Relationships between animal and human influenza

ANTIGENIC VARIATION IN INFLUENZA VIRUSES 485 TABLE 3 HAEMAGGLUTININ-INHIBITING AND NEURAMINIDASE- INHIBITING ANTIBODIES TO A1/FM/I/47 INFLUENZA VIRUS IN YOUNG ADULTS a Mean titre Test No. positive/ of positiveno. tested samples b (per ml) Neuraminidase-inhibition 36/55 50 Haemagglutination-inhibition 51/55 930 a These sera were kindly provided by Dr W. M. Marine, Atlanta, Ga., USA. b Titres expressed as in Table 1. they possessed A2 haemagglutinin antibodies. The evidence suggests that the virus that occurred in the late nineteenth century possessed a different neura- minidase from that present in Hong Kong influenza virus. I have not tried to provide answers to the 3 points that I have raised-(1) the origin of human influenza strains with one or the other antigen related to animal or avian influenzas, (2) the role of the neuraminidase antigen in protection, and (3) the nature of the neuraminidase antigen of viruses that occurred in humans before 1933. All I have done, I hope, is to provide enough information to stimulate further investigations in these fields. Relationships Between Animal and Human Influenza by M. M. KAPLAN a Prior to the 1957 pandemic only a few workers, led by Shope, paid any attention to animal influenza and its possible relationship to human influenza. The recognition about 15 years ago that fowl plague and equine influenza belonged to the same group of viruses spurred some interest in this field. In July 1957, soon after the onset of the new A2 epidemic along with the vague report from China that epizootics in pigs had also occurred, the World Health Organization sought the opinions of experts throughout the world, including Sir Christopher Andrewes and Sir MacFarlane Burnet, concerning the intriguing possibility that the strain may have emerged from an animal reservoir. Since that time the World Health Organization has been trying to stimulate and co-ordinate studies on animal influenza in different parts of the world: periodic information circulars on animal influenza are sent to interested workers throughout the world. Advances in knowledge in this field during the past few years have been very great. But the following fundamental questions remain unanswered. Are lower animals of any importance as a prime source of the major antigenic shifts in the influenza A group that cause the recurring epidemics and pandemics? If they are, is it because of the emergence of an a Chief, Veterinary Public Health, World Health Organi- zation, Geneva, Switzerland. animal strain, which because of a slight change, is able to spread in man, or do recombinations occur in nature between animal and human strains with the subsequent emergence of a new strain? Do both sorts of events occur? The study of these possibilities is clearly most fascinating and productive, as revealed by several of the preceding papers. Several of the earlier papers have referred to the haemagglutinin (HA) and neuraminidase (E) rela- tionships, and their variability, between the Hong Kong strain and the earlier A2 strains (and even AO and Al) on the one hand and some avian and equine strains on the other. The development during the past few years of precise techniques for studying the neuraminidase enzyme (E) has added a valuable new tool for clarifying this problem. However, the epidemiological significance of these findings remains to be ascertained. Fenner b noted that the appearance of A2 with clear shifts in both HA and E gives considerable support to the idea of emergence from an animal reservoir, rather than representing a shift from Al. It would be interesting to know whether analyses of sera from the aged people investigated included anti-neuraminidase studies, as well as studies of HI. This would give a clearer indication of the relation- b Fenner F. (1968) The biology of animal viruses, New York and London, Academic Press, vol. 2, p. 778. 2393B 486 DISCUSSION PAPERS-SESSION II ship between the present Hong Kong and A/Equi-2 strains aild those presumed to have been prevalent in the 1890s. Little notice seems to have been taken ofTumova's extraordinary finding of specific HI antibodies to A/Equi-2 in sera from Mongolian horses. Since in Mongolia importation of horses is strictly forbidden, and since the country is relatively isolated geographi- cally, it seems most unlikely that racehorses from Florida, where A/Equi-2 was first isolated in 1963, introduced the disease into Mongolia. Do we, then, have the surviving prototype of the 1889 pandemic in Mongolia just as we seem to have the prototype of the 1918 pandemic in pigs in the USA and other countries? If so, how did it get to Florida? Are we to incriminate the birds and the astonishingly wide range of influenza strains that has been isolated from them in recent years? The World Health Organization depends on the splendid co-operation it receives from collaborating laboratories in pursuing studies into these problems. The main lines of investigation are: (1) Continued attempts to isolate viral strains from a range of wild animal species, and to characterize them antigenically. (2) Experimental studies of swine influenza to understand better the natural history of this disease. The results of work in Czechoslovakia and in Madison, Wis., of great interest in this connexion, will be published soon. (3) Experimental inoculation of horses with Hong Kong and A/Equi-2 strains, similar to the work reported by Kasel & Couch. c (4) In vivo recombination experiments in which it is planned to use different animal and human strains. (5) Continued surveillance of animal influenza in different countries, with the provision of diagnostic kits and the development of screening techniques for such work. c See the paper by J. A. Kasel & R. B. Couch on page 447 of this issue. Discussion on Antigenic Relationships of Animal and Human Influenza Viruses by B. C. EASTERDAY a The foregoing papers have provided further interesting evidence for certain relationships between influenza viruses of animal and human origin. This evidence was concerned with the antigenic and biological properties of the viruses and suggests that interspecies transfer takes place. It remains, however, to isolate identical viruses from animals and human beings in association during an epidemic or, for that matter, during an interepidemic period. Speculation about interspecies transfer goes back at least to 1918. When the swine influenza and human influenza viruses were isolated in the 1930s, many became intrigued and frustrated by the idea ,of an extra-human reservoir for influenza. This curiosity and frustration was further intensified by a Department of Veterinary Science, University of Wisconsin, Madison, Wis., USA. the pandemic of 1957 and again by the appearance of the Hong Kong virus in 1968. The curiosity has been amplified by the isolation and characterization of many type A influenza viruses from several animal species between 1957 and 1968. We now know that several viruses from several different species have similar antigenic characteristics. This information may be used to support an hypo- thesis concerned with interspecies transfer of the inflenza viruses: that transfer is common, that transfer is rare, or that certain species are more likely than others to be a reservoir, etc. However, the available information does not exclude an hypothesis that there may be several separate evolutionary lines for antigenic variation which do not require inter- species transfer. The evidence accumulated over the past 40 years suggests that pigs are the reservoir for 2393c