The prevalence of Plasmodium vivax in Vanuatu Islands: Computer simulation of malaria control trails

We have estimated the degree of transmission of Plasmodium vivax malaria in Vanuatu Islands, eastern Melanesia with the aid of the computer simulations, which has been carried out on the platform of a mathematical transmission model. The malaria caused by Plasmodium vivax has a relapse character, which arises from hypnozoites in the liver. This phenomen makes a malaria control strategy difficult. When the mass drug administration is executed, the prevalence of Plasmodium vivax decreases moderately as compared with that of Plasmodium falciparum, and it recovers before long being affected by the relapses. The simulations suggest that one cannot attain the eradication of Plasmodium vivax malaria without the concentrated execution of the mass drug administration and the vector control that fairly reduces the vactorial capacity

Application of Long-Range Surface Plasmon Resonance for ABO Blood Typing

In this study, we demonstrate a long-range surface plasmon resonance (LR-SPR) biosensor for the detection of whole cell by captured antigens A and B on the surface of red blood cells (RBCs) as a model. The LR-SPR sensor chip consists of high-refractive index glass, a Cytop film layer, and a thin gold (Au) film, which makes the evanescent field intensity and the penetration depth longer than conventional SPR. Therefore, the LR-SPR biosensor has improved capability for detecting large analytes, such as RBCs. The antibodies specific to blood group A and group B (Anti-A and Anti-B) are covalently immobilized on a grafting self-assembled monolayer (SAM)/Au surface on the biosensor. For blood typing, RBC samples can be detected by the LR-SPR biosensor through a change in the refractive index. We determined that the results of blood typing using the LR-SPR biosensor are consistent with the results obtained from the agglutination test. We obtained the lowest detection limits of 1.58 × 105 cells/ml for RBC-A and 3.83 × 105 cells/ml for RBC-B, indicating that the LR-SPR chip has a higher sensitivity than conventional SPR biosensors (3.3 × 108 cells/ml). The surface of the biosensor can be efficiently regenerated using 20 mM NaOH. In summary, as the LR-SPR technique is sensitive and has a simple experimental setup, it can easily be applied for ABO blood group typing

PfMDR1: Mechanisms of Transport Modulation by Functional Polymorphisms

ATP-Binding Cassette (ABC) transporters are efflux pumps frequently associated with multidrug resistance in many biological systems, including malaria. Antimalarial drug-resistance involves an ABC transporter, PfMDR1, a homologue of P-glycoprotein in humans. Twenty years of research have shown that several single nucleotide polymorphisms in pfmdr1 modulate in vivo and/or in vitro drug susceptibility. The underlying physiological mechanism of the effect of these mutations remains unclear. Here we develop structural models for PfMDR1 in different predicted conformations, enabling the study of transporter motion. Such analysis of functional polymorphisms allows determination of their potential role in transport and resistance. The bacterial MsbA ABC pump is a PfMDR1 homologue. MsbA crystals in different conformations were used to create PfMDR1 models with Modeller software. Sequences were aligned with ClustalW and analysed by Ali2D revealing a high level of secondary structure conservation. To validate a potential drug binding pocket we performed antimalarial docking simulations. Using aminoquinoline as probe drugs in PfMDR1 mutated parasites we evaluated the physiology underlying the mechanisms of resistance mediated by PfMDR1 polymorphisms. We focused on the analysis of well known functional polymorphisms in PfMDR1 amino acid residues 86, 184, 1034, 1042 and 1246. Our structural analysis suggested the existence of two different biophysical mechanisms of PfMDR1 drug resistance modulation. Polymorphisms in residues 86/184/1246 act by internal allosteric modulation and residues 1034 and 1042 interact directly in a drug pocket. Parasites containing mutated PfMDR1 variants had a significant altered aminoquinoline susceptibility that appears to be dependent on the aminoquinoline lipophobicity characteristics as well as vacuolar efflux by PfCRT. We previously described the in vivo selection of PfMDR1 polymorphisms under antimalarial drug pressure. Now, together with recent PfMDR1 functional reports, we contribute to the understanding of the specific structural role of these polymorphisms in parasite antimalarial drug response