Influenza

by Warren T. Vaughan

Virulence Enhancement.

Before attempting to study the mechanism of origin of the 1918 pandemic it is highly essential that we devote some attention to a consideration of the processes by which the germs of infection, particularly the virus of influenza, may develop an increase in virulence. Followers of the theory of periodicity would base virulence enhancement primarily on some intrinsic property of the virus itself. We know from past experience and particularly from animal experiments that this is not the only manner by which virulence may be increased.

As far as we know there is no new infectious disease. Individuals who delve into the history of the past inform us of more and more diseases which were well known to the ancients. We are frequently amazed at the variety of diseases now known to be infectious that were very correctly described by the Hippocratic writers. The infectious diseases are with us always and live nearly always in man, the host. There are few exceptions. Very few of the contagious viruses can live for any long period of time outside of the human body. A few, such as the plague bacillus, may live on other hosts, but these are the exception. The remarkable feature is that for long periods of time the virus exists in the host in a quiescent state and only at intervals does it become highly invasive and thereby produces epidemics of greater or less extent. Under what conditions does the metamorphosis of the microorganisms occur?

Topley, in the Goulstonian lectures, discusses this subject. He says: “The first difficulty with which we were faced in forming any theory of the spread of bacterial infection, which should conform to the known facts of epidemiology, was to find some explanation of the perpetuation of the virus during interepidemic periods. The bacteriologic data which have accumulated, especially during the last twenty years, have shown that the causative agents of specific diseases are to be found in apparently normal persons who give no history of having been in contact with the disease in question, as well as in contact with actual cases of the disease. Moreover, the organisms in question have been shown, in certain cases, to persist for long periods of time in or upon the tissues of their hosts, and we must always remember that the difficulty of bacteriologic technic is likely to lead to a serious under-estimate. Clinical and epidemiologic investigations have yielded confirmatory evidence, and we are thus left with a conception of the virus of a given disease being distributed fairly widely throughout the world as an apparently harmless parasite on the human host, but taking on during epidemic periods a new and sinister role, only to relapse again into comparative quiescence as the epidemic subsides.”

He explains the rise of the epidemic wave as follows: “There are at least three possible explanations—an increase in the power of the parasite to produce disease, a decrease in the resistance of the host, and some attraction in the surrounding circumstances which favor the transference of parasites from case to case without any alteration of the pathogenicity of the one or in the resistance of the other. The third of these hypotheses may, I think, be disregarded. That alterations in environment may be the determining cause in initiating an outbreak of bacterial disease is probable enough; but they will almost certainly act through the variations which they bring about in the other two factors. The whole of bacteriologic knowledge is clearly against the occurrence of a considerable epidemic in which the pathogenicity of the parasite and the resistance of the host remain constant. Again, while we may well believe a lowered resistance of a certain number of the host-species to be an important factor in the initiation of the process, yet we cannot believe that it is the whole story. The widespread ravages of many epidemics would seem altogether to preclude such an explanation. We seem forced therefore to the conclusion that an increase in the pathogenicity of the specific parasite is an essential factor in the rise of epidemics, excluding from this category small sporadic outbreaks which may be due to the introduction of a fully virulent parasite by a healthy carrier in some other way.”

If a disease like measles is quiescent in a given community it must be that in that locality the hosts and parasites are existing in a state of biological equilibrium. They are living in a state somewhat akin to symbiosis. Such a condition could be attained either by a diminution of the invasive powers of the parasite, or by an increase in resistance of the host. Probably both elements are active; as the relative immunity of the host rises the infectivity or virulence of the parasite must rise to an equal extent to maintain the equilibrium. If this were true we would find that in those localities in which the disease is endemic and where the population is relatively resistant there is a normally more virulent virus in existence. A stranger coming into such a community would, in view of his lower resistance to the virus, be more susceptible of becoming actively infected. There would, however, be little danger of an epidemic spread because the number of susceptibles would, roughly, be limited to the number of strangers in the community. If, however, an individual from the community carrying the more virulent virus were to travel to another community where the greater proportion of the population was relatively less immune the field would be fertile for the beginning of an epidemic. Furthermore, there is the possibility of an outbreak in the first community if there should occur gross changes in its constitution; another infectious disease, a redistribution of the population with greater crowding, anything to change the balance between host and parasite.

Theobald Smith has described this possibility very clearly:

“During the elimination of the more virulent races of microorganisms, there goes on as well a gradual weeding out of the most susceptible hosts. In a state of nature in which medical science plays no part, there must occur a slight rise in the resistance of individuals, due to selection and perhaps acquired immunity, which meets the decline of virulence on the part of microbes until a certain norm or equilibrium between the two has been established. The equilibrium is different for every different species of microorganism, and is disturbed by any changes affecting the condition of the host or the means of transmission of the parasite. One result of the operation of this law is the low mortality of endemic as compared with epidemic diseases. Certain animal diseases while confined to the enzootic territory, cause only occasional, sporadic disease, but as soon as they are carried beyond this territory epizootics of high mortality may result. Climate in some cases enters as an important factor, but the most important, perhaps, is the slight elevation in virulence brought about by a more highly resistant host. The most susceptible animals are weeded out and the rest strengthened by non-fatal attacks. The virulence of the microbe rises slightly to maintain the equilibrium. In passing into a hitherto unmolested territory, the disease rises to the level of an epizootic until an equilibrium has been established.

“The same is true of human diseases, among which smallpox is a conspicuous example. The great pandemics of influenza, which seem to travel from east to west every one or two decades, soon give away to sporadic cases, and the careful work of many bacteriologists would indicate that the influenza bacilli found at present have fallen to the level of secondary invaders, and are parasites of the respiratory tract in many affections.”

Smith describes his hypothesis that the tendency of microbes in perfecting the parasitic habit is to act solely on the defensive. The aim of microorganisms, if we may speak of such, is to become able to live unharmed on the host. If they kill the host they have lost their home. The biologic tendency would be in this case for diseases which were once acute to become more and more chronic and indolent.