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


Journal

PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488

Informations de publication

Date de publication:
08 2023
Historique:
received: 24 11 2022
accepted: 30 06 2023
revised: 22 08 2023
medline: 24 8 2023
pubmed: 10 8 2023
entrez: 10 8 2023
Statut: epublish

Résumé

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. 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. 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 37561802
doi: 10.1371/journal.pntd.0011492
pii: PNTD-D-22-01470
pmc: PMC10443860
doi:

Substances chimiques

Paromomycin 61JJC8N5ZK
Antiprotozoal Agents 0
Aminoglycosides 0
Anti-Bacterial Agents 0
Gentamicins 0

Types de publication

Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0011492

Informations de copyright

Copyright: © 2023 Mouri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

I have read the journal’s policy and the authors of this manuscript have the following competing interests : PB is member of the scientific advisory committee of Drugs for Neglected Diseases initiative.

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Auteurs

Oussama Mouri (O)

AP-HP, Hôpital Pitié-Salpêtrière, Service de Parasitologie, Paris, France.

Cléa Melenotte (C)

Hôpital Necker Enfants Malades, Services de Maladies Infectieuses et Tropicales, Assistance-Publique des Hôpitaux de Paris, Paris, France.

Romain Guéry (R)

Department of Internal Medicine and Infectious Diseases, Hôpital du Confluent, Nantes, Paris, France.

Camille Cotteret (C)

Pharmacie, Hôpital Universitaire Necker-Enfants Malades Assistance-Publique des Hôpitaux de Paris, Paris, France.

Arnaud Schweitzer-Chaput (A)

Pharmacie, Hôpital Universitaire Necker-Enfants Malades Assistance-Publique des Hôpitaux de Paris, Paris, France.

Alice Perignon (A)

Service des maladies infectieuses et tropicales, groupe hospitalier Pitié-Salpêtrière, AP-HP, Paris, France.

Marc Thellier (M)

AP-HP, Hôpital Pitié-Salpêtrière, Service de Parasitologie, Paris, France.

Emmanuelle Bourrat (E)

Service de dermatologie Hôpital Saint Louis APHP Paris, Paris, France.
Service de pédiatre générale Hôpital Robert Debré APHP Paris, Paris, France.
Centre d'Investigations Cliniques, INSERM CIC1426, Hôpital Robert Debré, APHP.Nord, Université Paris Cité, Paris, France.

Florentia Kaguelidou (F)

Centre d'Investigations Cliniques, INSERM CIC1426, Hôpital Robert Debré, APHP. Nord, Université Paris Cité, Paris, France.

Jean Yves Siriez (JY)

Hôpital Robert-Debré, Service d'Accueil des Urgences pédiatriques, Assistance Publique-Hôpitaux de Paris, 48 boulevard Sérurier, Paris, France.

Denis Malvy (D)

Department of Infectious Diseases and Tropical Medicine, CHU Bordeaux, Bordeaux, France.
University of Bordeaux, National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Research Centre, Bordeaux, France.

Jean-Pierre Gangneux (JP)

Univ Rennes, CHU Rennes, Inserm, EHESP, IRSET (Institut de recherche en santé, environnement et travail)-UMR_S 1085, Rennes, France.

Alexandre Duvignaud (A)

Department of Infectious Diseases and Tropical Medicine, CHU Bordeaux, Bordeaux, France.
University of Bordeaux, National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Research Centre, Bordeaux, France.

Christophe Ravel (C)

Université de Montpellier, CNRS, IRD, Centre Hospitalo-Universitaire de Montpellier, MiVEGEC, Laboratoire de Parasitologie-Mycologie, CNR Leishmanioses, Montpellier, France.

Salvatore Cisternino (S)

Université de Paris, Necker-Enfants Malades University Hospital, Department of pharmacy, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Université de Paris, Inserm, UMRS-1144, Faculté de Pharmacie, Optimisation Thérapeutique en Neuropsychopharmacologie, Paris, France.

Janet Ransom (J)

Fast-Track Drugs and Biologics, North Potomac, Maryland, United States of America.

Eric Caumes (E)

Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
Centre de diagnostic, Hôpital de l'Hôtel-Dieu,-Paris, France.

Olivier Lortholary (O)

Hôpital Necker Enfants Malades, Services de Maladies Infectieuses et Tropicales, Assistance-Publique des Hôpitaux de Paris, Paris, France.
Paris University, Necker-Pasteur Center for Infectious Diseases and Tropical Medicine, Necker-Enfants Malades Hospital, AP-HP, IHU Imagine, Paris, France.

Max Grogl (M)

Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12). CIBERINFEC, ISCIII. Department of Medicine, Universidad Complutense, Madrid, Spain.
US Naval Medical Research Unit No. 6, Lima, Peru.

Pierre Buffet (P)

Centre d'Infectiologie Necker-Pasteur, Institut Pasteur, Paris, France.

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