Khayeka-Wandabwa Christopher, Zhou Guan, Magak Ng'wena Gideon, Choge Joseph K, Kemei William Kipchirchir, Makwali Judith Alice, Karani Lucy Wanja, Kisavi Mutila Phoebe, Ndulu James V, Anjili Christopher O
School of Pharmaceutical Science and Technology (SPST), Health Science Platform, Tianjin University, Tianjin, 300072, China; Centre for Biotechnology Research and Development (CBRD), Kenya Medical Research Institute (KEMRI), P.O Box 54840, Nairobi, 00200, Kenya.
School of Pharmaceutical Science and Technology (SPST), Health Science Platform, Tianjin University, Tianjin, 300072, China.
Exp Parasitol. 2019 Sep;204:107728. doi: 10.1016/j.exppara.2019.107728. Epub 2019 Jul 23.
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.
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.
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.
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.
利什曼原虫(Leishmania major)和曼氏血吸虫(Schistosoma mansoni)合并感染可能对疾病进展、严重程度及后续传播动态产生重大影响。五价锑化合物和吡喹酮(PZQ)分别用作治疗利什曼原虫和血吸虫感染的一线药物。然而,对于标准药物联合治疗在合并感染中如何影响宿主的了解有限。本研究旨在确定在同时感染利什曼原虫和曼氏血吸虫的小鼠模型中使用喷他脒(P)和吡喹酮联合化疗的疗效。
采用3×4析因设计,将三个寄生虫感染组(Lm、Sm、Lm + Sm分别代表利什曼原虫、曼氏血吸虫和利什曼原虫 + 曼氏血吸虫)和四种治疗方案[P、PZQ、P + PZQ以及PBS,分别代表喷他脒(英国葛兰素史克公司)、吡喹酮(拜耳公司,德国勒沃库森)、喷他脒 + 吡喹酮和磷酸盐缓冲盐水]作为因素。
在第8周和第10周之间,各治疗组的血清干扰素γ(IFN-γ)和巨噬细胞炎性蛋白-1α(MIP-1α)水平出现了显著变化(p < 0.05)。接受吡喹酮和磷酸盐缓冲盐水治疗的利什曼原虫感染小鼠以及接受P + PZQ治疗的利什曼原虫 + 曼氏血吸虫感染BALB/c小鼠中,IFN-γ水平升高。随后,在第8至10周期间,接受吡喹酮和磷酸盐缓冲盐水治疗的利什曼原虫感染小鼠以及接受P + PZQ联合化疗的利什曼原虫 + 曼氏血吸虫感染BALB/c小鼠中,MIP-1α水平均显著升高(p < 0.05)。在合并感染中同时进行化疗可减轻肝脏的组织病理学影响。
显然,联合一线治疗是管理利什曼原虫和曼氏血吸虫合并感染的更有效策略。研究结果表明,同时进行化疗有助于在蠕虫-原虫合并感染中发挥免疫调节作用,因此寄生虫感染后病理影响较轻。近期脊椎动物多重寄生虫感染发生率上升的病例表明,需要更好的方法来管理合并感染。本研究结果有必要从内在生物学角度探讨在蠕虫-原虫合并感染中最佳联合化疗药物策略以及相关感染减轻趋势与宿主-寄生虫关系。