Hematological consequences of malaria in mice previously treated for visceral leishmaniasis.

Gulab Fatima Rani,Helen Ashwin,Ian S Hitchcock,Najmeeyah Brown,Paul M Kaye

doi:10.12688/wellcomeopenres.16629.2

Gulab Fatima Rani, Helen Ashwin + Show 3 more

Open Access

https://doi.org/10.12688/wellcomeopenres.16629.2

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Abstract

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-treated Leishmania donovani infection followed by experimental Plasmodium 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 primary L. 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) to P. 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.

Highlights

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
Of note, red cell distribution width (RDW) increased during infection and continued to do so for two weeks post-Rx before it returned to baseline levels (Figure 1E), suggesting that erythrocytes of variable shapes and sizes are a feature of chronic L. donovani infection that recovers after parasite clearance
visceral leishmaniasis (VL)/HIV coinfection is prevalent and well-studied, there is an increasing incidence of other infections coexisting with VL . 11,13,32,33,35 In this study, we established a model of a sequential P. chabaudi infection in a AmBisome®-treated murine VL model to address the question of whether mice previously exposed to L. donovani and cured using a first line therapy would differ in their subsequent response to malaria challenge

Summary

Introduction

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. Blood parameters associated with anemia and thrombocytopenia, and serum thrombopoietin. Results: We found that the thrombocytopenia and anemia that accompanies primary L. 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). Architectural changes to the spleen were 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 version 2 (revision)

Methods

Results

Conclusion