Current and emerging therapies for the treatment of leishmaniasis

ABSTRACT

Introduction

Leishmaniasis, a neglected protozoan illness caused by kinetoplastid pathogens encompasses three major clinical subtypes: visceral, cutaneous and mucocutaneous leishmaniasis. Pentavalent antimonials (Sb^V) have long been the preferred treatment worldwide but increased drug resistance, and significant side effects, including cardiotoxicity have limited their use, particularly in visceral leishmaniasis in India. Similarly, other approved alternatives have concerns such as teratogenicity, high cost, and drug resistance.

Areas covered

This review aims to provide an overview of emerging therapy for leishmaniasis, highlighting the latest advancements in the field and discuss their potential impact on the treatment and prevention of this neglected tropical disease. It also discusses the limitation of current treatments and need for novel approaches to address them effectively.

Expert opinion

For almost eight decades, treatment for all forms of leishmaniasis was solely dependent on Sb^V, despite several drawbacks like long treatment regimens, cardiotoxicity, and drug resistance. In the past 20 years, three drugs with antileishmanial activity were developed for human disease, but their distribution to endemic regions and accessibility for patients remain neglected. We sorely need new antileishmanial drugs, and we present here the emerging targets for developing new antileishmanial compounds that could be brought into the clinics.

KEYWORDS:

• Leishmaniasis treatment
• drug resistance
• drug discovery
• drug targets
• metabolic pathways
• immunomodulation
• nanotechnology
• leishmania vaccines

Article highlights

• Generic pentavalent antimonials were once the first-line treatment for endemic visceral and other forms of leishmaniasis, but drug resistance in the Indian subcontinent, and serious adverse events like cardiotoxicity led to its decline for the treatment of leishmaniasis.

• Miltefosine, paromomycin, and amphotericin B are also approved alternatives, but each one of them has several disadvantages.

• Drug resistance, low success rates, toxicity, and high prices call for new antileishmanial therapeutic options drugs/modalities must be explored due to drug resistance, low success rates, toxicity, and high prices.

• Developing innovative treatments for vulnerable populations is vital. The current study describes major components of existing antileishmanial treatment and current and upcoming therapeutic developments.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or mending, or royalties.

Reviewer disclosure

This manuscript’s peer reviewers have no financial or other affiliations to disclose.

Additional information

Funding

Research in the authors’ laboratory is supported through the funding from Banaras Hindu University (BHU) Institution of Eminence (IoE) grant.