1. Tuberculosis

3. Pathophysiology
• Mycobacterium tuberculosis (obligate aerobe)
• Inhalation of droplet nuclei suspended in air
---host defenses---> some survive and be
transported to the regional LN >> Granulomas
(tubercles) ---may progress to caseation
necrosis and calcification (= Ghon foci)

4. Pathophysiology
• If fails to contain the infection --> hematogenous/
lymphatic/ direct mechanical spreading
• Immunocompromised: spread rapidly, early active dz
• Immunocompetent: survive in areas of high O2/blood
– apical and posterior segments of the upper lobe
– superior segment of the lower lobe
– renal cortex
– meninges
– epiphyses of long bones
– vertebrae
=> Latent infection --- as the host defense system
weakens ---> progress to active tuberculosis

5. From Mason: Murray and Nadel's Textbook of Respiratory Medicine

7. Risk for Reactivation of TB

8. Clinical Features
Primary Tuberculosis
• Usually asymptomatic & PPD-positive
• Symptoms: fever, malaise, weight loss, chest
pain
• Pneumonitis ≈ a viral or bacterial infection
• Hilar adenopathy
• Some (esp. immunocompromised) rapidly
progressive and fatal

9. Clinical Features
Reactivation Tuberculosis
• Symptom: fever, night sweats, malaise,
fatigue, weight loss, productive cough,
hemoptysis, dyspnea, pleuritic chest pain
• PE - unremarkable, +/- rales
• 20% extrapulmonary
– LN, adrenal glands, bones and joints, GI, GU,
meninges, pericardium, peritoneum, pleura

10. Tuberculin Skin Test (TST)
• Most common method to detect exposure
• Mantoux test: PPD 0.1 mL ID  read
induration at 48-72 h
• If PPD positive or recent conversion 
treatment of latent TB

12. Tuberculin Skin Test (TST)
• False positive:
– exposure to nontuberculosis mycobacteria
– receive BCG
• False negative:
– improper administration technique
– abnormal immune systems
• Unreliable in acute stages of the disease
(>20% of active TB pts = false-negative results)

13. Chest Radiograph
• Most useful study for making a presumptive
diagnosis of pulmonary TB
• Normal CXR - high NPV  screening ED pts for
active pulmonary TB
• No specific abnormalities - not exclude active
TB

14. CXR – Primary TB
• Infiltrates
– Homogeneous
– any lobe, most = single lobe
• Enlarged hilar/mediastinal LN (most common)
– hallmark in children, less common in adults
– usually unilateral and assoc/w infiltrate
 atelectasis (esp. < 2 y/o)
• Normal CXR (common)

15. CXR – Primary TB
• Other findings:
– moderate to large pleural effusion
– miliary TB
– tuberculoma
• Calcified 1o focus = Ghon focus
• Ghon focus + calcified hilar LN = Ranke
complex
• Calcified 2o foci = Simon’s foci

16. CXR – Primary TB
• Progressive primary TB
– progressive parenchymal consolidation often
including secondary foci in the upper lobes
– multiple cavitary lesions
– single large abscess

20. CXR – Reactivation TB
• Upper lung infiltrate/consolidation
– usually apical/posterior segment of the upper
lobe, superior segment of the lower lobe
+/-cavitation
• high infectivity
• assoc/w bronchogenic spread

21. CXR – Reactivation TB
Alveolar opacity (exudative)
↓
Reticulonodular opacity (fibroproductive)
↓
Fibrotic scar
?Infectivity?
Only serial CXR can reliably differentiate active from
inactive disease

22. CXR – Reactivation TB
• Atypical radiographic patterns:
– Hilar adenopathy +/- RML collapse
– Infiltrates or cavities in the middle or lower lung
– Bronchogenic spread  multiple lobes
– Pleural effusion
– Solitary nodule
• Normal CXR

27. AFB Sputum Microscopy
• Most rapid test to support diagnosis
• Sensitivity 20-80% (Fluorochrome > Ziehl-
Neelsen or Kinyoun), Specificity 90-100%
• For pts unable to expectorate sputum:
– nebulized induction of sputum
– gastric aspiration
– fiberoptic bronchoscopy with bronchial washings,
brushings, and BAL or transbronchial biopsy may
be necessary

29. Culture
• “gold standard”
• (solid C/S) available in ≈ 4-8 wk
• (liquid C/S) available in ≈ 1-2 wk
– BACTEC, MGIT (mycobacteria growth indicator
tube)
– detect 10 - 100 bacilli/mL

30. Other Methods
• Nucleic Acid Amplification Tests
• The Ligase Chain Reaction
• Interferon-γ Release Assay (IGRA)
• Serology

31. Case Definition
• Tuberculosis suspect: symptoms or signs suggestive of TB
– most common = productive cough >2 wks
– +/- dyspnea, chest pains, hemoptysis
– +/- constitutional symptoms (loss of appetite, weight loss,
fever, night sweats, fatigue)
• Case of tuberculosis
– definite case of TB or
– one in which a health worker has diagnosed TB and has
decided to treat with a full course of TB treatment.
Note. Incomplete “trial” TB treatment should not be given as a
method for diagnosis.

32. Case Definition
• Definite case of tuberculosis
– M. tuberculosis complex identified from a clinical
specimen (culture or newer method)
– In countries that lack the laboratory capacity, a pulmonary
case with one or more initial AFB-positive sputum is also
considered to be a “definite” case, provided that there is a
functional external quality assurance (EQA) system with
blind rechecking

33. Case Definition
• Pulmonary TB (PTB): TB involving lung parenchyma or both
pulmonary and extrapulmonary TB
• Extrapulmonary TB (EPTB): TB involving organs other than
lung parenchyma, e.g. pleura, LN, abdomen, etc.
• Smear positive case: only one sputum specimen smear
positive AFB
• Smear negative case: 2 specimens are smear negative AFB
(at least one early-morning specimen) in a well functional
EQA system
(take sputum culture in all settings with an HIV prevalence
of >1% in pregnant women or ≥5% in TB pts)
• Smear not done

34. Management
• Suspected TB pts should be placed in separate
waiting areas, wear surgical masks, and be
instructed to cover the mouth and nose when
coughing.
• Immunocompromised pts with respiratory
symptoms should be isolated until TB can be
excluded.

35. Treatment
• New pts
– “new patient regimen” containing 6 mo of rifampicin:
2HRZE/4HR
• Previously treated pts
– culture
– drug susceptibility testing (DST) for at least H & R
– Rapid DST (1-2 d) >> wait for result
– Conventional DST/unavailable
• Tx failure/high risk MDR >> “MDR regimen”
• Default/Relapse >> “retreatment regimen with first-
line drugs”: 2HRZES/1HRZE/5HRE

41. Drug-induced Hepatitis
• Stop all drugs
• If severely ill with TB and unsafe to stop TB
treatment  streptomycin, ethambutol and a
fluoroquinolone should be started

42. INH-induced Peripheral Neuropathy
• Numbness/tingling/burning sensation of the
hands or feet
• Common in
– pregnant women - HIV infection
– alcohol dependency - malnutrition
– DM - chronic liver disease
– renal failure
• Prevention: pyridoxine 10 mg/day

43. Paradoxical Reaction or Immune
Reconstitution Disease
• clinically worsen after the initiation of anti-TBs
• common in HIV pts
• ↑ fever, radiographic infiltrates,
lymphadenopathy, worsening sign/symptom
• dDx: treatment failure, drug resistance,
noncompliance
• Tx: supportive, systemic steroids often added

44. Special Situations
• Pregnancy: streptomycin should not be used
(ototoxic to the fetus )
• Contraception: Rifampicin >> ↓T½ of pills
• Renal failure: ethambutol and pyrazinamide
doses = 3 times per week (significant renal
excretion)
• Advanced liver disease: LFT at the start >> if
↑ALT > 3X  different regimen

48. Miliary TB
= wide hematogenous spread (primary inf.) or
= secondary seeding of multiple organs in the
young or immunocompromised host
• Dx by 1) diffuse miliary nodules on CXR (1-3
mm) or 2) demonstration of mycobacteria in
multiple organs
• Choroidal tubercles on ocular exam are
pathognomonic

49. Miliary TB

50. Multidrug-resistant Tuberculosis
(MDR-TB)
• resistance to at least H & R
• Risks:
– prior TB treatment
– contact with a proven MDR case
– AFB positive at month 2 or 3 of treatment
– exposed in institutions with an MDR outbreak or a high
prevalence of MDR (such as certain prisons or mines)
– co-morbid conditions assoc/w malabsorption or rapid-
transit diarrhea
– HIV infection (in some settings)
– DM type 2

52. Extensive Drug-resistant Tuberculosis
(XDR-TB)
• resistance to H & R plus
• resistance to any fluoroquinolone and
• resistance to at least one injectable second-
line drug (kanamycin, amikacin , capreomycin,
strepyomycin)

53. Disposition
• Outpatient:
– D/C instructions = home isolation and follow-up
– Antituberculosis medications should not be
instituted in the ED unless physicians are
directed to do so by health care professionals
who will coordinate the treatment and monitor
adverse effects

54. Disposition
• Admission: I/C
– clinically toxic, hypoxic, or dyspneic
– uncertain diagnosis
– noncompliant
– difficult to obtain a proper Dx and institute Tx
– active drug-resistant TB
• Hospitalized pts require respiratory isolation

55. TB & HIV
• HIV >> ↑ risk of latent disease (≈ 10X)
↑ initial inf => active disease
↑ extrapulmonary TB
↑ sputum smear-negative TB
• CXR: ↑ typical of primary inf / atypical
findings
• “provider-initiated” HIV testing for suspected/
confirmed-TB pts of all ages  early Dx & Tx

56. Latent TB Infection (LTBI)
• Asymptomatic + Positive TST + No active dz
• Tx. considered for pts with
1. recent conversion to PPD-positive status
2. close contact with an individual with active TB
3. anergic individuals with known TB contact
• > 20 million Thais have LTBI >> impossible to
treat all
• Tx. INH 9 mo or Rifampicin 4 mo

57. EXTRAPULMONARY TB

58. Extrapulmonary TB
1. Lymphatic 42%
2. Pleural 18%
3. Bone/joint 12%
4. Genitourinary 6%
5. Meningeal 6%
6. Peritoneal 5%
7. Other sites 11%
CXR for ALL (exclude pulmonary TB)

59. Tuberculous Lymphadenitis
• “Scrofula”
• Common site: cervical > supraclavicular
• Other sites: inguinal, axillary, mesenteric,
mediastinal, intramammary
• enlarging, painless, mobile, red, firm mass 
matted, harder, overlying skin inflamed
• Dx = excisional biopsy (FNA is adequate in HIV
pts)

60. Pleural Tuberculosis
• Usually small to moderate unilateral effusion
+/- pulmonary lesions, pleural thickening
• CT scan may reveal lymphadenopathy,
infiltrates, cavitation
• Pleural fluid: exudative, lymphocytic
predominance (neutrophils may predominate
early on), ↓/↔glucose, ↑protein

61. Pleural Tuberculosis
• AFB positive 5% (higher in tuberculous
empyema), positive cultures 25-30%
• Lymphocyte activity markers such as
adenosine deaminase (ADA) and interferon-
gamma (INF-γ) can be useful
• Pleural effusions with an ADA <40 U/L rarely
caused by TB
• Caseating granulomas seen on pleural biopsy
are classic and diagnostic

62. Skeletal Tuberculosis
• most common = spinal TB
• Tuberculous arthritis involving monoarticular
weight-bearing joints
• Extraspinal tuberculous osteomyelitis

63. Spinal TB (Pott’s disease)
• Hx. back pain or stiffness
• PE. fever, point tenderness, ↓ROM
• Lesion at intervertebral disk  adjacent
vertebrae (film = anterior wedging of two
vertebral bodies + disk destruction)
• Film: early changes = loss of the “white stripe”
of the vertebral end plate (difficult to detect)
• Suspected disease  CT / MRI

64. Spinal TB (Pott’s disease)
• Paraspinal “cold” abscesses +/- sinus tract
• Main complication = spinal cord compression
• Bone Bx or aspiration Bx of abscess may
confirm

65. Cold abscess Spinal TB
http://images.rheumatology.org

66. CNS Tuberculosis
1. Meningitis
2. Intracranial tuberculoma
3. Spinal tuberculous arachnoiditis

67. Tuberculous Meningitis
• Nuchal rigidity may be absent
• Diplopia from basilar exudate (70%)
• +/- Hyponatremia (SIADH is common)
• CSF: WBC 0-1,500 (lymphocyte predominance;
PMN may predominate early); ↑protein,
↓glucose, positive AFB 37% (90% in pooled
samples from multiple LP)

68. Tuberculous Meningitis
• Classic triad of neuroradiologic findings
1. basal meningeal enhancement
2. hydrocephalus
3. cerebral or brainstem infarction

69. Intracranial Tuberculoma
• solitary or multiple; usually frontal or parietal

70. Genitourinary Tuberculosis
• Typically, renal function is preserved until there is
(typically unilateral) granulomatous erosion into the
calyceal system, or tuberculous interstitial nephritis
develops
• UA: sterile pyuria +/- microscopic hematuria
• IVP: a moth-eaten calyx or papillary necrosis
• CT may show calculi; scarring; hydronephroses;
ureteral strictures; and calcifications in the kidney,
seminal vesicles, prostate, and vas deferens
• Three morning urine samples cultured fo MTB establish
the diagnosis in 90% of cases.
• Co-infection with bacteria is not unusual

71. Tuberculous Peritonitis
• abdominal pain, fever, hepatomegaly, ascites
• Peritoneal fluid analysis: not diagnostic, WBC
150 - 4000/mm3 (lymphocytic predominance),
and SAAG < 1.1 g/dL
• Dx. = peritoneal Bx & fluid for histopathology
and culture

72. Extrapulmonary TB: Treatment
• Same regimens as pulmonary TB
• Experts recommend
– TB meningitis: treat 9–12 mo
– TB bone&joint: treat 9 mo
• Corticosteroid is recommended for TB
meningitis and pericarditis (unless suspected
drug resistance)
• In TB meningitis, ethambutol should be
replaced by streptomycin

73. Prevention
1. early detection and treatment of active cases
2. education and screening of HCW
3. engineering controls
Engineering Controls to Reduce TB Transmission
High airflow (> 6 room air changes per hour) with external exhaust
High-efficiency particulate filters on ventilation system
UV germicidal irradiation
Negative-pressure isolation rooms
Personal respiratory protection: high-efficiency particulate filter
masks or respirators

74. Thank You

75. References