Cold season ailments [full issue]

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One year Two years Three years USA USA USA $ 5.00 $ 8.00 $10.00 UK UK UK 4.0 0.0 £2.12.0 Switzerland Switzerland Switzerland 12.- 22.- 30.- WORLD HEALTH The mermen* al the Wald HmIth Orgensermon December 1969 contents The fangs of winter 3 Living with a runny nose, by Dr D. A. J. Tyrrell 4 Against influenza, by Dr Walter Hennessen . . . 12 Tracking down the flu epidemics, by Dr R. Gillon 15 Two winter killers, by Dr R. Gillon 20 The stab of earache, by Kyllikki Kauttu 26 Below zero 30 Books 34 Nobel Prize for ILO 35 Order form Please complete, detach and mail this order form to the agent for WHO publications in your country. Please enter my subscription to World Health: 1 year: -* 1 2 years * 3 years * I enclose cheque/postal order in the amount of Name: Street : City : Country : * Subscriptions are entered for the calendar year 2 the fangs of winter 01111111110" 44 vi Thoever wishes to investigate medicine properly should proceed thus: VI in the first place, consider the seasons of the year, and what effect each of them produces; then, the winds, the hot and the cold, especially such as are common to all countries, and then such as are peculiar to each locality... And, if it shall be thought that these things belong rather to meteorology, it will be admitted on second thought that astronomy contributes not a little, but a very great deal indeed, to medicine. For, with the seasons, the digestive organs of men undergo a change." Thus wrote Hippocrates over 2,300 years ago. Despite the fact that frost and cold have been man's enemy for centuries, Hippocrates' advice has not been followed. Few studies have been made of seasonal incidence of disease. It is true, however, that nowadays man is better equipped to protect himself from the cold, mainly through better nutrition and a higher general standard of living. From another point of view, low temperatures can be used to advantage now that they can be controlled; medicine and surgery use refrigeration to preserve bone and tissues, and in biology too, refrigeration techniques open entirely new perspectives. However, in spite of the remarkable progress being made in some fields we must not forget how harsh cold weather is for the elderly who may be poor and undernourished. This is the time of year when many workers undergo severe strain in order to allow the rest of the community to live more easily,— railroad men, electricians, those who clean and clear the streets, keep homes warm, well lit, and protect our health and comfort. Some ills assail all of us with particular intensity during cold weather, such as flu, bronchitis, pneumonia and otitis. In this issue, World Health takes a look at how far man has gone in eliminating or just learning to live with winter's ills. living with a runny nose World Health: What is the common cold? Dr Tyrrell: It is an infectious runny nose. That's the definition I like because it distinguishes it from things like hay-fever, which is an allergic runny nose, and from psychological runny noses, neither of which can be transmitted from one person to another. In the case of the common cold the discharge from the nose contains a virus which can be transmitted to other people by sneezing or blowing the nose. A little drop of fluid passes through the air, is breathed in, and the next victim now has the virus. We can do this experimentally at the Common Cold Unit by putting some of the nasal fluid in a test-tube and trans- ferring it to the nose of a volunteer who may or may not develop a cold. So the common cold is an infectious runny nose. It used to be thought that bacteria caused colds, but we now know that this is not so. This means that the drugs we use against bacterial infections—antibiotics and so on—are of no use against the common cold and similar diseases. The result is a problem for medical science as well as for practical medicine. W.H.: Might a vaccine be the answer? Dr Tyrrell: It is true that with the virus diseases we can control at the moment —poliomyelitis, smallpox, yellow fever and others—vaccines are the method of choice. They stop the virus infection ever starting in a patient, and it was thought of course, at one time, that there was the common by Dr D. A. J. Tyrrell * cold virus and that when the common cold virus was discovered we would make a vaccine of it and deal with common colds as we had with polio. It hasn't worked out that way, because the common cold is a disease or group of diseases which can be caused by a very large number of viruses. Dr D. A. J. Tyrrell. There are at least five different families of viruses, as different in their way, we might say, as are cows and birds in the animal kingdom. These viruses all invade the nose and damage the cells of its lining. So we contract diseases that resemble each other even when the agents that cause them are quite different. Not only are there different families of viruses, but within certain families there are large numbers of different serotypes of virus. For example, there are three sorts of polio virus, types 1, 2 and 3, so we have to put three different types of virus into the vaccine. In the case of the rhino-viruses, which are known to be one of the most important causes of colds, there are about ninety different serotypes, the first fifty- odd of which were classified by an inter- national programme organized by the Virus Unit of WHO in Geneva, which co- ordinated the work of laboratories in the United States and Great Britain. It is simply beyond the power of medical tech- nology at the moment to make a vaccine with ninety different components in it to combat the ninety different rhino-viruses and thus prevent all colds. The reason why we get so many colds is that we become infected with one virus after another, although the type of illness which results is always much the same. W.H.: How would you describe the symptoms and duration of the disease, and what can be done to cure it? Dr Tyrrell: Well, the symptoms are mainly associated with the nose. I men- tioned a runny nose, but of course the nose is also blocked. There may be headache, due to some extent to the general effects of the virus infection, and some fever. Because the membranes lining the nose are conti- nuous with those that line the throat and subsequently go down into the trachea, or windpipe, in some common colds the virus spreads to the respiratory tract and merges into diseases which doctors call bronchitis or tracheitis, and so on. So this is not a very sharply defined thing. Also, of course, 4 * Head of the Common Cold Research Unit, National Institute for Medical Research, London. Inoculating a common cold virus.... r " U'+A' • J :Y' 6 Abb._ They are told how they can best help research. Voluntary "guinea pigs" arriving at the Research Centre, Salisbury. a patient may start with something that looks like a common cold and then gradu- ally get worse ; this may be just because the virus has spread, or because the cells which have been damaged by the virus cannot keep out bacteria. So bacterial in- fections may follow colds: ear infections in children, or pneumonia in old people. Sometimes it is difficult to separate the common cold from what we would call pharyngitis, or a sore throat. There is always a bit of sore throat in the illness, on some occasions more than on others. This entire explanation may appear rather vague, but if one is truthful about this range or group of diseases one has to say that the divisions among them are some- what arbitrary. You asked about curing the common cold : I don't believe there are any cures. At the Common Cold Research Unit at Salisbury we keep a file of things that people do to prevent or cure colds. It's quite interesting. Some drink lemon juice, others wash their noses out with all sorts of concoctions, mostly salt water. One of my favourites is the man who rubs his socks every day with an onion—I have a feeling that nobody else can get within sneezing distance of him and that is why he doesn't get a cold! Seriously though, in order to cure a cold one would have to reverse the damage done by the virus to the cells, which is not really practicable. What we might hope to do would be to prevent colds not with vaccines but by giving some medicine or drug which would stop the virus multiplying. This is a very difficult task, scientifically speaking, be- cause these viruses are growing inside living cells, and if you produce a medicine that will stop the virus growing it may very well damage the cell in some way. How- ever, there is hope. A former colleague of mine who died recently, Dr Isaacs, dis- covered a naturally occurring substance called interferon. This substance is a pro- tein produced by infected cells : it has absolutely no harmful effect on them, and yet it can prevent almost any known virus from multiplying in a cell. It can get into other cells, and when it does it makes them produce a second protein: this second protein attaches itself to a particular organ in the cell called a ribosome, which makes new virus ingredients, virus proteins. The A preliminary examination of one of the volunteers. The volunteers being tested and the workers administering the fluid do not know whether the fluid used is infective or not: this is a double-blind trial. result is that the cell cannot make proteins for the virus particles, so no virus particles can be formed. The unbelievable thing about it is that this is so specific that the cell can go on making its own proteins. In this way the cell grows and behaves per- fectly normally, but it has a specific block which prevents it making the strange virus protein, and so the virus has no effect, does no harm to the cell. W.H.: How is interferon research pro- gressing? Dr Tyrrell: It is a very difficult substance to work with and is still not completely purified, though great progress has been made. Asa practical treatment for diseases, it has two great disadvantages. One is that because of the size of this protein it is unlikely that any laboratory will ever be able to synthesize it. It will therefore have to be made in biological systems from other living cells, and will always be diffi- cult and expensive to produce. The second disadvantage is that it is what we call species specific. I said that it prevents almost any virus growing, but it will only do so in cells similar to those in which it was made. For instance, if you make inter- feron in chicken cells, which is quite easy, it will not prevent infection of human cells. To prevent infection of human cells you must use interferon made either in human or in monkey cells. It is difficult to get substantial amounts of either of these. In the last years of Dr Isaacs' work he became very interested in what are now called interferon inducers. These are substances which are not, in fact, viruses : sometimes they are substances that can be made very easily, and when they get into a cell they trigger off the mechanism so that the cell starts producing interferon. Now this interferon, although not induced by a virus, will prevent virus infection; so there is a hope that if we can successfully stimulate people's bodies to make their own interferon, and quite a lot of work is going on along these lines, we may be able to overcome diseases like the common cold and possibly other virus diseases as well. W.H.: Has the discovery of interferon contributed to other fields of research? 8 Dr Tyrrell: Yes, the other importance of interferon is that it has raised hopes of discovering a synthetic chemical, much simpler than interferon, which would have the same effects. The old belief that the virus was so much like the cell that you could not control the multiplication of one without damaging the other has been discarded, and work on anti-viral drugs has thus been considerably stimulated. There is one such substance, called aman- tadine, which was discovered in the United States. It is still in the trial stage, but may well be able to prevent influenza. Another, discovered in Britain and first tested on man at the Common Cold Unit in 1968, was found to prevent not only influenza A infections, as does amantadine, but in- fluenza B infections as well. As you see, it is a long and arduous process to develop a drug to the point where widespread and effective use can be made of it. W.H.: What is the name of this new British drug? Dr Tyrrell: At the moment it has just a code number, UK 2371; it belongs to a family of chemicals called isoquinolines. W.H.: What exactly is the procedure at the Common Cold Unit in Salisbury? A technician pipettes the suspension of influenza virus. Dr Tyrrell: Once every two weeks between twenty and thirty volunteers from various parts of Britain, and sometimes from Europe, arrive at the Unit. Their expenses are paid and they agree, before they come, that they will let us drop viruses into their noses and sometimes give them drugs which may have been given to man before and been demonstrated to be harmless but have not so far been shown to prevent a virus infection. One of the difficulties in testing drugs at the moment is that we have so many viruses. New drugs are not necessarily active against every virus, and we should have to wait for months, if not years, before we happened to find the right patient in a clinic or hospital to give the right drug to at the right time. But at Salisbury we can arrange a little epidemic any time we want; we can also arrange for people to have the drug for two or three days, so as to give it A dish of virus-infected cells. every chance to work. And so, whereas in the past our volunteers mainly served to tell us whether we had a new virus or not, now that we feel we know most of the common cold viruses, we use the volunteers to find out whether anti-viral agents or treatments really work. W.H.: To what extent do the public co-operate? Dr Tyrrell: It is only when you have a disease which is mild, and which doctors agree it is ethical to ask volunteers to have, that you can do this sort of work. We are fortunate in having excellent co-operation from the public in Britain. I think in many parts of the world people might not offer themselves in this way, and we owe our volunteers a great debt of gratitude. About ten thousand members of the British public have come over the last twenty years for one sort of experiment or another. W.H.: Are some people more suscep- tible to colds than others? Dr Tyrrell: Work done in the early days of the Unit, and since confirmed in other parts of the world, has shown that infants and schoolchildren are the most likely to pick up the virus from other people who have got colds. They also seem to be the most likely to pass it on. Women tend to 244.2,¢t • Dr E. J. Stott inspecting a bottle containing cells used for the growth of rhinoviruses. 9 have more colds, or they did in this parti- cular study, possibly because they are exposed to children more closely than their husbands; but it may well be that in other cases, when the husband is out and about meeting a lot of people, he gets more colds than his wife. It is certainly true that as time goes on, as people get older, they become more resistant to colds. The reason for this is simply that after an infection with any one virus we develop antibodies that circulate in the body just as they do after a vaccination : once we have them we can't be re-infected with the same virus. Of course, we still go on having colds, because it is unlikely, even if a person lives to be seventy or eighty, that he will be exposed to all the viruses that exist. W.H.: Do seasonal changes affect the incidence of colds? Dr Tyrrell: The general season of colds and other respiratory diseases is in Britain the winter. Of course, some parts of the world don't have winter and summer in the way we do, but even so there may be a seasonal incidence of colds. A colleague of mine found, to everyone's surprise, that in Trinidad, in the West Indies, people had just as many colds as they do in our cold and miserable climate, but they got theirs mainly in the wet season. Here we get them in the winter, which is slightly colder than the summer but not wetter. There are a number of subtle factors that we fail to understand. There is some evidence that since the air indoors becomes drier as a result of heating this may favour some sorts of viruses, though not others. We are beginning to dissect, so to speak, this winter wave of colds, and we have discovered, for example, that the rhino- viruses nearly always cause the wave of colds that come to Britain in September: this is the time when we shut our windows a bit, and the children go back to school, and thus there is more chance of the viruses spreading. Then, also, rhino-viruses are common in the spring; but we may find influenza between about January and March, while certain other newly iden- tified viruses, called corona viruses, cause colds around December, January and February, and not so much at other times of the year. So, although viruses tend to spread more easily in the winter, some types are more frequent in one month than in another. It is a fact, of course, that, when winter begins, a number of different viruses are all spreading at the same time. This pro- duces a very complicated situation, and it can never be true to say that there are no people with colds in any large town. If you enquire carefully enough you will find that there are always some, and we suspect that in general the viruses go on spread- ing from person to person. Because they spread less in summer we are not so much aware of them, but the rate steps up in winter and the results are obvious. Some people suggest that the viruses that cause colds lurk in the nose for months and months, but there is quite a lot of evidence against this. We have also been studying the islanders of Tristan da Cunha, who live out in the south Atlantic, just two or three hundred of them. They have colds after a ship arrives, but once the epidemic is over nobody gets a cold again until the arrival of the next ship. Furthermore, if with people like this who are not normally exposed to infection you do the sort of things that are generally imagined to provoke colds, like chilling them, they still do not develop colds. There is no evidence that to become chilled awakens a virus which, people believe, is lying dor- mant in their nose or throat. One of the best examples is that of a trapper in Spitzbergen who spent the winter on his own and fell into a freezing cold river during the spring thaw. He had to continue in wet clothes across the wilderness, yet he did not catch cold at all. A few weeks later, however, when the ice pack had broken up, he walked into a town where a ship had just arrived and then he really did get a cold, and a bad one. W.H.: Is there any evidence that the common cold can be passed from animal to man? Dr Tyrrell: The short answer is no, but it is becoming clear that animals do have respiratory infections which in many ways are similar to those of human beings. Children suffer from para-influenza virus infections, for example: so do calves and lambs. We have mentioned the rhino- viruses of man. Rhino-viruses have now been isolated from cattle, and it is known that poultry and other birds have influenza viruses similar to man's. However, the cells and other details of the anatomy of animals are so different that there is little likelihood that viruses spread from man to them, except perhaps in the case of animals which zoologically resemble man. For instances, chimpanzees can get human cold infections. In fact, this was one of the early obstacles to keeping them healthy in captivity. W.H.: And what of the future? Dr Tyrrell: Well, I feel that I have been trained to find things out, not to predict the future, so I'm rather cautious about answering this sort of question. I think we need to know much more about the way viruses spread across the world, or even within a country. Work of this sort—iden- tifying viruses, finding what sort of diseases they cause, and which are the important or dangerous ones—will go on, as will research into vaccines against the viruses that cause severe diseases of children like pneumonia and croup. A great deal of effort has already been expended on vaccines, particularly in the United States; only limited progress has been achieved, but nobody expected it to be easy. Further- more, the rewards of preventing such a severe disease as pneumonia, which affects children all over the world, are so great that I am sure we shall continue to strive for this. So far as the milder respiratory diseases are concerned, where there are very many viruses, my hope is that we shall find a usable anti-viral drug of some sort, preferably something which can easily be synthesized in a laboratory. I think perhaps that the most reasonable target to set ourselves is that of preventing the mild sort of cold from becoming a severe one. You see, if we stopped all virus infections of this sort the end result could be that nobody would have any immunity. We know from experience with bacteria that the viruses would sometimes find a way round our chemical defences, and then they might cause serious trouble and we should be worse off than if we had not done anything at all. 10 A constant temperature bath in which bottles of cells infected with rhinoviruses are maintained. The question being investigated is why rhinoviruses grow best at just below body temperature: 33° rather than 37°. All virus research work, in our own and in other fields, is interconnected. An example of this is that we described a way of cultivating some of the first rhino- viruses using certain cells and then chal- lenging them with a second virus, and we knew that the rhino-virus, the first virus, was there because the second virus could not grow in these cells. It is interesting that the people who first cultivated the virus of German measles, rubella, were in fact trying to repeat these experiments or were using the technique we developed on mate- rial from patients with German measles. They found that rubella virus would ac- tually grow very well under these condi- tions, and so the whole sequence of events, which has now led us to the point where we are in fact making and using the first rubella vaccines, to some extent arose out of work on common colds. Another example is that in the last three or four years we have used a method called organ culture, in which tiny pieces of human trachea, or windpipe, and nose are kept alive intact in the laboratory, and thus we have cells in which viruses will grow which would not grow in the older tissue- culture method. It is quite clear that this type of approach is going to be of value in many ways. People are using this technique for studying the pathology of viruses, or the way in which they damage tissue. They are also using it or going to use it for attempts to cultivate other viruses which, so far, have not been grown. These pro- jects were started because we had tackled a specific problem in the common cold. The solutions may in fact lead to valuable applications well outside that field. W.H.: What do you do when you have a cold? Dr Tyrrell: I try to forget about it. I take some aspirin if need be, and if I find I have a very raw throat I breathe some steam from a jug and get into bed, and the next day it's usually a lot better. ■ 11 against influenza World Health: Dr Hennessen, we notice very often that public discussions on the effectiveness of flu vaccination, in the press for example, are confusing. Do you have an explanation? Dr Hennessen: Discussions on vaccina- tion against influenza are, to a certain extent, contradictory and somewhat un- rewarding, because they are usually not founded on fact. The protection afforded is either underestimated or else exaggerated, as if the vaccine could prevent all winter sickness. We should start by looking at the con- tribution of influenza to the overall level of disease in the community. Then there is the matter of comparing the number of influenza cases and influenza deaths. Fi- nally, for practical reasons, the economic impact of influenza should be investigated. W.H.: Dr Hennessen, can you give some indication of the place of flu in the total disease picture of Germany? Dr Hennessen: Perhaps. I have tried to determine this objectively from a variety of sources. The illness figures recorded by the social insurance system are an indicator of the state of health of the economically active population between the ages of 18 and 65. These figures also reflect the eco- nomic importance of illness since all cases leading to absence from work are recorded. In the Federal Republic it is not possible, on the basis of the data supplied by the social insurance system, to make an analysis of morbidity by cause. I think we may, however, use some other sources, and by way of analogy get some idea of the importance of influenza in the general pattern. Moebest and his collaborators by Dr Walter Hennessen* recently published a detailed epidemiolo- gical study of morbidity in the German army, which comprises about 500,000 men, aged 20 to 60 years. Moebest stresses that high illness peaks in the army, which occur exclusively during the cold season, generally January-March, are accounted for by influenza. Comparison between the Dr Walter Hennessen. state of illness in the army and that among the working population covered by social insurance reveals great similarities, but in the army the high peaks invariably show up a month before they do so in the social insurance figures. This arises through differences in recording systems. In both, a monthly reporting system is used, but whereas the army records all new cases as they occur during the month, the social insurance administration gives the actual position at the beginning of each month. The differences can be reduced by pre- dating the social insurance figures. Analysis of general morbidity and in- fluenza morbidity in the army during the cold season shows that increases in both occur at the same time. More than that, it can be shown that with an increase in general morbidity there is an increase in the proportional contribu- tion of influenza to the total—the higher the number of ill persons, the larger the proportion of influenza cases among them : when general morbidity doubles, there is a four-fold increase in influenza morbidity. Clinically, epidemiologically and statisti- cally it may be concluded with reasonable safety that, in this large group of 0.5 mil- lion people, general morbidity depends to a large extent on influenza morbidity. The next step is to consider whether there is a relationship between influenza morbidity in the army and general morbidity within the framework of social insurance. It can be shown with a high correlation (0.58) that an increasing general morbidity among the working population is accompanied by an increase of influenza morbidity in the army. A doubling of general morbidity among the insured population is paralleled by a ten-fold increase in the number of influenza cases in the army. The contribu- tion of influenza to general morbidity be- comes even more obvious if years with or without influenza epidemics are considered separately. W.H.: In the public mind, the impor- tance of infectious diseases depends not only on the number of cases but especially on the number of deaths. 12 * Assistant Professor, Marburg University. An absolutely sterile environment is required for the preparation of flu vaccines. P. • Dr Hennessen: In the Federal Republic of Germany, deaths from influenza are notifiable. Most of these deaths are re- ported on clinical evidence and are not confirmed by laboratory diagnosis. There is no accurate surveillance of influenza in this country, although we have a nation- al influenza centre, several regional in- fluenza centres and about ten virus diagnostic centres. The part influenza plays in mortality can only be estimated by comparison with countries where epidemi- ological surveillance is more intensive. For a number of reasons, the USA seemed suitable for such a comparison. An analysis of figures for influenza deaths during the years 1956-1966 shows that the trend in the two countries is very similar. The correlation of the mortality figures in the USA and in this country is in fact very high (0.98). During the same period, 1956-1966, there were several years in which both countries experienced a steep increase in influenza mortality. The peaks may represent as much as six times the number of deaths in the intervening period. The years with a large excess mortality are recorded in both countries as the influenza epidemic years 1957-1958, 1960 and 1963. In both coun- tries, the epidemic waves spread from west to east. In both countries, the excess mor- tality affected the age group over 50 years. So it seems that the course and the con- sequences of influenza epidemics are simi- lar if not identical in the two countries. There is, however, a big different in rela- tive mortality. For the Federal Republic, 58,008 influenza deaths were recorded during the period; for the USA, 44,408. The difference is all the more important since the total population in the USA is 3.3 times as large as in the Federal Repub- lic. The figures give a rate of one death per 11,000 inhabitants a year in this country and one for 44,000 in the USA. The question arises whether the differ- ence in these figures is due to different recording systems, but I am afraid I cannot go into this question now. In any case it should be pointed out that the difference is particularly pronounced in epidemic years and is smaller in non-epidemic years. No figures are available to compare the vaccination status in both countries, so I cannot say anything about that either. One point worth mentioning is that the age distribution of the population is different, the concentration of old people being higher in the Federal Republic. The popu- lation density is also higher: the Federal Republic, with 216 inhabitants per square kilometre, has a density eleven times greater than that of the United States (19 inhabitants per square kilometre). Regardless of what the significance of these various factors may be, it can be said that deaths from influenza represent simi- lar problems in both countries, but the problems are not of the same rank since, relative to population size, death from influenza is diagnosed four times more fre- quently in the Federal Republic than in the USA. W.H.: Public information media— press, radio, television but also the scientific papers have drawn attention to the fact that influenza, in addition to being a health problem, is an economic one. Whole coun- tries and even continents are said to have suffered great economic losses because of influenza epidemics. Do you have any figures with reference to Germany? Dr Hennessen: On the basis of the argu- ments I have been putting forward, we may consider that, if 4.8% of the economi- cally active population are ill, the percent- age of influenza patients in that population will be 0.77%. The loss for the economy caused by a five-day absence of that num- ber of flu patients may be set at DM 80m. If the percentage of ill persons in the economically active population goes up to 7.1%, the proportion of flu patients will amount to 2.13%, and the five-day "flu loss" can be set at DM 220.8m. These figures are calculated for 1968, when the number of economically active persons was 26,354,000 and the gross national product was DM 528,000m. On the subject of vaccination, it seems clear that it is not possible to express pro- tection in a single protection rate; in other words, a protection rate for a given popu- lation during a given period is not imme- diately comparable with another protec- Painless flu vaccination by pressure injection. Influenza Trends 1955-1966 Year England and Wales Federal Republic of Germany France H ungary United States Japan Australia Number of deaths Death rate per 100,000 population Number of deaths Death rate per 100,000 population Number of deaths Death rate per 100,000 population Number of deaths Death rate per 100,000 population Number of deaths Death rate per 100,000 population Number of deaths Death rate per 100,000 population Number of deaths Death rate per 100,000 population 1955 2,983 6.7 5,920 11.8 3,061 7.1 919 9.4 2,755 1.7 539 0.6 129 1.4 1956 2,626 5.9 3,874 7.7 4,206 9.6 858 8.7 2,323 1.4 543 0.6 182 1.9 1957 6,716 15.0 1 0,1 24 20.1 11,899 27.0 2,129 21.7 7,463 4.4 7,735 8.5 445 4.6 1958 2,401 5.3 5,686 10.9 3,270 7.3 988 10.0 4,442 2.6 1,973 2.1 103 1.0 1959 7,862 17.3 3,956 7.5 6,853 15.2 2,371 23.8 2,845 1.6 1,001 1.1 693 6.9 1960 1,098 2.4 12,085 22.6 12,323 27.1 2,025 20.3 7,872 4.4 4,012 4.3 124 1.2 1961 7,102 15.4 1,910 3.5 2,471 5.4 806 8.0 2,137 1.2 1,593 1.7 100 1.0 1962 3,308 7.1 3,353 6.1 7,092 15.1 2,136 21.2 3,431 1.8 7,014 7.4 144 1.3 1963 3,214 6.8 10,282 17.9 8,867 18.5 672 6.7 7,083 3.8 226 0.2 67 0.6 1964 1,043 2.2 1,435 2.5 2,447 5.1 410 4.1 1,687 0.9 609 0.6 302 2.7 1965 814 1.7 2,854 4.8 9.309 19.0 1,197 11.8 2,295 1.2 5,024 5.1 142 1.3 1966 3,672 7.6 2,349 3.9 3,116 6.3 355 3.5 2,830 1.4 383 0.4 249 2.2 Source: WHO World Health Statistics Annual This table shows peaks corresponding to epidemics, i.e. in 1957, 1960 and 1963 in most countries. However, the epidemic may start earlier in one country than in another and may also be spread across the months of December and January thus affecting the main figure for two consecutive years. It will be noted that important changes occurred in death rates corresponding to years with or without epidemics. It is not advisable to compare figures from one country to another since diagnostic practice can vary considerably. tion rate in different circumstances. Fischer, in a recent comparative study between vaccinated and non-vaccinated groups, was able to show that the influenza- vaccinated group was significantly pro- tected. Vaccination prevented the sharp increase in morbidity that occurred in the non-vaccinated groups. Pechet and his colleagues similarly found that vaccinated employees of a large indus- trial concern were protected during a period when influenza morbidity peaks were occurring among non-vaccinated persons. In addition, they considered that vaccinations repeated yearly gave a relati- vely better protection than a single vacci- nation. Similar observations were made in a number of other industrial concerns. It does not seem possible, however, on the basis of these studies to give any exact indi- cation concerning the duration of protec- tion, since there are regional differences in the length of the illness and since protec- tion can only be assessed in the presence of an epidemic. In the world literature, nothing suggests that protection lasts longer than twelve months, so for the time being this period should be accepted as a maximum valid approximation. ■ 15 tracking down the flu epidemics Dotted around 55 countries of the world are some 85 highly specialized labor- atories whose small staffs spend a good deal of their time studying one of man's most persistent enemies. The object of their intensive scrutiny? The viruses which cause influenza. Their purpose in studying it? To help us beat an affliction which even at its most benign causes mankind con- siderable discomfort, and at its most malignant causes acute disease, economic disruption, and death. Essentially, the WHO influenza pro- gramme, to which these 85 laboratories belong, involves the rapid isolation and analysis of the myxoviruses which cause influenza, with fast provision of interna- tional information when epidemic influ- enza occurs. To achieve these ends, national labora- tories keep up a constant surveillance of the flu viruses present in their areas. As soon as an unusual type appears they send it to one of two wHo Influenza Centres, in London or in Atlanta, Georgia, USA. There the virus is more throroughly identified, propagated, distributed to na- tional laboratories in other parts of the world and, if there are signs of an epi- demic, samples are also sent to labora- tories concerned with the production of vaccines so that supplies can be built up in time. Situated in the country on the outskirts of London, in the huge complex of labo- ratories comprising part of Britain's National Institute for Medical Research, the World Influenza Centre is certainly physically extremely compact. Working in it are its part-time director, Dr H. G. Pereira, assisted by a visiting scientist (who has a World Health Organization fellowship), a senior technical officer, two by Dr R. Gillon* junior technicians, and a part-time sec- retary. This small team routinely identify influenza viruses sent in from all over the world except North and South America where laboratories send their strains to the Atlanta Centre. The London team collect well-defined strains for their living "library" of viruses, samples of which they distribute as reference material when these are required by other laboratories; and they collaborate with the Atlanta Centre in checking the reagents prepared annually by the Atlanta Centre. As well as this, when any flu outbreak is threatening to spread, the Centre col- laborates with wHo Geneva in giving national centres up-to-the-minute infor- mation on its progress. Finally, the Centre Specimens arrive from all over the world. also carries out basic research into the nature of flu viruses, their genetics, their chemistry and their behaviour in various host animals. Complicated task Investigations of viruses tend to be highly complicated. For example, to iden- tify a virus sent to it by a national labora- tory, the Centre's technicians must first grow it successfully. Since the virus will grow only in living cells, it must be care- fully inoculated either into fertilized eggs, where it multiplies in the cells of the dev- eloping chicken embryo, or else into special animal or human tissues grown in a carefully balanced chemical environ- ment. Once the virus is growing properly the identification tests can begin. Various chemical and biological reagents are added to the virus and the pattern of reactions reveals its type. If the virus is a fairly standard one these tests will be sufficient and identification takes only two or three days. On the other hand, if the virus reacts unusually to these tests, more com- plicated investigations are needed. For these the virus must be inoculated into a group of experimental ferrets kept at the laboratory. The ferrets catch flu, and as a result of the changes this produces in their blood, the serum can be tested against standard strains of virus (obtained from the Centre's virus "library") and so iden- tified. Unfortunately, producing ferret antiserum and testing it is time-consuming: the process cannot be completed in less than two to three weeks. The last time the WHO emergency pro- gramme went into action was in 1968 16 * Editor of "Medical Tribune". The World Influenza Centre in England receives many research workers from other countries. when a sample of a new type of influenza virus was sent to the London and Atlanta Centres from Hong Kong, where an epidemic was raging. The pre- liminary tests were suspicious, so in both centres' the strains were inoculated into ferrets. The serum tests showed that without doubt the virus was a new type of influenza A2, substantially different from the notorious A2 "Asian flu" virus of the 1957 epidemic. Thanks to the rapid implementation of the \Arm influenza plan, valuable time was saved and the lengthy business of vaccine production—three to four months are needed to produce epi- demic supplies of vaccine—was started before the flu actually arrived in most countries. In the end the virus spread over large parts of the world, causing wide- spread epidemics, notably in Asia and North America. In most places in the northern hemi- sphere, the vital vaccine supplies urgently needed for treating people at special risk were not ready in good time, but ample supplies were available for the southern hemisphere before the influenza season began there. How does the vaccine work? Like other viruses, influenza viruses do their damage by invading the interior of the cells of the body, especially the cells of the respiratory tract, and taking over the normal redu- plication machinery for cell proliferation, so that instead of producing more human cells this machinery produces more viruses. Fortunately, the body does have its own defence mechanism for dealing with such in- vasions it manufactures antibodies which react with the various proteins (antigens) present in the virus and particularly in the outer part known as the "envelope". The reaction between the antibodies and the viral proteins inactivates the viruses and so cures the infection. Unfortunately, the production of these protective antibodies takes some time, and all the while the virus is busily multiplying and causing its host suffering. Eventually sufficient antibodies are produced to overcome the viruses and, except in those com- paratively rare cases which are fatal, the disease is usually over after a week or so (though full health may not be restored for several weeks afterwards). How vaccination works Once the antibodies are present in the blood they repel any new invasion by the same (or very similar) strains of flu virus for a year or so—but they do not repel different types. 17

Vaccination is a method of artificially preparing the body for a flu attack. All that happens is that a small dose of virus is injected into a muscle—but the virus has been previously killed, so that while it still causes the body to manufacture antibodies against the protein antigens present in the viral envelope, it cannot pro- duce any influenza. Another type of vac- cination, currently being tested extensively in the Soviet Union, involves the use of live flu viruses which have been made harmless by special growing techniques (attenuation) in the laboratory. If there were only one or two types of influenza virus causing the disease it would theoretically be possible to immunize everyone in childhood against flu, just as people can be immunized against typhoid. In fact, there are a large number of different types of influenza virus (grouped into three categories—A, B and C; viruses in group A tend to cause flu epidemics). Unfortunately, they have the disconcerting habit of periodically chang- ing their nature, following which the new variants are unaffected by antibodies dev- eloped through previous flu infections or vaccinations. Because of this, the only really effective vaccination policy is to inject people with a vaccine made from the virus which is responsible for a par- ticular outbreak. As we have seen, the dangerously lengthy business of vaccine production is mini- mized by the WHO influenza plan, under which vaccine producers are sent samples of new influenza virus as soon as the World Influenza Centre has decided that an epidemic seems likely. The manufac- turers immediately experiment to develop the best conditions for growing the virus rapidly (usually in fertilized chicken eggs). To make the vaccine, they harvest the virus from the eggs, kill it with formol, and purify it. Still a mystery While no one really knows how the influenza virus appears in a different guise so readily, there have been various theo- ries. One is that it involves a simple matter of mutation, with Darwinian selection of the fittest. The idea is that spontaneous changes occur in the virus genes, produc- ing an antigenically different virus; the new variant then has a better chance of surviving because it does not encounter hosts with ready-prepared antibodies wait- ing for it. This explanation may well be true for some of the minor changes which occur in influenza viruses over the years; but, as Dr Pereira said to me, the differences between, for example, the A2 of Asian flu in 1957 and the previously prevalent Al virus were too numerous, genetically speaking, for random mutations to be a likely cause. Another possibility which has been sug- gested is that the flu viruses go through a process known as genetic recombination. It is known, for example, that if two viruses grow together in one host cell they may sometimes produce a hybrid virus containing material from each "parent" virus. Possibly the same sort of process could account for major changes in the flu virus. A third possibility is that there is a large reservoir of different types of flu virus present in animals throughout the world and that from time to time they leave the animals and infect humans, pos- sibly returning to the animals when the humans have developed sufficient antibody resistance to repel them. This is only a theory, but it is interesting that various animals—including birds, swine and horses —have been shown to harbour influenza viruses, and the viruses that cause human influenza have been transmitted to experi- mental animals, for example to the ferrets used in the World Influenza Centre. So why not the other way round? Further- more, the antibody-antigen reactions of certain contemporary strains of human influenza viruses are chemically very simi- lar to the reactions of certain strains that infect animals. On the other hand, these same contemporary human strains differ from earlier strains known to infect humans, which does suggest that the current human strains could have been derived from animal sources rather than from earlier human sources. However, there has been no certain evidence of influenza spread from animals, and re- search into this problem is continuing at the World Influenza Centre and elsewhere. The large number of flu viruses makes it unlikely, according to Dr Pereira, that a vaccine will ever be produced giving immunity against all of them. Instead, he predicts, we shall probably learn to deal with influenza with drugs. "It should not be many years before we have effective drugs to cure this disease," he says confi- Test-tube cultures in which many respiratory viruses are grown on layers of cells. The fluid in the tube nourishes the cell layers. dently. Nonetheless, he adds that much can and should be done to improve our early warning and preparation programmes. Even earlier vaccine production when epidemics do arise is a priority, and for this still more comprehensive surveillance of the world influenza situation is required. "There are areas of the world—notably China—where we know nothing about the influenza situation, where the WHO pro- gramme does not operate. Quite probably the Hong Kong virus of 1968 started in China. If we could have know about it when it started we might have had an extra two months, which would have made an enormous difference to our ability to prepare sufficient vaccine in good time. "Unfortunately, this is a sad example of health advances being frustrated by politi- cal problems." ■ -4The virus is inoculated into a chicken embryo. 19 two winter killers Another winter—and in many parts of the world old people and their doctors see the prospect of illness becoming sud- denly more real. What frightens them? Respiratory illness —diseases of the lungs and their various pipes through which we obtain the oxygen that is vital to every cell in our bodies. There are of course a large number of respiratory disorders and their effects vary considerably: from the mild discomfort of the common cold through the capricious effects of influenza that at one time may cause but a few days of misery and at another start a deadly epidemic, to the disabling and perhaps fatal results of chro- nic bronchitis and pneumonia. In this article we shall take a look at two of these diseases : chronic bronchitis, which in certain countries rates as a major killer, and pneumonia, which despite the almost miraculous cures provided in many cases by modern drugs still carries off large numbers of people, especially old people. Bronchitis is a condition in which the inner lining of the bronchi—the tubes lead- ing from the throat to the lungs—becomes inflamed and produces an excessive amount of slimy mucus. Sometimes, especially in children, there is an infection in which the victim feels very ill, suffers a nasty hacking cough and a high temperature and then gets better again fairly rapidly —this is called acute bronchitis. If on the other hand the condition persists, with or without infection, it is called chronic bronchitis and it is this illness which is the major problem. Chronic bronchitis occurs all over the world to some extent, but it flourishes mainly in regions where the climate is by Dr R. Gillon* cold and damp and the atmosphere pol- luted. For reasons related to these facts but which are not fully understood, the United Kingdom is by far the worst afflicted country in the world, so much worse that chronic bronchitis is known in many other countries as the English disease, and kills over 35,000 Britons a year-710 in every million people, which is about twenty times the death rate in the rest of Europe. To understand how bronchitis wreaks its effects it is necessary to have an idea of how man's rather remarkable system for bringing air into his body and elimi- nating carbon dioxide works. If we were made of only one microscopic cell—like an amoeba—we would not need special apparatus for breathing. The oxygen neces- sary for the cell to survive could diffuse in from the ambient air straight through the cell wall. With our complex structure, however, most of our millions upon mil- lions of oxygen-hungry cells cannot pos- sibly be oxygenated by simple diffusion, and instead all mammals have a system of complicated branching air passages which end in perhaps 300 million minute sacs through which oxygen passes into the blood and carbon dioxide passes out. The total surface through which this exchange of gases occurs is vast: if all the sacs (alveoli) were flattened out they would completely cover a tennis court! To get air into these alveoli we have to breathe in : that is to say expand the chest cavity both by raising and pushing out the ribs and by contracting and lowering the diaphragm. As a result, air rushes in through the mouth and nostrils, down through the branching bronchi and bronch- ioles and into the alveoli. When we breathe out the sequence is reversed : the diaphragm pushes upwards, the chest wall sinks in, and this, combined with the natural elas- ticity of the lung tissues, causes air to be expelled. Unfortunately, air contains many impu- rities, including particles of dirt of one sort or another, and if these particles—they might be pollen, sand or dust in the country, soot in the cities, and bacteria in both—were allowed to fill up the alveoli, the exchange of oxygen and carbon dioxide would be prevented. Over the evolutionary aeons, a remarkably efficient system has evoluted for trapping such particles and removing them before they can enter the alveoli. First line of resistance is the fairly elaborate maze of passages through which air breathed in through the nose must travel before it reaches the bronchi. Parti- cles are trapped in the mucus covering the lining of these passages and excreted in the nasal secretions. Any country dweller who visits the city notices this when he looks at his handkerchief at the end of the day. When a cough helps At the back of the throat the first main tube of the respiratory system—the trachea —branches off from the oesophagus (the tube which carries food from the mouth into the stomach). The entrance to the trachea is protected by a sort of trap door called the epiglottis and during the act of swallowing this clamps down and so pre- vents food or liquid from going down the wrong tube. Sometimes the epiglottis is not successful and food or drink does 20 * Editor of "Medical Tribune". Air pollution and fog play a part in winter ailments.),

go down the wrong way. The resulting choking and coughing is another of the lung's defence mechanisms; the explosive breathing out which constitutes a cough helps to expel the intruding food or drink. All the way down the branching bronchi and the smaller bronchioles, the inner lining contains mucus cells which are constantly secreting their sticky, slimy protective mucus covering in order to trap any particles which have managed to slip in. As the air gets buffetted through the passages and is pushed through more and more divisions into finer and finer tubes most of the particles get caught in this "glue". Moreover if the lining becomes irritated by a large number of particles or by any noxious substance, the mucus cells produce extra slime to deal with the irritants. Finally, the inner lining of the bronchi and bronchioles have another mechanism to protect the alveoli—an abundant supply of minute hairs called cilia which grow out of the lining and paddle the mucus in the opposite direction from the alveoli back up towards the mouth. The paddling movements of the cilia are so efficiently staggered (a bit like the legs of a millipede) that the mucus, and any particles caught in it, is pushed upwards at the astonishing speed of about 1.5 cm per minute. So a particle which has managed to penetrate a metre of bronchial passages before getting trapped in the mucus is evicted in just over an hour. Once the moving tide of mucus and particles reaches the junction of the trachea and the throat it is either swallowed or accumulated and spat out. As well as cleaning the air, the elaborate system of branching bronchi and bron- chioles warms it up if it is cold and cools it if it is hot (animals have been made to breathe in air as hot as 5000C and as cold as -1000C and in both cases by the time the air reached the alveoli it was at the animal's normal body temperature). Perhaps nature hadn't counted on air pollution by modern man at any rate, the protective system for the alveoli is not 100 per cent effective, as post mortem examinations of the lungs of a miner and say an Eskimo soon demonstrate. The Eskimo's lungs are clean, pinkish and soft. The miner's lungs are black with coal dust and other dirt. What happens to the respiratory system in chronic bronchitis? The true answer no one really knows, but it seems that frequent irritation of the lining of the bronchi—particularly from polluted air or cigarette smoke—causes a persistent inflammation to develop. As soon as the irritation response, which is so useful in eliminating a limited number of particles or a small amount of noxious substances, becomes overworked, extra mucus cells appear, and all the existing ones become larger to secrete greater quantities of mucus into the bronchi. At the same time, how- ever, many of the cilia the paddling hairs which keep the mucus moving—are de- stroyed. As a result the mucus stagnates and thickens, and the bronchial network becomes narrowed by a lining of mucus and its embedded particles which cannot be properly removed. These changes cause various symptoms. The unfortunate sufferer develops a cough which expels some of the mucus—the importance of such a cough is commonly underestimated, especially by cigarette smokers who blithely dismiss it as "just a smoker's cough". In fact, a persistent productive cough is a warning that bron- chitis has started—and the wise person stops smoking before the bronchitis gets worse. After a while, bronchitis lungs lose much of their natural elasticity so that when the patient breathes out he has to use extra effort to make up for the elastic contraction of his lungs. Extra effort is also necessary to blow air through the clogged-up bronchi and bronchioles whose lumens have become reduced by all the extra mucus stuck inside them. At first this difficulty in breathing may only be noticed when the person does some extra exercise, especially winter exercise, but soon his bronchitis becomes a problem all the year round and he may find that even climbing the stairs is difficult. Even- tually he may have to stop work because he is so breathless. Things are often made worse by the increasing cough, which is especially troublesome at night: indeed the effort of coughing combined with continually inadequate sleep may make him lose much weight. Any cold may spread The next problem is that bacteria begin to multiply in the thick, dangerously stagnant mucus lining the bronchi and may add an acute bronchitis to the existing chronic bronchitis. The temper- ature rises, the cough gets worse, and probably there is pus in the sputum, which turns it a yellow or green colour. These infective episodes are particularly likely to occur when the person's resistance is low- ered by cold, and winter is therefore particularly risky. Furthermore, any infec- tion that occurs at the top end of the respiratory passage—for example influenza or even a common cold—may spread down into the bronchi to be followed by a bacterial infection which in turn exacer- bates the chronic bronchitis. It is clear that chronic bronchitis, despite its apparently minor beginnings either as "smoker's cough" or as apparently insignif- icant breathlessness, can be a dangerous disease. What causes it and what, if anything, can be done about it? Unfortunately, no one knows the whole story but it is definitely associated with various causal factors. First there seems to be some element of heredity and if your father and your grandfather had it you stand a greater than average chance of getting it yourself. Then, as we have seen, it occurs primarily in cold damp climates, especially in areas where the air is smoky or otherwise polluted. Cigarette smokers are particularly prone to the disease (through it generally affects only the over forties). It attacks men about four times more frequently than women (which may be related to smoking) and it occurs particularly among the lower socio- economic groups (often because of un- satisfactory living conditions). Finally, the older one gets the more likely one is to suffer and indeed to die from bronchitis. Polluted air contains a vast number of particles causing irritation (one American professor estimated that an average city In Britain, one in every two men who smoke 15 or more cigarettes a day suffers from chronic bronchitis. Pipe and cigar smokers inhale less smoke. dweller breathed in 20 million particles of foreign matter every day). It also may contain irritating chemicals dissolved in water: for example one of the commonest industrial pollutants is sulphur dioxide and if the air is at all humid this noxious chemical dissolves in minute droplets of water to form nothing less toxic than sulphuric acid ! Perhaps it is hardly sur- prising that people who regularly inhale sulphuric acid (mixed with a host of other polluting chemicals) are more prone to having the lining of their bronchi destroyed than those who only breathe in air. There are several possible answers to the serious problem of bronchitis. One is to clean the air of our cities and industrial areas by such measures as control of industrial and domestic smoke production and of emission of any other chemicals into the atmosphere. It took a long time for man to realize that he had a duty to keep his highways and his waterways clean it is high time that he extended this elementary hygiene to the air he breathes and lives in. Another answer is to discourage smok- ing. In Britain almost one in every two men who smoke 15 or more cigarettes a day suffers from some form of chronic bronchitis. The rate "drops" to two out of every ten men who smoke one to 14 cigarettes each day. On the other hand only some five in a hundred non-smokers have any form of chronic bronchitis. Most encouragingly for smokers who already have the disease, only about eight out of a hundred ex-smokers suffer from it. A third way of reducing the unpleasant effects of chronic bronchitis is careful avoidance of respiratory infection, partic- ularly in winter when the risk is greatest. It is therefore advisable to dress warmly during cold weather, to keep the house reasonably warm avoiding as far as pos- sible sudden changes of temperature, and, at least in cities or other places where the air outside is polluted, to keep the bedroom windows shut during the night so as to keep the pollution out. Finally, chronic bronchitis patients generally have to be prepared to see their doctors more often than usual during the winter, and to make sure that they go to him at the first signs of an added chest infection „or cold or influenza. They should use such reliefs as steam inhalations and expectorant medi- cines which bring up the stagnant mucus. Above all they should stop smoking. If there is a psychological block they should prefer the pipe or cigars (provided they do not inhale the smoke). At the very least, smokers should cut down their ciga- rettes to under ten per day. Pneumonia Chronic bronchitis is closely linked with another frequently fatal chest disease : pneumonia, which until relatively few years ago was one of the world's greatest killers and which even today still kills large numbers of people, especially in old age. Pneumonia is essentially an infection of the substance of the lungs themselves rather than of its tubes : however, one type of pneumonia, properly called bron- chopneumonia, is actually a mixture of bronchitis and pneumonia, usually starting as a bacterial infection in the bronchi and spreading down into the alveoli. The other sort, a "pure" pneumonia, is called lobar pneumonia and is confined to the tissues of alveoli in one section, or lobe, of a lung. The two types of pneumonia produce different symptoms. Lobar pneumonia usually starts suddenly, often with exag- gerated shivering, high fever —103 0F or more on the first day—and usually severe chest pains. The patient breathes rapidly and jerkily, his pulse is rapid, he may spit up sputum flecked with blood and he may become delirious at night. These unpleasant features are largely caused by poisons produced by the ball-shaped bac- terium called pneumococcus which causes the disease. The disease lasts for five to seven days and, as suddenly as they became ill, patients get better again. Doctors call this dramatic recovery "resolution by cri- sis". There would however be a heavy death rate if the disease were untreated. Fortu- nately nowadays penicillin and other anti- biotics are available in most places and these usually produce an improvement within 24 hours. Patients whose breathing is very disturbed may also be given oxygen through a special mask or by means of an oxygen tent, in addition to the treatment by antibiotics. Steam inhalations may also be given to make it easier for the patient to cough up the secretions which have accumulated in the lungs. If his body temperature is too high the patient may also be sponged all over with tepid water —the evaporation of the water has a cooling effect. 24 After the symptoms have disappeared the patient must be given special breathing exercises to restore the lungs to their normal functioning and ensure that other problems do not set in. Thanks to modern medical care, most people can return to their occupations within a few weeks of having had lobar pneumonia; the old or the very weak, however, need a longer period of convalescence. Stealthy beginnings Lobar pneumonia starts suddenly and dramatically, but bronchopneumonia creeps in stealthily. As we have seen, the infection-which is often caused by several other bacteria apart from the pneumo- coccus-spreads down the bronchi into the alveoli. Gradually the patient is more and more ill. He becomes apathetic, tired and breathless ; his temperature is irregular, he develops a nasty cough and produces sputum. There is often little or no chest pain, but the patient is distressed, he breathes very rapidly and shallowly, and his pulse is rapid. This illness continues for two to five weeks and there is no"crisis" ; all changes are gradual whether for the better or for the worse. Once again anti- biotics usually produce an improvement but they take longer to work than in lobar pneumonia-perhaps several weeks. Other treatments, including steam tents, are simi- lar to those in lobar pneumonia and doc- tors pay special attention to their patients' diets, giving frequent meals of such light ingredients as milk with prepared cereals, beaten eggs, jellies and large quantities of sugar and fluids. Oxygen treatment is generally given and breathing exercises are started as soon as possible. Nonetheless, despite modern treatments, if broncho- pneumonia follows some other sort of illness or infection in an old person, it is still a very dangerous disease. In the United Kingdom it is the last illness of 7000 in every million people over the age of 75. Why then is bronchopneumonia tradi- tionally called "the old man's friend" ? The answer is that after much suffering and pain from other diseases the quiet clouding of consciousness produced by bronchopneumonia reappears. It has an almost narcotic effect, that may come as a welcome relief to a tired old person who has reached the end of the road. Then, but only then, may it sometimes be justifiable to call this lethal disease an "old man's friend". ■ Bronchitis Trends 1957 - 1966 Eng and and Wales Federal Republic of Germany France Hungary United States Japan Australia Year Death Death Death Death Death Death Death Number rate per Number rate per Number rate per Number rate per Number rate per Number rate per Number rate per of deaths 100,000 population of deaths 100,000 population of deaths 100,000 population of deaths 100,000 population of deaths 100,000 population of deaths 100,000 population of deaths 100,000 population 1957 26,935 60.0 8,542 16.9 2,036 4.6 540 5.5 3.581 2.1 10,169 11.2 976 10.1 1958 29,396 65.2 7,914 15.2 2,003 4.5 448 4.5 3,973 2.3 8,580 9.3 1.031 10.5 1959 29,051 64.0 7,138 13.5 1,768 3.9 462 4.6 3,840 2.2 7,789 8.4 1,295 12.9 1960 26,485 57.9 8,787 16.5 1,970 4.3 537 5.4 4,343 2.4 8,511 9.1 1,452 14.1 1961 31,363 67.9 7,571 14.0 1,807 3.9 386 3.8 4,064 2.2 7,406 7.9 1,532 14.6 1962 33,293 71.3 8,750 16.0 2,296 4.9 543 5.4 4,665 2.5 8,022 8.4 1,867 17.4 1963 35,332 76.7 11,131 19.3 2,700 5.6 560 5.6 5,462 2.9 5,790 6,0 1,930 17.7 1964 28,740 60,6 9,112 15,6 1,977 4.1 479 4.7 5,410 2.8 5,665 5.8 2,237 20.1 1965 29,569 61.9 10,523 17.9 2,282 4.6 697 6.8 5,772 3.0 6,795 6.9 2,246 19.8 1966 31,862 66.2 10,465 17.5 2,251 4.6 654 6.4 6,151 3.1 5,288 5.4 2,586 22.4 Source: WHO World Health Statistics Annual These figures covering a ten-year period show a trend upwards in the United States and Australia and downwards in Japan, while a relative stability is noted in the other countries. It is not advisable to compare figures from one country to the other since diagnostic practice can vary considerably. 25 the stab of earache by Kyllikki Kauttu W inter seems long everywhere, but in Finland it may stretch out to five or six months, and the black autumn preced- ing may be even more depressing. Winter for the Finns usually means snow, which they look forward to as eagerly as they long for their short summer: both mean light. Yet in some years even the shortest day is still snowless in southern Finland; there are only four hours of grim, wet half-light, the earth black and hostile, the sky one solid cloud with no trace of colour or outline to offer hope. Both physically and psychologically, such an environment is conducive to disease. The contrast between seasons is more violent in northern Finland, which also has the greatest number of winter illnesses. Respiratory infections of the sort that send people scurrying to their practitioners are three to four times more common in winter than in summer A rise in the number of cases may be caused by sudden changes in the weather, for example warm rain followed by raging storms, or abrupt Arctic frost. Even in spring, when the sun has almost melted the snow and thoughts are turning to summer, the sky may suddenly grow black with a violent snow- storm. Little children usually manage to catch whatever is going round, wherever they are — at school, in the nursery, or just at home playing with their brothers and sisters. Infants are the most susceptible to violent changes in the weather. Also, long hours spent indoors add to the possibility of developing infections. A common complication of respiratory infections in very young children is acute otitis media, or inflammation of the middle ear, which may also develop as a sequel of measles and scarlet fever. This painful disease accounts for some 2,500 to 3,600 admissions to hospital each year in Fin- land (1960-67). Two-thirds of those ad- mitted are under fourteen; of these the majority are babies under one year of age. Proportionally, the highest incidence of the disease occurs in the north and east of the country. In these sparsely populated regions children often have to be kept in hospital instead of being treated and sent home, since many kilometres separate them from medical care. However, lack of reliable and uniform out-patient statis- tics for Finland as a whole makes it difficult to estimate the real incidence of acute otitis. As a result of acute otitis media, several complications may develop, especially in inadequately treated cases. Common com- plications are perforation of the eardrum resulting in chronic otitis media, tem- porary hearing impairment, mastoiditis (infection of the mastoid bone) and, occa- sionally, meningitis or brain abscess. Children susceptible At present, Finland has 100 otologists, most of whom practise in the south, as do the majority of other specialists. This number is relatively small for a population of 4.5 millions, and most cases must therefore be treated by general practi- tioners and pediatricians, with public health nurses assisting in case-finding. The Turku University Hospital serves a population of some 400,000 and at times treats up to 400 cases of otitis a month. 26 Turku is the second largest town in Finland, after Helsinki. "Otitis is almost entirely an infants' disease," says Professor Otto Meurman of the Turku Hospital. "In the very young, bacterial infection of the respiratory tract easily spreads to the middle ear, owing to the still not completely developed anatomy of the ear, nose and throat region, and because the infant may be lying down most of the time. Sinusitis or infected adenoids further increase a child's suscep- tibility to otitis. Other factors, such as living in a large family all crowded together, often prolong ill health. For these reasons, some children may re- contract the disease several times during the course of one year. It is hard to build up the resistance of such children against future attacks, althrough we have started a service of home visits and suggestions for improvement of home conditions by social workers, which should help." "Much research has been carried out into the causes of otitis," continues Professor Meurman. "Obviously, the ma- jority of cases are bacterial in origin and are complications of respiratory infections. The bacteria that most often cause otitis in Finland are Diplococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes and Staphylococcus aureus. "Recently it has been demonstrated that viruses can cause otitis. The virus may be the original cause of the inflam- mation and the bacteria appear only at a later stage; this condition has been called mixed otitis. However, some types remain purely viral in nature." Though the RS (respiratory syncytial) virus was isolated as early as 1956 from an infected respiratory tract, it was only during the RS epidemics in 1965 and 1967 that it was also found in pus taken from the middle ear by Dr Bo Berglund of the Department of Virology of Turku Uni- versity. "This RS viral infection is typically found in infants," Dr Berglund notes, "and may lead to otitis in from 17 to 50 per cent of cases studied. Sometimes the otitis is mild, without any symptoms or noticeable reddening of the eardrum. However, correct diagnosis is most im- portant—this undetected early condi- tion may pave the way for serious bacterial otitis. Haemophilus influenzae and pneu- mococcal bacteria have been found at the same time as RS virus in some otitis cases. In our present state of knowledge, it is still difficult to say how many cases of otitis are viral, bacterial or mixed. But since RS virus is one of the most frequent causes of respiratory infection in infants, it may well be a commoner cause of otitis than was previously suspected." Dr Berglund feels that further study may isolate viruses other than the RS that might cause otitis. In the middle of the night "Acute pain usually forces the patient to seek treatment at once — even in the middle of the night", says Professor Meurman. In the country, where the distance to the surgery or polyclinic may be long, treatment is based on the admin- istration of quick-acting antibiotics, fol- lowed by a day's pause. If the symptoms lessen during the night, as frequently 27

Snow is eagerly looked forward to in Finland because it means more light. happens with children, no surgical perfo- ration of the ear drum (medically called myringotomy) will be performed. If the symptoms continue, a puncture will be carried out immediately. However, treat- ment with full doses of antibiotics from 5 to 8 days, if started in time, will prevent the need for this minor surgical treatment. It is for this reason that most physicians prefer to try the antibiotic treatment first. After the preliminary treatment, a follow-up examination is given. At the same time any factors which seem to predispose the patient to otitis are considered. Gammaglobuline, given by injection once a month over a six- month period, has been tried on children who are highly susceptible to infection, but this is an expensive treatment and some parents are reluctant to subject a child to injections when he seems healthy. Antibiotics have almost completely e- liminated otitis as a complication of scarlet fever, and scarlet fever itself has become rare. Measles still occur, but here too antibiotics prevent the risk of sub- sequent otitis. However, one thing is clear: children with respiratory infec- tions, when seen by the doctor or nurse, should always be given an ear examination, even when no symptoms are apparent, and any ear-nose-throat infection should be promptly treated. A day's journey away In the south, treatment and surveil- lance of cases have greatly improved, but in northern Finland a cumulative series of factors encourages the wide prevalence of the disease. Nature is hard, most of the inhabitants are relatively poor, unemploy- ment is recurrent. Individual families are large, though the population is sparsely spread over a wide area. Physicians are rather few and far between as well. The province of Lapland measures 90,000 square kilometres and has only 221,000 inhabitants, giving a population density of 2.4 people per square kilometre. The "doctor density" is one per 2,572 inhab- itants. "The doctor is a day's journey away," people complain. Under these conditions, visits to the doctor tend to be put off until the last moment. Naturally, the number of otitis cases is proportionately higher here than elsewhere in Finland. Ten years ago there was not a single otologist in northern Finland. There were communal doctors, public health nurses, midwives and small local hospitals, but no specialists. Though health was gener- ally good, the provincial medical officer, Dr Aino Yliruokanen, was struck by the number of schoolchildren who were hard 4 Examining a young patient's ear. of hearing, usually as a result of chronic otitis, since hearing loss is certain to occur if chronic otitis is left untreated. Aided by the Finnish Hearing Society, she conducted a pilot study, using private funds. A mobile clinic, with two audio- meters and a specialist staff, examined 12,000 of the province's 33,000 primary- school children. Of these, 1,200 were sent on to otologists for further examination, and 180 operations were performed, most of them to remove adenoids since excessive adenoidal tissue may predispose to chronic otitis. Numerous cases of otitis and damage resulting from untreated cases of the disease were discovered. Dr Yliruokanen did not stop there; she decided to have the project followed up. Local authorities had gradually be- come interested and new services were put into operation. Today every commune has an audiometer and the 90 public health nurses in the province have been taught how to use the instrument. Training is given to local doctors, and the communes contribute , to the fees for a visiting consultant otologist. In 1963, two otologists were added to the staff of the province's hospitals. Now children who need it can be sent to special ear, nose and throat wards for examination and treatment. In the schools, primary- school teachers have been trained to watch for children who are hard of hearing. Most important of all, parents in Lapland are no longer indifferent to respiratory disease and earache. During the past decade, between 12,000 and 15,000 schoolchildren in Lapland have had their hearing tested each year. When the project started, 30 to 35 of them would be annually found to need hearing aids, but the figure has now dwindled to only one or two. Ten years ago, 700 to 800 children required exam- ination by a specialist ; this figure has dropped to 300. The emphasis remains on prevention. Statistics for the past ten years show that poor hearing is far more common among rural children than among those who live in urban areas. Obviously, there is less treatment available when the physician lives over a hundred kilometres away. In recent years as many as 7 per cent the province's children have been found to have hearing disorders, although this still represents a slight decline com- pared with earlier years. In south Finland today, the rate has been brought down to 4.4 to 5.5 per cent. Such favourable results have encouraged the authorities to extend screening now to pre-school children. • In Rio Turbio, Argentina, the winter is severe. Mineworkers here clear the snow from the tracks before loading the coal. below freezing point Over the years, the icy blasts of winter forced man to wrap himself in furs and woollen garments, to huddle round stoves, and finally to heat all of his dwelling. In many places, he has gone from fireplace to central heating, and today some architects even propose an artificial climate — a city under glass with the temperature to order. The fangs of winter seem to be drawn. There is a drop in the number of acci- dents at work and on the road during cold weather. On closer examination it turns out to be not very reassuring, since the figures say nothing about several impor- tant considerations ; for example, farm work slows down or stops entirely during the winter. Outdoor construction work grinds to a halt when water begins to freeze. A number of other industries work fewer hours or run at less than top capacity during cold weather. It is hardly surpris- ing, therefore, that the number of work accidents diminishes. The same holds generally true for road accidents. Fewer motorists take to the road when highways are iced and obviously dangerous. By contrast, the tide of new cars usually swells each spring. People also drive more often and for longer distances in the summer than in the winter. Not surprisingly, accidents are rarer in the middle of the winter than during the summer months. But we should not forget that ice, frost and fog still are the cause of many serious accidents though the number of miles travelled may be low. Office workers comfortably seated at a desk in a warm building have difficulty imagining what it is like out in the snow trying to keep a railway line open, or working in the woods transporting logs over icy roads. They forget the electrician clinging to a freezing perch on high-ten- sion poles while trying to make stiff fingers do essential work. Beyond a certain point, cold vanquishes man's defences and can cause trench foot, chilblains, frost- bite, swellings, and so on. Frost-bite takes the form of lesions on the feet, hands, ears or nose resulting from intense cold. Persons most easily affected are those under strain and tired, who are poorly nourished and dehydrated, whose defences are already weakened. Frost-bite can lead to gangrene. Trench foot does not require such intense cold as frost-bite in order to develop—just a little above or below Logging sleds in Que- bec Province, Canada. 31 freezing point; humidity and lack of hygiene seem to play a great role. Trench foot is a condition where feet are red, swollen and painful; it may also lead to gangrene. Chilblains are swellings and cracks in the skin that do not become gangrenous. They often result from a lack of vitamins and can easily be cured. A common danger in winter is asphyxia- tion as a result of a faulty stove or poor ventilation. Another classic peril is skating on thin ice. But long winter nights, even the gloomy approach of cold weather in autumn, may provoke depressive states which all too often are aggravated by alcohol. A new sport has brought with it a new type of accident... canes and plaster casts are the insignia of the skiing season in full swing. Statistics about the frequency of skiing accidents are hard to obtain since resort organizers do not wish to detract from the glamour of the sport. However, one systematic study was carried out in the United States in 1961*. It was done at Mount Snow in Vermont where, during four consecutive weekends, from the 28th of January to the 19th of February, one person out of fifty who skied downhill more than once each day was queried. In all 446 men and women skiers were questioned. The study took age, sex, ability of skier, type of skis and bindings, as well as the trails skied into account. A rate of 5.9 accidents per 1,000 skiers per day was arrived at. Half of the total number of accidents occurred to beginners. Women were more susceptible than men : although women only represented 35% of the sample, they accounted for 47% of the accidents. That was in 1961; perhaps as skiing becomes more widespread the aver- age ability of skiers will improve and thus the proportion of accidents will decline. Yet the glamour of snow sports should not allow us to forget that winter is the cruellest season of the year for the poor, the aged, and the undernourished. Colds, bronchitis, pneumonia still menace those most poorly equipped to fend them off. ■ 32 * For further details see "Accident Research" by Haddon, Suchman & Klein, New York, 1964 This picture was taken at the end of winter and he is skating on thin ice. Winter brings its traffic hazards. 33 Complete confidence. books Invasion by virus: Can it happen again?, by Charles Graves, Icon (London), 12/6. When the influenza pandemic of 1918- 1919 struck, many countries were in a state of turmoil from war or revolution or both. Official records are patchy for this reason and also because influenza then was rarely a notifiable disease. Moreover, doctors, nurses and others concerned with reporting were often too busy or them- selves laid low by the infection. This account of one of the greatest plagues ever known on our planet has been culled from medical journals, army archives and contemporary periodicals and newspapers. Much source material is re- produced verbatim, greatly enhancing the interest and value of the study. However, as the author moves from country to country, and figures and anecdotes accu- mulate, the picture becomes increasingly chaotic, an impression that is not alleviated by the real confusion that existed at the time about the nature of the disease. Its viral origin was only guessed at, and by few people: thus laboratory services were not able to back up the clinician, nor produce vaccines. At various times, the disease was thought to be pneumonia, ty- phus, dengue, bronchitis, bubonic plague, pneumonic plague, phlebotomus fever, Pfeiffer's disease. Some of these infections did, in fact, complicate the course of in- fluenza and add to the death toll. As far as is known, every part of the world except a few islands was affected. Australia, forewarned, made strenuous attempts to keep it out, but did not suc- ceed. No race was immune, rich and poor, country and city people from the tropics to the poles, living at high and low alti- tudes, all were attacked. The most alarm- ing anomaly was that young men in their prime were hardest hit. Pregnant women were also highly vulnerable. The disease appeared in successive waves, circling and re-circling the globe. As the evidence piles up, one wonders whether the estimate of 15,000,000 deaths is not conservative. In the belligerent coun- tries of Europe, official secrecy cloaked the existence and then the extent of epide- mics. As the end of a disastrous war ap- proached, no one wanted to give comfort to the enemy. However, influenza proved to be the common foe, more deadly than the hostilities. (Military fatalities accord- ing to official statistics totalled 8,538,315.) In the Allied countries, armistice celebra- tions helped spread the disease. People who should have stayed at home staggered out of doors to join in the excitement, seeding new cases. It was probably Spain's neutrality in the war that was responsible for the "Spanish flu" misnomer. The epidemic there, which had begun in May, 1918, was widely reported, while neighbouring countries clamped down on such news. Early in the spring of that year, many army camps in the USA were seriously affected and it is generally agreed that the first appearance of influenza in Europe was at the beginning of April among American troops disem- barking at Brest and in rest camps near Bordeaux, although there is some evidence that there was flu in Chaumont several weeks earlier. From France it spread like wildfire in all directions : how invasive it was is illustrated by a report from Ireland where a convalescent soldier attended a dance with the result that most of the sixty guests died. The second part of the title is a "sell": in one short paragraph Graves says it could happen again, without producing any evidence, adding lamely that it is unlikely to do so before 1998, "by which time the medical profession will know a great deal more about immunisation than it did in 1918 — or does now." This sounds like a shot in the dark. A fuller assessment would have been appreciated. A Fortunate Man, by John Berger and Jean Mohr, Allen Lane, The Penguin Press, and Penguin Books, London, 1969. The publication of A Fortunate Man as a paperback provides a welcome opport- unity of drawing attention to this poetic evocation of a country doctor's life. 34 However, this new edition is not recom- mended to anyone who feels like paying the 30 shillings or its equivalent for the hard-cover version. In the larger format, a so subtle blend of word and image was achieved between John Berger's text and Jean Mohr's pictures that certain impres- sions are fused, and in retrospect one searches vainly to remember their origin. This unity is disrupted in the new paper- back Penguin for, although Berger's story is reproduced in its entirety, the illustra- tions have lost much of their quality by being cropped and reduced. A superficial look at John Sassal's life as the only doctor in a deprived pocket of rural England would never reveal his right to be called a fortunate man. His patients' ills are not only of the body corporeal but also of the mind, his leisure limited, his social opportunities few. The rewards come from self-knowledge and moral freedom achieved through the years, as the enthusiastic one-man flying squad pursuing emergencies for their own sake matures and becomes the reflective doctor-priest confronting people rather than treating cases. With great fastidiousness Berger exam- ines some of the delicate areas in the rela- tionship of doctor and patient, the unique character of their intimacy, their mutual need. This discriminating scrutiny reveals a basic world where the local context and the medical system either are forgotten or lose their significance. Jean Mohr's sensitive photographs with their engaging and moving revelations of English char- acter and landscape have the same universality. ■ Nobel Prize for ILO The 1969 Nobel Prize for Peace has been awarded to the International Labour Organisation whose 50th Anniversary was commemorated this year. The prize will be handed to Mr D. Morse, Director-General of ILO, in the course of the month of December. On this occasion Dr M. G. Candau, Director-General of WHO has sent to Mr Morse his warmest congratulations. "Like me, all staff members of WHO are happy indeed to see mo's fifty years of sustained effort at reducing strife and promoting peace at all levels so well deservedly recognized." Photograph above is an aerial view of ILO headquarters on the shores of the lake of Geneva. Below, the Pope is greeted at ILO by Mr Morse during ILO's 50th anniversary ceremonies. photo credits ©KEYSTONE: Cover ©J. MOHR : pp. 3, 33, 34 WHO/FARKAS : pp. 4, 8, 9, 11, 16, 17, 18, 19 WHO/SPOONER: pp. 5, 6, 7 WHO/HOECHST A.G. : pp. 12, 13, 14 WHO/P. ALMASY : p. 21 WHO/CL. HUBER: p. 22 WHO/MANDELMAN : p. 23 ©YHTYNEITTEN KUVATOIMISTO : PP. 26, 27, 28 ILo : pp. 30, 31, back cover ©ED. BOUBAT : p. 32 3