Biological risk assessment of miltefosine in concomitant infection with opportunistic toxoplasmosis

  • Ashraf M Barakat Department of Zoonotic Diseases, National Research Center, Cairo, Egypt
  • Amal E Saafan Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Menoufia University, Menoufia, Egypt
  • Samuel T Melek Departments of Parasitology and Blood Research, National Organization for Drug Control and Research (NODCAR), Giza, Egypt
  • Tahany S Behour Biotechnology Research Unit, Animal Reproduction Research Institute, Giza, Egypt
  • Nehal M Khairy Departments of Parasitology and Blood Research, National Organization for Drug Control and Research (NODCAR), Giza, Egypt
  • Ahmed S Khairalla Department of Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
Keywords: miltefosine, toxoplasmosis, parasitic load, TNF-α, B1 gene, IGRA

Abstract

Introduction: Although miltefosine is the first line for treatment of leishmaniasis, it could have multiple un-recognized effects if any infection accidentally takes place during therapy. The aim is to precisely evaluate the molecular and biochemical remarks of miltefosine on Toxoplasma gondii accidental infection during miltefosine therapeutic course.

Methodology: changes implied by miltefosine daily parenteral administration to Toxoplasma-infected mice, subcutaneously or intraperitoneal, have been investigated. Tumor necrosis factor-Alfa, immunoglobulin G and M, IL-12 and interferon-gamma release assay (IGRA) were measured in the animals’ sera post-miltefosine administration in addition to monitoring Tissue parasite load by measuring the daily changes of copy number of B1 gene using quantitative PCR technique (qPCR).

Results: Miltefosine significantly increased inflammatory and immunological markers (TNF-α, IgG and IgM) measured on reference to control untreated group, with a significant increase in the parasite burden and distribution in all tested organs (F = 390.9, df = 9, P < 0.0001), (F = 4478.98, df = 4.75, P< 0.0001) and (F = 247.3, df = 4, P < 0.0001); heart, liver and lung, respectively, using MANOVA. Releasing capability of macrophages significantly increased during the first day of infection, however, it finally declined after seven consecutive doses of miltefosine (t = 7.96, P < 0.001).

Conclusion: Miltefosine could not control the pathogenesis and multiplication of accidental Toxoplasma infection. Cumulative low parenteral daily doses of miltefosine (1.5 µM) could inversely affected the normal humoral immunity against toxoplasmosis. Therefore, a periodical screening for accidental Toxoplasma infection during the course of therapy is strongly recommended.

Published
2019-06-30
How to Cite
1.
Barakat AM, Saafan AE, Melek ST, Behour TS, Khairy NM, Khairalla AS (2019) Biological risk assessment of miltefosine in concomitant infection with opportunistic toxoplasmosis. J Infect Dev Ctries 13:554-564. doi: 10.3855/jidc.11093
Section
Original Articles