Therapeutic and prophylactic uses of protein A in the control of Leishmania donovani infection in experimental animals.

The role of the immunomodulator Protein A (PA) (from Staphylococcus aureus, Cowan I strain) in the control of leishmanial infection was studied in experimental animals. Treatment of Leishmania donovani infected hamsters with PA led to a moderate level of reduction of parasite load in their spleen (68%) and liver (46%). However, combination therapy of PA with the antileishmanial drug stibanate induced a more marked reduction of the spleen (88%) and liver (85%) parasitemia compared to that induced by PA or drug treatment alone. Similar results were also obtained with L. donovani infected BALB/c mice as the combination therapy of PA and stibanate led to a significant reduction (84%) of liver parasite load in comparison to that induced by PA (38%) or drug (61%) treatment alone. Apart from its therapeutic use, PA could also be used as a prophylactic agent in the control of leishmanial infection. Thus, treatment of hamsters with PA before leishmanial challenge significantly reduced their organ parasite load (by 59-78%) compared to that observed in infected controls without prior PA treatment. The antileishmanial effect of PA was likely to be mediated through the activation of macrophages leading to an enhancement of their phagocytic as well as leishmaniacidal activities. Subsequent studies demonstrated that PA treatment led to an increased production of nitric oxide by macrophages which could primarily be responsible for their enhanced parasite killing ability.