An indisposition to do anything, or to be anything; a total deadness and distaste, a suspension of vitality; … an ossification all over; an oyster-like insensibility to the passing events; a mind-stupor; a brawny defiance to the needles of a thrusting-in conscience. —Charles Lamb
The victims of influenza are less articulate than Charles Lamb, but at this moment there are thousands of them, the world over, who have recently experienced the hang-over which is so characteristic of this infection, and thousands more will do so before this strange disease again retires to its normal level of incidence.
In discussing the health of our army, General James S. Simmons stated that respiratory diseases were the most troublesome in the last war and that influenza must still be considered one of the most formidable "disease enemies" of the soldier. Many of us this winter were reminded of the world outbreak of flu in the winter of 1918-1919: in this country alone there were then more than 20,000,000 cases resulting in about 430,000 deaths in less than six months.
During the present war England had to cope with the urgent problems of acute respiratory infection in overcrowded air-raid shelters and in factories; now these dangers are our concern wherever they are met in camps, schools, industrial concentrations, transports, or public carriers. The possibility of recurrent epidemics, perhaps of increasing virulence, even of another pandemic, must be faced.
Although influenza is still far below its 1918-1919 level, we must not be complacent. Some signals are flying. The number of influenza cases. 82,951, reported by our State Department Health for the week ending December 18, 1943, was more than three times greater than the previous week and more than twenty-seven times that of the corresponding week in 1942. While the fight goes on, let us consider what advances have been made since 1918-1919 in the prevention and treatment of influenza and its ally, pneumonia.
A comparison of what was known then with our present knowledge reveals that we have made amazing progress. It was generally believed in 1918 that influenza and all of the pneumonias were of bacterial origin. The viral nature of epidemic influenza was first established in England in 1933, but t was not until 1938 that "virus pneumonia" was clearly recognized. Thus we are across the frontier of explorations that promise to push the range of medical knowledge at least as far as did the pioneer bacteriologic investigations of the last century.
What is meant by the viruses? To most people they are as mysterious as spells of primitive magic. In 1935, Wendell M. Stanley isolated the crystalline protein which is the tobacco virus. Here are substances which seem to stand on the dividing line between the animate and the inanimate, and as more is known about them our whole concept of "life" may well be changed. The fact that to "live"—that is, to multiply —viruses must be associated with living cells is of fundamental importance in our treatment of viral infections. Much of the mystery of the viruses may be attributed to their smallness. While learned theologians used to argue about how many angels could stand on the head of a pin, today it is the size of the viruses which absorbs those scientists who are competent to take such minute measurements by means of the electron microscope. To gaze upon the photograph of an influenza virus stirs the philosophic biologist to a deeper awe of nature and to a sharper impulse to investigate the laws which must control these atomies.
Influenza exists in three forms: the world-sweeping pandemics such as that of 1918-1919, the epidemics such as we are now passing through, and the low-grade, constantly present or endemic form. It is from studies of epidemic influenza that the greatest progress has been made. It is plainly wrong to consider the flu as a war disease, although, as Edward Francis has noted, when virulent influenza coincides with the cruel shifts of population caused by war, the disease rises sharply.
What happens between epidemics is still a mystery. Richard E. Shope has discovered that the closely related virus of swine influenza can remain infective in the earthworm for as long as thirty-two months. Christopher H. Andrewes has suggested that human influenza viruses may have a basic, harmless form, in which they are harbored in human carriers and from which they become virulent. It is recognized that epidemics tend to recur every other year and that the present wave is not an example of spontaneous generation, but the continuation of what appears to be a cyclic pattern. This cycle has frequently run a course of thirty-three weeks. What effect the substitution of transcontinental and transoceanic aviation for caravan and ship will have on this cycle remains to be determined.
Until much more is known, "influenza" includes at least three types of infection, all of which present the same symptoms. The first of these is the catch-all, "acute febrile catarrh," from which the term "cat fever" is derived. This includes the influenza-like diseases from which specific viruses have not yet been isolated. The second form is influenza A, traceable to the specific virus isolated in England in 1933 or to related strains. It is this virus which seems to be largely responsible for the present epidemics and which is so widespread that it has been identified in England, in Martinique, in Minnesota, and in army cases in Michigan. The third form is influenza B, also due to a specific virus; this virus was isolated in New York State in 1940 and then traced back to a California epidemic in 1936.
Both of these viruses, A and B, are of world-wide distribution, but are apparently unrelated; both can cause epidemics, and alone or together they might cause a pandemic. Except for the fact that influenza A is often more severe than influenza B, their differentiation is important to the victims of the disease mainly from the point of view of immunity, since one apparently offers no protection against the other.
Epidemic influenza is characterized by its sudden appearance and rise to a peak in three or four weeks, followed by a prompt subsidence from six to eight weeks after the onset. Although from 10 to 40 per cent of a population may be attacked, the mortality is low. Important in its spread are not only the frank cases of obstinate people who refuse to go to bed, but also persons who are in the incubation period and who innocently remain at large, and finally the cases of "subclinical" infection—that is, of victims who have the disease like "walking typhoid." Such persons can spread the infection and may include as high as one fourth of the population. Convalescent carriers may also be important, but the concert coughers, however high their nuisance value, may be relatively innocuous.
Now what steps can be taken to prevent influenza? Avoidance of exposure is preached but too seldom practiced. Crowded trains, streetcars, and buses—here is the environment in which respiratory infection flourishes. While thousands of civilian workers and members of the armed forces are forced to take this risk, anyone who feels a cold coming on and has an ivory tower available should stay in it.
Two types of vaccination against influenza are being studied. In one of them the vaccine is put under the skin. In the other it is applied to the mucosa of the respiratory tract to increase resistance at the local barrier which the virus must pass to cause infection. Extensive trial of this type of vaccination has been made among Australian troops and in Russia. In general it may be said that vaccination against influenza is still in the experimental stage and that, while it may not prevent infection, it may modify the course of the disease to a milder form with fewer complications.
The possibility of stopping the viruses in mid-air is of great interest. On this side of the Atlantic we have little concept of the importance of such a control, say in air-raid shelters where thousands of people have had to sleep night after night. In the British shelters the emphasis has been mainly on the control of cross-infections in operating rooms and in hospital wards. It has been found that small droplets such as are expelled in coughing can float in the air for many hours, even days. Arthur T. Edwards recently found that 10 percent of an original amount of influenza virus can remain alive on blankets for days or weeks. It is difficult to know whether the persistence of influenza in certain households is due to this domestication of the virus or to its constant introduction as active members of the family carry home the infection from outside contacts. It is the killing of these droplets that is urgently important. For this, two promising methods have been found: the use of ultraviolet light and of germicidal mists or aerosols.
Since 1936 the value of ultraviolet light has been repeatedly demonstrated both experimentally and in practice. Edwards and his associates in England showed last year that ultraviolet light, operating at a short distance, killed 99 per cent of an influenza virus in the air in six seconds. It must be remembered that the use of ultraviolet light must be carefully controlled, that it is most effective in small spaces, and that the air must be directly exposed to the light. Its successful use in schools, in operating rooms, and in hospital cubicles is a promise ultimate value.
When Queen Victoria was under Lister's knife, she objected that his carbolic spray got in her face, but when she realized how serious the situation was for him, she hastened to add that she liked the smell of this drug. Later in his career Lister honestly stated that he believed himself wrong in trying to sterilize the air; and for about seventy years thereafter the idea of a germicidal mist was regarded as nonsense while surgery mastered the problems of the sterilization of tangibles. Fortunately interest in the use of such substances revived in the years before war, and by 1938 the Frenchman Trillat had introduced the term "aerosols" for these germicidal mists.
The theory of their action is simply that a small amount of a chemical which is known to be germicidal be finely dispersed into the atmosphere. Water was not a satisfactory solvent, partly because of its rapid evaporation, and for that reason propylene glycol, a pretty name with which everyone will probably soon be familiar, was used to carry a number of germicides, including Dakin's solution. The English, hard-pressed to improve conditions in their air-raid shelters, which sometimes, as in Bristol, were in deep caves or old tunnels, used aerosols with evident success.
By the crab-like motion which characterizes so many scientific advances, it was then found that propylene glycol alone was highly effective. As little as one part of this substance, in the form of an aerosol, was active in at least several million volumes of air. Its effectiveness against both bacteria and viruses was established in this country by Oswald II. Robertson and his associates at the University of Chicago and later confirmed in England.
The testing of the effect of both aerosols and ultraviolet light under epidemic conditions fortunately will take time. There is evidence that better aerosols may be developed. At present ultraviolet light and aerosols seem to be about equally effective when properly used, but the latter are simpler to apply. Forced upon us by the war, the use of these aerial tactics to prevent infection may become one of the great advances in public health. If their use is extended by technical advances from schools and hospitals to barracks, dormitories, transports, movies, theaters, wherever Homo sapiens is least cautious in his overcrowding, this may well be the simplest way of preventing a large proportion epidemics.
We still lack any chemical prophylactic for influenza and any drug of value in direct attack on the virus once the infection has been established. The sulonamides are not of value. Penicillin so far has been found ineffective. A wide range of chemicals has been studied in hope of stumbling upon one which would attack these viruses. One can only hope that by "cookbook chemistry," the laborious making and testing of thousands of compounds, or a lucky strike, someone will find an agent which can penetrate our cells and reach the viruses so securely ensconced within them. When this discovery comes, it will be one of the last steps needed for the control of infectious disease.
We know a good deal more about pneumonia, that handmaiden of influenza. So far the evidence shows that relatively few of the dreaded post-influenzal pneumonias are due to the influenza viruses, but the whole problem will have to be re-investigated with the techniques which have been recently developed. It is now hard to think back to those Dark Ages when the sulfonamides were not available for the treatment of bacterial pneumonias (which have been the killers in influenza); yet it was only in 1937 that sulfapyridine was introduced. The effect of the sulfonamides upon the death rate in pneumonia is indicated by the figures of the Metropolitan Life Insurance Company. In the year ending in August, 1937, their figures showed a mortality rate of 85.7 per 100,000 cases. By 1942 this rate had dropped to 31.9 per 100,000 cases, a decrease of 63 per cent. If selected series of pneumococcal pneumonias are studied, the mortality is now found to be about 10 per cent. These figures represent the saving of a great many lives. There has also been a measurable shortening of the length of illness.
But bacterial pneumonias are still on the list of living infections. No way, except common-sense hygiene, has yet been found to prevent pneumonia. The possible use of the sulfonamides to ward off bacterial pneumonias in victims of virulent influenza may be important, but little is yet known about it. The high number of carriers has been emphasized more recently by Dr. W. H. Harris, Jr., who reported last year that after sulfonamide treatment more than one third of the convalescents left the hospital carrying their pneumonia germs with them. It must also be remembered that, like Mithridates and his poisons, some bacteria can adapt themselves to the sulfonamides. While the incidence of these strains is now low in pneumonia, it may be of increasing importance. Yet these difficulties are relatively minor in comparison with the extraordinary advances which have been made with these drugs.
Individuals unfortunate enough to be susceptible to a sulfonamide-resistant germ or too sick to be saved by the sulfonamides need not despair. Immune serum can be used for the treatment of bacterial pneumonias, and on the horizon stand penicillin and other substances obtained from molds. Here is an enchanting revelation in the history of medicine. While civilians must yield their claim for penicillin to the armed forces until more of it is available, the day will come when it or related substances will supplement or possibly replace the sulfonamides.
Dr. F.G. Blake recently reported the strange case of the Connecticut farmer, some of whose family and ten of whose twelve cats came down with an atypical pneumonia in which there was a strong suggestion that both the felines and the human beings were having the same viral pneumonia. In these newly recognized groups of pneumonias due to viruses instead of bacteria are some of the most curious and interesting infections now known. Some of these strange diseases seem to reach us from animals, especially birds. About a fourth of the viral pneumonias in an eastern urban area were recently found to be due to the virus usually associated with an acute respiratory infection of parrots, a disease known as psittacosis. This virus and the one that prefers cats are now believed to be related. Similar viruses have been found among pigeons in our city parks and among domestic fowl, so that during epidemics of viral pneumonia even these apparently harmless creatures must be viewed with a suspicious eye.
The non-bacterial pneumonias do not respond to the sulfonamides, and no prophylactic for them is known. Hopes were recently raised in England when patullin, a mold derivative related to penicillin, was found to be effective in the treatment of the common cold, which is a virus disease. Unfortunately the first series of cases was small and others have not been able to confirm the results. It appears that neither the answer nor the key has yet been found.
Influenza and pneumonia are sometimes killers. We have learned much about them; we are bound to learn more. The possibility for their control seems brighter than it has ever been. As Theobald Smith said, "Among other aims adopted for the post-war period might well be included freedom from respiratory disease."
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