Quantitative analysis of morphological alterations in Plasmodium falciparum infected red blood cells through theoretical interpretation of spectral measurements

Serebrennikova, Yulia M.; Patel, Janus; Milhous, Wilbur K.; García‐Rubio, Luis H.

doi:10.1016/j.jtbi.2010.05.037

Cited by 24 publications

(45 citation statements)

References 41 publications

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“…[25]. In brief, the model included a three-layer Mie geometry (i.e., a sphere having three concentric layers) to account for changes in the refractive indices of the IRBC cytosol and the parasite’s cytoplasm and organelles.…”

Section: Methodsmentioning

confidence: 99%

“…This “average” organelle (ORG) was modelled using the average refractive index of non-chromophoric molecules of biological cells [29]. Validated approximation of additivity of the spectral contributions from the structural groups [25,29] was used. The extinction of each structural group was a function of the size parameters and refractive indices of the layers.…”

Section: Methodsmentioning

confidence: 99%

“…parasite cytoplasm) was modelled to be composed of water and non-absorbing macromolecules [29]. The core elements were modelled as following: nucleus was composed of nucleic acid, non-absorbing macromolecules, and water; digestive vacuole was composed of water and haemozoin [25]; and the “average” organelle was composed of water and non-absorbing macromolecules. The refractive index of nucleic acid was constructed from those of the purine and pyrimidine bases [29] assuming G + C fraction of 0.2 for P. falciparum [31].…”

Section: Methodsmentioning

confidence: 99%

“…Haemoglobin depletion of the host and haemozoin build up in the parasite’s vacuole progress with the parasite’s development and become the greatest at the schizont stage [22-24]. It has been demonstrated for different intraerythrocytic life stages of P. falciparum that the UV-visible spectroscopy can track these changes [25]. …”

Section: Introductionmentioning

confidence: 99%

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Spectrophotometric detection of susceptibility to anti-malarial drugs

Serebrennikova

Patel

Milhous

et al. 2013

Malar J

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BackgroundWith malaria drug resistance increasing in prevalence and severity, new technologies are needed to aid and improve the accuracy and clinical relevance of laboratory or field testing for malaria drug resistance. This study presents a method based on simple and reagentless spectroscopic measurements coupled with comprehensive spectral interpretation analysis that provides valuable quantitative information on the morphological and compositional responses of Plasmodium falciparum and infected red blood cells (IRBCs) to anti-malarial treatment.MethodsThe changes in the size, internal structure, nucleotide and haemozoin composition of the parasites as well as the morphology (size and shape) and haemoglobin composition of the IRBCs treated with dihydroartemisinin (DHA) and mefloquine (MFQ) were investigated using a spectral interpretation analysis.ResultsDHA treatment reduced the sizes of the parasites and their structural organelles. The haemoglobin composition of the host IRBCs determined from spectroscopic analysis changed negligibly following DHA treatment. MFQ treated parasites grew to the same size as those from parallel non-treated cultures but lacked haemozoin. Lesser deformation of the cell shape and no haemoglobin depletion were detected for the IRBCs of MFQ treated cultures.ConclusionsThe spectroscopic analysis method proved to be sensitive for recognition of the effects of anti-malarial treatment on the structure and composition of the parasites and IRBCs. The method can have significant potential for research and clinical applications such as evaluating patient specimens for drug action, drug effects or for therapeutic monitoring.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Spectrophotometric detection of susceptibility to anti-malarial drugs

Serebrennikova

Patel

Milhous

et al. 2013

Malar J

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“…Many methods for detecting haemozoin have been proposed as an alternative to conventional malaria diagnostics. These methods include depolarization side scatter (DPSS) flow cytometry [1,2], Raman scattering [3-5], magneto-optics [6,7], magnetic aggregation [8], photoacoustics [9-11], optical spectroscopy [12], third harmonic generation [13,14], and dark-field microscopy [5,15-19]. A haemozoin-based diagnostic is desirable because it does not require the chemical staining or other sample preparation methods of manual Giemsa-stain microscopy that tend to lower the overall sensitivity and specificity of the test [20].…”

Section: Introductionmentioning

confidence: 99%

Limitations of haemozoin-based diagnosis of Plasmodium falciparum using dark-field microscopy

Delahunt

Horning

Wilson

et al. 2014

Malar J

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BackgroundThe haemozoin crystal continues to be investigated extensively for its potential as a biomarker for malaria diagnostics. In order for haemozoin to be a valuable biomarker, it must be present in detectable quantities in the peripheral blood and distinguishable from false positives. Here, dark-field microscopy coupled with sophisticated image processing algorithms is used to characterize the abundance of detectable haemozoin within infected erythrocytes from field samples in order to determine the window of detection in peripheral blood.MethodsThin smears from Plasmodium falciparum-infected and uninfected patients were imaged in both dark field (DF) unstained and bright field (BF) Giemsa-stained modes. The images were co-registered such that each parasite had thumbnails in both BF and DF modes, providing an accurate map between parasites and DF objects. This map was used to find the abundance of haemozoin as a function of parasite stage through careful parasite staging and correlation with DF objects. An automated image-processing and classification algorithm classified the bright spots in the DF images as either haemozoin or non-haemozoin objects.ResultsThe algorithm distinguishes haemozoin from non-haemozoin objects in DF images with an object-level sensitivity of 95% and specificity of 97%. Ring stages older than about 6 hours begin to show detectable haemozoin, and rings between 10–16 hours reliably contain detectable haemozoin. However, DF microscopy coupled with the image-processing algorithm detect no haemozoin in rings younger than six hours.DiscussionAlthough this method demonstrates the most sensitive detection of haemozoin in field samples reported to date, it does not detect haemozoin in ring-stage parasites younger than six hours. Thus, haemozoin is a poor biomarker for field samples primarily composed of young ring-stage parasites because the crystal is not present in detectable quantities by the methods described here. Based on these results, the implications for patient-level diagnosis and recommendations for future work are discussed.

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Optical discrimination of pathological red blood cells

Vergari,

Niccolini,

Pitocco

et al. 2024

Biotech & Bioengineering

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Fast diagnostic methods are crucial to reduce the burden on healthcare systems. Currently, detection of diabetes complications such as neuropathy requires time‐consuming approaches to observe the correlated red blood cells (RBCs) morphological changes. To tackle this issue, an optical analysis of RBCs in air was conducted in the 250–2500 nm range. The distinct oscillations present in the scattered and direct transmittance spectra have been analyzed with both Mie theory and anomalous diffraction approximation. The results provide information about the swelling at the ends of RBCs and directly relate the optical data to RBCs morphology and deformability. Both models agree on a reduction in the size and deformability of RBCs in diabetic patients, thus opening the way to diabetes diagnosis and disease progression assessment.

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Quantitative analysis of morphological alterations in Plasmodium falciparum infected red blood cells through theoretical interpretation of spectral measurements

Cited by 24 publications

References 41 publications

Spectrophotometric detection of susceptibility to anti-malarial drugs

Spectrophotometric detection of susceptibility to anti-malarial drugs

Limitations of haemozoin-based diagnosis of Plasmodium falciparum using dark-field microscopy

Optical discrimination of pathological red blood cells

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