ReviewFalciparum Malaria: Sticking up, Standing out and Out-standing
Section snippets
Why focus on cytoadherence?
We believe that cytoadherence is a key determinant of parasite virulence and is responsible for the development of severe disease in malaria, or at least, that part of severe disease associated with frequently fatal syndromes such as cerebral malaria (CM). By the late 19th century, clinicians had already recognized that P. falciparum, a species that sequestered in the microvasculature, was more virulent in humans than was P. vivax, a species that did not sequester. In 1985, Langreth and
From cytoadherence to clinical disease
The overwhelming conclusion from studies over the past five years is that cytoadherence is undoubtedly incredibly complex. We seem to have described more receptors to which PRBC can bind than we really need to explain the pathophysiology (Fig. 1). Other pathogens, including viruses and bacteria, seem to make do with just one or two receptors for invasion, survival and propagation in vivo, so why should P. falciparum require such a complex ensemble? How do we make sense of which are the more
New receptors and ligands
Although new studies addressing some unanswered questions were presented at the conference, generally, more questions were generated than definitive answers were gained. At least two further receptors, one new RBC-expressed ligand and one additional cellular interaction were described to add to the complexity of the situation. Beeson and co-workers (The Walter & Eliza Hall Institute, Melbourne, Australia) described the identification of hyaluronic acid (HA) as a new receptor for PRBC in the
PfEMP1, RIFINs and Pf60 proteins
Much recent effort has also focused on the precise mapping of multiple functional domains of PfEMP1. The complex and highly variable extracellular head structure of the molecule is composed of between two and seven DBL domains and one or two CIDRs (Cys-rich-inter-domain regions). Specific and distinct domains of PfEMP1 have now been identified that mediate binding to a number of endothelial-cell-expressed receptors (see Fig. 1) as well as to normal, non-immune human serum immunoglobulins (IgM
Future focus
In our view, this area of research is going to become increasingly more complicated, with further interactions, receptors, ligands and functional domains described. The polymorphism of the PfEMP1 family is such that individual members will have measurable affinity with even more molecules than we are currently aware. We should also have a much clearer understanding of how this and other multigene families are controlled. The challenge will be not to lose ourselves in the molecular detail, but
Website of Interest
Malaria Transmission Blocking Vaccines: An Ideal Public Good A document published by WHO under this title can be downloaded from http://www.who.int/tdr/publications/publications/pdf/tbv.pdf
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