For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
7
views
32
references
 Top references
cited by
1
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      176
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      In Vitro Susceptibility to Miltefosine of Leishmania infantum (syn. L.  chagasi) Isolates from Different Geographical Areas in Brazil

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Treatment of visceral leishmaniasis in Brazil still relies on meglumine antimoniate, with less than ideal efficacy and safety, making new therapeutic tools an urgent need. The oral drug miltefosine was assayed in a phase II clinical trial in Brazil with cure rates lower than previously demonstrated in India. The present study investigated the susceptibility to miltefosine in 73 Brazilian strains of Leishmania infantum from different geographic regions, using intracellular amastigote and promastigote assays. The EC 50 for miltefosine of 13 of these strains evaluated in intracellular amastigotes varied between 1.41 and 4.57 μM. The EC 50 of the 73 strains determined in promastigotes varied between 5.89 and 23.7 μM. No correlation between in vitro miltefosine susceptibility and the presence of the miltefosine sensitive locus was detected among the tested strains. The relatively low heterogeneity in miltefosine susceptibility observed for the 73 strains tested in this study suggests the absence of decreased susceptibility to miltefosine in Brazilian L. infantum and does not exclude future clinical evaluation of miltefosine for VL treatment in Brazil.

          Related collections

          Most cited references32

          • Record: found
          • Abstract: found
          • Article: not found

          Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis.

          Thomas Dorlo, Manica Balasegaram, Jos H. Beijnen … (2012)
          Miltefosine is an alkylphosphocholine drug with demonstrated activity against various parasite species and cancer cells as well as some pathogenic bacteria and fungi. For 10 years it has been licensed in India for the treatment of visceral leishmaniasis (VL), a fatal neglected parasitic disease. It is the first and still the only oral drug that can be used to treat VL and cutaneous leishmaniasis (CL). The standard 28 day miltefosine monotherapy regimen is well tolerated, except for mild gastrointestinal side effects, although its teratogenic potential severely hampers its general use in the clinic and roll-out in national elimination programmes. The pharmacokinetics of miltefosine are mainly characterized by its long residence time in the body, resulting in extensive drug accumulation during treatment and long elimination half-lives. At the moment, different combination therapy strategies encompassing miltefosine are being tested in multiple controlled clinical trials in various geographical areas of endemicity, both in South Asia and East Africa. We here review the most salient pre-clinical and clinical pharmacological aspects of miltefosine, its mechanism of action against Leishmania parasites and other pathogens, and provide a systematic overview of the efficacy and safety data from all clinical trials of miltefosine, either alone or in combination, in the treatment of VL and CL.
          Article 0 comments Cited 233 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Oral miltefosine for Indian visceral leishmaniasis.

            Shyam Sundar, T Jha, C P Thakur … (2002)
            There are 500,000 cases per year of visceral leishmaniasis, which occurs primarily in the Indian subcontinent. Almost all untreated patients die, and all the effective agents have been parenteral. Miltefosine is an oral agent that has been shown in small numbers of patients to have a favorable therapeutic index for Indian visceral leishmaniasis. We performed a clinical trial in India comparing miltefosine with the most effective standard treatment, amphotericin B. The study was a randomized, open-label comparison, in which 299 patients 12 years of age or older received orally administered miltefosine (50 or 100 mg [approximately 2.5 mg per kilogram of body weight] daily for 28 days) and 99 patients received intravenously administered amphotericin B (1 mg per kilogram every other day for a total of 15 injections). The groups were well matched in terms of age, weight, proportion with previous failure of treatment for leishmaniasis, parasitologic grade of splenic aspirate, and splenomegaly. At the end of treatment, splenic aspirates were obtained from 293 patients in the miltefosine group and 98 patients in the amphotericin B group. No parasites were identified, for an initial cure rate of 100 percent. By six months after the completion of treatment, 282 of the 299 patients in the miltefosine group (94 percent [95 percent confidence interval, 91 to 97]) and 96 of the 99 patients in the amphotericin B group (97 percent) had not had a relapse; these patients were classified as cured. Vomiting and diarrhea, generally lasting one to two days, occurred in 38 percent and 20 percent of the patients in the miltefosine group, respectively. Oral miltefosine is an effective and safe treatment for Indian visceral leishmaniasis. Miltefosine may be particularly advantageous because it can be administered orally. It may also be helpful in regions where parasites are resistant to current agents. Copyright 2002 Massachusetts Medical Society
            Article 0 comments Cited 161 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Increasing failure of miltefosine in the treatment of Kala-azar in Nepal and the potential role of parasite drug resistance, reinfection, or noncompliance.

              Murari Das, Bart Ostyn, Surendra Uranw … (2013)
              Miltefosine (MIL), the only oral drug for visceral leishmaniasis (VL), is currently the first-line therapy in the VL elimination program of the Indian subcontinent. Given the paucity of anti-VL drugs and the looming threat of resistance, there is an obvious need for close monitoring of clinical efficacy of MIL. In a cohort study of 120 VL patients treated with MIL in Nepal, we monitored the clinical outcomes up to 12 months after completion of therapy and explored the potential role of drug compliance, parasite drug resistance, and reinfection. The initial cure rate was 95.8% (95% confidence interval [CI], 92.2-99.4) and the relapse rate at 6 and 12 months was 10.8% (95% CI, 5.2-16.4) and 20.0% (95% CI, 12.8-27.2) , respectively. No significant clinical risk factors of relapse apart from age <12 years were found. Parasite fingerprints of pretreatment and relapse bone marrow isolates within 8 patients were similar, suggesting that clinical relapses were not due to reinfection with a new strain. The mean promastigote MIL susceptibility (50% inhibitory concentration) of isolates from definite cures was similar to that of relapses. Although more tolerant strains were observed, parasite resistance, as currently measured, is thus not likely involved in MIL treatment failure. Moreover, MIL blood levels at the end of treatment were similar in cured and relapsed patients. Relapse in one-fifth of the MIL-treated patients observed in our study is an alarming signal for the VL elimination campaign, urging for further review and cohort monitoring.
              Article 0 comments Cited 126 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                David S. Lindsay: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Microorganisms
                Journal ID (iso-abbrev): Microorganisms
                Journal ID (publisher-id): microorganisms
                Title: Microorganisms
                Publisher: MDPI
                ISSN (Electronic): 2076-2607
                Publication date (Electronic): 05 June 2021
                Publication date Collection: June 2021
                Volume: 9
                Issue: 6
                Electronic Location Identifier: 1228
                Affiliations
                [1 ]Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-000, Brazil; caroline.respada@ 123456gmail.com (C.R.E.); ericavclevatti@ 123456gmail.com (E.V.d.C.L.)
                [2 ]Laboratório de Pesquisa em Leishmanioses, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-900, Brazil; maricboite@ 123456gmail.com (M.C.B.); elisa.cupolillo@ 123456gmail.com (E.C.)
                [3 ]Universidade Federal do Piauí, Hospital de Doenças Tropicais Natan Portela, Teresina, Piauí 64002-510, Brazil; dorcas.lc@ 123456gmail.com (D.L.); chncosta@ 123456gmail.com (C.H.N.C.)
                [4 ]Drugs for Neglected Diseases initiative (DNDi), 1202 Geneva, Switzerland; jalvar@ 123456dndi.org
                [5 ]Drugs for Neglected Diseases initiative (DNDi), Rio de Janeiro 20010-020, Brazil; jrode@ 123456dndi.org
                Author notes
                [* ]Correspondence: srbulian@ 123456icb.usp.br
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-1391-8091
                https://orcid.org/0000-0002-9537-2987
                https://orcid.org/0000-0002-2903-6280
                https://orcid.org/0000-0001-7302-2006
                https://orcid.org/0000-0002-8070-3704
                Article
                Publisher ID: microorganisms-09-01228
                DOI: 10.3390/microorganisms9061228
                PMC ID: 8228039
                PubMed ID: 34198947
                SO-VID: 109d530d-3dab-4941-a3e7-1f12fe9e41f9
                Copyright © © 2021 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 29 March 2021
                Date accepted : 02 June 2021
                Categories
                Subject: Article

                Keywords: clinical strains,miltefosine,susceptibility,visceral leishmaniasis
                Data availability:
                Keywords: clinical strains, miltefosine, susceptibility, visceral leishmaniasis

                Comments

                Comment on this article

                scite_

                Similar content176

                See all similar

                Cited by1

                See all cited by

                Most referenced authors415

                See all reference authors