This document provides an overview of tuberculosis (TB), including its causative agent, epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment. It describes Mycobacterium tuberculosis as the typical bacteria that causes TB. It outlines the differences between TB infection and active disease, and lists risk factors for developing active TB. Key topics covered include pulmonary and extrapulmonary TB symptoms and presentations, as well as considerations for HIV-associated TB and drug-resistant TB.

1. TUBERCULOSIS
Tola Bayisa,MD
Internist
Pulmonary/critical care
Assistant professor
Jan 2016
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2. Objectives
 At the end of the lecture he student will be able to :
 Basic feature of mycobacterium bacteria
 Describe Pathogenesis mechanism of tb
 Differentiate Infection vs. disease
 Describe clinical features of all forms tuberculosis
 Outline Treatment principle and regimens
 Follow up
 prevention
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3. cases
1. 20 yr old ,40 kg, diagnosed to haveTB involving lung parenchyma,
pleura with massive effusion.
 Category of disease?
 What are important tests?
 Regimen?
 Dose?
 Duration
2. 50 years smear positive 2 times, living with family
Category of disease?
 Regimen? Duration ?
 Follow up schedule? Education/precaution?
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4. Introduction
 Serous treat to public and individual health (Africa)
 Global emergency(WHO-1993)
 Millions-die-may worsen-HIV/MDR
 History
 Consumption
 Oldest disease-Egypt>3000 BC ,Ethiopia
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5. EPIDEMIOLOGY
 WHO : 2011
 9 million new cases ,1.2 million among HIV
 1.1 million death,
 >90% developing country estimated more
 Increasing in Sub-Saharan b/c HIV
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6. EPIDEMIOLOGY
 Probability of transmission depend on → exogenous
 intimacy & duration of contact
 Degree of infectiousness of the case
 Shared environment(poorly ventilated rooms)
 Degree of infectiousness depend on
 Positive sputum smear-highly infectious
 Cavitary-↑↑bacteria→↑infections
 Smear negative/culture +ve → less infectious
 Smear-ve + culture –ve,EPTB → noninfectious
 HIV+TB →less infectious (less cavities)
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7. Infection-transmitted by droplet nuclei-coughing, sneezing-small
droplet-hrs→ reach alveoli 3000 droplet/cough
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8. Infection Vs disease
 Infection:
 state of carrying bacteria in the body (small /dormant
bacilli,1/3 of the world)
 Disease (TB):
 state in which one or more organs in the body becomes
disease as shown by clinical sx / sn, b/c bacteria multiply
and overcome body’s defense
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9. Infection Vs disease
 The risk of developing disease depend on
 endogenous factors
 Individuals innate susceptibility to disease
 Level of function of cell mediated immunity
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10. Infection Vs disease
 Risk factors for active TB among infected
 Late adolescence(women 25-34 yrs)
 Older age
 HIV infection
 Recent infection<1 year
 Fibrotic lesion
 Silicosis
 CRF/hemodyalysis
 Diabetes
 Iv drug use
 Immunosuppressive drugs
 Gastroctomy,Jujunoileal bypass
 Post trasplantation
 Malnutrition/severe decrease in weight
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11. Natural history of disease(without HIV)
if untreated
 50% die in 5 year
 25% cured
 25 % chronically positive ( infectious)
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12. Etiology of TB
 Mycobacteria:
 family of mycobacteriacea / order actinomycetale
 Common species mycobacteria tuberculosis complex is M.tuberculosis
 M .tuberculosis complex includes
 M.bovis,
 M.caprea,
 M.africanum,
 M.microti,
 M.pennipeddi,
 M.canneti
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13. Etiology of TB
 M.tbc: road shaped, nonspore forming, thin ,aerobic bacterium, neutral on gram
stain
 Acid fast due to mycolic acid, FA and lipids in cell wall
 Other organisms AFB positive
 Nocardia,leigionella,isospora,cryptospordium
 Resistant to most antibiotics due to impermeable lipid and glycopeptide rich cell
wall
 Lipoarabinomannon-helps M.O to live inside macrophages
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14. Schematic diagram of Mycobacterial cell wall.
1.outer lipids
2.mycolic acid
3.polysaccharides (arabinogalactan)
4.peptidoglycan
5.plasma membrane
6.lipoarabinomannan (LAM)
7.phosphatidylinositol mannoside
8.cell wall skeleton
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15. AFB stain-rods in chain
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16. Pathogenesis
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17. Pathogenesis
 Granuloma:
 collection of macrophages called epithelloid cells surrounding the tubercle bacilli often
multinucleated giant cells-fusion of epitheloid cells (Langhan cells)→↑enzyme/free
radicals→kill m.o
 Lymphocytes,CD4 around the granulomas (THo→TH1→macrophage )
 Granuloma fuse+/_ central necrosis →caseous (cheese)
 Histopathology-depend on immunity
 Strong-good granuloma with scanty bacilli
 Weak-more necrosis-poor granuloma with abundant bacilli
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18. Granuloma with central necrosis in a lung TB. Note the
Langhans-type giant cells (with many nuclei arranged in a
horseshoe-like pattern at the edge of the cell) around the
periphery of the granuloma. Langhans-type giant cells are seen
in many types of granulomas, and are not specific for
tuberculosis.
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19. Granulation tissue with a poorly formed granuloma to the left
of centre. Within this area there is a multinucleate giant cell of
the Langhans type. The patient had a healing mycobacterial
infection of the skin (M. ulcerans infection).
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20. Clinical manifestation
 Pulmonary and extrapulmonary
 Prior to HIV era-80 %-90% pulmonary
 In HIV era <70%pulmonary
 60% of HIV-EPTB and pul TB or EPTB alone
 Pulmonary TB-primary/post primary
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21. Clinical manifestation
 Primary-result from initial infection with bacilli
 In high prevalent –children-middle and lower lobe
 Lesion usually peripheral + hilar or parathracheal LAP
 Majority heal –later calcification(Ghon focus)
 In children /HIV +ve→rapid progression to clinical illness, increased size of
lesion, pleural/pericardial effusion
 Lymph node involvement → obstruction + collapse
→bronchoectasis/emphysema
 Hematogeneous spread →milliary +meningitis
 Hypersensitivity reaction →erythema nodosum, phylectunar conjunctivitis
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22. Clinical manifestation
 Post primary TB
 Also called 2⁰/adult type/reactivation
 Result from endogenous reactivation of latent infection or re infection
 Usually localized to apical & posterior segments of upper lobe(b/c ↑ O2 tension)
& superior segment of lower lobe.
 Lesion range- small infiltrate to large cavity
 Highly infectious.
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23. Clinical manifestation
 Early in the coarse Sx / Sn non specific & insidious
 Fever , night sweats ,wt loss , anorexia, general malaise, weakness
 Cough – productive purulent haemoptysis
 Massive haemoptysis →blood vessel erosion
 Dyspenia & ARDS
 Physical findings-normal, rales, ronki, amphoric,fever,wt loss, clubbing, pale
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24. Extra Pulmunary TB
 ↑ ed with HIV infection
 TB lymphedenitis
 Most common EPTB >25%
 Common in HIV
 scrolofula cervical/supraclavicular LN
 LN painless/discrete→flactuate →drain
 Systemic symptoms+/_
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25. Extra Pulmunary TB
 TB pleursy
 Penetrating bacilli
 fever,pleutic chest pain
 Pleural effusion,dullness,dyspenea
 TB of upper airways
 Larynx,pharynx,epiglottis,hoarseness/dysphagia
 Dx laryngoscopy(ulcer),AFB+culture
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26. Extra Pulmunary TB
 Genitourinary TB-15 % of EPTB
 Due to hematogenuos seeding
 Local sx-dysuria,hematuria,frequency,flank pain
 Urine abnormal in 90%
 Calcification and urethral strictures →hydronephrosis and renal damage
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27. Extra Pulmunary TB
 Skeletal TB
 10% of all extrapulmonary case
 Reactivation of hematogenous foci or adjacent LN
 Weight bearing joints(spine,hip,knee)
 Spinal tbc(Pott”s Dx)= adjacent vertebrae thoracic/lumbar
 Collapse of vertabrae –kyphosis (gibbus)
 Paravertebral”cold”abcess
 Psoas abcess
 Paraparesis/paraplegia
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28. Extra Pulmunary TB
 TB meningitis/Tuberculoma
 5% extrapulmonary
 Children/HIV-adult
 Hematogenuos -primary/post primary or ependymal rupture
 50% CXR-miliary /old lesion
 Presentation
 Subtle→headache,mental change or acute confusion ,lethargy, change in sensorium, neck
rigidity
 Cranial nerve palsy
 Hydrocephalus, space occupying lesion- tuberculoma
 CSF protein, WBC / lymphocyte, glucose
 AFB yield by increased volume, repeated LP
 Anti TB + steroids
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29. 29 8/28/2022

30. Extra Pulmunary TB
 Gastrointestinal tuberculosis
 Any part
 Source-swallowing sputum, unpasteurized milk, hematogenous
 Common- cecum/ileum
 Clinical picture
 Depend on the organ
 Hepatobilliary-jaundice,hepatomegaly
 Splenomegaly
 Abdominal pain, diarrea,constipation
 Hematochezia
 Fever, wt loss, night sweat, anal fistula
 Ascites,(peritonitis),lymph node
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31. Extra Pulmunary TB
 Pericardial TB
 Hematogenous
 Reativationof latent focus
 Rupture of lymph node
 Increased with HIV
 High mortality
 Acute presentation-fever,pain,firiction rub,effusion,sn of tamponade
 ECHO strands→pericardiocentesis
 Exudative+lymphocytic→AFB+culture
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32. Extra Pulmunary TB
 Milliary or disseminated TB
 Hematogenous spread/ local spread(pleura,hilar ln)
 Child primary/adult-recent infection/reactivation of disseminated foci
 Small granuloma 1-2 mm-millet size
 Clinical feature
 Nonspecific/protean(fever,wt loss,sweating)
 Fever of unknown origin, organomegaly, lymph node
 Choroidal tubercle(pathognomonic)-30%
 +/_ Cough, menigismus(<10%)
 Dx high index of suscipicion
 CXR typical
 Sputum _ve(80%)
 Pancytopenea,DIC,abnormal liver test
 Granuloma on biopsy(BM,Liver)
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33. HIV associated TB
 Important OI in HIV/AIDS
 70-80% TB patients-HIV +ve(Africa)
 15% annual risk of TB disease if infected(10Xnormal) in HIV infected
 TB-all spectrum immunity status
 Pictures depend on level of immunity
 CD4>200-same as other patients
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34.  CD4<200-atypical presentation
 Primary type ,disseminated, lower lobe, LAP, pleural effusion,+EPTB, milliary, no
cavitary
 Atypical lung involvement
 Atypical CXR
 Diagnosis difficult
 Negative PPD
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35. HIV associated TB
 Less cavitary-less infectious
 Less smear positivity
 High burden of bacilli in body –high Blood culture positivity
(mycobacterium)
 EPTB is common >30%(40-60%)-
lymphatic,DTB,pleura,percardium,meninges
 Dx-difficult ”atypical granuloma”
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36. Drug-resistant tuberculosis (MDR- and XDR-TB)
 Multi-drug resistant tuberculosis (MDR-TB) is defined as TB that is resistant at
least to INH and RMP.
 Isolates that are multiply-resistant to any other combination of anti-TB drugs but
not to INH and RMP are not classed as MDR-TB.
 "Extensively drug-resistant tuberculosis" (XDR-TB) is defined as MDR-TB that is
resistant to quinolones and also to any one of kanamycin, capreomycin, or
amikacin.
 The principles of treatment for MDR-TB and for XDR-TB are the same.
 2nd line drugs
 The mortality higher in XDR
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37. Diagnosis of TB(pul+others)
 Key-high index of suspicion
 In high risk patients-not difficult
 May be difficult-old age,immunocompromised,asymptomatic
 AFB microscopy
 Sputum(3X,spot,morning,spot)
 Tissue
 Urine/ gastric lavage-false positive(mycobacterial commensals)
 Zeil-nelson’s stain or Kinyoum-based on fulscion dye
 Auramine rhodamine-staining→ with flourscene microscopy
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38. Culture
 Culture-sputum/other specimen
 Lowenstein-Jensen or Middle brookmedia(takes 4-
8 wek for growth)-popular
 Liquid media-2-3 wk for growth-by PCR or paper
chromatography
 Solid media/ Liquid media
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39. Diagnosis of TB(pul+others)
 Neuclic acid amplification
 Within hours-lower sensitivity/high cost
 To confirm-smear +ve or for smear _ve or EPTB
 LPA
 Gene Xpert
 Drug susceptibility test
 Relapse,failure cases
 Media (solid-slow,fluid-fast)
 PCR-mutation-markers
 Radiography
 “Classic”-upper lobe inflitrate/cavity-post primary, lower lobe/hilar Lap-primary/atypical
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40. Fibrotic- cavity
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41. Primary tuberculosis: A 31-year-old woman from
Taiwan with mild cough and fever. There is an infiltrate in the right
lower lobe. PPD was positive. Primary TB must be considered in
the differential of this radiograph. (Courtesy of Wallace Miller, Jr.,
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42. Primary tb
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43. Reactivation tuberculosis: A 31-year-old man with
persistent right chest pain. A. View of the lung apices demonstrates
an indistinct pulmonary opacity in the left apex.Sputum cultures were positive for M. tbc
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44. Milliary tb
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45. Diagnosis of TB(pul+others
 PPD skin test
 For screening test for M.tbc infection
 Limited value for diagnosis b/c low sensitivity/specificity
 Additional diagnostic procedures
 Smear/ culture on
 Sputum induction-dry cough
 Bronchoscopic BAL/transbronchial biopsy
 Gastric lavage-children(early morning)
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46. Diagnosis of TB(pul+others
 EPTB
 CSF analysis, culture
 Body fluids: analysis/smear/culture/ADA
 Tissues: Pleural tissue/LN
 Bone marrow-milliary
 Liver biopsy/culture-high in HIV
 Urine-AFB on culture _ve pyuria ,IVP
 U/S,C/T/MRI
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47. TREATMENT OF TB
 Chemotherapy
 1.cure of the patients
 2.prevention of death from active TB and late effect
 3.avoid relapse or recurrence
 4.prevention of spread of drug resistance organism
 5.protection of the community
 First line essential drugs
 bactericidal-R,H,Z,S
 bacteriostatic-E,T
 Second line drugs
 The bacteria population consists of
 1.metabolically active,continuosly growing bacteria which are in walls of tuberculous cavity
 2.intracellular bacilli
 3.semidormant bacteria which undergo spurts of metabolism and
 4.dormant bacilli which die off gradually on their own
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48. TREATMENT OF TB
 Mechanism of action
 INH-most potent bactercidal
 Kills 90% bacilli in few days
 Most active againist metabolical active/growing m.o
 Rifa
 Good bactericidal(for semidormant)good sterilizing agent-prevent relapse
 PZA
 Kills intracellular mo
 Sterlizing agent
 For initial phase-no importance beyond 2 months
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49. Principles of antiTB chemotherapy
 Combination-
 ↓resistance(mutants will be killed by one of the drugs)
 Bacteria of different population
 Given for several months(>6 months)
 To kill slow growing organisms/semi dormant bacilli
 To prevent relapse
 Resistance low probability-even lower when drugs combined
 MDR
 XDR
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50. Categories
 Categorization of TB patients by outcome of recent treatment
 New: never treated with anti TB or <1 month treatment
 Relapse: previously treated /completed treatment/smear /culture +ve TB
 Failure: newly diagnosed TB smear +ve at 5th month of treatment
 Return after default: patient come after discontinuation of drugs for 2 month
smear +ve
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51. Classification of TB
 Cases of TB are also classified according to the:
 1. anatomical site of disease;
 2. bacteriological results (including drug resistance);
 3. history of previous treatment;
 4. HIV status of the patient.
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52. Definitions of TB Cases Classifications
 (PTB+)
 2 +ve AFB , Or 1 +ve AFB /culture positive, Or one AFB +ve /CXR
abnormalities consistent with active TB as determined by a clinician.
 (PTB-)
 Sx of TB with 3 -ve smear/ No response to a course of broad-spectrum
antibiotics/Again 3 -ve smear by direct microscopy,
 Radiological abnormalities consistent with pulmonary tuberculosis,
 Decision by a clinician to treat with a full course of anti- tuberculosis Or
 A patient whose diagnosis is based on culture positive for M. tuberculosis but
three initial smear examinations negative by direct microscopy
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53. Definitions of TB Cases Classifications
 (EPTB)
 TB in organs other than the lungs, proven by one culture-positive specimen from
an extra-pulmonary site or histo-pathological evidence from a biopsy,
 Or
 TB based on strong clinical evidence consistent with active EPTB and the
decision by a physician to treat with a full course of anti-TB therapy.
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54. Status of treatment and HIV
 New ,Previously treated(failure,defaulted,relapse)
 HIV status-
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55. Standardized antiTB treatment regimens
 General-standard and effective
 Decrease transmission and magnitude of Tb in community
 Categorized according to priority of treatment
 Newly diagnosed, smear +ve, clinically serous disease high priority
 All regimens have 2 phases
 1st-initial(intensive)
 Rapid killing of actively growing bacilli and semi dormant
 Noninfectious in 80-90% in 2-3 months
 Supervised drug administration
 4-5 drugs use
 2nd continuation phase
 Sterilize slow growing bacilli
 Reduce failure and relapse rate
 2 drugs
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56. 56 8/28/2022

57. Treatment in special condition
 Pregnancy-S
 Liver disease-Z
 2SERH/6RH, 9RHE or 2SEH/10EH
 CKD-S,E,
 prefered 2RHZ/4RH
 Oral contraceptive-R caution
 Breast feeding-No contraindication
 ART-NVR,PI
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58. Monitoring
 DOTS
 Monitoring of new case smear +ve
 2nd,5th,6th month
 Retreatment -3rd,5th,8th month
 Dosing
 Range of weight
 Daily vs intermittent-3X/week
 Response -clinical
 2 wk non infectious
 4-8 wk sx improve
 Smear –ve at 2 months
 Response the same in HIV
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59. Monitoring
 Drug side effects
 INH: hepatitis, peripheral neuropathy
 RIFA:GI reaction, hepatitis
 PZA: hepatitis,arthralgia
 STM: hypersensitivity, vestibular/ fetal auditory damage
 ETM: optic neuritis
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60. Mx of drug side effects
 Minor –observe/continue
 Major- stop and replace the responsible
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61. Prevention of TB
 BCG-Milliary/meningitis prevented
 IPT-high risk –HIV/contact child with mother, prisoners
 1st rule out active TB
 Contraindication-CLD/alcoholic
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62. Summary
 Etiology/bacteriology
 Pathogenesis
 Clinical picture
 Principle and regimens, monitoring treatment
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