A Prospective Comparative Study of Knowlesi, Falciparum, and Vivax Malaria in Sabah, Malaysia

High Proportion With Severe Disease from Plasmodium Knowlesi and Plasmodium Vivax But No Mortality With Early Referral and Artesunate Therapy

Bridget Barber, Timothy William, Matthew Grigg, Jayaram Menon, Sarah Auburn, Jutta Marfurt, Nicholas Anstey, Tsin Yeo

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Background: Plasmodium knowlesi commonly causes severe malaria in Malaysian Borneo, with high case-fatality rates reported. We compared risk, spectrum, and outcome of severe disease from P. knowlesi, Plasmodium falciparum, and Plasmodium vivax and outcomes following introduction of protocols for early referral and intravenous artesunate for all severe malaria.

     

    Methods: From September 2010 to October 2011 we prospectively assessed nonpregnant patients aged ≥12 years admitted to Queen Elizabeth Hospital (QEH), Sabah, with polymerase chain reaction–confirmed Plasmodiummonoinfection. Standardized referral and prereferral intravenous artesunate were instituted at district hospitals.

     

    Results: Severe malaria occurred in 38 of 130 (29%) patients with P. knowlesi, 13 of 122 (11%) with P. falciparum, and 7 of 43 (16%) with P. vivax. The commonest severity criteria in knowlesi malaria included parasitemia >100 000/µL (n = 18), jaundice (n = 20), respiratory distress (n = 14), hypotension (n = 13), and acute kidney injury (n = 9). On multivariate analysis, P. knowlesi was associated with a 2.96-fold (95% confidence interval, 1.19–7.38-fold) greater risk of severity than P. falciparum (P = .020); only parasitemia and schizontemia >10% independently predicted knowlesi severity. Risk of severe knowlesi malaria increased 11-fold with parasitemia >20 000/µL, and 28-fold with parasitemia >100 000/µL. Nearly all (92%) knowlesi malaria patients received oral artemisinin therapy; 36 of 38 (95%) and 39 of 92 (42%) with severe and nonsevere disease, respectively, also received ≥1 dose of intravenous artesunate. No deaths occurred from any species.

     

    Conclusions: Plasmodium knowlesi is the commonest cause of severe malaria at QEH, with parasitemia the major risk factor for severity. Early referral and treatment with artesunate was highly effective for severe malaria from all species and associated with zero mortality.

    Original languageEnglish
    Pages (from-to)383-397
    Number of pages15
    JournalClinical Infectious Diseases
    Volume56
    Issue number3
    DOIs
    Publication statusPublished - 2013

    Fingerprint

    Plasmodium knowlesi
    Vivax Malaria
    Plasmodium vivax
    Falciparum Malaria
    Malaysia
    Malaria
    Referral and Consultation
    Prospective Studies
    Parasitemia
    Mortality
    Plasmodium
    Therapeutics
    Borneo
    District Hospitals
    artesunate
    Plasmodium falciparum
    Jaundice
    Acute Kidney Injury
    Hypotension
    Multivariate Analysis

    Cite this

    @article{ec916ceba28d40d78dffc4362548744b,
    title = "A Prospective Comparative Study of Knowlesi, Falciparum, and Vivax Malaria in Sabah, Malaysia: High Proportion With Severe Disease from Plasmodium Knowlesi and Plasmodium Vivax But No Mortality With Early Referral and Artesunate Therapy",
    abstract = "Background: Plasmodium knowlesi commonly causes severe malaria in Malaysian Borneo, with high case-fatality rates reported. We compared risk, spectrum, and outcome of severe disease from P. knowlesi, Plasmodium falciparum, and Plasmodium vivax and outcomes following introduction of protocols for early referral and intravenous artesunate for all severe malaria.   Methods: From September 2010 to October 2011 we prospectively assessed nonpregnant patients aged ≥12 years admitted to Queen Elizabeth Hospital (QEH), Sabah, with polymerase chain reaction–confirmed Plasmodiummonoinfection. Standardized referral and prereferral intravenous artesunate were instituted at district hospitals.   Results: Severe malaria occurred in 38 of 130 (29{\%}) patients with P. knowlesi, 13 of 122 (11{\%}) with P. falciparum, and 7 of 43 (16{\%}) with P. vivax. The commonest severity criteria in knowlesi malaria included parasitemia >100 000/µL (n = 18), jaundice (n = 20), respiratory distress (n = 14), hypotension (n = 13), and acute kidney injury (n = 9). On multivariate analysis, P. knowlesi was associated with a 2.96-fold (95{\%} confidence interval, 1.19–7.38-fold) greater risk of severity than P. falciparum (P = .020); only parasitemia and schizontemia >10{\%} independently predicted knowlesi severity. Risk of severe knowlesi malaria increased 11-fold with parasitemia >20 000/µL, and 28-fold with parasitemia >100 000/µL. Nearly all (92{\%}) knowlesi malaria patients received oral artemisinin therapy; 36 of 38 (95{\%}) and 39 of 92 (42{\%}) with severe and nonsevere disease, respectively, also received ≥1 dose of intravenous artesunate. No deaths occurred from any species.   Conclusions: Plasmodium knowlesi is the commonest cause of severe malaria at QEH, with parasitemia the major risk factor for severity. Early referral and treatment with artesunate was highly effective for severe malaria from all species and associated with zero mortality.",
    keywords = "artemether plus benflumetol, artesunate, artesunate plus mefloquine, chloroquine, primaquine, acute kidney failure, adolescent, adult, aged, anemia, article, comparative study, disease severity, early intervention, female, human, hypotension, jaundice, major clinical study, malaria falciparum, Malaysia, male, outcome assessment, parasitemia, Plasmodium knowlesi malaria, Plasmodium vivax malaria, polymerase chain reaction, priority journal, prospective study, respiratory distress, thrombocytopenia, treatment response, Adult, Aged, Antimalarials, Artemisinins, Female, Humans, Malaria, Malaria, Falciparum, Malaria, Vivax, Male, Middle Aged, Parasitemia, Plasmodium falciparum, Plasmodium knowlesi, Plasmodium vivax, Prospective Studies, Risk Factors, Severity of Illness Index, Time Factors, Treatment Outcome, Young Adult",
    author = "Bridget Barber and Timothy William and Matthew Grigg and Jayaram Menon and Sarah Auburn and Jutta Marfurt and Nicholas Anstey and Tsin Yeo",
    year = "2013",
    doi = "10.1093/cid/cis902",
    language = "English",
    volume = "56",
    pages = "383--397",
    journal = "Clinical Infectious Diseases",
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    }

    TY - JOUR

    T1 - A Prospective Comparative Study of Knowlesi, Falciparum, and Vivax Malaria in Sabah, Malaysia

    T2 - High Proportion With Severe Disease from Plasmodium Knowlesi and Plasmodium Vivax But No Mortality With Early Referral and Artesunate Therapy

    AU - Barber, Bridget

    AU - William, Timothy

    AU - Grigg, Matthew

    AU - Menon, Jayaram

    AU - Auburn, Sarah

    AU - Marfurt, Jutta

    AU - Anstey, Nicholas

    AU - Yeo, Tsin

    PY - 2013

    Y1 - 2013

    N2 - Background: Plasmodium knowlesi commonly causes severe malaria in Malaysian Borneo, with high case-fatality rates reported. We compared risk, spectrum, and outcome of severe disease from P. knowlesi, Plasmodium falciparum, and Plasmodium vivax and outcomes following introduction of protocols for early referral and intravenous artesunate for all severe malaria.   Methods: From September 2010 to October 2011 we prospectively assessed nonpregnant patients aged ≥12 years admitted to Queen Elizabeth Hospital (QEH), Sabah, with polymerase chain reaction–confirmed Plasmodiummonoinfection. Standardized referral and prereferral intravenous artesunate were instituted at district hospitals.   Results: Severe malaria occurred in 38 of 130 (29%) patients with P. knowlesi, 13 of 122 (11%) with P. falciparum, and 7 of 43 (16%) with P. vivax. The commonest severity criteria in knowlesi malaria included parasitemia >100 000/µL (n = 18), jaundice (n = 20), respiratory distress (n = 14), hypotension (n = 13), and acute kidney injury (n = 9). On multivariate analysis, P. knowlesi was associated with a 2.96-fold (95% confidence interval, 1.19–7.38-fold) greater risk of severity than P. falciparum (P = .020); only parasitemia and schizontemia >10% independently predicted knowlesi severity. Risk of severe knowlesi malaria increased 11-fold with parasitemia >20 000/µL, and 28-fold with parasitemia >100 000/µL. Nearly all (92%) knowlesi malaria patients received oral artemisinin therapy; 36 of 38 (95%) and 39 of 92 (42%) with severe and nonsevere disease, respectively, also received ≥1 dose of intravenous artesunate. No deaths occurred from any species.   Conclusions: Plasmodium knowlesi is the commonest cause of severe malaria at QEH, with parasitemia the major risk factor for severity. Early referral and treatment with artesunate was highly effective for severe malaria from all species and associated with zero mortality.

    AB - Background: Plasmodium knowlesi commonly causes severe malaria in Malaysian Borneo, with high case-fatality rates reported. We compared risk, spectrum, and outcome of severe disease from P. knowlesi, Plasmodium falciparum, and Plasmodium vivax and outcomes following introduction of protocols for early referral and intravenous artesunate for all severe malaria.   Methods: From September 2010 to October 2011 we prospectively assessed nonpregnant patients aged ≥12 years admitted to Queen Elizabeth Hospital (QEH), Sabah, with polymerase chain reaction–confirmed Plasmodiummonoinfection. Standardized referral and prereferral intravenous artesunate were instituted at district hospitals.   Results: Severe malaria occurred in 38 of 130 (29%) patients with P. knowlesi, 13 of 122 (11%) with P. falciparum, and 7 of 43 (16%) with P. vivax. The commonest severity criteria in knowlesi malaria included parasitemia >100 000/µL (n = 18), jaundice (n = 20), respiratory distress (n = 14), hypotension (n = 13), and acute kidney injury (n = 9). On multivariate analysis, P. knowlesi was associated with a 2.96-fold (95% confidence interval, 1.19–7.38-fold) greater risk of severity than P. falciparum (P = .020); only parasitemia and schizontemia >10% independently predicted knowlesi severity. Risk of severe knowlesi malaria increased 11-fold with parasitemia >20 000/µL, and 28-fold with parasitemia >100 000/µL. Nearly all (92%) knowlesi malaria patients received oral artemisinin therapy; 36 of 38 (95%) and 39 of 92 (42%) with severe and nonsevere disease, respectively, also received ≥1 dose of intravenous artesunate. No deaths occurred from any species.   Conclusions: Plasmodium knowlesi is the commonest cause of severe malaria at QEH, with parasitemia the major risk factor for severity. Early referral and treatment with artesunate was highly effective for severe malaria from all species and associated with zero mortality.

    KW - artemether plus benflumetol

    KW - artesunate

    KW - artesunate plus mefloquine

    KW - chloroquine

    KW - primaquine

    KW - acute kidney failure

    KW - adolescent

    KW - adult

    KW - aged

    KW - anemia

    KW - article

    KW - comparative study

    KW - disease severity

    KW - early intervention

    KW - female

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    KW - major clinical study

    KW - malaria falciparum

    KW - Malaysia

    KW - male

    KW - outcome assessment

    KW - parasitemia

    KW - Plasmodium knowlesi malaria

    KW - Plasmodium vivax malaria

    KW - polymerase chain reaction

    KW - priority journal

    KW - prospective study

    KW - respiratory distress

    KW - thrombocytopenia

    KW - treatment response

    KW - Adult

    KW - Aged

    KW - Antimalarials

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    KW - Female

    KW - Humans

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    U2 - 10.1093/cid/cis902

    DO - 10.1093/cid/cis902

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