The World Health Organization guideline development group convened to review the evidence for new treatments for visceral leishmaniasis and PKDL in Eastern Africa and South Asia in November 2023. The process is ongoing, with the recommendations expected in 2025. In parallel, the regional technical advisory group for kala-azar and ministries of health of the endemic countries in the region are also expected to review the evidence and release new recommendations for the treatment of PKDL in South Asia. 

The Phase II clinical trial in South Asia was completed, demonstrating the suitability of safer, shorter, efficacious treatments for PKDL as alternatives to current long-course treatments that present toxicity risks. The manuscript prepared following the Phase II trial is under review. It is expected that these alternative therapies will be recommended for patients with PKDL. 

The Phase II study in India and Bangladesh aims to assess the safety and efficacy of liposomal amphotericin B monotherapy and a combination of liposomal amphotericin B and miltefosine for patients with PKDL. The two-year follow-up of study participants was completed in April 2021, and final study results are expected in the first quarter of 2022. 

Patient follow-up for DNDi’s Phase II study in India to assess the safety and efficacy of liposomal amphotericin B (LAmB) monotherapy and a combination of liposomal amphotericin B and miltefosine (LAmB+MF) continued through 2020. Results are expected by mid-2021 following completion of a 24-month follow-up period. 

Patient enrolment at three sites in India (KAMRC and RMRI) and Bangladesh (icddr,b) was completed in January 2019 for DNDi’s Phase II study to assess the safety and efficacy of liposomal amphotericin B (LAmB) monotherapy and a combination of liposomal amphotericin B and miltefosine (LAmB+MF). Results are expected by mid-2021 following completion of a 24-month follow-up period. 

Recruitment was completed at three sites in South Asia: KAMRC and RMRI in India, and icddr,b in Bangladesh, with 126 patients enrolled in DNDi’s Phase II study to assess the safety and efficacy of liposomal amphotericin B (LAmB) monotherapy and a combination of liposomal amphotericin B and miltefosine (LAmB+MF). 

The results of an infectivity study conducted in Bangladesh in 65 patients confirmed that PKDL acts as a reservoir for ongoing leishmaniasis infection. To assess long-term infectivity and the impact of treatment, the study protocol was amended to repeat xenodiagnosis on PKDL patients after treatment completion.  

In late 2017, recruitment started for a Phase II study in Asia to test both liposomal amphotericin B (LAmB) monotherapy and a combination of liposomal amphotericin B and miltefosine (LAmB+MF), with six patients enrolled in clinical sites in India (RMRI in Patna and KAMRC in Muzzafarpur), while a clinical site in Bangladesh is preparing for initiation. The target recruitment of 110 patients is expected to be completed by January 2019. 

A PKDL infectivity study – studying the ability of a pathogen to establish a horizontal infection, that is not from parent to child – in Bangladesh completed the recruitment of 65 patients and results are under analysis. 

A Phase II study testing both liposomal amphotericin B (LAmB) monotherapy and a combination of liposomal amphotericin B and miltefosine (LAmB+MF) is underway in India and Bangladesh to assess the safety and efficacy for patients with PKDL. Site visits have been undertaken at the participating sites, and protocols and study documents are under finalization for submission to ethical and regulatory review. In addition, a PKDL infectivity study is under preparation in Bangladesh. Their objective is to establish the infectivity of PKDL patients to sandflies, to determine if PKDL patients maintain interepidemic transmission of visceral leishmaniasis.