciparum malaria, and may be more frequent in regions where Plasmodium knowlesi also commonly occurs.

    Methods: This prospective study in Sabah, Malaysia, evaluated the accuracy of routine district and referral hospital-based microscopy, and microscopy performed by an experienced research microscopist, for the diagnosis of PCR-confirmed Plasmodium falciparum, P. knowlesi, and Plasmodium vivax malaria.

    Results: A total of 304 patients with PCR-confirmed Plasmodium infection were enrolled, including 130 with P. knowlesi, 122 with P. falciparum, 43 with P. vivax, one with Plasmodium malariae and eight with mixed species infections. Among patients with P. knowlesi mono-infection, routine and cross-check microscopy both identified 94 (72%) patients as "P. malariae/P. knowlesi"; 17 (13%) and 28 (22%) respectively were identified as P. falciparum, and 13 (10%) and two (1.5%) as P. vivax. Among patients with PCR-confirmed P. falciparum, routine and cross-check microscopy identified 110/122 (90%) and 112/118 (95%) patients respectively as P. falciparum, and 8/122 (6.6%) and 5/118 (4.2%) as "P. malariae/P. knowlesi". Among those with P. vivax, 23/43 (53%) and 34/40 (85%) were correctly diagnosed by routine and cross-check microscopy respectively, while 13/43 (30%) and 3/40 (7.5%) patients were diagnosed as "P. malariae/P. knowlesi". Four of 13 patients with PCR-confirmed P. vivax and misdiagnosed by routine microscopy as "P. malariae/P. knowlesi" were subsequently re-admitted with P. vivax malaria.

    Conclusions:
    Microscopy does not reliably distinguish between P. falciparum, P. vivax and P. knowlesi in a region where all three species frequently occur. Misdiagnosis of P. knowlesi as both P. vivax and P. falciparum, and vice versa, is common, potentially leading to inappropriate treatment, including chloroquine therapy for P. falciparum and a lack of anti-relapse therapy for P. vivax. The limitations of microscopy in P. knowlesi-endemic areas supports the use of unified blood-stage treatment strategies for all Plasmodium species, the development of accurate rapid diagnostic tests suitable for all species, and the use of PCR-confirmation for accurate surveillance.

    Original languageEnglish
    Pages (from-to)1-6
    Number of pages6
    JournalMalaria Journal
    Volume12
    Issue number8
    DOIs
    Publication statusPublished - 2013

    Fingerprint

    Plasmodium knowlesi
    Plasmodium vivax
    Plasmodium
    Plasmodium falciparum
    Microscopy
    Plasmodium malariae
    Vivax Malaria
    Polymerase Chain Reaction
    Malaysia
    Diagnostic Errors
    Therapeutics
    District Hospitals
    Falciparum Malaria
    Chloroquine
    Cross Infection
    Coinfection
    Routine Diagnostic Tests
    Malaria

    Cite this

    @article{3fe5cc4280ad434cbf0648b6b23cfb2a,
    title = "Limitations of microscopy to differentiate Plasmodium species in a region co-endemic for Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi",
    abstract = "Background: In areas co-endemic for multiple Plasmodium species, correct diagnosis is crucial for appropriate treatment and surveillance. Species misidentification by microscopy has been reported in areas co-endemic for vivax and falciparum malaria, and may be more frequent in regions where Plasmodium knowlesi also commonly occurs. Methods: This prospective study in Sabah, Malaysia, evaluated the accuracy of routine district and referral hospital-based microscopy, and microscopy performed by an experienced research microscopist, for the diagnosis of PCR-confirmed Plasmodium falciparum, P. knowlesi, and Plasmodium vivax malaria. Results: A total of 304 patients with PCR-confirmed Plasmodium infection were enrolled, including 130 with P. knowlesi, 122 with P. falciparum, 43 with P. vivax, one with Plasmodium malariae and eight with mixed species infections. Among patients with P. knowlesi mono-infection, routine and cross-check microscopy both identified 94 (72{\%}) patients as {"}P. malariae/P. knowlesi{"}; 17 (13{\%}) and 28 (22{\%}) respectively were identified as P. falciparum, and 13 (10{\%}) and two (1.5{\%}) as P. vivax. Among patients with PCR-confirmed P. falciparum, routine and cross-check microscopy identified 110/122 (90{\%}) and 112/118 (95{\%}) patients respectively as P. falciparum, and 8/122 (6.6{\%}) and 5/118 (4.2{\%}) as {"}P. malariae/P. knowlesi{"}. Among those with P. vivax, 23/43 (53{\%}) and 34/40 (85{\%}) were correctly diagnosed by routine and cross-check microscopy respectively, while 13/43 (30{\%}) and 3/40 (7.5{\%}) patients were diagnosed as {"}P. malariae/P. knowlesi{"}. Four of 13 patients with PCR-confirmed P. vivax and misdiagnosed by routine microscopy as {"}P. malariae/P. knowlesi{"} were subsequently re-admitted with P. vivax malaria. Conclusions: Microscopy does not reliably distinguish between P. falciparum, P. vivax and P. knowlesi in a region where all three species frequently occur. Misdiagnosis of P. knowlesi as both P. vivax and P. falciparum, and vice versa, is common, potentially leading to inappropriate treatment, including chloroquine therapy for P. falciparum and a lack of anti-relapse therapy for P. vivax. The limitations of microscopy in P. knowlesi-endemic areas supports the use of unified blood-stage treatment strategies for all Plasmodium species, the development of accurate rapid diagnostic tests suitable for all species, and the use of PCR-confirmation for accurate surveillance.",
    keywords = "adolescent, article, child, diagnostic accuracy, endemic disease, human, major clinical study, malaria falciparum, Malaysia, microscopy, Plasmodium, Plasmodium knowlesi malaria, Plasmodium vivax malaria, prospective study, school child, Adolescent, Adult, Aged, Aged, 80 and over, Child, Diagnosis, Differential, Diagnostic Errors, Endemic Diseases, Female, Humans, Malaria, Male, Microscopy, Middle Aged, Parasitology, Plasmodium falciparum, Plasmodium knowlesi, Plasmodium vivax, Polymerase Chain Reaction, Prospective Studies, Young Adult",
    author = "Bridget Barber and Timothy William and Matthew Grigg and Tsin Yeo and Nicholas Anstey",
    year = "2013",
    doi = "10.1186/1475-2875-12-8",
    language = "English",
    volume = "12",
    pages = "1--6",
    journal = "Malaria Journal",
    issn = "1475-2875",
    publisher = "BioMed Central",
    number = "8",

    }

    Limitations of microscopy to differentiate Plasmodium species in a region co-endemic for Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi. / Barber, Bridget; William, Timothy; Grigg, Matthew; Yeo, Tsin; Anstey, Nicholas.

    In: Malaria Journal, Vol. 12, No. 8, 2013, p. 1-6.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Limitations of microscopy to differentiate Plasmodium species in a region co-endemic for Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi

    AU - Barber, Bridget

    AU - William, Timothy

    AU - Grigg, Matthew

    AU - Yeo, Tsin

    AU - Anstey, Nicholas

    PY - 2013

    Y1 - 2013

    N2 - Background: In areas co-endemic for multiple Plasmodium species, correct diagnosis is crucial for appropriate treatment and surveillance. Species misidentification by microscopy has been reported in areas co-endemic for vivax and falciparum malaria, and may be more frequent in regions where Plasmodium knowlesi also commonly occurs. Methods: This prospective study in Sabah, Malaysia, evaluated the accuracy of routine district and referral hospital-based microscopy, and microscopy performed by an experienced research microscopist, for the diagnosis of PCR-confirmed Plasmodium falciparum, P. knowlesi, and Plasmodium vivax malaria. Results: A total of 304 patients with PCR-confirmed Plasmodium infection were enrolled, including 130 with P. knowlesi, 122 with P. falciparum, 43 with P. vivax, one with Plasmodium malariae and eight with mixed species infections. Among patients with P. knowlesi mono-infection, routine and cross-check microscopy both identified 94 (72%) patients as "P. malariae/P. knowlesi"; 17 (13%) and 28 (22%) respectively were identified as P. falciparum, and 13 (10%) and two (1.5%) as P. vivax. Among patients with PCR-confirmed P. falciparum, routine and cross-check microscopy identified 110/122 (90%) and 112/118 (95%) patients respectively as P. falciparum, and 8/122 (6.6%) and 5/118 (4.2%) as "P. malariae/P. knowlesi". Among those with P. vivax, 23/43 (53%) and 34/40 (85%) were correctly diagnosed by routine and cross-check microscopy respectively, while 13/43 (30%) and 3/40 (7.5%) patients were diagnosed as "P. malariae/P. knowlesi". Four of 13 patients with PCR-confirmed P. vivax and misdiagnosed by routine microscopy as "P. malariae/P. knowlesi" were subsequently re-admitted with P. vivax malaria. Conclusions: Microscopy does not reliably distinguish between P. falciparum, P. vivax and P. knowlesi in a region where all three species frequently occur. Misdiagnosis of P. knowlesi as both P. vivax and P. falciparum, and vice versa, is common, potentially leading to inappropriate treatment, including chloroquine therapy for P. falciparum and a lack of anti-relapse therapy for P. vivax. The limitations of microscopy in P. knowlesi-endemic areas supports the use of unified blood-stage treatment strategies for all Plasmodium species, the development of accurate rapid diagnostic tests suitable for all species, and the use of PCR-confirmation for accurate surveillance.

    AB - Background: In areas co-endemic for multiple Plasmodium species, correct diagnosis is crucial for appropriate treatment and surveillance. Species misidentification by microscopy has been reported in areas co-endemic for vivax and falciparum malaria, and may be more frequent in regions where Plasmodium knowlesi also commonly occurs. Methods: This prospective study in Sabah, Malaysia, evaluated the accuracy of routine district and referral hospital-based microscopy, and microscopy performed by an experienced research microscopist, for the diagnosis of PCR-confirmed Plasmodium falciparum, P. knowlesi, and Plasmodium vivax malaria. Results: A total of 304 patients with PCR-confirmed Plasmodium infection were enrolled, including 130 with P. knowlesi, 122 with P. falciparum, 43 with P. vivax, one with Plasmodium malariae and eight with mixed species infections. Among patients with P. knowlesi mono-infection, routine and cross-check microscopy both identified 94 (72%) patients as "P. malariae/P. knowlesi"; 17 (13%) and 28 (22%) respectively were identified as P. falciparum, and 13 (10%) and two (1.5%) as P. vivax. Among patients with PCR-confirmed P. falciparum, routine and cross-check microscopy identified 110/122 (90%) and 112/118 (95%) patients respectively as P. falciparum, and 8/122 (6.6%) and 5/118 (4.2%) as "P. malariae/P. knowlesi". Among those with P. vivax, 23/43 (53%) and 34/40 (85%) were correctly diagnosed by routine and cross-check microscopy respectively, while 13/43 (30%) and 3/40 (7.5%) patients were diagnosed as "P. malariae/P. knowlesi". Four of 13 patients with PCR-confirmed P. vivax and misdiagnosed by routine microscopy as "P. malariae/P. knowlesi" were subsequently re-admitted with P. vivax malaria. Conclusions: Microscopy does not reliably distinguish between P. falciparum, P. vivax and P. knowlesi in a region where all three species frequently occur. Misdiagnosis of P. knowlesi as both P. vivax and P. falciparum, and vice versa, is common, potentially leading to inappropriate treatment, including chloroquine therapy for P. falciparum and a lack of anti-relapse therapy for P. vivax. The limitations of microscopy in P. knowlesi-endemic areas supports the use of unified blood-stage treatment strategies for all Plasmodium species, the development of accurate rapid diagnostic tests suitable for all species, and the use of PCR-confirmation for accurate surveillance.

    KW - adolescent

    KW - article

    KW - child

    KW - diagnostic accuracy

    KW - endemic disease

    KW - human

    KW - major clinical study

    KW - malaria falciparum

    KW - Malaysia

    KW - microscopy

    KW - Plasmodium

    KW - Plasmodium knowlesi malaria

    KW - Plasmodium vivax malaria

    KW - prospective study

    KW - school child

    KW - Adolescent

    KW - Adult

    KW - Aged

    KW - Aged, 80 and over

    KW - Child

    KW - Diagnosis, Differential

    KW - Diagnostic Errors

    KW - Endemic Diseases

    KW - Female

    KW - Humans

    KW - Malaria

    KW - Male

    KW - Microscopy

    KW - Middle Aged

    KW - Parasitology

    KW - Plasmodium falciparum

    KW - Plasmodium knowlesi

    KW - Plasmodium vivax

    KW - Polymerase Chain Reaction

    KW - Prospective Studies

    KW - Young Adult

    UR - http://www.scopus.com/inward/record.url?scp=84871956766&partnerID=8YFLogxK

    U2 - 10.1186/1475-2875-12-8

    DO - 10.1186/1475-2875-12-8

    M3 - Article

    VL - 12

    SP - 1

    EP - 6

    JO - Malaria Journal

    JF - Malaria Journal

    SN - 1475-2875

    IS - 8

    ER -