Full blood count and haemozoin-containing leukocytes in children with malaria: diagnostic value and association with disease severity

Hänscheid, Thomas; Längin, Matthias; Lell, Bertrand; Pötschke, Marc; Oyakhirome, Sunny; Kremsner, Peter G.; Grobusch, Martin P.

doi:10.1186/1475-2875-7-109

Cited by 41 publications

(67 citation statements)

References 33 publications

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“…The rise in platelets over time can be interpreted as a sign of recovery from malaria and is known to cause thrombocytopenia. 31 The transitory fall in haemoglobin, mostly in the artemether-lumefantrine group, might be related to a haematological eff ect of artemisinins 32 or directly related to the pathophysiology of malaria infection. Early Chinese studies of artemether and oral dihydroartemisinin treatments 33 recorded low reticulocyte counts in 10-20% of patients during the fi rst week after treatment.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of artemether–lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial

Piola¹,

Nabasumba²,

Turyakira³

et al. 2010

The Lancet Infectious Diseases

168

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Efficacy and safety of artemether-lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial MSF Field Research SummaryBackground Malaria in pregnancy is associated with maternal and fetal morbidity and mortality. In 2006, WHO recommended use of artemisinin-based combination treatments during the second or third trimesters, but data on effi cacy and safety in Africa were scarce. We aimed to assess whether artemether-lumefantrine was at least as effi cacious as oral quinine for the treatment of uncomplicated falciparum malaria during the second and third trimesters of pregnancy in Mbarara, Uganda. MethodsWe did an open-label, randomised, non-inferiority trial between October, 2006, and May, 2009, at the antenatal clinics of the Mbarara University of Science and Technology Hospital in Uganda. Pregnant women were randomly assigned (1:1) by computer generated sequence to receive either quinine hydrochloride or artemetherlumefantrine, and were followed up weekly until delivery. Our primary endpoint was cure rate at day 42, confi rmed by PCR. The non-inferiority margin was a diff erence in cure rate of 5%. Analysis of effi cacy was for all randomised patients without study deviations that could have aff ected the effi cacy outcome. This study was registered with ClinicalTrials.gov, number NCT00495508.Findings 304 women were randomly assigned, 152 to each treatment group. By day 42, 16 patients were lost to followup and 25 were excluded from the analysis. At day 42, 137 (99·3%) of 138 patients taking artemether-lumefantrine and 122 (97·6%) of 125 taking quinine were cured-diff erence 1·7% (lower limit of 95% CI -0·9). There were 290 adverse events in the quinine group and 141 in the artemether-lumefantrine group.Interpretation Artemisinin derivatives are not inferior to oral quinine for the treatment of uncomplicated malaria in pregnancy and might be preferable on the basis of safety and effi cacy.Funding Médecins Sans Frontières and the European Commission.

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of artemether–lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial

Piola¹,

Nabasumba²,

Turyakira³

et al. 2010

The Lancet Infectious Diseases

168

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“…21 Three prototypes of analyzers have been evaluated for malaria diagnosis. The Cell-Dyn analyzers detect monocyte-coded depolarizing events corresponding to hemozoin-laden macrophages 8 with a maximum sensitivity and specificity of 97% 22 and 98%, 23 respectively. For the Coulter analyzers, a malaria discriminant factor that uses monocyte and lymphocyte DC measurements has a maximum sensitivity and specificity of 98% and 96.9%, respectively.…”

Section: Discussionmentioning

confidence: 99%

Design of Malaria Diagnostic Criteria for the Sysmex XE-2100 Hematology Analyzer

Campuzano-Zuluaga¹,

Álvarez-Sánchez²,

Escobar-Gallo³

et al. 2010

The American Journal of Tropical Medicine and Hygiene

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Hygiene INTRODUCTIONEarly detection of malaria in patients not suspected of having the disease is a potential novel application for modern hematology analyzers like the Sysmex XE-2100 (Sysmex Corporation, Kobe, Kansai, Japan). A prompt and accurate diagnosis is critical to reduce adverse outcomes associated with malaria, including death. 1 In endemic regions, malaria is a prime diagnostic concern in febrile patients, and expert thickfilm evaluation is usually available.2 However, the accuracy of microscopic malaria diagnosis in less experienced centers or in non-endemic regions may be lower, and health personnel is less likely to consider the disease, leading to delayed diagnoses.1 Automated full blood counts (FBC) are usually performed in patients with febrile illnesses, providing a unique opportunity to guide a timely parasitological malaria diagnosis.Hematology analyzers evaluated for malaria detection include the Cell-Dyn (Abbott Diagnostics, Santa Clara, CA), 3 the GEN.S and LH-750 (Beckman Coulter, Miami, FL), 4 and the XE-2100 and XS-1000 i (Sysmex Corporation, Kobe, Kansai, Japan). 5,6 The Sysmex XE-2100 is an automated hematology analyzer that uses flow cytometry, direct current (DC) impedanciometry, and radiofrequency conductance (RF) to detect and measure blood corpuscular elements.7 Flow cytometry may detect malaria parasites or parasite debris such as free hemozoin or hemozoin-laden macrophages as reported for Cell-Dyn instruments.8 For the Sysmex XE-2100, two case series reported a gap between the manual and automated eosinophil counts (pseudoeosinophilia) and abnormal granulocyte-coded events in the DIFF scatterplot used for white blood cell (WBC) separation based on fluorescence versus side-scatter signals in samples from Plasmodium vivaxinfected patients.9, 10 Later, Huh and others 5 found that the two previously reported abnormalities, compared with thick film, had a sensitivity of 69.4% and a specificity of 100% for P. vivax diagnosis. These findings suggest the potential clinical utility of malaria detection by the XE-2100. Ideally, to improve the clinical impact of this detection method, it should be an automated process relying on the analyzer's quantitative data and expressed as a "malaria alarm" that could motivate the microscopic search for malaria.The primary aim of this study was to develop, validate, and test the accuracy of one observer-dependent (OD) and two non-observer-dependent (N-OD) diagnostic prediction models for P. vivax and P. falciparum malaria. The approach for developing the OD models was similar to previous studies using the XE-2100 for malaria diagnosis 5 with the inclusion of other clinical and scatterplot variables not previously investigated. The N-OD models were developed to obtain a framework for an automated malaria-detection algorithm for the XE-2100. Secondary aims were to determine the occurrence of pseudoeosinophilia and to explore a possible cause for the XE-2100 FBC malaria-related abnormalities. MATERIALS AND METHODSStudy population. Blood samples were col...

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“…In one study, this was observed in 77 of 152 children with malaria [34]. Yet, lymphocytes are not phagocytic cells.…”

Section: Cell-dyn Analysers and Detection Of Malaria Pigment (Haemozoin)mentioning

confidence: 99%

Automated haematology analysis to diagnose malaria

Campuzano-Zuluaga

Hänscheid

Grobusch

2010

Malar J

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For more than a decade, flow cytometry-based automated haematology analysers have been studied for malaria diagnosis. Although current haematology analysers are not specifically designed to detect malaria-related abnormalities, most studies have found sensitivities that comply with WHO malaria-diagnostic guidelines, i.e. ≥ 95% in samples with > 100 parasites/μl. Establishing a correct and early malaria diagnosis is a prerequisite for an adequate treatment and to minimizing adverse outcomes. Expert light microscopy remains the 'gold standard' for malaria diagnosis in most clinical settings. However, it requires an explicit request from clinicians and has variable accuracy. Malaria diagnosis with flow cytometry-based haematology analysers could become an important adjuvant diagnostic tool in the routine laboratory work-up of febrile patients in or returning from malaria-endemic regions. Haematology analysers so far studied for malaria diagnosis are the Cell-Dyn®, Coulter® GEN·S and LH 750, and the Sysmex XE-2100® analysers. For Cell-Dyn analysers, abnormal depolarization events mainly in the lobularity/granularity and other scatter-plots, and various reticulocyte abnormalities have shown overall sensitivities and specificities of 49% to 97% and 61% to 100%, respectively. For the Coulter analysers, a 'malaria factor' using the monocyte and lymphocyte size standard deviations obtained by impedance detection has shown overall sensitivities and specificities of 82% to 98% and 72% to 94%, respectively. For the XE-2100, abnormal patterns in the DIFF, WBC/BASO, and RET-EXT scatter-plots, and pseudoeosinophilia and other abnormal haematological variables have been described, and multivariate diagnostic models have been designed with overall sensitivities and specificities of 86% to 97% and 81% to 98%, respectively. The accuracy for malaria diagnosis may vary according to species, parasite load, immunity and clinical context where the method is applied. Future developments in new haematology analysers such as considerably simplified, robust and inexpensive devices for malaria detection fitted with an automatically generated alert could improve the detection capacity of these instruments and potentially expand their clinical utility in malaria diagnosis.

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Full blood count and haemozoin-containing leukocytes in children with malaria: diagnostic value and association with disease severity

Abstract: Background: Diligent and correct laboratory diagnosis and up-front identification of risk factors for progression to severe disease are the basis for optimal management of malaria.

Cited by 41 publications

References 33 publications

Efficacy and safety of artemether–lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial

Efficacy and safety of artemether–lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial

Design of Malaria Diagnostic Criteria for the Sysmex XE-2100 Hematology Analyzer

Automated haematology analysis to diagnose malaria

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