Self-application of aminoglycoside-based creams to treat cutaneous leishmaniasis in travelers

Abstract

Background: In endemic foci, the use of an aquaphilic cream containing paromomycin with/without gentamicin to treat cutaneous leishmaniasis (CL) is safe, painless and cures 78-82% of patients with New and Old World CL. Self-application in travelers requires evaluation.

Methods: Travelers with 1-10 lesions of confirmed CL were prospectively treated with the paromomycin-gentamicin formulation (WR279396, 2012-2017, Group 1) and carefully follow up, or treated with a locally produced paromomycin-only cream (2018-2022, Group 2). The cream was applied once under supervision, then self-applied daily for 20-30 days. A cured lesion was defined as 100% re-epithelialization at day 42 without relapse at three months.

Results: Medical features were similar in Group 1 (17 patients), and Group 2 (23 patients). Patients were infected with either Leishmania major, L. infantum, L. killicki, L. guyanensis, L. braziliensis, or L. naiffi. Intention-to-treat and per-protocol cure rates were 82% (95% confidence interval (CI) [64.23;100.00]) and 87% (95% CI [71,29;100.00]) in Group 1, and 69% (95% CI [50.76; 88.37]) and 76% (95% CI [57.97; 94.41]) in Group 2. In the pooled Group 1&2, 75% (95% CI [61.58;88.42]) (30/40) and 81% (95% CI [68,46;93.6]) (30/37) of patients were cured in intention-to-treat and per-protocol, respectively. There were no significant differences observed in the success rates between Old World and New World CL (83.3% vs. 60%, p = 0.14). Prospective observations in Group 1 showed that adverse events were mainly pruritus (24%) and pain (18%) on lesions (all mild or moderate). No mucosal involvement was observed in either group.

Discussion: In this representative population of travelers who acquired CL either in the Old or New World, the 81% per-protocol cure rate of a self-applied aminoglycoside cream was similar to that observed in clinical trials.

Fig 1. Study flowchart for Group 1 & 2.

Fig 2

Lesions cure rate over time (Panel A. B). Lesions Cure Rate over Time (Intention-to-treat). Percentage cure of both index and all lesions that met criteria for clinical cure at each scheduled follow-up visit during the study. Clinical cure (intention-to-treat analysis) of index lesions occurred as early as day 20, the last day of drug application, at a rate of 35.3% for the ITT dataset. By day 42, 70% of index lesions were cured, while 88.6% of all lesions met clinical cure criteria. At day 100, the clinical cure rate for index lesions and all lesions reached 82.3% and 87.2% in ITT patients, respectively. (Panel C.D) Lesions Cure Rate over Time (Per Protocol). Percentage cure of both index and all lesions that met criteria for clinical cure at each scheduled follow-up visit during the study. Clinical cure (Per Protocol analysis) of index lesions occurred as early as day 20, the last day of drug application, at a rate of 37.5% for the Per Protocol dataset. By day 42, 68.75% of index lesions were cured, while 82.2% of all lesions met clinical cure criteria. At day 100, the clinical cure rate for index lesions and all lesions reached 87.2% and 91.2% in Per Protocol patients, respectively.

Fig 3. Evolution of the index lesion over time during the study.

In response to the drug treatment, lesion area increased for the index lesion during the treatment period (20 day), then decreased after the cream application period ended. By day 28, the mean index lesion size reduced by approximately 40% compared with the baseline lesion size. By day 28, the mean index lesion size reduced by approximately 50% and 99% by day 100 compared with the baseline lesion.

Fig 4. Summary in pictures of the evolution of the index lesion of patients treated with cream over the time during the study.

The squares in green indicates patients who meet the criterion for final clinical cure of the index lesion.