Caroline Wightman TB Clinical Nurse Specialist The Hillingdon Hospital 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 Past history of TB exposure 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.) Multiple sputum samples for AAFB and culture (acid alcohol fast bacilli) Minimum of 3 (including 1 early morning) Examine Film/ smear under microscopy on slide Concentrate sample (auramine) positive = infectious TB Liquid culture up to 8 weeks or more

Investigations(cont.) Microscopy = pot. infectious TB Ref Lab Concentrate ID & Sensitivities Culture Ref Lab 8 weeks

Investigations Adults Productive cough spontaneous sputum Dry cough/ unable to produce sputum bronchial lavage induced sputum Children 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 BCG early on RD1 is present in 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)