Malaria diagnosis for malaria elimination

Zimmerman, Peter A.; Howes, Rosalind E.

doi:10.1097/qco.0000000000000191

Cited by 74 publications

(79 citation statements)

References 79 publications

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“…Due to their cost and relative complexity, the WHO and malaria diagnostic community in general understandably do not consider NAATs-including PCRs-a viable alternative for routine diagnostics in most countries [50]. However, while experts are debating the clinical utility of detecting subclinical malaria infections [20,51,52], detection of low density parasitaemia in asymptomatic patients by DNA-based diagnostics offers significant epidemiological value, particularly if coupled with strategic elimination efforts; detecting subclinical infections allows more targeted and effective interventions [53]. Furthermore, tracking of the emergence and spread of anti-malarial drug resistance mutations and strains carrying these determinants can only be performed using the specificity inherent within nucleic acid-based technology [50,54].…”

Section: Discussionmentioning

confidence: 99%

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Use of real-time multiplex PCR, malaria rapid diagnostic test and microscopy to investigate the prevalence of Plasmodium species among febrile hospital patients in Sierra Leone

Łęski

Taitt

Swaray

et al. 2020

Malar J

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Background: Malaria continues to affect over 200 million individuals every year, especially children in Africa. Rapid and sensitive detection and identification of Plasmodium parasites is crucial for treating patients and monitoring of control efforts. Compared to traditional diagnostic methods such as microscopy and rapid diagnostic tests (RDTs), DNA based methods, such as polymerase chain reaction (PCR) offer significantly higher sensitivity, definitive discrimination of Plasmodium species, and detection of mixed infections. While PCR is not currently optimized for routine diagnostics, its role in epidemiological studies is increasing as the world moves closer toward regional and eventually global malaria elimination. This study demonstrates the field use of a novel, ambient temperature-stabilized, multiplexed PCR assay in a small hospital setting in Sierra Leone.Methods: Blood samples from 534 febrile individuals reporting to a hospital in Bo, Sierra Leone, were tested using three methods: a commercial RDT, microscopy, and a Multiplex Malaria Sample Ready (MMSR) PCR designed to detect a universal malaria marker and species-specific markers for Plasmodium falciparum and Plasmodium vivax. A separate PCR assay was used to identify species of Plasmodium in samples in which MMSR detected malaria, but was unable to identify the species.Results: MMSR detected the presence of any malaria marker in 50.2% of all tested samples with P. falciparum identified in 48.7% of the samples. Plasmodium vivax was not detected. Testing of MMSR P. falciparum-negative/universal malaria-positive specimens with a panel of species-specific PCRs revealed the presence of Plasmodium malariae (n = 2) and Plasmodium ovale (n = 2). The commercial RDT detected P. falciparum in 24.6% of all samples while microscopy was able to detect malaria in 12.8% of tested specimens.

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Section: Discussionmentioning

confidence: 99%

“…Limit of detection (LOD) for PCR is typically 1-5 parasites/µL [13][14][15][16][17] compared to 50-500 parasites/µL for microscopy [13,14,18] and more than 100 parasites/µL for RDT's [14,19]. Depending on the assay, PCR can be used for accurate species identification, detection of mixed infections, and parasite density estimation [20].…”

Section: Introductionmentioning

confidence: 99%

Use of real-time multiplex PCR, malaria rapid diagnostic test and microscopy to investigate the prevalence of Plasmodium species among febrile hospital patients in Sierra Leone

Łęski

Taitt

Swaray

et al. 2020

Malar J

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“…Typically, the diagnosis of malaria is carried out by inspecting the Giemsa/Leishman stained blood smears under a bright field microscope. Though there are other methods such as antigen‐based rapid diagnostic tests and the use of the polymerase chain reaction to detect the parasite's DNA (deoxyribonucleic acid), microscopic examination remains as the gold standard for the diagnosis of malaria due to the low‐cost and widespread acceptance. However, the manual examination of the slides is cumbersome and demands highly experienced clinicians.…”

Section: Introductionmentioning

confidence: 99%

Convolutional neural network‐based malaria diagnosis from focus stack of blood smear images acquired using custom‐built slide scanner

Gopakumar

Murali

Siva

et al. 2017

Journal of Biophotonics

125

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The present paper introduces a focus stacking‐based approach for automated quantitative detection of Plasmodium falciparum malaria from blood smear. For the detection, a custom designed convolutional neural network (CNN) operating on focus stack of images is used. The cell counting problem is addressed as the segmentation problem and we propose a 2‐level segmentation strategy. Use of CNN operating on focus stack for the detection of malaria is first of its kind, and it not only improved the detection accuracy (both in terms of sensitivity [97.06%] and specificity [98.50%]) but also favored the processing on cell patches and avoided the need for hand‐engineered features. The slide images are acquired with a custom‐built portable slide scanner made from low‐cost, off‐the‐shelf components and is suitable for point‐of‐care diagnostics. The proposed approach of employing sophisticated algorithmic processing together with inexpensive instrumentation can potentially benefit clinicians to enable malaria diagnosis.

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“…The ability of different diagnostic tools to detect infections34, the severity of clinical symptoms56, and transmission potential78 are all closely related to parasite densities. Parasite densities also show pronounced age patterns, reflecting lifetime exposure and naturally acquired immunity on a population level7.…”

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confidence: 99%

Sensitive and accurate quantification of human malaria parasites using droplet digital PCR (ddPCR)

Koepfli

Nguitragool

Hofmann

et al. 2016

Sci Rep

100

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Accurate quantification of parasite density in the human host is essential for understanding the biology and pathology of malaria. Semi-quantitative molecular methods are widely applied, but the need for an external standard curve makes it difficult to compare parasite density estimates across studies. Droplet digital PCR (ddPCR) allows direct quantification without the need for a standard curve. ddPCR was used to diagnose and quantify P. falciparum and P. vivax in clinical patients as well as in asymptomatic samples. ddPCR yielded highly reproducible measurements across the range of parasite densities observed in humans, and showed higher sensitivity than qPCR to diagnose P. falciparum, and equal sensitivity for P. vivax. Correspondence in quantification was very high (>0.95) between qPCR and ddPCR. Quantification between technical replicates by ddPCR differed 1.5–1.7-fold, compared to 2.4–6.2-fold by qPCR. ddPCR facilitates parasite quantification for studies where absolute densities are required, and will increase comparability of results reported from different laboratories.

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Malaria diagnosis for malaria elimination

Abstract: Microscopy and rapid diagnostic tests provide effective surveillance for malaria control. Strategies that detect a reservoir of submicroscopic infection must be developed and standardized to guide malaria elimination.

Cited by 74 publications

References 79 publications

Use of real-time multiplex PCR, malaria rapid diagnostic test and microscopy to investigate the prevalence of Plasmodium species among febrile hospital patients in Sierra Leone

Use of real-time multiplex PCR, malaria rapid diagnostic test and microscopy to investigate the prevalence of Plasmodium species among febrile hospital patients in Sierra Leone

Convolutional neural network‐based malaria diagnosis from focus stack of blood smear images acquired using custom‐built slide scanner

Sensitive and accurate quantification of human malaria parasites using droplet digital PCR (ddPCR)

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