Premature rupture of the membranes.

One-third of the recent British Medical Bulletin on influenza' is on this aspect of the virus, including two complete articles on the chemistry of one surface component alone. Admittedly, this is the haemagglutinin, a glycoprotein which largely determines the pathogenicity of the virus. Nevertheless, it is now a far cry from the days when a distinguished virologist could write that ". what viruses do and how they do it is very much more important than what they are. " Not surprisingly, what viruses are goes a long way to explaining what they do, and influenza virus is no exception. Its behaviour has for long puzzled virologists. The more or less sudden appearance of major new variants every few years seemed to have no reasonable genetic or biological explanation, even though it was accompanied by a more intelligible and less abrupt antigenic change of surface characters. The phenomenon of genetic recombination in influenza had certainly been observed in the laboratory in cells infected simultaneously with two strains of the virus.2 The puzzle was that the recombination rate was embarrassingly high compared with that of other viruses, and the ease with which a reassortment of genetic factors could occur seemed almost too good to be true. Two decades of intensive work have done much to explain these features. Genetically, the influenza virus is best considered as a set of eight little RNA viruses-that is to say, eight pieces of RNA each coding for a peptide. These RNA moieties have some independence of expression within the cell-as has been known for years from the work, for example, of Scholtissek and Rott3 on avian influenza4 virus. Nevertheless, the RNA moieties are not independently viable, and they must work as a team, requiring each one of the eight members. This behaviour contrasts with, for example, mumps or measles or even a plant virus such as tobacco mosaic virus. All of these are, like influenza, RNA viruses, but the RNA behaves essentially as one large genetic and biochemical unit. The relative independence of action enjoyed by the eight little viruses which make up influenza means that, in a cell infected with two different strains of influenza (with two "teams" of eight in the same cell at one time), a reassortment of the players can occur. This process can be followed by observing and identifying, in particular, the haemagglutinin (H) and also the neuraminidase (N), both of them surface proteins. When recombination occurs, strains of influenza with differing H and N components "swap" with each other-or, to continue the terminology of the football field, transfer one or more players. The World Health Organisation has proposed a nomenclature for the subtypes of H and N proteins, and there are now sixteen H and ten N subtypes known, making possible 160 combinations. Of these subtypes, five H and two N have been found in strains isolated from man, two of each from pigs, and two of each from horses. Interestingly, the largest variety is found in birds, especially domestic poultry and wild ducks. Several subtypes of influenza A may be circulating in the avian fauna of a single piece of water, and there may be two or even more subtypes infecting one duck at the same time.5 6 The sudden emergence of an influenza virus with a new H or N protein subtype (or both) on its surface demands an explanation, and the answer seems likely to be recombination of an existing strain in a duck, perhaps in a pig, or even in a horse. Direct transfer from an animal reservoir to man is another possibility, and the persistence of "old" strains in a reservoir of ducks or pigs could explain otherwise puzzling observations such as the reappearance of swine influenza (Hswl) in man and the recent emergence from retirement of an old combination such as HlNl after 30 years. Though HlNl has not been found contemporaneously in ducks, Shortridge7 has recently reported the presence of H2N2 (absent from man for 10 years) in domestic ducks from southern China, and it would not be surprising if there were more influenzas, new and old, still to emerge from that country -where the ducks are said to outnumber the Chinese. For years now the unpredictability of the major changes has combined with the steady drift of surface antigens within an H or N subtype to make influenza the despair of vaccine manufacturers. Their problems in trying to keep pace with new strains are all too familiar. Moreover, a recent publication of the results of a detailed study at a boys' boarding school8 suggests that those who were vaccinated were little better off (perhaps worse) after their first postvaccination encounter with the strain concerned. Once a new major strain difference ("shift") occurred they needed a completely fresh vaccine anyway. Improvement may, however, be possible through better ways of inactivating the virus or better ways of using adjuvants; and live vaccines may one day come into their own. Nevertheless, the prevailing mood is clearly one of qualified pessimism. So far as specific chemotherapy is concerned, the various compounds tried in hope have not yielded results that stand comparison with their counterparts in bacteriology. The cyclic primary amines of the amantadine series have a significant inhibitory effect, but in practical terms their use is limited by the need to give them prophylactically and the possibility of development of drug-resistant strains. All these aspects are discussed in the British Medical Bulletin' issue on influenza. On reflection, perhaps we have one ground for encouragement: we can at least rest assured that, if the stalemate over influenza continues, it will not be because of untried moves.