- Target disease: Post kala-azar dermal leishmaniasis (PKDL)
- Main partners (since project start): International Centre for Diarrhoeal Disease Research, Bangladesh; Instituto de Salud Carlos III, Spain; Institute of Endemic Disease, Khartoum University, Sudan; Institute of Medical Sciences, Banaras Hindu University, India; i+solutions, The Netherlands; Kala Azar Medical Research Centre, India; Lambda Therapeutic Research Ltd., India; LEAP; Ministry of Health, Sudan; Muzaffarpur Hospital, India; National Institute of Pathology, India; Netherlands Cancer Institute; The Netherlands; Rajendra Memorial Research Institute of Medical Sciences, India; SK Hospital, Mymensingh, Bangladesh; University of Gedaraf, Sudan; Uppsala University, Sweden.
- Project start: March 2015
- Funding (since project start): Bill & Melinda Gates Foundation, USA; Department for International Development (DFID), UK; Dutch Ministry of Foreign Affairs (DGIS), The Netherlands; French Development Agency (AFD), France; Médecins Sans Frontières/Doctors without Borders; Special Programme for Research and Training in Tropical Diseases (WHO-TDR), Switzerland.
PKDL is a non-lethal complication of VL which can develop months or years after VL treatment has been completed, and can be severely disfi guring and stigmatizing, as the symptoms are characterized by a skin rash, often on the face. Better treatment options are needed, as existing treatments include options that are expensive and lengthy, with complex administration and potentially toxic effects. DNDi is prioritizing the management of PKDL patients who are believed to constitute a potential reservoir of infection for visceral leishmaniasis in South Asia and East Africa. Early treatment of PKDL patients could be critical elements of any visceral leishmaniasis public health and elimination strategy.
In Sudan, a Phase II study to test both liposomal amphotericin B in combination with miltefosine, and paromomycin in combination with miltefosine began in Dooka, Sudan in 2018 and had recruited 39 patients by January 2019. Results are expected by mid-2021.
In South Asia, with 126 patients enrolled in three sites in India (KAMRC and RMRI) and Bangladesh (icddr,b), recruitment has been completed in DNDi’s Phase II study to assess the safety and efficacy of liposomal amphotericin B monotherapy and a combination of liposomal amphotericin B and miltefosine.
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 Sudan, preparation for a similar infectivity study is underway.
In late 2017, recruitment started for a Phase II study in Asia to test both AmBisome® monotherapy and a combination of AmBisome® and miltefosine, 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 Phase II study to test both AmBisome in combination with miltefosine, and paromomycin in combination with miltefosine is under preparation in Sudan. Target recruitment will be 110 patients over two years.
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. In Sudan, the preparation of an insectarium for infectivity studies continues.
A Phase II study testing both AmBisome® monotherapy and a combination of AmBisome® and miltefosine is underway in India and Bangladesh to assess the safety and efficacy for patients with PKDL. A separate Phase II study to assess the safety and efficacy of both AmBisome® in combination with miltefosine, and paromomycin in combination with miltefosine, is planned in Sudan. Site visits have been undertaken at all participating sites in the three countries, and protocols and study documents are under finalization for submission to ethical and regulatory review. In addition, two PKDL infectivity studies are under preparation in Bangladesh and Sudan. Their objective is to establish the infectivity of PKDL patients to sand flies, to determine if PKDL patients maintain interepidemic transmission of VL.
Last update: August 2019