In October 2023, the World Health Organization announced that Bangladesh has eliminated visceral leishmaniasis (VL) as a public health problem – the first country in the world to achieve elimination status, reporting fewer than 1 case per 10,000 people over three consecutive years. Research conducted by DNDi and partners from 2012-2015 provided key evidence to support VL treatment policy change in Bangladesh, India, and Nepal, including the recommendation of single-dose liposomal amphotericin B as the first treatment option and a combination of paromomycin and miltefosine as the second option. The new options shortened the length of treatment, reduced the risk of resistance, and made it easier for people to complete their full course of treatment.

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.