Tuberculosis

• 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

• 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

• 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 

• 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

• 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

• 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 

• 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

• 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

• 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