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Title: Pathophysiological aspects of severe falciparum malaria in Thailand and Ghana
Author: Angus, Brian John
ISNI:       0000 0001 3424 7659
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2001
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The mechanisms of parasite clearance in falciparum malaria are still unclear but the spleen is considered to be the major site of parasite removal. The process of removing intraerythrocytic parasites leaving the host erythrocyte intact is termed "pitting". We have investigated several possible mechanisms for parasite clearance. Using monoclonal antibodies to Ring Erythrocyte Surface antigen, (RESA or Pf 155) an early antigen expressed on the erythrocyte surface and staining for intraerythrocytic plasmodial DNA we have demonstrated that removal of intracellular parasites by host phagocytes leaving the erythrocyte intact, occurs in vivo. During acute falciparum malaria infection, red blood cells (RBC) containing abundant RESA, but no intracellular parasites, are present in the circulation. These RESA-positive parasite-negative RBC are not seen in parasite cultures in vitro. This indicates that in acute falciparum malaria there is active removal of intra-erythrocytic parasites by a host mechanism in vivo (probably the spleen) without destruction of the parasitized RBC. The ability of parasites to form rosettes has been considered a marker of pathogenicity in malaria and those parasites with a greater potential for this phenomenon were considered inherently more pathogenic. We have reported rosetting in a Thai patient with Plasmodium ovale infection suggesting that rosetting is in fact a common property of all plasmodia. Using a laser diffraction technique, we measured red blood cell (RBC) deformability over a range of shear stresses and related this to the severity of anemia in 36 adults with severe falciparum malaria. The RBC deformability at a high shear stress of 30 Pa, similar to that encountered in the splenic sinusoids, showed a significant positive correlation with the nadir hemoglobin concentration during hospitalization (r = 0.49, P < 0.002). Reduction in RBC deformability resulted mainly from changes in non-parasitised erythrocytes. Since reduced red blood cell deformability (RBC-D) can also contribute to impaired microcirculatory flow, RBC-D was measured and compared in 23 patients with severe falciparum malaria (seven of whom subsequently died), 30 patients with uncomplicated malaria, and 17 healthy controls. The RBC-D was significantly reduced in severe malaria and was particularly low in all fatal cases. At a low shear stress of 1.7 Pascal (Pa), a red blood cell elongation index less than 0.21 on admission to the hospital predicted fatal outcome with a sensitivity of 100% (confidence interval [Cl] 59 - 100%) and a specificity of 88% (Cl = 61 - 98%). The reduction in the RBC- D appeared to result mainly from changes in unparasitized erythrocytes. This finding may provide a rationale for the use of exchange transfusion in severe malaria since this process will replace rigid cells with more deformable cells.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Parasite removal; Clearance; Pathogenic