Tuberculosis
 Richard H. Simon
Pulmonary and Critical Care Medicine
Department of Internal Medicine
 richsimo@umich.edu
...
Objectives: To Understand
 When TB belongs in the differential
diagnosis of a patient presenting with
pulmonary symptoms
...
Case History - 1
 43 y.o. female with a 10 day history
of:
– Cough, producing yellow sputum
– Fever and night sweats
– Mi...
Diagnostic Questions
 Is the cause of symptoms likely to be
infection?
 If so, could this be tuberculosis?
Why is it imp...
Common Symptoms of Pulmonary TB
 Cough and sputum production
– Usually insidious onset, increasing over
weeks to months
–...
Common Radiological Features of TB
 Primary disease
– Parenchymal infiltrate
– Ipsilateral hilar node enlargement
 React...
Deciding Whether to Keep Tuberculosis in
the Differential Diagnosis
 Use demographic information to adjust
probably that ...
Incidence of Tuberculosis in US
1953 - 1999
0
10
20
30
40
50
60
1950 1960 1970 1980 1990 2000
Incidence/100,000population
Reported TB Cases
United States, 1982-2002
Year
No.ofCases
10000
12000
16000
20000
24000
28000
83 85 87 89 91 93 95 97 99 ...
TB Morbidity
United States, 1998-2002
Year Cases Rate*
1998 18,361 6.8
1999 17,531 6.4
2000 16,377 5.8
2001 15,989 5.6
200...
TB Case Rates, United States, 2002
< 3.5 (year 2000 target)
3.6 - 5.2
> 5.2 (national average)
D.C.
Rate: cases per 100,000
TB Case Rates by Age Group
United States, 1992-2002
0
5
10
15
20
1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002
<1...
Number of TB Cases in
U.S.-born vs. Foreign-born Persons
1992-2002
0
5000
10000
15000
20000
1992 1994 1996 1998 2000 2002
...
>50%
25%-49%
<25%
1992 2002
Percentage of TB Cases Among
Foreign-born Persons
Countries of Birth for Foreign-born Persons
Reported with TB
United States, 2002
Mexico
(25%)
Philippines
(11%)
Vietnam
(8...
Length of U.S. Residence Prior to TB
Diagnosis, United States, 2002
0%
20%
40%
60%
80%
100%
All Philippines Mexico Vietnam...
TB Incidence by Income
0
10
20
30
40
Incidence/100,000/yr
$10,000 $20,000 $30,000
Income
Use of Skin Test in Diagnosis of
Active TB
 Reactivity indicates:
– Past exposure to TB, or
– False positive
 Absence of...
Case History - 2
 Patient recent immigrant
from Southeast Asia
 History of 15 mm PPD
reaction
 Chest x-ray shows right
...
Sputum Evaluation for Diagnosis of TB
 Smear
– Techniques:
 Kinyon or Ziehl-Neelsen stain
 Auramine/rhodamine stain
– F...
Culture for M. tuberculosis
 Organisms grow slowly
 Species identification
– Colony morphology (weeks)
– Nucleic acid pr...
Case History - 3
 Positive smear for acid fast bacillus
 Positive nucleic acid amplification test for
M. tuberculosis
 ...
Short Course Chemotherapy for
Active Tuberculosis
 First 2 months:
– Isoniazid
– Rifampin (beware of complex interactions...
Adherence to Treatment
 Nonadherence is a major problem in
TB control
 Use case management and directly
observed therapy...
Public Health Considerations - 1
 Has patient infected others?
– Assume “yes”, and evaluate contacts
(skin test)
– Factor...
Public Health Considerations - 2
 Where should patient be isolated?
– Goal of isolation
Minimize new contacts
Minimize ...
Public Health Considerations - 3
 Patients no longer considered
infectious if they meet all of these
criteria:
– On adequ...
Preventing New Cases of Active
Tuberculosis
 Prevent new infections
 Prevent reactivation of latent
infections
Preventing New Infections
 Eliminate the source of infectious
organisms
– Identify and treat patients with active disease...
Preventing Reactivation of Latent
Infections
 Identify previously infected
individuals, particularly those most
likely to...
Identifying Previously Infected
Individuals -- PPD Skin Test
 Highly accurate in majority of people
 False positives
– P...
Identify Previously Infected Individuals
-- PPD Skin Test
 Use smaller induration cut-off when:
– Likelihood of TB infect...
Incidence of Reactivating TB in Previously
Infected Patients (+ PPD)
TB cases / 1,000 person-years
 No additional risk fa...
Treatment Regimens for Latent Tuberculosis
Infection
 Isoniazid 6 - 9 months
 Rifampin and pyrazinamide 2 months
(Higher...
Treatment of Latent TB Infection
 Highly effective at killing bacteria
 Major side effect: Hepatitis (age related for IN...
Candidates for Treatment of Latent TB Infection
Based on PPD Result
 > 5 mm
– HIV- positive persons
– Close contacts of p...
Candidates for Treatment of Latent TB Infection
Based on PPD Result
 > 10 mm
– Immigrants ( w/i 5 yrs) from high prevalen...
Medical Conditions Associated
with TB Reactivation
 Silicosis
 Gastrectomy or jejunoileal bypass
 Body weight 10% or mo...
Candidates for Treatment of Latent TB Infection
Based on PPD Result (?)
 > 15 mm
– Persons with no risk actors*
– Controv...
Before Treatment for LTBI Is Started...
 Rule out possibility of active TB disease
– Screen for fever, cough, sputum prod...
Reference:
 http://www.cdc.gov/nchstp/tb/pubs/m
mwrhtml/maj_guide.htm
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Tuberculosis Richard H. Simon Pulmonary and Critical Care ...

  1. 1. Tuberculosis  Richard H. Simon Pulmonary and Critical Care Medicine Department of Internal Medicine  richsimo@umich.edu  764-4554
  2. 2. Objectives: To Understand  When TB belongs in the differential diagnosis of a patient presenting with pulmonary symptoms  The tests used to diagnose TB  Isolation of patients with TB  Treatment of active TB  Diagnosis and treatment of latent TB
  3. 3. Case History - 1  43 y.o. female with a 10 day history of: – Cough, producing yellow sputum – Fever and night sweats – Mild shortness of breath – Fatigue – Loss of appetite
  4. 4. Diagnostic Questions  Is the cause of symptoms likely to be infection?  If so, could this be tuberculosis? Why is it important to make a decision if tuberculosis belongs on differential diagnosis list?
  5. 5. Common Symptoms of Pulmonary TB  Cough and sputum production – Usually insidious onset, increasing over weeks to months – Less commonly, acute onset with rapid progression – Hemoptysis frequent  Fever, night sweats  Anorexia, weight loss
  6. 6. Common Radiological Features of TB  Primary disease – Parenchymal infiltrate – Ipsilateral hilar node enlargement  Reactivation disease – Upper lobe (apical posterior)  Infiltrate  Cavity  Pleural disease  In HIV, “atypical” appearances frequent, e.g hilar/mediastinal lymphadenopathy only
  7. 7. Deciding Whether to Keep Tuberculosis in the Differential Diagnosis  Use demographic information to adjust probably that patient has tuberculosis – Consider likelihood of prior contact with tuberculosis – Consider likelihood of developing active disease, if previously infected
  8. 8. Incidence of Tuberculosis in US 1953 - 1999 0 10 20 30 40 50 60 1950 1960 1970 1980 1990 2000 Incidence/100,000population
  9. 9. Reported TB Cases United States, 1982-2002 Year No.ofCases 10000 12000 16000 20000 24000 28000 83 85 87 89 91 93 95 97 99 2001
  10. 10. TB Morbidity United States, 1998-2002 Year Cases Rate* 1998 18,361 6.8 1999 17,531 6.4 2000 16,377 5.8 2001 15,989 5.6 2002 15,075 5.2 *Cases per 100,000
  11. 11. TB Case Rates, United States, 2002 < 3.5 (year 2000 target) 3.6 - 5.2 > 5.2 (national average) D.C. Rate: cases per 100,000
  12. 12. TB Case Rates by Age Group United States, 1992-2002 0 5 10 15 20 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 <15 15-24 25-44 45-64 65+
  13. 13. Number of TB Cases in U.S.-born vs. Foreign-born Persons 1992-2002 0 5000 10000 15000 20000 1992 1994 1996 1998 2000 2002 U.S.-born Foreign-born
  14. 14. >50% 25%-49% <25% 1992 2002 Percentage of TB Cases Among Foreign-born Persons
  15. 15. Countries of Birth for Foreign-born Persons Reported with TB United States, 2002 Mexico (25%) Philippines (11%) Vietnam (8%)India (7%)China (5%) Haiti (3%) S. Korea (3%) Other Countries (38%)
  16. 16. Length of U.S. Residence Prior to TB Diagnosis, United States, 2002 0% 20% 40% 60% 80% 100% All Philippines Mexico Vietnam <1 yr 1- 4 yrs >5 yrs
  17. 17. TB Incidence by Income 0 10 20 30 40 Incidence/100,000/yr $10,000 $20,000 $30,000 Income
  18. 18. Use of Skin Test in Diagnosis of Active TB  Reactivity indicates: – Past exposure to TB, or – False positive  Absence of reactivity doesn’t exclude active TB – < 10 mm induration seen in up to ~20% of active TB patients
  19. 19. Case History - 2  Patient recent immigrant from Southeast Asia  History of 15 mm PPD reaction  Chest x-ray shows right upper lobe cavitary  Therefore, tuberculosis likely -- initiate treatment
  20. 20. Sputum Evaluation for Diagnosis of TB  Smear – Techniques:  Kinyon or Ziehl-Neelsen stain  Auramine/rhodamine stain – False negative smears common – False positive smears can occur  Nucleic acid amplification tests  Culture
  21. 21. Culture for M. tuberculosis  Organisms grow slowly  Species identification – Colony morphology (weeks) – Nucleic acid probes after micro-colonies appear (1-2 additional days) – Biochemical analyses after macro-colonies appear (1 day)
  22. 22. Case History - 3  Positive smear for acid fast bacillus  Positive nucleic acid amplification test for M. tuberculosis  Diagnosis confirmed, treatment continues
  23. 23. Short Course Chemotherapy for Active Tuberculosis  First 2 months: – Isoniazid – Rifampin (beware of complex interactions with drugs used to treat HIV) – Pyrazinamide – Ethambutol or Streptomycin (if chance of drug resistant organisms >4%)  Final 4 months – Isoniazid – Rifampin  A subset of patient should be extend their treatment of a total of 9 months
  24. 24. Adherence to Treatment  Nonadherence is a major problem in TB control  Use case management and directly observed therapy (DOT) to ensure patients complete treatment
  25. 25. Public Health Considerations - 1  Has patient infected others? – Assume “yes”, and evaluate contacts (skin test) – Factors making transmission more likely Infectiousness of person with TB  Actively coughing  Cavitary disease  Smear positive Poorly ventilated environment Duration of exposure
  26. 26. Public Health Considerations - 2  Where should patient be isolated? – Goal of isolation Minimize new contacts Minimize continuing exposure to children or highly susceptible persons – Isolation at home permissible, if above goals are met
  27. 27. Public Health Considerations - 3  Patients no longer considered infectious if they meet all of these criteria: – On adequate therapy – Demonstrating a significant clinical response to therapy – Have had 3 consecutive negative sputum smear results
  28. 28. Preventing New Cases of Active Tuberculosis  Prevent new infections  Prevent reactivation of latent infections
  29. 29. Preventing New Infections  Eliminate the source of infectious organisms – Identify and treat patients with active disease  Implement effective TB control measures at high risk locations – Decrease chances that a non-infected person inhales viable TB bacteria ( = good ventilation)
  30. 30. Preventing Reactivation of Latent Infections  Identify previously infected individuals, particularly those most likely to reactive their latent infection  Treat latent TB infection when benefits outweigh risks of treatment
  31. 31. Identifying Previously Infected Individuals -- PPD Skin Test  Highly accurate in majority of people  False positives – Previous exposure to non-tuberculous mycobacteria – Previous vaccination with BCG  False negatives (anergic to PPD antigen) – Cachexia – Immunosuppressed (particularly HIV infection)
  32. 32. Identify Previously Infected Individuals -- PPD Skin Test  Use smaller induration cut-off when: – Likelihood of TB infection is higher – Likelihood of re-activating latent disease is higher  Use larger induration cut-off when: – Likelihood of infection is lower – Likelihood of re-activation is lower
  33. 33. Incidence of Reactivating TB in Previously Infected Patients (+ PPD) TB cases / 1,000 person-years  No additional risk factors 0.8  HIV infection 35 - 162  Recent TB infection – Infection < 1 yr past 25-30 – Infection 1-7 past 10-20  IV drug users 10  CXR evidence of old TB 2 - 14
  34. 34. Treatment Regimens for Latent Tuberculosis Infection  Isoniazid 6 - 9 months  Rifampin and pyrazinamide 2 months (Higher incidence of liver toxicity in non HIV-infected patients)  Rifampin 4 months
  35. 35. Treatment of Latent TB Infection  Highly effective at killing bacteria  Major side effect: Hepatitis (age related for INH)  Guidelines for decision to treat based on: – Likelihood that a positive skin test is a true positive – Likelihood that the patient will progress to active disease – Likelihood that patient will develop hepatitis
  36. 36. Candidates for Treatment of Latent TB Infection Based on PPD Result  > 5 mm – HIV- positive persons – Close contacts of persons known or suspected of having TB – Fibrotic changes on chest x-ray suggesting past TB – Patients with organ transplants – Immunosuppressed patients
  37. 37. Candidates for Treatment of Latent TB Infection Based on PPD Result  > 10 mm – Immigrants ( w/i 5 yrs) from high prevalence countries – Intravenous drug users – Residents and employees of high risk settings  Prisons  Nursing homes  Health care facilities – Mycobacteriology laboratory personnel – Children < 4 years of age – Children and adolescents exposed to adults at high risk – Persons with medical conditions that increase risk of TB reactivation
  38. 38. Medical Conditions Associated with TB Reactivation  Silicosis  Gastrectomy or jejunoileal bypass  Body weight 10% or more below ideal level  Chronic renal failure  Diabetes mellitus  Prolonged use of corticosteroid or other immunosuppressive drugs  Certain hematological conditions, e.g. leukemia and lymphomas  Other malignancies
  39. 39. Candidates for Treatment of Latent TB Infection Based on PPD Result (?)  > 15 mm – Persons with no risk actors* – Controversial whether this group benefits from therapy * Don’t skin test this group
  40. 40. Before Treatment for LTBI Is Started...  Rule out possibility of active TB disease – Screen for fever, cough, sputum production, weight loss – Check chest x-ray for evidence of active disease  Obtain information about current and previous drug therapy  Determine contraindications to treatment  Recommend HIV testing if risk factors are present
  41. 41. Reference:  http://www.cdc.gov/nchstp/tb/pubs/m mwrhtml/maj_guide.htm

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