A simple and fast method to exclude high Plasmodium falciparum parasitaemia in travellers with imported malaria

Gool, Tom van; Wolfswinkel, Marlies E van; Koelewijn, Rob; Thiel, Pieter P. A. M. van; Jacobs, Jan; Hellemond, Jaap J. van; Genderen, Perry J.J. van

doi:10.1186/1475-2875-10-300

Cited by 10 publications

(6 citation statements)

References 14 publications

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“…We have demonstrated that the BinaxNOW commercial RDT and a validated qPCR based on the Plasmodium 18S rRNA region were unable to differentiate asexual from sexual stages of P. falciparum , however, the presence of the pan- Plasmodium aldolase T2 band was correlated to both higher parasitemia by microscopy and 18S rRNA gene copy number. This latter finding is consistent with previous research in which the absence of the aldolase T2 band served as a reasonable basis on which to rule out high parasitemia [ 19 ]. Although RNA transcript expression of eba-175 had a low positive predictive value (62.5 %) in this study, it provided a negative predictive value of 100 % for asexual stages, suggesting that it is potentially a good marker to rule-out asexual parasitemia in specimens received at the laboratory.…”

Section: Discussionsupporting

confidence: 92%

Correlating quantitative real-time PCR to rapid diagnostic test and RNA transcript expression in isolated gametocytemia and asexual parasitemia of Plasmodium falciparum malaria

Lau

Phuong

Ralevski

et al. 2015

Trop Dis Travel Med Vaccines

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BackgroundAt present, only microscopic examination of stained thick and thin blood smears for malaria can differentiate clinically relevant asexual parasitemia from clinically irrelevant isolated gametocytemia. Microscopy is time consuming, labour intensive, and requires significant technical expertise to perform. Simple and rapid tests that can distinguish asexual from isolated sexual parasitemia are needed.MethodsTo determine if parasitemia and cycle threshold (CT) values on Plasmodium genus and P. falciparum-specific quantitative polymerase chain reaction (qPCR) assays correlate to positivity of rapid diagnostic test (RDT), and 18S rRNA gene copy number, we analyzed blood samples from Ontario patients with isolated P. falciparum gametocytemia or asexual stages. RNA transcripts were evaluated to determine whether there is correlation of expression to different life cycle stages of P. falciparum.Results45 specimens containing isolated P. falciparum gametocytes, and 40 specimens containing isolated asexual stages by microscopy were identified and analyzed. By RDT, 40 of 45 (88.9 %) isolated gametocytemia specimens and 40 of 40 (100 %) asexual-stage specimens were positive for Plasmodium falciparum-specific histidine rich protein-2 (HRP-2). Fourteen of 45 (31.1 %) isolated gametocytemia specimens, and 36 of 40 (90 %) asexual-stage specimens were positive for Plasmodium genus aldolase T2 band. Positivity of the aldolase T2 band was associated with lower mean Plasmodium genus and P. falciparum-specific CT values, and to higher mean 18S rRNA gene copy by qPCR for both isolated gametocytemia and asexual-stage specimens. There was also a negative correlation of asexual parasitemia to both CT values, and positive correlation to 18S rRNA gene copy number. Analysis of asexual stage-specific erythrocyte binding antigen (eba-175) transcripts on 25 isolated gametocytemia and 20 asexual-stage specimens gave a positive predictive value of 62.5 % and negative predictive value of 100 % for asexual parasitemia. Thus, an absence of eba-175 transcripts excluded the presence of asexual (clinically relevant) parasitemia.ConclusionsPositivity of the aldolase T2 band of BinaxNow RDT correlated to higher parasite load in both isolated gametocytemia and asexual-stage specimens. Asexual stage-specific eba-175 RNA transcript expression provided reasonable negative predictive value for exclusion of asexual parasitemia in clinical samples, but was present in both isolated gametocytemia and asexual stage specimens.

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Section: Discussionsupporting

confidence: 92%

Correlating quantitative real-time PCR to rapid diagnostic test and RNA transcript expression in isolated gametocytemia and asexual parasitemia of Plasmodium falciparum malaria

Lau

Phuong

Ralevski

et al. 2015

Trop Dis Travel Med Vaccines

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“…Reactivity with the aldolase antibody would not be unexpected with P. falciparum, as aldolase is a panmalarial antigen; however, the absence of HRP-2 reactivity is puzzling. A recent report described a positive association between P. falciparum parasitemia and coreactivity of aldolase and HRP-2 in the BinaxNOW test (18). Given that the parasitemia was not high, a prozone effect is unlikely to explain this phenomenon.…”

Section: Discussionmentioning

confidence: 94%

Performance of BinaxNOW for Diagnosis of Malaria in a U.S. Hospital

et al. 2012

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Microscopic diagnosis and species identification of Plasmodium in areas of nonendemicity provide a robust method for malaria diagnosis but are technically challenging. A prospective study was conducted to measure the performance of BinaxNOW compared to microscopy (the gold standard) in a U.S. teaching hospital. Overall, BinaxNOW was 84.2% sensitive and 99.8% specific. Excluding patients on antimalarial therapy, the sensitivity was 92.9%. Importantly, BinaxNOW initially misclassified a case of Plasmodium falciparum malaria as non-falciparum. These results support the judicious use of BinaxNOW in screening of individuals suspected of having malaria in areas of nonendemicity. T he accurate diagnosis of malaria by microscopy in the UnitedStates is complicated by a number of factors, including lack of experienced technologists, variable methodology and quality of smears, and partial morphological overlap between Plasmodium falciparum and other Plasmodium species (12,14). Although the incidence of malaria in returned febrile travelers is approximately 21%, only 1,300 cases were reported in the United States in 2008, in comparison to 243 million cases worldwide during the same period (15,19,20). The development of rapid diagnostic tests (RDTs) has aided diagnosis of malaria in resource-poor settings, but these tests have limited capability for species identification, as they were originally designed to distinguish P. falciparum from other Plasmodium species that cause disease in humans. Numerous studies have demonstrated the utility of RDTs, which have sensitivity and specificity comparable to those of microscopy while offering rapid diagnosis, in Africa and Asia (1, 16). The performance of RDTs in areas of low malaria prevalence is less well investigated. Studies in France have demonstrated 96% sensitivity, 99% specificity, and high negative predictive values (NPV) with certain RDTs but conclude that microscopy is necessary for definitive confirmation (3, 4). A similar study in the United States demonstrated 99% overall sensitivity and 99.6% NPV for the diagnosis of malaria with the BinaxNOW Malaria test; sensitivity for P. falciparum was 100% (17). BinaxNOW Malaria, the only U.S. Food and Drug Administration-approved RDT for malaria, qualitatively detects both the histidine-rich protein 2 (HRP-2), specific to P. falciparum, and aldolase, a panmalarial antigen found in all Plasmodium species (11).Here, we report on the performance of the BinaxNOW in a major U.S. academic medical center, describe a unique case of misidentification of P. falciparum by BinaxNOW, and discuss the advantages and disadvantages of using BinaxNOW as a screening tool in the United States. MATERIALS AND METHODSFrom July 2008 to March 2012, 484 BinaxNOW Malaria tests, on 407 unique patients, were performed concurrently with thin and thick blood smears in the Stanford Hospital Clinical Hematology Laboratory on consecutive blood samples from patients with suspected malaria. For each sample, one thick and two thin smears were prepared from venous ED...

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“…The standard procedure to diagnose malaria comprised a quantitative buffy coat (QBC) analysis, a rapid diagnostic test (RDT) for malaria antigens (Binax NOW ® Malaria Test Binax, Inc, Maine, USA), and thick and thin blood smears using freshly collected blood specimens from finger pricks. The RDT and the QBC analysis were performed according to the manufacturer’s instructions [ 23 , 24 ]. QBC capillaries were examined independently by two technicians by microscopic analysis of two complete rows of the region between the bottom of the capillary and the polynuclear leukocyte layer using an Olympus BX-60 fluorescence microscope equipped with UV-filter, 50× objective and 12.5× oculars (total magnification 625×).…”

Section: Methodsmentioning

confidence: 99%

Neutrophil gelatinase-associated lipocalin (NGAL) predicts the occurrence of malaria-induced acute kidney injury

Wolfswinkel

Koopmans

Hesselink

et al. 2016

Malar J

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BackgroundAcute kidney injury (AKI) is a frequently encountered complication of imported Plasmodium falciparum infection. Markers of structural kidney damage have been found to detect AKI earlier than serum creatinine-based prediction models but have not yet been evaluated in imported malaria. This pilot study aims to explore the predictive performance of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for AKI in travellers with imported P. falciparum infection.MethodsThirty-nine patients with imported falciparum malaria from the Rotterdam Malaria Cohort with available serum and urine samples at presentation were included. Ten of these patients met the criteria for severe malaria. The predictive performance of NGAL and KIM-1 as markers for AKI was compared with that of serum creatinine.ResultsSix of the 39 patients (15 %) developed AKI. Serum and urine NGAL and urine KIM-1 were all found to have large areas under the receiver operating characteristics curves (AUROC) for predicting AKI. Urine NGAL was found to have an excellent performance with positive predictive value (PPV) of 1.00 (95 % CI 0.54–1.00), a negative predictive value (NPV) of 1.00 (95 % CI 0.89–1.00) and an AUROC of 1.00 (95 % CI 1.00–1.00).ConclusionA good diagnostic performance of NGAL and KIM-1 for AKI was found. Particularly, urine NGAL was found to have an excellent predictive performance. Larger studies are needed to demonstrate whether these biomarkers are superior to serum creatinine as predictors for AKI in P. falciparum malaria.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1516-y) contains supplementary material, which is available to authorized users.

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A simple and fast method to exclude high Plasmodium falciparum parasitaemia in travellers with imported malaria

Cited by 10 publications

References 14 publications

Correlating quantitative real-time PCR to rapid diagnostic test and RNA transcript expression in isolated gametocytemia and asexual parasitemia of Plasmodium falciparum malaria

Correlating quantitative real-time PCR to rapid diagnostic test and RNA transcript expression in isolated gametocytemia and asexual parasitemia of Plasmodium falciparum malaria

Performance of BinaxNOW for Diagnosis of Malaria in a U.S. Hospital

Neutrophil gelatinase-associated lipocalin (NGAL) predicts the occurrence of malaria-induced acute kidney injury

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