Introduction: In 2010, WHO recommended a new first-line treatment for visceral leishmaniasis (VL) in Eastern Africa. The new treatment, a combination of intravenous (IV) or intramuscular (IM) sodium stibogluconate (SSG) and IM paromomycin (PM) was an improvement over SSG monotherapy, the previous first-line VL treatment in the region. To monitor the new treatment's safety and effectiveness in routine clinical practice a pharmacovigilance (PV) programme was developed.

Methods: A prospective PV cohort was developed. Regulatory approval was obtained in Sudan, Kenya, Uganda and Ethiopia. Twelve sentinel sites sponsored by the Ministries of Health, Médecins Sans Frontières (MSF) and Drugs for Neglected Diseases initiative (DNDi) participated. VL patients treated using the new treatment were consented and included in a common registry that collected demographics, baseline clinical characteristics, adverse events, serious adverse events and treatment outcomes. Six-monthly periodic safety update reports (PSUR) were prepared and reviewed by a PV steering committee.

Results: Overall 3126 patients were enrolled: 1962 (62.7%) from Sudan, 652 (20.9%) from Kenya, 322 (10.3%) from Ethiopia and 190 (6.1%) from Uganda. Patients were mostly male children (68.1%, median age 11 years) with primary VL (97.8%). SSG-PM initial cure rate was 95.1%; no geographical differences were noted. HIV/VL co-infected patients and patients older than 50 years had initial cure rates of 56 and 81.4%, respectively, while 1063 (34%) patients had at least one adverse event (AE) during treatment and 1.92% (n = 60) had a serious adverse event (SAE) with a mortality of 1.0% (n = 32). There were no serious unexpected adverse drug reactions.

Conclusions: This first regional PV programme in VL supports SSG-PM combination as first-line treatment for primary VL in Eastern Africa. SSG-PM was effective and safe except in HIV/VL co-infected or older patients. Active PV surveillance of targeted safety, effectiveness and key VL outcomes such us VL relapse, PKDL and HIV/VL co-infection should continue and PV data integrated to national and WHO PV databases.

Funding

The Drugs for Neglected Diseases initiative is grateful to the following donors for their financial support of this study: Department for International Development (DFID) UK; Spanish Agency for International Development Cooperation (AECID), Spain; Dutch Ministry of Foreign Affairs (DGIS), The Netherlands; Federal Ministry of Education and Research (BMBF) through KfW / Germany and part of the EDCTP2 programme supported by the European Union; Swiss Agency for Development and Cooperation (SDC), Switzerland; Médecins Sans Frontières (Doctors Without Borders), International; Medicor Foundation, Liechtenstein; Fondation Pro Victimis, Switzerland; BBVA Foundation, Spain; and other foundations.

Conflict of interest

Robert Kimutai, Ahmed M. Musa, Simon Njoroge, Raymond Omollo, Fabiana Alves, Asrat Hailu, Eltahir A.G. Khalil, Ermias Diro, Peninah Soipei, Brima Musa, Khalid Salman, Koert Ritmeijer, Francois Chappuis, Juma Rashid, Rezika Mohammed, Asfaw Jameneh, Eyasu Makonnen, Joseph Olobo, Lawrence Okello, Patrick Sagaki, Nathalie Strub, Sally Ellis, Jorge Alvar, Manica Balasegaram, Emilie Alirol and Monique Wasunna declare that they have no conflicts of interest.

Ethical approval

All procedures in this study were in accordance with the 1964 Helsinki Declaration and its amendments. Regulatory approvals were obtained in Sudan, Kenya, Uganda and Ethiopia from the National Medicines and Poisons Board, Pharmacy and Poisons Board, National Drug Authority and Food Medicines Health Care Administration and Control Authority, respectively. In Kenya, the KEMRI Ethical Review Committee also approved the PV program. A waiver was obtained from the MSF Ethics Committee.

Informed consent

All patients or their caregivers provided written consent before being enrolled in the PV programme.

Fig. 1

Fig. 1

Pharmacovigilance schema and flow. DAT ...

Fig. 1

Pharmacovigilance schema and flow. DAT direct agglutination test, DNDi drugs for neglected diseases...