Tuberculosis The greatest killer in the history of mankind

TuberculosisTuberculosisThe greatest killer in the history of mankindThe greatest killer in the history of mankind

Brig Jawad AnsariBrig Jawad Ansari FCPS,FCCP,FRCPEFCPS,FCCP,FRCPE

Professor of Medicine & PulmonologistProfessor of Medicine & Pulmonologist

EPIDEMIOLOGYEPIDEMIOLOGY

1/31/3rdrd of world population is infected of world population is infected

TB contribute 25% of avoidable deathsTB contribute 25% of avoidable deaths

95% cases in developing world95% cases in developing world

98% of TB deaths in developing world98% of TB deaths in developing world

75% of TB cases in productive age group75% of TB cases in productive age group

Pakistan is 7Pakistan is 7thth in ranking with reported cases 0f 361000 in ranking with reported cases 0f 361000

per annum and prevalence of 1810/100,000per annum and prevalence of 1810/100,000

What are these ?What are these ?

Acid Fast BacilliAcid Fast Bacilli

What is this ? What is this ?

Tubeculous Granuloma Tubeculous Granuloma

• Mycobacterium TB ComplexMycobacterium TB Complex

(Tubercle bacilli)(Tubercle bacilli)

(Acid Fast bacilli:AFB)(Acid Fast bacilli:AFB) M.tuberculosis (majority)M.tuberculosis (majority) M. bovisM. bovis M.africanumM.africanum

• Can remain dormant / persist for many yearsCan remain dormant / persist for many years• Atypical Mycobacterium/ OpportunisticAtypical Mycobacterium/ Opportunistic

Transmission of InfectionTransmission of Infection

Coughing patient of pulmonary TBCoughing patient of pulmonary TB Single cough: 3000 droplets nucleiSingle cough: 3000 droplets nuclei Also spread by talking, sneezing, spitting , singingAlso spread by talking, sneezing, spitting , singing Direct sunlight kill AFB in 5 minutesDirect sunlight kill AFB in 5 minutes Transmission is mostly indoorTransmission is mostly indoor Risks of exposure; concentration of droplet nuclei Risks of exposure; concentration of droplet nuclei

and the time spent in contaminated airand the time spent in contaminated air Bovine TB: cervical lymph node/ intestinal TBBovine TB: cervical lymph node/ intestinal TB

Is TB transmitted by following?Is TB transmitted by following?

FoodFood WaterWater Sexual intercourseSexual intercourse Blood transfusionBlood transfusion mosquitoesmosquitoes

Is TB transmitted by following?Is TB transmitted by following?

FoodFood WaterWater Sexual intercourseSexual intercourse Blood transfusionBlood transfusion mosquitoesmosquitoes

Infection to diseaseInfection to disease

90% of infected individuals do not develop disease90% of infected individuals do not develop disease Only evidence of infection is positive tuberculin testOnly evidence of infection is positive tuberculin test Chances of disease are higher soon after infectionChances of disease are higher soon after infection Higher in infants and childrenHigher in infants and children Emotional and physical stressEmotional and physical stress HIV infectionHIV infection

Natural History of TBNatural History of TB

If Untreated: then by 5 yearsIf Untreated: then by 5 years• 50%: will be dead50%: will be dead• 25%: cured by their immune system25%: cured by their immune system• 25%: become chronic25%: become chronic

TUBERCULOSIS

EXTRAPULMONARY TB

PULMONARY TB

WHO/CDS/TB/2003.313TREATMENT OF TUBERCULOSIS:GUIDELINESFOR NATIONAL PROGRAMMESTHIRD EDITION 2003

Pulmonary TB is much more common than

Extra-pulmonary TB ( 80% v 20%)

EXTRA-PULMONARY TBEXTRA-PULMONARY TB (WHO Categorization) (WHO Categorization)

MeningitisMeningitis MiliaryMiliary PericarditisPericarditis PeritonitisPeritonitis Bilateral/ Extensive Bilateral/ Extensive

pleural effusionpleural effusion SpinalSpinal IntestinalIntestinal GenitourinaryGenitourinary

SEVERE FORMS: Cat 1

EXTRA-PULMONARY TBEXTRA-PULMONARY TB (WHO Categorization) (WHO Categorization)

MeningitisMeningitis MiliaryMiliary PericarditisPericarditis PeritonitisPeritonitis Bilateral/ Extensive Bilateral/ Extensive

pleural effusionpleural effusion SpinalSpinal IntestinalIntestinal GenitourinaryGenitourinary

Lymph nodesLymph nodes Unilateral pleural Unilateral pleural

effusioneffusion Bones ( excluding Bones ( excluding

spinespine Peripheral jointsPeripheral joints Adrenal glandsAdrenal glands

SEVERE FORMS: Cat 1 LESS SEVERE FORMS: Cat 3

First year MBBS First year MBBS Teacher to student “Be good You will be fine”Teacher to student “Be good You will be fine”

In 3In 3rdrd year year

Must Work Hard ManMust Work Hard Man

In fourth yearIn fourth year

Must Work Very Hard You KnowMust Work Very Hard You Know

In final yearIn final year

Can You hear me ? You must work hardCan You hear me ? You must work hard

Diagnosing TuberculosisDiagnosing Tuberculosis

Diagnosis: Clinical SuspicionDiagnosis: Clinical Suspicion

• Cough for more than 2-3 weeksCough for more than 2-3 weeks• Sputum productionSputum production• Weight lossWeight loss• Night sweatsNight sweats• Fatigue & tirednessFatigue & tiredness• No sign is specificNo sign is specific

Diagnosis: Lab TestsDiagnosis: Lab Tests

Detection of AFBs in sputum smearsDetection of AFBs in sputum smears Culturing of AFB & sensitivityCulturing of AFB & sensitivity Chest X-rayChest X-ray Tuberculin Skin Test ?Tuberculin Skin Test ? ESR ???ESR ??? PCRPCR

SPUTUM SAMPLINGSPUTUM SAMPLING

At least three isolated samplesAt least three isolated samples Sputum and not salivaSputum and not saliva Early morning samples preferableEarly morning samples preferable If no cough:If no cough:

• Assisted coughAssisted cough• Induced Sputum Induced Sputum

Alternate to sputumAlternate to sputum• Gastric washingsGastric washings• Bronchial washingsBronchial washings

Slide reportingSlide reportingUsing 1000x magnificationUsing 1000x magnification

Number of bacilliNumber of bacilli Result reportedResult reported

No AFB No AFB 00

1-9 AFB per 100 oil immersion 1-9 AFB per 100 oil immersion fieldsfields

ScantyScanty

10-99 AFB per 100 oil immersion 10-99 AFB per 100 oil immersion fieldsfields

++

1-10 AFB per oil immersion field1-10 AFB per oil immersion field ++++

11-100 AFB / oil immersion field11-100 AFB / oil immersion field ++++++

InterpretationInterpretation

Smear positiveSmear positive• At least 2 smears examined and both At least 2 smears examined and both

positive for AFBpositive for AFB Smear NegativeSmear Negative

• At least 02 smears reported as negativeAt least 02 smears reported as negative IndeterminateIndeterminate

• Only one smear examinedOnly one smear examined• 03 smears examined and only one 03 smears examined and only one

reported as positivereported as positive

MYCOBACTERIAL CULTURESMYCOBACTERIAL CULTURES

Growing AFB on culture confirms diagnosisGrowing AFB on culture confirms diagnosis AFB grown can be tested for their AFB grown can be tested for their

sensitivity against various drugssensitivity against various drugs MethodsMethods

• Lowenstein JensenLowenstein Jensen• Liquid mediaLiquid media• Bactec Bactec

Limitations: 6-8 weeks, skilled lab, Limitations: 6-8 weeks, skilled lab,

Tuberculin Skin TestTuberculin Skin Test

In population with high prevalence of In population with high prevalence of TB, skin test is of little diagnostic TB, skin test is of little diagnostic valuevalue

Does not distinguish disease from Does not distinguish disease from infectioninfection

Positive Tuberculin Test

1.1. Active TBActive TB

2.2. Previous TBPrevious TB

3.3. Previous BCG vaccinationPrevious BCG vaccination

4.4. Atypical mycobacteriaAtypical mycobacteria

5.5. Sarcoidosis ( in less than 30%)Sarcoidosis ( in less than 30%)

False Negative Tuberculin Test

1.1. HIV infectionHIV infection

2.2. MalnuitritionMalnuitrition

3.3. Immunosupressive drugs like steroidsImmunosupressive drugs like steroids

4.4. Severe bacterial infection Severe bacterial infection

5.5. Milliary TB/ Fulminant TBMilliary TB/ Fulminant TB

6.6. Viral infections like measles, chicken pox, glandular Viral infections like measles, chicken pox, glandular feverfever

7.7. CancerCancer

8.8. Incorrect injection of PPDIncorrect injection of PPD

ESR AND TBESR AND TB

It can not be relied upon for the It can not be relied upon for the diagnosis of Tuberculosis and should diagnosis of Tuberculosis and should not be advised in routine.not be advised in routine.

Not recommended by WHO and by Not recommended by WHO and by local guidelineslocal guidelines

Role of Raidiology Role of Raidiology

There is no radiological findings which There is no radiological findings which can be diagnostic of Pulmonary can be diagnostic of Pulmonary TuberculosisTuberculosis

ButBut

There are certain typical patterns, There are certain typical patterns, where TB can be strongly suspectedwhere TB can be strongly suspected

GHON’S COMPLEXPRIMARY TB

Tuberculous PericarditisTuberculous Pericarditis

TUBERCULOMAS TUBERCULOMAS

TREATMENT OF TREATMENT OF TUBERCULOSISTUBERCULOSIS

Tuberculosis

Pulmonary Extra-pulmonary

Smear positive Smear negative

Histopathology Cultures

WHO/CDS/TB/2003.313TREATMENT OF TUBERCULOSIS:GUIDELINESFOR NATIONAL PROGRAMMESTHIRD EDITION 2003

Smear positive ( PTB+ )

>02 sputum smear pos

01 sputum smear pos(plus) c/s + M. tuberculosis

01 sputum smear pos(plus) radiological evidence of active TB

WHO/CDS/TB/2003.313TREATMENT OF TUBERCULOSIS:GUIDELINESFOR NATIONAL PROGRAMMESTHIRD EDITION 2003

Smear Neg Pulmonary Tuberculosis (PTB-)

Three sputum smears negative for AFB

Strong clinical suspicion

No response to broad spectrum antibiotics

Radiographic findings suggestive of active TB

WHO/CDS/TB/2003.313TREATMENT OF TUBERCULOSIS:GUIDELINESFOR NATIONAL PROGRAMMESTHIRD EDITION 2003

DRUG SENSITIVE TBDRUG SENSITIVE TB

Tuberculosis where AFBs are Tuberculosis where AFBs are sensitive to first line anti-tuberculosis sensitive to first line anti-tuberculosis drugsdrugs

FIRST LINE DRUGSFIRST LINE DRUGS

RIFAMPICIN (R)RIFAMPICIN (R) ISONIAZID (H)ISONIAZID (H) ETHAMBUTOL (E)ETHAMBUTOL (E) PYRIZINAMIDE (Z)PYRIZINAMIDE (Z)

VERY POTENTVERY POTENT LESS SIDE EFFECTSLESS SIDE EFFECTS ECONOMICALECONOMICAL SHORT DURATIONSHORT DURATION

• (6-8 months)(6-8 months)

D

O

T

S

DIRECTLY

OBSERVED

TREATMENT

SHORT- COURSE

TB case

Re-treatment case

Previous ATT

NO YES

New case

relapse

Treatment after default

chronic

Treatment failure

never taken ATT or ATT < 1 month

Rarely sputum smear negative

Completed ATT

Incomplete ATT

Not responded to standard regimen

after re-treatment regimen

WHO/CDS/TB/2003.313 Treatment Of Tuberculosis:guidelinesfor National Programmesthird Edition 2003

New Cases New Cases (PTB +/- and Extra PTB)(PTB +/- and Extra PTB)

04 Drugs-02months

2 HRZE

02 Drugs-06months

6 HE02Drugs-05months

5 HE

Repeat initial phase-01month

1 HRZE

Initial phase

Continuation phase

Check sputum smear

Smear +

Smear -

Smear -

Guidelines for Diagnosis & Management of Tuberculosis. Pakistan Chest Society. March 2002.

4HR 4HRE

Re-treatment cases Re-treatment cases (Relapse, Failures, Default: Smear positive)(Relapse, Failures, Default: Smear positive)

2 HRZES / 1 HRZE

5 HRE 4 HRE

Check sputum smear

Chronic case

1HRZE

If smear+, send c/s

Still smear positive

Smear +Smear -

Initial phase

Continuation phase

Guidelines for Diagnosis & Management of Tuberculosis. Pakistan Chest Society. March 2002.

MDR-TB ?