TB Flashcards
What animal is the natural reservior for TB and how is TB spread?
• what percentage of people infected with TB will actually develope diseae?
TB spread:
• Person to person (people are the reservior)
• Most transmission generated by aerosols generated by coughing people who have the disease
What percentage:
• only 10% that have become infected actually develope disease
What makes TB acid fast? Shape of TB?
• why it difficult to make a quick Dx?
Mycolic acid in the wall makes these bacteria ACID FAST Bacilli
• 18 hour doubling time means it takes 6-8 weeks to culture
Why are we able to Isoloate TB in mucous despite the fact that its a lower respiratory tract infection that is in granulomas?
• Erosion of cavities into bronchioles allows the bug into mucous so that it can be stained
Jim who has rheumatoid arthritis meets Tom who is coughing like crazy when he meets him. Jim then goes to his pulmonologist to get an annual CXR to check up on emphysema when a fibrocalcific nodule is spotted in the lungs. The nodule is biopsied and is positive for an acid-fast bacillus.
• In what ways is this a paradigm case of TB?
• Where in the lungs do you suspect the lesion was most likely spotted?
Paradigm case:
• TB was most likely spread by aerosolized dropplets to a susceptible host (TNF-alpha mAb for Rh. Arthritis)
- Jim does NOT experience any symptoms (remember only 5% develop clinically significant disease)
- Organisms (seen in biopsy) may lay dormant in the lungs for years before they reactivate
- Lesion was likely found in the APEX of the lung
ALSO, the fact that Jim has rheumatoid arthritis predisposes him to TB b/c he could be taking infliximab (a TNF-alpha mAb) .
Mycobacterium Tuberculosis lacks normal virulence factors like toxins, capsules, and fimbriae seen in other bacteria. Instead it contains a number of structural and physiologic properties that aid in virulence.
• Name 3 of these.
- Waxy cell wall - impermeable to many of the host defenses
- Cord Factor - virulent strains grow in a cord-like pattern (the others do not)
- Sulfatides (surface glycolipids) - inhibit phagolysosomal fusion
What are 4 important components that make up the MTB cell wall.
- Mycolic Acid
- Glycolipids
- Arabinogalactans
- Free Lipids
What does cord factor do?
• Inhibits macrophage maturation and induces TNF-alpha release
What key advantage is coferred to MTB by the fact that it lives intracellularly?
• what cell hosts this infection?
• Why is the bug not degraded after entering the cell?
Intracellular living of MTB inside of macrophages helps it to avoid antibodies and complement. Protien PknG is thought to prevent fusion of the lysosome and phagolysosome
Describe how MTB enters the macrophage and how infection progresses to granuloma formation.
- Mannose-capped glycolipid from MTB binds to mannose receptor on macrophage and its endocytosed
- Phagosome fails to fuse with lysosome as a result of PknG protein in MTB
- The macrophage then secretes IL-12 which activates niave T cells that bind to the MTB antigen on the MHCII receptor of the macrophage
- Th1 cell then secretes IFN-gamma that activates Macrophage
- Macrophage secretes TNF-alpha that recruits monocytes and causes macrophages to collect
What is the difference in the role of IFN-gamma and TNF-alpha in MTB infection.
- IFN-gamma ACTIVATES macrophage
- TNF-alpha RECRUITS macrophages
What are some risk factors for infection by MTB?
Risk Factors:
• Prison (crowded conditions)
• Immigrant from high burden country
• Malnourished
• Alcoholism
• Poverty
• Debilitating illness
• AIDS
• Elderly
• Diabetes Mellitus
• Hodgkin Lymphoma
• Chronic Kidney disease
• Malnutrition
• Immunosuppresion by TNF-alpha antagonists
Differentiate the Clinical Manifestations of Secondary/reactivated TB and Progressive Primary TB.
Secondary/Reactivated TB:
• INSIDIOUS ONSET
• Malaise, anorexia, low-grade fever, weight loss, night sweats, SOB, cough of productive blood-streaked and/or productive sputum.
• Pleuritic pain
Progressive primary TB:
• Resembles acute bacterial pneumonia (High Fever, Dyspnea, etc.)
• CXR shows infiltrates with lobar consolidation, hilar LAD, Pleural effusion
• HARD TO Dx.
Over the last 2 months mary has experienced increased dyspnea and has felt extremely lethargic. She has been coughing up sputum with red streaks. She took a trip abroad recently (returned 2 days ago) and also one in 2006 and is currently being treated for diabetes. She also has a strong family history of polycistic kidney disease and heart failure.
• Is this type of pneumonia more likely progressive primary or secondary reactivated?
• what are her risk factors?
• Insidious nature of this case implies Secondary/Reactivated TB
Risk Factors:
•Trip abroad - probably contracted in 2006 because this is a secondary reactivation
• Chronic Kidney Disease
• Diabetes M.
**Hrt dz. = not a risk factor
A 19 year old prison inmate presents to regional one with LAD, dyspnea, and dry cough. He has been vomitting for the last 3 hours. CBC indicates pancytopenia. Sputum cultures are positive for an acid fast bacillus.
• what does this guy have?
• What tests should you run?
• What are his risk factors?
Dx:
• Miliary/Disseminated TB - known to cause pancytopenia
Tests:
• HIV - most people don’t develope miliary TB, AIDS patients are at high risk and AIDS is common in prisons
• Should culture the sputum
What does the CXR look like in Miliary TB?
• What are some complications?
CXR:
• Diffuse, seed-like infiltrates
Complications:
• LIVER, Bone Marrow (pancytopenia), Spleen involvment
- Meningitis
- Pott’s disease (vertebral osteomyelitis)
- GI involvment
- Urinary Tract involvment
- Adrenal insufficiency
- Epididymitis
- Prostatitis
A 19 year old prison inmate presents to regional one with LAD, dyspnea, and dry cough. He has been vomitting for the last 3 hours. CBC indicates pancytopenia. Sputum cultures are positive for an acid fast bacillus.
• After several days without improvement, he begins to complain of back pain. Most likely cause?
• What are some indicators that the urinary tract might be involved in this miliary TB infection?
Back Pain:
• Pott’s Disease - vertebral osteomyelitis
Urinary Tract:
• Sterile pyuria, Hematuria, Proteinuria
If you get a positive smear specimen and you do not want to wait 3-6 weeks for TB to grow on solid agar what can you do?
• should you still get a culture?
• could use liquid culture - takes 2 weeks
BEST OPTION:
• use PCR or nuclei acid amplification - even with this you still NEED to get a culture
What media grow MTB?
Lowenstein-Jensen agar - required - contains substances to enrich growth and inhibit other flora
Mark presents with dyspnea, nodules on CXR, and cryptic fever. He remarks that his wife was diagnosed with TB in 2005.
• Should you start treatment before confirming a dx?
• If so what should you use?
Tx:
YES, start treatment for TB is suspicion is high - DO NOT wait
Drugs:
• RIPE - Isoniazid, Rifampin, Pyrazinimide, Ethamubutol
Mark presents with dyspnea, nodules on CXR, and cryptic fever. He remarks that his wife was diagnosed with TB in 2005.
• Cultures come back positive and MTB is susceptible. What are your steps to finish out treatment for this pt?
Tx:
• Patient’s bug is susceptible so stop the Ethambutol
• After 2 mo.of RIPE/RIP take off the Purazinimide
• Continue Rif. and INH for 4-7mo.
Total of 6-9mo. of therapy
How does treatment for Miliary TB differ from that of Secondary or Primary Pulmonary TB?
Secondary or Primary Pulmonary:
• RIPE/RIP (2 mo.) => RI (4-7mo.)
Mililary TB:
• Full RIPE THERAPY FOR 9-12 mo.
Why do MTB infections require such a long course of therapy?
- Slow growth of organism
- Located Intracellularly
- Caseous material makes access difficult
- Lesions contain metabolically inactive organisms
Why do many places require DOT (direct observed therapy)?
• what are the resistant strains of TB?
• Among what group are resistant strains most common?
Drug non-adherance is a huge problem for emergence of drug resistant TB
MDR TB: resistant to INH (isoniazide) and RIF (rifampin) is common => AIDS patients
XDR TB: resitance to INH, RIF, and Fluroquinoloes
Explain why AIDS patients are likely to have a false negative sputum smear for TB and absent granulomas.
• What is the most important risk factor of these people getting AIDS?
• Does HAART therapy protect these patients from TB?
Most important Risk Factor:
• LOW CD4+ count (b/c you need IFN-gamma to activate macrophages and wall off the infection)
Negative Sputum Smear:
• Less immune response means the cavitations won’t break through the bronchi.
• This reduces the amount of Acid-Fast bacilli in sputum
HAART therapy does not prevent infection by TB
Should you treat an Asymptomatic patient what has a suspected latent TB infection?
• In an otherwise healthy individual what would make you think they had latent TB?
• How should you treat them?
YES, treat this patient if you don’t they remain at a risk of the infection re-activating
• PPD (purified protein derivative) test greater than 15mm is a positive test
Tx:
• Isoniazid for 9 months
• Isoniazid and Rifapentine for 3 months
What type of reaction is the PPD (purified protein derivative) TB test?
• Why could a 15mm nodule be a false positive?
Delayed Type IV hypersensitivity - takes 24-48 hours to get a response
False positive:
• BCG immunization - most of the time we ignore this as a possibility of rxn in adults
• Other Mycobacteria can cause a false Postive
What group of people are likely to falsely test negative to TB?
HIV patients often have a false negative HIV test
How does the IGRA TB test work?
• Blood from patient is exposed the MTB antigens and the amount of INF-gamma released is measured
• NO FALSE POSITIVES
How do you read a PPD test?
Positive:
- Greater than 15mm even if no other risk factors
- 10-15mm in homeless, IV Drug user, nursing home resident, recent immigrand, children less than 4
- 5-10 mm HIV, recent contact of someone with TB, Fibrotic changes on CXR consistent with prior TB, organ Transplants, Immunosuppressed (Prednison, TNF alpha antagonists)
Someone with RA has a 5mm bump after getting the PPD test. Is this positive?
If they are takind TNF-alpha antagonist then YES that would make this a positive test
What should you do to isolate TB patients in hospital?
Masks and Respiratory Isolation
Who should be screened for TB?
HIV infected
Low income
Alcoholics and IVDU
Prison inmates
Foreign born from countries with high incidence
