Tuberculosis continues to be an important problem despite the availability of curative and preventive chemotherapy. Between 1987 and 1990, tuberculous cases among children younger than 5 years of age increased by 39% in the United States.1 This increase signals failure in our public health system since childhood cases almost exclusively represent recent transmission of disease from a contagious adult source case. Also, tuberculous infection in children poses a long-term public health threat comprising the pool of infected persons from which future cases will arise if they are not appropriately treated.
The communicability and prolonged treatment required for tuberculosis place an increased burden on our public health institutions, which are responsible for investigation of persons with disease and for programs designed to ensure adherence to long-term treatment. Unlike most infectious diseases, which can be treated with a short course of antibiotics, tuberculosis requires 6 to 12 months of therapy. In addition, many patients with tuberculosis face socioeconomic and cultural barriers that add difficulty to their care. Adherence to treatment is crucial to both the individual's health and to public health. In most diseases, if treatment is refused, the individual may suffer consequences but usually without affecting others. Inadequate treatment of tuberculosis may lead to relapse, spread of infection or disease to others, or to the development of drug-resistant forms of the illness. The long-term nature of treatment and the many barriers facing patients with tuberculosis contribute to the current inadequacy of tuberculosis control. Individual physicians, hospitals, and health departments must work together to take the necessary steps to prevent the spread of tuberculosis (Table).
TRANSMISSION OF TUBERCULOSIS
Mycobacterium tuberculosis is transmitted by airborne droplet nuclei generated by adults with pulmonary or laryngeal tuberculosis when they cough, sneeze, talk, or sing. The infectious particles are 1 to 5 µm in size and can remain suspended in air for many hours. Infection occurs when a susceptible person inhales the organism into his or her lungs. Likelihood of infection depends on a number of considerations including the degree of contagiousness of the source case, environment factors, and susceptibility of the contact. Persons are more likely to transmit disease if they have extensive involvement on chest radiograph, cough with sputum production, and acid-fast bacteria on sputum smear.
Important Steps in the Prevention of Tuberculosis
Environmental factors are very important since even a potentially contagious person will not transmit infection in a well-protected environment. The risk of transmission is increased if the volume of air in the environment is low, the ventilation is poor, the air is recirculated, and other protective measures such as ultraviolet lighting are not present.2 Persons spending long hours in close quarters with an infectious case are more likely to be infected, therefore the closest contacts are usually household members.
The susceptibility of contacts is also important in transmission. Young children and immunocompromised persons are the most vulnerable to tuberculous infection as well as progression to disease once infected. Evaluation of these individuals should be of very high priority even if the risk of infection is judged to be fairly low.
Children younger than 10 years of age with tuberculosis generally are not considered contagious.3 In children, tuberculosis usually represents a primary infection rather than reactivation of disease as is often seen in adults. The number of organisms is small, and acid-fast bacilli rarely appear in the sputum of children. Many children with tuberculosis are asymptomatic without cough.4 When children do cough, the amount of tussive force is much less than in adults, and they rarely produce sputum. Because of these factors, hospitalized children with tuberculosis do not need to be isolated, although they often are until the infectiousness of the parents can be established. Also, children younger than 10 years of age with tuberculosis need not be excluded from school since transmission of disease is unlikely. Occasionally, adolescents with extensive pulmonary disease and sputum production may be infectious and should be isolated until acid-fast smears are negative, usually about 3 weeks after initiation of therapy. Infected individuals - whether children or adults - with no evidence of disease on chest radiograph are not contagious and may return to their routine daily activities, although they will need treatment for infection.
Delays in recognition and treatment of tuberculosis often lead to prolonged transmission of infection to susceptible contacts. Most public health laws require that physicians report tuberculosis at the earliest suspicion of disease,5 but many physicians either fail to report or delay reporting until the diagnosis is confirmed by culture, which may take 6 to 8 weeks. Since children, especially young infants, can develop severe tuberculosis such as meningitis or miliary disease within a few weeks to months following infection, delays in reporting often result in more cases of tuberculosis in children.6
The vast majority of pediatric tuberculosis cases are found through contact investigation, which involves a process of conducting an epidemiologic investigation around a documented or suspected case of infectious tuberculosis.7,8 Once a suspected case has been reported, the health department initiates a contact investigation as soon as possible, ideally within 3 days. The purpose of this investigation is to identify exposed and infected individuals who need treatment to prevent disease. The first to be evaluated are close contacts of the index case, which usually consist of household members or other contacts who have spent a lot of time with the infected person. If the rate of infection in the closest contacts is higher than the rate in the general population, then other contacts who spend time with the source case, but not as much as the household contacts, should be investigated. Young infants and immunocompromised individuals are a high priority in contact investigations because they are more susceptible to infection and to more serious forms of rapidly progressive tuberculosis.
Associate investigation is the examination of all household contacts of a child with a positive skin test in an attempt to find the source case and other infected contacts. Many health departments conduct associate investigations for infected children younger than 6 years of age since their infection is usually recent and the potential sources of infection are usually limited to household contacts. Health departments often have budgetary or staffing limitations that prohibit associate investigations. Recommended practice for individual physicians seeing patients with tuberculous infection or disease is examination of ail household members with Mantoux skin tests.
Universal skin testing programs are an inefficient and ineffective way to spend public health dollars for case finding. While die yield in high-risk groups is often good, case finding through skin testing programs in the general US population is very unlikely. A study in Houston found that 50% of children with tuberculosis were discovered via contact investigation of adults with active disease, 44% through evaluation of symptomatic children, and 6% through routine screening.9 A similar study in North Carolina showed that 80% of the cases in children were found through contact investigation, 17% following evaluation of symptomatic children, and only 3% were found through routine screening.10 Routine skin testing programs have been shown to be valuable in high risk groups and should be continued in populations where the incidence of new positive tests is greater than l%.11 Clearly, the most effective system for early detection and prevention of childhood tuberculosis is reporting of adult cases to public health authorities followed by timely contact investigation and preventive treatment, if indicated.
ADHERENCE TO THERAPY
Nonadherence with treatment is a major barrier to the control and elimination of tuberculosis.12 There are many factors that contribute to patient nonadherence including the long duration of therapy required, lack of persistent symptoms, and poor public health infrastructure, as well as complicated socioeconomic and cultural factors. Generally, the reasons for poor adherence are not only multifaceted and complex but range from characteristics of individual patients to qualities of the socioeconomic environment that influence all tuberculosis prevention and control activities.13
All physicians would like to believe that their patients adhere to prescribed therapy, yet the length of treatment required for tuberculosis makes this assumption unrealistic. It is well established that at least 20% to 50% of tuberculosis patients fail to complete therapy within a 24-month period of time.12,14 It is difficult to anticipate which patients will adhere to therapy. Predictions by physicians of nonadherence are inaccurate, ranging from 32% to 50% correct, depending on the population studied.15,16 Physicians must realize that long-term treatment is difficult for anyone and that the physician-patient relationship must provide education, support, encouragement, and regular monitoring for children and their families to help them successfully complete therapy.
There are a number of interventions that may improve patient adherence. Patient education at the time of diagnosis and throughout treatment is very important and must address specific questions and concerns that the family may have with regard to treatment. Incentives and enablers are often used to improve adherence. Incentives are things that enhance the desirability of treatment, while enablers actually help the patient overcome specific barriers to care. Examples include such things as money, bus tokens, social services, food, or toys, which are used primarily to motivate the patient and family to continue treatment.
In some cases, barriers to treatment adherence are especially difficult to overcome. In these situations, directly observed therapy and the administration of medication directly by a health-care worker or other third party significantly improves adherence.13,17 Patients may present to the health department for therapy, or in some cases an outreach worker from the health department may visit the family's home to deliver medications 2 to 3 times per week. Twiceweekly medication, after one month of daily therapy, is adequate treatment for most cases of childhood tuberculosis.18 In Houston, Texas, about 50% of children with tuberculous disease are treated with twice-weekly, directly observed therapy. In the past 6 years, all have completed treatment, none have been lost to follow-up, none have relapsed, and outreach workers have delivered 96% of the prescribed doses (Starke JR. 1993. Personal communication).
The Centers for Disease Control and Prevention and the American Thoracic Society recently have recommended that directly observed tlierapy should be considered standard for all cases of tuberculous disease and that patients should receive daily self-administered medication only if the risk of nonadherence is judged to be very low.19 Patient adherence to therapy may be the most difficult problem facing tuberculosis control in the United States. Successful treatment of tuberculosis demands a great deal of commitment of time and effort by physicians, clinic or office staff and health departments. Many communities have clinics specializing in tuberculosis treatment that are able to monitor patients, quickly recognize breaks in therapy, and assist patients and families to return to treatment. Treatment in this type of setting may provide the best chance for successful completion of therapy.
PREVENTION OF TUBERCULOSIS
Tuberculosis is a preventable disease with a variety of techniques available for control including chemotherapy, contact investigation, environmental controls, and vaccination. Treatment with isoniazid for exposed contacts and against development o( disease in infected individuals is recommended. Clinical trials conducted by the US Public Health Service have demonstrated a protective efficacy of more than 90% for at least 30 years among infected patients who completed chemoprophylaxis.20'21 While most physicians are aware of the recommendations for treatment of tuberculous infection, few implement preventive therapy in exposed individuals.
Isoniazid is recommended for all children younger than 6 years of age with a history of household exposure to an adult with infectious tuberculosis, regardless of the results of the child's skin test.18 Those with negative skin tests should be retested 3 to 6 months after the first test, and if the repeat test is negative isoniazid may be discontinued.4 This recommendation is based on three important factors: 1) following initial infection, skin test sensitivity may take 6 to 12 weeks to develop, 2) young infants and children are at high risk of progression to disease once infected, and 3) severe forms of tuberculosis such as meningitis or miliary disease often develop within several months following infection in young children.22 Studies estimate that 20% to 25% of childhood tuberculosis cases could be prevented if contact investigation and preventative therapy for exposure or infection were implemented appropriately.10,17 Unfortunately, preventable cases still occur because preventive therapy often is not used.
Environmental measures to protect health-care workers and other individuals working with tuberculosis patients are especially important since outbreaks of multidrug-resistant tuberculosis are increasing. Early identification and effective treatment of infectious adults is the most important strategy to interrupt the generation of infectious droplet nuclei. Once the infectious person is identified, attempts can be made to prevent the spread of organisms, using exhaust ventilation, proper air mixing, and maintenance of the direction of airflow to the outside through negative pressure.2 When engineering controls cannot be fully used, high-efficiency particulate air (HEPA) filters and germicidal ultraviolet radiation can be helpful.23,24 As a last resort, health-care workers can wear particulate respirators to prevent the inhalation of infectious droplet nuclei.25 Since health-care personnel who come in contact with infectious persons constitute a high-risk group, surveillance of them through skin testing programs is an important measure to monitor transmission of infection in these environments.
Bacille Calmette-Guérin (BCG) vaccination is not used routinely in the United States, but may contribute to tuberculosis control in select high-risk groups when other measures have failed or cannot be successfully implemented. BCG vaccination is recommended for infants and children with negative tuberculin skin tests who: 1) cannot be removed from intimate exposure to persistently untreated patients with infectious pulmonary tuberculosis and cannot be placed on long-term preventive therapy, 2) are continuously exposed to persons with tuberculosis who have bacilli resistant to isoniazid and rifampin, or 3) are in groups that have infection rates with M tuberculosis that exceed 1% per year and for whom the usual surveillance and treatment programs have been attempted, but are not operationally feasible.26 BCG vaccine is still routinely used in many countries throughout the world because the high rates of tuberculosis and the lack of public health resources or infrastructure for surveillance and treatment persist.
In the United States, BCG vaccination is no longer recommended for health-care workers.26 This highrisk group should be protected by infection control measures, screening, and preventive treatment for infection. In settings with a high risk of transmission of multidrug-resistant tuberculosis where aggressive infection control measures have failed, BCG vaccination for health-care workers might be considered.
Even in these circumstances, the uncertain efficacy of BCG may make other control measures such as preventive chemotherapy preferable to vaccination alone.27 The low risk of tuberculous infection in the US general population and the unknown vaccine efficacy make a national BCG vaccination policy unnecessary. The most successful control measures include contact investigation, chemotherapy, and chemoprophylaxis for infection and exposure.
CONCLUSION Complex challenges face our public health system in tuberculosis control and elimination. The difficulties include economic, social, and cultural problems.
Despite these obstacles, the means for elimination are available, but the emergence of multidrug-resistant strains of tuberculosis threaten to make the task more difficult.
If tuberculosis is to be eliminated from the United States, physicians in general must be mindful of new developments and recommendations in the management of this disease. Pediatricians also will play a very important role since appropriate identification and treatment of children with tuberculous infection and disease will be necessary to diminish the pool of infected persons from which future cases will arise.
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3. WallgrenA. Onccintagic«snessofchildrKxxl tuberculosis. AceoRwÎfllr. 1937:22:229234.
4. Starke JR. Childhood tuberculosis during the 1990s, ftdieir Rev. 1992:1 3:343-353.
5. Gostin LO. Controlling the resurgent tuberculosis epidemic: a 50-state survey of TB statutes and proposals for reform. JAMA. 1993;269:255-261 .
6. Starke JR, Taylor-Watts KT. Preventable childhood tuberculosis in Houston, Texas. Am RevRespirDts. 1990; 141 (supp!):A336. Abstract.
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8. American Thoracic Society. Control of tuberculosis in the United States. Am Rev Rapir Dis. 1992;146:1623-1633.
9. Starke JR, Taylor-Watts KT. Tuberculosis in the pediatric population of Houston, Texas, Pediatria. 1989;84:28-35.
10. Nolan RJ Jr. Childhood tuberculosis in North Carolina: a study of the opportunities for the transmission of tuberculosis in children. AmJ Public Health. 1986;76:26-30.
11. Centers for Disease Control and Prevention. Approaches to improving adherence to antituberculosis therapy- South Carolina and New York. 1986-1991. MMWK. 1993;42:74-8t.
12. Aldington WW. Patient compliance: the most serious remaining problem in the control of tuberculosis in the United States. Chest. l979;76(suppl):741-743.
13. Sumanojo E. When tuberculosis treatment fails: a social behavioral account of patient adherence. Am Rev Respfr Dis. 1 993; 147:1 3 1 1 - 1 320.
14. Fox W. Seltadmmistration of medicaments: a review at published work and a study at the problems. Bulletin of the International Union Agamst Tuberculosis. 1962;32:307331.
15. Mushlin AI, Appel FA. Diagnosing patient noncompliance. Arch Intern Med. 1977;137:318-321.
16. Waidman A, Knox AJ, Muers MF, Page RL. Profiles of nun-compliance with antituberculosis therapy. BrJ Du Chest. 1988;82:285-289.
17. Nazar-Stewart V, Nolan CD. Results of a directly observed intermittent isoniazid preventive therapy program in a shelter for homeless men. Am Rev Respfr Dis. 1992;146:57-60.
18. American Academy of Pediatrics. Report of the Committee on Infectious Disease. 22nd ed. Elk Grove Village, IU: American Academy of Pediatrics; 1991 .
19. Centers for Disease Control and Prevention. Initial therapy for tuberculosis in the era of multidrug resistance- Recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR. I993;42(RR-7):1 -8.
20. Comstock GW, Ferebee SH, Hammes LM. A controlled trial of community-wide isoniazid prophylaxis in Alaska. Am Rev Respfr Dis. 1967;95:935-943.
21. Comstock GW, Baum C, Snider DE- Isoniazid prophylaxis among Alaskan Eskimos: a final report of the Bethel isoniazid studies. Am Rev Respfr Dis. 1979;1 19:827-830.
22. Wallgren A. The timetable of tuberculosis. Tufcerde. 1948;29:245-251 .
23. Sheretz RJ, Belani A, Kramer BS, et al. Impact of air filtration on nosocomial Aspergillus infections. Am J Med. 1987;83:709-718.
24. Riley RL, Nardell EA. Cleaning the air: the theory and application of UV air disinfection. Am Rev Respfr Dis. 1 989; 1 39: 1 286- 1 294.
25. Pippin DJ, Velderame RA, Weber KK. Efficacy of face masks in preventing inhalation of airborne contaminants. J Oral Manllofac Surg. 1987;45:319-323.
26. Centers for Disease Control and Prevention. Use of BCG vaccines in the control of tuberculosis: a joint statement by the ACIP and the Advisory ACIP Committee for Elimination of Tuberculosis. MMWR. 1988;37:663-664, 669-675.
27. Connelly KK. Bacille Calmette-Guérin (BOG) vaccine. Semm Pediatr Infect Dis. 1993;4:1-8.
Important Steps in the Prevention of Tuberculosis