A quantitative analysis of the microvascular sequestration of malaria parasites in the human brain.
Kamolrat Silamut,Nguyen Hoan Phu,Christopher J. M. Whitty,Gareth D. H. Turner,Karina Louwrier,Nguyen Thi Hoang Mai,Julie A. Simpson,Julie A. Simpson,Tran Tinh Hien,Nicholas J. White +9 more
Reads0
Chats0
TLDR
Antimalarial treatment arrests development at the trophozoite stages which remain sequestered in the brain, indicating that the adhesion characteristics of cerebrovascular endothelium change asynchronously during malaria and also that significant recirculation of parasitized erythrocytes following sequestration is unlikely.Abstract:
Microvascular sequestration was assessed in the brains of 50 Thai and Vietnamese patients who died from severe malaria (Plasmodium falciparum, 49; P. vivax, 1). Malaria parasites were sequestered in 46 cases; in 3 intravascular malaria pigment but no parasites were evident; and in the P. vivax case there was no sequestration. Cerebrovascular endothelial expression of the putative cytoadherence receptors ICAM-1, VCAM-1, E-selectin, and chondroitin sulfate and also HLA class II was increased. The median (range) ratio of cerebral to peripheral blood parasitemia was 40 (1.8 to 1500). Within the same brain different vessels had discrete but different populations of parasites, indicating that the adhesion characteristics of cerebrovascular endothelium change asynchronously during malaria and also that significant recirculation of parasitized erythrocytes following sequestration is unlikely. The median (range) ratio of schizonts to trophozoites (0.15:1; 0.0 to 11.7) was significantly lower than predicted from the parasite life cycle (P < 0.001). Antimalarial treatment arrests development at the trophozoite stages which remain sequestered in the brain. There were significantly more ring form parasites (age < 26 hours) in the cerebral microvasculature (median range: 19%; 0-90%) than expected from free mixing of these cells in the systemic circulation (median range ring parasitemia: 1.8%; 0-36.2%). All developmental stages of P. falciparum are sequestered in the brain in severe malaria.read more
Citations
More filters
Journal ArticleDOI
Artemisinin Resistance in Plasmodium falciparum Malaria
Arjen M. Dondorp,François Nosten,Poravuth Yi,Debashish Das,Aung Phae Phyo,Joel Tarning,Khin Maung Lwin,Frédéric Ariey,Warunee Hanpithakpong,Sue J. Lee,Pascal Ringwald,Kamolrat Silamut,Mallika Imwong,Kesinee Chotivanich,Pharath Lim,Trent Herdman,Sen Sam An,Shunmay Yeung,Pratap Singhasivanon,Nicholas P. J. Day,Niklas Lindegardh,Duong Socheat,Nicholas J. White +22 more
TL;DR: The overall median clearance times were 84 hours (interquartile range, 60 to 96) in Pailin and 48 hours in Wang Pha (P<0.001) in each of the two locations as discussed by the authors.
Journal ArticleDOI
Pathogenesis, clinical features, and neurological outcome of cerebral malaria.
TL;DR: The clinical features and epidemiology of cerebral malaria, including sequestration of infected erythrocytes within cerebral blood vessels, are described and recent insights provided by ex-vivo work on sequestration and examination of pathological specimens are highlighted.
Journal ArticleDOI
Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2
Arjen M. Dondorp,Varunee Desakorn,Wirichada Pongtavornpinyo,Duangjai Sahassananda,Kamolrat Silamut,Kesinee Chotivanich,Paul N. Newton,Paul N. Newton,Punnee Pitisuttithum,A. M Smithyman,Nicholas J. White,Nicholas J. White,Nicholas P. J. Day,Nicholas P. J. Day +13 more
TL;DR: Plasma PfHRP2 concentrations may be used to estimate the total body parasite biomass in acute falciparum malaria, and suggested that admission to hospital with uncomplicated malaria often follows schizogony—but in severe malaria is unrelated to stage of parasite development.
Journal ArticleDOI
The sick placenta: The role of malaria
Bernard J. Brabin,Bernard J. Brabin,Cleofé Romagosa,S. Abdelgalil,Clara Menendez,Francine H. Verhoeff,Rose McGready,Rose McGready,K. A. Fletcher,Stephen Owens,Umberto D'Alessandro,François Nosten,François Nosten,P. R. Fischer,Jaume Ordi +14 more
TL;DR: The review attempts to bring together local events at the maternal-fetal interface which encompass immunological and pathological processes which relate to the epidemiological pattern of malaria in pregnancy in areas of both high and low malaria transmission.
Journal ArticleDOI
Clinical features and pathogenesis of severe malaria
TL;DR: A major change in recent years has been the recognition that severe malaria is a complex multi-system disorder presenting with a range of clinical features, creating challenges both for elucidating key mechanisms of disease and for identifying suitable targets for adjunctive therapy.
References
More filters
Journal ArticleDOI
The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of plasmodium falciparum-infected erythrocytes
Xin-zhuan Su,Virginia M. Heatwole,Samuel P. Wertheimer,Frangoise Guinet,Jacqueline A. Herrfeldt,David S. Peterson,Jeffrey A. Ravetch,Thomas E. Wellems +7 more
TL;DR: A large and extremely diverse family of P. falciparum genes (var) that encode 200-350 kDa proteins having the expected properties of antigenically variant adhesion molecules are described.
Journal ArticleDOI
Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes
Dror I. Baruch,Britten L. Pasloske,Hardeep B. Singh,Xiahui Bi,Xin C. Ma,Michael Feldman,Theodore F. Taraschi,Russell J. Howard +7 more
TL;DR: The cloning of two related PfEMP1 genes from the Malayan Camp parasite strain are described and the molecular basis for antigenic variation in malaria and adherence of infected erythrocytes to host cells can now be pursued.
Journal ArticleDOI
Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes.
Joseph D. Smith,Chetan E. Chitnis,Alistar G. Craig,David J. Roberts,Diana E. Hudson-Taylor,David S. Peterson,Robert Pinches,Chris I. Newbold,Louis H. Miller +8 more
TL;DR: It is shown that expression of variant antigenic determinants is correlated with expression of individual members of a large, multigene family named var, which is consistent with the involvement of var genes in antigenic variation and binding to endothelium.
Journal Article
Human cerebral malaria. A quantitative ultrastructural analysis of parasitized erythrocyte sequestration.
TL;DR: It is concluded that there is no evidence for an inflammatory or immune pathogenesis for human cerebral malaria and that the clinical effects probably relate to anoxia and the metabolic activities of the parasites.
Journal Article
An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration.
Gareth D. H. Turner,H Morrison,Margaret Jones,T M Davis,Sornchai Looareesuwan,I D Buley,K C Gatter,Chris I. Newbold,S Pukritayakamee,B Nagachinta +9 more
TL;DR: Results suggest that ICAM-1 and CD36 receptors have a role in sequestration in vivo and indicate that systemic endothelial activation is a feature of fatal malaria.