The World Health Organization (WHO) has updated its treatment guidelines for visceral leishmaniasis (VL), commonly known as kala-azar, and post-kala-azar dermal leishmaniasis (PKDL), introducing shorter, safer, and more patient-friendly treatment regimens for patients in eastern Africa and South-East Asia.
Kala-azar, also known as black fever, is a deadly parasitic disease transmitted through the bite of infected sandflies. It is considered one of the world’s deadliest parasitic killers after malaria. Symptoms include high fever, weight loss, anaemia, and enlargement of the spleen and liver. If left untreated, the disease can be fatal. It is endemic in around 80 countries, with an estimated 50,000–90,000 cases annually, although only 25–45% are reported to WHO. The good news is that leishmaniasis is both treatable and curable.
PKDL is a skin rash that can develop as a complication of kala-azar. Although it is not life-threatening, it can act as a potential reservoir of infection. The condition is also highly stigmatizing, with many affected individuals facing social isolation and mental health challenges.
The revised WHO guidelines include:
- Shorter, safer alternatives for treating primary visceral leishmaniasis in eastern Africa.
- New treatment options for PKDL in both eastern Africa and South-East Asia.
- Relapse management in immunocompetent VL patients in South-East Asia.
- Updated safety profile of miltefosine, including allometric dosing recommendations.
“For too long, patients suffering from leishmaniasis have endured treatments nearly as punishing as the disease itself, especially in Africa. These new WHO guidelines mark a turning point,” said Dr Daniel Ngamije Madandi, WHO Director of Malaria and Neglected Tropical Diseases.
“By recommending safer, shorter and more patient-friendly regimens, we are not just improving care; we are accelerating our fight to eliminate this devastating disease and offering renewed hope to communities across Africa and Asia,” he added.
Shift Away from Older Injectable Treatments
Leishmaniasis treatment varies depending on the disease type, the patient’s immune status, the parasite species, co-existing medical conditionsand geographic region.
For many years, patients in Africa were primarily treated with the injectable drug sodium stibogluconate (SSG), which required lengthy treatments and painful daily injections and caused severe side effects.
For the first time, WHO is recommending SSG-free regimens for eligible patients. However, the drug will continue to be used for those who cannot receive the newer therapies.
In eastern Africa, WHO now recommends combining the oral medicine miltefosine with paromomycin injections for treating both VL and PKDL. In South-East Asia, new combination therapies using liposomal amphotericin B, either alone or together with miltefosine, are recommended for PKDL.
The updated VL regimen in eastern Africa shortens treatment to 14 days, requires one fewer injection, and reduces toxicity compared to the current 17-day sodium stibogluconate and paromomycin injections.
Previously, chronic cases of PKDL in eastern Africa were often treated with toxic sodium stibogluconate given for 30–60 days or with liposomal amphotericin B over 20 days, whereas in South-East Asia, a 12-week regimen of miltefosine was in practice.
The newly recommended regimens are expected to significantly reduce treatment burden while improving safety and effectiveness.
WHO estimates that nearly half of all primary VL patients and all PKDL patients could benefit from these updated recommendations. Patients who experience a relapse of VL in South-East Asia will also benefit from clearer guidance on disease management. However, some patients in Africa who are not eligible for the miltefosine combination will continue to rely on existing treatment options until new therapies become available.
DNDi-Developed Therapies Recognized
Many of the newly recommended therapies were developed by the non-profit medical research organization Drugs for Neglected Diseases initiative (DNDi) and partners.
“We are delighted that more patient-friendly treatments developed with our partners have been recognized in the WHO guidelines. These advances are important steps towards elimination, but we are already looking ahead,”said Dr Fabiana Alves, Leishmaniasis-Mycetoma Cluster Director at DNDi.
She added that DNDi is collaborating with Novartis to develop LXE408, a promising oral drug candidate that could eventually eliminate the need for injectable treatments.
Following the publication of the updated WHO guidelines, countries affected by VL and PKDL are expected to revise their national treatment protocols.
Wyckliff Omondi, Head, Division of Vector Borne & Neglected Tropical Diseases at Kenya’s Ministry of Healthsaid the country is already working to incorporate the new recommendations into its national guidelines so patients can benefit from the improved treatments as soon as possible.
