Field-Deployable Treatments For Leishmaniasis: Intrinsic Challenges, Recent Developments and Next Steps

Area of Science:

• Parasitology and Tropical Medicine
• Immunology
• Drug Discovery

Background:

• Leishmaniasis is a neglected tropical disease with limited treatment options, often causing severe side effects.
• Current therapies are hampered by parasite persistence in host cellular niches.
• Existing treatments like chemotherapy and thermotherapy have limitations in efficacy and applicability.

Purpose of the Study:

• To review the cellular niches exploited by Leishmania parasites for host persistence.
• To discuss therapeutic strategies targeting these cellular niches and parasite survival mechanisms.
• To explore novel treatment avenues, including repurposed drugs and targeting specific host cells.

Main Methods:

• Literature review of recent studies on Leishmania parasite persistence.
• Analysis of cellular, metabolic, and molecular mechanisms of Leishmania infection.
• Exploration of potential therapeutic targets, including cellular safe havens and host-directed therapies.

Main Results:

• Leishmania parasites utilize specific cellular niches, such as hematopoietic stem cells and monocytes, to evade immune responses and chemotherapy.
• Understanding these niches reveals vulnerabilities for therapeutic intervention.
• Repurposing therapies like those targeting cancer or ferroptosis may offer new treatment options.

Conclusions:

• Targeting the cellular safe havens of Leishmania parasites is a promising strategy for developing novel treatments.
• Hematopoietic stem cells and monocytes are critical for parasite survival and represent key therapeutic targets.
• Further research into host-directed therapies could lead to field-deployable treatments for leishmaniasis.