Leishmania donovani Resistance to Drugs and Host Defenses

Leishmania donovani, agent of visceral leishmaniasis, or kala-azar, has always known how to evade the human immune system. This parasite literally uses the cells of the immune system to survive and multiply: when it enters the body via a sand fly bite it is engulfed by a macrophage – part of the immune response – and then it multiplies until the cell is destroyed.

[caption id="attachment_376" align="alignleft" width="300" caption="Leishmania parasites inside macrophages"][/caption]

Nonetheless, the immune system does have some control over the infection and some infections are without symptoms of disease. An interesting paper published in 2011 (Vanaerschot et al.) reports on research that suggests that strains of L. donovani that are resistant to the commonly used antimonial drugs are also able to multiply to greater numbers in the host. So these strains not only fail to respond to antimonial drug treatment, but also cause worse disease than other strains. That is unfortunate.

It seems that antimonials work by enhancing the ability of macrophages to kill the parasites they ingest. Antimonial resistant strains appear to have evolved a way to swing things the other way somehow – they don’t do just as well as the sensitive strains; they actually do better. The authors write “all [sensitive] strains caused a similar parasite burden both in the liver and the spleen… [Resistant] strains displayed… an average 8-fold higher parasite burden in the liver and 3-fold higher parasite burden in the spleen compared to [sensitive] strains” (p. 3). That is an impressive increase, and not good news for the patient.

The authors also looked at whether these strains are also more resistant to the new drug of choice, miltefosine. They didn’t find evidence of this, but note that more study and surveillance are needed to be sure it’s not the case.

Vanaerschot M, De Doncker S, Rijal S, Maes L, Dujardin J-C, et al. (2011) "Antimonial Resistance in Leishmania donovani Is Associated with Increased InVivo Parasite Burden." PLoS ONE 6(8): e23120. doi:10.1371/journal.pone.0023120