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  • 1. Case historyCase history • T N, 20 years old student from ChhetrapatiT N, 20 years old student from Chhetrapati • C/O :C/O : Fever for 2 monthsFever for 2 months off and onoff and on mild fever with evening risemild fever with evening rise Cough with white sputumCough with white sputum Retrosternal chest discomfortRetrosternal chest discomfort Anorexia, some wt lossAnorexia, some wt loss haemoptysishaemoptysis
  • 2. Dr Krishna ShahDr Krishna Shah MDGP ResidentMDGP Resident Final yearFinal year
  • 3. Case presentationCase presentation Ranjit PandeyRanjit Pandey PharmacistPharmacist ranjitpandey17@gmail.comranjitpandey17@gmail.com
  • 4. • Contact history of PTB of his friendContact history of PTB of his friend • No treatment historyNo treatment history • Past history not significantPast history not significant
  • 5. ON EXAMINATIONON EXAMINATION • Conscious, well oriented , average build,Conscious, well oriented , average build, young adult not in any distressyoung adult not in any distress • AfeblileAfeblile • PR : 108/min RR : 18/min BP : 110/80PR : 108/min RR : 18/min BP : 110/80 mmHgmmHg • ENT : NADENT : NAD • Chest : clearChest : clear Heart : NAD P/A : NADHeart : NAD P/A : NAD • CNS : grossly intactCNS : grossly intact • LMS : NADLMS : NAD
  • 6. IMPRESSIONIMPRESSION • Prolonged fever without localizingProlonged fever without localizing signssigns • D/D PTBD/D PTB Enteric feverEnteric fever MalariaMalaria KalaazarKalaazar MalignancyMalignancy CTDCTD
  • 7. INVESTIGATIONSINVESTIGATIONS • HaemogramHaemogram WBC 13000/cmm N 74% L 26%WBC 13000/cmm N 74% L 26% Hct 38% ESR 10Hct 38% ESR 10 Blood culture : no growthBlood culture : no growth • UrineUrine Albumin : trace WBC 2-4Albumin : trace WBC 2-4 Bacteria : few Epi cells 0-2Bacteria : few Epi cells 0-2 • Chest x-ray : infiltrates RUZ, LMZChest x-ray : infiltrates RUZ, LMZ Koch’s lesionKoch’s lesion
  • 8. • Sputum for AFB 2 specimensSputum for AFB 2 specimens 3+3+ • Dx : sputum positive PTBDx : sputum positive PTB • Cat 1 ATT startedCat 1 ATT started
  • 9. TB EPIDEMIOLOGYTB EPIDEMIOLOGY WorldwideWorldwide • Third of world’s population infectedThird of world’s population infected • 9 million new cases with 3 million deaths (1995)9 million new cases with 3 million deaths (1995) • 25% of all avoidable deaths in developing25% of all avoidable deaths in developing countriescountries • 95% of TB cases and 98% of TB deaths in95% of TB cases and 98% of TB deaths in developing countriesdeveloping countries
  • 10. NEPALNEPAL • Over 80,000 people with TBOver 80,000 people with TB • 50,000 new cases every year50,000 new cases every year • 22,000 ( ½) with S+ TB22,000 ( ½) with S+ TB • 10,000 people die every year10,000 people die every year 200 deaths/week200 deaths/week 25 deaths/day25 deaths/day
  • 11. Why ?????Why ????? • Known for over 100 yrs that TB caused byKnown for over 100 yrs that TB caused by M. tbM. tb • Effective anti-TB drugs for nearly for 50Effective anti-TB drugs for nearly for 50 yrsyrs • Yet world’s TB problem always biggerYet world’s TB problem always bigger • Why ?Why ?
  • 12. CONTROL TARGETSCONTROL TARGETS • To reduce morbidity and mortality by 50%To reduce morbidity and mortality by 50% Cure rate 85%Cure rate 85% Case detection rate 70%Case detection rate 70%
  • 13. Tuberculosis epidemiologyTuberculosis epidemiology • AgentAgent : M. tb: M. tb M. bovisM. bovis Atypical mycobactriaAtypical mycobactria (tubercle bacilli, AFB)(tubercle bacilli, AFB) red, beaded rods, 2-4 mm long and 0.2-0.5 mm widered, beaded rods, 2-4 mm long and 0.2-0.5 mm wide • HostHost : persons 15-50 yrs old M>F: persons 15-50 yrs old M>F • EnvironmentEnvironment : close, prolonged: close, prolonged unventilated dark indoorsunventilated dark indoors
  • 14. • MOTMOT : airborne spread of infectious droplets: airborne spread of infectious droplets by coughing and sneezingby coughing and sneezing • Individual risk of exposureIndividual risk of exposure :: conc. of droplet nuclei in contaminated airconc. of droplet nuclei in contaminated air length of time breathing that airlength of time breathing that air • Source of infectionSource of infection :: sputum positive TB casesputum positive TB case • Risk of infection :Risk of infection : extent of exposure to droplet nucleiextent of exposure to droplet nuclei susceptibility to infectionsusceptibility to infection
  • 15. Outcome of primary infectionOutcome of primary infection • PrimaryPrimary complexcomplex • No clinical diseaseNo clinical disease Positive tuberculin skin testPositive tuberculin skin test (Usual outcome in >90% of cases)(Usual outcome in >90% of cases) • Hypersensitivity reactionsHypersensitivity reactions e.g. erythema nodosume.g. erythema nodosum Phlyctenular conjunctivitisPhlyctenular conjunctivitis DactylitisDactylitis • Pulmonary and pleural complicationsPulmonary and pleural complications e.g. tuberculosis pneumoniae.g. tuberculosis pneumonia lobar collapse, pleural effusionlobar collapse, pleural effusion • Disseminated diseaseDisseminated disease e.g. lymphadenopathy,e.g. lymphadenopathy, meningitis,meningitis, miliary diseasemiliary disease
  • 16. POST-PRIMARY TBPOST-PRIMARY TB • Either by reactivation or re-infectionEither by reactivation or re-infection • Pulmonary (80%)Pulmonary (80%) extensive lung destruction with cavitationextensive lung destruction with cavitation upper lobe involvement (infiltrates)upper lobe involvement (infiltrates) fibrosisfibrosis progressive pneumoniaprogressive pneumonia endobronchialendobronchial • Extra-pulmonary (20%)Extra-pulmonary (20%) pleural effusion, LN, CNS, pericarditis, GI,pleural effusion, LN, CNS, pericarditis, GI, spine, other bone and jointsspine, other bone and joints
  • 17. Natural History of Untreated TBNatural History of Untreated TB • Without treatmentWithout treatment after 5 yrsafter 5 yrs • 50% of PTB pts dead50% of PTB pts dead • 25% healthy25% healthy • 25% ill with chronic,25% ill with chronic, infectious TBinfectious TB
  • 18. Diagnostic Approach to PTBDiagnostic Approach to PTB • SymptomsSymptoms RRespiratoryespiratory CConstitutionalonstitutional CCough >3 wksough >3 wks Wt lossWt loss Sputum productionSputum production Fever/nightFever/night sweatssweats Haemoptysis TirednessHaemoptysis Tiredness Chest pain Loss of appetiteChest pain Loss of appetite BreathlessnessBreathlessness • Physical signsPhysical signs : non-specific: non-specific
  • 19. PTB Suspect with 3 –ve Sputum SmearsPTB Suspect with 3 –ve Sputum Smears Differential diagnosisDifferential diagnosis • CCF, LVFCCF, LVF • AsthmaAsthma • COPDCOPD • BronchiectasisBronchiectasis • Bronchial carcinomaBronchial carcinoma
  • 20. InvestigationsInvestigations • PTB suspectPTB suspect by clinical screeningby clinical screening • SputumSputum smear microscopy for AFB x 3smear microscopy for AFB x 3 daysdays Positive when at least 10,000 organismsPositive when at least 10,000 organisms present per 1 ml of sputumpresent per 1 ml of sputum Ziel-Neelsen stain, Fluorochrome stainZiel-Neelsen stain, Fluorochrome stain
  • 21. Slide ReportingSlide Reporting NoNo AFB per 100 OIFAFB per 100 OIF 00 1 - 9 AFB per 100 OIF1 - 9 AFB per 100 OIF scantyscanty 10 - 99 AFB per 100 OIF10 - 99 AFB per 100 OIF ++ 1 - 10 AFB per OIF1 - 10 AFB per OIF ++++ >10 AFB per OIF>10 AFB per OIF ++++++
  • 22. False ResultsFalse Results False positiveFalse positive resultsresults • Scratches on the slideScratches on the slide • Accidental transferAccidental transfer • EnvironmentalEnvironmental mycobactriamycobactria • Various acid fastVarious acid fast particlesparticles food particlesfood particles precipitatesprecipitates False –ve resultsFalse –ve results • Problems inProblems in collecting,collecting, processing, orprocessing, or interpreting smearsinterpreting smears • Administrative errorsAdministrative errors
  • 23. CHEST X-RAYCHEST X-RAY IndicationsIndications • Suspected complications in the breathless ptSuspected complications in the breathless pt • Frequent or severe haemoptysisFrequent or severe haemoptysis • Only 1 sputum smear +ve out of 3Only 1 sputum smear +ve out of 3 • TB suspect despite –ve sputum smear and 2TB suspect despite –ve sputum smear and 2
  • 24. X-RAY PATTERN IN PTBX-RAY PATTERN IN PTB • No CXR pattern absolutely typical of PTBNo CXR pattern absolutely typical of PTB • CXR findings : non-specificCXR findings : non-specific
  • 25. X-ray pattern in PTBX-ray pattern in PTB Classical patternClassical pattern • Upper lobe infiltratesUpper lobe infiltrates • B/L infiltratesB/L infiltrates • Cavitation (>90% S+)Cavitation (>90% S+) • Pul fibrosis andPul fibrosis and shrinkageshrinkage Atypical patternAtypical pattern (HIV(HIV)) • Interstitial infiltratesInterstitial infiltrates (esp. lower zones)(esp. lower zones) • No cavitationNo cavitation • No abnormalitiesNo abnormalities
  • 26. • 1. Linear Pattern1. Linear Pattern • Is defined as an abnormal network of fine linesIs defined as an abnormal network of fine lines running through the lines due to thickenedrunning through the lines due to thickened connective tissue septae. The most commonconnective tissue septae. The most common are:are: – Kerley A linesKerley A lines: long thin lines in the upper lobes,: long thin lines in the upper lobes, seen in both PA & lateral views (under the sternum inseen in both PA & lateral views (under the sternum in the latter)the latter) – Kerley B linesKerley B lines: short thin lines predominantly in the: short thin lines predominantly in the periphery of the lower zones extending 1-2cmperiphery of the lower zones extending 1-2cm horizontally inwards from the lung surface.horizontally inwards from the lung surface. – Kerley C linesKerley C lines: diffuse linear pattern through the: diffuse linear pattern through the entire lung: these can be difficult to recognise.entire lung: these can be difficult to recognise. Causes are interstitial pulmonary oedema andCauses are interstitial pulmonary oedema and lymphangitis carcinomatosis.lymphangitis carcinomatosis.
  • 27. Diseases which may causeDiseases which may cause miliary shadowingmiliary shadowing i.e. multiple small opacities less than 5mm ini.e. multiple small opacities less than 5mm in diameter are:diameter are: • TuberculosisTuberculosis • Miliary metastases –Miliary metastases – any primary site butany primary site but especially thyroid & chorion epitheliomaespecially thyroid & chorion epithelioma • ChickenpoxChickenpox • Pneumocystis Carinii pneumonia, CytomegalicPneumocystis Carinii pneumonia, Cytomegalic infectioninfection • SarcoidosisSarcoidosis • Dust inhalationDust inhalation – pneumoconioses– pneumoconioses • HaemosiderosisHaemosiderosis • Extrinsic allergic alveolitis, eosinophiliaExtrinsic allergic alveolitis, eosinophilia • Fibrosing alveolitisFibrosing alveolitis
  • 28. D/D : CXR FindingsD/D : CXR Findings • CavitationCavitation InfectionsInfections some bacterial pneumoniasome bacterial pneumonia lung abscesslung abscess some fungal infectionssome fungal infections Non-infectious diseasesNon-infectious diseases bronchial cabronchial ca CTDCTD occupational lung diseaseoccupational lung disease • Unilateral infiltratesUnilateral infiltrates pneumoniapneumonia bronchial cabronchial ca
  • 29. • B/L infiltratesB/L infiltrates pneumoniapneumonia CTDCTD OLDOLD sarcoidosissarcoidosis • Mediastinal LNMediastinal LN lymphomalymphoma bronchial cabronchial ca sarcoidosissarcoidosis
  • 30. Mantoux TestMantoux Test • Tuberculin skin test : infectionTuberculin skin test : infection • False –ve resultFalse –ve result (dm of skin induration <10mm)(dm of skin induration <10mm) HIV infectionHIV infection Severe malnutritionSevere malnutrition Miliary TBMiliary TB severe bacterial infectionsevere bacterial infection Viral infections e.g. measles, chickenpox, glandular feverViral infections e.g. measles, chickenpox, glandular fever CancerCancer Immunosuppressive drugs e.g. steroidsImmunosuppressive drugs e.g. steroids • False positiveFalse positive Previous exposure to environmental mycobacteria,Previous exposure to environmental mycobacteria,
  • 31. Flow chart for dx of PTB in people withFlow chart for dx of PTB in people with chronic respiratory symptomschronic respiratory symptoms Cough for 3 wks Give symptomatic treatment 3 sputum examinations X-ray chest No positive smear But X-ray positive 1 positive smear X-ray suggestive 2 or more positive smears Give antibiotics Non-TB abs No fluoroquinolones Treat for TB Treat for TB
  • 32. Clinical evaluation 2 wks after absClinical evaluation 2 wks after abs 3 sputum examination X-ray exam No positive smears But x-ray suggestive 1 positive smear X-ray suggestive 2 or more Positive smears Exclude other disease Esp. malignancy Treat for TB Treat for TB
  • 33. Standardized TB cases definitionsStandardized TB cases definitions • Why?Why? a) To determine treatmenta) To determine treatment b) For recording and reportingb) For recording and reporting • What determines a case definitionWhat determines a case definition a)a) Site of TBSite of TB b)b) Result of sputum smearResult of sputum smear c)c) Previous TB treatmentPrevious TB treatment d)d) Severity of TBSeverity of TB
  • 34. Pulmonary TBPulmonary TB • Smear positive caseSmear positive case at least 2 sputum smears positive orat least 2 sputum smears positive or at least 1 sputum positive and CXR + orat least 1 sputum positive and CXR + or at least 1 sputum positive & also culture +at least 1 sputum positive & also culture + • Smear negative caseSmear negative case 3 sputums negative & CXR positive & no3 sputums negative & CXR positive & no response with antibiotics orresponse with antibiotics or culture positiveculture positive
  • 35. Extra-pulmonary TBExtra-pulmonary TB At least 1 positive culture for M. tb fromAt least 1 positive culture for M. tb from extra pulmonary siteextra pulmonary site oror x-ray or histological or clinical evidencex-ray or histological or clinical evidence consistent with active TB at an extraconsistent with active TB at an extra pulmonary sitepulmonary site
  • 36. Case definitions by previousCase definitions by previous treatmenttreatment • NewNew • RelapseRelapse • Treatment failureTreatment failure • Return after defaultReturn after default • Transfer inTransfer in
  • 37. Treatment CategoriesTreatment Categories • Cat 1Cat 1 New sputum +ve PTBNew sputum +ve PTB Newly dx seriously ill pts withNewly dx seriously ill pts with severe forms of TBsevere forms of TB • Cat 2 RelapseCat 2 Relapse Treatment failureTreatment failure Return after defaultReturn after default • Cat 3 Sputum –ve PTB with limitedCat 3 Sputum –ve PTB with limited parenchymal involvementparenchymal involvement Extra pulmonary TB ( less severe forms)Extra pulmonary TB ( less severe forms)
  • 38. Severity of Extra-pulmonary TBSeverity of Extra-pulmonary TB Severe extra-pulSevere extra-pul TBTB • MeningitisMeningitis • MiliaryMiliary • PericarditisPericarditis • PeritonitisPeritonitis • B/L or extensive pleuralB/L or extensive pleural effusioneffusion • SpinalSpinal • IntestinalIntestinal • genitourinarygenitourinary • Less severe extra pulLess severe extra pul TBTB • L.N.L.N. • Pleural effusion (U/L)Pleural effusion (U/L) • Bone (excluding spine)Bone (excluding spine) • Peripheral jointPeripheral joint • Adrenal glandAdrenal gland
  • 39. Treatment of TB patientsTreatment of TB patients • Essential anti-TB drugsEssential anti-TB drugs Isoniazid (H) bactericidal 5 mg/kgIsoniazid (H) bactericidal 5 mg/kg Rifampicin (R) “ 10Rifampicin (R) “ 10 Pyrazinamide (Z) “ 25Pyrazinamide (Z) “ 25 Streptomycin (S) “ 15Streptomycin (S) “ 15 Ethambutol (E) bacteriostatic 15Ethambutol (E) bacteriostatic 15 Thiacetazone (T) “ 3Thiacetazone (T) “ 3
  • 40. Modes of Actions of TB DrugsModes of Actions of TB Drugs Population of TB bacilli – different groupsPopulation of TB bacilli – different groups a) Metabolically active, continuously growing-----a) Metabolically active, continuously growing----- IsoniazidIsoniazid b) Bacilli in acid environment inside cellsb) Bacilli in acid environment inside cells (macrophages) --(macrophages) -- PyrazinamidePyrazinamide c) Semi-dormant bacilli (persisters) --c) Semi-dormant bacilli (persisters) --RifampicinRifampicin d) Dormant bacillid) Dormant bacilli
  • 41. • Bactericidal drugsBactericidal drugs Isoniazid, Rifampicin, PyrazinamideIsoniazid, Rifampicin, Pyrazinamide • Sterilizing action (killing all bacilliSterilizing action (killing all bacilli )) Rifampicin, PyrazinamideRifampicin, Pyrazinamide • Preventing drug resistancePreventing drug resistance Isoniazid and RifampicinIsoniazid and Rifampicin Streptomycin and Ethambutol less effectiveStreptomycin and Ethambutol less effective
  • 42. TB treatment RegimensTB treatment Regimens Intensive phaseIntensive phase ContinuationContinuation • Cat 1Cat 1 2HRZE(HRZS) 6HE2HRZE(HRZS) 6HE 2HRZE(HRZS) 4HR2HRZE(HRZS) 4HR 2HRZE (HRZS) 4H3R32HRZE (HRZS) 4H3R3 2H3R3Z3E3 4H3R32H3R3Z3E3 4H3R3 • Cat 2Cat 2 2HRZES+1HRZE 5HRE2HRZES+1HRZE 5HRE ‘’ ‘’‘’ ‘’ 5H3R3E35H3R3E3 • Cat 3Cat 3 2HRZ2HRZ 6HE6HE 2HRZ2HRZ 4HR4HR 2HRZ2HRZ 4H3R34H3R3 7HR in continuation phase for spinal TB with7HR in continuation phase for spinal TB with
  • 43. ATT in Special SituationsATT in Special Situations • HIVHIV avoid S & T--- use E insteadavoid S & T--- use E instead • PregnancyPregnancy avoid S –- use E insteadavoid S –- use E instead • Renal failureRenal failure avoid S, E, Tavoid S, E, T RHZ safeRHZ safe • Liver diseaseLiver disease 2SHE / 10HE in jaundiced pts2SHE / 10HE in jaundiced pts Do not give Z in pts with liver diseaseDo not give Z in pts with liver disease • ContraceptionContraception
  • 44. Steroids in TBSteroids in TB IndicationsIndications • TB meningitisTB meningitis • TB pericarditisTB pericarditis • TB pleural effusion (when large with severeTB pleural effusion (when large with severe symptoms)symptoms) • HypoadrenalismHypoadrenalism • TB laryngitisTB laryngitis • Severe hypersensitivity reactions to ATTSevere hypersensitivity reactions to ATT • Renal tract TBRenal tract TB • Massive LN enlargement with pressureMassive LN enlargement with pressure symptomssymptoms
  • 45. Monitoring of TB pts duringMonitoring of TB pts during treatmenttreatment • Clinical monitoringClinical monitoring • Bacteriological monitoring (sputum smearBacteriological monitoring (sputum smear)) at time of dx (all pts)at time of dx (all pts) at end of initial phase (all pts)at end of initial phase (all pts) at month 5 of treatment (S +ve PTB pt)at month 5 of treatment (S +ve PTB pt) on completion of treatment (S +ve PTB ptson completion of treatment (S +ve PTB pts)) • CXRCXR at end of 1at end of 1stst month (S -ve PTB ptsmonth (S -ve PTB pts))
  • 46. Recording treatmentRecording treatment outcomes in PTB ptsoutcomes in PTB pts • CuredCured • Treatment completedTreatment completed • Treatment failureTreatment failure • DiedDied • Defaulted (treatment interrupted)Defaulted (treatment interrupted)
  • 47. Side-effects of Anti-TB drugsSide-effects of Anti-TB drugs IsonizidIsonizid • Common peripheral neuropathyCommon peripheral neuropathy hepatitishepatitis • Rare convulsionsRare convulsions joint painsjoint pains agranulocytosisagranulocytosis lupoid reactionslupoid reactions skin rashskin rash
  • 48. RifampicinRifampicin • CommonCommon GI (A/N/V/P)GI (A/N/V/P) orange/ red urineorange/ red urine hepatitishepatitis reduced effectiveness of OCPreduced effectiveness of OCP • RareRare ARFARF shockshock thrombocytopeniathrombocytopenia skin rashskin rash flu syndromeflu syndrome psedomembranous colitispsedomembranous colitis psedoadrenal crisispsedoadrenal crisis
  • 49. PyrazinamidePyrazinamide • CommonCommon joint painsjoint pains hepatitishepatitis • RareRare GI symptomsGI symptoms skin rashskin rash sideroblastic anaemiasideroblastic anaemia
  • 50. EthambutolEthambutol • Optic neuritis (poor vision & colorOptic neuritis (poor vision & color perception)perception) • Skin rashSkin rash • Joint painsJoint pains
  • 51. ThiacetazoneThiacetazone • Skin rash often with mucousSkin rash often with mucous membrane involvementmembrane involvement • HepatitisHepatitis • AgranulocytosisAgranulocytosis
  • 52. StreptomycinStreptomycin • CommonCommon auditory damage (hearing loss)auditory damage (hearing loss) vestibular damagevestibular damage (disturbed balance)(disturbed balance) (also to fetus)(also to fetus) renal damagerenal damage • RareRare skin rashskin rash
  • 53. ChemoprophylaxisChemoprophylaxis • 6 month course with daily Isoniazid (5mg/kg)6 month course with daily Isoniazid (5mg/kg) • Targets groupsTargets groups for prevention treatmentfor prevention treatment a) infants of mother with PTBa) infants of mother with PTB b) children <5 yrs of age without symptomsb) children <5 yrs of age without symptoms (house-hold contacts of S +ve PTB)(house-hold contacts of S +ve PTB) c) HIV-infected individualsc) HIV-infected individuals