Tuberculosis | Copyright © 2007 CEUFast.com

Course Contents

	Purpose/Goals    Objectives    Overview    Symptoms of TB    Tuberculin Skin Testing        Interpreting a Tuberculin Skin Test        Targeted Tuberculin Testing    BCG Vaccine    Chest X-rays    Sputum Examinations    Treatment        Active TB        Drug-Resistant TB        LTBI    Monitoring    Airborne Precautions    Precautions to Take at Home During      Treatment    Role of the Health Department    Pregnancy and Lactation    Children and Adolescents    Conclusion    References    Click any section in the index above to browse to the corresponding course section

Purpose/Goals

The purpose of this course is to update the healthcare professional on current diagnosis and treatment of Tuberculosis.

Objectives

After completing the course, the learner will be able to:

Overview

At one time, Tuberculosis (TB) was the leading cause of death in the United States (CDC, 2001). In the 1940s, scientists discovered the first of several drugs effective in the treatment TB. As a result, TB began to disappear in the United States. However, the number of TB cases increased from 1985 to 1992. The incidence of newly reported cases of TB has fallen in the US since 1992 to its lowest level ever (Murray, 2004). TB continues to be a problem in the US in immigrant populations, in elderly individuals with reactivating latent infection, and in local outbreaks (Brock, Welding, Lillebaek, Follmann & Anderson, 2004).

TB is a disease caused by the bacteria mycobacterium tuberculosis. It is a tough and resilient microorganism that is adapted to prolonged residence in its human host. The bacteria are shielded by a waxen cell wall that protects against the body's antibacterial defenses and foreign chemicals (Murray, 2004). TB can attack any part of the body; but, most commonly attacks the lungs. It is spread through the airborne transmission. When a person breathes in mycobacterium tuberculosis, it can settle in the lungs and begin to grow. From there, the bacteria can move through the blood to other parts of the body, such as the kidney, spine, and brain. TB is not spread through handshakes, sitting on toilet seats, or sharing dishes and utensils with someone who has TB (CDC, 2001). TB in the lungs or throat can be contagious. TB in other parts of the body, such as the kidney or spine, is usually not contagious. People with TB disease are most likely to spread it to people they spend time with every day.

TB disease may develop soon after becoming infected with mycobacterium tuberculosis, before the immune system can fight the bacteria. Latent mycobacterium tuberculosis infection (LTBI) means that a person is infected with mycobacterium tuberculosis, but has no symptoms and cannot spread the disease. LBTI is identified by a positive skin test reaction. People with LTBI may develop TB disease at some time in the future, if their immune system becomes weak for some reason.

The following are groups who are more susceptible to TB disease because they may have a weak immune system (CDC, 2001):

	Babies and young children
	HIV/AIDS
	Substance abuse
	Diabetes mellitus
	Silicosis
	Cancer of the head or neck
	Leukemia or Hodgkin's disease
	Severe kidney disease
	Low body weight
	Certain medical treatments (such as corticosteroid treatment or organ transplants)

Other at risk groups include African Americans, immigrants, and persons living in poverty with limited access to medical care, inadequate housing, and inadequate nutrition (CDC, 2003). Non-Hispanic blacks continued to have TB at rates eight times greater than non-Hispanic whites. Additionally, southeastern states have TB rates higher than the national average (Anonymous, 2004).

Symptoms of TB

The symptoms of active TB disease depend on what part of the body is affected. TB bacteria most commonly grow in the lungs and may cause (CDC, 2001):

	A bad cough that lasts longer than 2 weeks
	Pain in the chest
	Coughing up blood or sputum

Other symptoms are (CDC, 2001):

	Weakness or fatigue
	Weight loss
	No appetite
	Chills
	Fever
	Sweating at night

Tuberculin Skin Testing

The tuberculin skin test is used to diagnose latent tuberculosis infection, but it requires two visits and skilled personnel for test placement and interpretation. Additionally, the tuberculin skin test does not reliably separate latent tuberculosis infection from prior immunization with mycobacterium bovis bacilli calmette guerin (BCG) or infection with environmental mycobacteria (Barnes, 2004).

The preferred skin test for M. tuberculosis infection is the intradermal, or mantoux, method. It is administered by injecting 0.1 ml of 5 tuberculin units (TU) of purified protein derivative (PPD) intradermally into the dorsal or volar surface of the forearm. Test results must be read between 48 to 72 hours after administration. Test results read outside of this time limit give an invalid result and the test must be redone. Multiple puncture tests, Tine and Heaf, and PPD strengths of 1 TU and 250 TU are not sufficiently accurate and should not be used.

Interpreting a Tuberculin Skin Test

A tuberculin skin test is commonly called a PPD. The results of a PPD is the measurement of any area of induration at the injection site. Induration is an abnormal hard spot or place. Areas of erythema (redness of the skin) are clinically not significant and should be ignored when reading a PPD.

Palpate any area of induration and measure the width in millimeters. If there is no induration present, this should be recorded as a zero response. Documenting only negative or positive does not allow accurate interpretation of the results.

An interpretation of a PPD is determined by the millimeter measurement of induration at the PPD test site combined with the individual’s risk factors.

>5 mm of induration is considered positive for people who are at the highest risk for developing active TB (Geiter, Gordin, Hershfield, et. al., 2000):

	People with HIV infection
	Who are receiving immunosuppressive therapy
	Who have had recent close contact with persons with infectious TB
	Who have abnormal chest x-rays consistent with prior TB

>10 mm of induration is considered positive for other people with an increased probability of recent infection or with other clinical conditions that increase the risk for progression to active TB (Geiter, Gordin, Hershfield, et. al., 2000).

	Immigration within the last 5 years from high prevalence countries
	Injection drug users
	Residents and employees of high-risk congregate settings (including healthcare workers with exposure to TB)
	Mycobacteriology laboratory personnel
	Persons with clinical conditions such as silicosis, diabetes mellitus, chronic renal failure, leukemias and lymphomas, carcinoma of the head or neck and lung, weight loss of >10% ideal body weight, gastrectomy, and jejunoileal bypass
	Children younger than 4 yr of age
	Infants, children, and adolescents exposed to adults in high-risk categories

>15 mm of induration is considered positive for persons at low risk for TB. Tuberculin testing is not generally indicated for this group (Geiter, Gordin, Hershfield, et. al., 2000).

For people with negative tuberculin skin-test reactions who undergo repeat skin testing, like healthcare workers, an increase in reaction size of >10 mm within a period of 2 yr should be considered a skin-test conversion indicative of recent infection with m. tuberculosis (Geiter, Gordin, Hershfield, et. al., 2000).

Targeted Tuberculin Testing

Screening of low-risk populations is discouraged because it diverts resources from activities of higher priority. In addition, a substantial proportion of tuberculin-test-positive persons from low-risk populations may have false-positive skin tests. Programs that screen low-risk groups should be replaced by targeted testing (Geiter, Gordin, Hershfield, et. al., 2000).

Targeted tuberculin testing for LTBI identifies persons at high risk for TB who would benefit by treatment of LTBI. Persons at high risk for TB have either been infected recently with TB or have clinical conditions that are associated with an increased risk of progression of LTBI to active TB disease. Infected persons who are at high risk for developing active TB should be offered treatment of LTBI regardless of their age (Geiter, Gordin, Hershfield, et. al., 2000).

Epidemiologically defined groups of people with high rates of TB transmission and increased risk for being recently infected are the homeless, those with HIV infection, and injection drug users. People who reside or work in institutional settings, like hospitals, homeless shelters, correctional facilities, nursing homes, and residential homes for patients with AIDS may have an ongoing risk for acquiring TB infection (Geiter, Gordin, Hershfield, et. al., 2000).

People who have immigrated from areas of the world with high rates of TB have incidence rates similar to those of their countries of origin, for the first several years after arrival in the United States. This high rate likely results from infection acquired in the native country before immigration where TB disease develops soon after arrival in the United States. Areas of the world with high TB rates include countries in Latin America, the Caribbean, Africa, Asia, Eastern Europe, and Russia.

TB testing is discouraged unless there is a plan to complete a course of treatment in persons found to have LTBI. The plan should include arrangements for medical evaluation (e.g., chest x-ray) of people with positive skin tests and for the medical supervision of the course of treatment.

BCG Vaccine

BCG is a vaccine for TB, which is not always effective in preventing TB. This vaccine is not widely used in the US; but, it is often given to infants and small children in other countries where TB is common (Murray, 2004).

People who received the vaccine may have a positive reaction to a TB skin test. This reaction may be due to the BCG vaccine itself, but it most probably indicates LTBI (CDC, 2001). Tuberculin reactivity caused by BCG vaccination generally wanes over time but can be boosted by the tuberculin skin test (Geiter, Gordin, Hershfield, et. al., 2000).

Chest X-rays

A chest x-ray is indicated for all people being considered for treatment of LTBI, to exclude active pulmonary TB. Children younger than 5 yr of age should have both posterior/anterior and lateral x-rays. All other people should receive posterior/anterior x-rays. Because of the risk for progressive or congenital TB, pregnant women who have a positive tuberculin skin test or who have negative skin-test results but who had recent contact with someone who has infectious TB disease should have chest x-rays (with appropriate shielding) as soon as feasible, even during the first trimester of pregnancy (Geiter, Gordin, Hershfield, et. al., 2000).

If chest x-rays are normal and the person is asymptomatic, a tuberculin-positive person may be a candidate for treatment of LTBI. If radiographic or clinical findings are consistent with pulmonary or extrapulmonary TB, further studies should be done to determine if treatment for active TB is indicated (Geiter, Gordin, Hershfield, et. al., 2000).

Sputum Examinations

Sputum examination is not indicated for most people being considered for treatment of LTBI. However, people with chest radiographic findings suggestive of prior, healed TB infections should have three consecutive sputum samples, obtained on different days, submitted for AFB smear and culture. HIV-infected persons with respiratory symptoms who are being considered for treatment of LTBI should also have sputum specimens submitted for mycobacterial examination, even if the chest x-ray is normal.

The presumptive diagnosis of active pulmonary TB is often made on the basis of microscopic examination of a stained sputum smear for acid-fast bacilli (AFB). Confirmation of the diagnosis usually requires identification of m. tuberculosis in culture. In asymptomatic persons with normal chest x-rays, AFB are rarely seen on sputum smear examination and cultures of the respiratory specimens are usually negative for TB. However, some HIV-infected persons with sputum culture-positive TB have been described as having normal chest x-rays (Geiter, Gordin, Hershfield, et. al., 2000).

Sputum Specimen Collection for Suspected Pulmonary TB:

	Collect at least 5ml. of sputum
	Collect 3 specimens, each on a different day
	Early morning specimens are preferable
	Instruct the patient to produce a deep cough specimen to avoid sampling saliva
	A nebulizer may be used to induce a sputum specimen, if the patient’s cough is nonproductive

If the results of sputum smears and cultures are negative and respiratory symptoms can be explained by another etiology, the person is a candidate for treatment of LTBI. If bacteriologic results are negative but the activity or etiology of a radiographic abnormality is questionable, further evaluation with bronchoscopy or needle aspiration biopsy should be undertaken. Single drug treatment of LTBI should not be started until active TB has been excluded. In such situations, multi-drug therapy can be started and continued pending results of sputum cultures. A repeat chest film should be obtained to exclude active TB, as indicated by improvement in the abnormality even in the presence of negative cultures (Geiter, Gordin, Hershfield, et. al., 2000).

Treatment

Today, tuberculosis is relatively easy to diagnose; when the right combination of medications is made available and taken by the patient, the disease can be cured more than 95% of the time (Murray, 2004). Directly observed therapy is now routinely recommended for treatment of TB in the U.S. to assure compliance and reduce the risk of drug resistant TB (Griffith, 2004). This has proven effective in preventing new drug-resistant cases in the US; however, more than 50% of new TB cases and approximately 69% of the multidrug-resistant TB cases were diagnosed in persons born outside the US, who presumably acquired drug-resistant TB before entering the U.S. (Griffith, 2004).

Active TB

Active TB disease may require a multi-drug regime. This does a better job of killing all of the bacteria and preventing drug resistance. The most common drugs used to treat active TB disease are (CDC, 2001):

Serious side effects of these drugs are rare. When they occur, it should be reported to a physician and may require that treatment be discontinued. The serious side effects of the common drugs used to treat active TB disease are (CDC, 2001):

Minor side effects of these medications do not require an interruption of treatment. They are (CDC, 2001):

	Rifampin can turn urine, saliva, or tears orange. Soft contact lenses may become stained, so they should not be worn.
	Rifampin can make you more sensitive to the sun. A good sunscreen should be used and exposed areas should be covered to avoid sunburn.
	Rifampin also makes birth control pills and implants less effective. Women who take rifampin should use another form of birth control.
	Methadone withdrawal symptoms may occur when Rifampin is started. The methadone dosage may need to be adjusted.

Drug-Resistant TB

Because of the long course of treatment, compliance with the medication regime must be stressed and reinforced. Noncompliance with irregular use or discontinuation of treatment too early can lead to drug-resistant bacteria.

Causes for noncompliance can be varied, but the following are common causes. The concept of taking medicine to treat a latent infection that is not causing current health problems is unfamiliar to most people, so education of the patient is essential (Harborview, 2002). Other barriers include cultural health beliefs that differ from those of Western medicine, inability to communicate with medical providers in one's primary language, inability to afford the costs of medical evaluation and treatment, and lack of access to medical care (Carey, Oxtoby, Nguyen, Huynh, Morgan & Jeffery, 1997).

Sometimes the bacteria become resistant to more than one drug. This is called multi-drug resistant TB (MDR TB). This is a very serious problem. The drugs used to treat MDR TB are not as good as the usual drugs for TB and they may cause more side effects.

Drug-resistant TB is more common in people who (CDC, 2001):

	Have spent time with someone with drug-resistant TB disease
	Do not take their medicine regularly
	Do not take all of their prescribed medicine
	Develop TB disease again, after having taken TB medicine in the past
	Come from areas where drug-resistant TB is common

For LTBI after exposure to INH-resistant, rifampin-susceptible TB, rifampin and pyrazinamide should be given daily for 2 months. For patients with intolerance to pyrazinamide, give rifampin daily for 4 months (Geiter, Gordin, Hershfield, et. al., 2000).

For people who are likely to be infected with INH-resistant and rifampin-resistant TB and who are at high risk for developing TB, pyrazinamide and ethambutol or pyrazinamide and a quinolone for 6-12 months are recommended. Immunocompetent people may be observed or treated for at least 6 months, and immunocompromised people should be treated for 12 months.

LTBI

Elimination of tuberculosis in industrialized nations hinges on diagnosis and treatment of LTBI to prevent disease (Barnes, 2004). People in high-risk groups with LTBI need to take medicine to keep from developing TB disease. The medicine usually used for the treatment of LTBI is isoniazid (INH) (CDC, 2001). INH must be taken for at least 6 to 9 months (CDC, 2001). Treatment is recommended for foreign-born persons from countries with a high prevalence of TB who have LTBI and who have been in the US less than five years (CDC, 2000). After five years, treatment decisions should be made on the same basis as other patients. Treatment may be given to high-risk groups even if the skin test is negative. This is most often done with infants, children, and HIV-infected people who are exposed (CDC, 2001).

When INH is used for treatment of LTBI in people with HIV infection or people with radiographic evidence of prior TB, nine months of treatment rather that six months is recommended (Geiter, Gordin, Hershfield, et. al., 2000). For pregnant, HIV-negative women, give INH daily or twice weekly for six or nine months. For women at risk for progression of LTBI to TB disease, especially those who are infected with HIV or who have likely been infected recently, initiation of therapy should not be delayed based on the pregnancy alone, even during the first trimester. For women with lower risk for active TB, some experts recommend waiting until after delivery to start treatment (Geiter, Gordin, Hershfield, et. al., 2000). For children and adolescents, INH should be given either daily or twice weekly for nine months (Geiter, Gordin, Hershfield, et. al., 2000).

Active hepatitis and end-stage liver disease are relative contraindications to the use of INH or pyrazinamide for treatment of LTBI (Geiter, Gordin, Hershfield, et. al., 2000). Idiosyncratic liver injury can be caused by hypersensitivity or by toxic drug metabolites. Various medicines and alcohol have been implicated as potential co-factors for INH liver injury.

Monitoring

Patients should be educated about medication side effects and advised to stop the medication and promptly seek medical evaluation when they occur (Geiter, Gordin, Hershfield, et. al., 2000). Patients should be frequently reminded about the initial symptoms of hepatitis: fatigue, nausea, abdominal pain, and anorexia, and the importance of stopping medication if symptoms develop.

Baseline laboratory testing is not routinely needed. Patients whose initial evaluation suggests a liver disorder should have baseline hepatic measurements of serum aspartate aminotransferase (serum glutamic oxaloacetic transaminase) (AST [SGOT]) or alanine aminotransferase (serum glutamic pyruvic transaminase) (ALT [SGPT]) and bilirubin. Baseline testing is also indicated for patients with HIV infection, a history of chronic liver disease, who use alcohol regularly, at risk for chronic liver disease, pregnant women, and women in the immediate postpartum period. Baseline testing in older persons may be considered, particularly for patients who are taking other medications for chronic medical conditions (Geiter, Gordin, Hershfield, et. al., 2000).

Routine laboratory monitoring during treatment is indicated when baseline liver function tests are abnormal or there is a risk for hepatic disease. Laboratory testing may also be indicated for the evaluation of adverse effects of treatment. Liver function studies should be done for patients with symptoms compatible with hepatotoxicity. A uric acid measurement should be done to evaluate complaints of joint pain. Some experts recommend that INH should be withheld if transaminase levels exceed three times the upper limit of normal and the person is symptomatic; or five times the upper limit of normal if the patient is asymptomatic (Geiter, Gordin, Hershfield, et. al., 2000).

Airborne Precautions

In a healthcare facility, patients with suspected or confirmed TB must be isolated using Airborne Precautions. This type of precaution is implemented for diseases that are transmitted by microorganisms in airborne droplet nuclei. Droplet nuclei are tiny particle residues left when droplets evaporate. Droplet nuclei remain suspended in the air and can be widely dispersed by air currents. Airborne precautions must be ordered for patients with:

Airborne precautions require a specially ventilated room with at least six air changes per hour; negative air pressure relative to the hallway; and outside exhaust or HEPA-filtered recirculation. The door to the room must be kept closed. A N-95 mask or a powered air-purifying respirator (PARP) is used in airborne precautions.

	These masks and respirators should be labeled and stored in a paper bag between uses.
	These mask and respirators should be discarded if soiled or if it no longer maintains it’s structural or functional integrity.
	The N-95 mask should also be discarded at the end of each work shift.
	The disposable respirator should be discarded at the end of 2 weeks.

When the patient in airborne precautions has to be moved or transported, the patient should wear a surgical mask from the time he leaves the isolation room, until he returns.

Airborne precautions for suspected TB must be continued until three sputum specimens, collected on different days, have negative AFB smears.

With confirmed TB, airborne precautions must continue, during treatment, until there is clinical improvement and three sequential AFB smears are negative.

Precautions to Take at Home During Treatment

The following are instructions for patients with active TB disease to reduce disease transmission during treatment at home (CDC, 2001):

	Take your medicine as directed.
	Cover your mouth with a tissue when coughing, sneezing, or laughing. Put the tissue in a closed paper sack and throw it away.
	Separate yourself from others and avoid close contact with anyone. Do not go to work or school. Sleep in a bedroom away from others.
	TB spreads in small closed spaces where air doesn't move. Air out your room often, to the outside of the building. Put a fan in your window to blow air out of the room. If you open other windows in the room, the fan also will pull in fresh air.

After two or three weeks of medication, you may no longer be able to spread TB bacteria to others.

Role of the Health Department

TB must be reported to the local health department. In a community-based approach to targeted testing and treatment of LTBI, the health department should be planning, coordinating, setting performance standards, and overseeing quality of service. The health department is responsible for:

A community-based program should be monitored with indicators like rates of skin tests administered that are read, proportion of tests read that are positive, and initiation and completion rates of treatment. The health department should routinely collect and review these data to determine yield and relative effectiveness of targeted testing and treatment of LTBI in the community.

Pregnancy and Lactation

Pregnancy has little influence on the pathogenesis of TB or the likelihood of LTBI progressing to TB disease. There is no evidence that the tuberculin skin test has adverse effects on the pregnant mother or fetus. Pregnant women should be targeted for tuberculin skin testing only if they have a specific risk factor for LTBI or for progression of LTBI to TB disease. Although the need for treatment of active TB during pregnancy is unquestioned, the treatment of LTBI in pregnant women is controversial. Some experts prefer to delay treatment until after delivery because pregnancy itself does not increase the risk of progression to disease, and two studies suggest that women in pregnancy and the early postpartum period may be vulnerable to INH hepatotoxicity (CDC, 2001). However, because conditions that promote hematogenous spread of organisms to the placenta (e.g., recent infection and HIV infection) or progression of LTBI to disease can endanger both the mother and baby many experts agree that pregnant women with these conditions and LTBI should be treated during pregnancy and have careful clinical and laboratory monitoring for hepatitis.

INH readily crosses the placental barrier, but the drug is not teratogenic even when given during the first four months of gestation. Teratogenesis is the production of deformity in the developing embryo. Hemorrhagic disease of the newborn has been described following the use of rifampin in the mother. However, extensive experience with the use of rifampin to treat TB in pregnant women suggests it is safe in most circumstances. Although pyrazinamide has been used to treat TB in pregnant women, no published data exist concerning the effects of the drug on the fetus. Thus, although pyrazinamide may be considered after the first trimester in women with HIV infection, it should otherwise be avoided.

Toxic effects of antituberculosis drugs delivered in breast milk have not been reported. One study concluded that a breastfeeding infant would develop serum levels of no more than 20% of the usual therapeutic levels of INH for infants and less than 11% of other antituberculosis drugs. Breastfeeding is not contraindicated when the mother is being treated for LTBI. However, infants whose breastfeeding mothers are taking INH should receive supplemental pyridoxine. The amount of INH provided by breast milk is inadequate for treatment of the infant.

Children and Adolescents

Infants and children younger than five with LTBI have been infected recently and are at high risk for progression to disease. Data suggest that untreated infants with LTBI have up to a 40% likelihood of developing TB. The risk for progression decreases gradually through childhood. Infants and young children are more likely than older children and adults to develop life-threatening forms of TB, especially meningeal and disseminated disease. Children with LTBI have more years at risk to develop TB than adults. INH therapy for LTBI appears to be more effective for children than adults, with several large clinical trials demonstrating risk reduction of 70-90%. The risk for INH-related hepatitis is minimal in infants, children, and adolescents, who generally tolerate the drug better than adults. INH therapy is widely accepted for use in children.

Conclusion

New case of TB is at its lowest level ever in the US; however, TB continues to be a problem in the US in immigrant populations, in elderly individuals with reactivating latent infection, and in local outbreaks. Elimination of tuberculosis in the US hinges on diagnosis and treatment of latent tuberculosis infection to prevent disease. Appropriate treatment protocols must be followed and directly observed therapy should be done for treatment of TB to prevent the development of drug resistant TB. When appropriate, airborne precautions must be implemented to prevent transmission in a healthcare facility.

References

Anonymous, (2004). Racial disparities in Tuberculosis-selected southeastern states, 1991-2002. MMWR, Morbidity and Mortality Weekly Report. 53(25), 556-560. Retrieved August 4, 2004 from ProQuest.

Barnes, P. (2004). Diagnosing latent Tuberculosis infection: Turing glitter to gold. American Journal of Respiratory and Critical Care medicine. 170(1), 5 Retrieved August 4, 2004 from ProQuest.

Brock, I., Welding, K., Lillebaek, T., Follmann, F., & Anderson, P. (2004). Comparison of Tuberculin skin test in Tuberculosis contact. American Journal of Respiratory and Critical Care Medicine. 170(1), 65 Retrieved August 4, 2004 from ProQuest.

Carey, J. W., M. J. Oxtoby, L. P. Nguyen, V. Huynh, M. Morgan, and M. Jeffery. 1997. Tuberculosis beliefs among recent Vietnamese refugees in New York State. Public Health Rep. 112:66--72.

CDC (2003). Reported Tuberculosis in the United States, 2002. Retrieved August 4, 2004 from http://www.cdc.gov/nchstp/tb/surv/surv2002/default.htm.

CDC (2000) Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Resp Crit Care Med 161:S221--S247.

CDC. (2000b) Fatal and Severe Hepatitis Associated With Rifampin and Pyrazinamide for the Treatment of Latent Tuberculosis Infection --- New York and Georgia, MMWR; 50 (15).

CDC. (1999). 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: U.S. Public Health Service (USPHS) and Infectious Diseases Society of America (IDSA). M.M.W.R. 48(No. RR-10):13--14.

Geiter, LJ, Gordin, FM, Hershfield, E, et. al. (2000).Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection, ATS/CDC Statement Committee on Latent Tuberculosis Infection Membership List, June 2000 the American Journal of Respiratory and Critical Care Medicine 161:S221--S247.

Gordin F, Chaisson RE, Matts JP, et al. (2000). Rifampin and pyrazinamide versus isoniazid for prevention of tuberculosis in HIV infected persons: an international randomized trial. JAMA 283:1445--50.

Griffith, D. (2004). Treatment of multidrug-resistant Tuberculosis: Should you try this at home? American Journal of Respiratory and Critical Care Medicine. 169(10), 1082-1084. Retrieved August 4, 2004 from ProQuest.

Harborview Medical Center, (2002) University of Washington. Ethnic Medicine Guide. , http://www.hslib.washington.edu/clinical/ethnomed/.

Murray, J. (2004). A century of Tuberculosis. American Journal of Respiratory and Critical Care Medicine. 169(11) m 1181-1187. Retrieved August 4, 2004 from ProQuest.

Questions and Answers about TB – 2000, Last Reviewed: December 22, 2001, Centers for Disease Control & Prevention, National Center for HIV, STD, and TB Prevention, Division of Tuberculosis Elimination®