Hematological consequences of malaria in mice previously treated for visceral leishmaniasis

Wellcome Open Research

article

Gulab Fatima Rani¹  Helen Ashwin¹  Najmeeyah Brown¹  Ian S. Hitchcock²  Paul M. Kaye¹ 

[1] Hull York Medical School, University of York;Department of Biology, University of York

关键词: visceral leishmaniasis;    malaria;    mouse models;    hematology;    chemotherapy;    coinfection;   

DOI  :  10.12688/wellcomeopenres.16629.2

学科分类：内科医学

来源: Wellcome

【 摘 要 】

Background: Polyparasitism is commonplace in countries where endemicity for multiple parasites exists, and studies in animal models of coinfection have made significant inroads into understanding the impact of often competing demands on the immune system. However, few studies have addressed how previous exposure to and treatment for one infection impacts a subsequent heterologous infection.  Methods: We used a C57BL/6 mouse model of drug-treatedLeishmania donovani infection followed by experimentalPlasmodium chabaudi AS malaria, focusing on hematological dysfunction as a common attribute of both infections. We measured parasite burden, blood parameters associated with anemia and thrombocytopenia, and serum thrombopoietin. In addition, we quantified macrophage iNOS expression through immunohistological analysis of the liver and spleen.  Results: We found that the thrombocytopenia and anemia that accompanies primaryL. donovani infection was rapidly reversed following single dose AmBisome® treatment, along with multiple other markers associated with immune activation (including restoration of tissue microarchitecture and reduced macrophage iNOS expression). Compared to naive mice, mice cured of previous L. donovani infection showed comparable albeit delayed clinical responses (including peak parasitemia and anemia) toP. chabaudi AS infection. Thrombocytopenia was also evident in these sequentially infected mice, consistent with a decrease in circulating levels of thrombopoietin. Architectural changes to the spleen were also comparable in sequentially infected mice compared to those with Plasmodium infection alone.Conclusions: Our data suggest that in this sequential infection model, previously-treated L. donovani infection has limited impact on the subsequent development of Plasmodium infection, but this issue deserves further attention in models of more severe disease or through longitudinal population studies in humans.

【 授权许可】

CC BY