What is EP-TB? TB in sites other than the lung parnachyma.  Picture bone Spinal cord Lymphadenopathyrenal Laryngeal

Introduction  Extra Pulmonary Tuberculosis (EP –TB) was diagnosed in 33 % of all HIV negative patients with TB, in New Zealand between (1)  5% of patients had co-comitant pulmonary involvement (1)  It is common practice to obtain a chest radiograph (CXR) for all patients with EP-TB  Sputum examinations are typically limited to those with abnormal radiographic findings that are suggestive of pulmonary TB (1).  Recognition of pulmonary involvement in EP-TB is an important public health issue. 1 Patients with smear negative Pulmonary TB (PTB) are responsible for 17% of new infections. (2,3,) 2. Contact tracing is carried out only if the patient has confirmed PTB. 3. The recommended timeframe for starting contact tracing differs according to the “infectivity” of the patient. 1.Ministry of Health Guidelines for Tuberculosis Control in New Zealand Ministry of Health. Sept Hernandez-Garduno E, Cook V, Kunimoto D, et al. Transmission of tuberculosis from smear negative patients: a molecular epidemiology study. Thorax.2004;59:286–290 3.Behr MA, Warren SA, Salamon H, et al. Transmission of Mycobacterium tuberculosis from patients’ smear-negative for acid-fast bacilli. Lancet1999; 353:444–449

Does CXR reliably identify EP-TB patients with Pulmonary involvement?  It is uncertain (4).  Little is known about the yield of sputum examination in this group of patients.  Sputum examination may also provide useful culture and susceptibility data if samples from the extra pulmonary components are unexpectedly culture negative or  in a site where it is not readily accessible. 4.Tanyalak P, Christopher E et al, Unexpected Pulmonary Involvement in Extra pulmonary Tuberculosis Patients. Chest 2008:134:

Retrospective Clinical audit at Auckland Hospital (2007 January July) AIM In HIV negative EP-TB patients at our institution: -- To determine the yield of sputum cultures in pts with normal and abnormal chest X rays and -- To determine if there are any clinical features that distinguishes between those with and without pulmonary involvement

Methodology Study Design: Retrospective clinical audit of patients with EP-TB presenting to our unit between 2007 January – 2010 July. Inclusion criteria  Initial presentation was with a clinical manifestation of EP-TB  Not known to have pulmonary involvement at presentation Exclusion Criteria-  Confirmed culture or smear positive pulmonary TB at presentation. The sputum smear and culture reports were extracted from patient records. The CXR done at the time of initial presentation, which a consultant radiologist had reported was analysed. A normal CXR is defined as a CXR that does not have any identifiable abnormality to the reporting consultant radiologist. Ethics approval was given by the Auckland Regional Ethics Committee.

Results (n=103)  Age Mean  SD 41.1  Range 16 – 98  Gender Male: Female 48 (46.6) :55 (53.4)  Country of birth Asia (India/China) 70 (68.0) New Zealand 16 (15.5) Pacific Islands 13 (12.6) Africa 3 (2.9) Unknown 1 (1.0)

Results : Presentation site of EP-TB LN49.5 Pleural23.3 Bone5.8 Abcess2.9 Renal2.9 Other15.5 Other- Abdominal(3), pericardial (2),Meningitis (2),laryngeal (2),adrenal (1),Otologic (1), eye (2), Chest wall (2)

Results- Diagnostic specimen of EP-TB SPUTUM culture25.2 EP-TB site biopsy Only 3 cases were not confirmed on culture. (2 eye, 1 pleural) Diagnosed TB by, n (%) Bone biopsy EBUS TBNA FNA lump LN FNA LN TBNA LN excision LN mediastinoscopic biopsy LN neck SI joint biopsy Spine abcess drainage Sputum Tibial biopsy Abscess drainage by sx Ascetic fluid Biopsy aorta Laryngeal biopsy Mediastioscopy Pericardial biopsy Pericardial fluid Pleural Pleural aspirate Pleural biopsy Sputum Not done 1 (1.0) 2 (1.9) 15 (14.6) 1 (1.0) 15 (14.6) 1 (1.0) 4 (3.9) 1 (1.0) 12 (11.7) 7 (6.8) 25 (24.3) 3 (2.9)

Sputum testing and CXR findings. All patients N=103 Normal CXR N=27 Sample done for PTB N=15 Culture positive N=5 Culture negative N=10 Sample not done N=12 Abnormal CXR N=76 Sample done for PTB N=68 Culture positive N=47 Culture negative N=21 Sample not done N=8

CXR normal Reason for doing sputum testing To obtain a culture7 sputum test done by ORL1 Suspected CXR change-reported as normal1 Cough2 PUO2 ?Pulmonary involvement1 ?Isolation during ward admission1 15

Sputum testing and CXR findings. All patients N=103 Normal CXR N=27 Sample done for PTB N=15 Culture positive N=5 Culture negative N=10 Sample not done N=12 Abnormal CXR N=76 Sample done for PTB N=68 Culture positive N=47 Culture negative N=21 Sample not done N=8 1.The majority of the study population had abnormal CXR 73% (n=76). 2.55% (n=15) of patients with normal CXR had sputum testing done to look for pulmonary involvement with a surprising 18 % (n=5) of patients becoming culture positive % (n=12) of normal CXR patients did not have a sputum tests

Normal CXR with Culture positive PTB Presenting site of EP-TB Diagnosis made by CXR abnormality Sputum Sample Smear/cultur e AdrenalSputumNoSpontaneous2+/Positive Basal skullBone biopsyNoInduced0/Positive LN mediastinal LN FNANoBronchial wash 0/Positive LN neckLN FNANoInduced0/Positive SI jointSI joint biopsy NoInduced1+/Positive On immuno- supression No evidence of pneumonia or tuberculosis.

Clinical features and culture (+) EPTB There was a statistically significant difference in ESR (64.2 vs. 37.7, P=. 008) and CRP (50.8 vs. 28.2, P=. 02) showing higher inflammatory markers in the subjects with culture positive PTB. The clinical characteristics of weight loss, fever, night sweats, cough, haemoptysis, sputum production, malaise were compared between the above 2 groups and were found to be not statistically significant.

conclusion  In patients presenting with EP-TB, CXR is not a reliable method of identifying pulmonary involvement.  Induced sputum testing is cheap and convenient and should be used in all patients with EP-TB so as not to miss a diagnosis of PTB.  Only patients with proven PTB will have contact tracing carried on, hence an important public health issue.  Elevated inflammatory markers can be used as a pointer to identify the group with pulmonary involvement.  This emphasises the need to do sputum testing to establish a diagnosis of PTB as advocated by the WHO guidelines.

limitations  A weakness of this study is that not all patients had sputum or bronchoscopic sampling.  We may have underestimated the proportion of patients with EP-TB who have pulmonary involvement despite normal CXR.  A further prospective study to evaluate all patients with EP-TB for pulmonary involvement may be justified based on our findings.

Thank you.

Abnormal CXR- Reason for not testing sputum. Site of EP-TB Diagnost ic specime nCultureAgeGender Country of birth CXR chang e Expain change pleuralnot done Not available23femaleindiayeseffusion LN neck LN excisionpositive26femaleindiayes mediastinal adenopathy LN mediastinum LN mediastin oscopic biopsypositive37maleindiayes mediastinal adenopathy LN neck LN excisionpositive39femaleindiayes R.apical infiltrate LN mediastinum mediastio scopypositive36femaleindiayes mediastinal adenopathy LN neck mediastio scopypositive49maleindiayes mediastinal adenopathy pleural pleural aspiratepositive21maleNZ maoriyeseffusion LN neckLN FNApositive17femaleNZ maoriyes pleural thickening Reason for not testing sputum Treatment started in India sensitivity available/CXR thought to be normal sensitivity available/did not see the need for sputum's sensitivity available/CXR thought to be normal Treatment started in Wellington Treatment started in Tauranga