Evaluation of mono and combined nitrofurantoin therapy for toxoplasmosis in vivo using murine model

ABSTRACT

Toxoplasmosis is a frequent disease with an estimated prevalence of more than one billion human cases worldwide and over one million new infections each year. It is classified as a neglected tropical disease by the CDC since 2019. The disease may pass unnoticed in healthy individuals but could be fatal in the immunocompromised. Moreover, no effective treatment is available against the chronic form of the disease. Available anti-Toxoplasma drugs are associated with many side effects. Therefore, search for new more reliable, more efficient, and less toxic therapeutic agents is a continuous endeavor. This study assesses the potential use of nitrofurantoin, a compound with well-established antimicrobial properties, as a potential anti-Toxoplasma drug in vivo. It compares its efficacy to the commonly used anti-Toxoplasma agent spiramycin by molecular and histopathological methods in acute and chronic infection. The results demonstrate a significant ability to eliminate the parasite (P < 0.001) whether used as mono- or combined therapy with spiramycin in the acute and chronic stages. When compared to the anti-Toxoplasma drug spiramycin, nitrofurantoin achieved similar efficacy in the acute and chronic infection (P = 0.65 and P = 0.096, respectively). However, better results were obtained when using a combination of both drugs (P < 0.001). Additionally, nitrofurantoin showed good inhibitory effects on the inflammatory process in the liver, kidney, and uterus of the experimentally infected animals. In conclusion, nitrofurantoin can be considered as a potential anti-Toxoplasma agent. Nevertheless, further studies are recommended before consideration for clinical trials.

KEYWORDS:

• In vivo
• nitrofurantoin
• Toxoplasma gondii
• toxoplasmosis
• treatment

Acknowledgements

The authors would like to thank the animal house personnel at the National Research Center for taking care of the experimental animals.

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contributions

All authors contributed to the study conception and design. Material preparation was made by Dr Asmaa Elkholy and Dr Shereen Kishik. Molecular tests were performed by Dr Omnia Alsaied. Pathological examination was performed by Dr Ashraf Barakat and Dr Ashraf Sorour. Data collection and analysis were made by Dr Mona Elawady and Dr Rita Wassef. The first draft of the manuscript was written by Dr Rita Wassef, who is also the corresponding author. All authors revised and approved the final manuscript and agreed on submission to the chosen journal.

Ethics approval

This study was conducted at the National Research Center (NRC), Giza, Egypt, and the experiment was carried out according to the institutional guidelines and in line with the principles of the Declaration of Helsinki after approval of the Research Ethics Committee.

Data availability statement

The data that support the findings of this study are available from the corresponding author, [RW], upon reasonable request.

Additional information

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.