Friday, December 18, 2009

Malaria: Forcing us to destroy our own brains...

From a recent PLOSOne study, some interesting findings on malaria pathogenesis. What we know is that getting cerebral malaria is both very bad and very unpredictable, so that it's very difficult to decide which patient will require closer monitoring than others. Management is non-specific and supportive, and we still don't exactly know why it happens. There are a lot of theories out there, many of which center around the sludging of blood in the cerebral vessels, causing decreased brain blood flow and the symptoms we see. This has always been suspect, since there are a great deal of inconsistencies with this hypothesis, so investigation has continued.

Adding to some prior work that they've done, these investigators looked at a population in India where malaria is endemic. From screening the serum of patients with both severe malaria and cerebral malaria, they found some interesting differences. Notably, the patients with cerebral malaria had a specific cytokine response that seemed to induce a reaction to a series of brain-specific proteins in the form of antibody production. What the effect of this auto-antibody production is on the symptoms seen in cerebral malaria remains unclear, especially since their concentration wasn't related to disease severity. Determining whether these antibodies contribute to disease, or serve as simply a marker for disease progression or existence, still has to be sussed out. Interestingly, however, the strongest signal was to a different brain protein compared with their prior study in African patients, suggesting a variant host response, although there was some overlap in this data.

Getting more people into this study would have powered their results a bit more, and perhaps helped pinpoint the brain protein a bit better, but nevertheless, it's an interesting theory that deserves some more study, since it has sizable implications, both for therapeutic and for prognostic purposes. Given that we are making only slow progress in the battle against this disease, the more information and research on the topic, the better.

Bansal, D., Herbert, F., Lim, P., Deshpande, P., B├ęcavin, C., Guiyedi, V., de Maria, I., Rousselle, J., Namane, A., Jain, R., Cazenave, P., Mishra, G., Ferlini, C., Fesel, C., Benecke, A., & Pied, S. (2009). IgG Autoantibody to Brain Beta Tubulin III Associated with Cytokine Cluster-II Discriminate Cerebral Malaria in Central India PLoS ONE, 4 (12) DOI: 10.1371/journal.pone.0008245

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