Abstract
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. 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). 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). 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.
Highlights
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 virulent RH strain tachyzoites of T. gondii was maintained by intra-peritoneal (IP) inoculation of female albino mice in the zoonotic diseases department of the National Research Center (NRC), Egypt, according to the protocol suggested by McLeod et al, [11]
Our study aimed at exploring the effect of miltefosine on the release of inflammatory markers as Interferon gamma, tumor necrosis factor and specific anti-toxoplasma antibodies, in addition to quantitative follow up of toxoplasma count in different organs encountered by successive doses of miltefosine in mice infected with acute toxoplasmosis using quantitative PCR technique (qPCR) technique
Summary
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. Conclusion: Miltefosine could not control the pathogenesis and multiplication of accidental Toxoplasma infection. A periodical screening for accidental Toxoplasma infection during the course of therapy is strongly recommended. The superior activity of oral miltefosine was as an anti-leishmanial drug over the standard antileishmanial therapy, which resulted in its approval as the only drug available for visceral and cutaneous leishmaniasis in 2002 by WHO [2]. Treatment of toxoplasma is not an easy procedure, so far, there is no available
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