<jats:p>A retrospective analysis was performed of parasite count data recorded from the first 7 days of blood or mosquito transmitted <jats:italic>Plasmodium falciparum</jats:italic> infections given for the treatment of neurosyphilis in the USA before 1963. The objective of this study was to characterize initial growth dynamics before host defences have significant effects on the infecting parasite population. Of the 328 patients' data available for analysis, 83 were excluded because they had received anti-malarial treatment during the first 7 days of the patent infection. Nonlinear mixed effects modelling was performed to estimate the parameters of interest; \u2018parasite multiplication rate per 48\u00a0h\u2019 (PMR), and length of the parasite life-cycle (periodicity). The parasitaemia versus time profiles showed great variability between patients. The mean population estimate of \u2018PMR\u2019 was approximately 8, and was highly dependent on the <jats:italic>P. falciparum</jats:italic> \u2018strain\u2019. PMR also varied significantly between patients with a 90% prediction interval varying from 5\u00b75 to 12\u00b73-fold. Both intrinsic parasite multiplication rate (an intrinsic virulence determinant), and host susceptibility and defence contribute to expansion of the parasite biomass and thus disease severity in falciparum malaria.</jats:p>
\n \n\n \n \n1. Eight healthy Thai males, aged 19-27 years, received quinine or quinidine dihydrochloride 10 mg kg-1 body weight by intravenous infusion over 1 h. At least 1 week later, the alternative alkaloid was administered. 2. The terminal elimination half-time of quinidine was shorter than that of quinine (median [range]; 5.7 [5.0-10.0] vs 9.9 [8.8-15.1] h, P < 0.01), the volume of distribution at steady state (Vss) for quinidine was larger than that for quinine (3.5 [2.5-5.6] vs 3.1 [1.8-4.1] 1 kg-1; P = 0.02) and quinidine was less bound to plasma proteins (% free drug: 22.8 [15.4-47.2] vs 9.4 [7.3-15.0]%, P < 0.01). Total clearance was greater for quinidine (7.7 [3.9-11.4] vs 3.4 [1.8-4.6] ml min-1 kg-1, P < 0.01) but not for clearance of unbound drug (32.2 [14.6-50.4] vs 29.9 [20.2-50.9] ml min-1 kg-1 respectively, P > 0.2). 3. Side-effects, including transient hypotension after quinidine in two cases, were mild. 4. Both drugs produced prolongation of the rate-corrected QT interval (QTc), with similar rates of elimination from the cardiac conduction 'effect' compartment (keo; 4.14 [0.03-15.33] h-1 for quinine, 3.74 [1.63-13.14] h-1 for quinidine, P > 0.19). Using a linear concentration-response model, the intercept ('threshold') for quinidine effect was lower than that for quinine (P = 0.004) but the slopes (change in QTc for a given change in free drug concentration) were similar (P = 0.56).(ABSTRACT TRUNCATED AT 250 WORDS)
\n \n\n \n \nThe relationship between platelet counts and platelet bound (direct) or platelet directed (indirect) serum antibody concentrations was studied in 17 patients with Plasmodium falciparum malaria and 12 patients with P. vivax malaria. Platelet counts rose with recovery from infection from 196 +/- 84 x 10(9)/l (mean +/- SD) and 195 +/- 34 x 10(9)/l to 319 +/- 99 and 283 +/- 62 x 10(9)/l respectively (p less than 0.002), but there was no relationship between either absolute platelet count or changes in counts and either indirect or direct platelet antibody levels. These findings suggest that a non-immunologically mediated mechanism is involved in the pathogenesis of thrombocytopenia in malaria.
\n \n\n \n \nTo determine whether isolates of Plasmodium falciparum have intrinsically different cytoadherent properties and whether these differences contribute to the clinical severity of human falciparum malaria, we studied the cytoadherence to C32 melanoma cells in vitro of 59 parasite isolates from patients with naturally acquired infections in Thailand. Parasitized erythrocytes adhere to these melanoma cells principally via the glycoprotein CD36, which is also expressed on most vascular endothelium. In vitro cytoadherence was significantly greater for isolates from patients with biochemical evidence of severe malaria. The cytoadherent properties of P. falciparum parasites may thus be a virulence factor in human falciparum malaria. However, there was no correlation between the degree of in vitro cytoadherence and cerebral symptoms, which suggests that other receptors and/or host factors may be important in the adherence of malaria parasites to cerebral vascular endothelium. The cytokines tumor necrosis factor, interleukin-1, and gamma interferon, which have been implicated in the pathogenesis of cerebral malaria and are known to promote intercellular adhesion in other systems, did not enhance the cytoadherence of P. falciparum isolates to C32 melanoma cells.
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