- Target disease: VL
- Main partners (since project start): INDIA: Indian Council of Medical Research; Rajendra Memorial Research Institute of Medical Sciences; Bihar State Health Society; National Vector Borne Disease Control Programme; Kala Azar Medical Research Centre; GVK Biosciences; BANGLADESH: Ministry of Health and Family Welfare; International Centre for Diarrhoeal Disease Research; Shaheed Suhrawardy Medical College and Hospital; OTHER: Médecins Sans Frontières, Spain; London School of Hygiene & Tropical Medicine, UK; WHO-TDR, Switzerland; Institute of Tropical Medicine-Antwerp, Belgium; OneWorld Health/PATH, USA.
- Project start: July 2010 (Bangladesh)/December 2006 (India)
- Funding (since project start): Bill & Melinda Gates Foundation, USA; Department for International Development (DFID), UK; Médecins Sans Frontières/Doctors without Borders, International; Spanish Agency for International Development Cooperation (AECID), Spain; Swiss Agency for Development and Cooperation (SDC), Switzerland; The Starr International Foundation, Switzerland; Other private foundations and individuals.
The Phase III trial conducted in India in 2008-2010 demonstrated the efficacy of combination therapies based on AmBisome®, miltefosine, and paromomycin, and an additional study by Sundar et al. showed the efficacy of single-dose AmBisome® given as an intravenous infusion. To facilitate the introduction of these new treatments for VL in South Asia, DNDi conducted safety and effectiveness studies, including a pilot project in the Bihar State of India (2012-2015) implementing combination therapies at the primary healthcare level, and single-dose AmBisome® at the hospital level.
These regimens were observed to be safe and effective and, based on the study results, the Indian National Roadmap for Kala-Azar Elimination in August 2014 recommended use of single dose AmBisome® as a first option treatment for VL patients, with paromomycin and miltefosine as a second option; a policy also reflected in Bangladesh and Nepal. This removal of miltefosine monotherapy is an important policy change. The pilot study continued following up patients, documenting 12 month treatment outcomes, at the request of the national program; this follow up was completed in September 2015. Site close out activities were completed in January 2016.
In Bangladesh, a two-step Phase III study conducted from 2010-2014 in 602 patients (first in hospital settings, then in primary healthcare centres) used the same combination therapies as those tested in India. All tested treatments demonstrated excellent cure rates and were well tolerated by patients, in support of policy change in the country.
Following a 2016 pilot study in Bihar, India on three regimens (including new combination therapies (single dose AmBisome® (SDA), a combination of miltefosine and paromomycin, and a combination of AmBisome® and miltefosine) whose results contributed to a change in the national treatment guidelines in India, a follow-up protocol was developed for a cohort observational study to estimate the incidence of post-kala-azar dermal leishmaniasis (PKDL) during or more than 24 months post-treatment in VL patients treated with any of the three regimens. Enrolment started in June 2016, and by the end of 2017, recruitment was completed with 1622 participants assessed (representing 92% of the VL patients treated in the India implementation study). Preliminary results show that PKDL was observed in 3.6% of patients at least 24 months after treatment of VL. Further analysis is ongoing.
Last update: March 2018