Development and evaluation of a multiplex screening assay for Plasmodium falciparum exposure

Jepsen, Micha Phill Grønholm; Röser, Dennis; Christiansen, Michael; Larsen, Severin Olesen; Cavanagh, David; Dhanasarnsombut, Kelwalin; Bygbjerg, Ib Christian; Dodoo, Daniel; Remarque, Edmond J.; Dziegiel, Morten Hanefeld; Jepsen, Søren; Mordmüller, Benjamin; Theisen, Michael

doi:10.1016/j.jim.2012.07.009

Cited by 17 publications

(10 citation statements)

References 35 publications

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“…Through the ELISA assay, high IgG concentrations in Kenyan blood allowed samples to be diluted to 1:10 5 -fold before reaching the lower asymptote of the sigmoidal curve (Additional file 2 ), but the multiplex assay allowed further titration capacity. This observation has been reported in other falciparum malaria studies, which have found bead-based multiplex assays provided higher titration capacity when directly compared with ELISA [ 24 , 25 ]. Possible explanations for this finding include the 3-dimensional nature of the bead assay as well as the ability of flow cytometry emission detectors to read a wide range of fluorescence intensities.…”

Section: Resultssupporting

confidence: 82%

Multiple comparisons analysis of serological data from an area of low Plasmodium falciparum transmission

Rogier

Wiegand

Moss

et al. 2015

Malar J

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BackgroundAs a nation reduces the burden of falciparum malaria, identifying areas of transmission becomes increasingly difficult. Over the past decade, the field of utilizing malaria serological assays to measure exposure has grown rapidly, and a variety of serological methods for data acquisition and analysis of human IgG against falciparum antigens are available. Here, different immunoassays and statistical methods are utilized to analyse samples from a low transmission setting and directly compare the estimates generated.MethodsA subset of samples (n = 580) from a 2012 Haitian nationwide malaria survey was employed as sample population of low falciparum endemicity. In addition to the Haitian samples, samples from 247 US residents were used as a reference population of ‘true seronegatives’. Data acquisition was performed through standard ELISA and bead-based multiplex assays assaying for IgG antibodies to the Plasmodium falciparum antigens MSP-1p19, MSP-1p42(D), MSP-1p42(F), and AMA-1. Appropriate parametric distributions and seropositivity cutoff values were determined by statistical measures.ResultsData from both assays showed a strong positive skew, and the lognormal distribution was found to be an appropriate statistical fit to the Haitian and American populations. The American samples served as a good serological true negative population for the multiplex assay, but not for ELISA-based data. Mixture model approaches to determine seronegative and seropositive populations from the Haitian data showed a high degree of distribution overlap—likely due to the historical low falciparum transmission in this nation. Different fittings to the reversible catalytic model resulted depending upon the immunoassay utilized and seropositivity cutoff method employed. Data were also analysed through fitting to penalized B-splines, presenting another possible analytical tool for the analysis of malaria serological data.ConclusionsStandardization of serological techniques and analyses may prove difficult as some tools can prove to be more useful depending on the area and parasite in question, making clear interpretation a vital pursuit. The presented analysis in the low-endemic nation of Haiti found malaria-naive US residents to be an appropriate seronegative reference population for the multiplex assay, and this assay providing consistent estimates between MSP-1 and AMA-1 antigens of percent seropositives for this low-endemic population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0955-1) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 82%

Multiple comparisons analysis of serological data from an area of low Plasmodium falciparum transmission

Rogier

Wiegand

Moss

et al. 2015

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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“…Nash et al [ 66 ] have demonstrated that a gold and iron oxide magnetic nanoparticles (AuNP/mNP) system in addition to a polymer free poly ( N -isopropylacrylamide) (pNIPAm) could enrich and detect recombinant Pf HRP2 and pan-malarial aldolase antigens [ 66 ]. A multiplex assay (MPA) developed by Jepsen et al [ 67 ], using a bead-based multiplexed immunoassay system in a microplate format (Luminex xMAP® technology) to simultaneously analyze glutamate-rich protein (GLURP) antigens R0 and R2, merozoite surface protein 3 (MSP3), MSP1 hybrid and apical merozoite antigen 1 (AMA1) for screening P. falciparum in blood donors with suspected malaria. Their findings established a high diagnostic performance with 95.8% specificity and 90.4% sensitivity of [ 67 ].…”

Section: Multiplex Biomarker Detectionmentioning

confidence: 99%

“…A multiplex assay (MPA) developed by Jepsen et al [ 67 ], using a bead-based multiplexed immunoassay system in a microplate format (Luminex xMAP® technology) to simultaneously analyze glutamate-rich protein (GLURP) antigens R0 and R2, merozoite surface protein 3 (MSP3), MSP1 hybrid and apical merozoite antigen 1 (AMA1) for screening P. falciparum in blood donors with suspected malaria. Their findings established a high diagnostic performance with 95.8% specificity and 90.4% sensitivity of [ 67 ]. Given the advantages associated with the MPA, notably operator-independence and reliability, the assay has the potential for routine clinical application in endemic regions.…”

Section: Multiplex Biomarker Detectionmentioning

confidence: 99%

Recent Progress in the Development of Diagnostic Tests for Malaria

et al. 2017

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The impact of malaria on global health has continually prompted the need to develop effective diagnostic strategies. In malaria endemic regions, routine diagnosis is hampered by technical and infrastructural challenges to laboratories. These laboratories lack standard facilities, expertise or diagnostic supplies; thus, therapy is administered based on clinical or self-diagnosis. There is the need for accurate diagnosis of malaria due to the continuous increase in the cost of medication, and the emergence and spread of drug resistant strains. However, the widely utilized Giemsa-stained microscopy and immunochromatographic tests for malaria are liable to several drawbacks, including inadequate sensitivity and false-positive outcomes. Alternative methods that offer improvements in performance are either expensive, have longer turnaround time or require a level of expertise that makes them unsuitable for point-of-care (POC) applications. These gaps necessitate exploration of more efficient detection techniques with the potential of POC applications, especially in resource-limited settings. This minireview discusses some of the recent trends and new approaches that are seeking to improve the clinical diagnosis of malaria.

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Development and evaluation of a multiplex screening assay for Plasmodium falciparum exposure

Cited by 17 publications

References 35 publications

Multiple comparisons analysis of serological data from an area of low Plasmodium falciparum transmission

Multiple comparisons analysis of serological data from an area of low Plasmodium falciparum transmission

Recent Advances in the Development of Biosensors for Malaria Diagnosis

Recent Progress in the Development of Diagnostic Tests for Malaria

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