Etiology and Epidemiology

Perhaps no other disease better illustrates the principle of multifactorial causation: The tubercle bacillus is a necessary but not the only condition. In addition, the host and the host's environment contribute numerous other causes central to its pathogenesis.

Species Classification

Over 30 species of the genus Mycobacterium have been identified, more than 15 of which can cause disorders similar, but not identical, to tuberculosis. Human disease typically is caused by members of the species Mycobacterium tuberculosis. In addition, mycobacteria can cause disease in a wide variety of animals, including birds, fish, rodents, elephants, and cattle. Of its animal forms, only the bovine can infect people. Some bacteriologists consider the bovine form a separate species of the tubercle bacillus, whereas others group it with several variants that they classify together as the M. tuberculosis complex.

The human bacillus has also been divided into three types according to immunologic responses (phage types), which show marked variations in virulence. These are type I, found in India; type A, found in Africa, China, and Japan as well as in Europe and North America; and type B, found exclusively in Europe and North America. Type I is the least virulent of the three, making Indians more susceptible to disease when infected with type A or B. These differences probably result from the evolution of widely separated organisms over long periods of time. However, all forms of M. tuberculosis show a strong resistance to mutation, and thus it is unlikely that an increase in virulence caused the disease to become epidemic, or that a decrease in virulence prompted the decline in tuberculosis mortality rates that occurred in England, the United States, and other Western nations before the introduction of streptomycin and other specifics.

Transmission

Except for the bovine types, tubercle bacilli reach human hosts almost exclusively through aerial transmissions. By talking, coughing, sneezing, spitting, singing, and other respiratory functions, people produce airborne particles called droplet nuclei, which, if emitted by a tubercular individual, can contain between one and three bacilli. Just one is enough to establish a tuberculosis infection when inhaled. Once airborne in a closed space, these particles disperse and some remain suspended like tobacco smoke. Larger ones fall to the floor or ground where they present little threat of infection, al though dry tubercle bacilli can remain viable for months. Their transmission in dust particles is possible but rare; yet, from the late nineteenth century, this was believed to be the main form of transmission, and many countries passed laws that forbade spitting in public places. Bovine bacilli are ordinarily ingested through the digestive tract via milk and milk products and usually cause intestinal disease, but infrequently lead to pulmonary or miliary tuberculosis. The pasteurization of milk eliminates this source of infection.

Incubation Period

After entering the body, tubercle bacilli are remarkably durable and persistent. They can remain viable throughout their host's lifetime, dormant until resistance fails, whereupon they can cause active disease even if they failed to do so when they first entered the body. In contrast to most other infectious diseases, tuberculosis has an indefinite and variable incubation period.

Host-Dependent Factors

Whether or not tubercle bacilli cause active disease upon entering the body depends primarily on several host-dependent factors. Age, gender, and immuno-genetic factors along with a number of environmental factors such as crowding, quality of nutrition, and working conditions are all of importance.

Age. Once a person becomes infected with the bacillus, age has a powerful influence on what follows. Infancy, puberty, and old age are periods of low resistance and high susceptibility to tuberculosis. The younger the individual, the more likely that primary infection will become active disease and result in death. Infants are particularly susceptible to acute miliary tuberculosis. Unlike the organisms in many infectious diseases, however, the tubercle bacillus does not produce immunity in those exposed to it: Exposure early in life usually leads to relatively high mortality rates from tuberculosis in later middle or old age.

Gender. Gender is also an important determinant. Although the reasons remain as yet undiscovered, more females die from tuberculosis than do males in populations where tuberculosis epidemics are just beginning, and the converse is usually true where the disease is declining. In youth and early adulthood, females generally experience greater mortality from tuberculosis than males, but after age 30 years the mortality of males surpasses that of fe males. Biological evidence suggests that the onset of the menses brings on metabolic changes that increase the body's need for protein, and that when it is unavailable, resistance drops. Childbirth can induce or aggravate the disease by lowering resistance to infection and this contributes to increased mortality in females up to age 30.

Genetic Factors. Extensive research on heredity in tuberculosis has produced only ambiguous results. Some families experience more tuberculosis than others in similar circumstances, and specialists do agree that heredity influences an individual's risk of developing the disease, but the mechanisms of heredity have not been demonstrated. The role of race in tuberculosis also presents a difficult problem to researchers. For decades, American scientists attempted to ascertain whether blacks, who long had higher rates of mortality from the disease than whites, were biologically more susceptible to it because of an inherited characteristic. Results have been indeterminate, because in this case constitution and environment remain inseparably intertwined. Nevertheless, a population's genetic pool is an important influence on resistance to the tubercle bacillus. A long history of inhabiting urban environments seems to have made Jews more resistant to the disease than are most other ethnic groups. By contrast, a population's previous lack of exposure to tuberculosis can lead to acute epidemics of the disease, as exemplified by those that occurred among the Maori of New Zealand and the Eskimos of Alaska.

Some epidemiologists assert that natural selection determines the course of tuberculosis epidemics, based on the idea that genetic background and resistance to the disease are of paramount importance. Mortality rates drop, they say, as the more susceptible are weeded out. Others oppose this theory, in part because tuberculosis epidemics in Europe and the United States subsided more quickly than the theory would have predicted. Moreover, although natural selection has doubtless reinforced resistance to the disease, it has not played a leading role in the decline of its epidemics. Rather it would seem that economic and social changes made the most important contributions to the decline in tuberculosis mortality rates until the late 1940s, when medicinal cures became available.

Primary Environmental Factors

Where tuberculosis is present, the specific factors most important in the etiology of the disease are crowding, quality of nutrition, and working conditions.

Crowding. Crowding, as a function of persons per room, increases a person's chances of infection when diseased individuals are constantly releasing the bacilli into the air of small and cramped quarters. Population density, on the other hand, which is a ratio of persons per measure of land area, has little impact on tuberculosis mortality rates. Indeed, in most industrial nations, those rates are higher in rural than in urban areas because in sparsely populated rural areas, substandard living conditions, including crowded housing, often make the disease a major health problem.

Nutrition. Nutrition also plays a key role in the etiology of tuberculosis. Both epidemiological and laboratory evidence demonstrate the importance of protein in resistance to tuberculosis.

Working Conditions. Occupation and working conditions also can affect its pathogenesis and outcome. Textile mill laborers, masons, pottery factory operatives, metal grinders, and other workers in the "dusty trades" inhale particulate matter that inflames the lungs and increases their risk of developing the disease. The physical exertion and stress of exhausting work also magnify an individual's risk of developing tuberculosis, as does smoking. Socioeconomic status, which obviously has a powerful influence on all of these factors, may indirectly affect a population's tuberculosis mortality rates as well. Numerous studies have shown that groups with the lowest income levels suffer the most from the disease, and also that a rising income greatly reduces tuberculosis mortality.

This combination of factors means that industrialization alternatively exacerbates and improves rates of mortality from tuberculosis. The early stages of an industrial economy are generally those in which crowded and impoverished living conditions prevail for numerous people and lead to increased tuberculosis mortality. Eventually, however, industrialization's material benefits improve housing and nutrition, and reduce risks for infection and reinfection, thereby lowering both morbidity and mortality rates.

Other Environmental Factors. Other environmental factors seem to have little influence on tuberculosis mortality. Researchers long considered climate an important factor in the pathogenesis and treat ment of tuberculosis, but recent studies have not found that temperature, humidity, or other climatic factors influence either one's risk of developing tuberculosis or its course once the disease is developed.

Epidemiologists have faced numerous difficulties in the study of tuberculosis, and found it particularly difficult to determine the mortality from the disease until the advent of mass screening programs using tuberculin and X-ray photography. Nonetheless they have played a primary role in unraveling some of the mysteries of tuberculosis and determining the factors, such as age and nutritional deficiencies, which put populations at greater or lesser risk of developing the disease.

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