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

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",

}

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 -