Visceral leishmaniasis treatment: What do we have, what do we need and how to deliver it?

Abstract

Leishmaniasis is one of the most neglected tropical disease in terms of drug discovery and development. Most antileishmanial drugs are highly toxic, present resistance issues or require hospitalization, being therefore not adequate to the field. Recently improvements have been achieved by combination therapy, reducing the time and cost of treatment. Nonetheless, new drugs are still urgently needed. In this review, we describe the current visceral leishmaniasis (VL) treatments and their limitations. We also discuss the new strategies in the drug discovery field including the development and implementation of high-throughput screening (HTS) assays and the joint efforts of international teams to deliver clinical candidates.

Search for New Antileishmanial Chemotherapeutics

“…The parasite of the disease occurs in two distinct forms: the flagellated, extracellular promastigotes that resides in the gut of female sandfly vector; and the nonflagellated, nonmotile amastigote form that exists and multiplies within the phagolysosomal compartment of macrophages [2,3]. Depending on the causative species involved, human leishmaniasis may manifest in various forms that include cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), diffused cutaneous leishmaniasis (DCL), and visceral leishmaniasis (VL), of which visceral leishmaniasis is the most lethal form of disease caused by the species of Leishmania donovani [4].…”

(+)-Spectaline, a Piperidine Alkaloid from <i>Senna spectabilis</i> DC. Effective in Reducing the <i>In Vitro</i> Infection of <i>Leishmania major</i>

“…Leishmaniasis is considered as one of the most neglected tropical diseases (NTDs) in the world [1,2]. It is endemic in 98 countries worldwide with an estimated 1.3 million new cases and an annual mortality rate of 20,000 to 40,000 [3].…”

“…Although more efforts to come on vaccine development for leishmaniasis, there is no registered human leishmaniasis vaccine to date and pentavalent antimony or antimonials still act as the primary therapy [6,7]. Other drugs available in the market face great challenges such as acquired resistance by certain common species, depleted immune capability in HIV co-infection patients and organs toxicities [2]. The unfavorable side effects and resistance together with the increasing number of patients intensified the demand for alternative remedies to curtail this disease [8][9][10].…”

“…On being bitten, promastigotes are released into the skin and bloodstream which are then phygocytosed by the host macrophage [2]. The promastigotes are then transformed to amastigotes and then multiply, causing host cells to be burdened with parasites and thus becoming prone to lysis.…”

Cutaneous Leishmaniasis

“…İlaç geliştirilmesi ve keşfi açısından leishmaniasis en ihmal edilmiş hastalıklardan biridir (7). Mevcut antileishmanial ilaçların çoğu yüksek derecede toksiktir, direnç sorunu vardır ve sistemik tedavi için hastaneye yatış gerekir (8).…”