TB diagnosis: Quantiferon (plus): what? How? Filip Moerman, Infectiologist Liège, November 21st 2015.

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1 TB diagnosis: Quantiferon (plus): what? How? Filip Moerman, Infectiologist Liège, November 21st 2015.

2 Tuberculose General information Disease known in ancient times 1882 : Robert Koch : Bacil of Koch Acid fast bacilli (rods) Mycobacterium tuberculosis complex M. tuberculosis hominis M. tuberculosis bovis M. microti M. africanus

3

4 Incidence rates 2011

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6

7 Pulmonary histoplasmosis resembles lung tuberculosis Lung metastases

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9 Nov 2013: lady x, 28 yrs old, Rwanda Presents with glands (DD glands Afr), fever, B syndrome, cough++, tourist visa.. G4P4 (2 died) Clin Ex: low BMI, cachexis, LNN++ (H&N), EN (!) Lab: inflammation++, severe anaemia, thrombocytopenia, lymphopenia. Kidney ok, liver tests slightly disturbed. HIV+ (TEST!). ID and QFR X ray chest: suspicion of PTB What to do next?

10 Feb 2014: Belgian man 38 yrs old Feels uncomfortable two months after having travelled to South Africa to help in a hospital. Questions about TB Clin exam: no LNN, moderate gen cond, ausc nl X ray chest normal, ecg nl, echo abdo nl Lab: normal, but QFR+ (ID 2009 ) What to do next?

11 Merci à Jean Marc Senterre pour les 2 diapositifs suivants.

12 IGRA «l IDR in vitro» Lange C et al. (2007 Nat Clin Pract Rheumatol 3:

13 Positif > 8 spots Négatif < 4 spots Borderline 5, 6, or 7 spots Invalid

14 The (very) cooperative Doctor

15 Properties of the QFR test FDA/CDC approval as an aid for diagnosing M. tuberculosis infection in May 2005* Can be used in ALL circumstances in which ID is used, with the advantage of specificity towards BCG vaccination (immigrants); requires only ONE visit. Also ideal as screening tool for HCW and serial evaluation of M. tuberculosis infection. Usually not used in addition to an ID test except in HIV. *MMWR December 16, 2005/Vol 54/No. RR 15, pp

16 Interpretation of QFR (1) A positive QFR should prompt the same Health and Medical interventions as a positive ID result! ID after a pos QFR: NO REASON QFR after a pos ID: possibly useful Pos QFR: evaluate for TB disease* before the diagnois of LTBI is established Consider treatment of LTBI if active TB is not present. Our case II *X ray chest, urine exam, clin exam of the spine, clin exam for LNN, skin inspection, HIV test, firm anamn!

17 Interpretation of QFR (2) The majority of people with a neg QFR are unlikely to have M. tuberculosis infection and do not require further evaluation. Do NOT exlude M. tuberculosis infection on a neg QFR ALONE in patients with signs or symptoms suggestive of TB disease (cfr casus). Consider pre test probabilities. FN possible in lymphopenia!! HIV: mantoux AND IGRA: if one +: seriously considering treatment. Casus I: QFR

18 Epidemiologic use of QFR For persons with recent contact to an infectious TB patient, negative QFR results should be confirmed with a repeat test 8 10 weeks after exposure (window period)

19 In summary: NEGATIVE QFR Latent or active tuberculosis less probable (because no secretion of IFN gamma), but not entirely excluded. Take into account clinical ( ), biological (PCR, Culture, ZN) and radiological context, as well as epidemiological properties.

20 The Narcistic Doctor

21 In summary: POSITIVE QFR IFN gamma secretion present, therefore high probability of latent OR active TBC. Put in clin/radiol/microbiol/epidemiol context Mycobacterium kansasii, szulgai and marinum will equally make QFR positive.

22 The Cynic Doctor

23 INDETERMINATE QFR Little production of IFN gamma Immunosuppression? Where the tubes full? Did you shake well (Ag = on the wall) R/ Repeat!

24 Nov 2013: lady x, 28 yrs old, Rwanda Presents with glands (DD glands Afr), fever, B syndrome, cough++, tourist visa.. G4P4 (2 died) Clin Ex: low BMI, cachexis, LNN++ (H&N), EN (!) Lab: inflammation++, severe anaemia, thrombocytopenia, lymphopenia. Kidney ok, liver tests slightly disturbed. HIV+ (TEST!). ID and QFR X ray chest: suspicion of PTB What to do next?

25 Feb 2014: Belgian man 38 yrs old Feels uncomfortable two months after having travelled to South Africa to help in a hospital. Questions about TB Clin exam: no LNN, moderate gen cond, ausc nl X ray chest normal, ecg nl, echo abdo nl Lab: normal, but QFR+ (ID 2009 ) What to do next?

26 Soon available: QFR plus: 95% sensitivity, instead of 85% in ordinary QFR) less high in children better stimulation of T ly, not only T4 but T8 as well (T cytotox)

27 The Insecure Doctor

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