Pediatric Annals

Current Epidemiology of Tuberculosis

George McSherry, MD; Edward Connor, MD

Abstract

Despite continued multinational efforts at its control, tuberculosis remains a leading cause of morbidity and mortality in the world. Recently, the World Health Organization (WHO) estimated that approximately one third of the world's population has been infected with Mycobacterium tuberculosis. In 1990 alone, the WHO estimated that more than 8 million new cases of tuberculosis occurred and that tuberculosis caused 2.9 million deaths. About 1.3 million of these new cases and 450 000 deaths occurred in children younger than 15 years of age. It is expected that, given the human immunodeficiency virus (HIV) pandemic and the increasing prevalence of drug resistance, the tuberculosis situation worldwide will continue to worsen.1

In the United States, as in other developed countries, improvements in work and housing conditions, sanitation, nutrition, and the isolation of patients with tuberculous disease helped to reduce tuberculosisrelated mortality significantly between 1900 and 1950. This decrease was further hastened by the advent of antituberculosis drugs in the late 1940s and early 1950s and the case finding and treatment programs that followed.2 In 1953, standardized reporting of cases of tuberculosis began in the United States. That year, a total of 84 304 cases were reported. By the early 1980s, tuberculosis seemed well on its way to being controlled in the United States by the target year 2010. Cases continued to decline at an annual rate of 5% to 6%, as they had for three decades. In 1985, however, cases leveled off at 22 201 and in 1986, increased for the first time since reporting began.3 From that year through 1992, reported cases have increased by 20% to 26 673. 4 Case rates over the same years increased from 9.3/100 000 to 10.5/ 100 000 .4 When observed and expected case rates for tuberculosis are compared (based on 5% annual decline seen prior to 1985), it is estimated that a total of 28 000 excess cases occurred between 1985 and 1990 (Figure 1); that estimate rose to 55,000 in 1992.5

Containment of tuberculous infection in humans is accomplished through the coordinated actions of CD4 lymphocytes and macrophages. A latent phase of infection then usually ensues. Because HIV infection results in progressive CD4 lymphocyte depletion and dysfunction in conjunction with defects in macrophage function, HIV-positive patients who are infected with M tuberculosis are at a high risk of developing tuberculous disease. The risk of coinfected patients developing active disease is extraordinarily high when compared with healthy adults, approximately 10% per year.11,12 In addition, preexisting HIV infection increases the risk of progressive disease from new tuberculous infection.13

TUBERCULOSIS IN RACIAL AND ETHNIC MINORITIES

Between 1985 and 1990, increases in tuberculosis cases occurred among non-Hispanic blacks, Hispanics, and Asians/Pacific Islanders, while decreasing numbers of cases were seen in non-Hispanic whites and American Indians/Alaskan Natives. The increases were largest among blacks and Hispanics in tiie 5- to 14-year-old group (41-1% and 102.6%, respectively) and the 25- to 44-year-old group (55.1% and 76.7%, respectively). By 1990, almost 70% of all cases of tuberculosis and 86%of cases in children younger than 1 5 years of age occurred in racial and ethnic minorities. A number of factors have contributed to these case rates. The complex interaction of poverty, overcrowding and substandard housing, substance abuse, poor nutrition, homelessness, and limited access to health care tHat have affected minority communities for years have combined to sustain a reservoir of infected individuals in these inner-city areas.6,7,14

For example, although tuberculosis rates had declined substantially across all age-race -sex groups over trie 30 years prior to 1985, the decreases in incidence were much steeper among whites than other racial groups. By 1987, the…

Despite continued multinational efforts at its control, tuberculosis remains a leading cause of morbidity and mortality in the world. Recently, the World Health Organization (WHO) estimated that approximately one third of the world's population has been infected with Mycobacterium tuberculosis. In 1990 alone, the WHO estimated that more than 8 million new cases of tuberculosis occurred and that tuberculosis caused 2.9 million deaths. About 1.3 million of these new cases and 450 000 deaths occurred in children younger than 15 years of age. It is expected that, given the human immunodeficiency virus (HIV) pandemic and the increasing prevalence of drug resistance, the tuberculosis situation worldwide will continue to worsen.1

In the United States, as in other developed countries, improvements in work and housing conditions, sanitation, nutrition, and the isolation of patients with tuberculous disease helped to reduce tuberculosisrelated mortality significantly between 1900 and 1950. This decrease was further hastened by the advent of antituberculosis drugs in the late 1940s and early 1950s and the case finding and treatment programs that followed.2 In 1953, standardized reporting of cases of tuberculosis began in the United States. That year, a total of 84 304 cases were reported. By the early 1980s, tuberculosis seemed well on its way to being controlled in the United States by the target year 2010. Cases continued to decline at an annual rate of 5% to 6%, as they had for three decades. In 1985, however, cases leveled off at 22 201 and in 1986, increased for the first time since reporting began.3 From that year through 1992, reported cases have increased by 20% to 26 673. 4 Case rates over the same years increased from 9.3/100 000 to 10.5/ 100 000 .4 When observed and expected case rates for tuberculosis are compared (based on 5% annual decline seen prior to 1985), it is estimated that a total of 28 000 excess cases occurred between 1985 and 1990 (Figure 1); that estimate rose to 55,000 in 1992.5

Figure 1 . Observed and expected tuberculosis cases, United States, 1980-1990. Reprinted from reference 5.

Figure 1 . Observed and expected tuberculosis cases, United States, 1980-1990. Reprinted from reference 5.

Epidemiologic analysis of reported cases shows that tuberculosis has become a disease centered in focal segments of the population. Racial and ethnic minorities and foreign-bom individuals have been most affected. These groups have accounted for virtually all of the increase in cases that has been documented. Chronically entangled in the web of poverty, substandard and overcrowded housing, poor nutrition, and lack of access to health care, they recently have been further devastated by the HIV epidemic. Besides co-infection with HIV among young adults, two other major factors have contributed to the increasing numbers of cases being reported. They are the increase in immigration from countries with a high prevalence of tuberculosis and the deterioration of general health care and public health services in the communities hardest hit by both HIV and tuberculosis. The interrelationship of these variables have combined to stimulate the resurgence of tuberculosis that is now occurring. More ominously, the increase in new adult cases in these communities has been reflected in large increases in numbers of children with tuberculous infection and disease.5-7

TUBERCULOUS INFECTION VERSUS DISEASE

Phthisiologists traditionally have divided the interaction between M tuberculosis and its human hosts into the stages of infection and disease. With tuberculous infection, the patient has developed a positive tuberculin skin test but signs or symptoms of disease are absent. Tuberculous disease or tuberculosis, on the other hand, occurs when initial infection is not controlled or latent infection becomes reactivated and signs and symptoms of illness appear. It has been estimated that 5% to 10% of healthy adults with tuberculous infection will develop active disease over their lifetimes, although the greatest risk of developing disease is in the first few years following infection.

Table

TABLEGroups at High Risk for Tuberculosis in the United States*

TABLE

Groups at High Risk for Tuberculosis in the United States*

The risk of developing tuberculosis is higher for children. Young children are at greatest risk of developing disease in the time immediately following infection. Children under 4 years of age, for example, have the highest tuberculosis case rates and the most serious disease (nearly 45% with advanced pulmonary, miliary, or meningeal disease).8 A study comparing the rates of pulmonary findings revealed that radiologic evidence of tuberculous disease was seen in up to 43% of infected infants as opposed to 24% of 1 to 5 year olds and 15% of adolescents.6·9

TUBERCULOSIS AND HIV INFECTION

The most important factor in the resurgence of tuberculosis in the United States has been the epidemic of HIV infection.10 Comparisons of reported cases of acquired immunodeficiency syndrome (AIDS) and tuberculosis show that cities and states with the largest numbers of AIDS cases have had the greatest increases in tuberculosis. Also, demographic groups with the greatest increases in incidence of tuberculosis (ie, blacks and Hispanics aged 25 to 44 years) have the highest prevalence of AIDS. The incidence of tuberculosis in AIDS patients is approximately 500 times the incidence in the general population.10,11 Risk of infection with M tuberculosis varies directly with exposure to ,the high-risk groups noted in the Table. The likelihood of disease developing in an infected individual depends on the presence of cofactors, also noted in the Table. Although reactivation of dormant infection is mostly unpredictable, certain factors, in particular HIV infection, are recognized to increase the risk.2,12

Figure 2. Age distribution of reported tuberculosis cases by year of report, 1985-1990. Reprinted from reference 5.

Figure 2. Age distribution of reported tuberculosis cases by year of report, 1985-1990. Reprinted from reference 5.

Containment of tuberculous infection in humans is accomplished through the coordinated actions of CD4 lymphocytes and macrophages. A latent phase of infection then usually ensues. Because HIV infection results in progressive CD4 lymphocyte depletion and dysfunction in conjunction with defects in macrophage function, HIV-positive patients who are infected with M tuberculosis are at a high risk of developing tuberculous disease. The risk of coinfected patients developing active disease is extraordinarily high when compared with healthy adults, approximately 10% per year.11,12 In addition, preexisting HIV infection increases the risk of progressive disease from new tuberculous infection.13

TUBERCULOSIS IN RACIAL AND ETHNIC MINORITIES

Between 1985 and 1990, increases in tuberculosis cases occurred among non-Hispanic blacks, Hispanics, and Asians/Pacific Islanders, while decreasing numbers of cases were seen in non-Hispanic whites and American Indians/Alaskan Natives. The increases were largest among blacks and Hispanics in tiie 5- to 14-year-old group (41-1% and 102.6%, respectively) and the 25- to 44-year-old group (55.1% and 76.7%, respectively). By 1990, almost 70% of all cases of tuberculosis and 86%of cases in children younger than 1 5 years of age occurred in racial and ethnic minorities. A number of factors have contributed to these case rates. The complex interaction of poverty, overcrowding and substandard housing, substance abuse, poor nutrition, homelessness, and limited access to health care tHat have affected minority communities for years have combined to sustain a reservoir of infected individuals in these inner-city areas.6,7,14

For example, although tuberculosis rates had declined substantially across all age-race -sex groups over trie 30 years prior to 1985, the decreases in incidence were much steeper among whites than other racial groups. By 1987, the incidence of tuberculosis in whites had fallen from the 1953 rate of 44 cases/ 100 000 population to 5.6/100 000, while the incidence in non whites had fallen from 125.8 to 29.3. The nonwhite-to-white incidence ratio actually increased from 2.9 to 5.3 during this same time period. This suggests that a large reservoir of persons with latent tuberculosis remained in US minority groups.2

TUBERCULOSIS IN ADULTS

In the United States, prevalence of infection with M tuberculosis and, consequently, tuberculosis case rates, generally increase with age reflecting the much greater risk of infection that existed in the early years of this century.2,15 As rates of tuberculosis dropped among all age groups, it was felt that older cohorts of patients with higher infection rates were being replaced by younger, less-infected counterparts.2,14 This boded well for long-term control of the disease. Beginning in the late 1980s, however, an age distribution trend toward younger groups was noted, especially among minority populations (Figure 2).5-14

Between 1985 and 1991, the greatest increase in numbers of cases (51.9%) occurred in 25 to 44 year olds. Overall, the median age for tuberculosis cases dropped from 49 to 43 years of age. The effect of HIV-associated immunodeficiency probably has played a large role in these increases. High rates of tuberculosis in adults of reproductive age have ominous implications for attempts to control tuberculosis. These young adults are often in close contact with children, frequently in household situations. Tuberculosis among these young adults readily can lead to the infection of subsequent generations·2,6·14

TUBERCULOSIS IN IMMIGRANTS

Cases of tuberculosis among foreign-born persons immigrating to the United States have been increasing. From 1986 to 1990, the number of tuberculosis cases reported in immigrant groups increased by 27%. The percentage of total cases among foreign-born persons increased from 21.6% to 24-4%· Most cases (60%) of disease occurred in the first 5 years after entering the United States, reflecting high tuberculosis prevalence rates in their countries of origin. In 1989, persons from Mexico, the Philippines, Vietnam, South Korea, Haiti, and the People's Republic of China accounted for 63% of tuberculosis cases among the foreign-born.16

Three of the factors contributing to tuberculosis among foreign-born individuals are undocumented immigration, lack of tuberculin skin testing, and poor adherence to therapy regimens for tuberculous infection. Perhaps most important in contributing to the trend of decreasing age among reported cases of tuberculosis is the tact that a significant number of foreign-born patients with tuberculosis are young: 43% are in the 25- to 44-year-old age group. Finally, infection and disease are relatively common among children adopted from these countries.6,16

TUBERCULOSIS IN CHILDREN

Adults with pulmonary tuberculosis tend to develop cavitary lesions that contain large numbers of tubercle bacilli. This, combined with the adults? ability to generate a forceful cough, renders them highly infectious. Pulmonary lesions in children, on the other hand, contain sparse numbers of bacilli. In addition, children with pulmonary diseases rarely cough, and even when they do, they lack the tussive force of adults to expel bacilli.17 As a result, children seldom, if ever, infect one another. Virtually all cases of tuberculosis in children arise from contact with adults with infectious disease.

Primarily because of increases in tuberculosis among persons of childbearing/childrearing age, substantial increases in reported cases of tuberculosis among children have occurred since 1985. Overall, reported cases have increased by 28% in 0 to 4 year olds and by 39% in 5 to 14 year olds. Most of these new cases have been among racial and ethnic minority children, which accounted for 86% of all reported cases among children younger than 15 years of age in 1990.5,7

Besides the personal health effects on children who develop tuberculosis, transmission of M tuberculosis to children is of importance because of its broader public health consequences. From this perspective, tuberculosis in children can be considered a sentinel healthcare event.18,19 Most children who develop disease do so within 3 to 9 months after infection. Elevated rates of tuberculosis in children, therefore, may be the best indicator that transmission of tuberculosis is ongoing in a community, not only in children but also in persons of all ages. Whereas increased case rates among adults may be due to reactivation of infection, increased rates in children usually indicate an increase in current transmission of tuberculosis. These cases of disease in children represent only a fraction of new infections. The majority of infected children do not develop disease in the years immediately following infection, but form part of a new reservoir of infected persons at-risk of developing disease over their lifetimes and thus help prevent control of tuberculosis. Given the increases of reported cases of tuberculosis among children, it is likely that a large new group of infected at-risk persons is developing.2,6,18

TUBERCULOSIS IN CITIES AND COUNTIES

Because urban areas have large populations of persons at high risk for tuberculosis, they account for a disproportionate share of tuberculosis cases reported. In 1989, cities with populations of greater than 250 000 accounted for only about 18% of the nations population but for 40% of tuberculosis cases. When cities with populations of 100 000 to 250 000 are added to the above figures, the percentages increase to 26% of the nations population and 49.6% of tuberculosis cases.3 From a geographical standpoint, tuberculosis has become a very focal disease. In 1989, for example, approximately 11% of the 3138 counties in the United States accounted for 82% of the tuberculosis cases reported.3

Cases in persons younger than 35 years of age are considered potentially preventable by use of isoniazid therapy prior to the development of disease. In 1990, 85% of the 8381 potentially preventable cases occurred among racial/ethnic minorities. About 80% of these were reported from only 106 (3.4%) US counties. These counties comprise those that reported 10 or more cases and are located primarily in the southeastern United States, along the east and west coasts, and in Texas. Again, concentration of persons affected by poverty, HIV infection, homelessness, and the decline of public health services have combined to further aggravate already elevated tuberculosis case rates in these areas. Despite increasing case rates and decreasing inpatient beds for treatment of tuberculosis, public health agencies responsible for assuring adherence with outpatient treatment of tuberculosis have had to reduce their services due to financial constraints. As a result, adherence to treatment regimens has fallen to as low as 11%.20 This inability to treat those with disease or to treat them adequately contributes significantly to increased transmission of tuberculosis and to the development of drug resistance. Concentration of scarce resources in these few geographic areas with the highest incidence of tuberculosis could potentially lead to the control of tuberculosis in these regions.7

SUMMARY

After years of decline, tuberculosis has become an increasing cause of morbidity and mortality in the United States. Chronic problems of poverty, homelessness, substandard housing, and poor access to health care have combined to help maintain a reservoir of infected persons. The addition of HIVassociated immunodeficiency has allowed many of these infected individuals, whose infections ordinarily would have remained dormant, to develop tuberculosis at younger ages. In addition, increasing numbers of cases of tuberculosis are being identified among young foreign-born adults from countries of high tuberculosis prevalence. Transmission from these young adults has occurred in increasing numbers to children. These children form an enlarging pool of infected persons that will continue the cycle of tuberculous infection and disease for future generations.

Renewed emphasis and resources need to be placed on tuberculosis, particularly in the public health sector. Only in this manner will early detection and treatment of those with infection and disease occur and the cycle of tuberculosis be broken.

REFERENCES

1. Kochi A. The global tuberculosis situation and the new control strategy of the World Health Organization. Tubercle. 1991;71:1-6.

2. Rieder HL, Cauthen OM, Comstock GW, Snider DE Jr. Epidemiology of tuberculosis in the United States. Epidemiol Rev. 1989;11:79-98.

3. Centers for Disease Control. Tuberculosis Statistics m ifie United Situes, i989. Atlanta, Ga: Public Health Service; 1991. US Dept of Health and Human Services publication (CDC) 91-8322.

4. Centers for Disease Control and Prevention. Tuberculosis morbidity - United States, 1992. MMWR. 1993;42:363.

5. Centers for Disease Control. Tuberculosis morbidity in the United States: final data, 1990. MMWR. 1992;40(SS-3):23-27.

6. Starke JR, Jacobs RF, Jeteb J. Resurgence of tuberculosis in children. ] Pediatr. 1992;120:838-855.

7. Centers for Disease Control. Prevention and control of tuberculosis in US communities with at-risk minority populations: recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR. 1992;41(RR-5):1-11.

8. Comstock GW, Livesay VT, Woolpert SE The prognosis of a positive tuberculin reaction in childhood and adolescence. Am} Epidemiol. 1974;99:131-138. 9. Miller FJW1 Seale RME, Taylor MD. Tuberculosis m Children. Boston, Mass: Little, Brown; 1963.

10. Snider DE Jr, Roper WL. The new tuberculosis. N Engl I Med. 1992;326:703-705. Editorial.

11. Barnes PF, Bloch AB, Davidson PT, Snider DE Jr. Tuberculosis in patients with human immunodeficiency vims infection. N Engt] Med. 1991;234:1644-1650. 12. Selwyn PA, Hartel D, Lewis VA, et al. ? prospective study of tuberculosis among intravenous drug abusers with human immunodeficiency vims infection. N Engl J Med. 1989;320:545-550.

13. Daley CL, Small PM, Schecter GF, et al. An outbreak of tuberculosis with accelerated progression among persons infected with the human immunodeficiency virus - an analysis using restriction-fragment-length polymorphisms. N Engl J Med. 1992;326:231-235.

14. Bloch AB1 Rieder HL1 Kelly GD, Cauthen GM, Hayden CH, Snider DE. The epidemiology of tuberculosis in the United States: implications for diagnosis and treatment. Clin Cfiest Med. 1989;10:297-313.

15. Powell KE, Farer LS- The rising age of the tuberculosis patient: a sign of success and failure. J Infect Dis. 1980;142:946-948. Editorial.

16. Centers for Disease Control. Tuberculosis among foreign-bom persons entering the United States: recommendations of the Advisory Committee for Elimination of Tuberculosis. MMWR. 1990;39( RR- 18) 1 -2 1 .

17. Smith MHD, Starke JR, Marquis JR. Tuberculosis and opportunistic mycobacterial infections. In: Feigin RD1 Cherry JD, eds. TextfcooJc of Pediatric Infectious Diseases. 3rd ed. Philadelphia, Pa: WB Saunders Co; 1992:1321-1362.

18. Snider DE Jr, Rieder HL, Coombs D, Bloch AB, Hayden CH. Smith MHD. Tuberculosis in children. Pediatr Infect Dis}. 1988;7:271-278.

19. Bloch AB, Snider DE Jr. How much tuberculosis in children must we accept? Am J Public Health. 1986;76:14-15. Editorial.

20. Brudney K, Dobkin J. Resurgent tuberculosis in New York City: human immunodeficiency virus, homelessness, and the decline of tuberculosis control programs. Am Rev Respir Dis. 1991;144:745-749.

TABLE

Groups at High Risk for Tuberculosis in the United States*

10.3928/0090-4481-19931001-08

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