L. major+S. mansoni co-infection subjected to no chemotherapy post-infection showed severe L. major parasitized macrophages predominance affirming the exacerbation role of S. mansoni in concomitance converse to L. major infection whereas Praziquantel/Pentostam combined first line effective treatment was observed in managing the comorbidity. As such it is evident: 1) Combined first line treatment is more effective in managing co-infection and 2) Combined chemotherapy compliments immunomodulation.