Saturday, April 24, 2010

Mining for malaria cures

Malaria, as I've written about many times before, kills for reasons that we're not completely sure of yet. We give medications that work directly against the parasite itself, but oftentimes it's insufficient, and people die due to their body's inflammatory response to the invading parasite. Predicting, early on, who will die, and what we can do about it, is an active field of research, with some innovative discoveries over the past few years.

Adding to this is a mouse study looking at charcoal in the treatment of malaria. Oral charcoal doesn't get absorbed through your gut and has been safely used for years for adsorbing ingested toxins; it also has been shown to be an anti-inflammatory through unconfirmed mechanisms. It may be able to adsorb any intestinally-mediated toxins, as well as cytokines from the blood through a mechanism that I don't completely understand. Regardless of mechanism, these investigators randomized mice experimentally infected with malaria to oral charcoal or not, and the results were striking. All untreated mice died and only 55% of treated mice died. They reconfirmed their results with just the charcoal itself, and not its diluent - this time none of the untreated mice survived and 60% of the treated mice survived at day 10.

Mechanistically, there seems to be a moderate effect on the production of inflammatory cytokines, specifically by various T-cell lineages. They also looked at whole blood global gene expression analysis and found a significantly different profile amongst the treated mice, one that more closely resembled uninfected mice. Most importantly, they also wisely included a phase I human study, seeing if charcoal had any effects on the pharmacokinetics of antimalarials, one of the main concerns of this potential treatment (antimalarial overdose is often treated with activated charcoal, for example). It didn't have any effect on drug levels, but they used intravenous antimalarials - it remains to be seen if it is safe with administered with the more commonly given oral antimalarials.

Like they mention in their discussion, charcoal can never be used as a stand-alone therapy. As an adjunct in severe cases, it holds promise, given its safety and affordability. More importantly, understanding its molecular mechanism of activity in using the gut to reduce systemic inflammation in the malarial response could yield many other avenues of research. Human trials will need to happen, and I'm skeptical as to whether or not it can be given with oral medications, but a valuable addition to the adjunctive therapy in malaria literature.

de Souza, J., Okomo, U., Alexander, N., Aziz, N., Owens, B., Kaur, H., Jasseh, M., Muangnoicharoen, S., Sumariwalla, P., Warhurst, D., Ward, S., Conway, D., Ulloa, L., Tracey, K., Foxwell, B., Kaye, P., & Walther, M. (2010). Oral Activated Charcoal Prevents Experimental Cerebral Malaria in Mice and in a Randomized Controlled Clinical Trial in Man Did Not Interfere with the Pharmacokinetics of Parenteral Artesunate PLoS ONE, 5 (4) DOI: 10.1371/journal.pone.0009867