DOCSLIB.ORG

Pdf 331.71 K

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Pdf 331.71 K Mashhad University of Medical Sciences Clinical Research Development Center (MUMS) Reviews in Clinical Medicine Ghaem Hospital Systemic Treatments of Leishmaniasis: A Narrative Review Ahmad Reza Taheri (MD)1, Sara Sabouri Rad (MD)1, Sara Molkara (MD)2* 1Cutaneous Leishmaniasis Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. 2Resident of Dermatology, Imam Reza hospital, Mashhad University of Medical Sciences, Mashhad, Iran. ARTICLE INFO ABSTRACT Article type Cutaneous leishmaniasis is a prevalent parasitic infection in humans. According to the Review article reports published in several localities across the world, leishmaniasis is an endemic Article history and is often diagnosed through the smear examination of the affected area using a Received: 18 Aug 2019 microscope.disease in certain The treatments regions in ofIran. choice Leishmaniasis for leishmaniasis is transmitted involve the through use of sandfly pentavalent bites Revised: 8 Sep 2019 antimony compounds, such as meglumine antimoniate and sodium stibogluconate. Accepted: 22 Sep 2019 However, other medications have been proposed for the treatment of leishmaniasis, and there is ongoing research for effective, less harmful treatments. This narrative Keywords Cutaneous Leishmaniasis review aimed to summarize various systemic treatments for leishmaniasis. Systemic Treatment Please cite this paper as: Taheri AR, Sabouri Rad S, Molkara S. Systemic Treatments of Leishmaniasis: A Narrative Review. Rev Clin Med. 2019;6(3):91-97. Introduction Leishmaniasis is a prevalent disease of trop- less and might heal within a few months, while ic and sub-tropic regions, affecting 15 million they often cause impaired function, secondary in- individuals across the globe. Based on tropism, fections or persistent wounds (5,9,10). leishmaniasis is categorized into four clinical syn- - dromes, including cutaneous, mucocutaneous, dif- taneous clearing of the wounds without interven- fuse cutaneous, and visceral leishmaniasis (1-5). tionsThere in arethe severalpatients, influential including factors immunology in the spon and Cutaneous leishmaniasis is a chronic dermal genetics, locality, number and species of the para- condition, which is characterized by several clini- site, clinical symptoms, and severity of the lesions, cal symptoms due to the variable immunity status of the host, affected area, and age of the patients. of treatment. Considering the large variability of Leishmania major and L. tropica cause urban and theseand the factors, outcome spontaneous significantly recovery affects may the prolong, course rural leishmaniasis, respectively. The organism thereby leading to the scars that care particular- was transmitted to humans by Phlebotomus pa- ly problematic in various body parts that may be patasi in the Old World and is transmitted by the of cosmetic or functional importance. The leish- Lutzomyia species in the New World (1, 4-8). maniasis lesions in such areas require immediate - treatment. Therefore, treatments are considered ythematous papules, later developing into raised, crucial to controlling the dissemination of leish- ulceratedAfter the lesions biting (2,9,10).of the fly, The lesions lesions appear are aspain er- maniasis and its transmission between individu- *Corresponding author: Sara Molkara. This is an Open Access article distributed under the terms of the Resident of Dermatology, Imam Reza hospital, Mashhad Creative Commons Attribution License (http://creativecommons. University of Medical Sciences, Mashhad, Iran. org/licenses/by/3.0), which permits unrestricted use, distribution, E-mail: [email protected] and reproduction in any medium, provided the original work is Tel: 985138583845 properly cited. Rev Clin Med 2019; Vol 6 (No 3) 91 Published by: Mashhad University of Medical Sciences (http://rcm.mums.ac.ir) Taheri AR et al. als (especially in case of patients with immuno- maniasis. Glucantime is administered daily via intramuscular injection, while sodium stiboglu- the key objectives of leishmaniasis treatment in- conate is administered via slow intravenous injec- cludedeficiency) the treatment and preventing of all the recurrence.patients, limiting Some the of tion. Glucantime is available in Iran. According to spread of the lesions, eradicating the reservoirs of the guidelines of the World Health Organization the Leishmania species, controlling the spread of (WHO), the prescribed dose of antimony for sys- the disease, preventing the development of large temic treatment is 20 mg/kg of pentavalent anti- scars (particularly facial scars), and preventing mony, which is equal to 75 mg/kg of glucantime. the associated complications and disease recur- - rence (11,12). tains 425 milligrams of antimony (1.5 g of glucan- Various local and systemic treatments are avail- Since each five-milliliter shot of glucantime con able for leishmaniasis, including physical inter- be prescribed per 20 kilograms of the body weight ventions (e.g., curettage, surgery, thermotherapy, oftime), patients. 1-3 five-milliliter In general, shotsthe treatment of glucantime period could for cryotherapy, and laser therapy) and medications rural and urban leishmaniasis is two and three (e.g., derivatives of antimony and nanoparticle weeks, respectively. If the signs of recovery are not treatments). Since most of these treatments have observed within four weeks after the treatment, not been thoroughly examined in the clinical the treatment is considered a failure, and systemic setting, their dependability remains uncertain. treatment with the previous dosage is prescribed Meanwhile, some of the main causes of unreliable treatment methods for leishmaniasis include the of glucantime involves the gradual increase of the high costs, poor patient compliance due to the dosageagain (18). as one The quarter,most efficient one half, approach and three to the quar use- long-term need for intramuscular/intravenous in- jections, and risk of systemic toxicity (11,13). third day, respectively, followed by the adminis- One of the main challenges that limits the treat- trationters of theof the final full dosage dose on on the the fourth first, second,day and andon- ment options for leishmaniasis is the variable wards (19). Theoretically, glucantime acts by affecting the various Leishmania species (14,15). The present bioenergetic pathways of the amastigote form of studyefficacy aimed of the to medicationssummarize various that are systemic used against treat- Leishmania and disrupting oxidation and glycol- ments for leishmaniasis. ysis processes, thereby reducing the cell levels of adenosine triphosphate (20). According to re- Literature Review Pentavalent Antimony Compounds of glucantime include musculoskeletal pain, nau- Antimony has been used in medicine for cen- seaports, and the vomiting, most significant diarrhea, clinical abdominal adverse pain, effects head- turies, and its importance has long been recog- aches, cough, pneumonitis, loss of appetite, leth- application of this element was the treatment of of glucantime treatment, complications such as leishmaniasis.nized. In the pastIn the century, 20th century, the most Gaspar significant Vianna cardiac,argy, fever, hepatological, erythema, and and hives. nephrological At the final stagesdisor- (a pioneer in the treatment of leishmaniasis) re- ders have also been reported. Among the other ported the effects of potassium antimony tartrate adverse effects of this compound are the elevation (a trivalent antimony compound) on mucocutane- of pancreatic enzymes (observation of pancreati- ous leishmaniasis. However, the widespread use tis in some cases, particularly in patients with im- of this compound in the following years revealed paired renal function), dose-dependent changes its adverse effects, which led to the cessation of its in the electrocardiogram (most commonly T-wave use. Since the 1940s, other less harmful trivalent and ST-segment changes and QT prolongation), antimony compounds have become widespread and atrial and ventricular arrhythmia rarely (21). for the treatment of leishmaniasis, which are cur- The mechanism of action of sodium stiboglu- rently among the most common treatment op- conate remains unclear. It is speculated that this tions in this regard. However, their application is drug functions through affecting the enzymes that are involved in DNA synthesis. Several side-ef- the injection of these compounds and the asso- fects have been documented for sodium stibo- ciatedassociated complications with specific affect limitations. patient Forcompliance, instance, gluconate, and reports have suggested the risk thereby leading to the development of resistance of sodium stibogluconate intolerance syndrome. in some endemic regions (16,17). Some of the associated symptoms include fever, Currently, meglumine antimoniate (glucantime) arthralgia, myalgia, edema, and gastrointestinal and sodium stibogluconate (pentostam) are the complications, which may manifest at the initial most commonly prescribed pentavalent antimony stages of treatment. It is notable that these symp- derivatives for the treatment of cutaneous leish- toms are not dose-dependent and do not justify 92 Rev Clin Med 2019; Vol 6 (No 3) Published by: Mashhad University of Medical Sciences (http://rcm.mums.ac.ir) Taheri AR et al. the cessation of treatment. On the other hand, the ous leishmaniasis, 46% of the patients were re- main symptoms of sodium stibogluconate toxicity ported to recover after receiving treatment with include cardiotoxicity, pancreatitis,
Load more

Recommended publications
  • Review Article Use of Antimony in the Treatment of Leishmaniasis: Current Status and Future Directions
    SAGE-Hindawi Access to Research Molecular Biology International Volume 2011, Article ID 571242, 23 pages doi:10.4061/2011/571242 Review Article Use of Antimony in the Treatment of Leishmaniasis: Current Status and Future Directions Arun Kumar Haldar,1 Pradip Sen,2 and Syamal Roy1 1 Division of Infectious Diseases and Immunology, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, 4 Raja S. C. Mullick Road, Kolkata West Bengal 700032, India 2 Division of Cell Biology and Immunology, Institute of Microbial Technology, Council of Scientific and Industrial Research, Chandigarh 160036, India Correspondence should be addressed to Syamal Roy, [email protected] Received 18 January 2011; Accepted 5 March 2011 Academic Editor: Hemanta K. Majumder Copyright © 2011 Arun Kumar Haldar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In the recent past the standard treatment of kala-azar involved the use of pentavalent antimonials Sb(V). Because of progressive rise in treatment failure to Sb(V) was limited its use in the treatment program in the Indian subcontinent. Until now the mechanism of action of Sb(V) is not very clear. Recent studies indicated that both parasite and hosts contribute to the antimony efflux mechanism. Interestingly, antimonials show strong immunostimulatory abilities as evident from the upregulation of transplantation antigens and enhanced T cell stimulating ability of normal antigen presenting cells when treated with Sb(V) in vitro. Recently, it has been shown that some of the peroxovanadium compounds have Sb(V)-resistance modifying ability in experimental infection with Sb(V) resistant Leishmania donovani isolates in murine model.
    [Show full text]
  • T. Cruzi Invasion Summary Leishmania Phagosome
    What is happening in invasion? T. cruzi invasion- non phagocytic Phagocytosis Active invasion Yeast Trypanosoma cruzi Actin filaments Lamp-1 T. cruzi invasion summary Leishmania phagosome Treatment for kinetoplastid diseases HAT Early (these drugs cannot cross the blood/brain barrier) Suramin (1916) highly charged compound Mode of action (?) - inhibits metabolic enzymes (NAD+) Pentamidine (some resistance) Mode of action (?) - likely multiple targets Differential uptake of drug - parasite conc. mM quantites Late Melarsoprol (lipophilic) (1947) Highly toxic arsenical - up to 10% treated die Mode of action (?) - possibly energy metabolism Eflornithine (drug has similar affinity to mammalian enzyme) suicide inhibitor of ornithine decarboxylase blocking polyamine biosynthesis Treatments for HAT 1985 2005 Early Stage First-line drugs Pentamidine Pentamidine Suramin Suramin Clinical trials - DB 289 (Phase III) Pre-clinical stage - - Late-stage/CNS First-line drugs Melarsoprol Melarsoprol Eflornithine Clinical trials - Nifurtimox + Eflornithine Pre-clinical stage - - Treatment for kinetoplastid diseases Chagas Acute Nifurtimox 60-90 days Mode of action (?) ROS - then DNA damage Benznidazole 30-120 days Mode of action - thought to inhibit nucleic acid synthesis (ROS?) Chronic Virtually untreatable - just treat symptoms Treatments for Chagas 1985 2005 Acute Stage First-line drugs Benznidazole Benznidazole Nifurtimox Nifurtimox Clinical trials Allopurinal Indeterminate Stage Clinical trials - Benznidazole Chronic Stage First-line drugs -
    [Show full text]
  • A Comparative Study of Aminosidine Sulfate
    Iranian Journal of Pharmaceutical Research (2007), 6 (3): 209-215 Copyright © 2007 by School of Pharmacy Received: November 2005 Shaheed Beheshti University of Medical Sciences and Health Services Accepted: March 2006 Original Article A Comparative Study of Aminosidine Sulfate, Meglomine Antimoniate, Combination of both and Glucantime in Murine Leishmaniasis Treatment of Cutaneous Leishmaniasis, Caused by Leishmania tropica, with Topical Application of Paromomycin 20% in BALB-c Mice Mohammad Shahidi Dadras a*, Afshin Mirzaei b, Bahram Kazemi c, Leyla Nabai a and Ali Sharifian a aSkin Research Center, Shohada Hospital, Shaheed Beheshti University of Medical Sciences, Tehran, Iran. bFaculty of Medicine, Rafsanjan University of Medical Science, Rafsanjan, Iran. cCellular and Molecular Biology Research Center, Faculty of Medicine, Shaheed Beheshti University of Medical Sciences, Tehran, Iran. Abstract The current treatment of choice for cutaneous leishmaniasis is either parenteral or intralesional antimonial compounds. Each of these treatments has its own downfalls which include toxic side effects with the parentral injection and pain at the site of injection with the intralesional injection. In recent years, there has been more focus on Paromomycin as an alternative drug; however, current data arose many controversies. In this study, the efficacy of different therapeutic regimens including topical paromomycin 20%, topical gentamycin 0.5%, intralesional glucantime injections, topical paromomycin 20% combine with gentamycin 0.5%, and placebo were compared. The results showed that the topical application of paromomycin had better response, less recurrence. In conclusion, topical paromomycin 20% can be an appropriate substitute for intralesional injection of glucantime, but more studies are needed to support its efficacy in human cutaneous leishmaniasis.
    [Show full text]
  • Topical Treatment of Cutaneous Leishmaniasis
    Topical Treatment of Cutaneous Leishmaniasis Joseph EI-On, Ph.D., Rita Livshin, M.D., Zvi Even-Paz, M.D. , David Hamburger, Ph.D., and Louis Weinrauch, M. D . Department of Microbio logy and Immunology, Facult y of Hea lth Sciences, Dcn G urion University of the N cgev UE-O), Deer­ Sheva; Departmcnt of Dcrmatology, Hadassah Universi ty H ospital, Hebrcw University Had assa h Mcdical School (R L, ZE-P, LW), j erusalem; Teva Pharm aceutica l In dustries Ltd. (01-1 ), j erusa lem, Israel Six ty- seven patients, 19 fem :ll es and 48 m ales, 4-66 years develo pments did not affect the clinical he:ding process o ld , sufferin g fro m lesions o f cutaneous leishmaniasis which was generall y completed in a period of 10-30 d ays were treated to pica ll y with an o intme nt comprising 15% after termination of trea tment. In addition, 94% of the paro m o mycin sulfate and 12% m eth ylbenzethonium chl o­ treated lesio n s healed with little o r no scarring. N o adverse ride in white soft pa raffin (P-ointment, U .K . patent clinica l or laboratory side effe cts w ere observed except fo r GBll7237A). After 10 d ays of treatment, twice daily, the a burning sensation at the site of trea tment. Parasites iso_ lesio ns in 72% of the treated pati ents were free of parasites, lated fro m patients w ho failed to respond to topical treat_ 15% becam e free with in an additional 20 d ays, witho ut m ent were found to be susceptible to PR-MBC I in both further trea tment, and 13% failed to respond.
    [Show full text]
  • Identification and Characterization of Novel Anti-Leishmanial Compounds
    Identification and Characterization of Novel Anti-leishmanial Compounds Bilal Zulfiqar Master of Philosophy, Doctor of Pharmacy Discovery Biology Griffith Institute for Drug Discovery School of Natural Sciences Griffith University Submitted in fulfilment of the requirements of the degree of Doctor of Philosophy October 2017 ABSTRACT ABSTRACT Leishmaniasis is characterized as a parasitic disease caused by the trypanosomatid protozoan termed Leishmania. Leishmaniasis is endemic in 98 countries around the globe with increased cases of morbidity and mortality emerging each day. The mode of transmission of this disease is via the bite of a sand fly, genus Phlebotomus (Old World) and Lutzomyia (New World). The life cycle of Leishmania parasite exists between the sand fly (promastigote form) and the mammalian host (amastigote form). Leishmaniasis can be characterized as cutaneous, muco-cutaneous or visceral leishmaniasis based on clinical manifestations exhibited in infected individuals. Although leishmaniasis is treatable, it faces challenges largely due to emerging resistance and extensive toxicity for current drugs. Therapeutic efficacy varies depending upon the species, symptoms and geographical regions of the Leishmania parasite. The drug discovery pipeline for neglected trypanosomatid diseases remains sparse. In particular, the field of leishmaniasis drug discovery has had limited success in translating potential drug candidates into viable therapies. Currently there are few compounds that are clinical candidates for leishmaniasis, it is therefore essential that new compounds that are active against Leishmania are identified and evaluated for their potential to progress through the drug discovery pipeline. In order to identify new therapeutics, it is imperative that robust, biologically relevant assays be developed for the screening of anti-leishmanial compounds.
    [Show full text]
  • Manual for the Diagnosis and Treatment of Leishmaniasis
    Republic of the Sudan Federal Ministry of Health Communicable and Non-Communicable Diseases Control Directorate MANUAL FOR THE DIAGNOSIS AND TREATMENT OF LEISHMANIASIS November 2017 Acknowledgements The Communicable and Non-Communicable Diseases Control Directorate (CNCDCD), Federal Ministry of Health, Sudan, would like to acknowledge all the efforts spent on studying, controlling and reducing morbidity and mortality of leishmaniasis in Sudan, which culminated in the formulation of this manual in April 2004, updated in October 2014 and again in November 2017. We would like to express our thanks to all National institutions, organizations, research groups and individuals for their support, and the international organization with special thanks to WHO, MSF and UK- DFID (KalaCORE). I Preface Leishmaniasis is a major health problem in Sudan. Visceral, cutaneous and mucosal forms of leishmaniasis are endemic in various parts of the country, with serious outbreaks occurring periodically. Sudanese scientists have published many papers on the epidemiology, clinical manifestations, diagnosis and management of these complex diseases. This has resulted in a better understanding of the pathogenesis of the various forms of leishmaniasis and has led to more accurate and specific diagnostic methods and better therapy. Unfortunately, many practitioners are unaware of these developments and still rely on outdated diagnostic procedures and therapy. This document is intended to help those engaged in the diagnosis, treatment and nutrition of patients with various forms of leishmaniasis. The guidelines are based on publications and experience of Sudanese researchers and are therefore evidence based. The guidelines were agreed upon by top researchers and clinicians in workshops organized by the Leishmaniasis Control response at the Communicable and Non-Communicable Diseases Control Directorate, Federal Ministry of Health, Sudan.
    [Show full text]
  • Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set
    MTC eHealth DSI [eHDSI v2.2.2-OR] eHealth DSI – Master Value Set Catalogue Responsible : eHDSI Solution Provider PublishDate : Wed Nov 08 16:16:10 CET 2017 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 1 of 490 MTC Table of Contents epSOSActiveIngredient 4 epSOSAdministrativeGender 148 epSOSAdverseEventType 149 epSOSAllergenNoDrugs 150 epSOSBloodGroup 155 epSOSBloodPressure 156 epSOSCodeNoMedication 157 epSOSCodeProb 158 epSOSConfidentiality 159 epSOSCountry 160 epSOSDisplayLabel 167 epSOSDocumentCode 170 epSOSDoseForm 171 epSOSHealthcareProfessionalRoles 184 epSOSIllnessesandDisorders 186 epSOSLanguage 448 epSOSMedicalDevices 458 epSOSNullFavor 461 epSOSPackage 462 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 2 of 490 MTC epSOSPersonalRelationship 464 epSOSPregnancyInformation 466 epSOSProcedures 467 epSOSReactionAllergy 470 epSOSResolutionOutcome 472 epSOSRoleClass 473 epSOSRouteofAdministration 474 epSOSSections 477 epSOSSeverity 478 epSOSSocialHistory 479 epSOSStatusCode 480 epSOSSubstitutionCode 481 epSOSTelecomAddress 482 epSOSTimingEvent 483 epSOSUnits 484 epSOSUnknownInformation 487 epSOSVaccine 488 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 3 of 490 MTC epSOSActiveIngredient epSOSActiveIngredient Value Set ID 1.3.6.1.4.1.12559.11.10.1.3.1.42.24 TRANSLATIONS Code System ID Code System Version Concept Code Description (FSN) 2.16.840.1.113883.6.73 2017-01 A ALIMENTARY TRACT AND METABOLISM 2.16.840.1.113883.6.73 2017-01
    [Show full text]
  • Redalyc.Influence of Gentamicine on the Pharmacokinetic of A
    Archivos Venezolanos de Farmacología y Terapéutica ISSN: 0798-0264 [email protected] Sociedad Venezolana de Farmacología Clínica y Terapéutica Venezuela Vásquez de Ricciardi, Laura; Scorza, José Vicente; Vicuña-Fernández, Nelson; Petit de Peña, Yaneira; Bendezú, Herminia; Vasquez, Libia; Yanez, Carlos Influence of gentamicine on the pharmacokinetic of a pentavalent antimonial compound Glucantime® Influence of gentamicine on Glucantime kinetic Archivos Venezolanos de Farmacología y Terapéutica, vol. 25, núm. 2, 2006, pp. 60-63 Sociedad Venezolana de Farmacología Clínica y Terapéutica Caracas, Venezuela Disponible en: http://www.redalyc.org/articulo.oa?id=55925204 Cómo citar el artículo Número completo Sistema de Información Científica Más información del artículo Red de Revistas Científicas de América Latina, el Caribe, España y Portugal Página de la revista en redalyc.org Proyecto académico sin fines de lucro, desarrollado bajo la iniciativa de acceso abierto Influence of gentamicine on the pharmacokinetic of a pentavalent antimonial compound Glucantime® Influence of gentamicine on Glucantime kinetic Laura Vásquez de Ricciardi 1, José Vicente Scorza 2, Nelson Vicuña-Fernández 3, Yaneira Petit de Peña 4, Herminia Bendezú 5, Libia Vasquez 6, Carlos Yanez 7 1 Doctora en Ciencias Médicas. Laboratorio de Farmacología., Facultad de Medicina Escuela de Medicina Valera. ULA. 2 Doctor en Parasitología. Centro de Investigaciones Parasitológicas ¨José W. Torrealba¨ NURR. ULA. 3 Médico Especialista en Farmacocinética. Laboratorio de Farmacología y Toxicología Facultad de Medicina ULA. Mérida, Venzuela. 4 Doctora en Química. Laboratorio de Espectroscopía Molecular. Facultad de Ciencias. La Hechicera. ULA. 5 Magister en Protozoología. Centro de Investigaciones Parasitológicas ¨José W. Torrealba¨ NURR, ULA. 6 Medico Microbiologo. Laboratorio de Microbiología.
    [Show full text]
  • N-Metil Glucamine and Topical Miltefosine Association In
    Received: August 28, 2006 J. Venom. Anim. Toxins incl. Trop. Dis. Accepted: April 4, 2007 V.13, n.3, p.598-606, 2007. Abstract published online: April 5, 2007 Original paper. Full paper published online: August 31, 2007 ISSN 1678-9199. INEFFICACY OF THE ASSOCIATION N-METHYL GLUCAMINE AND TOPICAL MILTEFOSINE IN THE TREATMENT OF EXPERIMENTAL CUTANEOUS LEISHMANIASIS BY Leishmania (Leishmania) amazonensis SAMPAIO R. N. R. (1), LUCAS I. C. (1), TAKAMI H. L. (1) (1) Laboratory of Dermatomycology, University of Brasília, Brazil. ABSTRACT: Pentavalent antimonial (SbV) is the first treatment for cutaneous leishmaniasis (CL). Other drugs present similar side effects and higher cost. Oral miltefosine is effective to treat kala-azar. The aim of the present study was to compare the efficacy of glucamine (SbV) plus topical miltefosine with glucamine in the treatment of CL. Eighty isogenic C57BL/6 mice were inoculated with Leishmania (Leishmania) amazonensis and divided into two groups: one group was treated with SbV associated with miltefosine, and the other group received SbV plus saline solution. Groups were evaluated according to the diameter of the inoculated foot pad, the culture, and the parasite count using the limiting dilution assay. There was not statistical difference. The efficacy of glucamine in CL treatment did not increase when associated with topical miltefosine. KEY WORDS: Cutaneous Leishmaniasis, Miltefosine, N-methyl glucamine. CONFLICTS OF INTEREST: There is no conflict. CORRESPONDENCE TO: RAIMUNDA NONATA RIBEIRO SAMPAIO, Universidade de Brasília, Campus Universitário Darcy Ribeiro, Asa Norte, Brasília, 70910-900, DF, Brasil. Phone: +55 61 307 2502. Fax: +55 61 367 3825. Email: [email protected].
    [Show full text]
  • National Essential Medicine List of Afghanistan
    islamic republic of afghanistan ministry of public health general directorate of pharmaceutical affairs avicenna pharmaceutical institute National Essential Medicine List of Afghanistan 2014 NATIONAL ESSENTIAL MEDICINES LIST OF AFGHANISTAN 3 Contents List of Contributors and Collaborators ................................................................4 National Medicine Selection Committee members ................................................4 Contributing MoPH departments and partner institutions ........................................ 5 Abbreviations and Acronyms ..........................................................................6 Introduction ...........................................................................................8 Short History ........................................................................................8 Objectives of the Update ............................................................................8 Transparent Review Process of EML ...............................................................9 Classifications of Medicines ........................................................................9 Procedures for the Inclusion of New Products ....................................................10 Computerization ...................................................................................10 Medicine Listings in the EML ..................................................................... 11 Detailed Instructions for Use of the EML ........................................................
    [Show full text]
  • World Health Organization Model List of Essential Medicines, 21St List, 2019
    World Health Organizatio n Model List of Essential Medicines 21st List 2019 World Health Organizatio n Model List of Essential Medicines 21st List 2019 WHO/MVP/EMP/IAU/2019.06 © World Health Organization 2019 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. World Health Organization Model List of Essential Medicines, 21st List, 2019. Geneva: World Health Organization; 2019. Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data. CIP data are available at http://apps.who.int/iris.
    [Show full text]
  • 204684Orig1s000
    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 204684Orig1s000 MEDICAL REVIEW(S) Clinical Investigator Financial Disclosure Review Template Application Number: 204684 Submission Date(s): September 27, 2012 and April 19, 2013 Applicant: Paladin Therapeutics, Inc. Product: IMPAVIDO (miltefosine) Reviewer: Hala Shamsuddin, M.D. Date of Review: February 24, 2014 Covered Clinical Study (Name and/or Number): Study 3154 Study 3168 Study Z020a and b Study SOTO Study Z022 Dutch PK study Was a list of clinical investigators provided: Yes X No (Request list from applicant) Total number of investigators identified: Six (6) Number of investigators who are sponsor employees (including both full-time and part-time employees): None Number of investigators with disclosable financial interests/arrangements (Form FDA 3455): Six (6) If there are investigators with disclosable financial interests/arrangements, identify the number of investigators with interests/arrangements in each category (as defined in 21 CFR 54.2(a), (b), (c) and (f)): Compensation to the investigator for conducting the study where the value could be influenced by the outcome of the study: None Significant payments of other sorts: None Proprietary interest in the product tested held by investigator: None Significant equity interest held by investigator in sponsor of covered study: None Is an attachment provided with details Yes X No (Request details from of the disclosable financial applicant) interests/arrangements: Is a description of the steps taken to Yes X No (Request information minimize potential bias provided: from applicant) Number of investigators with certification of due diligence (Form FDA 3454, box 3) None Is an attachment provided with the NA No (Request explanation Reference ID: 3464181 reason: from applicant) Discuss whether the applicant has adequately disclosed financial interests/arrangements with clinical investigators as recommended in the guidance for industry Financial Disclosure by Clinical Investigators.
    [Show full text]