Combined chemotherapy manifest less severe immunopathology effects in helminth-protozoa comorbidity.

BACKGROUND: Co-infection with Leishmania major and Schistosoma mansoni may have significant consequences for disease progression, severity and subsequent transmission dynamics. Pentavalent antimonials and Praziquantel (PZQ) are used as first line of treatment for Leishmania and Schistosoma infections respectively. However, there is limited insight on how combined therapy with the standard drugs impacts the host in comorbidity. The study aimed to determine the efficacy of combined chemotherapy using Pentostam (P) and PZQ in murine model co-infected with L. major and S. mansoni. METHODS: A 3 × 4 factorial design with three parasite infection groups (Lm, Sm, Lm + Sm to represent L. major, S. mansoni and L. major + S. mansoni respectively) and four treatment regimens [P, PZQ, P + PZQ, and PBS designating Pentostam (GlaxoSmithKline UK), Praziquantel (Biltricide®, Bayer Ag. Leverkusen, Germany), Pentostam + Praziquantel and Phosphate buffered saline] as factors was applied. RESULTS: Significant changes were observed in the serum Interferon gamma (IFN-γ), and Macrophage inflammatory protein-one alpha (MIP-1α) levels among various treatment groups between week 8 and week 10 (p < 0.05). There was increased IFN-γ in the L. major infected mice subjected to PZQ and PBS, and in L. major + S. mansoni infected BALB/c mice treated with P + PZQ. Subsequently, MIP-1α levels increased significantly in both the L. major infected mice under PZQ and PBS and in L. major + S. mansoni infected BALB/c mice undergoing concurrent chemotherapy with P + PZQ between 8 and 10 weeks (p < 0.05). In the comorbidity, simultaneous chemotherapy resulted in less severe histopathological effects in the liver. CONCLUSION: It was evident, combined first line of treatment is a more effective strategy in managing co-infection of L. major and S. mansoni. The findings denote simultaneous chemotherapy compliments immunomodulation in the helminth-protozoa comorbidity hence, less severe pathological effects following the parasites infection. Recent cases of increased incidences of polyparasitism in vertebrates call for better ways to manage co-infections. The findings presented necessitate intrinsic biological interest on examining optimal combined chemotherapeutic agents strategies in helminth-protozoa concomitance and the related infections abatement trends vis-a-vis host-parasite relationships.

Experimental therapeutic assays of Tephrosia vogelii against Leishmania major infection in murine model: in vitro and in vivo.

BACKGROUND: Conventional targeted leishmanicidal chemotherapy has persistently remained prohibitive for most economically deprived communities due to costs, associated time to accessing health services and duration for successful treatment programme. Alternatives are bound to be incorporated in rational management of leishmaniasis by choice or default due to accessibility and cultural beliefs. Therefore, there is need to rigorously investigate and appraise the activity of medicinal compounds that may have anti-leishmanicidal activity especially in the context of products that are already being utilized by the populations for other ailments but have limited information on their therapeutic value and possible cytoxicity. Hence, the study examined both in vivo and in vitro response of L. major infection to Tephrosia vogelii extracts in BALB/c mice as the mouse model. METHODS: A comparative study design was applied for the in vivo and in vitro assays of the extract with Pentostam (GlaxoSmithKline, UK) and Amphotericin B [Fungizone™, X-Gen Pharmaceuticals (US)] as standard drugs. RESULTS: In BALB/c mice where the chemotherapeutic extract was administered intraperitoneally, there was significantly (p < 0.05) larger reduction in lesion size and optimal control of parasite burden than those treated orally. However, standard drugs showed better activity. Tephrosia vogelii had 50% inhibitory concentration (IC50) and IC90 of 12 and 68.5 µg/ml respectively, while the standard drugs had IC50 and IC90 of 5.5 and 18 µg/ml for Pentostam and 7.8 and 25.5 µg/ml for Amphotericin B in that order. In the amastigote assay, the infection rates decreased with increase in chemotherapeutic concentration. The multiplication indices for L. major amastigotes in macrophages treated with 200 µg/ml of the standard drugs and extract were significantly different (p < 0.05). 200 µg/ml of T. vogelii extract showed a multiplication index of 20.57, 5.65% for Amphotericin B and 9.56% for Pentostam. There was also significant difference (p < 0.05) in levels of Nitric oxide produced in the macrophages. CONCLUSIONS: The findings demonstrated that T. vogelii extract has anti-leishmanial activity and further assays should be done to ascertain the active compounds responsible for anti-leishmanial activity.