Leishmaniasis: treatment, drug resistance and emerging therapies

ABSTRACT

Introduction: Leishmaniasis is one of the most neglected tropical infectious diseases in the world. Emergence of drug resistance and toxicity and high cost of the available drugs with lack of new antileishmanial drugs highlight the need to search for newer molecules with antileishmanial activities.

Areas covered: This article describes the currently available antileishmanial drugs and their risk of developing resistance and discusses newer therapies. These include oral lipid-based formulations of amphotericin B, use of different drug delivery systems, and quinolone derivatives – naphthoquinone, buparvaquone, etc.

Expert opinion: There are only a handful of antileishmanial drugs, and even fewer in the pipeline. Guideline-based treatment, with proper selection of antileishmanial compound, should be practiced. Combination therapy should be used preferably to prevent or delay drug resistance. As most patients with PKDL (post-kala-azar dermal leishmaniasis) are asymptomatic, it is important that shorter regimens are developed, which will encourage patients to opt for complete treatment. Pharmaceutical industry and “not for profit’ organizations should be encouraged to enhance the efforts in finding clinically effective antileishmanial drugs.

KEYWORDS:

• Leishmaniasis
• drug resistance
• amphotericin B

Article highlights

• Single dose of L-AmB and combination therapy are the preferred treatment of VL in the ISC.

• Strict treatment monitoring for both is imperative to prevent the development of resistance.

• Short-course multidrug therapy is the need of the hour for PKDL as the treatment is long and arduous.

• Better treatment options are needed for HIV-VL coinfection especially in Africa.

• Drugs like sitamaquine and fexinidazole should be tried as part of combination regimens before being discarded.

• Robust randomized clinical trial is sorely needed for the treatment of CL in Old and New World.

• In the absence of risk factors for developing MCL, local therapy can be given for New World CL.

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 materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the National Institute of Allergy and Infectious Diseases, NIH, USA, U19 AI074321.