By: By:

Assist: Prof:Assist: Prof:Faculty of Community Medicine & Public Health Faculty of Community Medicine & Public Health SciencesSciencesLiaquat University of Medical & Health Sciences Liaquat University of Medical & Health Sciences (LUMHS)(LUMHS) Jamshoro, Sind, Pakistan Jamshoro, Sind, Pakistan e mail mnajeeb80@gmail.come mail mnajeeb80@gmail.com

LIAQUAT

MEDICAL

UNIVERSITY

DIAGNOSIS OF TUBERCULOSIS

Why diagnosis important?Why diagnosis important?

Diagnosis of tuberculosis in most casesDiagnosis of tuberculosis in most cases clinical diagnosis based upon the clinical clinical diagnosis based upon the clinical

presentation presentation

In 15-20% of p’t with suspected TB In 15-20% of p’t with suspected TB lab confirmation never obtainedlab confirmation never obtained

Early diagnosis and initiation of effective Early diagnosis and initiation of effective therapytherapy reducing morbidity and mortality from TBreducing morbidity and mortality from TB minimize the spread of infectionminimize the spread of infection

OutlineOutline

Screening for prior infectionScreening for prior infectionTuberculin skin test Tuberculin skin test

Diagnosis of pulmonary TBDiagnosis of pulmonary TBMedical historyMedical historyPhysical examinationPhysical examinationChest radiographChest radiographBacteriologic examBacteriologic exam

Screening for prior Screening for prior infectioninfection

Tuberculin skin testTuberculin skin test (little value as a case- finding (little value as a case- finding

tool )tool )

Screening for prior infectionScreening for prior infection

Whom to screenWhom to screenHigh prevalence and high risk High prevalence and high risk

population (HIV)population (HIV)How to screenHow to screen

Mantoux tuberculin test (ie, purified Mantoux tuberculin test (ie, purified protein derivative or PPD, tuberculin protein derivative or PPD, tuberculin skin test)skin test)

How to interpretHow to interpretDetermine maximum diameter of Determine maximum diameter of

induration by palpationinduration by palpation

Mantoux Tuberculin TestMantoux Tuberculin Test

Preferred method of testing for TB Preferred method of testing for TB infection in adults and childreninfection in adults and children

Tuberculin skin testing useful forTuberculin skin testing useful forExamining person who is not ill but may Examining person who is not ill but may

be infectedbe infectedDetermining how many people in group Determining how many people in group

are infectedare infectedExamining person who has symptoms Examining person who has symptoms

of TBof TB

Mantoux testMantoux test

Inject intradermally Inject intradermally 0.1 ml0.1 ml of PPD of PPD tuberculintuberculin

Produce wheal 6 Produce wheal 6 mm to 10mm to 10 mm in mm in diameterdiameter

Represent DTHRepresent DTH (delayed type (delayed type hypersensitivity)hypersensitivity)

Reading of Mantoux testReading of Mantoux test

Read reaction 48-Read reaction 48-72 hours after 72 hours after injectioninjection

Measure only Measure only indurationinduration

Record reaction in Record reaction in mmmm

Classifying the tuberculin reactionClassifying the tuberculin reaction

>>5 mm is classified as positive in5 mm is classified as positive inHIV-positive personsHIV-positive personsRecent contacts of TB caseRecent contacts of TB casePersons with fibrotic changes on CXR Persons with fibrotic changes on CXR

consistent with old healed TBconsistent with old healed TBPatients with organ transplants and Patients with organ transplants and

other immunosuppressed patientsother immunosuppressed patients

Classifying the tuberculin reactionClassifying the tuberculin reaction

>10>10 mm is classified as positive in mm is classified as positive inRecent arrivals from high-prevalence Recent arrivals from high-prevalence

countriescountriesInjection drug usersInjection drug usersResidents and employees of high-risk settingsResidents and employees of high-risk settingsMycobacteriology laboratory personnelMycobacteriology laboratory personnelPersons with clinical conditions that place Persons with clinical conditions that place

them at high riskthem at high riskChildren <4 years, or children and Children <4 years, or children and

adolescents exposed to adults in high-risk adolescents exposed to adults in high-risk categoriescategories

Classifying the tuberculin reactionClassifying the tuberculin reaction

>>15 mm is classified as positive in15 mm is classified as positive inPersons with no known risk factors for Persons with no known risk factors for

TBTB

Factors may affect TSTFactors may affect TST

False negativeFalse negative Faulty applicationFaulty application

Acute TB (2-10 wks to convert)Acute TB (2-10 wks to convert) Very young age (< 6 months old) Very young age (< 6 months old) Live-virus vaccinationLive-virus vaccination Overwhelming TB diseaseOverwhelming TB disease

False positiveFalse positive BCG vaccination (usually <10mm by BCG vaccination (usually <10mm by

adulthood)adulthood) Nontuberculous mycobacterial infectionNontuberculous mycobacterial infection

Two-Step TestingTwo-Step Testing

Use two-step testing for initial skin Use two-step testing for initial skin testing of adults who will be retested testing of adults who will be retested within 1-3 weekswithin 1-3 weeksIf first test (+), consider the person infectedIf first test (+), consider the person infectedIf first test (-), give second test 1-3 weeks If first test (-), give second test 1-3 weeks

laterlaterIf second test (+), consider person infectedIf second test (+), consider person infectedIf second test (-), consider person If second test (-), consider person

uninfecteduninfected

Diagnosis of Pulmonary Diagnosis of Pulmonary TBTB

Diagnosis of diseaseDiagnosis of disease

1. Medical history1. Medical history 2. Physical 2. Physical

examinationexamination 3. Chest 3. Chest

radiographradiograph 4. Bacteriologic 4. Bacteriologic

examexam AFBAFB CultureCulture

1.Medical1.Medical 2. Laboratory2. Laboratory TuberculinTuberculin X-ray exam:X-ray exam: Mass miniature Mass miniature

radiographyradiography Sputum exam:Sputum exam: Sputum cultureSputum culture Biochemical testBiochemical test Luciferase assayLuciferase assay ATP enzymeATP enzyme Blood C.P ( ESR Blood C.P ( ESR

normocytic anemia and and lymphopenia

1. Medical History1. Medical History

1. Medical History1. Medical History

Symptoms of diseaseSymptoms of diseaseHistory of TB exposure, infection, or History of TB exposure, infection, or

diseasediseasePast TB treatmentPast TB treatmentDemographic risk factors for TBDemographic risk factors for TBMedical conditions that increase risk Medical conditions that increase risk

for for TB diseaseTB disease

Medical HistoryMedical History

High prevalence populationHigh prevalence populationMore likely to be exposed to and More likely to be exposed to and

infected with bacillusinfected with bacillusImmigrant from high prevalence areaImmigrant from high prevalence areaResident or worker in jailResident or worker in jailLong term care facilityLong term care facilityClose contact to p’t with active TBClose contact to p’t with active TB

Medical HistoryMedical History

High risk populationHigh risk population More likely to progress from infection to active More likely to progress from infection to active

TBTBHIV (+) or other immunodeficiencyHIV (+) or other immunodeficiencyCRFCRFDMDM IVDAIVDAAlcoholicsAlcoholicsMalnourishedMalnourishedMalignancyMalignancyGastrectomyGastrectomy

2. Physical Examination2. Physical Examination

2. Physical Examination2. Physical Examination

Productive, prolonged cough Productive, prolonged cough duration of duration of ~~3 weeks3 weeks

Chest painChest pain HaemoptysisHaemoptysis Fever/ChillsFever/Chills Night sweatsNight sweats Appetite lossAppetite loss Weight lossWeight loss Easily fatiguedEasily fatigued

3. Chest radiography3. Chest radiography

3. Chest radiography3. Chest radiography

Classical radiograph appearanceClassical radiograph appearance InfiltrationInfiltration CavitationCavitation Fibrosis with tractionFibrosis with traction Enlargement of hilar and mediastinal lymph Enlargement of hilar and mediastinal lymph

nodenode In reactivation TBIn reactivation TB

Classically fibrocavitary apical diseaseClassically fibrocavitary apical disease Primary TBPrimary TB

Middle or lower lobe consolidationMiddle or lower lobe consolidation

Chest radiographyChest radiography

Abnormalities often Abnormalities often seen in apical seen in apical or or posteriorposterior segments segments of upper of upper llobe or obe or superior segments superior segments of lower lobeof lower lobe

May have unusual May have unusual appearance inappearance in HIV-HIV-positive persons positive persons

Cannot confirm Cannot confirm diagnosis of TBdiagnosis of TB!!!!

cavity in patient‘s RUL classic" for adult-type, reactivation tuberculosis

Classic adult TB CXRClassic adult TB CXR

PA viewPA view diffuse parenchymal diffuse parenchymal

disease with multiple disease with multiple cavities and bulla cavities and bulla formation on the leftformation on the left

Sputum smear was Sputum smear was positive for AFB positive for AFB

Chest radiographyChest radiography

No chest X-ray pattern is absolutely No chest X-ray pattern is absolutely typical of TBtypical of TB

10-15% of culture-positive TB 10-15% of culture-positive TB patients not diagnosed by X-raypatients not diagnosed by X-ray

40% of patients diagnosed as having 40% of patients diagnosed as having TB on the basis of x-ray alone do not TB on the basis of x-ray alone do not have active TBhave active TB

Mass miniature radiography:-Mass miniature radiography:-

(By Who expert committee )(By Who expert committee )

Indiscriminate TB case finding by it Indiscriminate TB case finding by it should be abandoned.should be abandoned.

0

20

40

60

80

100

Diagnosed by X-ray alone

Actual cases

X-ray-based evaluation causes over-diagnosis of

TB

NTI, Ind J Tuberc, 1974

Over-diagnosis

4. Bacteriologic 4. Bacteriologic EExamxam

Specimen CollectionSpecimen Collection

Obtain 3 sputum specimens for Obtain 3 sputum specimens for smearsmear examination and cultureexamination and culture

Persons unable to cough up sputumPersons unable to cough up sputuminduceinduce sputumsputumbronchoscopy bronchoscopy gastric aspirationgastric aspiration

Follow infection control precautions Follow infection control precautions during specimen collectionduring specimen collection

Three SpecimensThree Specimens

Three specimens optimalThree specimens optimal• Spot specimen on first visitSpot specimen on first visit; sputum ; sputum

container given to patientcontainer given to patient• Early morning collection by patient on Early morning collection by patient on

next daynext day

• Spot specimen during second visitSpot specimen during second visit

Three sputum smears are Three sputum smears are optimaloptimal

81%

93%100%

0%

50%

100%

First Second Third

Cum

ulat

ive

Pos

itivi

ty

Number of sputum samples requiredNumber of sputum samples required

overall diagnostic yield for sputum overall diagnostic yield for sputum examination related toexamination related to

the quantity of sputum (at least 5 mL) the quantity of sputum (at least 5 mL) the quality of sputumthe quality of sputummultiple samples obtained at different multiple samples obtained at different

times to the laboratory for processingtimes to the laboratory for processing3 samples obtained at least eight hours apart 3 samples obtained at least eight hours apart

with at least one sample obtained in the early with at least one sample obtained in the early morningmorning

Number of sputum samples Number of sputum samples requiredrequired

several studies have suggested that several studies have suggested that only two samples may be sufficient to only two samples may be sufficient to capture the majority of cases:capture the majority of cases: Retrospective studyRetrospective study

Nelson, SM, Deike, MA, Cartwright, CP. Value of examining multiple sputum specimens in the diagnosis of pulmonary tuberculosis. J Clin Microbiol 1998; 36:467.

overall, 92 percent of cases would overall, 92 percent of cases would have been detected with two have been detected with two specimensspecimens

a third sputum smear was of no a third sputum smear was of no additional valueadditional value

Smear ExaminationSmear Examination

Strongly consider TB in patients with Strongly consider TB in patients with smears containing acid-fast bacilli smears containing acid-fast bacilli (AFB)(AFB)

Results should be available within 24 Results should be available within 24 hours of specimen collectionhours of specimen collection

Presumptive diagnosis of TBPresumptive diagnosis of TBNot specific for M. tuberculosisNot specific for M. tuberculosis

AFB smearAFB smear

AFB (shown in red) are tubercle bacilli

Reporting on AFB MicroscopyReporting on AFB Microscopy

Number of bacilli seen Result reported

None per 100 oil immersion fields Negative

1-9 per 100 oil immersion fields Scanty, reportexact number

10-99 per 100 oil immersion fields 1+

1-10 per oil immersion field 2+

> 10 per oil immersion field 3+

Open tuberculosisOpen tuberculosis

A tuberculous ulceration or other A tuberculous ulceration or other form of tuberculosis in which form of tuberculosis in which tubercle bacilli are present in the tubercle bacilli are present in the excretions or secretionsexcretions or secretions..

Pulmonary tuberculosis, Pulmonary tuberculosis, especially with cavitation.especially with cavitation.

開放性結核就是在病人咳出的痰液中有結核開放性結核就是在病人咳出的痰液中有結核桿菌的存在 桿菌的存在

Sputum Cultures 22ndnd in importance in case- finding programme. in importance in case- finding programme. DifficultDifficult TediousTedious ExpensiveExpensive Needs special trainingNeeds special training lengthy ( takes at least 6 - 8 wks ) L. J medialengthy ( takes at least 6 - 8 wks ) L. J media Method offered with chest symptoms & Method offered with chest symptoms &

sputum smear –ve.sputum smear –ve. Culture of sputum is necessary for carrying Culture of sputum is necessary for carrying

out sensitivity tests & monitoring drug out sensitivity tests & monitoring drug treatment treatment

( drug susceptibility test )( drug susceptibility test )

Liquid mediaLiquid media ( BACTEL media is ( BACTEL media is used )used )

production of coproduction of co22 in 2 wks in 2 wks

Cultures

Colonies of M. tuberculosis growing on media

•Gold standard for TB diagnosis•Use to confirm diagnosis of TB•Culture all specimens, even if smear negative•Results in 4 to 14 days when liquid medium systems used

98%

70%

0

20

40

60

80

100

AFB Microscopy X-ray

Microscopy is more objective and reliable than X-ray

Inter-observeragreement

50%

98%

0

20

40

60

80

100

AFB Microscopy X-ray

Microscopy is a more specific test than X-ray for TB

diagnosis

Specificity

Diagnosis of Pulmonary TB

Cough 3 weeks

AFB X 3

Broad-spectrum antibiotic 10-14 days

If symptoms persist, repeat AFB smears, X-ray

If consistent with TB

Anti-TB Treatment

If 1 positive, X-ray and evaluation

If 2/3 positive: Anti-TB Rx

If negative:

Recommended Diagnostic ApproachRecommended Diagnostic Approach

Thanks for your Thanks for your attention!attention!