Characteristics of Plasmodium vivax-infected erythrocyte rosettes (original) (raw)
Related papers
Rosette formation by Plasmodium vivax
Transactions of the Royal Society of Tropical Medicine and Hygiene, 1995
In contrast to Plasmodium falciparum, infections with P. vivax are seldom fatal. Red blood cells containing mature forms of P. falciparum sequester in the microvasculature of vital organs, and adhere to vascular endothelium (cytoadherence) and to uninfected red cells (rosetting). Rosetting of P. falcipatum has been associated with the lethal syndrome of cerebral malaria. We have studied the rosetting properties of red blood cells infected with P. vivax obtained from adults with acute malaria in Thailand. Of 35 parasite isolates studied, 25 (71%) showed rose&g with a mean proportion of 41% of infected red cells (SD 34%, range 14-100%). Rosetting of P. vivax was related to maturation of the parasite; only cells containing parasites with visible malaria 2 igment rosetted. Rosetting and parasitaemia were not correlated. However, unlike P. falciparum, cells m ected with P. vivan did not adhere to human umbilical vein endothelial cells, to C32 melanoma cells, to platelets, or to purified adhesion receptor molecule CD36. These findings suggest that thrombocytopenia in vivax malaria is not related to platelet-red cell attachment, and that rosetting alone is insufficient to cause the syndrome of cerebral malaria.
Rosette formation of Plasmodium falciparum-infected erythrocytes from patients with acute malaria
Infection and Immunity
Noninfected erythrocytes form rosettes around those infected with trophozoites and schizonts of Plasmodium falciparum in vitro. These rosettes are thought to contribute to the microvascular obstruction which underlies the pathophysiology of severe falciparum malaria. To determine whether the percentage of infected erythrocytes forming rosettes for a parasite isolate in vitro correlates with the in vivo severity of disease, we studied the rosette formation behavior of 35 isolates of P. falciparum from patients with uncomplicated, severe, and cerebral malaria. There was a wide variation in the degree of rosette formation (0 to 53%). Four parasite isolates formed rosettes well (30 to 53%), and seven isolates formed rosettes poorly or not at all (0 to 5%), while the majority of the isolates formed rosettes to various degrees between these two extremes. In this relatively small sample of patients, we were unable to demonstrate a significant association between in vitro rosette formation and patients with cerebral malaria or conscious patients with significant renal (serum creatinine >200 ,umol/liter) or hepatic dysfunction (serum bilirubin >50 ,mol/liter and aspartate aminotransferase >50 Reitman-Frankel units). However, there was an inverse relationship between rosette formation and cytoadherence (r = -0.575, P < 0.01) which could not be explained on the basis of steric hindrance. This finding suggests that cytoadherence and rosette formation properties are intrinsic to the parasites, with isolates having a greater propensity for one or the other bqt not both. Further studies are required to establish the occurrence and pathophysiological role of rosette formation in vivo.
Rosetting Responses of Plasmodium-infected Erythrocytes to Antimalarials
The American Journal of Tropical Medicine and Hygiene
ABSTRACT. In malaria, rosetting is a phenomenon involving the cytoadherence of uninfected erythrocytes to infected erythrocytes (IRBC) harboring the late erythrocytic stage of Plasmodium spp. Recently, artesunate-stimulated rosetting has been demonstrated to confer a survival advantage to P. falciparum late-stage IRBC. This study investigated the rosetting response of P. falciparum and P. vivax clinical isolates to ex vivo antimalarial treatments. Brief exposure of IRBC to chloroquine, mefloquine, amodiaquine, quinine, and lumefantrine increased the rosetting rates of P. falciparum and P. vivax. Furthermore, the ex vivo combination of artesunate with mefloquine and piperaquine also resulted in increased the rosetting rates. Drug-mediated rosette-stimulation has important implications for the therapeutic failure of rapidly cleared drugs such as artesunate. However, further work is needed to establish the ramifications of increased rosetting rates by drugs with longer half-lifves, suc...
The role of rosette formation in pathogenesis of vivax malaria / Lee Wenn Chyau
2014
Rosette formation is one of the unique biological phenomena that have been linked to pathobiology of malaria. It is believe to be associated with the severe outcomes of falciparum malaria. Most of the knowledge about rosetting is obtained from in-depth studies conducted on Plasmodium falciparum. However, the rosetting phenomenon and pathobiology of vivax malaria is not well studied. This research project aimed at deciphering the unknown aspects behind rosetting phenomenon of P. vivax, and investigating the role of rosette formation in pathobiology of vivax malaria. In total, 121 fresh P. vivax isolates, 48 cryopreserved P. vivax isolates, 122 fresh P. falciparum isolates and 5 cryopreserved P. falciparum isolates were recruited into this research project. A novel technique suitable for reticulocyte characterization and rosetting assay in field setting was developed from this research project. Based on the field studies conducted, rosette formation is common in P. vivax. However, rosetting is not significantly correlated to clinical parameters such as reticulocyte count and parasitaemia. Besides, cryopreservation and thawing processes affect the rosetting capability of P. vivax isolates. Rosette formation was found to be initiated at the early trophozoite stage of P. vivax and the rosetting development reached plateau at the end of the erythrocytic maturation. Giant rosettes were found more frequently in P. vivax than P. falciparum. In addition, gametocytes were found to be involved in rosette formation. Unlike P. falciparum, the rosetting phenomenon of P. vivax is independent of human ABO blood groups and complement receptor 1 (CR1/CD35). However, rosetting phenomena of P. vivax and P. falciparum are dependent on the BRIC4 region of human glycophorin C (CD236R), strongly indicating the BRIC4 region of CD236R as another rosetting coreceptor for P. vivax and P. falciparum. On elucidating the roles of rosette formation in pathobiology of malaria, the significantly high preference for normocytes instead of reticulocytes in rosette formation clearly shows that rosetting is iii unlikely to assist merozoite reinvasion in vivax malaria. Furthermore, increased rosetting rates upon exposure to anti-malaria drug compounds and human white blood cells suggest that the rosetting phenomenon may serve as an intrinsic protective mechanism of the malaria parasites against their environmental threats. iv ABSTRAK Pembentukan rosette merupakan salah satu fenomena biologikal yang telah dikaitkan dengan patobiologi malaria. Fenomena ini dipercayai berkaitan dengan keparahan penyakit malaria. Kebanyakan ilmu pengetahuan tentang pembentukan rosette telah diperoleh dari kajian-kajian yang mendalam terhadap Plasmodium falciparum. Namun demikian, fenomena pembentukan rosette and patobiologi vivax malaria kurang dikaji and diketahui. Project ini berobjektif untuk menyiasat soal-soal tentang pembentukan rosette oleh P. vivax, dan peranan yang dimain oleh rosette dalam patobiologi vivax malaria. Secare keseluruhannya, 121 sampel segar P. vivax, 48 sampel pepbekuan awet P. vivax, 122 sampel segar P. falciparum dan 5 sampel pembekuan awet P. falciparum telah digunakan dalam projek kajian ini. Sebuah teknik baru untuk pengiraan korpuskal merah muda (reticulocyte) dan eksperimen rosette yang sesuai digunakan dalam kerja lapangan telah dihasilkan menerusi projek ini. Berdasarkan projek ini, fenomena pembentukan rosette adalah biasa di kalangan P. vivax. Namun begitu, pembentukan rosette tidak berkaitan langsung dengan parameter klinikal seperti kiraan reticulocyte and parasitemia. Selain itu, proses pembekuan awet and pemanasan sel menjejaskan keupayaan P. vivax untuk membentuk rosette. Kejadian pembentukan rosette bermula pada tahap trophozoite awal dan berkembang sehingga mencecah tahap tepu pada tahap akhir proses permatangan dalam darah. Rosette gergasi telah ditemui dengan lebih banyak di P. vivax berbanding dengan P. falciparum. Selain itu, gametocyte juga terlibat dengan proses pembentukan rosette ini. P. vivax didapati berbeza dengan P. falciparum di mana pembentukan rosettenya tidak bergantung pada kumpulan ABO darah manusia dan reseptor complement 1 (CR1/CD35). Pembentukan rosette P. vivax dan P. falciparum didapati bergantung pada bahagian BRIC4 glycophorin C manusia (CD236R). Dengan ini, bahagian CD236R dipercayai memainkan peranan penting sebagai satu lagi reseptor sampingan pembentukan rosette untuk P. falciparum dan P. v vivax. Bagi kajian mencari peranan rosette dalam malaria, adalah didapti bahawa korpuskal merah dewasa (normocytes) lebih dipilih untuk pembentukan rosette berbanding dengan reticulocyte. Dengan ini, jelaslah bahawa pembentukan rosette tidak membantu penjangkitan baru merozoite P. vivax. Lebih-lebih lagi, peningkatan tahap pembentukan rosette semasa pertembungan dengan ubat anti-malaria dan korpuskal putih manusia mencadangkan bahawa pembentukan rosette merupakan satu tindakan pertahanan diri oleh parasite daripada unsur-unsur merbahaya di keliling mereka. vi ACKNOWLEDGEMENTS After two and a half years of learning and studying, with so many fieldtrips and travelling, coupled with countless challenges, falls and obstacles, finally, this work is approaching its finishing line. This project would never be successfully accomplished without the help, guidance and support from various people, whom I ought to acknowledge and express my gratitude. Firstly, the project would never be initiated without the effort, supervision, support and assistance provided by my supervisors, Assoc. Prof. Dr. Lau Yee Ling and Prof. Dr. Fong Mun Yik. Their motivating advises and encouragement had driven me to take on this project and endure the challenges. I am so grateful to have them supporting me, guiding me and helping me throughout this journey. Without them, this PhD project would be unbelievably difficult, if not impossible. Thank you for your help, support and trust. I would like to express my gratitude to my foreigner advisors, Prof. Dr. Laurent Rénia and Asst. Prof. Dr. Bruce Russell for their guidance and supervision during the course of this research project. Many thanks to them for offering such an interesting research topic and encouraging me to take on this particular research project that was deemed "weird" and "too challenging for a PhD student" by many parties at the very first place. Without their guidance, the work and goals in this project would never be accomplished and I would never have the opportunity to learn, see and experience so much in the field of medical sciences. Thanks for taking me under your wings, and many thanks to the knowledge, advises, experience and of course inspiring and downright funny stories that you guys shared with me, and thank you for offering me this wonderful opportunity to learn with you. Once again, to these four incredible scientists from different parts of the world: A very big thank you! vii I am grateful to have the opportunity to visit and work with the staff in Shoklo Malaria Research Unit, Mae Sot, Thailand. I am grateful to Prof. Dr. Francois Nosten, the director of the institute, for his warm welcome whenever I visited the institute. Thank you for providing me the space and opportunity to conduct my experiments. And of course, to all the staff of SMRU, especially Madam Kanlaya Sriprawat (P'Poo), Mr.
Blood, 1990
To understand the molecular mechanisms that lead to sequestration of red blood cells infected with mature stages of Plasmodium falciparum and to examine the relevance of earlier studies on adherence properties of laboratory-derived P falciparum parasites to the natural parasite population, we analyzed Gambian and Tanzanian isolates for in vitro cytoadherence and antibody-mediated microagglutination. Eighteen cryopreserved isolates of ring-stage parasites were cultured for 20 to 30 hours in vitro, in the patients original erythrocytes, to the trophozoite and schizont stage. All parasites were positive in the microagglutination assay with at least one of four African hyperimmune sera. In a rosetting assay, only 2 of the 18 isolates were strongly positive (35% and 41% of parasitized erythrocytes with more than two uninfected cells bound). Thirteen isolates showed either intermediate (5% to 18%) or low (less than 5%) rosetting while three isolates did not form rosettes. Infected cell-bi...
Rosetting in Plasmodium vivax: A Cytoadhesion Phenotype Associated with Anaemia
PLoS Neglected Tropical Diseases, 2013
Background: Plasmodium vivax can potentially lead to life-threatening episodes but the mechanisms underlying severe disease remain poorly defined. Cytoadhesion of infected erythrocytes may contribute to P. vivax sequestration and organ injury although its physiological impact is still unknown. Here, we aimed to describe clinically-relevant cytoadhesive phenotypes of P. vivax isolates.
Rosettes integrity protects Plasmodium vivax of being phagocytized
Scientific Reports
Plasmodium vivax is the most prevalent cause of malaria outside of Africa. P. vivax biology and pathogenesis are still poorly understood. The role of one highly occurring phenotype in particular where infected reticulocytes cytoadhere to noninfected normocytes, forming rosettes, remains unknown. Here, using a range of ex vivo approaches, we showed that P. vivax rosetting rates were enhanced by plasma of infected patients and that total immunoglobulin M levels correlated with rosetting frequency. Moreover, rosetting rates were also correlated with parasitemia, IL-6 and IL-10 levels in infected patients. Transcriptomic analysis of peripheral leukocytes from P. vivax-infected patients with low or moderated rosetting rates identified differentially expressed genes related to human host phagocytosis pathway. In addition, phagocytosis assay showed that rosetting parasites were less phagocyted. Collectively, these results showed that rosette formation plays a role in host immune response b...
HEMATOLOGICAL CHANGES IN P.FALCIPARUM & P.VIVAX MALARIA
National Journal of Medical Research, 2013
Introduction: Malaria continues to be a great health problem in some of the most populated areas of the world & continues to cause significant morbidity and mortality worldwide. The hematological abnormalities that have been reported to consistently with malaria are anemia, thrombocytopenia, atypical lymphocytosis and infrequently disseminated intravascular coagulation. Methodology: This cross sectional study was conducted in central hospital laboratory of a tertiary care hospital of Surat, Gujarat. The laboratory confirmed cases of malaria from August to October, 2012 were included in the study. Hematological profile of different spices of malaria was compared. Results: The difference in mean platelet count according to severity of infection was highly statistically significant according to ANOVA test both for P.Vivax and P.Falciparum. Platelet counts show decreasing trend according to severity of infection. Difference in the mean haemoglobin level and mean platelet counts of P.Vivax cases and P.Falciparum cases was also statistically significant. Conclusion: The low level of platelet can be used as predictor of severity of the infection. And thus, prediction of the hematological changes enables the clinician to establish an effective and early therapeutic intervention in order to prevent the occurrence of major complications.