This month's issue of Pediatric Annals, which addresses tuberculous infection and disease, has as its Guest Editor Jeffrey R. Starke, MD, Assistant Professor of Pediatrics at the Baylor College of Medicine.
Tuberculosis has a fascinating and frightening history. During the 19th and 20th centuries alone, tuberculosis has been estimated to have caused 1 billion deaths worldwide1; it was the leading cause of death in the United States and Europe throughout the 19th century. But in developed countries, it began to wane during the early and middle part of the 20th century2 due to:
* isolation of its victims in tuberculosis sanatoriums and hospitals, thereby reducing the spread of the disease to others - especially household members - and providing the individual nursing care, nutrition, rest, and support patients needed to recover,
* general improvement in socioeconomic status, leading to decreased crowding in homes and to improved nutrition, which reduced the communicability of and enhanced resistance to the disease,
* implementation of shorter work weeks, which reduced stress and fatigue and thereby increased resistance to developing the disease,
* improvement of ventilation in homes, workplaces, and institutions (eg, schools, hospitals, and prisons), which also reduced communicability,
* development of the tuberculin skin test and the chest x-ray as means to detect, through mass screening, infection and disease in individuals so that they could be treated and isolated, if required, early on,
* discovery of specific antibiotics to treat the disease - streptomycin and para-aminosalicylic acid in the 1940s, isoniazid and pyrazinamide in the 1950s, and ethambutol and rifampin in the 1960s, and
* institution of case reporting, with follow-up by public health authorities to ensure that all close contacts were tested and that appropriate treatment was instituted.
These events and measures resulted in a decline in reported new cases of tuberculosis from 84300 in 1953, when standardized reporting was established in the United States, to 22 200 in 1985.3 Since 1986, however, the number of cases reported has increased annually to a level of 26 700 in 1992. Case rates were 9.3/100 000 in 1985 and 10.5 in 1992. This alarming resurgence of tuberculosis is the result of:
* the development by Mycobacterium tuberculosis of resistance to the antibiotics used to treat the diseases it causes,
* the increase in the number of immigrants who have tuberculous disease from countries that have high prevalence rates for tuberculosis, particularly those from Southeast Asia,
* the difficulties many patients have in adhering to multidrug, long-term treatment regimens, which obviate their cure and sustain their communicability.
* our inability to provide adequate general health care and preventive health services to the populations at greatest risk for acquiring tuberculosis, particularly those who live in our large cities under conditions of poverty, malnourishment, and overcrowding, and who account for more than 75% of all cases, and
* the ever- increasing number of persons who are immunodeficient due to human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) and whose resistance to tuberculosis is greatly reduced.
These reasons for the resurgence of tuberculosis overlap in many instances. The prospects for changing any of them for the better are not good.
Most frightening is the association between tuberculosis and HIV infection, which represent the two most lethal chronic infections we have ever faced, albeit, some might rank syphilis up there with them, even though it is not currently life threatening. They are different in their modes of acquisition. Tuberculosis is acquired, for the most part, by inhalation of small, tubercle bacilli-laden droplets dispersed into the air by persons who have pulmonary tuberculosis when coughing, sneezing, laughing, or singing; transmission also may occur through mouth-to-mouth kissing. Human immunodeficiency virus infection is acquired through intravenous substance abuse, vaginal, anal, and oral homosexual and heterosexual contacts, antenatal, perinatal, and postnatal mother-toinfant transmission (including breast-feeding), blood and blood-product transfusions (extremely rare since 1985 when universal HIV testing of donors was established), and from contact with an infected person's blood or body fluids, particularly when this occurs on nonintact skin or mucous membranes.
Tuberculosis and HIV infection also are different in their pathophysiology. Typically, tubercle bacilli, when they reach the alveoli into which they are inhaled, multiply and destroy the cells they invade. The body mobilizes its immunologic cellular defenses, which cause an initial inflammatory reaction - a tubercle - surrounding the infected cells. A similar inflammatory reaction occurs in a hilar or mediastinal lymph node that drains that portion of the lung. Eventually, the tubercle is surrounded by fibrous tissue and often becomes calcified.
The tubercle and the draining lymph node, which becomes enlarged, make up the primary complex (Ghon complex) of pulmonary tuberculosis, often detected on chest x-ray. It represents the initial infection, and in 90% of cases, the infection goes no further. Sometimes, early in this process, some tubercle bacilli enter the bloodstream and lodge elsewhere in the body, establishing small foci of infection, usually without ever causing evidence of disease. However, if the inhaled bacillary inoculum is large, hematogenous spread may be generalized and cause life-threatening illnesses such as tuberculous meningitis and miliary tuberculosis. This is most likely to occur in young children. The body responds to the primary infection by developing resistance to future invasion by tubercle bacilli, making reinfection unlikely. This resistance, which is immunologic in nature, is the basis for tuberculin test positivity.
While most initial infections remain dormant and cause no signs or symptoms of disease, in persons whose resistance and immunocompetence are lowered, the tubercle bacilli may spread from the primary tubercle to the surrounding lung tissue or to other parts of the body, causing the serious disease we call tuberculosis. This is most likely to happen 1 ) at any age within 1 to 2 years following the initial infection, 2) at ages when resistance is likely to be low (children younger than 3 years of age, young adults between the onset of puberty and the mid-20s, and the elderly), and 3) whenever immunodeficiency from whatever cause occurs.
The pathophysiology of HIV infection is much more complex. Human immunodeficiency virus causes a generalized infection invading many cells, causing syncytium formation among them, and then degeneration and lysis. Most frequently affected are the T4 cells responsible for destruction of pathogenic organisms. These cells undergo qualitative and quantitative changes, which are the basis for immunologic abnormalities and profound immunodeficiency, and their clinical consequences. Thus, patients who have HIV infection are susceptible to a broad range of serious secondary diseases including, among others, infection by a variety of opportunistic organisms, progressive neurological disease, lymphoid interstitial pneumonia, secondary cancers, and tuberculosis. The Centers for Disease Control and Prevention has categorized the various stages of HIV infection and disease to include these ills in its definition of AIDS.4 The incubation period between the time of HIV infection and the beginning of AIDS is usually 8 to 10 years, but is only 1 to 3 years in mother-to-infant transmitted HIV infection.
While M tuberculosis and HIV infection differ in their modes of acquisition and in their pathophysiology, they have many things in common.
* They are slow-acting, lethal pathogens.
* They produce chronic illness and prolonged dependency.
* They create scientific frustration and uncertainty surrounding efforts to treat infection and disease caused by them.
* They prompt the health-care system to use fear to persuade people to change their lifestyle in order to avoid disease or to get well.
* They cause their victims to be barred from employment, to be ineligible for insurance, and to be shunned by their friends and society.
* They, while knowing no social barriers, predominantly affect the underprivileged among us.
The World Health Organization (WHO) estimates that one third of the world's population has been infected with M tuberculosis and that it remains the leading cause of morbidity and mortality worldwide, with 8 million new cases and 2.9 million deaths recorded in 1990.5 The WHO also reported that during 1990, more than 3 million women, most of childbearing age, were infected with HIV worldwide and estimated that by the end of 1992, approximately 1 million children would have acquired HIV perinatally.6 Further, the WHO has estimated that by the year 2000, 20 million people will have HIV infection and 6 million will have developed AIDS. No mortality figures were projected, but unless an effective therapy for HIV infection is discovered, all 20 million who have this infection will die eventually from it. We must remember that it took more than 70 years from the discovery of the cause of tuberculosis to the discovery of a cure. We might be optimistic that our modern-day scientific knowledge and higher investment in funding research directed to a prevention and a cure for HIV infection will narrow this time gap, but the international meeting on AIDS research held in Berlin earlier this year; more than a decade after the discovery of the cause of HIV-related infection, did not offer much optimism for finding any effective treatment or prevention of it in the immediate future.
1 . Ryan F. The Forgotten Plague: How the Barde Against Tuberculous Was Won - and Lost. Boston. Mies: Little. Brown & Co; 1993.
2. Bates B. Bargaining for Life: A Social History of Tuberculosis. 1876-1938. Philadelphia, Pa: University of Pennsylvania Press, 1992.
3. McSherry G, Connor E. Current epidemiology of tuberculosis. Pediatr Am. 1993;22:600-604.
4. Centers for Disease Control and Prevention. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adole*· cents and adults. MMWR. 1992;42:1-19.
5. Kochi A. The global tuberculosis situation and the new control strategy of the World Health Organization- Tubercle. 1991;71:1-6.
6. Chin J. Current and future dimensions of the HIV/AIDS pandemic in women and children. Lancet. 1990;336:221-224.