Liposomal amphotericin B in travelers with cutaneous and muco-cutaneous leishmaniasis: Not a panacea

Romain Guery (1) , Benoît Henry (1) , Guillaume Martin-Blondel (2) , Claire Rouzaud (1) , Florence Cordoliani (3) , Gundel Harms (4) , Jean-Pierre Gangneux (5) , Francoise Foulet (6) , Emmanuelle Bourrat (3, 7) , Michel Baccard (3) , Gloria Morizot (8) , Paul-Henri Consigny (9, 1) , Antoine Berry (2) , Johannes Blum (10) , Olivier Lortholary (1) , Pierre Buffet (11)

1 Centre d'infectiologie Necker-Pasteur [CHU Necker]
2 CPTP - Centre de Physiopathologie Toulouse Purpan
3 Hôpital Saint-Louis
4 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
5 Irset - Institut de recherche en santé, environnement et travail
6 CHU Henri Mondor [Créteil]
7 Hôpital Robert Debré
8 ICAReB - Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources
9 CMIP - Centre Médical de l'Institut Pasteur
10 Swiss Tropical and Public Health Institute [Basel]
11 INTS - Institut National de la Transfusion Sanguine [Paris]

BACKGROUND:Complex cutaneous and muco-cutaneous leishmaniasis (CL and MCL) often requires systemic therapy. Liposomal amphotericin B (L-AmB) has a strong potential for a solid clinical benefit in this indication.METHODS:We conducted a retrospective analysis of data from a French centralized referral treatment program and from the "LeishMan" European consortium database. All patients with parasitologically proven CL or MCL who received at least one dose of L-AmB were included. Positive outcome was based on ulcer closure as per recent WHO workshop guidelines.RESULTS:From 2008 through 2016, 43 travelers returning from 18 countries (Old World n = 28; New World n = 15) were analyzed with a median follow-up duration of 79 days [range 28-803]. Main clinical forms were: localized CL with one or multiple lesions (n = 32; 74%) and MCL (n = 8; 19%). As per published criteria 19 of 41 patients (46%) were cured 90 days after one course of L-AmB. When the following items -improvement before day 90 but no subsequent follow-up, delayed healing (>3 months) and healing after a second course of L-AmB- were included in the definition of cure, 27 of 43 patients (63%) had a positive outcome. Five patients (MCL = 1; CL = 4) experienced a relapse after a median duration of 6 months [range 3-27] post treatment and 53% of patients (23/43) experienced at least one adverse event including severe hypokalaemia and acute cardiac failure (one patient each). In multivariate analysis, tegumentary infection with L. infantum was associated with complete healing after L-AmB therapy (OR 5.8 IC 95% [1.03-32]) while infection with other species had no impact on outcome.CONCLUSION:In conditions close to current medical practice, the therapeutic window of L-AmB was narrow in travellers with CL or MCL, with the possible exception of those infected with L. infantum. Strict follow-up is warranted when using L-AmB in patients with mild disease.

Domains: Life Sciences [q-bio]; Ecology, environment; Health

Romain Guery, Benoît Henry, Guillaume Martin-Blondel, Claire Rouzaud, Florence Cordoliani, et al.. Liposomal amphotericin B in travelers with cutaneous and muco-cutaneous leishmaniasis: Not a panacea. PLoS Neglected Tropical Diseases, 2017, 11 (11), pp.e0006094. ⟨10.1371/journal.pntd.0006094⟩. ⟨hal-01688584⟩