• inhalation of droplet nuclei from infectious individual who is coughing, sneezing, talking, etc.
• infrequently via aerosolization (ex: pathology suite)
• infrequently by skin inoculation

• how close (highest in closed spaces and unlikely outdoors)
• how long (usually need more than 4 hrs)
• how many infectous droplet nuclei

1. inhalation of infectious aerosol droplets
2. macrophage ingestion of bacilli
3. local focus of disease (the Ghons focus)
4. lymphatic spread to local hilar lymph nodes
5. hematogenous dissemination includes apical post. areas of lung
6. dev. cell mediated hypersensitivity and skin test conversion
   • destroy macrophage containing intracellular organisms
   • extracellular killing of mycobact. within necrotic sites
   • result is caseous necrosis, liquefaction and tissue destruction

1. bacilliary mult. may be contained or disease may progress
2. three months- mainly TB or meningitis due to hematogenous spread
3. 3-4 mnths- TB pleurisy or progressive primary TB due to hematogenous or direct spread from primary lesion
4. up to three yrs- bone, joint, renal TB

• after severeal years of latent TB infection (LTBI)
• occurs with waning cell mediated immunity
• also caused by local or systemic stress, intercurrent illness, advancing age

• normal- 5% risk in first two years and 5% risk of disease throughout life (10% overall risk of active disease)
• HIV- 5-10% risk every year of disease

• lungs (85%)
• pleura
• lymphatics (foreign born, kids)
• GU
• bone, joints
• CNS (meningitis, tuberculomas)
• disseminated (miliary)

• should be targeted at persons who would benefit from preventative therapy
• avoid screening low risk populations
• skin test conversion defined as an increase of greater than 10 mm in two years
• BCG- IGNORE and follow normal guidelines
• anergy test- not recommended for routine use
• process
  • read after 48-72 hrs
  • measure only the induration
  • ignore erythema

• 5-10 mm
  • HIV (or IV drug user and unknown HIV)
  • close contact of active case
  • fibrotic chest X ray lesions
  • steroids, transplant patients
• 10-15 mm
  • high prevalence country
  • IV drug user and HIV negative
  • long term care facilities
  • certain medical conditions
• 15+ mm- no increased risk

• not sensitive (false negatives)
  • 20% of normal hosts with active TB do not react (just because skin test is negative, dont rule out)
  • up to 80% of HIV positive persons with TB do not react
• not specific (false positives)
  • interactions with non TB mycobact. can increase reaction size
  • BCG has temporary impact on PPD reaction

• process
  1. whole blood from patient incubated with proteins to detect presence of sensitized WBC as evidence of prior TB
• advantages
  • endorsed this tests in all times skin test is used
  • more specific
• disadvantage
  • cost (not widely used)
  • logistics
  • uncertainty over interpretation
  • less sensitive

• positive PPD or IGRA w/ no symptoms and normal chest X ray
• not considered active because:
  • cannot spread to others, but
  • potential for active disease in future

• abnormalities in apical or posterior segments of upper lobe or superior segments of lower lobe
• may have unusual appearance in HIV positive patients
• cannot confirm TB diagnosis

• Ziehl Neelsen stain process
  1. fixed smear
  2. covered with carbol fuschsin
  3. heat
  4. rinse decolorize w/acid alcohol
  5. counterstain with methylene blue
• Kinyoun stain- modification doesnt require heating

Need 10⁴ organisms per mL of sputum required for positive stain

• types
  • phenolic auraminem
  • auramine-rhodamine
• improved sensitivity (rapid scanning under lower magn.)

• M tuberculosis (2/3 of cases)
• M avium,
• M kansasii

Process of culturing mycobacteria: different types available

• first, liquefication
  • decontamination of N acetyl L cystein in 1% sodium hydroxide solution
    • mycobact. protected by their fatty acid rich cell wall
• two options
  • solid media (grow in 3-6 wks)
    • agar based- Middlebrook 7H11
    • egg based- Lowenstein Jensen
  • liquid media (5 days-2 wks)
    • BACTEC radiometric system
    • septicheck AFB
    • isolator tube
    • mycobacteria growth indicator tube (MGIT)

• MT: rough, adherant organisms
• MAC: smooth but no pigment
• M kansasii: smooth

• initial two months
  • INH
  • Rifampin
  • PYrazinamide
• final four months
  • INH
  • Rifampin

Add ethambutol if greater than 4% chance of INH resistance

• 9 months
  • INH
  • RIF

Add ethambutol if greater than 4% chance of INH resistance

• Rifamate: INH and RIF
• Fifater: INH + Rifampin + PYZ

• definition- implies resistant to at least INH and Rifampin
• NYC area
• HIV positive
• prior reaction

Rates decreasing in US

Increasing in Russia, eastern Europe.

• no cookbook approach: try to use 4,5 drugs that organism susceptible to
• surgery may be indicated

• resistance to INH, rifampin, quinolones, injectables
• epidemiology- increassing in industrialized nations
  • emerging problem in HIV positive parts of South Africa (100% mortality)
• prognosis poor (limited tx options)

• same tx regimes as HIV negative
• if slow to respond, tx 9 months instead of six months
• Rifampin cannot be used with most patients and NNRTI's due to drug interactions with P450 system
• use rifabutin at modified dose

• causative agents- both TB and MAC
• most common in those started on both mycobacterial and HIV therapy
  • potentially cause improved immune status and exagerrated host response
• clinical manifestations
  • worsening fever
  • local manifestations- cavitation, swelling of lymph nodes
• normal time course is 2-4 wks after init. of tx

• recommended for those at high risk for reactivation of TB
  • those with PPD positive test and less than 60 yrs old, or medical risk factor
• provide tx at latent stage prevent activation and complications of active TB

• mech: kills slowly multiplying organism
• efficacy- estimates range from 40-90% (highly dep. on pateint compliance)
• toxicity- hepatitis, mortality

• ID patients with active TB
• isolate patients in rooms with negative airflow
• initiate effective TB tx
• mask for patients/respirators for health care workers of secondary importance