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

Saturday, December 5, 2009

Justifying my existence

As somebody training in both critical care and infectious diseases, I'm often left trying to explain what I hope to do with my career, struggling with coherent answers to both laypeople and other doctors. People get sick because of infections. Also, sick people end up getting infections. That's how I look at it, and hence my training.

This study, published by some of my bosses, helps validate all of this. Looking at one day in ICUs across the planet, they captured a point-in-time, just to see what the burden of 'infection' is in our planet's ICUs. Obviously, there are huge problems with potential reporting bias and the like, but it's as good a global survey as you can justifiably get. And the results are interesting, showing that half of all patients in ICUs were considered infected, with these patients doing significantly worse overall. Nearly three quarters of the patients were receiving antibiotics, some just for propylaxis. Also, the longer that you were sick, the more likely you were to have an infection. There was also a correlation between national GDP and rates of ICU infection, which, once again, isn't surprising, since we know that infection control procedures aren't always cheap

The types of bacteria and infections reported were interesting, with pneumonias as the most common infection, and a reasonable distribution of types of bacteria. There is an increasing prevalence of dangerous gram-negative bacteria, and a persistently worrisome rate of antibiotic-resistant bacteria. I've talked about this quandary before, since as we're able to care for sicker and sicker patients, we're also using more and more antibiotics, leading to all sorts of resistance problems for future generations. Also, what constitutes an 'infection' is a difficult distinction, one that we typically err on the side of caution by treating. In the end, with very few new antibiotics coming down the research pipeline, we will face a tremendous challenge outwitting these ever-shifting, diverse group of organisms.

Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, Moreno R, Lipman J, Gomersall C, Sakr Y, Reinhart K, & EPIC II Group of Investigators (2009). International study of the prevalence and outcomes of infection in intensive care units. JAMA : the journal of the American Medical Association, 302 (21), 2323-9 PMID: 19952319