Sodium Stibogluconate (SSG) & Paromomycin Combination Compared to SSG for Visceral Leishmaniasis in East Africa: A Randomised Controlled Trial

Abstract

BackgroundAlternative treatments for visceral leishmaniasis (VL) are required in East Africa. Paromomycin sulphate (PM) has been shown to be efficacious for VL treatment in India.MethodsA multi-centre randomized-controlled trial (RCT) to compare efficacy and safety of PM (20 mg/kg/day for 21 days) and PM plus sodium stibogluconate (SSG) combination (PM, 15 mg/kg/day and SSG, 20 mg/kg/day for 17 days) with SSG (20 mg/kg/day for 30 days) for treatment of VL in East Africa. Patients aged 4–60 years with parasitologically confirmed VL were enrolled, excluding patients with contraindications. Primary and secondary efficacy outcomes were parasite clearance at 6-months follow-up and end of treatment, respectively. Safety was assessed mainly using adverse event (AE) data.FindingsThe PM versus SSG comparison enrolled 205 patients per arm with primary efficacy data available for 198 and 200 patients respectively. The SSG & PM versus SSG comparison enrolled 381 and 386 patients per arm respectively, with primary efficacy data available for 359 patients per arm. In Intention-to-Treat complete-case analyses, the efficacy of PM was significantly lower than SSG (84.3% versus 94.1%, difference = 9.7%, 95% confidence interval, CI: 3.6 to 15.7%, p = 0.002). The efficacy of SSG & PM was comparable to SSG (91.4% versus 93.9%, difference = 2.5%, 95% CI: −1.3 to 6.3%, p = 0.198). End of treatment efficacy results were very similar. There were no apparent differences in the safety profile of the three treatment regimens.ConclusionThe 17 day SSG & PM combination treatment had a good safety profile and was similar in efficacy to the standard 30 day SSG treatment, suggesting suitability for VL treatment in East Africa.Clinical Trials Registration www.clinicaltrials.gov NCT00255567

Oral azithromycin versus its combination with miltefosine for the treatment of experimental Old World cutaneous leishmaniasis

“…Among the anti-leishmanials, miltefosine and paromomycin were found appropriate for combination therapy because of less interference with other drugs. The use of different dose regimen in combination therapy of antileishmanial drugs was applied by many researchers (Hailu et al 2010;Sundar et al 2011;Musa et al 2012). They all showed that combination treatment is safe and effective in visceral leishmaniasis (VL), offering a significant reduction in treatment duration.…”

“…Furthermore, a control trial was carried out in East Africa for the treatment of VL comparing paramomycin (PM) 20 mg/kg/day for 21 days monotherapy with PM and sodium stibogluconate combination(PM 15 mg/kg/day and SSG 20 mg/kg/ day for 17 day) and SSG (30 mg/kg/day for 30 days) alone. The 17 day combination regimen found equally efficacious and safer in comparison to 30 days regimen (Musa et al 2012). In a trial to achieve this goal, in this study, combination of miltefosine with azitheromycin in their effective doses for shorter duration therapy of only 10 successive days was tested against L. major.…”

Synthesis and Antitrypanosomastid Activity of 1,4-Diaryl-1,2,3-triazole Analogues of Neolignans Veraguensin, Grandisin and Machilin G

“…After complete addition of n-BuLi, the reaction solution was kept at room temperature for one hour. Then, it was added 100 mL of saturated solution of NH 4 Cl and the product was extracted with ethyl acetate (3 × 100 mL). The organic phase was dried over anhydrous MgSO 4 and the solvent was removed under reduced pressure.…”

“…All these drugs, however, have important limitations regarding toxicity, pronounced side effects or high cost. 2,3 Recent studies have focused on combinations of these drugs, such as sodium stibogluconate-paromomycin 4 or miltefosine-paromomycin 5 in order to circumvent the resistance problems of different strains related to this disease. Despite the efforts of the Drugs for Neglected Diseases initiative (DNDi) in the clinical studies, only a few candidate drugs are under the development.…”

“…Therefore, current and new strategies must be expanded in the search for antileishmanial compounds. 4,5 Chagas disease is also a neglected, potentially lethal disease caused by a protozoan parasite, Trypanosoma cruzi. This disorder is an important health problem in Latin America, where it affects about eight million people.…”