title: Safety and Effectiveness of Sodium Stibogluconate and Paromomycin Combination for the Treatment of Visceral Leishmaniasis in Eastern Africa: Results from a Pharmacovigilance Programme.
abstract: BACKGROUND
  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.
authors.affiliation: Centre for Clinical Research, Kenya Medical Research Institute, PO Box 20778-00202, Off Mbagathi Rd, Nairobi, Kenya. rkimutai@dndi.org.|Drugs for Neglected Diseases Initiative (DNDi), Nairobi, Kenya. rkimutai@dndi.org.
authors.forename: Robert
authors.identifier: http://orcid.org/0000-0002-1039-378X
authors.initials: R
authors.lastname: Kimutai
authors.affiliation: Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Musa
authors.affiliation: Centre for Clinical Research, Kenya Medical Research Institute, PO Box 20778-00202, Off Mbagathi Rd, Nairobi, Kenya.
authors.forename: Simon
authors.initials: S
authors.lastname: Njoroge
authors.affiliation: Drugs for Neglected Diseases Initiative (DNDi), Nairobi, Kenya.
authors.forename: Raymond
authors.initials: R
authors.lastname: Omollo
authors.affiliation: Drugs for Neglected Diseases Initiative (DNDi), Geneva, Switzerland.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Alves
authors.affiliation: School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
authors.forename: Asrat
authors.initials: A
authors.lastname: Hailu
authors.affiliation: Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
authors.forename: Eltahir A G
authors.initials: EA
authors.lastname: Khalil
authors.affiliation: University of Gondar, Gondar, Ethiopia.
authors.forename: Ermias
authors.initials: E
authors.lastname: Diro
authors.affiliation: Drugs for Neglected Diseases Initiative (DNDi), Nairobi, Kenya.
authors.forename: Peninah
authors.initials: P
authors.lastname: Soipei
authors.affiliation: Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
authors.forename: Brima
authors.initials: B
authors.lastname: Musa
authors.affiliation: Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
authors.forename: Khalid
authors.initials: K
authors.lastname: Salman
authors.affiliation: Médecins Sans Frontières, Geneva, Switzerland.
authors.forename: Koert
authors.initials: K
authors.lastname: Ritmeijer
authors.affiliation: Médecins Sans Frontières, Geneva, Switzerland.|Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Francois
authors.initials: F
authors.lastname: Chappuis
authors.affiliation: Centre for Clinical Research, Kenya Medical Research Institute, PO Box 20778-00202, Off Mbagathi Rd, Nairobi, Kenya.
authors.forename: Juma
authors.initials: J
authors.lastname: Rashid
authors.affiliation: University of Gondar, Gondar, Ethiopia.
authors.forename: Rezika
authors.initials: R
authors.lastname: Mohammed
authors.affiliation: Arba Minch Hospital, Regional Health Bureau of SNNPR State, Arba Minch, Ethiopia.
authors.forename: Asfaw
authors.initials: A
authors.lastname: Jameneh
authors.affiliation: School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
authors.forename: Eyasu
authors.initials: E
authors.lastname: Makonnen
authors.affiliation: Makerere University, Kampala, Uganda.
authors.forename: Joseph
authors.initials: J
authors.lastname: Olobo
authors.affiliation: Amudat Hospital, Amudat, Uganda.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Okello
authors.affiliation: Amudat Hospital, Amudat, Uganda.
authors.forename: Patrick
authors.initials: P
authors.lastname: Sagaki
authors.affiliation: Drugs for Neglected Diseases Initiative (DNDi), Geneva, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Strub
authors.affiliation: Drugs for Neglected Diseases Initiative (DNDi), Geneva, Switzerland.
authors.forename: Sally
authors.initials: S
authors.lastname: Ellis
authors.affiliation: Drugs for Neglected Diseases Initiative (DNDi), Geneva, Switzerland.
authors.forename: Jorge
authors.initials: J
authors.lastname: Alvar
authors.affiliation: MSF Access Campaign, Geneva, Switzerland.
authors.forename: Manica
authors.initials: M
authors.lastname: Balasegaram
authors.affiliation: Médecins Sans Frontières, Geneva, Switzerland.|Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Emilie
authors.initials: E
authors.lastname: Alirol
authors.affiliation: Centre for Clinical Research, Kenya Medical Research Institute, PO Box 20778-00202, Off Mbagathi Rd, Nairobi, Kenya.|Drugs for Neglected Diseases Initiative (DNDi), Nairobi, Kenya.
authors.forename: Monique
authors.initials: M
authors.lastname: Wasunna
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000351:Africa, Eastern; D000967:Antimony Sodium Gluconate / Q000008:administration & dosage*; D000981:Antiprotozoal Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D060085:Coinfection; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010303:Paromomycin / Q000008:administration & dosage*; D060735:Pharmacovigilance; D011446:Prospective Studies; D012008:Recurrence; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000981:Antiprotozoal Agents; D010303:Paromomycin; D000967:Antimony Sodium Gluconate