OVERVIEW OF TUBERCULOSIS

1
OVERVIEW OF TUBERCULOSIS

• Shehla P Islam
• Assistant Professor
• UF- Division of Infectious Diseases
• October 27, 2009.

2
Clinical Presentation

• Mr. WC is a 42 yo WM homeless alcoholic Eastern
  European immigrant CC. Cough with yellow
  sputum x 3 mo
• 3 mo PTA he began feeling poorly and stopped
  drinking. He began noting fever and night sweats
• 2 mo PTA he noted increased cough productive of
  yellow sputum
• 2 weeks PTA he realized he had lost nearly 30 lbs
• PE Temp 39C, BP 112/58, HR 88 RR 24Very thin,
  chronically ill appearing. Lungs - normal breath
  sounds without rales or rhonchi, no post-tussic
  ralesExtremities - clubbing

3
Questions you should be asking yourself?

• How ill is he? Is this an emergency?
• How did he contract this infection?
• Did he have risk factors that predisposed him to
  infection?
• Do his symptoms help you to decide the cause of
  his pulmonary infection?
• What tests should I order?
• What is the most likely cause?
• How should I treat him?

4
Mycobacterium Tuberculosis Microbiology

• Higher bacterium
• Possibly evolved from M.bovis in Indo-Europeans
• Slow growing
• Lowenstein Jensen Media Usually 4-6 wks to grow
• Not seen on Gram stain.
• Acid-fast---appears red with Acid Fast staining

5
M.Tuberculosis Epidemiology

• Humans only reservoir
• Person-to-person spread via aerosolized
  infectious droplets following sneezing or
  coughing.
• Some patients more infectious

6
DISEASE BURDEN

• In 2005, there were 9 million new cases in the
  world, with 1.6 million deaths from it.
• Estimated 10-15 million persons in U.S. infected
  with M. tuberculosis
• Without intervention, about 10 will develop TB
  disease at some point in life

7
M.Tuberculosis Epidemiology

• Which group is most commonly presents with TB in
  the US?
• Immigrants from developing nations
• The urban poor
• Alcoholics
• Single males
• IV drug abusers

8
(No Transcript)
9
(No Transcript)
10
PERSONS AT HIGHER RISK OF DEVELOPING TB DISEASE
ONCE INFECTED

• HIV infected
• Recently infected
• Persons with certain medical conditions
• Persons who inject illicit drugs
• History of inadequately treated TB

11
Mycobacterium TuberculosisPathogenesis

• The lipid wall resists drying and many
  disinfectants
• Macrophages carry to the lymph nodes Survive
  within macrophages for years
• Cell mediated immune response.
• Caseating granulomascell mediated immune
  response lipid-rich bacteria
• Increased levels of IL-1 cause fever
• Increased levels of TNF cause weight loss

12
EVALUATION FOR TB

• Medical history
• Physical examination
• Mantoux tuberculin skin test
• Chest radiograph
• Bacteriologic or histologic exam

13
MEDICAL HISTORY

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

14
GENERAL SYMPTOMS OF TB

• Fever
• Chills
• Night sweats
• Appetite loss
• Weight loss
• Easy fatigability

15
FOCAL SYMPTOMS depend on site

• COMMON SITES
• Lungs
• Pleura
• Central nervous system
• Lymphatic system
• Genitourinary systems
• Bones and joints
• Disseminated (miliary TB)

16
PULMONARY SYMPTOMS

• Productive, prolonged cough
• (duration of 3 weeks or more)
• Chest pain
• Hemoptysis

17
Diagnosis of TB

• Zeil Nielson acid fast stain can detect 1 x 104
  organisms/ml, 60 sensitivity
• 3 negative smears to assure low infectivity (Does
  this exclude TB?)
• Culture most sensitive and specific test.
• PCR
• PPD

18
(No Transcript)
19
(No Transcript)
20
Clinical Forms of TB

• Primary
• Secondary or Reactivation
• Miliary

21
Primary TB

• First exposure
• Inhalation followed by a flu-like illness
• Bacteremia develops can silently seed multiple
  sites in the body.
• The bacteria take hold in specific sites in the
  body.
• 4-8 weeks cell-mediated immunity
• May see a Ghon complex

22
Primary TB
23
Clinical Presentation

• Pt A is a 42 yo WM homeless alcoholic Eastern
  European immigrant CC. Cough with yellow
  sputum x 3 mo
• 3 mo PTA he began feeling poorly and stopped
  drinking. He began noting fever and night sweats
• 2 mo PTA he noted increased cough productive of
  yellow sputum
• 2 weeks PTA he realized he had lost nearly 30 lbs
• PE Temp 39C, BP 112/58, HR 88 RR 24Very thin,
  chronically ill appearing. Lungs - normal breath
  sounds without rales or rhonchi, no post-tussic
  ralesExtremities - clubbing

24
Pt A Initial CXR
Extensive left upper lobe disease, RUL as well
25
(No Transcript)
26
What type of tuberculosis does this man have?

• Primary tuberculosis
• Cancer with an incidental positive AFB smear
• Sarcoidosis
• Miliary tuberculosis
• Secondary tuberculosis

27
Secondary Tuberculosis

• Reactivation occurs in 10-15 of patients 1/2
  within 2 years of primary disease
• Usually an Apical infection
• Most commonly males 30-50 yo

28
Secondary Tuberculosis

• Slowly Progressive (several months)
• Worsening cough with sputum production
• Low grade fever, night sweats, fatigue and weight
  loss
• Hemoptysis or pleuritic pain are rare (seen only
  in severe disease)

29
Secondary Tuberculosis

• PE minimal findings, post tussic rales
• CXR apical cavities (without fluid), apical
  lordotic CT scan often helpful
• Cavitary disease very infectious. Why?
• Isolate all patients.
• In HIV, abnormal CXR tuberculosis (atypical
  CXR) Why are lesions atypical in AIDS?

30
PT A Initial CXR
Extensive left upper lobe disease, RUL as well
31
PT A2 weeks into Rxminimal change
32
Pt A - 3 months into RX scarring LUL
33
Cavitary TB
34
Who is at highest risk for disseminated
tuberculosis? (Miliary TB)

• Teenagers exposed to TB for the first time
• Elderly patients with a past history of Tb
  exposure
• Young children exposed to TB for the first time
• HIV patients with a past history of TB exposure.
• Middle aged single men with a 1st exposure to TB

35
Miliary TB

• Mycobacterial infection not controlled.
• Persistent dissemination occurs with primary
  disease and occasionally with reactivation
• See in patients with depressed cell-mediated
  immunity

36
Miliary TB Clinical Manifestations

• Symptoms are nonspecific
• Children - High fever Night
  sweats Weight loss
  Hepatosplenomegally Lymphadenopathy
• Adults - Moderate to low grade fever Night
  sweats Malaise and anorexia Weakness Weight
  loss

37
Miliary TB Diagnosis Treatment

• Funduscopic exam - choroid tubercles
• Laboratory - leukemoid reaction anemia low
  serum Na abnormal LFTs
• CXR - Micronodular interstitial pattern (millet
  seeds) Normal elderly and HIV patients. Why?

38
Miliary TB
39
Miliary TB Diagnosis Treatment

• Diagnosis - blood cultures transbronchial
  biopsy bone marrow culture and pathology
  Liver biopsy
• Treatment - Early therapy for all suspected cases
  (4 drugs)

40
Isolate All Suspected TB patients
41
ISOLATION AND PERSONAL RESP PROTECTION
A negative pressure room and the N-95
respirator will be fine!!!
42
Isolate All Suspected TB patients

• Negative pressure room
• Masks that remove microdroplets
• Contact Infection Control
• PPD for all exposed individuals
• Importance of identifying 2ndary cases
• AFB smear directly correlates with infectiousness

43
(No Transcript)
44
Treatment of TB

• 1/ 106 organisms naturally resistant to one
  drug.Calculate how many organisms it would take
  to select for a bacteria resistant to 2 drugs.
• 106
• 108
• 1010
• 1012
• 1014

45
Treatment of TB

• 4-drug regimen pending sensitivity testing
• -1/ 106 organisms naturally resistant to one
  drug- Cavitary lesions have 109-1010
  organisms- Two drugs sufficient
• - However, primary INH resistance common. INH
  resistance associated with poorer outcome.
• - Primary cidal agent, therefore to prevent
  resistance
• INH, rifampin, pyrazinimide, ethambutol

46
Use multiple drugs to which the organisms are
susceptible
47
(No Transcript)
48
Non-adherence is a major problem in TB treatment
49
Treatment of TB

• INH-resistance is now common.
• Multi-drug resistance is most common in parts of
  Eastern Europe, Africa, and HIV pos pts.
• As a public health official how would reduce the
  incidence of multi-drug resistant tuberculosis?

50
(No Transcript)
51
Treatment of TB

• Directly observed therapy (DOT)
• Now the treatment of choice
• Involves high does of anti-tuberculosis drugs
  twice a week
• Has markedly reduced
• The incidence of drug resistance TB
• The over all incidence of TB in the US

52
Prevention of TB

•  It seems that if humans are the only reservoir
  for TB and it is spread by aerosolized droplets,
  than it should be a disease targeted for
  eradication.  Once again, I understand that
  because it afflicts developing nations where
  people live in crowded quarters this is not a
  particularly lucrative investment for
  pharmaceutical companies.  But what are the
  efforts of the WHO with regards to this and what
  kinds of improvements have been made so far, if
  any?

53
Prevention of TB

• TB is strictly spread from person to person.
• Need to Identify exposed individuals and prevent
  them from developing active disease
• Skin test can often accomplish this task
• Test only those in whom there is an identified
  risk

54
What is the meaning of a reactive PPD?

• You have active tuberculosis and need immediate
  treatment
• You have been exposed to tuberculosis and need to
  take INH to prevent active disease
• Your reactive PPD may be a false positive
  depending on where you come from.
• A reactive PPD has no meaning if you have
  received a BCG vaccination

55
(No Transcript)
56
(No Transcript)
57
Reading the Tuberculin Skin Test

• Read reaction 48-72 hours after injection
  
• Measure only induration
• Record reaction in millimeters

58
Classifying the Tuberculin Reaction

• 5 mm is classified as positive in
• HIV-positive persons
• Recent contacts of TB case
• Persons with fibrotic changes on chest radiograph
  
• consistent with old healed TB
• Patients with organ transplants and other
• immunosuppressed patients

59
Classifying the Tuberculin Reaction (cont.)

• 15 mm is classified as positive in
• Persons with no known risk factors for TB
• Targeted skin testing programs should only be
  conducted among high-risk groups

60
Classifying the Tuberculin Reaction (cont.)

• 10 mm is classified as positive in
• Recent arrivals from high-prevalence countries
• Injection drug users
• Residents and employees of high-risk congregate
  settings
• Mycobacteriology laboratory personnel
• Persons with clinical conditions that place them
  at high risk
• Children lt4 years of age, or children and
  adolescents
• exposed to adults in high-risk categories

61
Prevention of TB

• PPD 5 TU carefully standardized
• Positive test exposure in the past
• Negative to positive conversion

62
Prevention of TB

• INH Prophylaxis (INH 300 mg QD x 9 mo)
• Who should receive prophylaxis? All individuals
  with a positive PPD?
• Problem of hepatotoxicity. Increases in those
  over 35 y. Need to follow LFTs monthly
• What test should be ordered in all patients with
  a positive PPD?

63
(No Transcript)
64
TB Conclusions

• - Primary
• - Miliary
• - Secondary
• A chronic disease - Weight loss, fever
• AFB smear critical to determine infectiousness
  (importance of isolation)
• CXR - apical lesions (CXR atypical AIDS)
• Treatment - 4 drugs to start to prevent selection
  of resistance and DOT
• Prevention depends on PPD INH prophylaxis

65
(No Transcript)