Abstract
Cryptosporidium parvum is a species of protozoa that causes cryptosporidiosis, an intestinal disease affecting many mammals including humans. Typically, in healthy individuals, cryptosporidiosis is a self-limiting disease. However, C. parvum can cause a severe and persistent infection that can be life-threatening for immunocompromised individuals, such as AIDS patients. As there are no available treatments for these patients that can cure the disease, there is an urgent need to identify treatment options. We tested the anti-parasitic activity of the alkylphosphocholine oleylphosphocholine (OlPC), an analog of miltefosine, against C. parvum in in vitro and in vivo studies. In vitro experiments using C. parvum infected human ileocecal adenocarcinoma cells (HCT-8 cells) showed that OlPC has an EC50 of 18.84 nM. Moreover, no cell toxicity has been seen at concentrations ≤50 μM. C57BL/6 interferon gamma receptor knock-out mice, were infected by gavage with 4000 C. parvum oocysts on Day 0. Oral treatments, with OlPC, miltefosine, paromomycin or PBS, began on Day 3 post-infection for 10 days. Treatment with OlPC, at 40 mg/kg/day resulted in 100% survival, complete clearance of parasite in stools and a 99.9% parasite burden reduction in the intestines at Day 30. Doses of 30 and 20 mg/kg/day also demonstrated an increased survival rate and a dose-dependent parasite burden reduction. Mice treated with 10 mg/kg/day of miltefosine resulted in 50% survival at Day 30. In contrast, control mice, treated with PBS or 100 mg/kg/day of paromomycin, died or had to be euthanized between Days 6 and 13 due to severe illness. Results of parasite burden were obtained by qPCR and cross-validated by both flow cytometry of stool oocysts and histological sections of the ileum. Together, our results strongly support that OlPC represents a potential candidate for the treatment of C. parvum infections in immunocompromised patients.
Highlights
Cryptosporidium parvum is an obligate parasite of the phylum Apicomplexa that infects the microvilli of the small intestine of many mammalian hosts including humans (Ryan and Xiao, 2014)
This study reports the strong activity of OlPC, both in vitro and in vivo in an immunocompromised C57BL/6 IFNγR-KO mouse model of C. parvum infection
OlPC and Miltefosine Inhibit C. parvum Infection in HCT-8 Cells In Vitro To test the efficacy of OlPC to inhibit C. parvum infection in vitro, we used HCT-8 cells which allowed the parasite to replicate (Widmer et al, 2000)
Summary
Cryptosporidium parvum is an obligate parasite of the phylum Apicomplexa that infects the microvilli of the small intestine of many mammalian hosts including humans (Ryan and Xiao, 2014). Considered as a major waterborne pathogen (drinking and recreational water) that can be transmitted through contaminated foods (Fayer et al, 2000; Cacciò and Putignani, 2014), C. parvum outbreaks have been widely reported in numerous countries from all continents (Cacciò et al, 2005; Putignani and Menichella, 2010; Cacciò and Putignani, 2014). This study reports the strong activity of OlPC, both in vitro and in vivo in an immunocompromised C57BL/6 IFNγR-KO mouse model of C. parvum infection
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
