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==History==
*Died from or infected by Tb
==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
