TB Diagnosis

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					TB Diagnosis

Caroline Wightman
TB Clinical Nurse Specialist
     The Hillingdon Hospital
NW London TB rates per 100,000
TB in Hillingdon – Aug 2008
TB in NW London by Ethnic Group
TB in Hillingdon by Ethnic Group
TB in Hillingdon by Age and Sex
Summary of Some TB Statistics for
     NW London in 2008
 1111 reported cases
 The overall TB incident rate 60.2 per 100,000
 population
 Brent had highest rate 113.7
 Westminster had lowest rate 29.9
 Hillingdon had rate of 61.0 (153 cases) a 20.4%
 increase from 2007 (127 cases)
 Ethnic groups
 – Indian 38% (424 cases)
 – Black African 27% with 50% from Somalia
Summary of Some TB Statistics for
   NW London in 2008 (cont.)
 86% (956 cases) born abroad, 51% (341
 cases) entered UK within last 5 yrs.

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

 Multi Drug Resistant TB was identified in
 1.3% of cases tested
     Signs and Symptoms
Cough (with or without haemoptysis) for
more than 3 weeks
• Most patients report cough for 2 – 3 months
Fevers / temperature (low grade)
Night sweats
Weight loss
Lethargy
          Medical History
History of past TB
– When
– Length of treatment
– Medication used
Past history of TB exposure
Place of birth/ how long in UK
– 86% of TB patients born abroad
– 51% of TB patients entered the UK < 5 years
     Medical History (cont.)
Other chronic medical conditions
– Diabetes
– Alcohol dependence
– Any immunodeficient conditions
HIV infection
History of BCG?
History of recent travel
      Physical examination
To assess patient’s general health
Lymph nodes
– Cervical, axilla, groin, sub-clavicular
Examination of affected area
– Erythema induratum / nodosum
Investigations - Respiratory TB

 CXR if suspicious for
 TB should initiate
 further investigations
  Investigations - Respiratory TB
               (cont.)

1) Multiple sputum samples for AAFB and
      culture             (acid alcohol fast bacilli)
  •     Minimum of 3 (including 1 early morning)

       1. Examine Film/ smear under microscopy on slide
       2. Concentrate sample (auramine)
          positive = infectious TB
       3. Liquid culture up to 8 weeks or more
         Investigations(cont.)

Microscopy
        = pot. infectious TB   Ref Lab
Concentrate                                     ID &
                                         Sensitivities
 8
weeks




Culture                        Ref Lab
                 Investigations
Adults
Productive cough
     •   spontaneous sputum
Dry cough/ unable to produce sputum
     •   bronchial lavage
     •   induced sputum
Children
Productive cough
     •   spontaneous sputum
Unable to expectorate
     •   Induced sputum (nebulised saline)
     •   Gastric aspirates (early morning via NG tube)
Management of Respiratory TB
Treatment should start before culture
results are available if clinical picture is
consistent with TB

Standard treatment should continue even
when culture results are negative

Samples should be sent for culture from
autopsy if respiratory TB was suspected
Investigations - Non-Respiratory
               TB
Discuss advantages / disadvantages of biopsy
and needle aspiration
Samples for TB culture (dry pot)
–   Lymph node biopsy
–   Pus aspirated from lymph nodes
–   Pleural biopsy
–   Any surgical sample sent for routine culture
–   Any radiological sample sent for routine culture
–   Histology sample
–   Aspiration sample
–   Autopsy sample
Management of Non- Respiratory
            TB
Treatment should be started without
waiting for culture results if clinical /
histological picture consistent with TB

Chest X-ray to exclude co-existing
respiratory TB

Continue drug regimen even if culture
results are negative
         Other Diagnostic Aids
Diagnostic Molecular Tests
 PCR (polymerase chain reaction) detects & amplifies
 presence of DNA unique to specific organisms

 Detects mutations to Rifampicin
  – Used for rapid confirmation of TB diagnosis in sputum smear
    positive cases that would alter their care or
  – Before conducting large contact tracing initiatives
  – Used infrequently as expensive

 Negative PCR does not rule out TB diagnosis
   Other Investigations (cont.)
Mantoux test (purified protein derivative)
- 2 Tuberculin units by Intradermal injection
- Measured 48 to 72 hours
- Requires 2 visits
- Skilled operator
Main use – contact and new entrant screening

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

Negative Mantoux may rule out Sarcoid
IFN-γ release assays (IGRA)
ex-vivo immune assay
     – Previously sensitised T cells exposed to MTb antigens
     – measure release of IFN-γ
                  IGRA
Advantages :
– Single visit
– Objective
– Incorporate controls
– Potentially faster

– Big advantage: choice of antigen…
              RD1 contains the genes for ESAT6 and CFP10

     M. bovis                           M. tuberculosis



RD1 was lost from                                                  RD1 is present in
BCG early on                                                       all strains of
                                                                   M. tuberculosis




                    BCG        BCG

        ESAT6-early secretory antigen target 6, CFP10 –culture filtrate protein 10
Quantiferon Gold In-Tube

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
T-SPOT™.TB (Oxford Immunotec)
Summary: IGRAs in Diagnosis
Overall in active disease both IGRAs are
more sensitive than TST

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

IGRAs are more specific than TST
              Uses of IGRA
IGRA cannot distinguish between active and LTBI

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

False negatives can occur in immunosuppression

Expensive

NICE 2006 suggests 2-step testing with TST in contact
tracing, new entrant screening & before
immunosuppressive treatment (anti-TNF)
        Conclusion – Think TB
    Keep a high index of suspicion
-   Un-resolving cough
-   Chronic symptoms (back pain)
-   Recently arrived in UK from endemic
    countries - esp. Somalia
-   Early request for sputum / CXR
-   If in doubt refer
               References
Health Protection Agency www.hpa.org.uk
Tuberculosis in the UK, Annual Report on Tuberculosis
Surveillance in the UK 2008. HPA October 2008.
Tuberculosis in North West London. 2008 Annual
Report. Health Protection Agency.
NICE TB Guidance. Clinical Diagnosis and management
of Tuberculosis, and measures for its prevention and
control. March 2006.
Image source: Core Curriculum on Tuberculosis - What
the Clinician Should Know. 4th ed. 2000. Division of
Tuberculosis Elimination, US Centres for Disease
Control and Prevention (CDC)

				
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