Remodeling of the malaria parasite and host human red cell by vesicle amplification that induces artemisinin resistance

In the autumn of 1913 Major Kenrick, I. M. S., kindly sent me, from Pachmari, Central Provinces, India, a blood slide from a native child, containing numerous malaria parasites. On examining these, which I at first took to be malignant tertian parasites, the suspicion arose in my mind that there was something peculiar about their appearance. I happened just previously to have been studying a blood slide from Rhodesia, containing very numerous malignant tertian parasites. The peculiarity of the Indian parasite, as far as I could at first define it, was that it was an irregular parasite as compared with the regular, almost monotonous, contour of the “rings” of the malignant tertian parasite ( Plasmodium falciparum ). I proceeded then to study the Indian parasite more carefully; and, after-daily observations for many weeks of it, and of control malignant tertian parasites from various sources, I came definitely to the conclusion that it was unlike any malignant tertian parasite that I had ever seen or that I could find figured in the text-books or journals. I also considered carefully the possibility of its being the simple tertian parasite, but to this point I shall return later. During this study, in order to fix my impressions, I drew 150 consecutive parasites from the Indian slide and the Rhodesian slide respectively, as the former appeared in the field of view of an ocular so restricted by placing a diaphragm in it that only half a dozen red cells were visible in the field at a time, thus effectively preventing any selection on my part. I reproduce as pen-and-ink drawings 35 of each series taken at random, as they show very well in a general way the different aspect of the two parasites. For the same purpose I also drew a number of young simple tertian parasites. I now proceed to define as far as possible in detail the peculiarities of this parasite.

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An Ultrastructural Study of the Red Pulp of the Spleen in Malaria

Blood ◽

10.1182/blood.v41.2.207.207 ◽

1973 ◽

Vol 41 (2) ◽

pp. 207-218 ◽

Cited By ~ 25

Author(s):

B. Schnitzer ◽

T. M. Sodeman ◽

M. L. Mead ◽

P. G. Contacos

Keyword(s):

Rhesus Monkey ◽

Ultrastructural Study ◽

Plasmodium Knowlesi ◽

Red Cells ◽

Red Cell ◽

Malaria Parasites ◽

Red Pulp

Abstract An ultrastructural study was undertaken of the spleen of a rhesus monkey infected with Plasmodium knowlesi to determine whether the spleen is able to pit malaria parasites from red cells. It was found that in the spleen parasitized cells are: (1) phagocytized in toto by cordal macrophages, (2) pitted of parasites, and (3) hemolyzed in the splenic microvasculature. Phagocytosis of the entire parasitized red cell appears to occur most frequently of the three mechanisms and probably accounts for most of the anemia. Pitting of parasitized red cells may account in part for the hemolysis in excess of the number of parasitized red cells seen in malaria. The red cells that have had their parasites removed would become spherocytic and hence, would be more susceptible to removal from the circulation during subsequent passages through the spleen.

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Postartesunate delayed hemolysis is a predictable event related to the lifesaving effect of artemisinins

Blood ◽

10.1182/blood-2014-02-555953 ◽

2014 ◽

Vol 124 (2) ◽

pp. 167-175 ◽

Cited By ~ 74

Author(s):

Stéphane Jauréguiberry ◽

Papa A. Ndour ◽

Camille Roussel ◽

Flavie Ader ◽

Innocent Safeukui ◽

...

Keyword(s):

Red Cells ◽

Malaria Parasites ◽

Key Points ◽

Predictable Event

Key Points After being killed by artesunate, malaria parasites are expelled from red cells and then these pitted red cells reenter the circulation. When many pitted red cells are produced during therapy, their delayed clearance a few weeks later triggers hemolytic episodes.

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A new molecular link between defective autophagy and erythroid abnormalities in chorea-acanthocytosis

Blood ◽

10.1182/blood-2016-07-727321 ◽

2016 ◽

Vol 128 (25) ◽

pp. 2976-2987 ◽

Cited By ~ 24

Author(s):

Francesca Lupo ◽

Elena Tibaldi ◽

Alessandro Matte ◽

Alok K. Sharma ◽

Anna Maria Brunati ◽

...

Keyword(s):

Protein Turnover ◽

Kinase Activity ◽

Red Cells ◽

Red Cell ◽

Cell Integrity ◽

Lyn Kinase ◽

Key Points

Key Points In chorea-acanthocytosis, spiculated red cells are characterized by heightened Lyn kinase activity and dysregulated autophagy. Regulation of protein turnover by autophagy plays a key role in erythropoiesis and red cell integrity.

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LACK OF EFFECT OF CORTICOSTEROIDS ON THE IN VIVO DISAPPEARANCE OF SULFHYDRYL-INHIBITED AND ANTIBODY-COATED ERYTHROCYTES

Acta Endocrinologica ◽

10.1530/acta.0.047s028 ◽

1964 ◽

Vol 47 (3_Suppl) ◽

pp. S28-S36

Author(s):

Kailash N. Agarwal

Keyword(s):

Red Cells ◽

List Type ◽

Red Cell

ABSTRACT Red cells were incubated in vitro with sulfhydryl inhibitors and Rhantibody with and without prior incubation with prednisolone-hemisuccinate. These erythrocytes were labelled with Cr51 and P32 and their disappearance in vivo after autotransfusion was measured. Prior incubation with prednisolone-hemisuccinate had no effect on the rate of red cell disappearance. The disappearance of the cells was shown to take place without appreciable intravascular destruction.

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Determinants of Erythrocyte Size in Chronic Liver Disease

Blood ◽

10.1182/blood.v34.6.739.739 ◽

1969 ◽

Vol 34 (6) ◽

pp. 739-746 ◽

Cited By ~ 10

Author(s):

THOMAS M. KILBRIDGE ◽

PAUL HELLER

Keyword(s):

Bone Marrow ◽

Liver Disease ◽

Chronic Liver Disease ◽

Peripheral Blood ◽

Hepatic Cirrhosis ◽

Alcoholic Cirrhosis ◽

Clinical Findings ◽

Red Cells ◽

Red Cell ◽

Cell Volumes

Abstract Serial determinations of red cell volumes were made with an electronic sizing device in 30 patients with hepatic cirrhosis. Variations in red cell volumes were correlated with other hematologic and clinical findings. The results of these studies suggest that volume macrocytosis in patients with alcoholic cirrhosis is either due to megaloblastosis of the bone marrow or to an accelerated influx of young red cells into the peripheral blood.

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Reduction in massive postpartum haemorrhage and red blood cell transfusion during a national quality improvement project, Obstetric Bleeding Strategy for Wales, OBS Cymru: an observational study

BMC Pregnancy and Childbirth ◽

10.1186/s12884-021-03853-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sarah F. Bell ◽

Rachel E. Collis ◽

Philip Pallmann ◽

Christopher Bailey ◽

Kathryn James ◽

...

Keyword(s):

Risk Assessment ◽

Quality Improvement ◽

Blood Loss ◽

Postpartum Haemorrhage ◽

Red Cells ◽

National Database ◽

Care Bundle ◽

Red Cell ◽

National Quality ◽

Red Cell Transfusion

Abstract Background Postpartum haemorrhage (PPH) is a major cause of maternal morbidity and mortality and its incidence is increasing in many countries despite management guidelines. A national quality improvement programme called the Obstetric Bleeding Strategy for Wales (OBS Cymru) was introduced in all obstetric units in Wales. The aim was to reduce moderate PPH (1000 mL) progressing to massive PPH (> 2500 mL) and the need for red cell transfusion. Methods A PPH care bundle was introduced into all 12 obstetric units in Wales included all women giving birth in 2017 and 2018 (n = 61,094). The care bundle prompted: universal risk assessment, quantitative measurement of blood loss after all deliveries (as opposed to visual estimation), structured escalation to senior clinicians and point-of-care viscoelastometric-guided early fibrinogen replacement. Data were submitted by each obstetric unit to a national database. Outcome measures were incidence of massive PPH (> 2500 mL) and red cell transfusion. Analysis was performed using linear regression of the all Wales monthly data. Results Uptake of the intervention was good: quantitative blood loss measurement and risk assessment increased to 98.1 and 64.5% of all PPH > 1000 mL, whilst ROTEM use for PPH > 1500 mL increased to 68.2%. Massive PPH decreased by 1.10 (95% CI 0.28 to 1.92) per 1000 maternities per year (P = 0.011). Fewer women progressed from moderate to massive PPH in the last 6 months, 74/1490 (5.0%), than in the first 6 months, 97/1386 (7.0%), (P = 0.021). Units of red cells transfused decreased by 7.4 (95% CI 1.6 to 13.2) per 1000 maternities per year (P = 0.015). Red cells were transfused to 350/15204 (2.3%) and 268/15150 (1.8%) (P = 0.001) in the first and last 6 months, respectively. There was no increase in the number of women with lowest haemoglobin below 80 g/L during this time period. Infusions of fresh frozen plasma fell and there was no increase in the number of women with haemostatic impairment. Conclusions The OBS Cymru care bundle was feasible to implement and associated with progressive, clinically significant improvements in outcomes for PPH across Wales. It is applicable across obstetric units of widely varying size, complexity and staff mixes.

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A cornucopia of research resources for the fourth rodent malaria parasite species

BMC Biology ◽

10.1186/s12915-021-01019-y ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Jane M. Carlton

Keyword(s):

Malaria Parasite ◽

Parasite Species ◽

First Century ◽

Model Systems ◽

Rodent Malaria Parasite ◽

Malaria Parasites ◽

Rodent Malaria ◽

Human Malaria ◽

Plasmodium Vinckei ◽

Research Resources

AbstractThe study of human malaria caused by species of Plasmodium has undoubtedly been enriched by the use of model systems, such as the rodent malaria parasites originally isolated from African thicket rats. A significant gap in the arsenal of resources of the species that make up the rodent malaria parasites has been the lack of any such tools for the fourth of the species, Plasmodium vinckei. This has recently been rectified by Abhinay Ramaprasad and colleagues, whose pivotal paper published in BMC Biology describes a cornucopia of new P. vinckei ‘omics datasets, mosquito transmission experiments, transfection protocols, and virulence phenotypes, to propel this species firmly into the twenty-first century.

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Malaria parasite detection in thick blood smear microscopic images using modified YOLOV3 and YOLOV4 models

BMC Bioinformatics ◽

10.1186/s12859-021-04036-4 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Fetulhak Abdurahman ◽

Kinde Anlay Fante ◽

Mohammed Aliy

Keyword(s):

Object Detection ◽

Malaria Parasite ◽

Blood Smear ◽

Clustering Algorithm ◽

State Of The Art ◽

Detection Accuracy ◽

Small Object ◽

Thick Blood Smear ◽

Malaria Parasites ◽

Microscopic Images

Abstract Background Manual microscopic examination of Leishman/Giemsa stained thin and thick blood smear is still the “gold standard” for malaria diagnosis. One of the drawbacks of this method is that its accuracy, consistency, and diagnosis speed depend on microscopists’ diagnostic and technical skills. It is difficult to get highly skilled microscopists in remote areas of developing countries. To alleviate this problem, in this paper, we propose to investigate state-of-the-art one-stage and two-stage object detection algorithms for automated malaria parasite screening from microscopic image of thick blood slides. Results YOLOV3 and YOLOV4 models, which are state-of-the-art object detectors in accuracy and speed, are not optimized for detecting small objects such as malaria parasites in microscopic images. We modify these models by increasing feature scale and adding more detection layers to enhance their capability of detecting small objects without notably decreasing detection speed. We propose one modified YOLOV4 model, called YOLOV4-MOD and two modified models of YOLOV3, which are called YOLOV3-MOD1 and YOLOV3-MOD2. Besides, new anchor box sizes are generated using K-means clustering algorithm to exploit the potential of these models in small object detection. The performance of the modified YOLOV3 and YOLOV4 models were evaluated on a publicly available malaria dataset. These models have achieved state-of-the-art accuracy by exceeding performance of their original versions, Faster R-CNN, and SSD in terms of mean average precision (mAP), recall, precision, F1 score, and average IOU. YOLOV4-MOD has achieved the best detection accuracy among all the other models with a mAP of 96.32%. YOLOV3-MOD2 and YOLOV3-MOD1 have achieved mAP of 96.14% and 95.46%, respectively. Conclusions The experimental results of this study demonstrate that performance of modified YOLOV3 and YOLOV4 models are highly promising for detecting malaria parasites from images captured by a smartphone camera over the microscope eyepiece. The proposed system is suitable for deployment in low-resource setting areas.

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Genome sequence, transcriptome, and annotation of rodent malaria parasite Plasmodium yoelii nigeriensis N67

BMC Genomics ◽

10.1186/s12864-021-07555-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Cui Zhang ◽

Cihan Oguz ◽

Sue Huse ◽

Lu Xia ◽

Jian Wu ◽

...

Keyword(s):

Dna Sequences ◽

Malaria Parasite ◽

Vaccine Development ◽

De Novo ◽

Gene Families ◽

Plasmodium Yoelii ◽

Control Measures ◽

Effective Control ◽

Malaria Parasites ◽

Rodent Malaria

Abstract Background Rodent malaria parasites are important models for studying host-malaria parasite interactions such as host immune response, mechanisms of parasite evasion of host killing, and vaccine development. One of the rodent malaria parasites is Plasmodium yoelii, and multiple P. yoelii strains or subspecies that cause different disease phenotypes have been widely employed in various studies. The genomes and transcriptomes of several P. yoelii strains have been analyzed and annotated, including the lethal strains of P. y. yoelii YM (or 17XL) and non-lethal strains of P. y. yoelii 17XNL/17X. Genomic DNA sequences and cDNA reads from another subspecies P. y. nigeriensis N67 have been reported for studies of genetic polymorphisms and parasite response to drugs, but its genome has not been assembled and annotated. Results We performed genome sequencing of the N67 parasite using the PacBio long-read sequencing technology, de novo assembled its genome and transcriptome, and predicted 5383 genes with high overall annotation quality. Comparison of the annotated genome of the N67 parasite with those of YM and 17X parasites revealed a set of genes with N67-specific orthology, expansion of gene families, particularly the homologs of the Plasmodium chabaudi erythrocyte membrane antigen, large numbers of SNPs and indels, and proteins predicted to interact with host immune responses based on their functional domains. Conclusions The genomes of N67 and 17X parasites are highly diverse, having approximately one polymorphic site per 50 base pairs of DNA. The annotated N67 genome and transcriptome provide searchable databases for fast retrieval of genes and proteins, which will greatly facilitate our efforts in studying the parasite biology and gene function and in developing effective control measures against malaria.

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