Quantiferon (plus): what? How?

TB‐diagnosis:
Quantiferon (plus): what? How?
Filip Moerman, Infectiologist
Liège, November 21st 2015.
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
Incidence rates 2011
Pulmonary histoplasmosis resembles lung tuberculosis
Lung metastases
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…?
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?
Merci à Jean‐Marc Senterre pour les 2 diapositifs suivants.
IGRA
« l’IDR in vitro »
Lange C et al. (2007 Nat Clin Pract Rheumatol 3: 528–534
Positif > 8 spots
Négatif < 4 spots
Borderline 5, 6, or 7 spots
Invalid
The (very) cooperative Doctor
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. 49‐55
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!
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‐
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)
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.
The Narcistic Doctor
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.
The Cynic Doctor
INDETERMINATE QFR
Little production of IFN‐gamma
‐Immunosuppression?
‐Where the tubes ‘full’?
‐Did you shake well (Ag = on the wall)
R/ Repeat!
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…?
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?
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)
The Insecure Doctor