![[back]](../../left.gif){kind=small}
"The captain of all these men of death that came against him to take him away, was the consumption, for it was that that brought him down to the grave." -- John Bunyan: The Life and Death of Mr. Badman.
Tuberculosis, the leading cause of death in the world from a single infectious disease, is on the march again after a century of decline. The reappearance of TB in the U.S. and an increase in cases worldwide--especially in Africa and Asia--is attributable to the AIDS epidemic and to the failure to provide treatment programs for patients, particularly in America's inner cities. TB has emerged in pockets of high-risk groups from which the disease has spread to the general public. And a growing resistance to antibiotics has made treatment with them less effective.
The dramatic decline of tuberculosis in Europe, England and the United States throughout the 20th century resulted from early detection and public health measures that limited its spread. This public effort-including the sale of Christmas seals, mass chest X rays of school children and heightened public awareness-was remarkably effective in controlling the disease. Beginning in 1945, we thought the use of streptomycin and other antibiotics delivered the coup de grâce.
By the 1980s many believed the battle had been won and our attention could be directed elsewhere-to heart disease, cancer, AIDS and other afflictions. We were dead wrong. We ignored the persistence of tuberculosis in Africa and Asia, where it remains, even today, a major cause of death. In this age of air travel, whatever festers in foreign soil will soon be transported to our doorstep. And we foolishly believed that the disease had been eliminated in the United States. But TB was still here, infecting 10,000 to 15,000 patients a year. As soon as we dropped our vigilance, the microbes multiplied and spread.
On July 5, 1990, a front page headline in the New York Times read: "Tuberculosis germ resurges as peril to public health; highest threat in the cities; re-emergence born on the tide of AIDS, homelessness, drugs and alcohol abuse." Another newspaper story reported that TB spread from an infected person to a fellow passenger during a long flight and among students in a classroom.
In some parts of the United States, measures to contain the disease have collapsed or been abandoned. One study revealed that 89 percent of the TB patients discharged from Harlem Hospital failed to continue taking their medicine, remained infectious and spread the disease to relatives and neighbors. In 1985, as a result of complacency, the downward trend ended, and the number of cases is 51,000 more than would have been predicted.
For a brief period during the Romantic Age, consumption became a stylish mark of tragic beauty. The pale and wan English poets, Keats and Shelley, symbolized the romantic and consumptive youth of the 19th century. In the 17th century Sir John Suckling asked, "Why so pale and wan, fond lover? Prithee, why so pale?" Mimi, in Puccini's La Bohème, represented the melancholy ideal, a character drawn from a young lady who died of TB. Romantics began to believe consumption was associated with gifted and talented people. It was the professional and popular opinion then, before the discovery of germs, that consumption was a constitutional trait. Sculptor Daniel Chester French captured the delicate and sensitive features of the tubercular John Harvard in the statue of him which stands in the Harvard Yard. Many talented young people, among others, were condemned to early death by consumption: Thoreau, dead at 45; Chopin, 39; and Robert Louis Stevenson, 34. In that earlier age TB was called "consumption," from the Latin, consumere, to waste away.
Although tuberculosis has been known since antiquity, it did not reach epidemic proportions in Europe until the 19th century's industrial revolution. The slums of teeming cities became cauldrons for the incubation of TB, and it boiled over to spread to the upper classes and into rural communities. Microbes, then as now, thrive in undercurrents of opportunity.
René Dubos in The White Plague wrote of the tragic story:
"As the number of deaths mounted throughout the first half of the century, it became obvious that the gravity of the disease could no longer be concealed under a genteel but misleading expression. Tuberculosis was the great white plague threatening the very survival of the European race. Miserable humanity was living in the dreary tenements born of the industrial revolution. Men, women and pale children were cold and starving. They worked long hours in dark and crowded shops. Tuberculosis was there, breeding suffering and misery without romance."
On March 24, 1882, Robert Koch delivered a paper entitled simply Über Tuberkulose at the monthly meeting of the Physiological Society of Berlin. Suddenly romance gave way to reality as patients were shunned by their friends and society. Tuberculosis went into the "closet," and people became secretive about TB in their family. Koch had returned several years earlier from an International Congress of Bacteriology in London determined to find the cause of tuberculosis. He was convinced that it resulted not from one's constitution or poor nutrition although these might be contributing factors and, indeed, we know now that they are. Intense bacteriologic research often carried out late into the night, month after month, was rewarded with his discovery of the TB bacillus as the cause of the disease. A sputum test to detect the microbes was soon developed and, later, chest X rays to detect the disease in the lungs and the tuberculin skin test.
Who was Robert Koch? Where was his genius born, and where did it thrive? He was a miner's son, third in a family of 13 children, who escaped poverty, practiced medicine in a rural village and made time to pursue his scientific studies. Part of his medical consulting room served as a laboratory, with a microscope, an incubator and other paraphernalia for microbial investigation. It was here, not in a university, that he discovered the cause of anthrax, at the time a serious and often fatal illness in the rural population. His research won acclaim throughout Europe. As a result, he became head of a Berlin laboratory which attracted talented young men who would achieve their own fame and glory through their discoveries: Emil Adolph von Behring, the diphtheria antitoxin which was the first miracle cure for this deadly disease of children; Paul Ehrlich, salvarsan for the treatment of syphilis; and August von Wassermann, the first blood test for syphilis.
Koch's success can be traced to parents who fostered his natural abilities. His mother presided over a harmonious household where the children were taught self-reliance. Robert's early interest in plants and animals was encouraged by his mother and a maternal grandfather. Like young Charles Darwin, he became an avid naturalist, a collector of mosses, insects and mineralized stones. As a student, he planned a career in philology, but his school principal steered him into science. He thought Koch was only "satisfactory" in languages. Fortunately, Koch did not accept an opportunity to migrate to America as an apprentice to a shoe merchant!
He enrolled at Göttingen University as a student in the natural sciences but transferred to medicine when he realized this profession was an extension of his primary passion for bacteriology. It was not taught at Göttingen, but in the 1860s there were vigorous debates in European universities on Pasteur's discoveries concerning the fermentation properties of lower fungi and the contagious nature of diseases for which there was, as yet, no formal proof. Koch, an active participant in the discussions, became a believer in the infectious nature of disease and was "turned on" by these new revolutionary ideas.
After graduation from Göttingen, Koch attended the Charité Clinic in Berlin, where the renowned pathologist Rudolf Virchow opposed the concept that disease was infectious. The lectures were so overcrowded that Koch returned home and started to practice medicine. His hope to be a ship's doctor, see the world and indulge in his passion to be a naturalist was never realized because, among other things, his fiancˇe refused to travel. Thus began 10 years of practice in various German cities. In 1872 he was appointed District Medical Officer at Wollstein, now Wolsztyn, Poland. For eight years he and his family lived happily in this lakeside town, where he discovered the bacteria that cause anthrax, earned acclaim and received the invitation to begin studies in Berlin. After the report of his discovery of the bacterial cause of TB in 1882, the German government created the Robert Koch Institute, where he remained as director until his death in 1910. For his research on the bacteria that cause infectious diseases, including tuberculosis, he received the Nobel Prize in 1906.
We become infected with tuberculosis when we inhale the microbes discharged by infected patients when they cough or sneeze. Decreasing the risk of catching tuberculosis from an infected person involves the early detection and treatment of the patient. When coughing, sneezing and speaking, one releases microbe-bearing particles of saliva and phlegm which disseminate into the air. A sneeze may contain over 1 million particles which can bear infectious organisms. Transmission of infection can occur when contaminated air is inhaled by any passerby.
Once inhaled into the lung tissue, the microbes multiply and produce a small patch of pneumonia and an infection in the lymph nodes of the chest. At this stage, even without antibiotics, the immune response often ablates the illness. Although the infection subsides, it may remain quiescent, only to break out of confinement as reactivated TB, which is usually more severe than the initial attack. This happens as the power of the immune system wanes, particularly in older people. Eleanor Roosevelt died of reactivated tuberculosis. Because the immune systems of HIV/AIDS patients have diminished powers to ward off infections, their latent tuberculosis is often reactivated. Such patients are particularly infectious because their sputum contains millions of tuberculosis organisms. They require prolonged treatment with antibiotics.
Treatment before antibiotics was a protracted affair consisting of bed rest in a sanitarium. A young tubercular physician recalls his experience: His case was detected early by clinical and laboratory tests. The cure, however, was non-specific since no medication to combat the tubercle bacillus existed. It was accomplished by special sanitarium treatment, consisting of plenty of fresh air, rest, regular exercise and a simple diet. Companionship also was considered important. After nine months the young man recovered sufficiently to be asked to stay on as a physician. His elation was understandable. The rehabilitation was complete. The physician-novelist, the late Walker Percy, commented on these matters from his own experience as a patient at the Trudeau Sanitarium at Saranac Lake, New York.
With early detection of TB followed by sanitarium treatment, the mortality rate for tuberculosis in New York City dropped from 350 deaths per 100,000 in 1885 to 100 in 1920. At that time, there were 10,000 hospital beds for tuberculosis patients in New York City.
Everyone thought the introduction of antibiotics in the mid- 1940s would end the occurrence of tuberculosis. As a medical student in the late 1940s as antibiotics were being introduced, I witnessed the afterglow of the TB epidemic while working in the two TB hospitals left in Cleveland. Many patients had advanced TB, and the antibiotics had not entirely replaced the old drastic treatment for advanced disease.
In such cases the advanced state of pulmonary infection required surgery to remove diseased tissue. In addition, several procedures were used to "rest" the lung to enhance-it was believed-the healing process. In one procedure air was injected into the peritoneum. This pushed up the diaphragm and decreased the extent of expansion and contraction of the lungs during breathing. It put the lungs to rest as much as possible so they could heal naturally.
In the decade after the introduction of antibiotics the two hospitals in Cleveland and elsewhere were closed. A medical specialty and research which dealt solely with tuberculosis virtually disappeared. Everyone was convinced the battle had been won. The U.S. death rate from TB of 50 per 100,000 in 1940 fell to 22 per 100,000 in 1950, a decline which continued until the recent resurgence. It is to the factors that have fueled this resurgence that we now turn.
In 1984 the decline in the rate of tuberculosis reversed and it began to increase. By 1992 there were 28,000 cases per year in the United States If the prior declining trend had continued, it is anticipated there would have been only 17,000, or less than one case per 100,000.
Factors that have contributed to the century-long reversal of the decline in the number of cases include: (1) the demise of previously strong treatment and control programs by city and state governments; indeed, in 1972 federal grants for state TB control from the Center for Disease Control (CDC) were terminated; (2) an increasing homeless population with high potential for transmission; (3) an increasing number of drug users with similar living conditions; (4) the HIV epidemic; and (5) antibiotic resistance.
Several studies hint at the importance of active transmission in certain risk groups, such as those in homeless shelters and prisons, and among health care workers. There is also evidence that active transmission has been spilling out of high-risk groups and into the general population.
Especially vulnerable to contracting TB are people infected with HIV, the AIDS virus. HIV infection causes a gradual decline of the immune system, making patients in the advanced stage of HIV susceptible to many infectious diseases. At least 50 percent of the resurgence of TB in the U.S. is the result of the infection in AIDS patients.
TB has joined such infectious diseases as pneumonia, gonorrhea, meningitis and hospital-acquired infections in developing resistance to antibiotics. The most effective drugs thus far in the treatment of tuberculosis are a combination of isoniazid and rifampin. In 1986 nine percent of the microbes isolated from patients were resistant to one or more drugs. In 1994 15 percent were resistant to one or more drugs. A few patients have developed TB resulting from microbes that are resistant to all known antibiotics, and nothing could be done to prevent their death. The global emergence of drug-resistant TB may be largely the result of poor compliance with treatment, which has generated drug-resistant strains that outlive interrupted, incomplete treatment. As with many antibiotic regimens, patients frequently discontinue front-line drugs when they start to feel better.
Worldwide tuberculosis numbers are up though it was never really controlled in Africa and Asia. The World Health Organization (WHO) estimates 8.79 million cases a year worldwide with deaths annually of 2.98 million. Most of the cases are in developing countries where the HIV/AIDS epidemic is also the greatest, probably because HIV patients are especially susceptible to TB (figure 2). Policy planners have responded, but a recent review of health problems in developing countries concluded that the impact of tuberculosis on development had been largely overlooked. The World Bank recently has made substantial loans to China and Bangladesh for TB control.
What Needs To Be Done?
In the U.S. nearly a generation of expertise was lost as tuberculosis waned. But the downward trend is slowly being reversed. New control programs have been instituted by the CDC and research and training efforts by the National Institutes of Health (NIH). A growing number of young people have sensed the challenge of TB research and treatment and prevention programs. Local, state and federal governments and voluntary agencies must again mobilize the tried-and-true methods of case detection, early treatment and clinical follow-up to ensure compliance with the prolonged three to six months of antibiotic regimen. Public awareness, as in the early years, must again be fostered. All of these efforts have been implemented in various cities, including New York. As a consequence, the number of TB cases in New York fell in 1995 for the third year in a row although there are still more cases than in 1985.
A search must be made for new antibiotics that circumvent microbial resistance. This will require far more knowledge about the metabolism of the microbe than we now possess. Research to circumvent drug resistance in bacterial infections such as TB is only now evolving, with the design of "rational" drugs ("designer drugs") that selectively destroy specific microbes.
Finally, the mechanisms of tuberculosis immunity must be re-examined in the light of recent knowledge on the processes of the immune system that prevent and overcome infectious diseases. One of the reasons for TB resurgence may have been premature confidence in bacille Calmette-Guˇrin (BCG) vaccine. Although the vaccine has had some success in preventing tuberculosis meningitis and tuberculosis in children, it is only occasionally effective in preventing pulmonary TB in adults. There is still hope that it will be possible to develop a vaccine that is relatively easy to administer as an injection along with the other childhood vaccines.
In all of this the NIH and its international counterparts are key since clinical progress relies on fundamental advances to provide understanding of biological mechanisms that underlie tuberculosis pathogenesis and immunity and antibiotic resistance.
The international effort against tuberculosis must not be neglected. The burden is greatest overseas. The WHO estimates there will be over 30 million deaths from TB in the current decade. Officials estimate that it would require at least $100 million a year to mount an effective global assault. And yet only $16 million is currently spent for this purpose. Any expanded effort will require operational studies on the design and management of TB control and treatment programs, especially in developing nations.
As with so many other aspects of life, Machiavelli wrote about fundamental principles for the control of infectious diseases. Hear his advice to The Prince, and to leaders of all ages since:
It happens then as it does to physicians in the treatment of Consumption, which in the commencement is easy to cure and difficult to understand; but when it has neither been discovered in due time nor treated upon a proper principle, it becomes easy to understand and difficult to cure. The same thing happens in state affairs; by foreseeing them at a distance, which is only done by men of talents, the evils which might arise from them are soon cured; but when, from want of foresight, they are suffered to increase to such a height that they are perceptible to everyone, there is no longer any remedy.
Return
to COSMOS 1996 Table of Contents Return
to COSMOS Journals Return
to COSMOS Home Page