• Read DNDi's Press Release on the project
• Read about it on the WHO-TDR website
• Listen to audio podcast about the consortium: Interview with consortium partners: Dr. Bhawna Sharma (Head of DNDi India), Sally Ellis (Clinical Manager, DNDi), Dr. Philippe Desjeux (Senior Programme Officer, OWH), and Dr. Byron Arana (Scientist, TDR)

Status: DNDi’s objective is to identify a safe and effective shortcourse therapy using existing drugs, which could be easily deployed in control programmes and replace current treatment regimens which either lack efficacy (SSG in some regions), require long treatment courses (miltefosine, SSG, paromomycin) or are have some associated toxicity (conventional amphotericin B, SSG). Following preclinical and Phase II studies, an open label, randomized, prospective, non-inferiority Phase III trial was conducted to study the combination of drugs already registered in India: AmBisome®, miltefosine, and paromomycin. Three arms investigating the three possible 2-drug combinations with a maximum duration of 11 days were compared with the standard 30-day therapy (15 infusions every other day using amphotericin B). This study, involving a total of 634 patients, was completed in 2010. All three combination treatments were highly efficacious (> 97.5% cure rate), and none was inferior to the standard treatment using amphotericin B.

This project was developed in collaboration with ICMR, the Rajendra Memorial Research Institute of Medical Sciences (RMRI) in Patna and the Kala Azar Medical Research Centre (KAMRC) in Muzaffarpur. The complete results were published in The Lancet in January 2011 (1).

In parallel to this work, Sundar et al. conducted another Phase III study that showed the efficacy of a single dose of 10mg/kg of AmBisome® (n=304) given as an i.v. infusion, which cured 95.7% of patients at 6 months (95% CI 93.40-97.90). The treatment was shown to be non-inferior in both safety and efficacy to the standard treatment of amphotericin B 1mg/kg i.v. given as 15 infusions on alternate days (n=108).

In March 2010, a WHO Expert Committee on the Control of Leishmaniases met in Geneva and recommended that all 4 of the new treatments (the 3 combinations and single dose AmBisome®) be used preferentially to the monotherapy treatments for VL in South Asia used at the time.

A two-step Phase III trial (first in hospital settings followed by treatment in primary healthcare centres) using the same combinations have also been initiated in Bangladesh, with recruitment commencing in July 2010. In October 2011, about 152 patients had been enrolled in the study. In Nepal, OWH is also working on the introduction of combinations with the same drugs. In addition, discussions are in progress with the Indian National Vector Borne Disease Control Programme.

Following up on this set of activities and the obtained results, DNDi has actively developeda consortium with  OWH and TDR, to facilitate the introduction of these new treatments for VL in South Asia. This will be done in collaboration with health authorities at state, national, and regional levels. DNDi and its partners intend to implement effectiveness studies in the region to demonstrate that such treatments can be feasibly and safely implemented in primary healthcare settings in both the public and private sectors.

(1) Comparison of short-course multidrug treatment with standard therapy for visceral leishmaniasis in India: an open-label, non-inferiority, randomized controlled trial by Sundar S. et al. The Lancet, 2011 January, DOI:10.1016/S0140-6736(10)62050-8.