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Slide Set — Core Curriculum on Tuberculosis: What the Clinician Should Know (Text Only)

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Slide 1 (title slide). Core Curriculum on Tuberculosis: What the Clinician Should Know. Fifth edition 2011

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Slide 2. Core Curriculum Contents

  1. Overview of Tuberculosis (TB) Epidemiology in the United States
  2. Transmission and Pathogenesis of TB
  3. Testing for TB Infection and Disease
  4. Diagnosis of TB Disease
  5. Treatment for Latent TB Infection
  6. Treatment for TB disease
  7. TB Infection Control
  8. Community TB Control

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Slide 3 (title slide). Chapter 1. Overview of TB Epidemiology in the United States

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Slide 4. Progress Toward TB Elimination in the U.S.

  • 1989: Release of A Strategic Plan for the Elimination of Tuberculosis in the United States, MMWR 1989; 38 (Suppl. No. S-3), with goal of TB elimination in 2010
  • 1985–1992: Resurgence of TB in the United States, fueled by several factors
  • In response to resurgence, U.S. renewed commitment and support for TB control
  • In 1993, upward trend was reversed; that decline has continued

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Slide 5. Factors Contributing to the Increase in TB Morbidity: 1985-1992

  • Emerging HIV/AIDS epidemic
  • Immigration from countries where TB was common
  • Transmission of TB in congregate settings
  • Development of multidrug-resistant (MDR) TB
  • Decades of funding cuts had impaired effectiveness of TB control programs

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Slide 6. Factors Contributing to the Decrease in TB Morbidity Since 1993

  • Success attributed to increased efforts to
  • Promptly identify persons with TB
  • Initiate appropriate treatment
  • Ensure completion of therapy
  • But TB elimination faces barriers

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Slide 7. Areas of Concern Remain

  • U.S. TB cases occur largely in high-risk populations
  • In these populations, TB is difficult to detect, diagnose, and treat
  • Global TB epidemic persists
  • Current TB control measures are limited; new tests, vaccines, drugs needed

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Slide 8. TB Disease Trends in the United States

  • During resurgence, 1985–1992, reported TB cases increased every year
  • 1993–2009: cases decreased
  • 1993–2002: cases decreased 5%-7% annually
  • 2003–2008 decline continued but at a more moderate 3%-5%
  • 11,545 cases reported in 2009

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Slide 9. Reported TB Cases, United States, 1982–2009

[Image: A graph illustrating U.S. TB trends, 1982–2009. It shows U.S. TB cases declining at a steady rate from 1982 until 1985, then shows several years of increasing case counts, reaching a peak in 1992. A bracket superimposed on the graph marks the start and end points (1985–1992) of the resurgence. Case counts began decreasing again in 1993, and 2009 marked the seventeenth year of decline in the total number of TB cases reported in the United States since the peak of the resurgence.]

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Slide 10. TB Trends, United States

  • While TB is declining overall, high rates persist among some groups
  • Local epidemiology affects trends in individual areas
  • 34 states have achieved annual rate ≤3.5/100,000 (elimination interim target for year 2000)

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Slide 11. TB Case Rates, United States, 2009.

[Image: A map depicting U.S. TB case rates for 2009. For the decade leading up to 2009, a group of 34 states had a rate ≤3.5/100,000; 11 states and the District of Columbia had a rate above 3.8/100,000, the 2009 national average; and a small group of states reported rates of 3.6–3.8, less than the national average but not meeting the year 2000 interim goal.]

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Slide 12. Reported Cases of TB by Country of Origin – United States.

  • Cases among U.S.-born and foreign-born persons declining, but much less so in foreign born persons
  • 2002: Foreign-born persons first accounted for majority of U.S. TB cases (51%); in 2009, accounted for 59%
  • 1993–2009: TB in foreign-born persons was roughly level (7,000–8,000/year); in U.S.-born, dropped from >17,000 to 4,571

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Slide 13. Percentage of TB Cases among Foreign-Born Persons in the U.S., 1999 and 2009.

  • States with ≥50% of cases in foreign born: from 13 states in 1999 to 31 states
  • States with ≥70% of cases in foreign born: from 2 states to 14 states (not shown on slide).

[Image: Side-by-side maps of the United States showing the percentage range of the total number of TB cases that occurred in foreign-born persons in each state for 1999 and 2009.]

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Slide 14. Countries of Origin of Foreign-Born Persons Reported with TB, United States, 2009.

[Image: Pie chart showing the overall distribution of the countries of origin of foreign-born persons reported with TB in 2009, with the top seven highlighted. The seven top countries accounted for 62% of the total, with Mexico accounting for 23%; the Philippines, 12%; India, 8%; Vietnam; 8%; China, 5%; Guatemala, 3%; and Haiti, 3%. Persons from more than 135 other countries accounted for 2% or less of the total, but altogether accounted for 38% of foreign-born persons reported with TB.]

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Slide 15. TB Rates in Racial and Ethnic Minorities Groups, 1993–2009.

[Image: Graph showing the trend in TB rates by race/ethnicity in the United States, 1993–2009. Asians and Pacific Islanders had the highest TB rates, with a rate of 41.2 per 100,000 beginning in 1993 and declining to 23.1 in 2009. Asians and Pacific Islanders also had the smallest percentage decline over the same time period (43%). Rates declined by at least 65% over the same time period in the other racial/ethnic groups, including non-Hispanic blacks or African Americans, Hispan­ics, American Indians and Alaska Natives, and  non-Hispanic whites.]

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Slide 16. Factors Contributing to Burden of Disease in Minorities

  • In foreign born, disease may result from infection in country of origin
  • Some minority groups have higher proportion of risk factors for exposure and for progression from infection to disease
  • Lower socioeconomic status and crowded housing linked to increased TB risk

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Slide 17. HIV-Infected Persons, 1993-2009.

  • Persons coinfected with TB and HIV are at high risk of developing TB disease
  • Percentage of HIV coinfection (all ages) decreased, from 15% to 6%
  • Age group 25–44 decreased, from 29% to 10%

[Image: Graph illustrating estimated HIV coinfection in persons reported with TB, 1993–2009. These are minimum estimates because of incomplete reporting of HIV status. Two lines on the graph illustrate 1) a decrease in the percentage coinfection for all age groups, and 2) a more substantial decrease in percentage of coinfection among persons in the 25-44 age group.]

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Slide 18. Multidrug-Resistant (MDR) TB Remains a Serious Public Health Concern.

  • MDR TB has decreased in foreign born and U.S. born, but much more in U.S. born
  • 1993–2009, proportion of primary MDR TB in foreign born increased from 25% to 88%

[Image: Graph showing primary MDR TB in U.S.-born versus foreign-born persons. The percentage with primary MDR TB has declined among both groups, although the decline in the U.S.-born has been greater; as a result, the proportion of primary MDR TB cases reported in foreign-born persons has increased. Among U.S.-born, the percentage with primary MDR TB remained between 0.4% and 0.7% from 1998 through 2008 and was 0.3% in 2009. The percentage among foreign-born persons has fluctuated year by year, averaging approximately 1.5% from 1999 through 2009.]

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Slide 19. Extensively Drug-Resistant (XDR) TB.

  • XDR TB is a rare type of MDR TB
    • Resistant to INH, RIF, fluoroquinolones, and ≥1 of 3 injectable 2nd-line drugs
  • No apparent trend for XDR TB in the U.S.

[Image: A bar chart showing the annual number of XDR TB cases for 1993 to 2009. The most reported in a single year was 10 in 1993, while there were no cases reported in 2003 and 2009. There is no apparent trend in the number of XDR TB cases in the United States.]

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Slide 20. Persons at Higher Risk for Exposure to or Infection with TB

  • Close contacts of person known or suspected to have active TB
  • Foreign-born persons from areas where TB is common
  • Persons who visit TB-prevalent countries
  • Residents and employees of high-risk congregate settings

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Slide 21. Persons at Higher Risk for Exposure to or Infection with TB (cont.)

  • Health care workers (HCWs) who serve high-risk clients
  • Populations defined locally as high risk for infection or disease, such as medically underserved, low-income persons who abuse drugs or alcohol
  • Children and adolescents exposed to adults at increased risk for infection or disease

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Slide 22. (title slide). Chapter 2. Transmission and Pathogenesis of TB

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Slide 23. Introduction

  • Airborne disease caused by the bacterium Mycobacterium tuberculosis (M. tb)
  • M. tb complex (M. tb, M. bovis, M. africanum, M. microti, M. canetti, M. caprae, M. pinnipedii, and M. mungi) can cause TB disease
  • Majority of TB cases caused by M. tb
  • M. tb organisms also called tubercle bacilli

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Slide 24. Transmission of M. tuberculosis

  • M. tb spread via airborne particles called droplet nuclei
  • Expelled when person with infectious TB coughs, sneezes, shouts, or sings
  • Transmission occurs when droplet nuclei inhaled and reach the alveoli of the lungs, via nasal passages, respiratory tract, and bronchi

[Image: Drawing of two facing figures, with their airway passages and lungs shown. Dots in the air between them represent droplet nuclei containing tubercle bacilli organisms. The organisms are spreading, via the droplet nuclei, from person to person.]

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Slide 25. Probability TB Will Be Transmitted

  • Susceptibility of the exposed person
  • Infectiousness of person with TB (i.e., number of bacilli TB patient expels into the air)
  • Environmental factors that affect the concentration of M. tb organisms
  • Proximity, frequency, and duration of exposure (e.g., close contacts)
  • Can be transmitted from children, though less likely

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Slide 26. Pathogenesis

Droplet nuclei containing tubercle bacilli are inhaled, enter the lungs, and travel to the alveoli

[Image: Drawing of a left-facing figure, with airway passages and lungs visible. Dots in the air in front of figure, in airways, and in lungs represent tubercle bacilli being inhaled, entering the lungs, and traveling to the alveoli.]

Tubercle bacilli multiply in the alveoli

[Image: A drawing showing the tiny air sacs, alveoli, at the end of the airway branches in the lungs. A cutaway view of one air sac shows that it contains bacilli.]

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Slide 27. Pathogenesis

A small number of tubercle bacilli enter the bloodstream and spread throughout the body. The tubercle bacilli may reach any part of the body, including areas where TB disease is more likely to develop (such as the brain, larynx, lymph node, lung, spine, bone, or kidney).

[Image: Drawing of the upper part of a human torso showing areas where TB can develop: brain, larynx, lymph nodes, lung, spine, bone, kidney.]

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Slide 28. Pathogenesis (cont.)

Within 2 to 8 weeks, special immune cells called macrophages ingest and surround the tubercle bacilli. The cells form a barrier shell, called a granuloma, that keeps the bacilli contained and under control (LTBI).

[Image:  Drawing of an air sac in which special immune cells (macrophages) have formed a barrier shell / granuloma and surrounded the bacilli]

If the immune system cannot keep the tubercle bacilli under control, the bacilli begin to multiply rapidly (TB disease). This process can occur in different areas in the body, such as the lungs, kidneys, brain, or bone.

[Image:  Drawing of air sac with shell breaking down and bacilli escaping and multiplying]

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Slide 29. Latent TB Infection (LTBI)

  • Granulomas may persist (LTBI), or may break down to produce TB disease
  • 2 to 8 weeks after infection, LTBI can be detected via TST or interferon-gamma release assay (IGRA)
  • The immune system is usually able to stop the multiplication of bacilli
  • Persons with LTBI are not infectious and do not spread organisms to others

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Slide 30. TB Disease

  • In some, the granulomas break down, bacilli escape and multiply, resulting in TB disease
  • Can occur soon after infection, or years later
  • Persons with TB disease are usually infectious and can spread bacteria to others
  • Positive M. tb culture confirms TB diagnosis

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Slide 31. Sites of Disease

  • Lungs (pulmonary): most common site; usually infectious
  • Miliary: occurs when bacilli spread to all parts of the body; rare, but fatal if untreated
  • Central nervous system: usually occurs as meningitis, but can occur in brain or spine

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Slide 32. Sites of Disease (cont.)

Outside the lungs (extrapulmonary): usually not infectious, unless person has

  • Concomitant pulmonary disease,
  • Extrapulmonary disease in the oral cavity or larynx, or
  • Extrapulmonary disease with open site, especially with aerosolized fluid.

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Slide 33. Risk of Developing Disease

Normal Immune System

  • Untreated, 5% of infected persons with normal immunity develop TB in first 1–2 years post infection, another 5% later in life
  • Thus, about 10% of infected persons with normal immunity will develop TB at some point in life if not treated

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Slide 34. Risk of Developing Disease (cont.)

Weak Immune System

  • Persons with weak immunity at increased risk of progressing to TB disease
  • Untreated HIV infection highest risk factor: risk of developing TB disease is 7%–10% each year;
  • Children <5 years of age also at increased risk

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Slide 35. LTBI vs. TB Disease

Person with LTBI (Infected):

  • Has a small amount of TB bacteria in his/her body that are alive, but inactive
  • Cannot spread TB bacteria to others
  • Does not feel sick, but may become sick if the bacteria become active in his/her body
  • Usually has a TB skin test or TB blood test reaction indicating TB infection
  • Radiograph is typically normal
  • Sputum smears and cultures are negative
  • Should consider treatment for LTBI to prevent TB disease
  • Does not require respiratory isolation
  • Not a TB case

Person with TB Disease (Infectious):

  • Has a large amount of active TB bacteria in his/her body
  • May spread TB bacteria to others
  • May feel sick and may have symptoms such as a cough, fever, and/or weight loss
  • Usually has a TB skin test or TB blood test reaction indicating TB infection
  • Radiograph may be abnormal
  • Sputum smears and cultures may be positive
  • Needs treatment for TB disease
  • May require respiratory isolation
  • A TB case

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Slide 36. Drug-Resistant TB

  • Caused by organisms resistant to one or more TB drugs
  • Transmitted same way as drug-susceptible TB, and no more infectious
  • Delay in detecting drug resistance may prolong period of infectiousness because of delay in starting correct treatment

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Slide 37. Multidrug-Resistant (MDR) and Extensively Drug-Resistant (XDR) TB

  • MDR TB caused by bacteria resistant to best TB drugs, isoniazid and rifampin
  • XDR TB caused by organisms resistant to isoniazid and rifampin, plus fluoroquinolones and ≥1 of the 3 injectable second-line drugs

[Image: Four nested/concentric ovals. The largest oval represents “All TB.” The next largest is labeled “TB with any drug resistance.” The third largest is “MDR TB* with drug resistance to at least the first-line drugs isoniazid and rifampin.” The smallest oval is “XDR TB** with resistance to the first-line drugs isoniazid and rifampin and to specific second-line drugs.”

*Often resistant to additional drugs

**Resistant to any fluoroquinolone and at least one of three injectable drugs, i.e., amikacin, kanamycin, or capreomycin)]

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Slide 38. Types of Drug Resistance

Drug resistance develops in two ways:

  • Primary resistance develops in persons initially infected with resistant organisms
  • Secondary (acquired) resistance develops during TB therapy

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Slide 39. Circumstances Increasing the Risk of Drug-Resistant TB

Risk of drug-resistant TB is increased with exposure to a person who

  • Has confirmed drug-resistant TB
  • Had prior unsuccessful treatment for TB, and drug susceptibility results not known
  • Originated in a drug-resistant TB prevalent country
  • Has positive smear and culture 2 months after treatment start

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Slide 40. Classification System for TB

  • Based on TB pathogenesis (stage of disease)
  • Helps clinician track the development of TB in patients
  • Persons with class 3 or 5 TB should be reported to health department
  • Patients should not have class 5 classification for more than 3 months

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Slide 41. TB Classification System

0 – No exposure, no infection
1 – Exposure, no evidence of infection
2 – TB infection, no disease
3 – TB, clinically active
4 – TB, not clinically active
5 – TB suspect

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Slide 42. (title slide). Chapter 3. Testing for TB Infection and Disease

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Slide 43. Identifying High-Risk Groups for M. tb Testing

  • Health-care providers should find and test
  • Uninfected persons at high risk for LTBI, and/or
  • Persons at high risk for progression to TB disease
  • Flexibility needed in defining high-risk groups
  • Risk for TB or LTBI in current high-risk groups may decrease over time, and groups currently not at risk may subsequently become high risk

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Slide 44. Evaluation of Persons with Positive TB Tests

  • Facilities should consult with local health department before starting testing program to ensure evaluation and treatment resources are available
  • Persons with positive TST or IGRA should be evaluated for disease
  • If disease is ruled out, consider for LTBI treatment
  • If patient not willing or able to take treatment, educate on TB signs and symptoms

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Slide 45. Methods for Detecting M. tb Infection in U.S.

  • Mantoux tuberculin skin test (TST)
  • IGRAs:
    • QuantiFERON-TB Gold In-Tube (QFT-GIT)®, and
    • T-Spot.TB®
  • These tests do not exclude LTBI or TB disease
  • Decisions about medical/public health management should include other info/data, and not rely only on TST/IGRA results

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Slide 46. Mantoux Tuberculin Skin Test

  • Purified protein derivative (PPD), derived from tuberculin, is injected between skin layers using the Mantoux technique
  • Infected person’s immune cells recognize TB proteins in PPD, respond to site, causing wheal to rise
  • Takes 2-8 weeks after exposure and infection for the immune system to react to PPD
  • Reading and interpretation of TST reaction must be done within 48–72 hours

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Slide 47. Administering the TST

  • Inject 0.1 ml of PPD (5 tuberculin units) into forearm between skin layers
  • Produce wheal (raised area) 6–10 mm in diameter
  • Follow universal precautions for infection control

[Image: Drawing of gloved hands holding a tuberculin syringe and injecting PPD into an arm. The drawing shows a discrete, pale elevation of the skin (wheal) has been formed.]

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Slide 48. Reading the TST

  • Trained health care worker assesses reaction 48–72 hours after injection
  • Palpate (feel) injection site to find raised area
  • Measure diameter of induration across forearm; only measure induration, not redness
  • Record size of induration in millimeters; record “0” if no induration found

[Image: Drawing of a hand holding a TST ruler and measuring the diameter of an induration. Only the induration is being measured; this is the correct way to read the TST reaction.]

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Slide 49. Interpreting the TST Reaction

≥5 mm induration is classified as positive in

  • HIV-infected persons
  • Recent contacts of infectious TB
  • Persons with fibrotic changes on chest radiograph consistent with prior TB
  • Patients with organ transplants and other immunosuppressed patients

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Slide 50. Interpreting the TST Reaction (cont.)

≥10 mm induration is classified as positive in

  • Recent arrivals from high-prevalence countries
  • Injection drug users
  • Residents and employees of high-risk congregate settings

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Slide 51. Interpreting the TST Reaction (cont.)

≥10 mm induration is classified as positive in

  • Mycobacteriology laboratory personnel
  • Persons with conditions that increase risk for progressing to TB
  • Children <4 years of age, or children and youth exposed to adults at high risk

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Slide 52. Interpreting the TST Reaction (cont.)

≥15 mm is classified as positive in

  • Persons with no known risk factors for TB

Targeted skin testing should only be conducted among high-risk groups

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Slide 53. Factors that May Affect the Skin Test Reaction

Type of reaction: False positive
Possible cause:

  • Nontuberculous mycobacteria
  • BCG vaccination
  • Problems with TST administration

Type of reaction: False negative
Possible cause:

  • Anergy
  • Viral, bacterial, fungal coinfection
  • Recent TB infection
  • Very young age; advanced age
  • Live-virus vaccination
  • Overwhelming TB disease
  • Renal failure/disease
  • Lymphoid disease
  • Low protein states
  • Immunosuppressive drugs
  • Problems with TST administration

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Slide 54. Special Considerations When Using TST

Boosting

  • Some may have negative (waned) TST reaction when tested years after infection (e.g., older adults)
  • Initial skin test may stimulate (boost) ability to react to PPD
  • Subsequent positive boosted reaction may be misinterpreted as a new infection
  • May still be considered for treatment if currently at high risk for TB disease

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Slide 55. Special Considerations When Using TST (cont.)

Two-Step Testing

  • Used for initial skin testing of adults to be retested periodically, to reduce likelihood that boosted reaction will be misinterpreted as recent infection
  • If 1st test positive, consider infected; if negative, give 2nd test 1–3 weeks later
  • If 2nd test positive, consider infected; if negative, consider uninfected

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Slide 56. Special Considerations When Using TST (cont.)

Pregnant women

  • TST is safe and reliable for mother and fetus throughout pregnancy
  • Give TST to pregnant women who have risk factors for infection or disease

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Slide 57. Special Considerations When Using TST (cont.)

Occupational exposure to TB

  • Cutoff for defining a positive TST reaction depends on
  • Individual risk factors for TB
  • Prevalence of TB in the facility
  • High-risk sites should test residents and staff at entry and hire and at intervals determined by annual risk assessment

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Slide 58. Interferon Gamma Release Assays (IGRAs)

  • IGRAs detect M. tb infection by measuring immune response in blood
  • Cannot differentiate between TB and LTBI; other tests needed
  • May be used for surveillance/screening, or to find those who will benefit from treatment
  • FDA-approved IGRAs are QFT Gold In-Tube and T-Spot.TB test

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Slide 59. General Recommendations for Using IGRAs

  • May be used in place of, but not in addition to, TST
  • Preferred when testing persons
  • Who might not return for TST reading
  • Who have received BCG vaccination
  • Generally should not be used to test children <5 years of age, unless used in conjunction with TST

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Slide 60. General Recommendations for Using IGRAs (cont.)

May be used in place of TST to test recent contacts of infectious TB

  • Detect M. tb infection with greater specificity than TST
  • Data are limited on ability to predict subsequent TB
  • In contact investigations, confirm negative via retest 8–10 weeks postexposure
  • Use same test for repeat testing to reduce misclassification errors

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Slide 61. General Recommendations for Using IGRAs (cont.)

  • May be used for periodic screening, e.g., for health care workers
  • IGRAs do not boost subsequent test results; administered with one patient visit
  • Results from both IGRA and TST may be useful when initial test is
  • Negative, and patient has high risk of TB infection or disease
  • Positive, and additional evidence is required/desired
  • Unclear or indeterminate

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Slide 62. BCG Vaccination

  • Vaccine made from live, attenuated (weakened) strain of M. bovis
  • Early version first given to humans in 1921
  • Many TB-prevalent countries vaccinate infants to prevent severe TB disease

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Slide 63. Recommendations for BCG Vaccination

  • BCG not generally recommended in the U.S.
  • However, its use may be considered in very limited circumstances
  • Use BCG only after consultation with local health department and TB experts

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Slide 64. Recommendations for BCG Vaccination (cont.)

Infants and Children

  • Can be considered for infant or child with negative skin-test result who
  • Is continually exposed to untreated or ineffectively treated adult
  • Will be continually exposed to adult with MDR TB
  • BCG vaccination not recommended for HIV-infected children

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Slide 65. Recommendations for BCG Vaccination (cont.)

Health-Care Workers
Should be considered on individual basis for health-care workers in settings in which

  • High percentage of MDR TB patients has been found,
  • Transmission of drug-resistant TB strains and subsequent infection are likely, and
  • Comprehensive TB infection-control precautions implemented but not successful.

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Slide 66. BCG Contraindications

  • Contraindicated in persons with impaired immune response from
  • HIV infection, congenital immunodeficiency
  • Leukemia, lymphoma, generalized malignancy
  • High-dose steroid therapy
  • Alkylating agents
  • Antimetabolites
  • Radiation therapy
  • BCG vaccination should not be given to pregnant women

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Slide 67. Interpretation of TB Test Results in BCG-Vaccinated Persons

  • TST or IGRA not contraindicated for BCG-vaccinated persons
  • Results used to support or exclude diagnosis of infection
  • In BCG-vaccinated, interpret TST with same criteria used for non BCG vaccinated
  • Booster phenomenon may occur in BCG-vaccinated persons

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Slide 68. (title slide). Chapter 4. Diagnosis of TB Disease

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Slide 69. Medical Evaluation for TB

  • Medical history
  • Physical examination
  • Test for TB infection
  • Chest radiograph
  • Bacteriologic examination

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Slide 70. Medical Evaluation for TB

1. Medical History

  • Symptoms of disease; how long
  • History of TB exposure, infection, or disease
  • Past TB treatment
  • Demographic risk factors for TB
  • Medical conditions that increase risk for TB disease

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Slide 71. Medical Evaluation for TB (cont.)

1. Medical History (cont.)
Symptoms of pulmonary TB:

  • Prolonged cough (3 weeks or longer), hemoptysis
  • Chest pain
  • Loss of appetite, unexplained weight loss
  • Night sweats, fever
  • Fatigue

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Slide 72. Medical Evaluation for TB (cont.)

1. Medical History (cont.)
Symptoms of possible extrapulmonary TB:

  • Blood in the urine (TB of the kidney)
  • Headache/confusion (TB meningitis)
  • Back pain (TB of the spine)
  • Hoarseness (TB of the larynx)
  • Loss of appetite, unexplained weight loss
  • Night sweats, fever
  • Fatigue

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Slide 73. Medical Evaluation for TB (cont.)

2. Physical Examination

  • Provides valuable information about the patient’s overall condition
  • Cannot be used to confirm or rule out TB disease

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Slide 74. Medical Evaluation for TB (cont.)

3. Test for M. tuberculosis Infection

  • Two methods for detecting M. tb infection: TST and IGRAs
  • TST and IGRAs help differentiate persons with M. tb infection from those not infected
  • Negative reaction to either does not exclude diagnosis of TB or LTBI

[Image: photo of Mantoux tuberculin skin test materials]
[Image: photo of QuantiFERON-TB Gold In-Tube test kit]
[Image: photo of T-Spot.TB test kit]

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Slide 75. Medical Evaluation for TB (cont.)

4. Chest Radiograph

  • Chest abnormalities suggest, but do not confirm, TB disease
  • Posterior-anterior view is standard
  • Apical/posterior areas of upper lobe or superior areas of lower lobe often show abnormalities
  • In immunosuppressed (e.g., HIV infected), lesions may have atypical appearance

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Slide 76. Chest Radiograph with Lower Lobe Cavity

[Image: Chest radiograph with arrows pointing to cavity in lower lobe]

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Slide 77. Medical Evaluation for TB (cont.)

4. Chest Radiograph (cont.)

  • Old TB can produce dense, hard nodules or lesions containing live bacilli
  • Fibrotic nodules/lesions from old TB + positive TB test = high-priority candidate for LTBI treatment
  • Calcified lesions pose low risk for progressing to TB
  • Active versus inactive disease cannot be determined from chest radiograph alone

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Slide 78. Medical Evaluation for TB (cont.)

4. Chest Radiograph (cont.)

  • In HIV infected, pulmonary TB may present atypical radiograph
  • Less common: cavitary disease (with higher CD4 counts)
  • More common: infiltrates, adenopathy, or normal radiograph (with lower CD4 counts)
  • With signs/symptoms, negative radiograph does not rule out disease
  • With no signs/symptoms and positive TB test, negative radiograph may rule out TB in HIV-negative person

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Slide 79. Medical Evaluation for TB (cont.)

5. Bacteriologic Examination of Specimens

  • Specimen collection
  • AFB smear classification
  • NAA testing
  • Culture and identification
  • Drug-susceptibility testing

[Image: Patient coughing up sputum into a tube; supervising health care worker is wearing respirator.]
[Image: Photo of Lowenstein-Jensen agar plate and tube (slant). Either can be used to culture clinical specimens for examination when extrapulmonary TB is suspected. The green substance in each is agar, on which the bacteria are grown.] Kit Whitworth helped with this one.
[Image: Patient undergoing bronchoscopy; the two health care workers performing the procedure are wearing respirators]

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Slide 80. Medical Evaluation for TB (cont.)

5. Bacteriologic Examination of Specimens (cont.)
Specimen collection, processing, and review

  • All persons suspected of TB disease should have sputum cultured
  • Collect at least 3 sputum specimens at 8- to 24-hour intervals, at least 1 in the morning
  • Follow infection control precautions during specimen collection
  • Collection methods include coughing, sputum induction, bronchoscopy, gastric aspiration

[Image: A TB patient has coughed up sputum and is spitting it into a sterile container. The patient is sitting in a special sputum collection booth that, if properly ventilated, prevents the spread of tubercle bacilli.]

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Slide 81. Medical Evaluation for TB (cont.)

5. Bacteriologic Examination of Specimens (cont.)
Specimen collection methods for extrapulmonary TB

  • TB disease can occur in almost any site
  • Variety of clinical specimens other than sputum can be submitted
  • Before collection, ensure transport and processing procedures are in place

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Slide 82. Medical Evaluation for TB (cont.)

5. Bacteriologic Examination of Specimens (cont.)
Smear examination     

  • Detecting AFB in smears may be first evidence of mycobacteria
  • Quickest (results within 24 hours) and easiest procedure
  • Provides a preliminary presumptive diagnosis of TB
  • AFB in a smear are counted and classified as 4+, 3+, 2+, or 1+

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Slide 83. AFB Smear

AFB (shown in red) are tubercle bacilli
[Image: Photo of acid-fast bacilli (AFB) smear. Detection of AFB in stained and acid-washed smears examined microscopically may provide the initial bacteriologic evidence of the presence of mycobacteria in a clinical specimen.]

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Slide 84. Direct Detection Using Nucleic Acid Amplification (NAA)

  • NAA tests rapidly identify a specimen via DNA and RNA amplification
  • Benefits may include
  • Earlier lab confirmation of TB disease
  • Earlier respiratory isolation and treatment initiation
  • Improved patient outcomes; interruption of transmission
  • Perform at least 1 NAA test on each pulmonary TB suspect
  • A single negative NAA test does not exclude TB

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Slide 85. Nucleic Acid Amplification (NAA) Test

[Image: Photo of contents of NAA test kit]

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Slide 86. Culture

  • Remains gold standard for confirming diagnosis of TB
  • Culture all specimens, even if smear or NAA negative
  • Results in 4–14 days when liquid medium systems used
  • Culture monthly until conversion, i.e., 2 consecutive negative cultures

Slide 87. Colonies of M. tuberculosis Growing on Media
[Image: Photo showing several light-colored, granular clusters or colonies of M. tuberculosis]

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Slide 88. Drug-Susceptibility Testing

  • Conduct drug-susceptibility testing on initial M. tb isolate
  • Promptly forward results to the health department
  • Repeat for patients who
  • Do not respond to therapy or
  • Have positive cultures despite 3months of therapy

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Slide 89. Drug-Susceptibility Testing

[Image: Photo of one of the liquid broth-based methods available for performing rapid drug-susceptibility testing for primary drugs (Becton Dickinson MGIT 960 tubes).]

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Slide 90. Second-line Drug-Susceptibility Testing

Limit to persons at increased risk for drug resistance:

  • Have history of treatment with TB drugs
  • Had contact with a person with drug-resistant TB
  • Demonstrated resistance to first-line drugs
  • Has positive smears or cultures despite 3 months of TB treatment

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Slide 91. Molecular Detection of Drug Resistance

  • Drug resistance is caused by mutations in specific M. tb genes
  • Several molecular assays and tests can detect mutations
  • Molecular detection should be used for patients with high risk for rifampin resistance (MDR TB)
  • Conventional drug susceptibility testing should be done in conjunction with molecular tests

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Slide 92. Genotyping

  • Laboratory-based approach that analyzes the genetic material of patient isolates
  • Different strains of M. tb have different genotype patterns
  • M. tb isolates with identical genotypes often indicates recent transmission
  • Main purpose of genotyping: add to TB controllers’ understanding of TB transmission in their community

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Slide 93. Genotyping (cont.)

Used with traditional epi investigations, genotyping has

  • Confirmed/detected transmission
  • Identified risk factors for recent infection
  • Demonstrated re-infection with different strains
  • Identified weaknesses in conventional contact investigations
  • Documented lab cross-contamination
  • Identified outbreaks not previously recognized

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Slide 9. (title slide). Chapter 5. Treatment for Latent Tuberculosis Infection

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Slide 95. Treatment for Latent TB Infection (LTBI)

  • Treatment of LTBI essential to controlling and eliminating TB disease
  • Reduces risk of LTBI to TB disease progression
  • Use targeted testing to find persons at high risk for TB who would benefit from LTBI treatment
  • Several treatment regimens available

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Slide 96. Candidates for Treatment of LTBI

High-risk persons with positive IGRA test or TST reaction of ≥5 mm:

  • HIV-infected persons
  • Recent contacts of persons with infectious TB
  • Persons with fibrotic changes on chest radiograph consistent with prior TB
  • Patients with organ transplants and other immunosuppressed patients

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Slide 97. Candidates for Treatment of LTBI (cont.)

High-risk persons with positive IGRA test or TST reaction of ≥10 mm:

  • Recent arrivals (<5 yrs) from high-prevalence countries or regions (e.g., Asia, Africa, Eastern Europe, Latin America, and Russia)
  • Injection drug users
  • Residents and employees of high-risk congregate settings (e.g., correctional facilities, homeless shelters, hospitals, and long term care facilities)
  • Mycobacteriology laboratory personnel

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Slide 98. Candidates for Treatment of LTBI (cont.)

High-risk persons with positive IGRA test or TST reaction of ≥10 mm (cont.):

  • Persons with conditions that increase risk for TB:
  • Silicosis
  • Diabetes mellitus
  • Chronic renal failure
  • Certain cancers (e.g., leukemia and lymphomas, or cancer of the head, neck, or lung)
  • Gastrectomy or jejunoileal bypass
  • Weight loss of at least 10% below ideal body weight
  • Children <4 yrs of age; children/adolescents exposed to adults in high-risk categories

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Slide 99. Candidates for Treatment of LTBI (cont.)

  • Low-risk persons with positive IGRA test or TST reaction of ≥15 mm:
  • Persons with no known risk factors for TB generally should not be tested
  • Targeted testing programs should only be conducted among high-risk groups
  • If low-risk persons are tested and have positive IGRA test or TST reaction ≥15 mm, evaluate for LTBI treatment

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Slide 100. Close Contacts with Negative IGRA or TST Results

    • Some contacts should be evaluated and treated for LTBI even with negative TB test results:
    • Children under 4 yrs of age
    • Immunosuppressed persons
    • Others at high risk for progressing to disease once infected
    • Always rule out TB disease with chest radiograph and medical evaluation before treating for LTBI
    • Give LTBI treatment (window prophylaxis) regardless of test result
    • Retest 8–10 weeks after last exposure to allow for delayed immune response

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    Slide 101. LTBI Treatment Regimens

    Isoniazid (INH)

    • 9-month daily regimen is preferred: 270 doses within 12 months
    • Effective for HIV-infected as well as HIV-uninfected persons
    • Can be given twice weekly via DOT: 76 doses within 12 months
    • Children should always receive 9 months of therapy

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    Slide 102. LTBI Treatment Regimens

    Isoniazid (INH) (cont.)

    • 6-month regimen also generally acceptable: 180 doses within 9 months
    • Can be given twice weekly via DOT: 52 doses within 9 months
    • Not recommended for children, HIV infected, persons whose x-rays suggest previous TB

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    Slide 103. Adverse Reactions to INH

    Use of INH is associated with some adverse reactions

    • Peripheral neuropathy – give vitamin B6 if patient has risk factors, or if signs/symptoms develop
    • Elevation of liver enzymes – discontinue INH if adverse reactions develop, or if liver enzyme levels exceed 3X normal with symptoms, or 5X upper limit of normal with no symptoms
    • Fatal hepatitis – pregnant/postpartum women at increased risk; monitor closely

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    Slide 104. Rifampin (RIF)

    • Alternative to INH is 4 months daily RIF:120 doses within 6 months
    • Use of RIF contraindicated with some combinations of antiretroviral therapy
    • In some instances where RIF cannot be used, rifabutin can be substituted

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    Slide 105. Recommendations Against the RIF/PZA Regimen

    • LTBI regimen of 2 months of RIF/PZA is no longer recommended owing to associated severe liver injury.
    • PZA should not be offered to persons with LTBI, but should be included in multidrug regimens for treatment of TB as described in TB disease treatment section

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    Slide 106. LTBI Treatment Regimens for Specific Situations

    HIV-Infected Persons

    • Consult an expert in managing HIV and TB
    • INH daily for 9-mo, rather than 6-mo, is optimal: 270 doses within 12 months
    • RIF is generally contraindicated for persons taking protease inhibitors or delavirdine
    • Rifabutin with dose adjustments can sometimes be substituted for RIF

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    Slide 107. LTBI Treatment Regimens for Specific Situations (cont.)

    Persons with Fibrotic Lesions Suggesting Previous TB

    • Should be treated for LTBI if they have
    • A positive TST reaction (at least 5 mm) or IGRA result
    • No symptoms of infectious TB disease
    • No history of treatment for TB disease
    • Treat only after active disease excluded with sputum testing
    • Acceptable regimens include
    • 9 months of INH
    • 4 months of RIF (with or without INH)
    • Persons with evidence of primary, healed TB not at increased risk for TB

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    Slide 108. LTBI Treatment Regimens for Specific Situations (cont.)

    Contacts of Persons with Multidrug-Resistant TB

    • Consider risk for progressing to MDR disease before recommending LTBI treatment
    • When prescribing treatment for these contacts, consult an MDR TB expert

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    Slide 109. LTBI Treatment Regimens for Specific Situations (cont.)

    Pregnancy and Breast-Feeding

    • 9 months of INH daily or twice weekly; give with vitamin B6
    • If cannot take INH, consult with TB expert
    • Women at high risk for progression to TB disease should not delay LTBI treatment; monitor carefully
    • Breast-feeding not contraindicated

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    Slide 110. Patient Monitoring

    Before starting treatment for LTBI, clinicians should

    • Exclude possibility of disease (symptoms, chest radiograph)
    • Determine if patient has history of treatment for LTBI or disease
    • Determine contraindications to treatment
    • Obtain information about current and previous drug therapy, including adverse reactions
    • Recommend HIV testing, unless the patient declines (opt-out screening)

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    Slide 111. Patient Monitoring (cont.)

    Establish rapport with patient and emphasize

    • Benefits of treatment
    • Importance of adherence to treatment regimen
    • Possible adverse side effects of regimen
    • Establishment of optimal follow-up plan

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    Slide 112. Patient Monitoring (cont.)

    • Baseline laboratory testing not routinely indicated for all patients
    • Baseline hepatic measurements are indicated for
    • Patients with a liver disorder or liver disease
    • Patients with HIV infection
    • Pregnant women and those in immediate postpartum period
    • Patients with abnormal baseline tests should be monitored regularly

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    Slide 113. Patient Monitoring (cont.)

    At least monthly, evaluate for

    • Adherence to prescribed regimen
    • Signs and symptoms of TB disease
    • Signs and symptoms of adverse effects, especially hepatitis
    • Jaundice, loss of appetite, fatigue, and/or muscle and joint aches

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    Slide 11. (title slide). Chapter 6. Treatment of TB Disease

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    Slide 115. Major Goals of TB Treatment

    • Cure patient, minimize risk of death/disability, prevent transmission to others
    • Provide safest, most effective therapy in shortest time
    • Prescribe multiple drugs to which the organisms are susceptible
    • Never treat with a single drug or add single drug to failing regimen
    • Ensure adherence and completion of therapy

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    Slide 116. Develop Treatment and Monitoring Plan

    Plan should include

    • Description of treatment regimen
    • Methods for assessing/ensuring adherence
    • Monitoring methods for treatment response and adverse events

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    Slide 117. Adherence

    • Nonadherence results in inadequate treatment
    • Can lead to treatment failure, relapse, ongoing transmission, and drug resistance
    • Clinician responsible for completion of therapy
    • To ensure adherence, provide education, case management, DOT, incentives and enablers, and combination pills
    • If these fail, take more restrictive action

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    Slide 118. Case Management

    Strategy to ensure patients complete treatment; includes

    • Assigning responsibility to case manager
    • Conducting regular systematic review
    • Developing plans to address barriers to adherence
    • Case managers must ensure patients are educated about TB, therapy is continuous, and contacts are evaluated properly

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    Slide 119. Directly Observed Therapy (DOT)

    • Health care worker watches patient swallow each dose
    • DOT is preferred management strategy for all patients
    • Can reduce acquired drug resistance, treatment failure, and relapse
    • Nearly all regimens can be intermittent if given as DOT
    • DOT reduces total number of doses and encounters
    • For drug-resistant TB, use daily regimen and DOT

    [Image: Health care worker and patient meeting outdoors; patient holds pills and drink.]
    [Image: Display of examples of incentives and enablers.]
    [Image: Health care worker and patient meeting in clinic; both wear respirators; pill bottles are on desk.]

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    Slide 120. Current Anti-TB Drugs

    10 drugs FDA-approved for treatment of TB

    • Isoniazid (INH)
    • Rifampin (RIF)
    • Pyrazinamide (PZA)
    • Ethambutol (EMB)
    • Rifapentine (RPT)
    • Streptomycin (SM)
    • Cycloserine
    • Capreomycin
    • ρ-Aminosalicylic acid
    • Ethionamide

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    Slide 121. Current Anti-TB Drugs (cont.)

    • Four first-line drugs considered standard treatment:
    • Isoniazid (INH)
    • Rifampin (RIF)
    • Pyrazinamide (PZA)
    • Ethambutol (EMB)
    • Rifabutin and rifapentine also considered first-line drugs in some circumstances
    • Streptomycin (SM) formerly first-line drug, but now less useful owing to increased SM resistance

    [Image: photo of 1 white INH pill, 2 red RIF capsules, 3 white PZA pills, 3 white EMB pills]

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    Slide 122. TB Disease Treatment Regimens

    • Four regimens recommended for treatment of drug-susceptible TB, with different options for number of doses and for length of continuation phase
    • Initial phase: standard four drugs (INH, RIF, PZA, EMB) for 2 months (one excludes PZA)
    • Continuation phase: additional 4 months; 7 months for some patients

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    Slide 123. TB Disease Treatment Regimens (cont.)

    • When to use 7-month continuation phase:
    • Disease is cavitary and sputum culture is positive at end of initial phase;
    • Initial phase excluded PZA; or
    • Once-weekly INH and RPT used in continuation phase, and culture is positive at end of initial phase.

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    Slide 124. Regimen 1 for Treatment of Pulmonary, Drug-Susceptible TB

    6-Month Standard Regimen for Most Patients

    Initial phase
    INH, RIF, PZA, EMB daily (7 or 5 days/week) for 8 weeks

    4-month continuation phase options
    1) INH, RIF daily (7 or 5 days/week) for 18 weeks
    2) INH, RIF intermittently (2 days/week or 1 day/week for INH, rifapentine) for 18 weeks

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    Slide 125. Regimen 2 for Treatment of Pulmonary, Drug-Susceptible TB

    6-Month Daily + Intermittent Dosing Options

    Initial phase
    INH, RIF, PZA, EMB daily (7 or 5 days/week) for 2 weeks, then 2 days/week for 6 weeks

    4-month continuation phase options
    1) INH, RIF intermittently (2 days/week) for 18 weeks
    2) INH, RPT intermittently (1 day/week) for 18 weeks

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    Slide 126. Regimen 3 for Treatment of Pulmonary, Drug-Susceptible TB

    6-Month Intermittent Dosing Options

    Initial phase
    INH, RIF, PZA, EMB intermittently (3 days/week) for 8 weeks

    4-month continuation phase
    INH, RIF intermittently (3 days/week) for 18 weeks

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    Slide 127. Regimen 4 for Treatment of Pulmonary, Drug-Susceptible TB

    7-Month Regimen without Pyrazinamide

    Initial phase
    INH, RIF, EMB daily (7 or 5 days/week) for 8 weeks

    7-month continuation phase options
    1) INH, RIF daily (7 or 5 days/week) for 31 weeks
    2) INH, RIF intermittently (2 days/week) for 31 weeks

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    Slide 128. Treatment Completion

    • Defined as ingesting prescribed number of doses within specified time
    • Duration depends on drugs used, isolate’s susceptibility, and patient’s response to drugs
    • Most patients can be treated with 6- or 9-mo therapy;  6 mo is used for most patients

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    Slide 129. Follow-up After Treatment

    • Not necessary for patients with satisfactory response
    • Patients with susceptible TB should report symptoms
    • Patients with resistant organisms must have individualized follow-up evaluation

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    Slide 130. Treatment Interruptions

    • Treatment interruption is common
    • Restart or continue therapy based on when interruption occurred and duration of interruption

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    Slide 131. Treatment Interruption During Initial Phase

    • If lapse ≥14 days, restart treatment
    • If lapse <14 days, continue treatment to completion as long as all doses completed within 3 months

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    Slide 132. Treatment Interruption During Continuation Phase

    • If patient received ≥80% of doses and
    • Sputum smear was negative on initial testing, further therapy may not be needed
    • Sputum smear was positive on initial test, continue therapy
    • If patient received <80% of doses, and lapse is
    • <3 months long, continue therapy
    • >3 months long, restart therapy from beginning of initial phase

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    Slide 133. Treating Culture-Negative Disease

    • Some patients may have culture-negative pulmonary TB disease
    • Start culture-negative patient on four-drug therapy if high clinical suspicion for TB

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    Slide 134. Treatment Regimens for Specific Situations

    Pregnant Women

    • Initial regimen should consist of INH, RIF, and EMB
    • SM is contraindicated; PZA not contraindicated, but detailed data on teratogenicity not available
    • If PZA not used, duration of therapy is 9 months
    • If treating MDR TB in pregnancy, consult MDR TB expert
    • Breast-feeding not contraindicated for women being treated for TB disease
    • Vitamin B6 supplementation recommended if taking INH

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    Slide 135. Treatment Regimens for Specific Situations (cont.)

    Infants and Children

    • Treat with same regimens recommended for adults, with exception that EMB not used routinely in children
    • Treat as soon as diagnosis suspected
    • For disseminated TB or TB meningitis in children, treat for 9–12 months

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    Slide 136. Treatment Regimens for Specific Situations (cont.)

    HIV-Infected Persons

    • Management of HIV-related TB is complex
    • Should be provided in consultation with experts in treatment of both HIV and TB
    • Can be treated with standard regimens except:
      • Do not use once-weekly continuation-phase INH and RPT
      • In patients with advanced HIV, use daily or 3x weekly therapy

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    Slide 137. Treatment Regimens for Specific Situations (cont.)

    HIV-Infected Persons (cont.)

    • If possible, use a rifamycin for the entire course of therapy, along with ARV therapy
    • A major concern: RIF interacts with some PIs and NNRTIs
    • Rifabutin has fewer drug interactions and may be used instead of RIF
    • Drug dosages may need adjusting; consult expert

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    Slide 138. Treatment Regimens for Specific Situations (cont.)

    HIV-Infected Persons (cont.)

    • These guidelines are likely to change over time
    • For more information, see Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis at:

    http://www.cdc.gov/tb/publications/guidelines/TB_HIV_Drugs/default.htm

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    Slide 139. Pregnancy in HIV-Infected Women

    • Treatment is complicated in HIV-infected pregnant women with TB
    • Pregnancy alters distribution/metabolism of some drugs, including ARV drugs
    • Protease inhibitor concentrations reduced in pregnancy

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    Slide 140. HIV-Infected Children

    HIV-infected children with TB at greater risk for severe forms of disease

    • For more information, see Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis at:

    http://www.cdc.gov/tb/publications/guidelines/TB_HIV_Drugs/default.htm

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    Slide 141. Conditions Requiring Additional Considerations

    • Renal insufficiency/end-stage renal disease
      • Some TB drugs are cleared by the kidneys; thus the dosing must be altered with renal disease
      • Rather than decrease dosage size, increase dosing interval
    • Hepatic disease – consider regimens with fewer hepatotoxic agents
    • Extrapulmonary TB – In most cases, treat with same regimens used for pulmonary TB

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    Slide 142. Conditions Requiring Additional Considerations (cont.)

    Drug-resistant TB: can develop as primary or secondary resistance

    • Primary resistance is caused by initial infection with resistant organisms
    • Secondary or acquired resistance develops during therapy owing to
      • Patient being treated with inadequate regimen,
      • Patient not taking drugs as prescribed, or
      • Other conditions such as drug malabsorption or drug-drug interactions.

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    Slide 143. Conditions Requiring Additional Considerations (cont.)

    Multidrug-resistant TB (MDR TB)

    • Presents high risk for treatment failure, relapse, further acquired resistance, and/or death
    • Clinicians unfamiliar with its treatment should seek expert consultation
    • Always use DOT to ensure adherence

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    Slide 144. Conditions Requiring Additional Considerations (cont.)

    Culture-negative TB

    • Failure to isolate TB bacilli from person with clinical evidence does not exclude TB
    • At minimum, TB suspects should have 3 specimens for smear and culture
    • If high likelihood of TB, initiate therapy with INH, RIF, PZA, and EMB

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    Slide 145. Patient Monitoring

    Recommended Examinations for Baseline Monitoring

    • All Patients: Measure aminotransferases (i.e., AST, ALT), bilirubin, alkaline phosphatase, and serum creatinine and a platelet count
    • Patients at risk for hepatitis B or C (e.g., injection drug user, born in Asia, or HIV infected): Conduct serologic tests
    • Patients who are taking EMB: Test visual acuity (Snellen chart) and color vision (Ishihara)
    • HIV-infected patients: Obtain CD4+ lymphocyte count

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    Slide 146. Patient Monitoring (cont.)

    Monitoring During Treatment
    All patients: Repeat at least monthly clinical evaluations to

    • Identify possible adverse reactions to medications
    • Assess adherence

    Patients who are taking EMB:

    • Question monthly regarding visual disturbances
    • Repeat monthly testing for visual acuity (Snellen chart) and color vision (Ishihara) for  patients whose dose exceeds 15-20 mg/kg and those who have been receiving EMB for >2 months

    Patients who have extrapulmonary disease:
    Evaluation depends on

    • Sites involved
    • Ease with which specimens can be obtained

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    Slide 147. Evaluating Response to Treatment

    • Assess patient’s response to treatment using three methods:
      • Clinical evaluation, bacteriological examination, chest radiograph
    • Conduct clinical evaluations at least monthly; after 2 months of therapy, if symptoms do not resolve, reevaluate for
      • Potential drug-resistant disease
      • Nonadherence to drug regimen

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    Slide 148. Evaluating Response to Treatment (cont.)

    • Bacteriological examination

    If cultures do not convert to negative after 3 months of therapy, evaluate patient for drug resistance or adherence issues; after 4 months, consider treatment failed

    • Chest radiograph

    Patients with initially negative cultures should have chest radiograph after 2 months of treatment and at completion of therapy

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    Slide 149. Evaluating Response to Treatment (cont.)

    • Monitor for adverse reactions
    • Common adverse reactions include
      • Gastrointestinal problems
      • Hepatitis
      • Rash
      • Fever

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    Slide 15. (title slide). Chapter 7. TB Infection Control

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    Slide 151. Introduction

    • M. tb can be transmitted in any setting
    • Transmission has been documented in health-care settings where there is exposure to persons with infectious TB who
      • Have unsuspected TB disease,
      • Have not received adequate treatment, or
      • Have not been isolated from others.

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    Slide 152. Infectiousness

    • Directly related to number of bacilli-laden droplets expelled into the air
    • Infection occurs when person inhales droplets, which travel to alveoli
    • Young children with TB less likely to be infectious, but can transmit M. tb
    • Infectiousness usually declines rapidly with treatment
    • However, some remain infectious for weeks or month

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    Slide 153. Infectiousness (cont.)

    Patient factors associated with infectiousness:

    • Coughing
    • Cavity in the lung
    • Sputum smears positive for acid-fast bacilli (AFB)
    • TB disease of the lungs, airway, or larynx
    • Undergoing cough-inducing or aerosol-generating procedures
    • Not receiving adequate therapy
    • Culture positive

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    Slide 154. Criteria to Be Considered Noninfectious

    Patients no longer considered infectious if:

    • They have 3 consecutive negative sputum smears,
    • Their symptoms have improved, and
    • They are adhering to an adequate treatment regimen for at least 2 weeks

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    Slide 155. Environmental Factors that Enhance Risk of Transmission

    • High concentration of droplet nuclei in the air
    • Exposure in small, enclosed spaces
    • Poor ventilation that inadequately dilutes or removes droplet nuclei
    • Recirculation of air containing droplets
    • Improper specimen handling procedures
    • Positive air pressure in patient’s room causing flow to other areas

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    Slide 156. TB Infection Control Measures

    • TB infection control (IC) measures should be based on TB risk assessment for the setting
    • The goals of IC programs are
      • Detect TB disease early and promptly
      • Isolate persons with known/suspected TB
      • Start treatment in persons with known/suspected TB

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    Slide 157. Detection of TB Disease

    • Primary risk in health-care settings: unsuspected persons with TB disease
    • Protocols for detecting, isolating, and managing TB suspects should be implemented
    • Staff admitting patients should be trained to know signs/symptoms of TB

    [Image: doctor and patient seated at a desk in a clinic setting, facing each other; doctor is speaking; both wear personal respiratory protection]

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    Slide 158. Airborne Precautions

    • Separate and isolate persons with TB signs/symptoms
      • Preferably use airborne infection isolation (AII) room
      • Single-patient room with controlled environment to minimize transmission of infection
      • Continue precautions until 3 negative smears, 2 weeks therapy, and improved symptoms
    • Start TB patients/suspects on standard TB therapy

    [Image: Patient seated alone in clinic setting, wearing personal respiratory protection and reading patient literature]

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    Slide 159. Hierarchy of controls

    TB IC program should be based on three levels of controls:

    • Administrative controls to reduce risk of exposure
    • Engineering controls to prevent spread and reduce concentration of droplet nuclei
    • Personal respiratory protection to further reduce risk of exposure

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    Slide 160. Administrative Controls

    To reduce risk of exposing uninfected persons to infectious disease:

    • Assign responsibility for IC in the facility
    • Conduct annual facility risk assessment by examining
      • Number of TB patients in the setting
      • Promptness of detecting, isolating, and evaluating TB suspects
      • Evidence of transmission in the setting
      • Community TB rate

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    Slide 161. Administrative Controls (cont.)

    • As part of risk assessment, do risk classification to determine need for testing
      • Low risk: Settings where persons with TB not likely to be seen
      • Medium risk: Settings where HCWs will possibly be exposed to TB
      • Potential ongoing transmission: Settings with evidence of transmission in past year

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    Slide 162. Administrative Controls (cont.)

    • Institute IC plan to ensure TB suspects found, isolated, evaluated, treated
    • Ensure recommended laboratory services are available
    • For HCWs, implement effective work practices and test as classification indicates
    • Ensure equipment is properly cleaned, disinfected, and sterilized
    • Educate, train, and counsel HCWs, patients, visitors about TB

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    Slide 163. Environmental controls

    Prevent spread and reduce concentration of infectious droplet nuclei through

    • Primary controls: ventilation technologies
      • Natural ventilation: relies on open doors, windows
      • Mechanical ventilation (local exhaust and general): equipment,  use of AII room
    • Secondary controls: HEPA filters and ultraviolet germicidal irradiation (UVGI)

    [Image: Diagram of TB exam or counseling room, with furniture arranged so that health care worker sits near source of fresh air supplied to room (vented door) and infectious patient sits near open window]

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    Slide 164. Environmental controls (cont.)

    AII rooms designed to prevent spread of droplet nuclei

    • TB suspect/patient should be put in AII room immediately
    • Facilities that see TB patients should have at least one AII room

    [Image: Diagram of AII room, showing bed, private bathroom, window, door, and sources of air supply and air exhaust]

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    Slide 165. Environmental controls (cont.)

    Characteristics of AII room:

    • Single-patient room with private bathroom
    • Negative pressure relative to hallway
    • Air sent outdoors or through HEPA filter
    • Six or more air changes per hour (in some settings 12 or more air changes per hour are recommended)
    • Visitors should use N95 respirator

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    Slide 166. Respiratory Protection Controls

    Consists of using personal protective equipment in areas with increased risk of exposure:

    • TB AII rooms
    • Rooms where cough- or aerosol-producing procedures are done
    • Vehicles transporting infectious patients
    • Homes of infectious TB patients

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    Slide 167. Respiratory Protection Controls (cont.)

    • Settings that use respiratory protection controls should develop, implement, and maintain a respiratory protection program
    • Train HCWs on respiratory protection
    • Educate patients on respiratory hygiene
    • Test HCWs for mask fit and functionality

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    Slide 168. Respirator for Health Care Workers

    [Image: Health care worker wearing a respirator]
    [Image: Display of several types of respirators]
    Respirators

    • Designed to filter out droplet nuclei from being inhaled by the health-care worker and other individuals.
    • Should properly fit different face sizes and features.
    • Should NOT be worn by the patient.

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    Slide 169. Surgical Mask for Persons with Infectious TB disease

    [Image: TB patient wearing a surgical mask]
    [Image: Display of several surgical masks]
    Surgical masks

    • Designed to stop droplet nuclei from being spread (exhaled) by the patient.
    • Should NOT be worn by the health-care worker.

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    Slide 170. Infection Control Programs in Nontraditional Settings

    Nontraditional settings seeing TB patients must have an IC program. These include

    • Correctional facilities
    • Homeless shelters
    • Long-term care facilities
    • Home-based health-care and outreach settings
    • Emergency medical services

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    Slide 171. TB Infection Control in the Home

    Patients can be sent home while still infectious if

    • A follow-up plan has been made
    • Patient is on standard treatment and DOT arranged
    • No very young (under 4 years) or immunocompromised persons in household
    • Patient willing to refrain from travel outside the home except for health-care visits

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    Slide 172. TB Infection Control in the Home (cont.)

    HCWs visiting patients at home should:

    • Instruct patients to cover mouth/nose when coughing or sneezing
    • Wear a respirator when visiting or transporting an infectious patient
    • Collect specimens in well-ventilated area

    HCWs whose responsibilities include visiting patients at home should participate in an annual TB testing program

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    Slide 17. (title slide). Chapter 8. Community TB Control

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    Slide 174. Responsibility for TB Control

    • Health departments maintain primary responsibility for TB prevention and control
    • Complexity of TB control requires public health sector to collaborate with others

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    Slide 175. Roles and Responsibilities of Public Health Sector

    Public health sector plans, coordinates, and evaluates TB control efforts
    Requires state and local health departments to focus on

    • Planning and policy development
    • Contact investigation
    • Clinical/diagnostic services for TB patients and their contacts
    • Training and education
    • Surveillance and information management
    • Monitoring and evaluation

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    Slide 176. Roles and Responsibilities of Public Health Sector (cont.)

    Planning and Policy Development

    • TB control programs should collaborate with community stakeholders to develop plan
    • Written plan should be based on the following:
      • Local epidemiologic data
      • Availability of clinical and support services
      • Availability of fiscal resources
      • Current legal statutes and standards of care

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    Slide 177. Roles and Responsibilities of Public Health Sector (cont.)

    Planning and Policy Development (cont.)

    • Plan should
      • Assign specific roles and responsibilities
      • Define pathways of communication
      • Assign sufficient human and financial resources
      • Provide for expert consultation and oversight
      • Provide guidance to TB laboratories

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    Slide 178. Roles and Responsibilities of Public Health Sector (cont.)

    Planning and Policy Development (cont.)
    Plan should

    • Ensure complete/timely contact investigations (CIs) are done; assist local providers in CIs and providing DOT
    • Provide culturally appropriate info to patients
    • Minimize financial and cultural barriers to TB control
    • Ensure clinicians promptly report all suspected and confirmed TB cases

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    Slide 179. Roles and Responsibilities of Public Health Sector (cont.)

    Clinical and Diagnostic Services
    Health department must ensure

    • TB patients can access diagnostic/treatment services
    • Completeness of TB-related services and continuity of care, regardless of where patient seeks care
    • Standards of care are met

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    Slide 180. Roles and Responsibilities of Public Health Sector (cont.)

    Clinical and Diagnostic Services (cont.)
    Health department must ensure

    • Radiology and lab services readily accessible
    • Radiograph and AFB results available within 24 hours
    • All TB smear, culture, and drug-susceptibility results reported promptly by laboratories

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    Slide 181. Roles and Responsibilities of Public Health Sector (cont.)

    Training and Education
    TB control programs should

    • Provide training for TB control program staff
    • Educate other HCWs, community members, public health officials, and policy makers
    • Create and implement educational activities using resources from CDC, RTMCCs, NIH-supported TB curriculum centers, NTCA, and others

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    Slide 182. Roles and Responsibilities of Public Health Sector (cont.)

    Surveillance and Information Management

    • Surveillance and information management systems should be priorities of all TB control programs
    • Patient care can be improved through standardized data collection and test result tracking
    • Other benefits include ready access to details of treatment regimens, DOT administration, drug-drug interactions

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    Slide 183. Roles and Responsibilities of Public Health Sector (cont.)

    Monitoring and Evaluation

    • Evaluation provides programs evidence-based means of improving TB control strategies
    • Develop evaluation priorities based on local TB challenges and how services are organized
    • First priority for evaluation should be on key TB control strategies:
      • Identify and treat all persons with infectious TB disease
      • Find contacts and others at high risk; offer therapy
      • Interrupt transmission in high-risk settings

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    Slide 184. Roles and Responsibilities of Specific Private Sector Providers

    Private sector includes

    • Clinicians
    • Community health centers
    • Hospitals
    • Academic institutions
    • Medical professional organizations
    • Community-based organizations
    • Correctional facilities
    • Civil surgeons
    • Pharmaceutical and biotechnology industries

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    Slide 185. Roles and Responsibilities of Specific Private Sector Providers (cont.)

    Role of Clinicians

    • Understand prevalent medical conditions of their patient populations
    • Be aware of local TB reporting laws
    • Know procedures for suspected TB: diagnose, hospitalize, report case, plan treatment
    • Follow current guidance for screening, diagnosis, treatment of TB and LTBI
    • Be able to administer TB tests, rule out TB disease, administer treatment

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    Slide 186. Roles and Responsibilities of Specific Private Sector Providers (cont.)

    Role of Community Health Centers

    • Ensure staff ability to assess, diagnose, and start treatment for TB and LTBI
    • Work closely with local physicians, hospitals, labs, and public health agencies
    • Arrange for reporting of TB suspects; refer patients to necessary services

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    Slide 187. Roles and Responsibilities of Specific Private Sector Providers (cont.)

    Role of Community Health Centers (cont.)

    • Be aware of local programs providing TB services for high-risk patients
    • Educate and motivate patients about implications of TB
    • Establish recommended infection control practices

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    Slide 188. Roles and Responsibilities of Specific Private Sector Providers (cont.)

    Role of Hospitals

    • Develop infection control policies and plans to prevent transmission
    • Promptly report suspected/confirmed TB cases
    • Provide training to staff
    • Ensure TB patients are discharged on a standard regimen and with follow-up plan

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    Slide 189. Roles and Responsibilities of Specific Private Sector Providers (cont.)

    Role of Academic Institutions

    • Incorporate TB into their curricula
    • Serve as a community resource in TB management issues
    • Partner with local public health agencies in TB control activities
    • Provide leadership in conducting TB-related research

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    Slide 190. Roles and Responsibilities of Specific Private Sector Providers (cont.)

    Role of Medical Professional Organizations

    • Train/educate members regarding TB
    • Provide professional leadership on clinical practice and control of TB
    • Advocate for adequate TB control funding
    • Promote global TB control; link U.S. health professionals with those outside the U.S.

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    Slide 191. Roles and Responsibilities of Specific Private Sector Providers (cont.)

    Role of Community Based Organizations

    • Partner with local public health sector to facilitate access to services for target population
    • Participate in advocacy/support activities
    • Coordinate with public health sector to develop education materials tailored to their populations

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    Slide 192. Roles and Responsibilities of Specific Private Sector Providers (cont.)

    Role of Correctional Facilities

    • Coordinate with local public health sector to develop epi profile of TB risk in inmate population
    • Develop written policies and establish effective TB control program
    • Ensure persons under TB treatment are linked to needed services upon discharge
    • Develop infection control program
    • Evaluate institution’s TB control program, in collaboration with local public health sector
    • Develop ongoing training/education for staff

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    Slide 193. Roles and Responsibilities of Specific Private Sector Providers (cont.)

    Role of Civil Surgeons

    • Understand and follow current guidelines for diagnosis/treatment of TB and LTBI
    • Work with local public health sector; report suspected and confirmed TB cases
    • Develop referral mechanism for evaluation of TB in persons seeking status adjustment

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    Slide 194. Roles and Responsibilities of Specific Private Sector Providers (cont.)

    Role of Pharmaceutical and Biotechnology Industries

    • Understand their role in developing tools for diagnosing, treating, preventing TB
    • Review costs/markets for new product development and potential funding sources
    • Join coalitions such as Global Partnership to Stop TB, Global Alliance for TB Drug Development, FIND
    • Work with other stakeholders to ensure access to products for patients

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