By Ayele Addis Ambelu
Nairobi, Kenya — 17 Jul 2024
A groundbreaking clinical trial has unveiled a safer, shorter, and more effective treatment for post-kala-azar dermal leishmaniasis (PKDL), a debilitating skin disease prevalent in Eastern Africa and South Asia. Conducted by the non-profit medical research organization Drugs for Neglected Diseases initiative (DNDi) and the Institute of Endemic Diseases at the University of Khartoum, the trial’s results, published in PLOS Neglected Tropical Diseases, promise a significant improvement in managing this condition.
PKDL, which can develop following treatment for visceral leishmaniasis (VL) or kala-azar, manifests as a rash around the mouth, potentially spreading to the arms and upper body, and, in severe cases, across the entire body. In Sudan, nearly 20% of VL patients develop PKDL within six months post-treatment, marking the highest rate globally. The current standard treatment, sodium stibogluconate (SSG), requires a lengthy 60-90 day hospital stay and carries life-threatening toxicity risks, posing substantial challenges for patients, particularly children.
Clinical Trial Design and Findings
Beginning in 2018, the Phase II trial in Doka, Sudan, tested two treatment regimens involving nearly 90% of participants aged 12 years or younger. Arm 1 combined oral miltefosine and injectable paromomycin (MF+PM) for 42 days, necessitating only a 14-day hospital stay during the paromomycin treatment. The remaining treatment was completed at home. This regimen achieved a remarkable 98% complete cure rate at the 12-month follow-up, proving highly effective for both moderate and mild PKDL cases.
Arm 2 tested a regimen of miltefosine and injectable liposomal amphotericin B (MF+LAmB) for 28 days, requiring just a 7-day hospital stay until the LAmB treatment concluded, followed by oral treatment at home. This group saw an 80% cure rate, establishing MF+LAmB as a viable alternative.
Expert Insights
“Treatment for PKDL in Sudan has been reserved for severe or persistent cases due to the prolonged, toxic, and expensive nature of SSG,” stated Professor Ahmed Musa, Senior Investigator for Leishmaniasis from the Institute of Endemic Diseases at the University of Khartoum. “We now have a safer and more patient-friendly option where hospitalization is minimized to 14 days, followed by home-based oral treatment. This is particularly crucial for children, who are most affected by PKDL.”
Dr. Fabiana Alves, Director of the Leishmaniasis Cluster at DNDi, emphasized the broader implications: “Patients with PKDL in Eastern Africa have long been neglected by medical research because the disease is not life-threatening. They have endured stigma and costly, prolonged treatments with significant toxicity risks. This new regimen will vastly improve their quality of life and reduce VL transmission, advancing our goal of eliminating VL.”
Public Health Impact and Future Directions
The World Health Organization (WHO) highlights the importance of detecting and treating PKDL to eliminate VL as a public health issue. The WHO’s recent VL elimination framework for Eastern Africa aims to ensure all PKDL cases are detected, reported, and managed by 2030. The trial’s findings support these objectives, providing critical evidence for policymakers to adopt more patient-friendly treatments.
WHO’s Special Programme for Research and Training in Tropical Diseases (WHO-TDR), the French Development Agency (AFD), Médecins Sans Frontières, the UK International Development, and the Swiss Agency for Development and Cooperation (SDC) provided financial backing for the study.
THE RESULTS
• Of the 55 patients treated with the combination of paromomycin and miltefosine, 98% had 100% healing of their lesions and no additional PKDL treatment after 12 months, even those with worse (grade 2 and 3) PKDL.
• Of the 55 patients treated with the combination of liposomal amphotericin B and miltefosine, 80% had
100% healing of their lesions and no additional PKDL treatment after 12 months.
• Nearly 90% of the 110 study participants were children. It was essential to study treatment efficacy in
children and adolescents because more than half of those affected by visceral leishmaniasis are kids.
• Patients were followed up for one year to assess the treatment outcome, though most patients were cured much earlier than one year.
• Both treatment combinations were safe and well tolerated. Drug reactions were primarily mild or
moderate, with more of the drug reactions found in the group that received liposomal amphotericin B and miltefosine.
The results of this clinical trial represent a significant step forward in treating PKDL, offering hope for better patient outcomes and contributing to the broader fight against VL. As policymakers consider these findings, the path to eliminating this neglected disease becomes clearer, promising a brighter future for affected communities in Eastern Africa and beyond.
