Simultaneous capture and sequential detection of two malarial biomarkers on magnetic microparticles

Markwalter, Christine F.; Ricks, Keersten M.; Bitting, Anna L.; Mudenda, Lwiindi; Wright, David W.

doi:10.1016/j.talanta.2016.08.078

Cited by 22 publications

(19 citation statements)

References 18 publications

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“…This observation points to a disadvantage of HRP2 as a biomarker, as its persistence can result in misdiagnosis of patients and improper treatment [ 22 ]. To address this issue, an alternative protein biomarker that quickly clears from the bloodstream, Plasmodium lactate dehydrogenase ( p LDH), is being further explored in our lab [ 20 , 23 ]. Nonetheless, the importance of detection of HRP2 remains, as it continues to be the most sensitive and prevalently used protein biomarker for detection of falciparum malaria infections [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Plasmodium falciparum HRP2 ELISA for analysis of dried blood spot samples in rural Zambia

Gibson

Markwalter

Kimmel

et al. 2017

Malar J

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BackgroundDried blood spots are commonly used for sample collection in clinical and non-clinical settings. This method is simple, and biomolecules in the samples remain stable for months at room temperature. In the field, blood samples for the study and diagnosis of malaria are often collected on dried blood spot cards, so development of a biomarker extraction and analysis method is needed.MethodsA simple extraction procedure for the malarial biomarker Plasmodium falciparum histidine-rich protein 2 (HRP2) from dried blood spots was optimized to achieve maximum extraction efficiency. This method was used to assess the stability of HRP2 in dried blood spots. Furthermore, 328 patient samples made available from rural Zambia were analysed for HRP2 using the developed method. These samples were collected at the initial administration of artemisinin-based combination therapy and at several points following treatment.ResultsAn average extraction efficiency of 70% HRP2 with a low picomolar detection limit was achieved. In specific storage conditions HRP2 was found to be stable in dried blood spots for at least 6 months. Analysis of patient samples showed the method to have a sensitivity of 94% and a specificity of 89% when compared with microscopy, and trends in HRP2 clearance after treatment were observed.ConclusionsThe dried blood spot ELISA for HRP2 was found to be sensitive, specific and accurate. The method was effectively used to assess biomarker clearance characteristics in patient samples, which prove it to be ideal for gaining further insight into the disease and epidemiological applications.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-1996-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Plasmodium falciparum HRP2 ELISA for analysis of dried blood spot samples in rural Zambia

Gibson

Markwalter

Kimmel

et al. 2017

Malar J

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“…Moreover, the benefit directly translates to convenient sampling and low cost to providers and patients at the same time ensuring optimum outcome. A combination of antigens and genes have been reported in ICT and nucleic-acid-based methods respectively and are discussed elsewhere [111][112][113]. Multiplexed malaria testing is aimed primarily at differential diagnosis between parasite species.…”

Section: Multi-panel Biomarker Arrays For Malaria Detectionmentioning

confidence: 99%

Recent Advances in the Development of Biosensors for Malaria Diagnosis

Krampa

Aniweh

Kanyong

et al. 2020

Sensors

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The impact of malaria on global health has continually prompted the need to develop more effective diagnostic strategies that could overcome deficiencies in accurate and early detection. In this review, we examine the various biosensor-based methods for malaria diagnostic biomarkers, namely; Plasmodium falciparum histidine-rich protein 2 (PfHRP-2), parasite lactate dehydrogenase (pLDH), aldolase, glutamate dehydrogenase (GDH), and the biocrystal hemozoin. The models that demonstrate a potential for field application have been discussed, looking at the fabrication and analytical performance characteristics, including (but not exclusively limited to): response time, sensitivity, detection limit, linear range, and storage stability, which are first summarized in a tabular form and then described in detail. The conclusion summarizes the state-of-the-art technologies applied in the field, the current challenges and the emerging prospects for malaria biosensors.Sensors 2020, 20, 799 2 of 21 emergence and spread of drug resistance. It could also reduce the pool of individuals who can contribute to malaria transmission [5].To date, many technologies have attempted to circumvent the challenges in malaria diagnostics with technologies that address point-of-care needs and early stage asymptomatic detection. In this review, we first comprehensively summarize the biomarkers targeted during the course of malaria with emphasis on the importance of sensitive early detection. Next, we provide an overview of the recent advances in biosensor technologies for the detection of the most targeted biomarkers, focusing on: development, analytical performances, and suitability for point of care testing. The prevailing challenges and future outlook of the use of these technologies in the field are also highlighted. Parasite Development in Humans, Biomarkers, and DiagnosisThe developmental cycle of Plasmodium species that infect humans is briefly illustrated in Figure 1 [6]. The cycle begins with the injection of sporozoites into the host's circulation by an infected female Anopheles mosquito. The sporozoites then target and enter hepatocytes where they multiply and differentiate into merozoites. This stage of the parasite life cycle is known as pre-erythrocytic. In infections involving P. vivax and P. ovale, dormant forms of the liver stage, called hypnozoites may persist in the liver [7] and cause relapse of the infection, thereby making it difficult to eradicate. The pre-erythrocytic stage is essential in the establishment of malaria infection. This stage is asymptomatic, however, it is difficult for diagnostic tools to detect sporozoites because hepatocytes invasion occurs within 30-45 min after sporozoites are inoculated by the infected mosquito [8,9]. This short time and low numbers of sporozoites injected leaves little time for their detection. Some efforts in finding biomarkers for detection of early liver stage or the dormant form have identified the Plasmodium liver-specific protein 2 (LISP2) [10,11]. The sporozoite surface circum...

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“…To address these disadvantages, we previously developed a highly sensitive, magnetic bead–based assay that simultaneously captured and sequentially detected Plasmodium lactate dehydrogenase ( p LDH) and HRP2 from a single whole blood sample. 19 Because p LDH is a metabolic enzyme required for parasite survival, it is present during infections from any of the five species of malaria known to infect humans. 20 , 21 In addition, p LDH has been shown to clear within days after treatment.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the lower limit of detection of the SCSD assay, 2.0 parasites/μL for both p LDH and HRP2, was an order of magnitude improved over commercially available enzyme-linked immunosorbent assay (ELISA) kits and would allow for detection of individuals with asymptomatic or submicroscopic malaria infections. 19 …”

Section: Introductionmentioning

confidence: 99%

Characterization of Plasmodium Lactate Dehydrogenase and Histidine-Rich Protein 2 Clearance Patterns via Rapid On-Bead Detection from a Single Dried Blood Spot

Markwalter

Gibson

Mudenda

et al. 2018

The American Journal of Tropical Medicine and Hygiene

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Abstract.A rapid, on-bead enzyme-linked immunosorbent assay for Plasmodium lactate dehydrogenase (pLDH) and Plasmodium falciparum histidine-rich protein 2 (HRP2) was adapted for use with dried blood spot (DBS) samples. This assay detected both biomarkers from a single DBS sample with only 45 minutes of total incubation time and detection limits of 600 ± 500 pM (pLDH) and 69 ± 30 pM (HRP2), corresponding to 150 and 24 parasites/μL, respectively. This sensitive and reproducible on-bead detection method was used to quantify pLDH and HRP2 in patient DBS samples from rural Zambia collected at multiple time points after treatment. Biomarker clearance patterns relative to parasite clearance were determined; pLDH clearance followed closely with parasite clearance, whereas most patients maintained detectable levels of HRP2 for 35–52 days after treatment. Furthermore, weak-to-moderate correlations between biomarker concentration and parasite densities were found for both biomarkers. This work demonstrates the utility of the developed assay for epidemiological study and surveillance of malaria.

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Simultaneous capture and sequential detection of two malarial biomarkers on magnetic microparticles

Cited by 22 publications

References 18 publications

Plasmodium falciparum HRP2 ELISA for analysis of dried blood spot samples in rural Zambia

Plasmodium falciparum HRP2 ELISA for analysis of dried blood spot samples in rural Zambia

Recent Advances in the Development of Biosensors for Malaria Diagnosis

Characterization of Plasmodium Lactate Dehydrogenase and Histidine-Rich Protein 2 Clearance Patterns via Rapid On-Bead Detection from a Single Dried Blood Spot

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