COURSE INTRODUCTION Many people think that tuberculosis is a disease of the past. However, tuberculosis is still a leading killer worldwide. One third of the world s population is infected with tuberculosis. Three million people die each year. This CE module will review the history of tuberculosis, the importance of tuberculosis in today s world, the epidemiology of the disease, and guidelines set forth by The Centers for Disease Control and Prevention and the Occupational Health and Safety Administration to prevent work-related transmission of tuberculosis. Ver 6.0 January 2012 1
2006 COURSE TITLE: TUBERCULOSIS: FROM CONSUMPTION TO MOLECULAR DIAGNOSIS Author: Lucia Johnson, MA Ed, CLS(NCA), MT(ASCP)SBB Director of Continuing Education National Center for Competency Testing Number of Clock Hours Credit: 3.0 Course # 1225914 P.A.C.E. Approved: _ Yes _X_ No Course Objectives Upon completion of this CE module, the professional will be able to: 1. Describe tuberculosis from an historical perspective. 2. Name the bacterium that causes tuberculosis. 3. Describe how tuberculosis is transmitted from person to person. 4. Describe tuberculosis disease. 5. Compare and contrast latent and active tuberculosis. 6. Describe how tuberculosis is diagnosed. 7. List four drugs used to treat tuberculosis. 8. Describe tuberculosis prevention and screening programs. 9. Describe administrative, work practice, and engineering controls used to prevent the spread of tuberculosis in the healthcare environment. 10. Identify the seriousness of multidrug-resistant tuberculosis. Disclaimer The writers for NCCT continuing education courses attempt to provide factual information based on literature review and current professional practice. However, NCCT does not guarantee that the information contained in the continuing education courses is free from all errors and omissions. 2
INTRODUCTION After several years of decline, the United States experienced an increase of tuberculosis (TB) in 1989. The increase was attributed to the expansion of HIV infection, hospital-acquired transmission of tuberculosis, multi-drug resistant TB, and increasing immigration from countries with a high incidence of TB. Government agencies realized that the infrastructure for TB control had deteriorated over the years. The problem was corrected by an increase of resources at the national, state, and local levels. As a result, the increasing incidence of TB was arrested; during 1993--2003, an uninterrupted 44% decline in incidence occurred, and in 2003, TB incidence reached an historic low level in the United States. Tuberculosis is, however, still a problem; more than 14,000 cases were reported in the United States in 2003. Worldwide, TB threatens one-third of the world s population. Nine million new cases of active disease occur annually, resulting in three million deaths, mostly in developing countries. HISTORICAL PERSPECTIVE Skeletal remains show that prehistoric humans (4000 BC) had tuberculosis. Tubercular decay has been found in the spines of Egyptian mummies from 3000-2400 BC. There are references to TB in India around 2000 BC and evidence exists that TB was present in the Americas from about 2000 BC. The disease was not named tuberculosis until 1839. Throughout history, it has been known as: consumption (TB seemed to consume people with its symptoms of bloody cough, fever, pallor, and long relentless wasting), wasting disease (people wasted away), white plague (TB sufferers appeared markedly pale), phthisis (Greek for consumption), and scrofula (swollen neck glands). Tuberculosis claimed the lives of many famous individuals including Ralph Waldo Emerson, Edgar Allen Poe, Paul Gauguin, Wolfgang Amadeus Mozart, Ulysses S. Grant, Eleanor Roosevelt, Florence Nightingale, and Vivien Leigh. Historical Key Facts In 1882, Robert Koch described the bacteria causing tuberculosis, Mycobacterium tuberculosis. For this discovery, he received the Nobel Prize for medicine. Once it was established that TB was contagious, infected persons were encouraged to enter sanitariums that more closely resembled prisons. Three fourths of those who entered a sanitarium were dead within 5 years. TB lead to campaigns stop spitting in public places in both England and the U.S. Improvements in public health lead to the reduction of TB even before the arrival of antibiotics. In Europe, deaths from TB fell from 500 out of 100,000 to 50 out of 100,000 by 1950. It was not until 1946 with the development of the antibiotic streptomycin that treatment rather than prevention became a possibility. 3
THE DISEASE The Organism The cause of tuberculosis is Mycobacterium tuberculosis, a slow-growing aerobic bacterium. It may take up to six weeks for the organism to grow in culture. This is extremely slow compared to other bacteria that can be grown in culture within 24 hours. M. tuberculosis is a small rod-like bacillus that stains very weakly Gram positive or does not stain at all. M. tuberculosis is identified microscopically after being treated with acidic solutions and is, therefore, classified as an acid-fast bacillus (AFB). Transmission TB is spread through the air from one person to another. The bacteria are put into the air when droplets (called droplet nuclei) come out of the mouth of an infected person when he/she coughs, sneezes, speaks, or spits. The droplets contain infectious bacteria. People nearby may breathe in the infectious droplets and become infected. Close contacts (people with prolonged, frequent, or intense contact such as family members, friends, and coworkers) are at highest risk of becoming infected. A person with untreated, active TB can infect an estimated 20 other people per year. Others at risk for infection are: foreign-born individuals from areas where TB is common, immunocompromised patients (such as those with HIV/AIDS), residents and employees of high-risk settings such as nursing homes, prisons and healthcare facilities, homeless people, people who inject illegal drugs, and medically underserved, low-income populations. TB Disease About five percent of infected persons with a normal immune system will develop TB disease within the first two years, and another five percent will develop the disease later in life. In all, about 10 percent of infected persons with normal immune systems will develop TB disease in their lifetime. Certain medical conditions increase the risk of developing TB disease to about 10 percent each year. This includes the high risk groups listed above and those individuals with leukemia, Hodgkin s disease, malabsorption syndromes, end-stage renal disease, head and neck cancers, diabetes mellitus, prolonged corticosteroid therapy, and more. TB most often infects the lungs, where it is causes pulmonary TB. The bacteria destroy tissue in the lungs eventually causing permanent damage. In many patients, the infection waxes and wanes. Tissue destruction is balanced by tissue healing. As the disease progresses, acute respiratory inflammations develop leading to lesions and fluid in the lungs. These lesions often create masses of dead tissue that harden forming tubercles. In more serious cases, the organisms spread to other areas of the body infecting bones, the brain, and reproductive, urinary, and digestive organs. Without treatment, death is inevitable. 4
Latent TB Infection Most people who become infected with TB are able to fight off the bacteria and stop them from growing. The bacteria become inactive but remain alive in the body. The bacteria can become active later. This is called latent TB infection. People with latent TB: have no symptoms, do not feel sick, cannot spread TB to others, have a normal chest x-ray, have a negative laboratory culture, usually have a positive skin test, and can develop active TB disease if they do not receive treatment. Many people with latent TB never develop active TB. In other people, the bacteria become active and cause TB disease. Active TB Disease When the body cannot stop the bacteria from growing, the bacteria begin to multiply and destroy tissue. This is called active TB disease. Some people develop active TB soon after becoming infected. Other may get sick months to years later. Persons with active TB disease: Have symptoms such as a productive prolonged cough of more than three weeks (productive = brings up sputum from the lungs), chest pain, hemoptysis (coughing up blood), fever, chills, night sweats, appetite loss, weight loss, and fatigue. spread TB to others, usually have a positive skin test, have an abnormal chest x-ray, have a positive laboratory culture, and must be treated to cure the disease. 5
Other TB Disease If TB bacteria gain entry to the blood stream, the disease can spread throughout the body. This is called miliary tuberculosis and it has a high death rate. Tuberculosis can also occur in the central nervous system, bones/joints, urinary tract, genital tract, gastrointestinal tract, heart, and lymphatic system. Patients with infections in areas other than the lungs, have symptoms that depend upon where the bacteria are multiplying. This can include bone compression fractures, destruction of the ureters, destruction of the fallopian tubes, swollen lymph nodes, meningitis, etc. Diagnosis A complete medical evaluation for TB includes a medical history, a physical examination, a tuberculin skin test, a chest x-ray, laboratory serologic tests, and microbiologic studies. Medical history Productive prolonged cough lasting at least 3 weeks Chest pain Hemoptysis Fever, chills, night sweats, appetite loss, weight loss, fatigue Persistent respiratory illness in an otherwise healthy individual that does not respond to regular antibiotics Physical exam Appearance consistent with symptoms listed above Chest X-ray Abnormalities may be suggestive of, but are never diagnostic of, TB. In active pulmonary TB, infiltrates or consolidations and/or cavities are often seen in the upper lungs with or without lymphadenopathy or pleural effusions. Diffuse tiny nodules throughout the lungs (miliary TB) Tuberculin skin test The Mantoux skin test is used in the U.S. This test used purified protein derivative (PPD) from M. tuberculosis. An induration (palpable raised hardened area of skin) of more than 5 15 mm to 10 Mantoux units is considered a positive result and indicates TB infection. False positive reactions can occur if the person has been vaccinated for TB. Laboratory serologic tests FDA approval of the QuantiFERON-TB Gold serologic test for latent or active M. tuberculosis is expected in December of 2005. This test measures interferon released from whole blood lymphocytes sensitized to purified protein derivative (PPD). This test will most likely replace the tuberculin skin test in the near future. It is not subject to false positive reactions due to TB vaccination. A positive test result indicates that infection with M. tuberculosis is likely; a negative result indicates that infection with M. tuberculosis is unlikely. Microbiology studies Acid-fast bacillus smears are positive only during advanced tuberculosis, Culture of bacteria is the "gold standard" for tuberculosis diagnosis, but M. tuberculosis may require up to six weeks to grow on culture medium. Molecular diagnostic techniques, such as the polymerase chain reaction, can detect antigens to M. tuberculosis in a few hours with a high degree of sensitivity and specificity. However, molecular assays neither replace nor reduce the need for conventional smear and culture, speciation, and antibiotic sensitivity assays. Positive molecular diagnostic tests provide the physician with information that can be used to treat the disease until the culture and sensitivity are completed. 6
Treatment With appropriate antibiotic treatment, TB can be cured in more than nine out of ten patients. Successful treatment depends on close cooperation between the patient, the doctor, and other healthcare workers. Treatment usually combines several different antibiotic drugs that are given for at least six months, sometimes for as long as 12 months. Frequently used medications are: isoniazid (INH), rifampin (RIF), ethambutol, and pyrazinamide. Patients with both latent and active TB must be treated. However, the treatment options are different. LATENT TB Isoniazid for 9 months (270 doses within 12 months) is optimal regimen. Isoniazid for 6 months (180 doses within 9 months) when costeffectiveness and patient compliance are issues. Rifampin for 4 months (alternative for those who are unable to take isoniazid or pyrazinamide). ACTIVE TB The current accepted optimal drug regimen is a combination of rifampin, isoniazid, ethambutol, and pyrazinamide taken for two months followed by two months of rifampin and isoniazid. If the initial 4-drug therapy fails, Streptomycin is used in conjunction with capreomycin, cycloserine, new macrolides, quinolones, and protionamide. Approximately 20-25% of patients have adverse drug reactions. However, only 5% of all patients have a reaction severe enough to change the drug regimen. The development of hepatitis is the most significant of the drug reactions. Other drug reactions include: loss of appetite, nausea, vomiting, fever for more than 3 days, abdominal pain, tingling of fingers or toes, skin rash, easy bleeding, aching joints, dizziness, tingling or numbness around the mouth, ringing in the ears, blurred or changed vision, and hearing loss. 7
All of these side effects are serious and should be immediately reported to a doctor or nurse. Drug regimens may need to be changed to eliminate the drug reactions. Minor problems may also occur but these do not require a change in the drug regimen: Rifampin can turn urine, saliva, or tears orange. Rifampin can make the patient more sensitive to the sun. Rifampin makes birth control pills and implants less effective. Therefore, other forms of birth control may be required. Treatment of both latent and active TB should be monitored monthly for adherence to the drug regimen and signs/symptoms of active TB. Patients with active TB should have cultures performed monthly until no organisms grow. If after three months of drug treatment, the cultures remain positive and/or symptoms do not resolve, the patient should be evaluated for potential multi-drug resistant TB or non-adherence to the drug protocol. If non-compliance to drug regimens is suspected, the World Health Organization (WHO) recommends a treatment called DOTS for Directly Observed Treatment, Short course. DOTS involves healthcare workers directly monitoring tuberculosis patients actually swallowing their tuberculosis drugs for at least the first two months of treatment. DOTS has a success rate exceeding 95% and prevents the emergence of multi-drug resistant strains of tuberculosis. Multi-drug resistant TB will be reviewed later. The Food and Drug Administration has approved Rifater, a medication that combines the three main drugs (isoniazid, rifampin, and pyrazinamide) into one pill. This reduces the number of pills a person needs to take each day thus improving patient compliance with drug therapy. The Food and Drug Administration has also approved the first new drug for TB in 25 years. The drug, rifapentine (Priftin), has been approved for use with other drugs to fight TB. One advantage of rifapentine is that it can be taken less often in the final four months of treatment, thus improving patient compliance with drug therapy. Prevention Prevention and control efforts include three strategies: Identifying and treating all persons who have TB disease, Finding and evaluating persons who have been in contact with TB patients to determine if they have TB infection or disease, and treating them appropriately, and Testing high-risk groups for TB infection to identify candidates for treatment of latent TB infection and to assure the completion of treatment. Many countries use a TB vaccine as part of their TB control program, especially for infants. The United States does not routinely provide vaccination for TB. The TB vaccine is efficient in preventing serious forms of TB in children and is useful in developing countries where the disease is prevalent. 8
TB Screening Programs The most common method of screening for exposure to TB is a skin test. With this test, minute quantities of purified protein derivative (PPD), a noninfectious TB antigen, are injected just under the skin on the forearm. If an individual has been exposed to and infected with TB, the skin surrounding the injection site will become red and swollen within 48 hours. This is a positive test. Further testing and treatment is necessary to prevent the person from developing active TB. An individual should be skin tested for TB if he/she has had a cough for longer than three weeks, shows any symptoms of TB, or is in a high-risk group. HEALTHCARE WORKERS AND TUBERCULOSIS By the spring of 1993 when TB was once again on the increase in the U.S., the Centers for Disease Control and Prevention (CDC) knew of more than 100 cases of active TB disease in health care workers that were acquired from the workplace. Twelve health care workers died. Nationwide, several hundred health care workers have become infected and required medical treatment after workplace exposure to TB. In 1994, the CDC published Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Healthcare Facilities. The purpose of the document was to describe the importance of administrative and engineering controls, personal respiratory protection, risk assessment, development of a written tuberculosis control plan, early detection, management of persons with tuberculosis, purified protein derivative (PPD) skin testing, and employee education. Specific information regarding the CDC guidelines follows. Administrative and Work Practice Controls early identification and treatment of persons with TB, isolation of infected persons, screening and medical surveillance of persons at risk, including health care workers, use of adequate respiratory protection by health care workers, education of patients about hygiene practices (such as covering the nose and mouth with tissue when they sneeze or cough), compliance with treatment protocols, and per Transmission Based Precautions, warnings must be posted outside a respiratory isolation room stating "Airborne Precautions. These precautions are designed to provide protection from extremely tiny airborne bacteria or dust particles, which may be suspended in the air for an extended period. Guidelines include the use of respiratory protection and the use of special air handling systems to control the airborne bacteria. For respiratory protection, a properly fitted N95 particulate respiratory mask must be worn when entering the room of a person known or suspected to have active tuberculosis. 9
Engineering Controls isolating patients with active TB in a negative-pressure room with a minimum of 6 air changes per hour, exhaust ventilation in the room where an infected patient is, directing air flow away from adjoining, non-infected areas/rooms, diluting contaminated air with clean air and removing contaminants through general ventilation, cleaning the air using air filtration or ultraviolet radiation units, and keeping isolation room doors closed at all times. Employee Training Employers are required to educate employees regarding tuberculosis that is relevant to their work-related duties. This training should to be conducted before their initial work assignment and annually thereafter. Recommended training content includes: the danger of TB transmission in the workplace, signs and symptoms of TB, medical observation and treatment of patients with TB, how to use protective respiratory equipment. For more information about respiratory personal protective equipment, refer to CE Course 1220506 Personal Protective Equipment. the procedure for working in a contaminated area or in close contact with infectious TB patients, and medical testing programs for employees. Periodic screening of health care personnel (at least annually, more often for high risk personnel) by using the skin test is necessary for early detection and treatment. If an individual receives a work-related exposure to TB, the employer must provide him/her with a baseline skin test immediately and again in 10 weeks. If employees are required to use respiratory protection to protect themselves from TB exposure, their employer must follow the Occupational Health and Safety Administration (OSHA) general industry standard 29CFR1910.134. To meet the requirements of this standard, employers need to create a written respiratory protection program, conduct annual respirator fit testing, and perform a medical evaluation and annual respirator training for those employees using respirators. MULTIDRUG-RESISTANT TUBERCULOSIS Multidrug-resistant tuberculosis is a form of TB that is resistant to two or more of the primary drugs used for the treatment of TB. Multidrug-resistant TB (MDR TB) occurs in the same manner as other bacteria that acquire drug resistance. (For more information, refer to CE Course 1220806 Antibiotic Resistance.) Resistance may also develop during TB therapy due to inadequate antibiotic treatment, failure of the patient to take the antibiotics as scheduled, or using low quality antibiotics. In 2003, the CDC reported that 7.7 % of tuberculosis cases in the U.S. were resistant to isoniazid. The CDC reported that 1.4 % of tuberculosis cases in the U.S. were resistant to both isoniazid and rifampin. 10
Over 44 % of the MDR TB cases were reported from New York City, California, and Texas. The World Health Organization estimates that up to 50 million persons worldwide may be infected with MDR TB. MDR TB is a particular concern among HIV-infected persons. HIV-infected persons with MDR TB appear to have a more rapid and deadly disease course. As many as eight out of ten may die, often within months of diagnosis. MDR TB is more difficult to treat than other types of TB. The success of treatment depends upon how quickly it is determined that the bacteria is drug resistant and whether effective drug therapy is available. Tests to determine resistance usually take several weeks to complete. Second-line drugs used in cases of MDR TB are often less effective and more likely to cause side effects. When second-line drugs must be used to treat MDR TB, the cure rate decreases from over 90 % to less than 50 %. CONCLUSION Tuberculosis remains a major cause of illness and death worldwide. The number of TB cases in the United States has decreased in the last few years due to effective screening, prevention, and treatment programs. However, the resurgence of cases seen in the late 1980s and early 1990s demonstrates what can happen when programs such as these are allowed to lapse. With the development of multidrug-resistant tuberculosis and the huge numbers of people with the disease worldwide, healthcare workers must be knowledgeable about tuberculosis safety practices to protect themselves on the job. REFERENCES The Centers for Disease Control and Prevention. Tuberculosis for Healthcare Workers. www.cdc.gov/niosh Wikipedia. Tuberculosis. http://en.wikipedia.org/wiki/tuberculosis Occupational Health and Safety Administration. Fit testing requirements for employees who wear respirators to protect against M. tuberculosis, SARS, Smallpox and Monkeypox. www.osha.gov The Centers for Disease Control and Prevention. Questions and Answers About TB. www.cdc.gov American Lung Association. Multidrug-Resistant Tuberculosis Fact Sheet. www.lungusa.org National Institute of Allergy and Infectious Diseases. Tuberculosis. www.niaid.nih.gov 11
TEST QUESTIONS Tuberculosis: From Consumption to Molecular Diagnosis # 1225914 Directions: Before taking this test, read the instructions on how to complete the answer sheets correctly. If taking the test online, log in to your User Account on the NCCT website www.ncctinc.com. Select the response that best completes each sentence or answers each question from the information presented in the module. If you are having difficulty answering a question, go to www.ncctinc.com and select Forms/Documents. Then select CE Updates and Revisions to see if course content and/or a test questions have been revised. If you do not have access to the internet, call Customer Service at 800-875-4404. 1. The United States experienced an increase of tuberculosis cases in the late 1980s. a. True b. False 2. Which of the following historic names is NOT a name for tuberculosis? a. consumption b. scrofula c. white plague d. whooping cough 3. All of the following are associated with the organism that causes tuberculosis EXCEPT. a. acid fast b. organism name is Mycoplasma tuberculosis c. small bacillus d. very slow to grow in culture 4. About what percent of tuberculosis infected persons with normal immune systems will develop tuberculosis disease within two years? a. 5 % b. 10 % c. 15 % d. 20 % 5. What percent of tuberculosis infected persons in high risk groups will develop tuberculosis disease within one year? a. 5 % b. 10 % c. 15 % d. 20 % 12
6. Tuberculosis disease most often affects the. a. bone b. brain c. lungs d. reproductive system 7. All of the following are groups of people at increased risk of tuberculosis infection EXCEPT. a. diabetic persons b. HIV positive persons c. homeless persons d. surgery patients 8. Which of the following statements is TRUE regarding persons with latent tuberculosis infections? a. They can spread the disease. b. They have symptoms of tuberculosis. c. They usually have positive laboratory culture test. d. They usually have a positive skin test. 9. Everyone who has latent tuberculosis will eventually develop active tuberculosis. a. True b. False 10. Persons with latent tuberculosis do not need to receive treatment. a. True b. False 11. Symptoms of active tuberculosis include all of the following EXCEPT. a. bone pain b. chest pain c. coughing up blood d. prolonged cough of at least 3 weeks 12. An induration of more than mm is a positive Mantoux skin test. a. 2 b. 3 c. 4 d. 5 13
13. Which of the following drugs are used with pyrazinamide for initial treatment of active tuberculosis? a. ethambutol b. isoniazid c. rifampin d. all answers are correct 14. Patients with active TB are treated with combined with various other drugs if the initial four-drug therapy does not work. a. ethambutol b. penicillin c. streptomycin d. vancomycin 15. Noncompliance with prescribed drug regimens increases the chance of the patient developing multidrug-resistant tuberculosis. a. True b. False 16. In the United States, tuberculosis prevention and control efforts include all of the following EXCEPT. a. finding and identifying persons who have been in contact with persons with TB so they can be treated as appropriate b. identifying and treating all persons with TB c. testing high-risk groups to identify persons who need treatment d. vaccinating persons in high-risk groups 17. Healthcare workers are at risk for workplace exposure to tuberculosis. a. True b. False 18. Per OSHA, employers must provide annual respirator fit testing and training to those employees who are required to protect themselves against tuberculosis. a. True b. False 14
19. All of the following statements are TRUE regarding multidrug-resistant tuberculosis EXCEPT. a. HIV-infected persons with multidrug-resistant TB have a more rapid and deadly disease course b. Over 44% of persons in the U.S. infected with TB have a multidrug-resistant strain of TB c. Second-line drugs used to treat multidrug-resistant TB are more likely to cause side effects d. The cure rate decreases when second-line drugs must be used to treat multidrug-resistant TB 20. In the U.S. the majority of persons infected with multidrug-resistant cases are seen in the Midwest. a. True b. False *end of test* 15