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Malaria Patients (malaria + patient)
Selected AbstractsA glimpse into the clinical proteome of human malaria parasites Plasmodium falciparum and Plasmodium vivaxPROTEOMICS - CLINICAL APPLICATIONS, Issue 11 2009Pragyan Acharya Abstract Malaria causes a worldwide annual mortality of about a million people. Rapidly evolving drug-resistant species of the parasite have created a pressing need for the identification of new drug targets and vaccine candidates. By developing fractionation protocols to enrich parasites from low-parasitemia patient samples, we have carried out the first ever proteomics analysis of clinical isolates of early stages of Plasmodium falciparum (Pf) and P. vivax. Patient-derived malarial parasites were directly processed and analyzed using shotgun proteomics approach using high-sensitivity MS for protein identification. Our study revealed about 100 parasite-coded gene products that included many known drug targets such as Pf hypoxanthine guanine phosphoribosyl transferase, Pf L -lactate dehydrogenase, and Plasmepsins. In addition, our study reports the expression of several parasite proteins in clinical ring stages that have never been reported in the ring stages of the laboratory-cultivated parasite strain. This proof-of-principle study represents a noteworthy step forward in our understanding of pathways elaborated by the parasite within the malaria patient and will pave the way towards identification of new drug and vaccine targets that can aid malaria therapy. [source] Ursodeoxycholic acid and artesunate in the treatment of severe falciparum malaria patients with jaundiceJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2010Sombat Treeprasertsuk Abstract Background and Aims:,Plasmodium falciparum (PF) infection can lead to severe complications. Ursodeoxycholic acid (UDCA) is increasingly used for the treatment of cholestatic liver diseases. The present study aims to determine the effects of combined UDCA and artesunate compared to placebo and artesunate on the improvement of liver tests in severe PF jaundiced patients. Methods:, All severe PF jaundiced patients, aged , 15 years and diagnosed as having severe malaria according to WHO 2000 criteria, were enrolled. Patients with evidence of biliary obstruction, other cholestatic liver diseases and those who were pregnant were excluded. Patients were randomized to receive either oral UDCA or placebo for 2 weeks in additional to artesunate. All patients were admitted for at least 14 days to monitor the result of the treatment. Results:, Seventy-four severe PF malaria patients with jaundice were enrolled. Both groups had similar demographic and laboratory tests, with the exception being more males in the UDCA group than in the placebo group (P = 0.04). The median of percentage change of total bilirubin and aminotransferase levels at the end of weeks 1, 2, 3 and 4 showed no difference between the two groups. Only the median of percentage change of alkaline phosphatase at the end of week one compared with the baseline values showed less increment in the UDCA group than in the placebo group (P = 0.04). No serious adverse events were seen during the 4 weeks of follow up. Conclusions:, In severe PF malaria patients with jaundice, combined therapy with UDCA and artesunate is safe, but does not significantly improve liver tests compared to placebo and artesunate. [source] Predicting mortality in patients with malarial acute renal failureNEPHROLOGY, Issue 1-2 2000Eli K Westerlund SUMMARY: Acute Physiology and Chronic Health Evaluation (APACHE) III scores, calculated within the first 24 h of admission, were analysed in 108 patients with acute renal failure due to falciparum malaria who were admitted to Bangkok Hospital for Tropical Diseases, Thailand. Twelve (11.1%) patients died. The mean APACHE III score was 82.0 ± 25.5 (range, 45,171). There was a close relation between the APACHE III score and the hospital mortality rate. The non-survivors had significantly higher APACHE III scores than the survivors, 109.8 ± 36.7 and 75.7 ± 21.6, respectively (P < 0.001). Patients with APACHE III score , 82 had a 4.2-fold higher risk of dying compared with patients with a lower score (95% CI 1.2,14.7; P = 0.013). Haemodialysis treatment was performed in 97 (89.8%) of the patients. The mean APACHE III score for patients who were not treated with haemodialysis (95.9 ± 38.0) was not significantly higher than those who received haemodialysis (80.4 ± 23.5; P > 0.05), but the former had a 4.4-times higher risk of dying compared with those dialysed (95% CI 1.6,12.3; P = 0.019). Using the APACHE III score and its ability to predict death, we calculated its sensitivity, specificity and accuracy to be 0.92, 0.31 and 0.41, respectively, at a cut-off score of 67 points. The area under the receiver operating characteristic (ROC) curve was 0.75. The APACHE III scoring system correlated well with the outcome of critically ill malaria patients with acute renal failure, although it was not possible to identify individual survivors or non-survivors. APACHE III should not be used for individual prognosis or treatment decisions. [source] Cellular stress and injury responses in the brains of adult Vietnamese patients with fatal Plasmodium falciparum malariaNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2001I. M. Medana Immunohistochemical techniques have been used to investigate specific patterns of potentially reversible cellular injury, DNA damage, and apoptosis in the brainstems of Vietnamese patients who died of severe Plasmodium falciparum malaria. The degree and pattern of neuronal and glial stress responses were compared between patients with cerebral and non-cerebral malaria (CM), and appropriate non-malaria infected controls. The following markers were examined: (i) heat shock protein 70 (HSP70), for reversible injury; (ii) heme oxygenase-1, for oxidative stress; (iii & iv) two DNA-repair proteins, poly(ADP) ribose polymerase (PARP) and DNA-dependent protein kinase catalytic subunit; (v) poly(ADP) ribose, an end-product of PARP activity; and (vi) caspase-3-active, for apoptosis. Stress responses were found in a range of cell types as reflected by the widespread expression of HSP70. Oxidative stress predominated in the vicinity of vessels and haemorrhages. Some degree of DNA damage was found in the majority of malaria patients, but the distribution and frequency of the damage was much less than that observed in controls with irreversible neuronal injury. Similarly, caspase-3-active expression, as a measure of apoptosis, was no higher in the majority of malaria patients than the negative control cases, although 40% of CM cases expressed caspase-3-active in a small number of neurones of the pontine nuclei or within swollen axons of the pontocerebellar and corticospinal tracts. In conclusion, cells within the brainstem of all patients who died from severe malaria showed staining patterns indicative of considerable stress response and reversible neuronal injury. There was no evidence for a specific pattern of widespread irreversible cell damage in those patients with cerebral malaria. [source] Antigenic cross-reactivity between different alleles of the Plasmodium falciparum merozoite surface protein 2PARASITE IMMUNOLOGY, Issue 11-12 2003Ingrid Felger SUMMARY The polymorphic domain of the gene encoding Plasmodium falciparum merozoite surface protein 2 (MSP2) was PCR amplified from blood of malaria patients, genotyped, and 19 distinct fragments were cloned and expressed in E. coli. The reactivity of naturally occurring antibodies against this panel of recombinant MSP2 antigens was tested using 67 homologous or heterologous sera from a serum bank of travel clinic patients. Sera from semi-immune individuals strongly recognized almost all recombinant antigens. Sera from primary infected patients either did not react at all (9 sera), or reacted weakly against varying numbers of antigens (39 sera). The antigens that showed reactions were mostly of the allelic family corresponding to the infecting clone, but in very few cases also of the alternative allelic family. Single clone infections and repeated samples from the same individual were analysed in greater detail. Thus, we were able to quantify cross-reactivity induced by a single P. falciparum infection. Within the two allelic families of MSP2, cross-reactivity was observed between some but not all alleles of the same family, whereas antibodies cross-reactive between variants belonging to different allelic families were detected in only a few cases. [source] | ||||||||||