Multiplex Human Malaria Array: Quantifying Antigens for Malaria Rapid Diagnostics

Jang, Ihn Kyung; Tyler, Abby; Lyman, Chris; Rek, John; Arinaitwe, Emmanuel; Adrama, Harriet; Murphy, Maxwell; Imwong, Mallika; Proux, Stéphane; Haohankhunnatham, Warat; Barney, Rebecca; Rashid, Andrew; Kalnoky, Michael; Kahn, Maria; Golden, Allison; Nosten, François; Greenhouse, Bryan; Gamboa, Dionicia; Domingo, Gonzalo J.

doi:10.4269/ajtmh.19-0763

Cited by 17 publications

(32 citation statements)

References 19 publications

(26 reference statements)

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“…Black dotted line: Cutoff yielding > 99.5% specificity derived from ROC curve analysis of data from the 140 samples described here. Red dotted line: Cutoff yielding > 99.5% specificity derived from ROC curve analysis of data from 462 blood samples described previously (Jang et al 2020 ). Two cutoff lines for Pan LDH are located in close proximity …”

Section: Resultsmentioning

confidence: 99%

“…Using PCR results as reference, the sensitivity and specificity of the 5-Plex in diagnosing malaria infection were calculated. Cutoff values previously established for frozen whole blood specimens (Jang et al 2020) led to the similar sensitivity and specificity estimates for HRP2 assay in DBS and whole blood, but lower sensitivity and specificity estimates for pLDH assays in DBS 5% specificity derived from ROC curve analysis of data from 462 blood samples described previously (Jang et al 2020). Two cutoff lines for Pan LDH are located in close proximity Table 2 Summary of area-under-the-curve (AUC) values derived from the receiver operator characteristics curve analysis (Online Resource Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The cutoff and diagnostic sensitivity/specificity for each assay was assessed in 140 of matched DBS and whole blood pellet samples. The sensitivity and specificity estimates for assays testing the DBS and frozen whole blood specimens in comparison to results of PCR as reference method are shown using cutoffs previously established for frozen whole blood specimens which were tested by the 5-Plex (Jang et al 2020 Frozen blood 72.0 (61.8-80.9) 100.0 (92.5-100.0) specimens, and the smaller concentration range for each analyte resulted from including only asymptomatic malaria cases from two geographic regions. Consequently, the cutoffs for the 5-Plex using DBS-derived samples tested here may not be optimal and should be further validated with more specimens and from a broader geography.…”

Section: Hrp2mentioning

confidence: 99%

“…The SCSD assay detects Pan LDH and HRP2, and the Luminex bead-based assay detects pan aldolase, Pan LDH, and HRP2. The Q-Plex TM Human Malaria Array (5-Plex, Quansys Biosciences, Logan, Utah), simultaneously measures HRP2, Pf LDH, Pv LDH, Pan LDH, and CRP (Jang et al 2020 ). These multiplexed assays have shown potential for screening for P. falciparum with hrp2/3 deletions and the improved detection of P. vivax (Jang et al 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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Assessment of Plasmodium antigens and CRP in dried blood spots with multiplex malaria array

et al. 2021

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Dried blood spots (DBS) typically prepared on filter papers are an ideal sample type for malaria surveillance by offering easy and cost-effective methods in terms of sample collection, storage, and transport. The objective of this study was to evaluate the applicability of DBS with a commercial multiplex malaria assay, developed to concurrently measure Plasmodium antigens, histidine-rich protein 2 (HRP2), Plasmodium lactate dehydrogenase (pLDH), and a host inflammatory biomarker, C-reactive protein (CRP), in whole blood. The assay conditions were optimized for DBS, and thermal stability for measurement of Plasmodium antigens and CRP in dried blood were determined. Performance of the multiplex assay on matched DBS and whole blood pellet samples was also evaluated using the clinical samples. The results indicate the acceptable performance in multiplex antigen detection using DBS samples. At cutoff levels for DBS, with a diagnostic specificity with a lower 95% confidence bound > 92%, diagnostic sensitivities against polymerase chain reaction (PCR)–confirmed malaria for HRP2, Pf LDH, Pv LDH, and Pan LDH were 93.5%, 80.4%, 21.3%, and 55.6%, respectively. The half-life of pLDH was significantly less than that of HRP2 in thermal stability studies. Results with DBS samples collected from Peru indicate that the uncontrolled storage conditions of DBS can result in inaccurate reporting for infection with P. falciparum parasites with hrp2/3 deletions. With careful consideration that minimizing the unfavorable DBS storage environment is essential for ensuring integrity of heat-labile Plasmodium antigens, DBS samples can be used as an alternative to liquid whole blood to detect P. falciparum with hrp2/3 deletions in malaria surveillance.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Hrp2mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Assessment of Plasmodium antigens and CRP in dried blood spots with multiplex malaria array

et al. 2021

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“…The fact that there were ~ 20% of HRP2-negative samples that were falsely positive by cRDT or uRDT could be explained by the limit of HRP2 detection of the ELISA technique used. While the limit of detection on whole blood pellets is significantly lower than that of the uRDT [ 61 , 62 ], the performance of the ELISA on DBS is likely to be lower depending on the efficiency of antigen recovery and the antigen stability on the DBS (Jang et al 2020; pers. commun,).…”

Section: Discussionmentioning

confidence: 99%

Field performance of ultrasensitive and conventional malaria rapid diagnostic tests in southern Mozambique

Galatas

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Gupta

et al. 2020

Malar J

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Background An ultrasensitive malaria rapid diagnostic test (RDT) was recently developed for the improved detection of low-density Plasmodium falciparum infections. This study aimed to compare the diagnostic performance of the PfHRP2-based Abbott Malaria Ag P. falciparum ultrasensitive RDT (uRDT) to that of the conventional SD-Bioline Malaria Ag P. falciparum RDT (cRDT) when performed under field conditions. Methods Finger-prick blood samples were collected from adults and children in two cross-sectional surveys in May of 2017 in southern Mozambique. Using real-time quantitative PCR (RT-qPCR) as the reference method, the age-specific diagnostic performance indicators of the cRDT and uRDT were compared. The presence of histidine-rich protein 2 (HRP2) and Plasmodium lactate dehydrogenase (pLDH) antigens was evaluated in a subset from dried blood spots by a quantitative antigen assay. pfhrp2 and pfhrp3 gene deletions were assessed in samples positive by RT-qPCR and negative by both RDTs. Results Among the 4,396 participants with complete test results, the sensitivity of uRDTs (68.2; 95% CI 60.8 to 74.9) was marginally better than that of cRDTs (61.5; 95% CI 53.9 to 68.6) (p-value = 0.004), while the specificities were similar (uRDT: 99.0 [95% CI 98.6 to 99.2], cRDT: 99.2 [95% CI 98.9 to 99.4], p-value = 0.02). While the performance of both RDTs was lowest in ≥ 15-year-olds, driven by the higher prevalence of low parasite density infections in this group, the sensitivity of uRDTs was significantly higher in this age group (54.9, 95% CI 40.3 to 68.9) compared to the sensitivity of cRDTs (39.2, 95% CI 25.8 to 53.9) (p-value = 0.008). Both RDTs detected P. falciparum infections at similar geometric mean parasite densities (112.9 parasites/μL for uRDTs and 145.5 parasites/μL for cRDTs). The presence of HRP2 antigen was similar among false positive (FP) samples of both tests (80.5% among uRDT-FPs and 84.4% among cRDT-FPs). Only one false negative sample was detected with a partial pfhrp2 deletion. Conclusion This study showed that the uRDTs developed by Abbott do not substantially outperform SD-Bioline Pf malaria RDTs in the community and are still not comparable to molecular methods to detect P. falciparum infections in this study setting.

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Malaria diagnostic methods with the elimination goal in view

et al. 2022

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Malaria control measures have been in use for years but have not completely curbed the spread of infection. Ultimately, global elimination is the goal. A major playmaker in the various approaches to reaching the goal is the issue of proper diagnosis. Various diagnostic techniques were adopted in different regions and geographical locations over the decades, and these have invariably produced diverse outcomes. In this review, we looked at the various approaches used in malaria diagnostics with a focus on methods favorably used during pre-elimination and elimination phases as well as in endemic regions. Microscopy, rapid diagnostic testing (RDT), loop-mediated isothermal amplification (LAMP), and polymerase chain reaction (PCR) are common methods applied depending on prevailing factors, each with its strengths and limitations. As the drive toward the elimination goal intensifies, the search for ideal, simple, fast, and reliable point-of-care diagnostic tools is needed more than ever before to be used in conjunction with a functional surveillance system supported by the ideal vaccine.

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Multiplex Human Malaria Array: Quantifying Antigens for Malaria Rapid Diagnostics

Cited by 17 publications

References 19 publications

Assessment of Plasmodium antigens and CRP in dried blood spots with multiplex malaria array

Assessment of Plasmodium antigens and CRP in dried blood spots with multiplex malaria array

Field performance of ultrasensitive and conventional malaria rapid diagnostic tests in southern Mozambique

Malaria diagnostic methods with the elimination goal in view

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