Tuberculosis: A Preventable Cause of Death in the Elderly

Mary Ann E. Zagaria, PharmD, MS, CGP Senior Care Consultant Pharmacist and President of MZ Associates, Inc. Norwich, New York

7/18/2008
US Pharm. 2008;33(7):23-25. Along with the elderly population's growth in numbers, there has been an increase in the number of 1 tuberculosis (TB) cases among seniors. While TB is preventable and curable, approximately 1.5 million 2 people died from it in 2006 according to the World Health Organization (WHO). In addition, another 2 200,000 people died from HIV-associated TB. In the United States alone, a total of 13,293 TB cases 3 were reported in 2007. As a result of the growth of TB-control programs nationwide, there has been a 4 decline in the overall number of reported TB cases in the U.S. within the last 10 years. In fact, the TB 3 incidence rate in 2007 was the lowest recorded since national reporting began in 1953. Despite these 4 declines, however, the elderly continue to account for a disproportionate share of the cases. If TB--an airborne infectious disease--is diagnosed early and completely treated, patients with the disease 2 quickly become noninfectious and eventually cured. In elderly patients, many clinical features of TB are subtle or absent, making diagnosis difficult; the high number of cases diagnosed at autopsy among the 1,4 elderly suggests that TB frequently remains unrecognized. Compared with younger individuals, the 5 mortality rate of TB in seniors is six times higher. Pharmacists should take note that TB is a preventable 5 cause of death in seniors and should not be overlooked. The authors of one recent study suggested that an "increased awareness in disease recognition and better medical and social support are needed in 1 addressing the problem of tuberculosis in older people." Approximately three-quarters of all TB cases in seniors occur in the respiratory tract. Extrapulmonary sites (TABLE 1) are common and include the bones and joints (particularly the spine), and the genitourinary tract. A form of disseminated TB, called miliary TB, is also relatively common in 6 seniors. According to WHO, major challenges associated with this condition are multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), HIV-associated TB, and weak health 2 systems. Further challenges in the struggle against TB are faced by the WHO European Region: 1) the high rate of multidrugresistant TB (MDR-TB), mostly in the countries of the former Soviet Union; 2) the rapid growth of the HIV epidemic in eastern Europe and central Asia and, as a consequence, the sharp increase in HIV-related TB; 3) the need to reform the health sector, to include closer involvement of primary health care in TB control; 4) the still-limited political and financial commitment to TB control; and 7 5) lack of advocacy, communication, and social mobilization.
6

TB Infection Versus TB Disease

TB infection is the term used to describe individuals who have contained the primary infection and who 6 remain asymptomatic with a positive tuberculin skin test. Persons who have symptoms of infection are 6 6 noted to have TB disease. In 30% to 50% of cases, persistent TB infection is present without disease. A loss of cellular immune reactivity (i.e., negative tuberculin skin test) to Mycobacterium tuberculosis occurs in some seniors who were previously infected with this organism, thereby rendering them vulnerable to 6 reinfection. In an attempt to adhere to the national objective of elimination of this potentially curable disease, experts 8 recommend an aggressive approach to diagnosis, treatment, and prevention of TB in the elderly. It has been reported that TB prophylaxis is frequently withheld even when indicated, due to concern that elderly 4,8 persons are at greater risk for hepatic toxicity from TB treatment. Pharmacists can be assured, however, that the poor outcome of untreated TB in this age-group warrants more aggressive treatment of the condition and that through careful monitoring of seniors for adverse drug effects, successful treatment 4 may be achieved. Those individuals at risk for TB disease are outlined in TABLE 2. The most important known risk factor for

progression from latent TB infection (LTBI) to TB disease is HIV. The CDC recommends routine 3 screening for HIV for all persons with TB or LTBI at the initiation of TB or LTBI treatment. The CDC continues to work to increase national and international awareness of TB-HIV coinfection and to improve 3 the integration of TB-HIV health care services.

Signs and Symptoms

There is a major concern surrounding TB in seniors regarding failure to recognize or diagnose the 8 disease. Classic features of TB, including cough, sputum production, frank hemoptysis, fever, night 5,6,8 sweats, and weight loss, may not be exhibited in TB disease in the elderly (TABLE 1). Weight loss can 5 occur; however, it is nonspecific. Clinical features in the elderly may include anorexia, chronic fatigue, low-grade fever (prolonged and unexplained), cognitive impairment, and changes in functional ability 8 (e.g., activities of daily living). Compared to younger individuals, mental status changes are twice as 5 common in seniors.

Diagnosis
Tuberculin Skin Test: Skin testing with the Mantoux method is the standard screening procedure for TB 6 infection and reflects the delayed-type hypersensitivity response to M tuberculosis antigen. Elderly 5 patients with TB are far less likely to present with positive skin tests. Chest X-ray: Any lung segment can be involved by primary TB; lung involvement for reactivated TB usually includes the apical and posterior segments of the upper lobes and the superior segments of the 6 6 lower lobes. In the elderly, infiltrates may be interstitial, lobar, patchy or cavitary, and bilateral. Laboratory Findings: Clinical specimens (e.g., sputum, urine) from suspected sites of TB are first examined by smear to detect acid-fast bacilli and are subsequently cultured for M 6 tuberculosis . Serologic tests for antibody detection (i.e., against mycobacterial antigens) have not been 6 adequately refined for routine clinical use.

Treatment
An overview of the treatment of TB in the elderly is provided in TABLE 3. Since recommendations

change due to resistant strains and newly developed information, 9 consulting MMWR (www.cdc.gov/mmwr) for current CDC recommendations is advised. While the recommended treatment duration is often the same for HIV-negative and HIV-positive patients, some clinicians believe that the course of therapy should be extended for immunocompromised 5 patients. Treatment is extended by these clinicians to nine months, rather than six months, to treat HIV5 positive patients with drug-susceptible TB. All TB patients should remain under observation until 6 adherence with their treatment regimen is established. Although it is beyond the scope of this article to discuss the pharmacologic management of TB in detail, the interested reader is referred to Reference 6.

Monitoring
Monitoring with laboratory parameters includes baseline liver enzyme, bilirubin, and serum creatinine 6 levels; a CBC; and a platelet count (or estimate). Monitoring of serum uric acid concentration is 6 recommended when pyrazinamide is part of the regimen. Patients should be monitored monthly for symptoms of hepatitis (e.g., jaundice, fever, anorexia, dark urine, fatigue, weakness, nausea, vomiting), a 6,9 common adverse effect of isoniazid more frequently seen in the elderly. During the first six months of treatment, especially when hepatitis is most likely to occur, testing liver function with aspartate 6 transaminase is recommended. Isoniazid should be discontinued if transaminase levels increase five or 6 more times higher than the upper limit of normal values. A U.S. Boxed Warning for isoniazid states: 9 "Severe and sometimes fatal hepatitis may occur or develop even after many months of treatment." For patients with active disease, sputum should be examined at least monthly until cultures convert to negative; in approximately 90% of patients, cultures will convert within three months of commencement of 6,9 the recommended regimen. Evidence suggests that institutionalized seniors are at a greater risk for reactivation of latent TB and for 4 the acquisition of new TB infection compared with their community-dwelling counterparts. Patients in long-term care facilities and acute-care institutions should be under surveillance, control, and reporting for 6 TB, according to CDC recommendations. Initial skin testing and subsequent annual testing should be

performed on all new employees and new residents in long-term care facilities. The initial comprehensive assessment of all elderly patients should include the two-step purified protein derivative (PPD) 6 screening. All persons who test tuberculin positive on admission to a long-term care facility should have 6 a chest x-ray to ensure the absence of pulmonary infiltrates consistent with TB. Furthermore, a chest x6 ray should be performed on anyone suspected of having TB. REFERENCES 1. Chand N, Bhushan B, Singh D. Tuberculosis in the elderly (aged 50 years and above) and their treatment outcome under DOTS. Chest. http://meeting.chestjournal.org/cgi/ content/abstract/132/4/640b. Accessed June 16, 2008. 2. A World Free of TB. World Health Organization. www.who.int/tb/en/. Accessed June 16, 2008. 3. Trends in Tuberculosis--United States, 2007. Centers for Disease Control. MMWR. March 21, 2008. www.cdc.gov/mmwr/preview/mmwrhtml/mm5711a2.htm. Accessed June 16, 2008. 4. Zevallos M, Justman JE. Tuberculosis in the elderly. Clin Geriatr Med. 2003 Feb;19:121-138. 5. Peloquin CA. Tuberculosis. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 6th ed. New York, NY: McGraw-Hill, Inc; 2005:2015-2034. 6. Tuberculosis. The Merck Manual of Geriatrics. www.merck.com/mkgr/mmg/sec10/ch76/ch76b.jsp. Accessed June 16, 2008. 7. Challenges for TB control in the European Region. World Health Organization Regional Office for Europe. www.euro.who.int/tuberculosis/issues/20030312_1. Accessed June 16, 2008. 8. Rajagopalan S, Yoshikawa TT. Tuberculosis. In: Hazzard WR, Blass JP, Halter JB, et al, eds. Principles of Geriatric Medicine and Gerontology. 5th ed. New York, NY: McGraw-Hill, Inc; 2003:1099-1105. 9. Semla TP, Beizer JL, Higbee MD. Geriatric Dosage Handbook. 12th ed. Hudson, OH: Lexi-Comp, Inc; 2007. To comment on this article, contact rdavidson@jobson.com.

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ecommendations and Reports

July 13, 1990 / 39(RR-10);7-20

Prevention and Control of Tuberculosis in Facilities Providing Long-Term Care to the Elderly Recommendations of the

Advisory Committee for Elimination of Tuberculosis

These recommendations were developed by the Advisory Committee for Elimination of Tuberculosis, CDC staff, and public health consultants. They describe tuberculosis control activities appropriate for nursing homes and other facilities providing long-term care for elderly persons. Such facilities include long-term-care wings or units in hospitals, adult foster-care homes, board and care homes, and other congregate settings for the elderly (referred to hereafter as "facilities"). The recommendations are intended for use by staff and administrators of these facilities, consultants to these facilities, and regulatory and licensing bodies. This document is not intended for use as a primer on tuberculosis. More general information about tuberculosis is available in the American Thoracic Society (ATS)/CDC statements referenced in this document. State and local health departments are encouraged to continue the search for new, innovative, and more effective approaches for controlling and preventing tuberculosis in facilities providing long-term care for the elderly. BACKGROUND Persons greater than or equal to 65 years of age constitute a large repository of Mycobacterium tuberculosis infection in the United States. Tuberculosis case rates are higher for this age group than for any other. In 1987, the 6,150 tuberculosis cases reported for persons greater than or equal to 65 years of age accounted for 27% of the total U.S. tuberculosis morbidity, even though this age group represents only 12% of the U.S. population (1). The control and prevention of tuberculosis among the elderly must be addressed aggressively to achieve the goal of eliminating tuberculosis in the United States by the year 2010 (2). CDC surveillance data indicate that, as with younger age groups, most elderly tuberculosis patients (84%) have pulmonary disease; because more than half of these patients have sputum smears positive for acid-fast bacilli, they are potentially capable of transmitting the infection to other persons (CDC, unpublished data). In the United States, more elderly persons live in nursing homes than in any other type of residential institution; based on data from CDC's National Center for Health Statistics, approximately 5% of all elderly persons live in a nursing home (3). However, elderly persons represent 88% of the nation's approximately 1.7 million nursing home residents (3). Such concentrations of elderly persons, many of whom are infected with tubercle bacilli and some of whom are immunosuppressed, create high-risk situations for tuberculosis transmission. Elderly nursing home residents are at greater risk for tuberculosis than elderly persons living in the community. In 1984-1985, a CDC-sponsored study of 15,379 routinely reported tuberculosis cases from 29 states indicated that the incidence of tuberculosis

among nursing home residents was 39.2 cases per 100,000 population; in comparison, the incidence of tuberculosis among elderly persons living in the community was 21.5 cases per 100,000 population (CDC, unpublished data). Nursing home employees are also at increased risk for tuberculosis when compared with other employed adults. In the CDC study, the observed case rate among nursing home employees was three times higher than the rate expected for employed adults of similar age, race, and sex (CDC, unpublished data). Investigators have reported outbreaks in nursing homes in which transmission of tuberculosis was documented among residents and staff (4-8). The person having the source case has usually been a resident but may be a member of the staff. In such situations, isoniazid preventive therapy has effectively reduced the risk of tuberculosis among contacts of newly infected elderly persons (9,10). The following recommendations for addressing the problem of tuberculosis in facilities providing long-term care to the elderly have been developed in response to requests from state and local tuberculosis control officials, representatives of nursing homes and other long-term-care facilities, physicians in academic and clinical practice, and representatives of regulatory and resource-providing agencies. GENERAL GUIDELINES Each facility should assure that appropriate tuberculosis prevention and control measures are undertaken to protect residents and staff. In large facilities, an infection control committee will usually be responsible for operating the tuberculosis prevention and control program. In a system that has more than one facility providing long-term care to the elderly, a qualified person should oversee the control activities at all of the facilities. Responsibility for surveillance, containment, assessment, and education should be specified in this person's job description. --Surveillance refers to identifying and reporting all cases of tuberculosis in the facility and identifying all infected residents and staff. When an infectious case is identified, additional cases and new infections (as indicated by skin-test conversion) should be identified with the help of the state or local health department, and appropriate therapy should be instituted. --Containment refers to ensuring that transmission of tuberculous infection is stopped promptly. Persons for whom treatment of disease or preventive treatment is indicated should complete the appropriate course of treatment under direct supervision (i.e., the actual ingestion of medication is observed by a staff member). In addition, appropriate ventilation control measures should be applied. --Assessment refers to monitoring and evaluating the surveillance and containment activities throughout each facility. --Education refers to providing information and imparting skills to patients, families, visitors, and employees so that they understand and cooperate with surveillance, containment, and assessment activities. SURVEILLANCE Diagnosis The intracutaneous administration of 5 units of purified protein derivative tuberculin (PPD-T) (Mantoux test) should be used to identify persons infected with tubercle bacilli. Multiple-puncture devices are not recommended. False-negative reactions to the

tuberculin test may occur for up to 30% of persons with tuberculosis but without acquired immunodeficiency syndrome (AIDS); in comparison, false-negative reactions may occur for up to 60% of persons with tuberculosis and AIDS (11; CDC, unpublished data). Therefore, a negative skin test does not exclude the diagnosis of tuberculosis. Chest radiography and bacteriologic examinations are indicated for all residents and staff with symptoms compatible with tuberculosis, regardless of the size of the skin-test reaction. Skin tests should be administered to all new residents and employees as soon as their residency or employment begins unless they have documentation of a previous positive reaction. A two-step procedure is advisable for the initial testing of residents and employees in order to establish a reliable baseline (11-13). Appendix I explains this procedure and the rationale for using it. Each skin test should be administered and read by appropriately trained personnel and recorded (in mm induration) in the person's medical record. A record of all reactions of greater than or equal to 10 mm should be placed in a prominent location in order to facilitate the consideration of tuberculosis if the person develops signs or symptoms of tuberculosis, such as a cough of greater than 3 weeks' duration, unexplained weight loss, or unexplained fever. All persons with a reaction of greater than or equal to 10 mm should receive a chest radiograph to identify current or past disease. Skin-test-negative employees and volunteers having contact (of greater than or equal to 10 hours per week) with elderly residents should periodically have repeat skin tests; the recommended frequency of repeat testing depends upon the risk of tuberculosis infection in that facility (13). Each tuberculin-positive resident should be evaluated annually, and a record should be kept that documents the presence or absence of symptoms of tuberculosis (e.g., weight loss, cough, fever). Repeat skin tests should be provided for tuberculin-negative residents and employees after any suspected exposure to a documented case of active tuberculosis. A skin-test conversion is defined as an increase of greater than or equal to 10 mm for a person less than 35 years of age or an increase of greater than or equal to 15 mm for a person greater than or equal to 35 years of age*. Each skin-test converter should have a chest radiograph; if the radiograph is negative for tuberculosis, the individual should be treated preventively. If the source of infection is not known and/or if additional conversions occur, periodic retesting of residents and a careful search for the source case should be continued. Persons with reactions greater than or equal to 10 mm and persons with symptoms suggesting tuberculosis (e.g., cough, anorexia, weight loss, fever), regardless of the size of the skin-test reaction, should have a chest radiograph within 72 hours. Persons with abnormal chest radiographs and/or symptoms compatible with tuberculosis should also have sputum smear and culture examinations. In addition, sputum should be submitted for smear and culture for acid-fast bacilli for persons with a chronic cough, pneumonia, or bronchitis who do not respond promptly and completely to antibiotic treatment. At least three sputum specimens should be submitted. In the absence of spontaneous production of sputum, suction of laryngeal or pharyngeal mucus is satisfactory if sterile

water is used in clearing the catheter. Usually, the early detection of tuberculosis by such means either prevents or greatly diminishes the spread of infection. Staff members who are considered to have infectious tuberculosis should be relieved of work responsibilities until the diagnosis is excluded or until they become noninfectious as a result of effective chemotherapy. Case Reporting Whenever tuberculosis is suspected or confirmed among residents or staff, this information should be recorded and kept on file (in the medical record, personnel record, or other appropriate place). A prototype tuberculosis record is shown in Appendix II. The local or state health department should also be notified, as required by state and local laws or regulations. Tuberculosis and Human Immunodeficiency Virus Infection Staff members and residents with tuberculosis or tuberculous infection should be assessed for human immunodeficiency virus (HIV) infection because the medical management of tuberculosis and tuberculous infection must be altered in the presence of HIV infection. Factors** that are associated with an increased risk or prevalence of HIV infection should be routinely sought. If HIV infection is considered a possibility, counseling and HIV-antibody testing should be strongly encouraged. Previously published guidelines provide additional information about this topic (14). CONTAINMENT Isolation Persons with suspected or confirmed tuberculosis can remain in their usual environment, provided 1) chemotherapy is promptly instituted at the time the diagnosis is suspected or confirmed, 2) recent and current contacts are evaluated and placed on appropriate therapy, and 3) new contacts can be prevented for a 1- to 2-week period. If these conditions cannot be met, the person with suspected or confirmed tuberculosis should be placed under appropriate isolation precautions to prevent the spread of infection (15). The local health department should be contacted regarding the need for isolation and the methods used for achieving it. Treatment ATS/CDC recommendations should be followed in treating and managing persons with confirmed or suspected tuberculosis (14,16). For newly diagnosed, previously untreated patients, the treatment regimen should contain both isoniazid and rifampin. If the patient has been treated for tuberculosis in the past, other or additional drugs may be needed. Antituberculosis medication should be given along with other medication administered by nursing home staff. Each dose of medication should be dispensed by a staff person who watches the patient swallow the pills and who is trained to monitor for evidence of drug toxicity. Persons with positive sputum smears or cultures at the beginning of therapy should be monitored by repeat sputum examinations for treatment response until smears become negative. Failure to achieve negative smears and cultures is usually due to the patient's noncompliance with therapy but may be due to the presence of drugresistant organisms or other complications. Patients should also be monitored by trained personnel for signs and symptoms of adverse drug reactions during therapy (14,16). Expert medical consultation should be sought when treating patients with complications

(e.g., drug resistance, adverse reactions, nonpulmonary tuberculosis). Such consultation is usually available through the local or state health department. Investigation for Contacts Because tuberculosis is transmitted by the airborne route, persons who sleep, live, work, or who are otherwise in contact with an infectious person through a common ventilation system for a prolonged time are "close contacts" at risk of acquiring infection. These persons may include other residents, staff, and visitors. When a person with confirmed tuberculosis appears to be infectious (e.g., has pulmonary involvement as seen by chest radiograph and a cough and/or positive sputum smear), contacts who were previously tuberculin-negative should be retested (13). If the case occurs in a known tuberculin converter, a search for the person who has the source case (referred to hereafter as the "source patient") should be undertaken by performing chest radiographs for all persons known to be tuberculin reactors and by submitting sputum specimens for smear and culture for all patients with a cough. General guidelines for conducting a contact investigation in a nursing home or other facility are given in Appendix III, but health department personnel should be consulted to help determine which contacts should be examined. Preventive Therapy Contacts who have documented skin-test conversions and whose chest radiographs do not reveal tuberculosis should be given at least 6 months' preventive therapy unless it is medically contraindicated. Other residents and staff with positive tuberculin reactions should be given preventive therapy and monitored according to previously published guidelines (17). Preventive therapy for residents should be incorporated into the facility's routine for delivering medications (e.g., blister pack, cardex file) and should be dispensed by a staff person trained to monitor for signs and symptoms of drug toxicity (16). If such signs or symptoms appear, medication should be withheld pending evaluation by a physician. If tuberculosis preventive therapy is recommended, but individuals refuse or are unable to complete the recommended course, they should be advised to seek prompt medical attention if they develop signs or symptoms compatible with tuberculosis (e.g., persistent cough, anorexia, weight loss, night sweats). Routine periodic chest radiographs are not useful for detecting disease in the absence of symptoms; however, chest radiographs should be obtained promptly for persons with a cough that persists for more than 3 weeks and/or with a prolonged and unexplained fever. ASSESSMENT A record-keeping system, such as that shown in Appendix II, is essential for tracking and assessing the status of persons with tuberculosis and tuberculous infection in nursing homes/facilities that provide long-term care for elderly persons. This system should also provide data needed to assess the overall effectiveness of tuberculosis control efforts. The following information should be reviewed annually with health department staff and should be compared with previous data and data from other facilities in the area: -Percentage of residents and staff within each facility with positive skin tests --Percentage

of persons showing conversion of the tuberculin test if retesting is performed -Description of therapy and supervision --Percentage of persons recommended for therapy who complete the prescribed course (goal is greater than 95%) --Number of persons experiencing drug toxicity or intolerance --Number of persons discontinuing medication and reason for discontinuance ROLE OF THE HEALTH DEPARTMENT State and local health departments should assist in developing and updating policies, procedures, and record systems for tuberculosis control in nursing homes and other facilities that provide residential care for elderly persons. The health department should also provide access to expert tuberculosis medical consultation. A health department representative should be designated to provide epidemiologic and management assistance to such facilities, and this responsibility should be an element in that person's job performance plan. At a minimum, he or she should be required to complete an initial on-site consultation, to be available for telephone consultation, and to conduct an annual evaluation of individual facilities. State health departments should assist local units in developing programs to train facility staff to administer, read, and record tuberculin skin tests; to identify signs and symptoms of tuberculosis; to initiate and observe therapy; to monitor for side effects; to collect diagnostic specimens; and to maintain record systems. Health departments should also provide consultation for contact investigations within facilities, and they should assure appropriate examinations of nonresident contacts of persons with tuberculosis diagnosed in these facilities. State health departments have a responsibility to maintain a tuberculosis registry with updated medical information on all persons who currently have tuberculosis within their jurisdiction, including persons in nursing homes and other facilities providing residential care for elderly persons. Records should be assessed annually, and necessary revisions in policies or procedures should be recommended. In addition, state health departments should periodically assess the impact of tuberculosis acquired in a residential facility and the impact of tuberculous infection on the community as a whole. References 1. CDC. Tuberculosis statistics in the United States, 1987. Atlanta: 1989; HHS publication no. (CDC) 89-8322. 2. CDC. A strategic plan for the elimination of tuberculosis in the United States. MMWR 1989;38(suppl. no. S-3):1-25. 3. National Center for Health Statistics, E Hing. Use of nursing homes by the elderly: preliminary data from the 1985 national nursing home survey. Hyattsville, Maryland: National Center for Health Statistics, 1987. Vital and Health Statistics: Advance data

from vital and health statistics, no. 135. DHHS publication no. (PHS) 87-1250. 4. CDC. Tuberculosis--North Dakota. MMWR 1979;27:523-5. 5. CDC. Tuberculosis in a nursing home--Oklahoma. MMWR 1980;29:465-7. 6. Stead WW. Tuberculosis among elderly persons: an outbreak in a nursing home. Ann Intern Med 1981;95:606-10. 7. CDC. Tuberculosis in a nursing care facility--Washington. MMWR 1983;32:1212,128. 8. Stead WW, Lofgren JP, Warren E, Thomas C. Tuberculosis as an endemic and nosocomial infection among the elderly in nursing homes. N Engl J Med 1985;312:14837. 9. Stead WW, To T. The significance of the tuberculin skin test in elderly persons. Ann Intern Med 1987;107:833-42. 10. Stead WW, To T, Harrison RW, Abraham JH III. Benefit-risk considerations in preventive treatment for tuberculosis in elderly persons. Ann Intern Med 1987;107:843-5. 11. American Thoracic Society, CDC. Diagnostic standards and classification of tuberculosis. Am Rev Respir Dis 1989 (in press). 12. American Thoracic Society, CDC. The tuberculin skin test. Am Rev Respir Dis 1981;124:356-63. 13. American Thoracic Society, CDC. Control of tuberculosis. Am Rev Respir Dis 1983;128:336-42. 14. CDC. Tuberculosis and human immunodeficiency virus infection: recommendations of the Advisory Committee for Elimination of Tuberculosis. MMWR 1989;38:236-50. 15. CDC. Guidelines for prevention of TB transmission in hospitals. Atlanta, Georgia: US Department of Health and Human Services, Public Health Service, 1982; DHHS publication no. (CDC)82-837l. 16. American Thoracic Society, CDC. Treatment of tuberculosis and tuberculosis infection in adults and children. Am Rev Respir Dis 1986;134:355-63. 17. CDC. Screening for tuberculosis and tuberculous infection in high-risk populations, and The use of preventive therapy for tuberculous infection in the United States: recommendations of the Advisory Committee for Elimination of Tuberculosis. MMWR 1990;39(no. RR-8):912.

The Committee chose a larger increase in reaction size to

define a skin-test conversion among persons greater than or equal to 35 years of age because of the increased risk of isoniazid-associated hepatotoxicity in this age group. With the use of this criterion, the benefits of using isoniazid preventive therapy should clearly outweigh its risks. ** On the basis of seroprevalence studies, factors that place a person at risk for HIV infection include intravenous (IV)-drug use and homosexual/bisexual contact. Other factors that increase the risk for HIV infection among adults include having received blood or clotting-factor concentrate between 1978 and 1985 and having had sexual relations at any time since 1978 with 1) a person known to be infected with HIV or to

have AIDS, 2) a man who has had homosexual/bisexual contact, 3) prostitutes, 4) IVdrug users, or (5) persons born in countries where most transmission of HIV is thought to occur through heterosexual sexual contact. Appendix I Detection of Newly Infected Persons (Skin-Test Converters) The tuberculin test can be especially valuable when it is repeated periodically in the surveillance of tuberculin-negative persons likely to be exposed to tuberculosis. However, special problems exist in identifying newly infected persons. First, some errors may occur in even the most carefully performed tests. For this reason, small increases in reaction size are usually not meaningful. Only persons whose tuberculin reactions show marked increases in size (i.e., greater than or equal to 10 mm among persons less than 35 years of age and greater than or equal to 15 mm among those greater than or equal to 35 years) within a 2-year period should be considered newly infected. A second problem in identifying newly infected persons is the "booster phenomenon." Repeated testing of uninfected persons does not sensitize them to tuberculin. However, delayed hypersensitivity to tuberculin, once it has been established by infection with any species of mycobacteria or by Bacillus of Calmette and Guerin (BCG) vaccination, may gradually wane over the years. When tested at this point, these persons may have negative reactions. The stimulus of this test may then boost or increase the size of the reaction to a subsequent test, sometimes causing an apparent conversion or development of sensitivity. Although the booster phenomenon may occur at any age, its importance increases with age. When tuberculin skin testing of adults is to be repeated periodically, the use of two-step testing initially can reduce the likelihood that a boosted reaction will be interpreted as representing recent infection. If the reaction to the first test is negative, a second test should be given a week later. If the second test result remains below the cutting point for a positive test, the reaction is considered to be negative. If the reaction to the second test is positive, it probably represents a boosted reaction and not a new infection. Multiple-puncture devices should not be used in tuberculin-testing surveillance programs designed to detect newly infected persons (such as in periodic testing programs for employees of hospitals and other institutions or in the evaluation of contacts). Appendix II Tuberculosis Summary Record The Prototype Tuberculosis Summary Record is designed to update the tuberculosis status of each resident and employee in a facility. This record may be kept in a central location (e.g., in the infection control office) or may be kept in individual patient or staff medical records. The form should not replace the tuberculosis diagnostic and treatment information found in the medical records of persons with tuberculosis symptoms or of those persons receiving antituberculosis medications. The form can also be used to prepare statistical reports and to track residents and

employees requiring periodic skin testing. This information is important for assessing the overall effectiveness of tuberculosis control efforts in a facility. If kept current, the data on the forms can be summarized periodically and compared with previous data in order to determine: --The number of staff and residents having positive tuberculin skin tests -The number of persons whose tuberculin tests have shown conversions from negative to positive --The number of persons in the home receiving tuberculosis therapy and supervision --The number and percentage of persons recommended for therapy who complete the prescribed course (goal is greater than or equal to 95%) When tuberculosis is diagnosed, the form contains the necessary information for reporting the case to the state or local health department. The form also reflects 1) if the case was reported, 2) if a contact investigation was completed, or 3) if HIV testing was performed. Summary information regarding the use of chemotherapy for infection or disease can also be recorded. Many items on the form require only a check in the appropriate box. The format follows events in the order they are likely to occur in the diagnosis of tuberculosis infection and disease. The first section can be completed at the time of admission or employment; it documents personal information, as well as baseline skin-testing results. Space is provided for recording the results of a second initial skin test when the two-step procedure is used. If baseline skin testing is negative, the results of retesting can be recorded on the second section of the form. The final section of the form can be used to document x-ray and bacteriologic results, diagnosis, chemotherapy, and other information. This part of the form is generally used only for those residents or employees who have tuberculous infection or disease, those who have tuberculosis symptoms, or those who require follow-up after exposure to tuberculosis. Appendix III Investigation for Contacts Contacts of persons with newly diagnosed tuberculosis are at risk of infection and disease. The risk to contacts is related to various factors pertaining to the person who has the source case (the "source patient"), the contact, and the environment that they share. Many factors interact to influence the transmission of infectious particles (droplet nuclei) from the source patient to the contact. As soon as the diagnosis is reasonably established on laboratory and/or clinical bases, investigation of contacts should begin. Health-care personnel should not wait for positive cultures if history, sputum smears, and chest radiographs are suggestive of tuberculosis.A. Development of Transmission Probability Data When a source patient has been identified, the appropriate procedure in contact investigation entails the development of a data base and an evaluation of each of the factors noted below. These data are usually gathered by interviewing the source patient

and by reviewing related historic and laboratory records. A visit to the source patient's home or place of employment will usually be necessary to assemble a satisfactory initial data base. Source-patient characteristics. Any person who is generating aerosolized particles containing tubercle bacilli is a potential transmitter of infection. Factors that indicate the probability of spreading tuberculous infection are: --If the source patient is not receiving adequate antituberculosis chemotherapy, the probability of his or her producing infectious particles is enhanced. --The presence of acid-fast bacilli in the appropriately examined sputum smear is indicative of a greater potential for infection. -The ability to culture Mycobacterium tuberculosis from secretions of the source patient is less important quantitatively as an indicator than is the positive sputum smear. --The presence of tuberculous laryngitis increases infectiousness. --The presence of cough increases the probability of aerosol generation. --The volume and viscosity of respiratory secretions influence the production of infectious particles; high volume and watery sputum are regarded as risk factors. --Forceful exhalation (e.g., singing or shouting) may increase the potential for producing infectious particles. --Prolonged duration of respiratory symptoms may augument the likelihood that infection will be transmitted. Environmental air factors. Air is the vehicle by which the infectious particle or droplet nucleus is transported from the source patient to susceptible persons. The greater the concentration of these droplet nuclei in air shared by the source patient and his or her associates, the greater the risk to these contacts. The following factors alter the concentration of infectious particles in the air: --The volume of air common to the source patient and contact is critical. If low, the concentration of infectious particles is increased (e.g., as in sharing a small room). --Ventilation with outside air dilutes the concentration of potentially infectious droplets. --Recirculating air may result in the accumulation of high concentrations of infectious particles because droplet nuclei remain suspended in the air (e.g., ships, hospitals, and other structures with closed-circuit heating and airconditioning systems). --Filtering air by high-efficiency particulate air (HEPA) filters removes the droplet nuclei from recirculated air. --Ultraviolet irradiation of the upper air within the shared space (when feasible) may reduce the spread of infection by killing the tubercle bacilli suspended in the droplet nuclei. Contact risk factors. Persons who have recently shared air with the source patient may be considered potentially infected contacts. The following factors are known to modify the risk of infection for these persons: --Prior infection with tuberculosis, as indicated by a significant skin-test reaction before exposure to the identified source patient, reduces risk. --Increased time in association with the source patient influences the probability of infection. --Physical closeness between the source patient and the contact may influence the likelihood of infection. B. Structuring a Contact Investigational Program Establishment of investigational priorities. The estimated probability of transmission, based on information obtained by following the steps described above, should influence the priority, rapidity, and thoroughness with which a contact investigation is conducted. By using this systematic approach, appropriate and productive public health programs can be implemented. Classification of contacts. For each source patient, the contact investigation should proceed in an orderly manner, starting with persons who are most likely to have been infected. Members of the immediate family or others who have shared accommodations with the source patient in the recent past usually are labeled household contacts. Contacts in working, leisure, or other settings are designated by

other terms such as "close," "intimate," or "casual." The most important consideration in a contact investigation is the probability of infection among contacts; therefore, the first step is to allocate contacts into higher- and lower-risk contacts. A higher-risk contact is defined as any person who shared the environment air with a source patient for a relatively longer time and who has other risk factors relatively higher than those of other known contacts. Nursing home/facility residents sharing the same wing or ventilation circuit should usually be considered close contacts. C. Establishing Limits for Contact Investigations By initially evaluating the higher-risk contacts for evidence of tuberculous infection and/or disease, the actual infectiousness of the source patient can be inferred. The following are guidelines for limiting the extent of a contact investigation: --Initiate investigation with higher-risk contacts; if there is no evidence of recent transmission of infection in this group, extending the investigation is not appropriate. --If data indicate recent infection in the higher-risk group, extend the limits of investigation to progressively lower-risk contacts until the levels of infection detected approximate the levels of infection in the local community. --At each stage of the investigation, establish the number and identity of contacts to be examined. Establishing such a denominator helps to assure that no contact who should be examined is missed.

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