CHEMOTHERAPY. Volume 6 Parasites, Fungi, and Viruses

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1 CHEMOTHERAPY Volume 6 Parasites, Fungi, and Viruses

2 CHEMOTHERAPY Volume 1 Clinical Aspects of Infections Prophylaxis; life-threatening infections; infection in leukaemia; surgical infection; anaerobic infection; respiratory and urinary tract infections; amikacin_ Volume 2 Laboratory Aspects of Infections Sensitivity testing; assay methods; animal models of infection; sisomycin; tobramycin. Volume 3 Volume 4 Special Problems in Chemotherapy Tuberculosis; genital tract infections; antibiotic resistance and mode of action; topical chemotherapy and antisepsis. Pharmacology of Antibiotics Tissue concentrations; pharmacokinetics; untoward effects of antibiotics. Volume 5 Penicillins and Cephalosporins Penicillins and cephalosporins; betalactamases; new agents. Volume 6 Parasites, Fungi, and Viruses Parasitic infections; fungal infections; chemotherapy of viruses; co-trimoxazole. Volume 7 Cancer Chemotherapy I Symposia - new drugs and approaches; cell and pharmacokinetics; potentiators of radiotherapy; in vitro screening systems; immunological aspects. Volume 8 Cancer Chemotherapy II Free papers - new drugs and approaches; cell and pharmacokinetics; mechanisms of action; new analogues; cancer chemotherapy of specific organs.

3 CHEMOTHERAPY Volutne 6 Parasites, Fungi, and Viruses Edited by J. D Williams The London Hospital Medical College London, U.K. and A.M. Geddes East Birmingham Hospital Birmingham, U. K. Springer Science+Business Media, LLC

4 Library of Congress Cataloging in Publication Data International Congress of Chemotherapy, 9th, London, Parasites, fungi, and viruses. (Chemotherapy;v.6) Includes index. 1. Chemotherapy-Congresses. 2. Anti-infective agents-congresses. I. Williams, John David, M.D. I1. Geddes, Alexander McIntosh. III. Title. IV. Series. RM260.2.C45 vol '.58s [616.9'6'061] ISBN ISBN (ebook) DOI / Proceedings of the Ninth International Congress of Chemotherapy held in London, July, 1975 will be published in eight volumes, of which this is volume six Springer Science+Business Media New York Originally published by Plenum Press, New York in Softcover reprint of the hardcover 1 st edition 1976 United Kingdom edition published by Plenum Press, London A Division of Plenum Publishing Company, Ltd. Davis House (4th Floor), 8 Scrubs Lane, Harlesden, London, MW10 6SE, England All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher

5 CHEMOTHERAPY Proceedings of the 9th International Congress of Chemotherapy held in London, July, 1975 A. M. Geddes (Antimicrobial) East Birmingham Hospital. W. Brumfitt K.HeIlmann K.D. Bagshawe H.Smith EJ.Stokes F. Wrigley J.D. Williams Editorial Committee K. Hellmann, Chairman (Anticancer) Imperial Cancer Research Fund, London. J. D. Williams (Antimicrobial) The London Hospital Medical College. Congress Organising Committee I. Phillips M.R.W. Brown D.G.James C. Stuart Harris R.G.Jacomb D.T.D. Hughes T.Connors H.P. Lambert P.Tumer A.M. Geddes D.Armitage D.Crowther D.8.R_s R.E.O. Williams International Society of Chemotherapy Executive - to July 1975 P.Ma1ek C.Grassi G.B. Werner HoP. Kuemmerle Z.Modr K.H.Spitzy P. Rentchnick H. Ericsson G.M.Savage H. Umezawa

6 Preface The International Society of Chemotherapy meets every two years to review progress in chemotherapy of infections and of malignant disease. Each meeting gets larger to encompass the extension of chemotherapy into new areas. In some instances, expansion has been rapid, for example in cephalosporins, penicillins and combination chemotherapy of cancer - in others slow, as in the field of parasitology. New problems of resistance and untoward effects arise; reduction of host toxicity without loss of antitumour activity by new substances occupies wide attention. The improved results with cancer chemotherapy, especially in leukaemias, are leading to a greater prevalence of severe infection in patients so treated, pharmacokinetics of drugs in normal and diseased subjects is receiving increasing attention along with related problems of bioavailability and interactions between drugs. Meanwhile the attack on some of the major bacterial infections, such as gonorrhoea and tuberculosis, which were among the first infections to feel the impact of chemotherapy, still continue to be major world problems and are now under attack with new agents and new methods. From this wide field and the 1,000 papers read at the Congress we have produced Proceedings which reflect the variety and vigour of research in this important field of medicine. It was not possible to include all of the papers presented at the Congress but we have attempted to include most aspects of current progress in chemotherapy. We thank the authors of these communications for their cooperation in enabling the Proceedings to be available at the earliest possible date. The method of preparation does not allow for uniformity of typefaces and presentation of the material and we hope that the blemishes of language and typographical errors do not detract from the understanding of the reader and the importance of the Proceedings. K. HELLMANN, Imperial Cancer Research Fund A. M. GEDDES, East Birmingham Hospital J. D. WILLIAMS, The London Hospital Medical College vii

7 Contents What Are the Problems in Tropical In~ections?. 1 A. Bryceson Epidemic Diseases. D. A. Warrell, P. L. Perine, and D. W. Krause Progress Achieved in the Chemotherapy o~ Soil Transmitted Helminths. F. Ar~aa and I. Farahmandian The Treatment o~ Chloroquine-Resistant Falciparum Malaria.. A. P. Hall The Role o~ University Research Departments in the Development o~ Antiparasitic Chemotherapy W. Peters Current Problems in the Chemotherapy o~ Parasitic Diseases - The Role o~ the Pharmaceutical Industry O. D. Standen New Nitroimidazoles with a Chemotherapeutic Activity E. Winkelmann and W. Raether New 5-Nitroimidazoles with Antiprotozoal Activity: E~~ect o~ Hoe 088 (Pirinidazole) W. Raether and E. Winkelmann Pharmacokinetic and Metabolic Studies with Ornidazole in Man. Comparison with Metronidazole D. E. Schwartz and F. Jeunet The Diagnosis and Treatment o~ Lambliasis W. Altor~er ix

8 x Treatment of Giardiasis with a Single Oral Dose of Tinidazole T. Pettersson CONTENTS A Rural Study in Tanzania of the Chemosuppressant Activity of Various Regimes of Co-Trimoxazole or Chloroquine in Subjects with f. falciparum Parasi taemia 69 Th. J. Goosen, M. A. L. Goosen, and A. J. Salter Results of the Anti-X. cruzi Activity of Ro in Man J. A. Cerisola, C. A. Barclay, H. Lugones, and O. Ledesma 79 The Efficiency of Metronidazole "Flagyl" Against Trypanosoma evansi In Vivo 87 A. M. Mandour and A. M. Abd-El Rahman Emericid ( R.P.): A New Anticoccidial F. Benazet, J. R. Cartier, J. Florent, C. Johnson, J. Lunel, and D. Mancy Efficiency of Levamisole "Ketrax" on Some Nematode Infections in Assiut Province A. M. Mandour and L. A. M. Omran Review of Amphotericin B J. E. Bennett Polyenes: Actions and Prospects D. Kerridge and N. J. Russell Review of Imidazole Group R. J. Holt MOde of Action and Resistance to 5-Fluorocytosine 127 J. Schonebeck Combination of Amphotericin B and 5-Fluorocytosine A. Polak and H. J. Scholer 137 Combined Flucytosine - Amphotericin B Treatment of Cryptococcosis 143 J. P. Utz, I. L. Garriques, M. A. Sande, J. F. Warner, G. L. Mandell, R. F. McGehee, R. J. Duma, and S. Shadomy

9 CONTENTS The Tissue Culture Study of Antifungal Agents and Their Morphological Changes on Yeast and Yeast-Like Fungi A. Uetsuka, S. Satoh, M. Itoh, N. Oka~aki, Y. Ohno, and K. Yoshimura 157 xi Miconazole Plasma Levels in Healthy Subjects and in Patients with Impaired Renal Function J. Boelaert, R. Daneels, and H. Van Landuyt, and J. Symoens In Vitro Studies with Miconazole and Miconazole Ni trate S. Shadomy and L. Paxton 171 Clinical Studies with Clotrimazole: Efficacy, Tolerance H. Weuta Pharmacokinetics, 179 Oral Clotrimazole in the Treatment of Fungal Infection R. Y. Cartwright Clotrimazole (Canesten) Therapy of Fungal Keratitis D. B. Jones, B. R. Jones, and N. M. Robinson Replication of Picornaviruses F. Brown Molecular Biology of Influenza Virus Replication and Points of Action of Inhibitors J. S. Oxford Metalloenzymes: A New Focus for Antiviral Drug Design? 209 D. D. Perrin Inhibition of Influenza Virus Replication by 2-deoxY-2,3- dehydro-n-trifluoroacetylneuraminic Acid (FANA) 215 J. L. Schulman and P. Palese Virus Specified Enzymes in Herpes Simplex Virus Infected Cells.. J. H. Subak-Sharpe and J. Hay 219 Studies with IBT-Resistant and IBT-Dependent Mutants of Vaccinia Virus to Clarify the Mechanism of the Antipox Activity 227 E. Katz, E. Margalith, B. Winer, H. Felix, and N. Goldblum

10 xii The Role of Cell-Mediated Immunity in the Therapeutic Action of Isoprinosine of Viral Disease Processes A. J. Glasky, G. E. Friebertshauer,J. W. Holker, R. A. Settineri, and T. Ginsberg CONTENTS 235 Bonaphton - A New Antiviral Chemotherapeutic Drug 239 G. N. Pershin, N. S. Bogdanova, I. S. Nikolaeva, A. N. Grinev, G. Ya. Uretskaya, and N. V. Arkhangelskaya Chemotherapeutic Activity of Bonaphton in Herpetic Keratitis in Rabbits N. S. Bogdanova, I. S. Nikolayeva, S. M. Kutchak, and G. N. Per shin Effect of Ribavirin on Influenza Virus Infection in Ferrets.. K. P. Schofield, C. W. Potter, J. P. Phair, J. S. Oxford, and R. Jennings I. C. I A Potent Anti-Rhinovirus Compound D. L. Swallow, R. A. Bucknall, W. E. Stanier, A. Hutchinson, and H. Gaskin Assessment of Some Antirhinovirus Compounds in Tissue Culture and Against Experimental Challenge in Volunteers. S. E. Reed and D. A. J. Tyrrell The Potential of Nucleosides as Antiviral Agents R. W. Sidwell, L. B. Allen, J. H. Huffman, J. T. Witkowski, P. D. Cook, R. L. Tolman, G. R. Revankar, L. N. Simon, and R. K. Robins Bichlorinated Pyrimidines as Possible Antiviral Agents 295 P. La Colla, M. A. Marcialis, O. Flore, A. Firinu, A. Garzia, and B. Loddo Experimental Chemotherapy of Arbovirus Infections 303 A. N. Fomina and A. K. Schubladze The Use of Lung Weight Changes for Evaluating the Activity of Drugs Against Influenza Infections in the Mouse 307 M. F. Beeson and M. R. Boyd In Vivo Topical Activity of the Interferon Inducer BRL 5907 and Ribavirin in Ferrets Infected with Influenza Virus 313 M. R. Boyd and M. F. Beeson

11 CONTENTS of Pyrimidine Derivatives on RNA Dependent RNA Polymerase o~ Mengovirus In~ected FL Cells E. M. Tonew and B. Fahlbusch E~~ects "In Vivo" Depression of Either Endotoxin or Virus Induced Inter~erons by Ri~ampicin and Ri~amycin Derivatives E. Ronda, M. L. Alonso, and I. Barasoain Investigations upon the Mode of Action o~ Compound 48/80 on ss DNA o~ Phage ~Xl74. R. Dennin Anti-Herpes Simplex Virus (HSV) E~fect of Amphotericin B Methyl Ester In Vivo H. Shiota, B. R. Jones, and C. P. Scha~fner Comparative Drug Trial in Cholera A. F. B. Mabadeje Trimethoprim Resistance o~ Pathogenic Organisms Previous to Common Clinical Use o~ Sulprim S. Ortel Susceptibility o~ Chloramphenicol-Resistant Strains of Salmonella typhi to Trimethoprim/ Sulfamethoxazole. M. B. Bushby and S. R. M. Bushby xiii Activity o~ Trimethoprim and Sulphonamides Against Pseudomonas aeruginosa D. Gray and J. M. T. Hamilton-Miller Microbiological and Clinical Studies with Co-Trimoxazole M. Aguirre, J. M. Ales, F. Lahoz, and R. Vela Cotrimoxazole as an All-Purpose Antibacterial Agent J. C. Gould and B. Watt Treatment o~ Human Brucellosis with Doxycycline and Trimethoprim-Sulfonamide L. Telegdy and J. Keri Synergy and Prostatitis S. R. M. Bushby and M. B. Bushby Trimethoprim/Sul~amethoxazole

12 xiv The Concentration of Sulphamethoxazole and Trimethoprim in Human Prostate Gland W. Oosterlinck, R. Defoort, and G. Renders Long-Term Treatment with the Combination SMZ/TMP in Children with Urinary Tract Infections L. B. Hahn and C. A. Barclay Long-Term Low-Dosage Co-Trimoxazole in the Management of Urinary Tract Infection in Children J. M. Smellie, R. N. GrUneberg, A. Leakey, and W. S. Atkin A Double-Blind study of Sulfamethoxazole Trimethoprim vs. Its Components in Chronic Urinary Tract Infections C. Demos, J. Pinderhughes, and M. Oakes A New Combination of Trimethoprim and a Sulphonamide (Sulphadiazine) in Urinary Tract Infections, a Double-Blind Study A. Lovestad, B. Gastrin, and R. LundstrOm CONTENTS Comparative Clinical Trial of Parenteral Co-Trimoxazole in Major Respiratory Infections: 421 M. Janousek, L. Corbeel, and P. Stenier List of Contributors 433