Wednesday, 9 March 2011

Malaria: Artemisinin and P. falciparum Dormancy

Relapse, recurrence, recrudescence, resistance, dormancy: these terms are all relevant when explaining why malaria sometimes makes a reappearance after it has been treated. Plasmodium sp. parasites have a whole arsenal of ways to foil our best attempts to get rid of them.

The terms above all mean something quite specific. Garcia and Bruckner explain that relapse and recurrence refer to a return of the infection that arises from merozoites remaining in the liver (Diagnostic Medical Parasitology, 1997). This is well documented with P. vivax and P. ovale, and is also responsible for the long period of time that can pass between infection and onset of symptoms.

[caption id="attachment_255" align="alignleft" width="300" caption="Plasmodium falciparum parasites in blood: CDC, Dr. Mae Melvin"][/caption]

Recrudescence, according to Garcia and Bruckner, results from parasites remaining in the red blood cells after treatment. Drug therapy has failed to kill them. This is not necessarily due to drug resistance – it may be because too little drug was administered or because the drug did not remain in the blood long enough - but resistance can play a part. When some individual parasites have a genetic ability to escape the effects of a drug, and are able to multiply and re-establish the infection after all the rest have been killed, drug resistance is the basis of recrudescence. Recrudescence is often seen with P. falciparum.

Now, Andrea Codd and others report on research that provides scientific evidence for dormancy (“Artemisinin-induced Parasite Dormancy: A Plausible Mechanism for Treatment Failure," Malaria Journal 10:56). It seems that treatment with artemisinin induces a dormant state in P. falciparum parasites in the blood, from which they can return and begin to multiply once again. The researchers describe it as “a drug-induced temporary pause in the development of some parasites.” This is a distinctly different situation from parasite survival due to the drug failing to kill all the parasites, or actual drug resistance, and it is yet another way that malaria can appear to be gone, and then return.

While the effect has only been observed in the laboratory so far, Codd et al propose that dormancy may account for many instances of recrudescence, and speculate that dormancy may occur with other antimalarial drugs as well.

The more we learn about Plasmodium spp., the better we see how versatile they are, how well equipped to survive, no matter what we throw at them.

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