DOCSLIB.ORG

And Praziquantel-Resistant Beef Tapeworm Infection with Nitazoxanide

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
And Praziquantel-Resistant Beef Tapeworm Infection with Nitazoxanide International Journal of Infectious Diseases (2008) 12, 80—82 http://intl.elsevierhealth.com/journals/ijid Successful treatment of niclosamide- and praziquantel-resistant beef tapeworm infection with nitazoxanide Mohammad Lateef a, Showkat Ali Zargar b,*, Abdul Rashid Khan a, Muzzaffar Nazir b, Abid Shoukat b a Department of Zoology, University of Kashmir, Srinigar, India b Department of Gastroenterology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India Received 31 October 2006; received in revised form 22 January 2007; accepted 21 April 2007 Corresponding Editor: William Cameron, Ottawa, Canada KEYWORDS Summary Taenia saginata; Background: Beef tapeworm (Taenia saginata) infection is acquired by eating inadequately Prevalence; cooked beef that contains the larvae or cysticerci of T. saginata. Niclosamide and praziquantel Niclosamide; have proved effective for its treatment but treatment failures are well known. We report herein Praziquantel; the results of nitazoxanide therapy. Drug resistance; Methods: A prospective study was conducted in 18 children and 34 adults to assess the efficacy Nitazoxanide and safety of nitazoxanide in the treatment of niclosamide- and praziquantel-resistant T. saginata infection. Nitazoxanide was administered twice daily for 3 days in 500-mg doses for those aged over 14 years and at 20 mg/kg body weight/day in children aged 5—14 years. Post- treatment follow-up was undertaken at 1, 2, 4, 8, and 12 weeks for fecal samples for proglottides, and to check the presence, number, and viability of Taenia eggs. Results: Nitazoxanide cured 51 of 52 (98.1%) patients. Mild side effects occurred in seven patients, which resolved spontaneously. There were no abnormalities in laboratory parameters. Conclusions: Nitazoxanide is a safe, effective, inexpensive, and well-tolerated drug for the treatment of niclosamide- and praziquantel-resistant beef tapeworm infection. # 2007 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. Introduction cysticerci of T. saginata. It is found worldwide and about 45 million suffer from this disease. Its greatest economic Beef tapeworm (Taenia saginata) infection is acquired by impact, however, is within tropical and sub-tropical cattle eating inadequately cooked beef that contains the larvae or rearing countries: Africa, the Middle East, Central and South America, Europe, and Asia. * Corresponding author. Tel.: +91 194 2312092; Although many antimicrobial drugs are used to treat T. fax: +91 194 2403470. saginata infections, niclosamide and praziquantel have E-mail address: [email protected] (S.A. Zargar). proved effective for its treatment; however treatment 1201-9712/$32.00 # 2007 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijid.2007.04.017 Treatment of beef tapeworm infection with nitazoxanide 81 failures are well known.1—4 In Kashmir, India, with a 95% (n = 2), nausea (n = 2), and giddiness (n = 1). All adverse Muslim population and absence of pigs, T. s a g i n a t a is ende- events were mild and transitory in nature and resolved mic but Taenia solium infection is almost unknown. We spontaneously without discontinuation of treatment. No report herein the results of nitazoxanide therapy in 52 abnormality was observed in hemogram, blood chemistry patients, identified in a population-based epidemiological values, or urine analysis. survey, infected with T. s a g i n a t a resistant to multiple courses of niclosamide, praziquantel, or both. Discussion Materials and methods The present study demonstrated that a 3-day course of nitazoxanide cured 98.1% of patients infected with T. sagi- Between 2004 and 2005, an epidemiological survey for tae- nata unresponsive to niclosamide, praziquantel, or both. niasis was conducted in Sonawari tehsil in the district of Nitazoxanide was safe and well tolerated. Adverse events Baramulla, Kashmir, India involving 8894 persons from semi- reported by patients were mild and resolved easily without urban and urban villages. During this survey 55 persons with any treatment. In two previous clinical studies in patients confirmed T. saginata infection resistant to multiple courses infected with T. saginata, nitazoxanide cured 21 of 22 of niclosamide or praziquantel or both were identified. Three patients (95.5%) and five of five patients (100%).5,6 Taenia patients were excluded because one was pregnant and two saginata infections are endemic in Kashmir, India. Niclosa- were lactating. The remaining 52 gave written informed mide or praziquantel are safe and effective drugs for its consent to participate in the study. There were 18 children, treatment but therapeutic failures with these drugs are 24 men, and 10 women. They ranged in age from 5 to 65 encountered. years, with a mean of 26.2 Æ 16.1 years. The duration of Taeniasis is not only a significant public health problem but infection ranged from 8 months to 15 years with a mean of also an important economic problem in endemic areas. It is 3.7 Æ 3.1 years. All patients had received two to seven becoming increasingly clear that it should be given greater courses (median three) of niclosamide and 10 had received priority because of its economic impact, particularly in one to three courses of praziquantel (median two) but had resource-poor countries. Most patients are asymptomatic continued to pass proglottides with stools. All had demon- and become aware of the infection when they notice proglot- strated a relapse 3—6 weeks after initiation of treatment. tides or segments of tapeworm in stools or motile proglot- Symptoms included passage of proglottides in stools and/or tides emerging from the anus, in trousers, on bedding, while trousers while bending, running or washing (n = 52), bending, walking, and running, and this can cause huge increased appetite (n = 33), abdominal discomfort (n = 23), psychological distress. Rarely, migration of motile proglot- nausea (n = 15), and diarrhea (n = 3). Nitazoxanide was admi- tides or worm to ectopic sites such as the appendix, biliary nistered twice daily for 3 days in 500-mg doses for those aged tree, or pancreatic duct can cause morbidity. over 14 years and 20 mg/kg body weight/day in children aged Nitazoxanide (2-acetyloxy-N-(5-nitro-2-thiazolyl)benza- 5—14 years without prior fasting or laxative use. mide) is a new thiazolide antiparasitic agent that shows All patients underwent physical examination including ana- excellent activity against a wide variety of protozoa and lysis of hemogram, serum chemistry (liver function tests, helminths. Although developed in 1980, the literature on glucose, urea, sodium and potassium), and urine, and electro- its use is scanty because it only received approval by the US cardiogram before and 7 days after treatment. Stool speci- FDA in November 2002 for the treatment of diarrhea caused mens were collected for routine examination. Egg viability was by Cryptosporidium parvum and Giardia lamblia in children tested by staining with methylene blue, and egg count by and adults. It became available in India in June 2004. It is also Stoll’s method. Patients were followed at 1, 2, 4, 8, and 12 effective against a broad range of other parasitic infections weeks for the passage of proglottides, and fecal samples were including Hymenolepis nana, Trichuris trichiura, Ascaris lum- examined for the presence, number, and viability of Taenia bricoides, Fasciola hepatica, Entamoeba histolytica, and eggs. Overall 51 of 52 patients (98.1%) responded and passed Taenia solium/saginata.7 worms ranging from 1 to 6 meters in length, but no worm In conclusion nitazoxanide is a safe, effective, and inex- contained scolex. All responders stopped passing proglottides pensive drug for the treatment of niclosamide- and prazi- at a median of 3 days (range 1—5) days. Of the 41 patients who quantel-resistant T. saginata infections. It represents a provided stool specimens in the first week, 38 (92.7%) had significant addition to the antiparasitic arsenal in the treat- negative stool examinations for proglottides and eggs. The ment of intestinal parasitic infections. reduction was in excess of 98% in egg count and from a median of 100% to 0% in viability at 1 week. Subsequent stool exam- inations at 2, 4, 8, and 12 weeks were negative for proglottides Acknowledgments and eggs with a cure rate of 98.1% (51 of 52 patients). Thirty-two patients (15 children and 17 adolescents and Financial support for this study was provided by Sher-i-Kash- adults) were positive for another parasite in stool at study mir Institute of Medical sciences. enrollment. These included Ascaris lumbricoides (n = 19), Conflict of interest: No conflict of interest to declare. Trichuris trichiura (n = 6), Giardia lamblia (n = 4), and mixed infections (n = 3). Nitazoxanide cured 89.5% (17/19), 100% References (6/6), 75% (3/4), and 66.7% (2/3) of the cases of ascariasis, trichuriasis, giardiasis, and mixed infections, respectively. 1. Perera DR, Western KA, Schultz MG. Niclosamide treatment of Eleven adverse events occurred in seven patients including cestodiasis: clinical trials in the United States. Am J Trop Med Hyg diarrhea (n = 3), mild abdominal pain (n = 3), headache 1970;19:610—2. 82 M. Lateef et al. 2. Vermund SH, MacLeod S, Goldstein RG. Taeniasis unresponsive to a 5. Rossignol JF, Maisonneuve H. Nitazoxanide in the treatment of single dose of niclosamide: case report of persistent infection Taenia saginata and Hymenolepis nana infections. Am J Trop Med with Taenia saginata and a review of therapy. Rev Infect Dis Hyg 1984;33:511—2. 1986;8:423—6. 6. Romero Cabello R, Guerrero LR, Munoz Garcia MR, Geyne Cruz A. 3. Esteves FM, Silva-Vergara ML, Carvalho AC. Epidemiologic survey Nitazoxanide for the treatment of intestinal protozoan and hel- of taeniasis in Health and Family Program in Uberaba, MG. Rev Soc minthic infections in Mexico. Trans R Soc Trop Med Hyg Bras Med Trop 2005;38:530—1. 1997;91:701—3.
Load more

Recommended publications
  • Computational Studies of Drug Repurposing Targeting P-Glycoprotein Mediated Multidrug-Resistance Phenotypes in Agents of Neglect
    bioRxiv preprint doi: https://doi.org/10.1101/2020.06.12.147926; this version posted June 12, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Computational studies of drug repurposing targeting P- glycoprotein mediated multidrug-resistance phenotypes in agents of neglected tropical diseases Nivedita Jaishankar 1, Sangeetha Muthamilselvan 2, Ashok Palaniappan 1,2* 1 Department of Biotechnology, Sri Venkateswara College of Engineering, Post Bag No. 1, Pennalur, Sriperumbudur Tk 602117. India 2 Department of Bioinformatics, School of Chemical and BioTechnology, SASTRA Deemed University, Thanjavur 613401. India * Corresponding author: [email protected] ABSTRACT Mammalian ABCB1 P-glycoprotein is an ATP- dependent efflux pump with broad substrate specificity associated with cellular drug resistance. Homologous to this role in mammalian biology, the P-glycoprotein of agents of neglected tropical diseases (NTDs) mediates the emergence of multidrug- resistance phenotypes. The clinical and socioeconomic implications of NTDs are exacerbated by the lack of research interest among Big Pharma for treating such conditions. This work aims to characterise P-gp homologues in certain agents of key NTDs, namely (1) Protozoa: Leishmania major, Trypanosoma cruzi; (2) Helminths: Onchocerca volvulus, Schistosoma mansoni. PSI-BLAST searches against the genome of each of these organisms confirmed the presence of P-gp homologues. Each homologue was aligned against five P- gp sequences of known structure, to identify the most suitable template based on sequence homology, phylogenetic nearest neighbor, and query coverage.
    [Show full text]
  • Comparative Genomics of the Major Parasitic Worms
    Comparative genomics of the major parasitic worms International Helminth Genomes Consortium Supplementary Information Introduction ............................................................................................................................... 4 Contributions from Consortium members ..................................................................................... 5 Methods .................................................................................................................................... 6 1 Sample collection and preparation ................................................................................................................. 6 2.1 Data production, Wellcome Trust Sanger Institute (WTSI) ........................................................................ 12 DNA template preparation and sequencing................................................................................................. 12 Genome assembly ........................................................................................................................................ 13 Assembly QC ................................................................................................................................................. 14 Gene prediction ............................................................................................................................................ 15 Contamination screening ............................................................................................................................
    [Show full text]
  • I Comparative Activity of Anthelmintic
    Retour au menu Comparative activity of anthelmintic drugs, mebendazole, praziquantel and albendazole against Hymenolepis M. Gala1 ’ diminufa in experimentally infected S. R. Chin ’ Irats GALAL (MT), CHIN (S. R.). Comparaison de l’action de différents CAVIER and ROSSIGNOL (3) studied the taenicidal anthelminttuques (mébendazole, praziquantel et albendazole) contre properties of albendazole, mebendazole, niclosamide Hymenoleph diminuta chez des rats expérimentalement Infectés. Rev. Elev. Méd. vét. Pays trop., 1987, 40 (2) : 147-150. and praziquantel in experimentally infected mice and found that praziquantel and niclosamide have similar Des rats expérimentalement infectés avec If. diminufa ont été traités par voie orale avec trois anthelminthiques, administrés soit en dose taenicidal propet-ties. unique, soit en tiers de dose 3 jours consécutifs. Le praziquantel (250 mgkg ou 83 mg/k&j 3 fois) et I’alhendazole (800 mgkg ou Now are reported the comparative efficacy of meben- 167 mgkg/j 3 fois) ont totalement éliminé les vers, alors que le dazole, praziquantel and albendazole against experi- mébendazole (500 rng/kg- - ou 167 mg/kg/i- -. 3 fois) ne les a aue oartielle- mental infection of rats with H. diminuta, using single ment éliminés, avec une efficacité de 76 p. 160. Parmi ces j anthel- and divided oral doses for 3 consecutive days, 30 days mlnthlques, il n’a pas été relevé de différence signiiïcative d’efkacité entre les différents dosages pour chaque traitement. Aucune toxicité after infection. n’est apparue chez les rats traités. Mots CES : Rat - Helminthosc - Hymenolepis diminuta - Anthelminthique - Mébendazole - Prazi- quantel - Albendazole - Infection expérimentale. MATERIALS AND METHODS INTRODUCTION Definitive and intermediate hosts Albino rats (Rattus norvegicus) of both sexes and H.
    [Show full text]
  • Redalyc.Determination of Niclosamide and Its Metabolites in Liver And
    Acta Scientiae Veterinariae ISSN: 1678-0345 [email protected] Universidade Federal do Rio Grande do Sul Brasil Kartalovic, Brankica; Pucarevic, Mira; Markovic, Zoran; Stankovic, Marko; Novakov, Nikolina; Pelic, Milos; Cirkovic, Miroslav Determination of Niclosamide and its Metabolites in Liver and Muscles of Common Carp (Cyprinus carpio) Fingerlings Acta Scientiae Veterinariae, vol. 45, 2017, pp. 1-6 Universidade Federal do Rio Grande do Sul Porto Alegre, Brasil Available in: http://www.redalyc.org/articulo.oa?id=289053641022 How to cite Complete issue Scientific Information System More information about this article Network of Scientific Journals from Latin America, the Caribbean, Spain and Portugal Journal's homepage in redalyc.org Non-profit academic project, developed under the open access initiative Acta Scientiae Veterinariae, 2017. 45: 1490. RESEARCH ARTICLE ISSN 1679-9216 Pub. 1490 Determination of Niclosamide and its Metabolites in Liver and Muscles of Common Carp (Cyprinus carpio) Fingerlings Brankica Kartalović1 , Mira Pucarević2, Zoran Marković3, Marko Stanković3, Nikolina Novakov4, Milos Pelić1 & Miroslav Ćirković1 ABSTRACT Background: Niclosamide is a medication used to treat tapeworm infestation in animals and humans. It is also lampricide and molluscicide, and can be used in in agriculture as a pesticide. In the treatment of parasitic diseases in fish, niclosamide can be used as bath or mixed with the feed. Its most important use in common carp (Cyprinus carpio) is for the treatment of Bothriocephalus acheilognathi, which is a very common parasite in this fish species. The aim of this study was to de- termine the concentrations of niclosamide (NIC) and its metabolite 2-chloro 4-nitro aniline (CNA) and 5-chloro salycilic acid (CSA) in the liver and muscles of common carp fingerlings.
    [Show full text]
  • Praziquantel Treatment in Trematode and Cestode Infections: an Update
    Review Article Infection & http://dx.doi.org/10.3947/ic.2013.45.1.32 Infect Chemother 2013;45(1):32-43 Chemotherapy pISSN 2093-2340 · eISSN 2092-6448 Praziquantel Treatment in Trematode and Cestode Infections: An Update Jong-Yil Chai Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, Seoul, Korea Status and emerging issues in the use of praziquantel for treatment of human trematode and cestode infections are briefly reviewed. Since praziquantel was first introduced as a broadspectrum anthelmintic in 1975, innumerable articles describ- ing its successful use in the treatment of the majority of human-infecting trematodes and cestodes have been published. The target trematode and cestode diseases include schistosomiasis, clonorchiasis and opisthorchiasis, paragonimiasis, het- erophyidiasis, echinostomiasis, fasciolopsiasis, neodiplostomiasis, gymnophalloidiasis, taeniases, diphyllobothriasis, hyme- nolepiasis, and cysticercosis. However, Fasciola hepatica and Fasciola gigantica infections are refractory to praziquantel, for which triclabendazole, an alternative drug, is necessary. In addition, larval cestode infections, particularly hydatid disease and sparganosis, are not successfully treated by praziquantel. The precise mechanism of action of praziquantel is still poorly understood. There are also emerging problems with praziquantel treatment, which include the appearance of drug resis- tance in the treatment of Schistosoma mansoni and possibly Schistosoma japonicum, along with allergic or hypersensitivity
    [Show full text]
  • Optimisation and Validation of a Sensitive Bioanalytical Method For
    bioRxiv preprint doi: https://doi.org/10.1101/2021.01.13.426426; this version posted January 15, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Optimisation and validation of a sensitive bioanalytical method for niclosamide. Usman Arshad1,3, Henry Pertinez1,3, Helen Box1,3, Lee Tatham1,3, Rajith KR Rajoli1,3, Megan Neary1,3, Joanne Sharp1,3, Anthony Valentijn1,3, James Hobson2,3, Catherine Unsworth2,3, Andrew Dwyer2,3, Alison Savage2,3, Tom O Mcdonald2,3, Steve P Rannard2,3, Paul Curley1,3, Andrew Owen1,3. 1Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, L7 3NY, UK 2Department of Chemistry, University of Liverpool, Liverpool, L69 3BX, UK 3Centre of Excellence in Long-acting Therapeutics (CELT), University of Liverpool, Liverpool, L7 3NY, UK Author for correspondence: Dr Paul Curley Department of Pharmacology and Therapeutics Centre of Excellence in Long-acting Therapeutics (CELT) University of Liverpool United Kingdom Tel: +44 (0) 151 795 8560 E-mail: [email protected] Key words: COVID-19, niclosamide, LC-MS/MS, plasma, SARS-CoV-2 Conflicts of interest statement AO and SR have received research funding from AstraZeneca and ViiV and consultancies from Gilead; AO has additionally received funding from Merck and Janssen and consultancies from ViiV and Merck not related to the current paper. No other conflicts are declared by the authors. Funding This work was funded by UKRI using funding repositioned from EP/R024804/1 as part of the UK emergency response to COVID-19.
    [Show full text]
  • Overview of Planned Or Ongoing Studies of Drugs for the Treatment of COVID-19
    Version of 16.06.2020 Overview of planned or ongoing studies of drugs for the treatment of COVID-19 Table of contents Antiviral drugs ............................................................................................................................................................. 4 Remdesivir ......................................................................................................................................................... 4 Lopinavir + Ritonavir (Kaletra) ........................................................................................................................... 7 Favipiravir (Avigan) .......................................................................................................................................... 14 Darunavir + cobicistat or ritonavir ................................................................................................................... 18 Umifenovir (Arbidol) ........................................................................................................................................ 19 Other antiviral drugs ........................................................................................................................................ 20 Antineoplastic and immunomodulating agents ....................................................................................................... 24 Convalescent Plasma ...........................................................................................................................................
    [Show full text]
  • Comprehensive Analysis of Drugs to Treat SARS‑Cov‑2 Infection: Mechanistic Insights Into Current COVID‑19 Therapies (Review)
    INTERNATIONAL JOURNAL OF MOleCular meDICine 46: 467-488, 2020 Comprehensive analysis of drugs to treat SARS‑CoV‑2 infection: Mechanistic insights into current COVID‑19 therapies (Review) GEORGE MIHAI NITULESCU1, HORIA PAUNESCU2, STERGHIOS A. MOSCHOS3,4, DIMITRIOS PETRAKIS5, GEORGIANA NITULESCU1, GEORGE NICOLAE DANIEL ION1, DEMETRIOS A. SPANDIDOS6, TAXIARCHIS KONSTANTINOS NIKOLOUZAKIS5, NIKOLAOS DRAKOULIS7 and ARISTIDIS TSATSAKIS5 1Faculty of Pharmacy, 2Faculty of Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, 020956 Bucharest, Romania; 3Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University; 4PulmoBioMed Ltd., Newcastle‑Upon‑Tyne NE1 8ST, UK; 5Department of Forensic Sciences and Toxicology, Faculty of Medicine; 6Laboratory of Clinical Virology, School of Medicine, University of Crete, 71003 Heraklion; 7Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15771 Athens, Greece Received April 20, 2020; Accepted May 18, 2020 DOI: 10.3892/ijmm.2020.4608 Abstract. The major impact produced by the severe acute tions, none have yet demonstrated unequivocal clinical utility respiratory syndrome coronavirus 2 (SARS‑CoV-2) focused against coronavirus disease 2019 (COVID‑19). This work many researchers attention to find treatments that can suppress represents an exhaustive and critical review of all available transmission or ameliorate the disease. Despite the very fast data on potential treatments
    [Show full text]
  • A61k 47/32 (2013.01)
    US0092.594.17B2 (12) United States Patent (10) Patent No.: US 9.259,417 B2 Soll et al. (45) Date of Patent: Feb. 16, 2016 (54) PARASITICIDAL ORAL VETERINARY USPC .......................................................... 514/378 COMPOSITIONS COMPRISING See application file for complete search history. SYSTEMICALLY-ACTING ACTIVE AGENTS, METHODS AND USES THEREOF (56) References Cited (71) Applicant: MERIAL INC., Duluth, GA (US) U.S. PATENT DOCUMENTS 3,887.964 A 6, 1975 Richards (72) Inventors: Mark David Soll, Alpharetta, GA (US); 4,284,652 A 8, 1981 Christensen Diane Larsen, Buford, GA (US); Susan 4,327,076 A 4/1982 Puglia et al. Mancini Cady, Yardley, PA (US); Peter 4,393,085 A 7/1983 Spradlin et al. Cheifetz, East Windsor, NJ (US); is: A 2. 3. SE, Izabela Galeska, Newtown, PA (US) 4,997,671- - - A 3/1991 SpanierO C. a. 5,236,730 A 8, 1993 Yamada et al. (73) Assignee: MERLAL, INC., Duluth, GA (US) 5,262,167 A 1 1/1993 Vegesna et al. 5,380,535 A 1/1995 Geyer et al. (*) Notice: Subject to any disclaimer, the term of this 5.439,924 A 8, 1995 Miller patent is extended or adjusted under 35 5,578.336 A 1 1/1996 Monte U.S.C. 154(b) by O. davs. 5,605,889 A 2f1997 Curatolo et al. (b) by yS 5,637,313 A 6, 1997 Chau 5,753,255 A 5/1998 Chaukin et al. (21) Appl. No.: 14/627,499 5,824,336 A 10/1998 Janset al. (22) Filed: Feb. 20, 2015 5,827,5655:3.
    [Show full text]
  • The Selection of Essential Drugs
    This report contains the collective views of an, international group of experts and does not necessarily represent the decisions or the stated policy of the World Health Organization The selection of essential drugs Second report of the WHO Expert Committee World Health Organization Technical Report Series 641 • World Health Organization Geneva 1979 ISBN 92 4 120641 I © World Health Organization 1979 Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention. For rights of reproduction or translation of WHO publications, in part or in toto, appli­ cation should be made to the Office of Publications, World Health Organization, Geneva, Switzerland. The World Health Organization welcomes such applications. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers- or boundaries. - The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted; the names of proprietar j products are distinguished by initial capital letters. PRINTED IN SWlTZERL-\'-iD 79/4523 - 10000 - La Concorde CONTENfS Page I. Introduction . 7 2. General considerations 8 3. Guidelines for the selection of pharmaceutical forms 8 4. Revised model list of essential drugs .
    [Show full text]
  • Chemotherapeutic Effects of Praziquantel, Niclosamide, Mebendazole And
    [Jpn. J. Parasitol., Vol. 38, No. 4, 236—239, August, 1989] Chemotherapeutic Effects of Praziquantel, Niclosamide, Mebendazole and Bithionol on Larvae and Adults of Hymenolepis nana in Mice JUN MAKI AND TOSHIO YANAGISAWA (Accepted for publication; May 22, 1989) Abstract Praziquantel, niclosamide or mebendazole was orally administered to mice harbouring adult Hymenolepis nana 12 or 12—16 days post-infection. Praziquantel (25 mg/kg) was completely effective at the single administration, similar to the result of Thomas and Gonnert (1977). Worm reduction by niclosamide was about 25—50% at a single dose of 100 or 500 mg/kg and at five successive doses of 100 mg/kg/day. Worm reduction due to mebendazole was about 10—20% at a single dose of 100 or 500 mg/kg while the drug completely eliminated adult worms at five successive doses of 100 mg/kg/day. Praziquantel (25 mg/kg/day), niclosamide (500 mg/kg/day), mebendazole (500 mg/kg/day) or bithionol (500 mg/kg/day) was administered to mice harbouring cysticercoids of H. nana in the intestinal villi for 3 consecutive days (1—3 days post-infection). None of these drugs had larvicidal effect. However, praziquantel (25 mg/kg) was completely effective against larval H. nana in the intestinal lumen when the single dose was given 5 days post- infection or later. Key words: praziquantel, niclosamide, mebendazole, bithionol, Hymenolepis nana Introduction in the villi. To treat H. nana infection completely, cysticercoids as well as adults should be Recently, praziquantel, niclosamide, benzi- eliminated. To the best of the present authors' midazoles, bithionol, paromomycin sulphate and knowledge, however, no data have been pre other drugs have been used to treat human sented so far indicating the possibility of suc cestode infections.
    [Show full text]
  • Niclosamide Is Active in Vitro Against Mycetoma Pathogens
    molecules Article Niclosamide Is Active In Vitro against Mycetoma Pathogens Abdelhalim B. Mahmoud 1,2,3,† , Shereen Abd Algaffar 4,† , Wendy van de Sande 5, Sami Khalid 4 , Marcel Kaiser 1,2 and Pascal Mäser 1,2,* 1 Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland; [email protected] (A.B.M.); [email protected] (M.K.) 2 Faculty of Science, University of Basel, 4001 Basel, Switzerland 3 Faculty of Pharmacy, University of Khartoum, Khartoum 11111, Sudan 4 Faculty of Pharmacy, University of Science and Technology, Omdurman 14411, Sudan; [email protected] (S.A.A.); [email protected] (S.K.) 5 Erasmus Medical Center, Department of Medical Microbiology and Infectious Diseases, 3000 Rotterdam, The Netherlands; [email protected] * Correspondence: [email protected]; Tel.: +41-61-284-8338 † These authors contributed equally to this work. Abstract: Redox-active drugs are the mainstay of parasite chemotherapy. To assess their repurposing potential for eumycetoma, we have tested a set of nitroheterocycles and peroxides in vitro against two isolates of Madurella mycetomatis, the main causative agent of eumycetoma in Sudan. All the tested compounds were inactive except for niclosamide, which had minimal inhibitory concentrations of around 1 µg/mL. Further tests with niclosamide and niclosamide ethanolamine demonstrated in vitro activity not only against M. mycetomatis but also against Actinomadura spp., causative agents of actinomycetoma, with minimal inhibitory concentrations below 1 µg/mL. The experimental compound MMV665807, a related salicylanilide without a nitro group, was as active as niclosamide, indicating that the antimycetomal action of niclosamide is independent of its redox chemistry (which Citation: Mahmoud, A.B.; Abd Algaffar, S.; van de Sande, W.; Khalid, is in agreement with the complete lack of activity in all other nitroheterocyclic drugs tested).
    [Show full text]