Control of epidemic influenza virus: aspects of vaccines and antiviral compounds

  • J. S. Oxford


The earth is a unity for influenza A virus in a manner not yet found for any other parasite (Hope-Simpson 1979). Epidemics occur in all inhabited parts of the globe regardless of latitude, longitude, altitude climate, rainfall, temperature, humidity, race and sex (Stuart-Harris & Schild 1976; Pereira 1979 Stuart-Harris 1981). Influenza A is the classic pandemic virus infection of humans, but influenza B virus can also cause sharp outbreaks resulting in significant mortality. Mortality data from 1200 million people living in 88 of the 160 or so WHO member states (approximately one quarter of the world’s population) show that more than two million deaths from acute respiratory disease occur annually (reviewed by Lennette, 1981, see also Table 1) and that the majority of acute viral respiratory disease is attributed to viruses of 5 families. Influenza A and B viruses cause a significant number of these deaths.


Influenza Virus Influenza Vaccine Acute Respiratory Disease Lower Respiratory Tract Disease Amantadine Hydrochloride 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. ALEXANDROVA, G.I. & SMORODINTSEV, A.A. (1965). Obtaining of an additionally attenuated vaccinating cryophilic influenza strain. Rev. Roum. Inframicrobiol., 2, 179–186.Google Scholar
  2. ALLING, D.W., BLACKWELDER, W.C. & STUARTHARRIS, C.H. (1981). A study of excess mortality during influenza epidemics in the United States 1968–1976. Am. J. Epidemiol., 113, 30–43.Google Scholar
  3. AOKI, F.Y., SITAR, D.S. & OGILVIE, R.I. (1979). Amantadine kinetics in healthy young subjects after long-term dosing. Clin. Pharmac. Ther., 6, 729–736.Google Scholar
  4. BEARE, A.S. (1982). (ed.) Basic and Applied Influenza Research, Cleveland, Ohio: CRC Press.Google Scholar
  5. BLAAS, D., PATZELT, E. & KUECHLER, E. (1982). Cap recognizing protein of influenza virus. Virology, 116, 339–348.Google Scholar
  6. BLEIDNER, W.E., HARMON, J.B., NEWES, W.E., LYNES, T.E. & HERMANN, E.C. (1965). Absorption, distribution, and excretion of amantadine hydrochloride. J. Pharmac. exp. Ther., 150, 484–490.Google Scholar
  7. BUKRINSKAYA, A.G., VORKUNOVA, N.K. & NARMANBETOVA, R.A. (1980). Rimantadine hydrochloride blocks the second step of influenza virus uncoating. Arch. Virol., 66, 275–282.Google Scholar
  8. CENTERS FOR DISEASE CONTROL (1982). Influenza vaccine efficacy in nursing home outbreaks reported during 1981–1982. MMWR, 31, 190.Google Scholar
  9. CHANOCK, R.M. (1982). New Opportunities for development of safe effective live virus vaccines. Yale J. biol. Med., 55, 361–367.PubMedPubMedCentralGoogle Scholar
  10. CHRETIEN, J., HOLLAND, W., MACKLEM, P., MURRAY, J. & WOOLCOCK, A. (1984). Acute respiratory infections in children: a global health problem. N. Engl. J. Med., 982–984.Google Scholar
  11. CLOAD, P.A. & HUTCHINSON, D.W. (1983). The inhibition of the RNA polymerase activity of influenza virus A by pyrophosphate analogues. Nucl. Acid. Res., 11, 5621–5628.Google Scholar
  12. DAVIES, W.L., GRUNERT, R.R., HAFF, R.F., McGAHEN, J.W., NEUMAYER, E.M., PAULSHOCK, M. & 4 OTHERS (1964). Science, 144, 862–863.Google Scholar
  13. DOLIN, R., REICHMAN, R.C., MADORE, H.P., MAYNARD, R., LINTON, P.M. & WEBBER-JONES, J. (1982). A controlled trial of amantadine and rimantadine in the prophylaxis of influenza A infection. New. Engl. J. Med., 307, 580–584.Google Scholar
  14. DOLIN, R., BETTS, R.F., TREENER, J.J., ERB, S.M., O’BRIEN, D.H., ROTH, F.K., MILLER, P., DUFFY, P. (1983). Rimantadine prophylaxis of influenza A in elderly. Proceedings of the23rd ICAAC, October 1983, Abstract no.691, p.210.Google Scholar
  15. DOUGLAS, R.G., Jr (1980). Amantadine: Should it be used as an antiviral? In Controversies in therapeutics, Lasagna, L. (ed.) pp.271–280, Philadelphia: W.-B. Saunders.Google Scholar
  16. EATON, M.D., LOW, I.E., SCALA, A.R. & URETSKY, S. (1962). Inhibition by ammonium ion of the growth of influenza virus in chorio allantoic tissue. Virology, 118, 102–108.Google Scholar
  17. EMTAGE, J.S., TACON, W.C.A., CATLIN, G.H., JENKINS, B., POSTER, A.G. & CAREY, N.H. (1980). Influenza antigenic determinants are expressed from haemagglutinin genes cloned in E. coli. Nature, 283, 171–174.Google Scholar
  18. FIELDS, S., WINTER, G. & BROWNLEE, G.G. (1981). Structure of the neuraminidase gene in human influenza virus A/PR/8/34. Nature, 290, 213.Google Scholar
  19. GALBRAITH, A.W., OXFORD, J.S., SCHILD, G.C. & WATSON, G.I. (1969). Protective effect of 1-adamantamine hydrochloride on influenza A2 infections in the family environment. Lancet, 1026–1028.Google Scholar
  20. GALASSO, G.J., BEKTIMIROV, T.A., DOUGLAS, R.G., KRYLOV, V.F. & OXFORD, J.S. (1984). Current status of amantadine and rimantadine as anti influenza agents: memorandum of a WHO meeting. Bull. Wld Hlth Org. (in press).Google Scholar
  21. GETHING, M.J. & SAMBROOK, J. (1982). Construction of influenza haemagglutinin genes that code for intracellular and secreted forms of the protein. Nature, 300, 598–603.Google Scholar
  22. GOODMAN, R.A., ORENSTEIN, W.A., MUNRO, T.F., SMITH, S.C. & SIKES, R.K. (1982). Impact of influenza A in a nursing home. J. Am. med. Ass., 247, 1451–1453.Google Scholar
  23. GREEN, N., ALEXANDER, H., OLSON, A., ALEXANDER, S., SHINNICK, T.M., SUTCLIFFE, J.G. & LERNER, R.A. (1982). Immunogenic structure of the influenza virus haemagglutinin. Cell, 28, 477–487.Google Scholar
  24. GRUNERT, R.R., McGAHAN, J.W. & DAVIES, W.L. (1965). The in vivo antiviral activity of 1-adamantanamine (amantadine). 1. Prophylactic and therapeutic activity against influenza viruses. Virology, 26, 262–269.Google Scholar
  25. HAYDEN, F.G., COTE, K.M. & DOUGLAS, R.G. (1980). Plaque inhibition assay for drug susceptibility testing of influenza viruses. Antimicrob. Ag. Chemo., 17, 865–870.Google Scholar
  26. HAYDEN, F.G., HOFFMAN, H.E. & SPYKER, D.A. (1983). Differences in side effects of amantadine hydrochloride and rimantadine hydrochloride relate to differences in pharmacokinetics. Antimicrob. Ag. Chemo., 23, 458–464.Google Scholar
  27. HEIDER, H., ADAMCZCK, B., PRTESBER, H.W., SCHROEDER, C., FELDBLUM, R. & INDULEN, M.K. (1981). Occurrence of amantadine and rimantadine resistant influenza A virus strains during the 1980 epidemic. Acta. Virol., 25, 395–400.Google Scholar
  28. HELGSTRAND, E. & OBERG, B.O. (1978). Antiviral screening based on cell-free polymerase models and a new selective inhibitor. Current Chemotherapy. Google Scholar
  29. HO, P.P.K. & WALTERS, C.P. (1971). Inhibitors of influenza virus induced RNA polymerase. Ann. N.Y. Acad. Sci., 133, 438.Google Scholar
  30. HOFFMAN, C.E. (1980). Amantadine HCl and related compounds. In Carter, W.A. (ed.) Selective inhibitors of viral functions, pp. 199–211, Cleveland, Ohio: CRC Press.Google Scholar
  31. HOPE-SIMPSON, R.E. (1979). Epidemic mechanisms of Type A influenza. J. Hyg., 83, 11–26.Google Scholar
  32. HORNICK, R.B., TOGO, Y., MAHLER, S. & IEZZONI, D.G. (1970). Evaluation of amantadine hydrochloride in the treatment of A2 influenzal disease. Ann. N.Y. Acad. Sci., 173 (1), 10–19.Google Scholar
  33. INDULEN, M.K. & KALNINYA, V.A. (1980). Studies on the Antiviral effect and the mode of action of the anti-influenza compound rimantadine. In Development in Antiviral Therapy, Collier, L.H. & Oxford, J.S. (eds) pp. 107–118, London: Academic Press.Google Scholar
  34. JACKSON, G.C., MULDOON, R.L. & AKERS, L.W. (1963). Serological evidence for prevention of influenzal infection in volunteers by an anti-influenzal drug adamantanamine hydrochloride. Antimicrob. Ag. Chemo., 703–707.Google Scholar
  35. KILBOURNE, E.D. (1969). Future influenza vaccines and the use of genetic recombinants. Bull. Wld Hlth Org., 41, 643–645.Google Scholar
  36. KNIGHT, V., McCLUNG, H.W., WILSON, S.Z. et al. (1981). Ribavirin small-particle aerosol treatment of influenza. Lancet, ii, 945–949.Google Scholar
  37. LENNETTE, E.M. (1981). Viral respiratory diseases: Vaccines and antivirals. Bull. Wld. Hlth. Org., 59, 305–324.Google Scholar
  38. MAEDA, T., KAWASAKI, K. & OHNISHI, S.-I. (1981). Interaction of influenza virus haemagglutinin with target membrane lipids is a key step in virus-induced hemolysis and fusion at pH 5.2 Proc. natn. Acad. Sci. U.S.A., 78, 4133.Google Scholar
  39. MAASSAB, H.F. (1967). Adaptation and growth characteristics of influenza virus at 25°C. Nature, 213, 612–614.PubMedCrossRefGoogle Scholar
  40. McCLUNG, H.W., KNIGHT, V., GILBERT, B.E., WILSON, S.Z., QUARLES, J.M. & DIVINE, ?. (1983). Ribavirin aerosol treatment of influenza B virus infection. J. Am. med. Ass., 249, 2671–2674.Google Scholar
  41. MCCAULEY, J.W. & MAHY, B.W.J. (1983). Structure and function of the influenza virus genome. Biochem. J., 211, 281.Google Scholar
  42. MONTO, A.S., GUNN, R.A., BANDYK, M.G. & KING, C. (1979). Prevention of Russian Influenza by Amantadine., 241, 1003–1007.Google Scholar
  43. NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES. (1980). Amantadine: does it have a role in the prevention and treatment of influenza A. A National Institutes of Health Consensus Development Conference. Ann. Intern. Med., 92, 256–258.Google Scholar
  44. OXFORD, J.S. (1975). Inhibition of the replication of influenza A and B viruses by a nucleoside analogue (ribavirin). J. gen. Virol., 28, 409–414.PubMedCrossRefGoogle Scholar
  45. OXFORD, J.S. (1983). Amantadine — problems with its clinical usage. In Problems of antiviral chemotherapy. Stuart-Harris, C.H. & Oxford, J.S. (eds.) p. 231, London: Academic Press.Google Scholar
  46. OXFORD, J.S. & GALBRAITH, A. (1980). Antiviral activity of amantadine: a review of laboratory and clinical data. Pharmac. Rev., 11, 181–262.Google Scholar
  47. OXFORD, J.S., HAAHEIM, L.R., SLEPUSHKIN, A., WERNER, J., KUWERT, E. & SCHILD, G.C. (1981). Strain specificity of serum antibody to the haemagglutinin of influenza A (H3N2) viruses in children following immunization or natural infection. J. Hyg. Camb., 86, 17.Google Scholar
  48. OXFORD, J., LOGAN, I.S. & POTTER, C.W. (1970). In vivo selection of an influenza A 2-strain resistant to amantadine. Nature, 226, 82–83.Google Scholar
  49. OXFORD, J.S., McGEOCH, D.J., SCHILD, G.C. & BEARE, A.S. (198(. Analysis of virion RNA segments and polypeptides of influenza A virus recombinants of defined virulence. Nature, 273, 778–779.Google Scholar
  50. OXFORD, J.S. & PERRIN, D.D. (1974). Inhibition of the particle associated RNA dependent RNA polymerase activity of influenza viruses by chelating agents. J. gen. Virol., 23, 59.Google Scholar
  51. PATRIARCA, P.A., KATER, N.A., KENDAL, A.P., BREGMAN, D.J., SMITH, J.D. & SIKES, R.K. (1983). Safety of prolonged administration of rimantadine hydrochloride in the prophylaxis of influenza A infections in nursing homes. Interscience Conference on Antimicrobial Agents and Chemotherapy, Las Vegas, Nevada, October 1983. Google Scholar
  52. PALESE, P. & SCHULMAN, J.L. (1977). Inhibitors of viral neuraminidase as potential antiviral drugs. In Chemoprophylaxis and Virus Infections of the Respiratory Tract, vol. I, p. 689 Oxford, J.S. (ed.) Cleveland, Ohio: CRC Press.Google Scholar
  53. PAYLER, D.K. & PURDHAM, P.A. (1984). Influenza A prophylaxis with amantadine in a boarding school. Lancet, i, 502–504.Google Scholar
  54. PEREIRA, M.S. (1979). Global surveillance of influenza. Br. med. Bull., 35, 9–14.PubMedGoogle Scholar
  55. PERRIN, D.D. (1977). In Chemoprophylaxis and Virus Infections of the Respiratory Tract vol. II. Oxford, J.S. (ed.) Cleveland, Ohio: CRC Press.Google Scholar
  56. PERRIN, D.D. & STUNZI, H. (1980). Viral chemotherapy: antiviral actions of metal ions and metal chelating agents. Pharmac. Ther., 12, 255–297.Google Scholar
  57. POTTER, C.W., PHAIR, J.P., VODINELICH, L., FENTON, R. & JENNINGS, R. (1976). Antiviral, immunosuppressive and anti-tumour effects of ribavirin. Nature, 259, 496–497.Google Scholar
  58. RICHARDSON, C.D., SCHEID, A. & CHOPPIN, P.W. (1980). Specific inhibition of paramyxovirus and Myxovirus replication by oligopeptides with amino acid sequences similar to those at the N-termini of the Fl or HA2 viral polypeptides. Virology, 105, 205–222.Google Scholar
  59. RICHMAN, D.D. & MURPHY, B.R. (1979). The association of the temperature sensitive phenotype with viral attenuation in animals and humans: implication for the development and use of live virus vaccines. Rev. Infect. Dis., 1, 413–473.Google Scholar
  60. RICHMAN, D.D., YAZAKI, P. & HOSTETLER, K.Y. (1981). The intracellular distribution and antiviral activity of amantadine. Virology, 112, 81–90.Google Scholar
  61. SCHILD, G.C., OXFORD, J.S., JONG, J. DE. & WEBSTER, R.G. (1983). Evidence for host cell selection of antigenic variants of influenza B virus. Nature, 303, 706–709.Google Scholar
  62. SCHULMAN, J.L. & KILBOURNE, E.D. (1965). Induction of partial specific heterotypic immunity in mice by a single infection with influenza A virus. J. Bact., 89, 170–174.Google Scholar
  63. SCHWAB, R.S., POSKANZER, D.C., ENDLAND, A.C. & YOUNG, R.R. (1972). Amantadine in Parkinson’s disease — review of more than two years’ experience. J. Am. med. Ass., 222, 792–795.Google Scholar
  64. SELBY, P. (ed.) (1976). Influenza: virus, vaccines and strategy. New York: Academic Press.Google Scholar
  65. SIDWELL, R.W., HUFFMAN, J.H., KHARE, G.P., ALLEN. L.B., WITKOWSKI, J.T. & ROBINS, R.K. (1972). Broadspectrum antiviral activity of Virazole: 1-B-Dribofuranosyl-1,2,4-triazole-3-carboxamide. Science, 177, 705–706.Google Scholar
  66. SMITH, R.A. & KIRKPATRIC, W. (eds.) (1980). Ribavirin: a broad spectrum antiviral agent, pp. 59–71, New York: Academic Press.Google Scholar
  67. STRIDH, S., HELGSTRAND, E., LANNEROE, B., MISIORNY, A., STENING, G. & OBERG, B. (1979). The effect of pyrophosphate analogues on influenza virus RNA polymerase and influenza virus replication. Arch. Virol., 61, 245–250.Google Scholar
  68. STUART-HARRIS, C.H. (1981). The epidemiology and prevention of influenza. Am. Scient., 69, 166–172. STUART-HARRIS, C.H. & SCHILD, G.C. (1976) In Influenza, the virus and the Disease, London: Edward Arnold.Google Scholar
  69. SWALLOW, D.L. (1978). Antiviral agents. Progr. Drug. Res., 22, 267–326.Google Scholar
  70. TILLETT, H.E., SMITH, J.W.G. & CLIFFORD, R.E. (1980). Excess morbidity and mortality associated with influenza in England and Wales. Lancet, i, 793–795.Google Scholar
  71. VARGHESE, J.N., LAVER, W.G. & COLMAN, P.M. (1983). Structure of the influenza virus glycoprotein antigen neuraminidase at 2–9 A resolution. Nature, 303, 35.Google Scholar
  72. VAN VORIS, L.P., BETTS, R.F., HAYDEN, F.G., CHRISTMAS, W.A. & DOUGLAS, R.G., JR. (1981). Successful treatment of naturally occurring influenza A/USSR/77 HINI. J. Am. med. Ass., 245, 1128–1131.Google Scholar
  73. WEBSTER, R.G., LAVER, W.G., AIR, G.M. & SCHILD, G.C. (1982). Molecular mechanisms of variation in influenza viruses. Nature, 296, 115.Google Scholar
  74. WERNER, G.H. (1966). Immunité croisée Hétérotypique chez la souris entrevirus grippaux humains de types A et A2. C.R. Acad. Paris, 263, 1913–1916.Google Scholar
  75. WHITE, J., KARTENBECK, J. & HELENIUS, A. (1982). Membrane fusion activity of influenza virus, EMBO Journal, 1, 217.Google Scholar
  76. WORLD HEALTH ORGANISATION (1984). A programme for controlling acute respiratory infections in children: memorandum from a WHO meeting. Bull. Wld. Hlth. Org., 62, 47–58.Google Scholar
  77. WILEY, D.C., WILSON, I.A. & SKEHEL, J.J. (1981). Structural identification of the antibody binding sites of the Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature, 298, 373.Google Scholar
  78. WILSON, I.A., SKEHEL, J.J. & WILEY, D.C. (1981). The haemagglutinin membrane glycoprotein of influenza virus: structure at 3 A resolution. Nature, 289, 366.Google Scholar
  79. YOUNKIN, S.W., BETTS, R.F., ROGH, F.K. & DOUGLAS, R.G., JR. (1983). Reduction in fever and symptoms in young adults with Influenza A/Brazil/78 HINI infection after treatment with aspirin or amantadine. Antimicrob. Ag. Chemo., 23, 577–582.Google Scholar
  80. ZLYDNIKOV, D.M., KUBAR, O.I., KOVALEVA, R.P. & KAMFORIN, L.E. (1981). Study of rimantadine in the USSR: a review of the literature. Rev. Inf. Dis., 3, 408–421.Google Scholar

Copyright information

© Macmillan Publishers Limited 1984

Authors and Affiliations

  • J. S. Oxford
    • 1
  1. 1.Division of VirologyNational Institute for Biological Standards and ControlLondonUK

Personalised recommendations