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==History==
*Died from or infected by Tb
**<math>d</math> = duration of infectivity
***to reduce <math>d</math>
****treat patients appropriately ==Risk factors==*HIV*malnutrition**Tb risk inversely correlates with BMI*diabetes**diabetes and Tb are syndemic**diabetes and Tb pathophysiologically exacerbate each other even under treatment condition in terms of hepatotoxicity*overcrowding**people per room vs Tb rate per 100,000 (in Canada)***0.4-0.6 vs 18.9***1.0-1.2 vs 113*.... ==Natural history==#inhalation of M.tb containing droplets#macrophages phagocytosis#granuloma + lymphadenopathy#Ghon complex - primary infection## 5% local progression/disseminated Tb##95% latent Tb### 10% of latent Tb reactivates in lifetime - secondary Tb ===Latent Tb===*1/3 of the world's population have latent Tb**modelling approx. 1.7 bil. people*10% of those latent Tb people get reactivation in their lifetime ==Symptoms==*cough ± sputum ± hemoptysis > 2weeks*fever *malaise*weight loss ==Various presentations=====pulmonary===**80-85% of TB diagnosis are pulmonary ===extra-pulmonary=== ====lymphadenitis - hilar/other====*cold abscess*more common in cervical and hilar*possibly in axillar, inguinal and abdominal*hilar adenitis DDx - sarcoidosis, lymphoma, histoplasmosis====pleural====*usually uni-lateral*effusion high LDH, high protein, high lymphocyte====pericardial====*cardiac tamponade*sequele - carcified pericardium*very pauci-bacillary and bacterial investigation from pericardiocentesis is very much less sensitive ====intestinal====*can mimic Crohn's disease*most common in ileocecal====meningitis====*often involves 3rd and 6th cranial nerves*meningeal irritation signs often unaccompanied====cerebral tuberculoma====*DDx primary CNS lymphoma====Pott's disease (vertebral destruction due to TB)====*kyphosis, gibbus formation*sometimes extends to psoas muscle abscess; ====arthritis====*synovial fluid does not necessarily contains enough TB bacteria; fluid culture may miss diagnosis*IGRA could be clue===skin===*erythema nodosum **DDx - TB, cryptococcal, sarcoidosis, UC, oral contraceptive, ≈50% idiopathic*lupus vulgaris===miliary TB===*massive lymphohematogenous dissemination**nodules diameter <10mm*liver*spleen*bone marrow*lungs**pulmonary miliary TB easily missed by chest X-ray*meninges ==Diagnosis== ===baseline investigation=======blood====*full blood count**clues for TB - leukopenia, anemia, thrombocytopenia*liver enzyme, renal function, electrolyte**for baseline to monitor Tx side effect or to adjust dose*diabetes*co-infection**HIV**Hep B - HBsAg**Hep C - HCV-Ab====imaging====*chest X-ray*other targeted imaging ===microbiological=======smear/microscopy====*Ziehl-Neelsen of sputum**positive smear needs cavitation**children and HIV-positive tend not to cavitate**specificity 98%*fluorescent ====culture - 4-8weeks====*culture is definitive/reference standard*Lowenstein-Jensen medium*liquid medium 3 weeks ====PCR TB DNA====*Gene Xpert**Xpert MTB/RIF**can detect resistance to rifampicin ====histopathology====*tissue biopsy**caseating granuloma***multinucleated giant cells with nuclei arranged like a horseshoe ====urinary LAM antigen detection====*mycobacterial cell wall glycolipid antigen lipoarabinomannan (LAM)*marker of active TB*specificity 98%*sensitivity 40-70% ====Manteau text/tuberculin skin test (TST)====*low value for diagnosis ====Interferon gamma release assay (IGRA)====*T-SPOT/Quantiferon(QFT)*cannot distinguish between latent/active/used be treated ==Treatment==*needs prolonged Tx*needs multiple drugs ===1st line target===*cell wall synthesis**H - isoniazid (isoniotinic adid '''h'''ydrozide)**E - '''e'''thanbutol*DNA synthesis**R - '''r'''ifampicin*?**Z - pyra'''z'''inamide *2RHZE+4RH*2RHZE+4(RH)₃ ===side effects===*hepatotoxicity - H, R, Z*ocular toxicity - E*peripheral neuropathy - H**add vitamin B6 (pyridoxin)*gout - Z*fever - Z*lupus - H*drug interaction related to CYP 450P - R**carbamazepine**oral contraceptive**methadone ===interrupted Tx===*interrupted during intensive phase**interrupted for > 14 days - re-Tx from the beggining**interrupted for < 14 days - continue*during continuing phase ===spinal/bone TB===*needs 9 months ===TB meningitis===*needs 12 months*2RHZE+10RH ===latent TB===*some options ==Management=====paradoxical reaction===*inflammation after commencing Tx*problematic in CNS, pericardial*co-Tx with steroids**CNS/meningitis,tuberculoma - dexamethasone**pericardial - predonisolone ===Directoly Observed Treatment, short course (DOTs)===*in high risk stuation*in homeless/chaotic social circumstance*in poor adherence/treatment failure *Dr. Karlos Stybro ===TB in pregnancy===*RHZE are safe*supplementation with VitB6 (pyridoxine) recommended**hyperemesis gravidarum ===TB in breastfeeding===*no contraindication*rule out TB in baby ===hepatotoxicity===*any GI complaint may represent hepatotoxicity*suspend all TB drugs until lab test revealed*risk**co-infection HIV, hepB/C**other chronic liver disease**alcohol**advanced age*early - 2-3wks, R,H; good prognosis*late - after 1mo, E; bad prognosis ==Drug-resistant=====mono-resistant===*H-resistant approx. 7% *primary resistance**infected by resistant TB*secondary resistance** ===multi-resistant MDR===*resistant to H and R*risk**previous Tx**household contact with MDR**HIV*resistance to R is a marker of MDR**90% of R-resistance strains are also resistant to H → GeneXpert ===extensively resistant XDR===*MDR + fluoroquinolone-resistant and at least one additional group A drug ===pre-extensively resistant pre-XDR===*MDR + fluoroquinolone-resistant
