A single infusion of liposomal amphotericin B was not inferior to and was less expensive than conventional therapy with amphotericin B deoxycholate. (ClinicalTrials.gov number, NCT00628719.)

Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms. In addition antimony trioxide is possibly carcinogenic to humans. Improvements in working conditions have remarkably decreased the incidence of antimony toxicity in the workplace. As a therapeutic, antimony has been mostly used for the treatment of leishmaniasis and schistosomiasis. The major toxic sideeffects of antimonials as a result of therapy are cardiotoxicity (~9% of patients) and pancreatitis, which is seen commonly in HIV and visceral leishmaniasis co-infections. Quality control of each batch of drugs produced and regular monitoring for toxicity is required when antimonials are used therapeutically.

As compared to the phase III trial that led to registration of the drug a decade ago, there is a substantial increase in the failure rate of oral miltefosine for treatment of VL in India.

No abstract

Introduction Leishmaniasis broadly manifests as visceral leishmaniasis (VL), cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL). The treatment of leishmaniasis is challenging and the armamentarium of drugs is small, duration of treatment is long, and most drugs are toxic. Areas covered A literature search on treatment of leishmaniasis was done on PubMed. Single dose of liposomal amphotericin B (L-AmB) and multidrug therapy (L-AmB + miltefosine, L-AmB + paromomycin (PM), or miltefosine + PM) are the treatment of choice for VL in the Indian subcontinent. A 17-day combination therapy of pentavalent antimonials (Sbv) and paromomycin remains the treatment of choice for East African VL. L-AmB is the recommended regimen for VL in the Mediterranean region and South America. Treatment of CL should be decided by the severity of clinical lesions, etiological species and its potential to develop into mucosal leishmaniasis. Expert opinion There is an urgent need to implement a single dose L-AmB or combination therapy in the Indian subcontinent. Combination therapy with newer drugs needs to be tested in Africa. Due to the toxicity of systemic therapy, a trend towards local treatment for New World CL (NWCL) is preferred in patients without risk of mucosal disease.

There is an urgent need for exploratory studies with short course, highly efficient regimens such as single dose L-AmB or combination therapy for all the endemic regions of VL. Shorter and more acceptable regimens are needed for the treatment of post-kala-azar dermal leishmaniasis. Treatment of CL remains one of the neglected areas of leishmaniasis as data are scarce and drawn from uncontrolled studies.

The treatment options of leishmaniasis are limited and far from satisfactory. For more than 60 years, treatment of leishmaniasis has centered around pentavalent antimonials (Sbv). Widespread misuse has led to the emergence of Sbv resistance in the hyperendemic areas of North Bihar. Other antileishmanials could also face the same fate, especially in the anthroponotic cycle. The HIV/ visceral leishmaniasis (VL) coinfected patients are another potential source for the emergence of drug resistance. At present no molecular markers of resistance are available and the only reliable method for monitoring resistance of isolates is the technically demanding in vitro amastigote-macrophage model. As the armametrium of drugs for leishmaniasis is limited, it is important that effective monitoring of drug use and response should be done to prevent the spread of resistance. Regimens of simultaneous or sequential combinations should be seriously considered to limit the emergence of resistance.

Visceral leishmaniasis (VL) is a serious parasitic disease causing considerable mortality and major disability in the Indian subcontinent. It is most neglected tropical disease, particularly in terms of new drug development for the lack of financial returns. An elimination campaign has been running in India since 2005 that aim to reduce the incidence of VL to below 1 per 10,000 people at sub-district level. One of the major components in this endeavor is reducing transmission through early case detection followed by complete treatment. Substantial progress has been made during the recent years in the area of VL treatment, and the VL elimination initiatives have already saved many lives by deploying them effectively in the endemic areas. However, many challenges remain to be overcome including availability of drugs, cost of treatment (drugs and hospitalization), efficacy, adverse effects, and growing parasite resistance. Therefore, better emphasis on implementation research is urgently needed to determine how best to deliver existing interventions with available anti-leishmanial drugs. It is essential that the new treatment options become truly accessible, not simply available in endemic areas so that they may promote healing and save lives. In this review, we highlight the recent advancement and challenges in current treatment options for VL in disease endemic area, and discuss the possible strategies to improve the therapeutic outcome.Electronic supplementary materialThe online version of this article (doi:10.1186/s40249-016-0112-2) contains supplementary material, which is available to authorized users.