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

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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

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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",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "3",

}

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

KW - human

KW - hypotension

KW - jaundice

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

KW - Artemisinins

KW - Female

KW - Humans

KW - Malaria

KW - Malaria, Falciparum

KW - Malaria, Vivax

KW - Male

KW - Middle Aged

KW - Parasitemia

KW - Plasmodium falciparum

KW - Plasmodium knowlesi

KW - Plasmodium vivax

KW - Prospective Studies

KW - Risk Factors

KW - Severity of Illness Index

KW - Time Factors

KW - Treatment Outcome

KW - Young Adult

UR - http://www.scopus.com/inward/record.url?scp=84872341743&partnerID=8YFLogxK

U2 - 10.1093/cid/cis902

DO - 10.1093/cid/cis902

M3 - Article

VL - 56

SP - 383

EP - 397

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 3

ER -