2004A0019 - Evaluation of Compounds for Activity Against Leishmaniasis in Mice

This protocol was approved to use 3,525 BALB/c mice and 75 Golden Hamsters.

Background: Caused by various species of the protozoan parasite Leishmania, the disease is routinely transmitted by the bite of the Leishmania-infected sandfly. The parasite lives in the gut of the flies.

A November 2004 Columbus Dispatch articles states, "Symptoms vary from skin wounds that heal slowly to conditions that infect the liver, spleen and bone marrow. Without treatment, Satoskar (co-investigator) said, some victims can die within five months."

The 75 Golden Hamsters are used as a "stock" for the parasite. 8 weeks after infection, the hamster will be killed and their spleens removed. "Parasites will be isolated from the spleen and used to infect another hamster in the case of maintaining the stock or to infect mice in the case of drug studies."

A July 2005 amendment approved by ILACUC greatly changes the role of the hamster in these experiments.

2,126 hamsters will be used to examine anti-leishmanial compounds.

"BALB/c mice have been widely used as a model system for anti-leishmanial in vivo testing. However, we are concerned that this model system may not be the best choice for our anti-leishmanial drug discovery and development projects." Their concerns are:

• mice begin to control the infection. "In contrast, infection with L.donovani in golden hamsters results in a progressive increase in parasitemia which ends in death."
• Pentamidine is used clinically for treatment in humans. Pentamidine shows low activity in the mouse model and the mice tolerate the compound poorly. The drug is better tolerated in hamsters, and the compound displays higher activity.
• review of other drug compounds using mice