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Host-Directed Therapies for Cutaneous Leishmaniasis
Fernanda O Novais1, Camila Farias Amorim2, Phillip Scott2
1Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH, United States.
Abstract:
Cutaneous leishmaniasis exhibits a wide spectrum of clinical presentations from self-resolving infections to severe chronic disease. Anti-parasitic drugs are often ineffective in the most severe forms of the disease, and in some cases the magnitude of the disease can result from an uncontrolled inflammatory response rather than unrestrained parasite replication. In these patients, host-directed therapies offer a novel approach to improve clinical outcome. Importantly, there are many anti-inflammatory drugs with known safety and efficacy profiles that are currently used for other inflammatory diseases and are readily available to be used for leishmaniasis. However, since leishmaniasis consists of a wide range of clinical entities, mediated by a diverse group of leishmanial species, host-directed therapies will need to be tailored for specific types of leishmaniasis. There is now substantial evidence that host-directed therapies are likely to be beneficial beyond autoimmune diseases and cancer and thus should be an important component in the armamentarium to modulate the severity of cutaneous leishmaniasis.
Insights
Host-directed therapies, using anti-inflammatory drugs, show promise for treating severe cutaneous leishmaniasis when antiparasitics fail. Tailored treatments are key for this complex parasitic skin disease.
Area of Science:
- Immunology
- Infectious Diseases
- Dermatology
Background:
- Cutaneous leishmaniasis presents diverse clinical forms, from mild to severe chronic disease.
- Antiparasitic drugs are often insufficient for severe leishmaniasis, where inflammation, not just parasite load, drives disease severity.
- Host-directed therapies (HDTs) present a novel strategy to manage severe cases by modulating the host's immune response.
Purpose of the Study:
- To explore the potential of host-directed therapies as a treatment strategy for cutaneous leishmaniasis.
- To highlight the availability of existing anti-inflammatory drugs for repurposing in leishmaniasis treatment.
- To emphasize the need for tailored HDTs based on leishmaniasis clinical and etiological diversity.
Main Methods:
- Review of existing literature on cutaneous leishmaniasis pathogenesis and treatment.
- Analysis of the role of inflammatory responses in disease severity.
- Evaluation of the potential application of anti-inflammatory drugs as host-directed therapies.
Main Results:
- Severe cutaneous leishmaniasis can be driven by uncontrolled inflammation, suggesting host-directed approaches are viable.
- Numerous anti-inflammatory drugs with established safety profiles exist and could be repurposed.
- The heterogeneity of leishmaniasis necessitates personalized HDT strategies for optimal efficacy.
Conclusions:
- Host-directed therapies represent a promising addition to the treatment of cutaneous leishmaniasis, particularly severe forms.
- Repurposing existing anti-inflammatory drugs offers a practical avenue for developing new treatment protocols.
- Personalized approaches are crucial for effectively modulating leishmaniasis severity using host-directed strategies.
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