Tuberculosis: susceptibility and resistance.

Abstract

Introduction l h e ability of an animal host to limit multiplication of tubercle bacilli within its tissues and the degree to which its natural defenses are able to eradicate extracellular and intracellular organisms can be used as a measure of resistance to tuberculosis. This phenomenon was observed first by Koch (1), who showed that it is much more difficult to establish a progressive mycobacterial infection in animals that have been infected previously. The cellular and subcellular mechanisms responsible for this acquired ability to limit spread and replication of the tubercle bacillus have been partially explained in recent years, although many important questions remain. This report will review what has been learned by presenting a historical perspective of the tuberculosis epidemic that began in England in the 16th century and still continues, by reviewing individual risk factors, by examining the cellular and subcellular mechanisms that contain and kill tubercle bacilli within the infected host, and by evaluating data obtained from laboratory and clinical trials designed to induce immunity to tuberculosis. Tuberculosis can be shown to spread in an epidemic wave similar to that seen when other infectious diseases, such as whooping cough or hepatitis, are first introduced into a population of highly susceptible persons. Morbidity and mortality rates rise in a steep ascent, peak, and then show a longer and more gradual decline. In acute communicable diseases, the time course for these phases of the epidemic is measured in weeks, but for tuberculosis it is measured in decades. The present worldwide tuberculosis epidemic began in England in the 16th century, peaked there in 1750, spread to western Europe, and peaked there in the early 1800s. It then peaked in eastern Europe and North and South America by about 1890. At present the epidemic continues —its last peak occurred in Asia and Africa where high morbidity rates persist in many areas. Thus as the wave declined in one geographic area it was ascending and peaking in another. To what extent was the decline of new cases a result of resistance? The wave form of the epidemic is explained by natural selection. As the more susceptible persons are eliminated, the survivors become relatively resistant over a period of several generations, and the epidemic wanes as the disease resumes an endemic pattern (2). The peak tuberculosis mortality along the eastern coast of North America reached 1,000 per 100,000 cases per year in about 1800, and the disease had peaked throughout the continent by 1850, so that tuberculosis has been showing a progressive decline throughout the United States for the past 100 years. All efforts to examine racial and geographic variations in tuberculosis mortality and apparent resistance or susceptibilty must take into account the wave form of the epidemic and its time frame in the particular population under study. The variables of sex and age are especially influenced by the timing of the epidemic wave. In its early stage, occurring now in Asia and Africa, the infant mortality is much greater for males than females followed by a period of increased resistance in early childhood for both sexes. The major peak for females in early adulthood is surpassed at middle age by males, who show an increased susceptibility thereafter. During the late phase of the wave the increasing mortality in the aging population is the most significant feature, as can be seen presently in developed western countries. The proper understanding of the peak in the aged was first reported by Frost in 1939 (3). There is no clear evidence of any racial susceptibility to tuberculosis apart from that best explained as phase differences in the epidemic wave. The effect of poor nutrition is also minimal, because in experimental animals nutritional deficiences must be extreme to reduce resistance to infection. Individual Risk Factors