4.5 Article

Susceptibility to paromomycin in clinical isolates and reference strains of Leishmania species responsible for tegumentary leishmaniasis in Brazil

Journal

ACTA TROPICA
Volume 215, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.actatropica.2020.105806

Keywords

Paromomycin; Drug susceptibility; Cutaneous leishmaniasis; Leishmania

Funding

  1. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2016/21171-6]
  2. UK Research and Innovation via the Global Challenges Research Fund under grant agreement 'A Global Network for Neglected Tropical Diseases' [MR/P027989/1]
  3. FAPESP [2018/03299-0, 2017/18488-4, 2020/01948-1]

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Treatment of tegumentary leishmaniasis in Brazil is currently limited to a few drugs, highlighting the need for expansion of therapeutic options. Paromomycin, an aminoglycoside antibiotic already approved for visceral leishmaniasis, shows promising activity against clinical isolates of tegumentary leishmaniasis in Brazil.
Treatment of tegumentary leishmaniasis in Brazil is limited to pentavalent antimonial, amphotericin B and pentamidine. These drugs, administered parenterally, cause several side effects and have a varied clinical response, depending on the species of Leishmania. Urgent expansion of the therapeutic arsenal against the disease is therefore necessary. Pammomycin is an aminoglycoside antibiotic that has already been approved for the treatment of visceral leishmaniasis in Southeast Asia. Here, we provide an in vitro evaluation of the activity of paromomycin in fifteen clinical isolates from patients with tegumentary leishmaniasis at a reference center for the treatment of the disease. Furthermore, the in vitro susceptibility to this drug in reference strains of Leishmania species that are endemic in Brazil has also been evaluated. Among the clinical isolates, nine were typed as Leishmania (Viannia) braziliensis, five as L. (Leishmania) amazonensis and one as L. (V.) guyanensis. Although never exposed to paromomycin, we found variable susceptibility among these isolates and reference strains in promastigotes and intracellular amastigotes, with the drug being more active in the amastigote form of the parasite. This study provides a preclinical dataset that is useful for the evaluation of pammomycin in the treatment of tegumentary leishmaniasis caused by species that are endemic in Brazil.

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