Existing drugs for
visceral leishmaniasis (VL) are partially effective, toxic, having high cost and long term treatment. Their efficacies are also compromised due to suppression of immune function associated during the course of
infection. Combination
therapy including a potential and safe
immunostimulant with lower doses of effective
drug has proven as a significant approach which is more effective than
immunotherapy or
drug therapy alone. In the present study, we have used the combination of
Pam3Cys (an in-built
immunoadjuvant and TLR2
ligand) and
miltefosine. Initially dose optimization of both the agents was carried out and after that, antileishmanial effect of their combination was evaluated. All experiments were done in BALB/c mouse model. The immunomodulatory role of
Pam3Cys on the immune functions of the host receiving combination treatment was also determined using immunological and biochemical parameters viz. phagocytosis, Th1/Th2
cytokines and production of ROS, RNS and H(2)O(2). Combination group showed significant enhancement in parasitic inhibition as compared to groups receiving
miltefosine and
Pam3Cys separately. Enhanced production of Th1
cytokines as well as ROS, RNS and H(2)O(2) was witnessed during the study of immunological alterations. Remarkable increase in phagocytosis index was also observed. Thus, the risk of development of drug resistance against
miltefosine can be resolved through using low doses of it and
Pam3Cys (single-dose) in combination and also provide a promising alternative for cure of
leishmaniasis, with a pronounced transformation of the host immune response.