Tuberculosis

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  • Created by: z
  • Created on: 14-03-16 18:35

Introduction

  • airborne disease
  • largely caused by Mycobacterium tuberculosis (M. tb)
    • also M. bovis, M. africanum, M. mircoti, M. canetti, M. capre, M. pannipedii, M. mungi
    • M. tb also called tubercle bacilli
  • spead via droplet nuclei (airborne particles)
  • expelled when pt w/ infective tb coughs/sneezes/shouts/sings
  • transmission occurs whne droplet nuclei are inhaled and reach alveoli of lungs where they mutiply
  • probability of transmission dep on:
    • susceptibility of exposed person
    • infectiousness of pt w/ tb (no. of particle expelled)
    • environmental factors
    • proximity, frequency, duration of encounter
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Tb pathogenesis

  • person inhaled tubercle bacilli, they reach the alveoli and multiply
  • small number of bacilli enter the blood stream and travel anywhere in body, some places more likely to develop disease
    • brain, larynx, lymph node, lung, spine, bone, kidney
  • w/in 2-8wks macrophages ingest and surround bacilli
    • form a granuloma- Tb kepyt contained= latent infection
      • granulomas may persist of break down to reproduce Tb disease
      • LTBI can be detecetd via TST or IGRA (interferfon-gamma release assay)
      • persons w/ LTBI are NOT infectious
    • if immune system cannot control bacilli they rapidly multiply = Tb disease
      • persons w/ Tb disease are infectious
      • positive culture confirms diagnosis
      • sites of disease- lungs (most common)
        • miliary- rare but fatal
        • CNS - usually as meningitits (can be brain or spine)
        • extrapulmonary Tb normally not infectious unless in open site or oral cavity/larynx
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Risk of developing Tb disease

  • normal immune system:
    • untreated- 5% develop TB w/in 1-2 yrs of infection, 5% later in life
    • 10% in total if untreated
  • weak immune system
    • untreated HIV is highest RF 7-10% a year
    • children <5yrs 
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When to consider Tb and diagnosis

  • symptoms to look for
    • cough >3 weeks
    • fever > 3 weeks
    • unexplained weight loss
    • night sweats
  • what to do:
    • sputum for AFB smear and culture
    • CXR
    • ensure f/u
  • Dx
    • microbiology of patholigical samples (pus, biopsy material_
      • direct staining, culture=gold standard
      • PCR etc
    • histopathological pattern of inflammation
    • tuberculin skin testing (TST)
    • interferon gamma release assays (IGRA)
    • radiographic appearance
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Radiographic features of Tb

  • primary pulmonary Tb
    • initial focus of infection can be located anywhere within the lung   
    • calcified Ghon lesion
    • ipsilateral hilar and mediastinal lymphadenopathy in children
    • pleural effusions are more frequent in adults, seen in 30-40% of cases
    • calcification of nodes is seen in 35% of cases . When a calcified node and a Ghon lesion are present, the combination is known as a Ranke complex.
  • post-primary/reactivation tb
    • posterior segments of the upper lobes or superior segments of the lower lobes
    • patchy consolidation or poorly defined linear and nodular opacities, may cavitate
  • miliary Tb
    • Miliary deposits appear as 1-3 mm diameter nodules, which are uniform in size and uniformly distributed
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Tb treatment + control

  • multiple antibiotic regime prolonged (minimum 6 months)
  • initial phase (RIPE) for 2 months
    • rifampicin (RMP)
    • isoniazid (INH)
    • pyrazinamide (PZA)
    • ethambutol (EMB)
  • continuation phase to complete 6 months Rx in total
    • rifampicin
    • isoniazid
  • cure rate 98% if complinat + organism sensitive to Rx

control

  • prevention- BCG imm/ prophylactic chemotehrapy
  • treatment services- esp supervision
  • education 
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Microbiology of Tb

  • M. tuberculosis is agent of tb in humans- humans are its only resevoir
    • nonmoyile bacilli
    • oligate aerobe (thus find complexes in upper lobes as well aerated)
    • facultative intracellular parasite
    • slow generation time- 15-20hrs
    • unique(ish) alpha-branched lipids called mycolic acids in cell walls (also in corynebacterium)
    • mycolic acids thought to be determinant of virulence 
  • M. bovis may use cows or humans as a resevoir (humans can be infected by drinking unpasteurised milk)
  • M. avium causes Tb-like disease
  • M. leprae is the causative agent of leprosy
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Diagnosis of Tb

  • microscopy
    • acid fast bacilli
      • Ziehl Neelson stain for light microscope
      • auramin phenol stain for flourescent microscope
    • sensitivity of 10^4/ml, equivalent to conc reuiqred for transmission from sputum
    • at least 3 sputum samples, incl one early morning sample before Rx started
    • spont prod sputum best but if not induced or bronchoscopy and lavage
  • lymph node biopsy + pus aspirated form nodes/CSF/pleural biopsy and fluid
  • mycobacterial isolation
    • solid media (takes weeks)
    • rapid automated liquid culture systems - quicker (2-10 days)
    • PCR
  • serology (detecting antobody response)
  • TST: -ve does not exclude infection/+ve may be reflect LTBI, BCG imm, or exposure to other M. 
  • IGRA: -ve does not rule out/+ve may reflect LTBI
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Tb treatment s/e

  • Rifampicin
    • hepatotoxicity
    • red-orange hue to urine, sweat, tears
  • Isoniazid
    • peripheral neuropathy
    • decr in RBC, platelet, WBC etc
  • Pyrazinamide
    • arthralgia
    • hepatotoxicity
  • Ethambutol
    • eyes- field defect, loss of colour vision
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