9 results on '"Lu, Chan"'
Search Results
2. Susceptibility of human Plasmodium knowlesi infections to anti-malarials
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Mohammed Atique Ahmed, Lu Chan Woon, Erica M. Pasini, Balbir Singh, Clemens H. M. Kocken, Janet Cox-Singh, Sanjeev Krishna, Henry M. Staines, Angela Siner, Farrah A Fatih, University of St Andrews. School of Medicine, University of St Andrews. Infection Group, and University of St Andrews. Biomedical Sciences Research Complex
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Erythrocytes ,Plasmodium vivax ,Artesunate ,Plasmodium ,In-vitro ,0302 clinical medicine ,Sensitivity ,Parasitic Sensitivity Tests ,Chloroquine ,Borneo ,Zoonoses ,Vivax malaria ,Artemether ,Sabah ,0303 health sciences ,Mefloquine ,Mefloquine resistance ,Artemisinins ,3. Good health ,DHA ,Infectious Diseases ,Dihydroartemisinin ,Plasmodium knowlesi ,Artemisinin ,QR355 Virology ,medicine.drug ,Falciparum ,030231 tropical medicine ,Plasmodium falciparum ,Biology ,03 medical and health sciences ,Antimalarials ,SDG 3 - Good Health and Well-being ,parasitic diseases ,medicine ,PFMDR1 gene ,Animals ,Humans ,Adaptation ,QR355 ,030306 microbiology ,Research ,fungi ,Malaysia ,biology.organism_classification ,medicine.disease ,Virology ,Malaria ,Parasitology - Abstract
This study was funded by the Medical Research Council (MRC) UK; Grant number G0801971 and the European Community’s Seventh Framework Programme (FP7/2007-2013), EVIMALAR network of Excellence under grant agreement N° 242095 and NANOMAL under grant agreement N° 304948 Background: Evidence suggests that Plasmodium knowlesi malaria in Sarawak, Malaysian Borneo remains zoonotic, meaning anti-malarial drug resistance is unlikely to have developed in the absence of drug selection pressure. Therefore, adequate response to available anti-malarial treatments is assumed. Methods: Here the ex vivo sensitivity of human P. knowlesi isolates in Malaysian Borneo were studied, using a WHO schizont maturation assay modified to accommodate the quotidian life cycle of this parasite. The in vitro sensitivities of P. knowlesi H strain adapted from a primate infection to in vitro culture (by measuring the production of Plasmodium lactate dehydrogenase) were also examined together with some assays using Plasmodium falciparum and Plasmodium vivax. Results: Plasmodium knowlesi is uniformly highly sensitive to artemisinins, variably and moderately sensitive to chloroquine, and less sensitive to mefloquine. Conclusions: Taken together with reports of clinical failures when P. knowlesi is treated with mefloquine, the data suggest that caution is required if using mefloquine in prevention or treatment of P. knowlesi infections, until further studies are undertaken. Publisher PDF
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- 2013
3. Cytoadherence and virulence - the case of Plasmodium knowlesi malaria
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Alister Craig, Angela Siner, Balbir Singh, Farrah A Fatih, Janet Cox-Singh, Atique Ahmed, Sanjeev Krishna, Lu Chan Woon, University of St Andrews. School of Medicine, University of St Andrews. Infection Group, and University of St Andrews. Biomedical Sciences Research Complex
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CD36 Antigens ,Male ,Erythrocytes ,CD36 ,SICAvar ,0302 clinical medicine ,VCAM ,Coma ,Cells, Cultured ,0303 health sciences ,ICAM-1 ,Virulence ,biology ,wh_150 ,Middle Aged ,Intercellular Adhesion Molecule-1 ,Recombinant Proteins ,3. Good health ,Infectious Diseases ,medicine.anatomical_structure ,RB Pathology ,Plasmodium knowlesi ,Female ,Protein Binding ,Adult ,lcsh:Arctic medicine. Tropical medicine ,Adolescent ,Endothelium ,lcsh:RC955-962 ,Schizonts ,030231 tropical medicine ,Vascular Cell Adhesion Molecule-1 ,lcsh:Infectious and parasitic diseases ,P. knowlesi ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Antigen ,parasitic diseases ,Cell Adhesion ,medicine ,Humans ,lcsh:RC109-216 ,Trophozoites ,030304 developmental biology ,Research ,Plasmodium falciparum ,medicine.disease ,biology.organism_classification ,Virology ,Malaria ,wc_750 ,qx_135 ,Cytoadherence ,Erythrocyte Count ,biology.protein ,Parasitology ,Endothelium, Vascular ,RB ,Ex vivo - Abstract
Background Cytoadherence of infected red blood cells to brain endothelium is causally implicated in malarial coma, one of the severe manifestations of falciparum malaria. Cytoadherence is mediated by specific binding of variant parasite antigens, expressed on the surface of infected erythrocytes, to endothelial receptors including, ICAM-1, VCAM and CD36. In fatal cases of severe falciparum malaria with coma, blood vessels in the brain are characteristically congested with infected erythrocytes. Brain sections from a fatal case of knowlesi malaria, but without coma, were similarly congested with infected erythrocytes. The objective of this study was to determine the binding phenotype of Plasmodium knowlesi infected human erythrocytes to recombinant human ICAM-1, VCAM and CD36. Methods Five patients with PCR-confirmed P. knowlesi malaria were recruited into the study with consent between April and August 2010. Pre-treatment venous blood was washed and cultured ex vivo to increase the proportion of schizont-infected erythrocytes. Cultured blood was seeded into Petri dishes with triplicate areas coated with ICAM-1, VCAM and CD36. Following incubation at 37°C for one hour the dishes were washed and the number of infected erythrocytes bound/mm2 to PBS control areas and to recombinant human ICAM-1 VCAM and CD36 coated areas were recorded. Each assay was performed in duplicate. Assay performance was monitored with the Plasmodium falciparum clone HB3. Results Blood samples were cultured ex vivo for up to 14.5 h (mean 11.3 ± 1.9 h) to increase the relative proportion of mature trophozoite and schizont-infected red blood cells to at least 50% (mean 65.8 ± 17.51%). Three (60%) isolates bound significantly to ICAM-1 and VCAM, one (20%) isolate bound to VCAM and none of the five bound significantly to CD36. Conclusions Plasmodium knowlesi infected erythrocytes from human subjects bind in a specific but variable manner to the inducible endothelial receptors ICAM-1 and VCAM. Binding to the constitutively-expressed endothelial receptor CD36 was not detected. Further work will be required to define the pathological consequences of these interactions.
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- 2012
4. Susceptibility of human Plasmodium knowlesi infections to anti-malarials
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Fatih, Farrah A, primary, Staines, Henry M, additional, Siner, Angela, additional, Ahmed, Mohammed Atique, additional, Woon, Lu Chan, additional, Pasini, Erica M, additional, Kocken, Clemens HM, additional, Singh, Balbir, additional, Cox-Singh, Janet, additional, and Krishna, Sanjeev, additional
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- 2013
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5. Laboratory markers of disease severity in Plasmodium knowlesi infection: a case control study
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Willmann, Matthias, primary, Ahmed, Atique, additional, Siner, Angela, additional, Wong, Ing Tien, additional, Woon, Lu Chan, additional, Singh, Balbir, additional, Krishna, Sanjeev, additional, and Cox-Singh, Janet, additional
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- 2012
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6. Laboratory markers of disease severity in Plasmodium knowlesi infection: a case control study
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Sanjeev Krishna, Atique Ahmed, Janet Cox-Singh, Matthias Willmann, Balbir Singh, Angela Siner, Lu Chan Woon, Ing Tien Wong, University of St Andrews. School of Medicine, University of St Andrews. Infection Group, and University of St Andrews. Biomedical Sciences Research Complex
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Male ,Platelet count ,Neutrophils ,Parasitemia ,Parasite load ,Severity of Illness Index ,Parasite Load ,Leukocyte Count ,0302 clinical medicine ,Borneo ,030212 general & internal medicine ,Children ,Parasitaemia ,Containing Leukocytes ,Middle Aged ,Thailand ,3. Good health ,Infectious Diseases ,Plasmodium knowlesi ,Female ,Malaria pigment ,Adult ,Hemeproteins ,medicine.medical_specialty ,lcsh:Arctic medicine. Tropical medicine ,lcsh:RC955-962 ,030231 tropical medicine ,Biology ,R Medicine ,Models, Biological ,lcsh:Infectious and parasitic diseases ,Association ,Haemozoin ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Internal medicine ,Severity of illness ,parasitic diseases ,medicine ,Humans ,lcsh:RC109-216 ,Receiver operating characteristic ,Research ,Odds ratio ,Pigments, Biological ,medicine.disease ,biology.organism_classification ,Severity markers ,Confidence interval ,Malaria ,Case-Control Studies ,Immunology ,Parasitology ,Biomarkers - Abstract
Background Plasmodium knowlesi malaria causes severe disease in up to 10% of cases in Malaysian Borneo and has a mortality rate of 1 - 2%. However, laboratory markers with the ability to identify patients at risk of developing complications have not yet been assessed as they have for other species of Plasmodium. Methods A case control study was undertaken in two hospitals in Sarikei and Sibu, Malaysian Borneo. One hundred and ten patients with uncomplicated (n = 93) and severe (n = 17) P. knowlesi malaria were studied. Standardized pigment-containing neutrophil (PCN) count, parasite density and platelet counts were determined and analysed by logistic regression and receiver operating characteristic (ROC) analysis. Results The PCN count was strongly associated with risk of disease severity. Patients with high parasite density (≥ 35,000/μl) or with thrombocytopaenia (≤ 45,000/μl) were also more likely to develop complications (odds ratio (OR) = 9.93 and OR = 5.27, respectively). The PCN count yielded the highest area under the ROC curve (AUC) estimate among all markers of severity (AUC = 0.8561, 95% confidence interval: 0.7328, 0.9794). However, the difference between all parameter AUC estimates was not statistically significant (Wald test, p = 0.73). Conclusion Counting PCN is labour-intensive and not superior in predicting severity over parasitaemia and platelet counts. Parasite and platelet counts are simpler tests with an acceptable degree of precision. Any adult patient diagnosed with P. knowlesi malaria and having a parasite count ≥35,000/μl or ≥1% or a platelet count ≤45,000/μl can be regarded at risk of developing complications and should be managed according to current WHO guidelines for the treatment of severe malaria.
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- 2012
7. Cytoadherence and virulence - the case of Plasmodium knowlesi malaria
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Fatih, Farrah A, primary, Siner, Angela, additional, Ahmed, Atique, additional, Woon, Lu Chan, additional, Craig, Alister G, additional, Singh, Balbir, additional, Krishna, Sanjeev, additional, and Cox-Singh, Janet, additional
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- 2012
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8. Adaptation of in vitro cytoadherence assay to Plasmodium knowlesi field isolates
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Fatih, Farrah A, primary, Siner, Angela, additional, Ahmed, Atique, additional, Woon, Lu Chan, additional, Craig, Alister, additional, Staines, Henry M, additional, Singh, Balbir, additional, Krishna, Sanjeev, additional, and Cox-Singh, Janet, additional
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- 2010
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9. Adaptation of in vitro cytoadherence assay to Plasmodium knowlesi field isolates
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Alister Craig, Henry M. Staines, Lu Chan Woon, Angela Siner, Atique Ahmed, Sanjeev Krishna, Farrah A Fatih, Janet Cox-Singh, and Balbir Singh
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lcsh:Arctic medicine. Tropical medicine ,lcsh:RC955-962 ,Ligand binding assay ,CD36 ,fungi ,Biology ,biology.organism_classification ,Plasmodium ,Microbiology ,lcsh:Infectious and parasitic diseases ,Agglutination (biology) ,Infectious Diseases ,Antigen ,Plasmodium knowlesi ,parasitic diseases ,Immunology ,biology.protein ,Antigenic variation ,Oral Presentation ,Parasite hosting ,lcsh:RC109-216 ,Parasitology - Abstract
P. knowlesi was the first Plasmodium species in which antigenic variation was observed. Variation was due to schizont infected cell agglutination (SICAvar) antigens expressed by the parasite and transported to the exposed surface of the host erythrocyte [1]. PfEMP1 is P. falciparum’s orthologue of P. knowlesi’s SICA proteins [2]. In P. falciparum PfEMP1 is associated with infected erythrocytes binding to receptors such as ICAM-1 expressed on the endothelial cells of the host microvasculature. Here, we use a static protein assay [3] to determine if naturally occurring human P. knowlesi infections can cause erythrocytes to bind to ICAM-1, VCAM-1 and CD36.
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