TB DiagnosisTB Diagnosis

Caroline WightmanCaroline WightmanTB Clinical Nurse SpecialistTB Clinical Nurse Specialist

The Hillingdon HospitalThe Hillingdon Hospital

NW London TB rates per 100,000NW London TB rates per 100,000

TB in Hillingdon – Aug 2008TB in Hillingdon – Aug 2008

TB in NW London by Ethnic GroupTB in NW London by Ethnic Group

TB in Hillingdon by Ethnic GroupTB in Hillingdon by Ethnic Group

TB in Hillingdon by Age and SexTB in Hillingdon by Age and Sex

Summary of Some TB Statistics for Summary of Some TB Statistics for NW London in 2008NW London in 2008

1111 reported cases1111 reported casesThe overall TB incident rate 60.2 per 100,000 The overall TB incident rate 60.2 per 100,000 populationpopulationBrent had highest rate 113.7Brent had highest rate 113.7Westminster had lowest rate 29.9Westminster had lowest rate 29.9Hillingdon had rate of 61.0 (153 cases) a 20.4% Hillingdon had rate of 61.0 (153 cases) a 20.4% increase from 2007 (127 cases)increase from 2007 (127 cases)Ethnic groupsEthnic groups– Indian 38% (424 cases)Indian 38% (424 cases)– Black African 27% with 50% from SomaliaBlack African 27% with 50% from Somalia

Summary of Some TB Statistics for Summary of Some TB Statistics for NW London in 2008 (cont.)NW London in 2008 (cont.)

86% (956 cases) born abroad, 51% (341 86% (956 cases) born abroad, 51% (341 cases) entered UK within last 5 yrs.cases) entered UK within last 5 yrs.

49% of all cases in NWL in 2008 were 49% of all cases in NWL in 2008 were pulmonary, of which 31% were sputum pulmonary, of which 31% were sputum smear positivesmear positive

Multi Drug Resistant TB was identified in Multi Drug Resistant TB was identified in 1.3% of cases tested1.3% of cases tested

Signs and SymptomsSigns and Symptoms

Cough (with or without haemoptysis) for Cough (with or without haemoptysis) for more than 3 weeksmore than 3 weeks• Most patients report cough for 2 – 3 monthsMost patients report cough for 2 – 3 months

Fevers / temperature (low grade)Fevers / temperature (low grade)

Night sweatsNight sweats

Weight loss Weight loss

LethargyLethargy

Medical HistoryMedical History

History of past TBHistory of past TB– WhenWhen– Length of treatmentLength of treatment– Medication usedMedication used

Past history of TB exposurePast history of TB exposure

Place of birth/ how long in UK Place of birth/ how long in UK – 86% of TB patients born abroad86% of TB patients born abroad– 51% of TB patients entered the UK < 5 years51% of TB patients entered the UK < 5 years

Medical History (cont.)Medical History (cont.)

Other chronic medical conditions Other chronic medical conditions – DiabetesDiabetes– Alcohol dependenceAlcohol dependence– Any immunodeficient conditionsAny immunodeficient conditions

HIV infectionHIV infection

History of BCG?History of BCG?

History of recent travelHistory of recent travel

Physical examinationPhysical examination

To assess patient’s general healthTo assess patient’s general health

Lymph nodesLymph nodes– Cervical, axilla, groin, sub-clavicularCervical, axilla, groin, sub-clavicular

Examination of affected areaExamination of affected area– Erythema induratum / nodosumErythema induratum / nodosum

Investigations - Respiratory TBInvestigations - Respiratory TB

CXR if suspicious for CXR if suspicious for TB should initiate TB should initiate further investigationsfurther investigations

Investigations - Respiratory TB Investigations - Respiratory TB (cont.)(cont.)

1)1) Multiple sputum samples for Multiple sputum samples for AAFB and AAFB and cultureculture (acid alcohol fast (acid alcohol fast bacilli)bacilli)

• Minimum of 3 (including 1 early morning)Minimum of 3 (including 1 early morning)

1.1. Examine Film/ smear under microscopy on slideExamine Film/ smear under microscopy on slide

2.2. Concentrate sample (auramine) Concentrate sample (auramine)

positive = infectious TBpositive = infectious TB

3.3. Liquid culture up to 8 weeks or moreLiquid culture up to 8 weeks or more

Investigations(cont.)Investigations(cont.)

MicroscopyMicroscopy = pot. infectious TB = pot. infectious TB Ref LabRef Lab

ConcentrateConcentrate ID &ID &SensitivitiesSensitivities

CultureCulture Ref LabRef Lab

8 weeks

InvestigationsInvestigations

AdultsAdultsProductive coughProductive cough

• spontaneous sputumspontaneous sputum

Dry cough/ unable to produce sputum Dry cough/ unable to produce sputum • bronchial lavage bronchial lavage • induced sputuminduced sputum

ChildrenChildrenProductive cough Productive cough

• spontaneous sputumspontaneous sputum

Unable to expectorate Unable to expectorate • Induced sputum (nebulised saline)Induced sputum (nebulised saline)• Gastric aspirates (early morning via NG tube)Gastric aspirates (early morning via NG tube)

Management of Respiratory TBManagement of Respiratory TB

Treatment should start before culture Treatment should start before culture results are available if clinical picture is results are available if clinical picture is consistent with TB consistent with TB

Standard treatment should continue even Standard treatment should continue even when culture results are negativewhen culture results are negative

Samples should be sent for culture from Samples should be sent for culture from autopsy if respiratory TB was suspectedautopsy if respiratory TB was suspected

Investigations - Non-Respiratory TBInvestigations - Non-Respiratory TB

Discuss advantages / disadvantages of biopsy Discuss advantages / disadvantages of biopsy and needle aspirationand needle aspirationSamples for TB culture (dry pot)Samples for TB culture (dry pot)– Lymph node biopsyLymph node biopsy– Pus aspirated from lymph nodesPus aspirated from lymph nodes– Pleural biopsyPleural biopsy– Any surgical sample sent for routine cultureAny surgical sample sent for routine culture– Any radiological sample sent for routine cultureAny radiological sample sent for routine culture– Histology sampleHistology sample– Aspiration sampleAspiration sample– Autopsy sampleAutopsy sample

Management of Non- Respiratory Management of Non- Respiratory TBTB

Treatment should be started without Treatment should be started without waiting for culture results if clinical / waiting for culture results if clinical / histological picture consistent with TBhistological picture consistent with TB

Chest X-ray to exclude co-existing Chest X-ray to exclude co-existing respiratory TBrespiratory TB

Continue drug regimen even if culture Continue drug regimen even if culture results are negativeresults are negative

Other Diagnostic AidsOther Diagnostic Aids

Diagnostic Molecular TestsDiagnostic Molecular TestsPCR (polymerase chain reaction) detects & amplifies PCR (polymerase chain reaction) detects & amplifies presence of DNA unique to specific organismspresence of DNA unique to specific organisms

Detects mutations to RifampicinDetects mutations to Rifampicin– Used for rapid confirmation of TB diagnosis in sputum smear Used for rapid confirmation of TB diagnosis in sputum smear

positive cases that would alter their care orpositive cases that would alter their care or– Before conducting large contact tracing initiativesBefore conducting large contact tracing initiatives– Used infrequently as expensiveUsed infrequently as expensive

Negative PCR does not rule out TB diagnosisNegative PCR does not rule out TB diagnosis

Other Investigations (cont.)Other Investigations (cont.)

Mantoux test (purified protein derivative)Mantoux test (purified protein derivative)- 2 Tuberculin units by Intradermal injection- 2 Tuberculin units by Intradermal injection- Measured 48 to 72 hours- Measured 48 to 72 hours- Requires 2 visits- Requires 2 visits- Skilled operator- Skilled operator

Main use – contact and new entrant screeningMain use – contact and new entrant screening

Confounded by BCG vaccine, other Mycobacterium, viral Confounded by BCG vaccine, other Mycobacterium, viral illness, HIVillness, HIV

Negative Mantoux may rule out SarcoidNegative Mantoux may rule out Sarcoid

IFN-IFN-γγ release assays (IGRA) release assays (IGRA)

ex-vivoex-vivo immune assay immune assay– Previously sensitised T cells exposed to Previously sensitised T cells exposed to MTbMTb antigens antigens– measure release of IFN-measure release of IFN-γγ

IGRA IGRA

Advantages :Advantages :– Single visit Single visit – ObjectiveObjective– Incorporate controlsIncorporate controls– Potentially fasterPotentially faster

– Big advantage: choice of antigen…Big advantage: choice of antigen…

RD1 contains the genes for ESAT6 and CFP10RD1 contains the genes for ESAT6 and CFP10

M. bovis M. tuberculosis

BCG BCG

RD1 was lost from BCG early on

RD1 is present in all strains of M. tuberculosis

ESAT6-early secretory antigen target 6, CFP10 –culture filtrate protein 10

1. Take blood into pre-coated tubes (nil, TB antigen, PHA positive control)

2. Incubate at 37°C for 16-24 hours

3. Centrifuge (15mins, 3000G ~ 3729rpm)

4. Harvest supernatant – can now be stored

5. ELISA at your leisure

Quantiferon Gold In-TubeQuantiferon Gold In-Tube

T-SPOT™.TB (Oxford Immunotec)T-SPOT™.TB (Oxford Immunotec)

Summary: IGRAs in DiagnosisSummary: IGRAs in Diagnosis

Overall in active disease both IGRAs are Overall in active disease both IGRAs are more sensitive than TSTmore sensitive than TST

Overall in LTBI TSPOT is more sensitive Overall in LTBI TSPOT is more sensitive than TST, and QFN is as sensitive as TSTthan TST, and QFN is as sensitive as TST

IGRAs are more specific than TSTIGRAs are more specific than TST

Uses of IGRAUses of IGRA

IGRA cannot distinguish between active and LTBIIGRA cannot distinguish between active and LTBI

May increase confidence in diagnosis if unable to isolate May increase confidence in diagnosis if unable to isolate M.M.Tb from clinical specimensTb from clinical specimens

False negatives can occur in immunosuppression False negatives can occur in immunosuppression

ExpensiveExpensive

NICE 2006 suggests 2-step testing with TST in contact NICE 2006 suggests 2-step testing with TST in contact tracing, new entrant screening & before tracing, new entrant screening & before immunosuppressive treatment (anti-TNF)immunosuppressive treatment (anti-TNF)

Conclusion – Think TBConclusion – Think TB

Keep a high index of suspicion Keep a high index of suspicion - Un-resolving cough Un-resolving cough - Chronic symptoms (back pain)Chronic symptoms (back pain)- Recently arrived in UK from endemic Recently arrived in UK from endemic

countries - esp. Somaliacountries - esp. Somalia- Early request for sputum / CXREarly request for sputum / CXR- If in doubt referIf in doubt refer

ReferencesReferences

Health Protection Agency Health Protection Agency www.hpa.org.ukwww.hpa.org.ukTuberculosis in the UK, Annual Report on Tuberculosis Tuberculosis in the UK, Annual Report on Tuberculosis Surveillance in the UK 2008. HPA October 2008.Surveillance in the UK 2008. HPA October 2008.Tuberculosis in North West London. 2008 Annual Tuberculosis in North West London. 2008 Annual Report. Health Protection Agency.Report. Health Protection Agency.NICE TB Guidance. Clinical Diagnosis and management NICE TB Guidance. Clinical Diagnosis and management of Tuberculosis, and measures for its prevention and of Tuberculosis, and measures for its prevention and control. March 2006.control. March 2006.Image sourceImage source: Core Curriculum on Tuberculosis - What : Core Curriculum on Tuberculosis - What the Clinician Should Know. 4th ed. 2000. Division of the Clinician Should Know. 4th ed. 2000. Division of Tuberculosis Elimination, US Centres for Disease Tuberculosis Elimination, US Centres for Disease Control and Prevention (CDC) Control and Prevention (CDC)