Safety and Effectiveness of Sodium Stibogluconate and Paromomycin Combination for the Treatment of Visceral Leishmaniasis in Eastern Africa: Results from a Pharmacovigilance Programme

Abstract

IntroductionIn 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.MethodsA 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.ResultsOverall 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.ConclusionsThis 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.

Genomic and Metabolomic Polymorphism among Experimentally Selected Paromomycin-Resistant Leishmania donovani Strains

“…In Bangladesh, in combination with MIL or AmBisome, PMM showed efficacy similar to that of AmBisome monotherapy for the treatment of VL (7). A study has shown that combined sodium stibogluconate (SSG) and PMM treatment in Sudan, Kenya, Uganda, and Ethiopia was an effective first-line option for VL chemotherapy (8). A retrospective study on the treatment of post-kala azar dermal leishmaniasis (PKDL), a complication of VL, showed that combination therapy with PMM was more effective than monotherapy with SSG in East Africa (9).…”

Recent Development of Visceral Leishmaniasis Treatments: Successes, Pitfalls, and Perspectives

“…The SSG-PM combination is the first choice in the region (1), with an efficacy of 91% at 6 months, but it requires 17 days of hospitalization (46). Effectiveness data showed that this regimen is more toxic and results in greater mortality in patients Ͼ50 years old and in coinfected HIV-VL patients (47). Trained health personnel and upgraded hospitals are key to minimizing the limitations of this regimen until a new (ideally oral) combination is ready.…”

“…A pharmacovigilance program in which 3,126 VL patients were treated with SSG-PM in 12 facilities in Ethiopia, Kenya, Sudan, and Uganda has confirmed no new safety signals, a high effectiveness at the EoT (95.1%), and a low mortality of 0.9%. However, results from this program also showed that SSG-PM is not a suitable treatment for patients who are Ͼ50 years old and HIV-VLcoinfected patients due to its lower efficacy and higher mortality rate, although these represent a small proportion of all VL patients (47). In Sudan, MSF found that the efficacy of SSG-PM treatment was 86% (506/591) at 6 months.…”

Vaccines for Visceral Leishmaniasis: Hopes and Hurdles

“…Current control measures that include case detection, drug treatment, and insecticide-impregnated bed nets are failing as evidenced by repeated epidemics especially in East Africa. In addition, increasing drug resistance and geographical expansion of the leishmaniases due to global warming and wars make the search for vaccines for the leishmaniases a necessity [2,[10][11][12][13][14][15]].…”