Use of topical rSm29 in combination with intravenous meglumine antimoniate in the treatment of cutaneous leishmaniasis: A randomized controlled trial

Int J Infect Dis. 2024 Oct:147:107206. doi: 10.1016/j.ijid.2024.107206. Epub 2024 Aug 13.

Abstract

Background: Cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is associated with an inflammatory response. Granzyme (GzmB) and IL-1β play a key role in the pathology. Meglumine antimoniate (MA) is the first-choice drug for the treatment of CL, but therapy failure is observed in up to 50% of the cases. The protein, rSm29 of Schistosoma mansoni, down-modulates pro-inflammatory cytokine production. We evaluate if the combination of topical rSm29 plus MA increases the cure rate of CL.

Methods: In this randomized clinical trial, 91 CL patients were allocated in 3 groups. All cases received MA (20 mg/kg/weight) for 20 days. Group 1 used topical rSm29 (10 µg), group 2 a placebo topically applied, and group 3 received only MA.

Results: The cure rate on day 90 was 71% in subjects treated with rSm29 plus MA, and 43% in patients who received MA plus placebo or MA alone (P < 0.05). There was a decrease in GzmB and an increase in IFN-γ (P < 0.05) in supernatants of skin biopsies of the lesions obtained on D7 of therapy (P < 0.05) in patients who received rSm29.

Conclusion: rSm29 associated with MA reduces GzmB levels, is more effective than MA alone, and decreases CL healing time.

Clinical trials registration: ClinicalTrial.gov under NCT06000514.

Keywords: Cutaneous leishmaniasis; Inflammatory response; Leishmania (Viannia) braziliensis; Therapy; rSm29.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Intravenous
  • Administration, Topical*
  • Adolescent
  • Adult
  • Animals
  • Antiprotozoal Agents* / administration & dosage
  • Antiprotozoal Agents* / therapeutic use
  • Drug Therapy, Combination*
  • Female
  • Granzymes / metabolism
  • Humans
  • Leishmania braziliensis / drug effects
  • Leishmaniasis, Cutaneous* / drug therapy
  • Leishmaniasis, Cutaneous* / parasitology
  • Male
  • Meglumine / administration & dosage
  • Meglumine / therapeutic use
  • Meglumine Antimoniate* / administration & dosage
  • Meglumine Antimoniate* / therapeutic use
  • Middle Aged
  • Organometallic Compounds* / administration & dosage
  • Organometallic Compounds* / therapeutic use
  • Treatment Outcome
  • Young Adult

Substances

  • Meglumine Antimoniate
  • Antiprotozoal Agents
  • Organometallic Compounds
  • Meglumine
  • Granzymes

Associated data

  • ClinicalTrials.gov/NCT06000514