Adoption of new visceral leishmaniasis treatments in South Asia  

Policy change for control and elimination of visceral leishmaniasis brings better treatments to patients in Bangladesh, India, and Nepal

In the early 21st century, treatments for visceral leishmaniasis (also known as kala-azar) in South Asia were difficult for patients to take or growing ineffective. Resistance was increasing, including to the oral drug miltefosine. Antimonials such as sodium stibogluconate had lengthy treatment times, difficult treatment administration, and poor tolerability that caused frequent side effects.

In 2010, WHO recommended using new short-course treatments for visceral leishmaniasis in South Asia based on excellent results in Phase III studies. However, more evidence was needed on the safety and effectiveness of using these treatments for in wider populations under field conditions.

DNDi convened a consortium of partners to identify the best combination therapies for South Asia. The consortium conducted a four year-long implementation study in Bangladesh and India (2012 – 2015) to assess the safety, efficacy, and patient adherence of three new treatment options: single-dose liposomal amphotericin B; a paromomycin and miltefosine combination; and a single-dose liposomal amphotericin B and miltefosine combination. The results showed that these treatments are safe and effective, with cure rates above 95%. They also shorten the length of treatment, reduce the risk of resistance, and allow treatment of patients closer to their homes, making it easier for people to complete the full treatment course.

The research provided key evidence for policy changes by the Bangladeshi, Indian, and Nepali Ministries of Health, which made the following recommendations: single-dose liposomal amphotericin B as the first option for treatment of visceral leishmaniasis, and a combination of paromomycin and miltefosine as the second option.

Ambisome treatment

Treatment regimens

  • Indication: Visceral leishmaniasis in Asia
  • Dosage: First option: single-dose liposomal amphotericin B given as an intravenous infusion; Second option: paromomycin and miltefosine, both daily for 10 days


  • Treatments recommended by WHO Expert Committee on the Control of Leishmaniases in 2010 as safe and effective treatments for visceral leishmaniasis in Asia (liposomal amphotericin B single or multiple dose, and all combinations tested in DNDi’s clinical trial) 
  • Supported policy change for the control and elimination of visceral leishmaniasis in highly endemic countries: Bangladesh, India, and Nepal 
  • Result of partnership in India with the Bihar State Health Society, GVK Biosciences, Indian Council of Medical Research, Kala Azar Medical Research Centre, Médecins Sans Frontières, National Vector Borne Disease Control Programme, and Rajendra Memorial Research Institute of Medical Sciences 
  • Result of partnership in Bangladesh with the International Centre for Diarrhoeal Disease Research, Médecins Sans Frontières, Ministry of Health and Family Welfare, Shaheed Suhrawardy Medical College and Hospital 

‘Earlier the ward used to be full of visceral leishmaniasis patients because of the long 28-day treatment. But since single-dose liposomal amphotericin B has been included in the national treatment protocol, the face of the disease has changed dramatically. Now patients come, take treatment, and go home the same day. This is an effective treatment, and now with this the number of patients have come down.’

Nutan Kumari, Sadar Hospital in Hajipur, Bihar  

Project updates


To overcome the limitations of current treatment regimens and contribute to the sustainable elimination of visceral leishmaniasis in South Asia, DNDi aims to deliver a safe, highly effective oral therapy for children and adults that can be deployed at all levels of the health system. A dossier to conduct a Phase II clinical trial on LXE408, a new chemical entity selected and nominated by the DNDi Scientific Advisory Committee as a clinical candidate, was submitted to Indian Regulatory Authorities in August 2021. 


In 2010, WHO recommended the use of new short-course treatment regimens for VL in South Asia. Although Phase III studies have shown excellent results, there was a lack of evidence on a wider treatment population, and on the safety and effectiveness of these regimens under field conditions. From 2012 to 2016, DNDi and partners conducted a pilot study in Bihar, India on three regimens (including new combination therapies (single dose liposomal amphotericin B, a combination of miltefosine and paromomycin (AmB+PM), and a combination of liposomal amphotericin B and miltefosine (AmB+Milt)) in 1761 patients. All regimens showed acceptable outcomes and safety profiles under field conditions. Cure rates were: for SDA 95.5%, AmB+Milt 95.5% and AmB+PM 99.6%. These results contributed to national treatment policy change in India, Bangladesh, and Nepal.


Following a 2016 pilot study in Bihar, India on three regimens (including new combination therapies (single dose liposomal amphotericin B (SDA), a combination of miltefosine and paromomycin, and a combination of liposomal amphotericin B 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.


In India, DNDi continues to support the rolling out of treatments as per the Indian National Kala-Azar Elimination Roadmap, after data from a DNDi implementation study contributed to a change in the national guidelines, which now recommend the use of single-dose liposomal amphotericin B in areas of high prevalence, and paromomycin/miltefosine combination in low-prevalence districts.


In Asia, DNDi and partners, working closely with the Indian government, have provided data from an implementation study (1761 enrolled patients) to support policy change expressed in the revised National Kala-Azar Elimination Roadmap, which recommends the use of liposomal amphotericin B single infusion in areas of high prevalence and paromomycin/miltefosine combination as appropriate in low prevalence districts. Follow-up visits continue to assess long-term efficacy and identify development of PKDL.

*Project cost includes direct and indirect costs, but it does not include in-kind contributions.