A chronic bioluminescent model of experimental visceral leishmaniasis for accelerating drug discovery

Area of Science:

• Parasitology
• Infectious Diseases
• Drug Development

Background:

• Visceral leishmaniasis is a neglected disease with limited, unsafe drug options.
• Drug development faces challenges due to relapses, resistant strains, and a gap between early and late stages.
• There is a critical need for novel therapeutic strategies and improved drug development tools.

Purpose of the Study:

• To develop a novel tool for monitoring visceral leishmaniasis progression.
• To enable long-term, in vivo tracking of parasite burden in individual animals.
• To accelerate the drug discovery and development pipeline for visceral leishmaniasis.

Main Methods:

• Generated a red-shifted luminescent *Leishmania infantum* strain.
• Administered varying doses of infected metacyclic parasites to mouse models.
• Monitored disease progression and parasite colonization in target organs (liver, spleen, bone marrow) for up to 21 weeks.
• Utilized bioluminescence imaging for in vivo parasite detection.

Main Results:

• Achieved an in vivo detection limit of 10^6 intracellular amastigotes 48 hours post-infection.
• Demonstrated sequential parasite colonization of liver, spleen, and bone marrow via bioluminescence.
• Showcased a significant decrease in spleen weight, parasite burden, and bioluminescence upon miltefosine treatment.

Conclusions:

• In vivo bioimaging with the modified *Leishmania infantum* strain effectively appraises both acute and chronic stages of infection.
• This technique serves as a powerful tool for accelerating drug development against visceral leishmaniasis.
• The method helps bridge the gap between early drug discovery and subsequent development stages.