Liposomes in leishmaniasis: effects of parasite virulence on treatment of experimental leishmaniasis in hamsters

Abstract

During studies on the use of liposomes as drug carriers in experimental leishmaniasis in hamsters, we noted incidentally that the apparent virulence of the infection often varied widely between different large groups of animals. When the death rates among control animals (injected only with saline) were compared with hepatic parasite counts of survivors in the same group, three distinctive types of infection were observed: type I, low death rate, low parasite count in survivors; type II, high death rate, low parasite count in survivors; type III, high death rate, high parasite count in survivors. The apparent virulence, based on death rates both at early and late stages of infection, was in the order I < II < III. Therapeutic efficacy of a drug (meglumine antimoniate) or liposome-encapsulated drug against each type of infection was in the order I > II > III. Liposomes reduced the drug dose required for each infection type many hundred-fold and reduced the death rate for type I to zero. However, among animals with type III (or even type II) infection certain individuals were completely refractory to treatment, even when liposome-encapsulated drug was employed, and the lowest mortality rate achieved was approximately 30%. This latter resistance to treatment may have been due to irreversible tissue damage caused by advanced disease, or it may have reflected resistance of certain virulent infections to treatment.