「Tuberculosis」の版間の差分

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==Treatment&Management==
 
==Treatment&Management==
 +
*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
  
 
==Drug-resistant==
 
==Drug-resistant==

2021年4月15日 (木) 16:15時点における版

History

  • Died from or infected by Tb
    • John Keats (poet)
    • George O'well
    • Nelson Mandella
  • Hippocrates description
    • Phthisis (to waste away, consumption)
  • Robert Koch found the bacteria 1882

Epidemiology

est. case est. death all form 10mil 1.4mil HIV-ass 0.9 mil 208,000 MDR-Tb ≈558,000 ≈190,000

  • 8 countries account for 2/3 of all worldwide Tb
  1. India
  2. China
  3. Indonesia
  4. the Phillippines
  5. Pakistan
  6. Nigeria
  7. Bangladesh
  8. South Africa

Transmission

  • transmission-influencing factors
    • sputum status of index case
    • proximity - distance between each other
    • time
  • susceptibility of person
  • [math]\displaystyle{ R_0 \approx r \times c \times d }[/math]
    • [math]\displaystyle{ r }[/math] = transmissibility
      • to reduce [math]\displaystyle{ r }[/math]
        • ealier detection
        • rapid commencing of treatment
        • reduce aerolization (surgical masks on patients)
          • surgical masks on patients reduce infectivity by 56%
    • [math]\displaystyle{ c }[/math] = susceptibility of contacts
      • to reduce [math]\displaystyle{ c }[/math]
        • open windows
          • Tb airborne transmission risk: windows closed 97%, negative pressure room (ACH12) 39%, windows and doors fully open 33%
        • N95 respirator
        • ARTs for HIV patients
    • [math]\displaystyle{ d }[/math] = duration of infectivity
      • to reduce [math]\displaystyle{ 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

  1. inhalation of M.tb containing droplets
  2. macrophages phagocytosis
  3. granuloma + lymphadenopathy
  4. Ghon complex - primary infection
    1. 5% local progression/disseminated Tb
    2. 95% latent Tb
      1. 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

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 drug resistant

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&Management

  • needs prolonged Tx
  • needs multiple drugs

1st line target

  • cell wall synthesis
    • H - isoniazid (isoniotinic adid hydrozide)
    • E - ethanbutol
  • DNA synthesis
    • R - rifampicin
  • ?
    • Z - pyrazinamide

Drug-resistant