| What is TB? | Ancient disease caused by Mycobacterium tuberculosis, multi-systemic disease, affects respiratory system, GI, lymph, skin, CNS, musculoskeletal system, reproductive system and liver.
Human pathogen with no environmental reservoire, been here for thousands of years.
Still seen in developing countries (60% of TB deaths in India, china, indonesia, pakistan and south africa)
In developed countries affects immunocompromised (HIV) as well as children (1 million illnesses in children in 2015) |
| How is etiology of TB? | Complex of bacteria (M.tb, M.africanum, M.bovis, M.microti.
Other mycobacteria are non-TB organisms.
Non-spore forming, non-motile, obligate aerobe, catalase -, intracellular bacteria that is acid-fast.
Weakly gram+ cells may appear on gram stain (Called Ghost cells)
Presence of several lipids in cell wall (mycolic acid, cord factor, Wax-D) is unique for it, which contributes to its infection properties (resistance to Abx, difficult gram stain, survival in extreme conditions.
Ziehl-Neelsen stain is used to dx TB (carbol fushion stain) decolorize with acid-alcohol, counter stain (+ pink color for TB) |
| How is epidemiology of TB? | Present globally, developing countries more burden.
Advanced countries burden in HIV+ pt, healthcare, endemic areas.
Pt using corticosteroids... should screen for TB before and during their tx.
Other risk factors include socioeconomy (poverty, malnutrition), immunosupression, occupation (mining, construction, silicosis) |
| How is pathophysiology of TB? | Spread through inhalation of infected aerosols, genetics and immunity play a role in defense, although TB comes with virulence factors to alveolar macrophages.
Primary TB is first contact with M.tb, usually in middle portion of lungs known as Ghon focus (usually goes latent)
Then when pt is immunocompromised, latent infection maybe reactivated (only small portion of people get activated without latency - primary progressive TB seen in children, malnutrition...)
Secondary TB is activation of latent TB, causes lesions in lung apices
Secondary TB sometimes may be caused by reinfection of M.tb |
| How is TB type IV hypersensitivity and Caseating granuloma formation? | As a delayed hypersensitivity rxn, TB stimulates immune cells (CD4+ T, macrophages using IFN-gamma), form multinucleated giant cells and formation of epithelioid cells, these cells aggregate around mycobacteria and form granuloma.
Epithelioid cells are macrophages forming cytokines which merge together to form giant cells (tuberculoid granuloma)
IL4, IFN-g, IL6, TNF-a form this granuloma, Caseous (cheese-like) granuloma, explained by mycolic acid of mycobacterium cell wall (necrosis of granuloma forms caseating necrosis which presents as a central area of uniform eosinophilia on H&E stain) |
| How is histopathology of TB? | Caseating necrosis with central eosinophilia, multinucleated giant cell, granuloma (caseating) |
| What are Hx & PE findings in TB? | Chronic cough, hemoptysis, weight loss, low grade fever, night sweats (most common in pulmonary TB)
Secondary TB differs from primary progressive (secondary more severe, cavities in upper portions of lungs)
Pulmonary/ systemic dissemination of tubercles (miliary TB) millet shaped lesions seen on CXR, seen in spine, CNS or bowel as well |
| What is the screening test of TB? | Tuberculin skin testing (mantoux test PPD)
Injection of a dose of PPD into skin, and see mantoux reaction, three classifications:
low risk (minimal exposure, no known hx of exposure, considered positive if 15mm cut off point)
Intermediate risk (residents of TB endemic countries, microbiologists..., positive if induration 10mm)
High risk (HIV +, previous TB evidence, contact with pt, positive if induration 5 mm)
It indicates exposure or latent TB, but not specific (needs CXR confirmatory, and may give false positive (if exposed to BCG vaccine) |
| What is a screening test for TB other than PPD? | Interferon release assay (IGRA, Quantiferon)
More specific and equally sensitive as PPD, level of cytokines and IFN-gamma.
single blood draw (advantage), costly and need expertise (disadvantage) |
| What is the significance of screening for TB? | + test indicates previous exposure, and high chance of future active TB, + tests is between 2-10% without tx.
Pt with + test should have CXR, and in some cases they may get other tests and take prophylaxis (isoniazid) |
| What are confirmatory dx tests for TB? | CXR (rules out active disease), acid-fast stain (Ziehl-Neelsen), Culture, PCR |
| How is the treatment of latent TB? | Rifamycin based regimen and two monotherapy regimen with daily isoniazid.
3 months, once weekly isoniazid + rifapentine (for children more than 2 years and adults)
other option: 4 months daily rifampin (HIV - adults and children)
3 months of daily isoniazid + rifampin for adults and children and HIV+ pt
6-9 months of daily isoniazid alternative regimen as well |
| How is the treatment of active TB? | RIPE (rifampin, isoniazid, pyrazinamide, ethambutol)
for 2-6 months, vitamin B6 given with isoniazid to prevent neuropathies.
Several other Abx can be effective (MDR-TB, XDR-TB) as second/third line drugs |
| What is the toxicity and side effects of anti-TB tx? | Isoniazid (ALT increase, hepatitis, neurotoxicity, hypersensitivity)
Rifampin (pruritis, vomit, nausea, flu-like, hepatotoxicity, orange discoloration)
Rifabutin (neutropenia, uveitis, polyarthralgia, hepatotoxicity)
Rifapentine (same as rifampin)
Pyrazinamide (hepatotoxicity, nausea, polyarthralgia, gouty arthritis, rash, photosensitive dermatitis)
Ethambutol (retrobulbar neuritis 18%)
So we should monitor and manage the doses according to side effects |
| What are the complications caused by TB? | Most pt benign.
Complications include extensive lung destruction, cervical sympathetic ganglia damage (Horner's syndrome), ARDS, miliary spread (TB meningitis...), empyema, pneumothorax, systemic amyloidosis. |
| What are lung non-TB mycobacterial infections? | They are non-TB mycobacterial infections, serious, not as common as TB, misdiagnosed and undertreated |
| How is etiology of non-TB mycobacterial infections? | NTM may be fast or slow growing (unlike TB which is slow) grows days to weeks
there are almost 100 NTMs, most common ones are M.avium, M.kansaii, M.abscessus
acquired by inhalation of infected aerosols, living in closed quarters, coughing and not using face masks are risk factors
Advanced age, immunosupression and corticosteroids are also risk factors.
Usually settle in lower airways, sometimes make inflammatory reaction with influx of lymphocytes which may cause pneumonia. |
| How is clinical manifestation of non-TB mycobacteria? | Similar to TB, cough, dyspnea, increased sputum, systemic manifestations (fever, malaise, weight loss)
Symptoms duration days to few weeks.
On radiology, mostly we see fibro-cavitary/ nodular bronchiectatic patterns |
| How is the treatment of non-TB mycobacterial infections? | Specific and different for each type of NTM, most important thing is identification of NTM species by PCR.
doesn't require immediate initiation of tx upon dx, therapy remains until 12 months of negative cultures obtained. |
