IGRAs for Diagnosis of Tuberculosis: 2010 Update

Size: px
Start display at page:

Download "IGRAs for Diagnosis of Tuberculosis: 2010 Update"

Transcription

1 IGRAs for Diagnosis of Tuberculosis: 2010 Update Nira Pollock, M.D., Ph.D. Division of Infectious Diseases Beth Israel Deaconess Medical Center Boston, MA May 1, 2010

2 Problems with the PPD False positives Recent BCG vaccine non-tb mycobacteria (NTM) False negatives 25-30% patients with active pulmonary TB initially negative Newborn/elderly, immunosuppression, renal failure, acute non-tb infection, etc unable to distinguish active disease from past exposure

3 Interferon-gamma Release Assays (IGRAs): basic concepts Expose T cells (isolated, or within whole blood) to: TB antigens (in peptide form), vs positive control antigen ( mitogen, e.g. phytohemagglutinin A), vs negative control (e.g. saline) Incubate overnight : T cells (both CD8 and CD4) previously sensitized to these TB antigens in vivo release IFN- Mitogen stimulates cells non-specifically to release IFN- as control for general T-cell anergy Saline control defines level of background (should be low) Quantify amount of IFN- produced under each condition

4 IGRAs: basic concepts, cont. Theory: overnight incubation detects sensitized effector T cells, i.e. already activated in vivo (longer incubation could activate resting central memory T cells also)? Primarily CD4+ (Mack et al, 2009) Like PPD, IGRAs are unable to distinguish between LTBI and active disease Mack et al, TBNET consensus statement; Eur Respir J 2009

5 Quantiferon-TB-Gold (Cellestis, Inc.) FDA-approved May 2005 for detection of LTBI and TB disease ** must incubate cells with antigen within 12 hours of collection

6 Quantiferon-TB Gold Peptide antigens used in assay simulate two proteins specific to Mycobacterium tuberculosis complex (MTBC: M. tuberculosis, M. bovis, M. africanum, M. microti, M. canettii): ESAT-6, CFP-10 (genes coding for both are found within MTBC RD1 region, which is deleted in M. bovis BCG strain) Eliminates false-positives due to BCG vaccination and to almost all NTM (**exceptions: M. kansasii, M. marinum, M. szulgai)

7 3rd generation: QFT-Gold In Tube (IT) FDA-approved October 2007 NOW FORMALLY REPLACING 2 nd GENERATION company no longer making prior version! Specimen collection: draw whole blood directly into three proprietary 1 ml blood collection tubes: 1) TB-specific Ag (dried onto wall of tube) 2) Nil (-) control 3) Mitogen (+) control (dried onto wall of tube). TB-specific peptide antigens: ESAT-6, CFP-10, TB7.7. Goal of adding extra antigen: increase sensitivity. (Like ESAT-6/CFP-10, TB 7.7 is not present in BCG strains and most NTM.)

8 QFT-Gold IT (continued) Must not under or over-fill tube. Shake 10x vigorously after draw. Keep at room temp. Must put at 37ºC within 16h of collection. Incubate upright at 37ºC for 16-24h Tubes can then be held at 2-27ºC for up to 3 days prior to centrifugation (so can ship at room temp). Centrifuge 15 to separate plasma from cells, remove >150 L plasma to assay (can store spun tube or plasma at 4ºC for 28 days). Quantify IFN- in plasma by ELISA, as for QFT-G IT test format allows o/n incubation at site of draw (e.g. hospital or clinic), vs central testing center QFT-G IT is being done at the Hinton State Lab (contact them to obtain tubes and arrange submission); also offered at e.g. Quest

9

10 QFT-G IT, continued Quantification of IFN- : ELISA, as for QFT-G Results readout: positive, negative, or indeterminate Ideally, lab should report absolute value result in IU/mL, so that clinician can evaluate how close absolute value is to the cutoff Lab should also report reason for indeterminate Low mitogen response: insufficient or dysfunctional lymphocytes, reduced lymphocyte activity due to prolonged specimen transport, improper specimen handling High background in nil control: heterophile antibodies (interfering human anti-mouse antibodies), intrinsic IFN-gamma secretion (? recent vaccination,? just true for some people--1-2% of population per Cellestis website)

11 QFT-G IT results interpretation Note: for QFT-G this value was >50%; seems that new cutoff would generate more positives Note: for QFT-G nil cutoff was 0.7 IU/mL; seems that new cutoff of 8.0 would generate a lot fewer indeterminates..

12 T-Spot.TB (Oxford Immunotec; Elispot technology) FDA-approved July 2008 in vitro diagnostic test based on an enzymelinked immunospot (ELISPOT) method enumerates M.tuberculosis-sensitized effector T cells responding to stimulation with a combination of peptides simulating ESAT-6 and CFP10 antigens, by capturing interferongamma (IFN-γ) in the vicinity of T cells from which it was secreted

13 T-Spot.TB Each spot=one reactive effector T-cell

14 TSpot.TB results interpretation Positive: (ESAT-6-Nil) and/or (CFP-10-Nil) are > 8 spots. (***note: this cutoff used to be 6 spots) Negative: both (ESAT-6-Nil) and (CFP-10-Nil) are < 4 spots. (includes values less than zero). Borderline (equivocal): highest (TB antigen-nil) spot count is 5, 6 or 7 spots Collect a new specimen and retest Indeterminate: nil control count is >10 spots, OR mitogen control count is <20 spots and (TB Ag-nil) counts are <4 spots

15 Doing T-Spot in MA Oxford Immunotec has a testing facility in Marlborough (since July 2009): CLIA/CAP certified Specimens (blood only) must be shipped at room temp day of draw and have 32 hours to reach testing center (package insert says 8 hours, but Oxford has validated longer time frame); contact Oxford for details (tubes, shipping)

16 Assessing the accuracy of IGRAs General principles used to date: Sensitivity: approximated by measuring proportion of positive tests in patients with cultureconfirmed active TB Specificity: approximated by measuring proportion of negative tests in patients with low risk for TB infection Problem: no confirmatory test exists for diagnosis of LTBI or culture-negative TB disease (no gold standard!)

17 QFT-G IT package insert (Jan 2009) Sensitivity in culture-confirmed active TB (all with <8days treatment prior to testing): Japanese study (n=92): QFT-G IT 93.5%, QFT-G 83.7% Australian study (n=27): QFT-G IT 88.9%, QFT-G 74.1% US study (n=44): QFT-G IT 84.1%, QFT-G 77.3% Overall sensitivity: QFT-G IT 89%, QFT-G 81% Specificity in subjects at low reported risk for TB infection (US study; subjects had no reported TB risk factors, and none had BCG history): Overall specificity: QFT-G IT 99.2%, QFT-G 99.8%, TST 99.1%

18 QFT-G IT package insert (Jan 2009) Cautions that the performance of the USA format of QFT-G IT has not been extensively evaluated in: Individuals who have impaired or altered immune function such as HIV infection/aids, s/p transplantation managed with immunosuppressive treatment, patients on immunosuppressive drugs (e.g. corticosteroids, methotrexate, azathioprine, cancer chemotherapy) Patients with the following clinical conditions: diabetes, silicosis, chronic renal failure, hematological disorders (e.g., leukemia and lymphomas), and other specific malignancies (e.g., carcinoma of the head or neck and lung). Individuals younger than age 17 years Pregnant women

19 Review of TSpot.TB FDA approval document/pi (July 2008) Sensitivity in culture-confirmed active disease (n=183): 95.6% using >6 spots, 90.7% using >8 spots. Specificity (used individuals with no TB risk factors and negative TST) (n=306): 97.1% using >6 spots, 99.0% using >8 spots (i.e. if equivocal (5,6, or 7 spots) are counted as negative). Equivocal or borderline result (TB Ag-nil = 5,6, or 7 spots): represents the area of overlap between results obtained for culture-confirmed positive samples and low risk TB negative samples Note: Oxford Immunotec website (4/12/10) quotes 95.6% sensitivity and 97.1% specificity, but these are for >6 spot cutoff, whereas current version uses >8 spot cutoff and equivocal range.

20 TSpot.TB FDA approval/pi (July 2008): clinical studies Goal: include subjects from all major risk groups indicated for TB screening by CDC guidelines (including those with potential for false positive/negative TST) TSpot.TB vs TST evaluated in typical candidates for routine LTBI screening, with various risk of exposure and progression (n=1403) (NOTE: used >6 spot cutoff) Included 328 HIV+, 229 recent contacts, 122 druginduced immunosuppression, 97 IVDU, 108 DM, 195 ESRD. Many BCG-vaccinated and foreign-born. 93 children/adolescents.

21 TSpot.TB FDA approval/pi clinical studies: aggregate results (not by clinical subgroup) After controlling for the other variables, positive results for both T-SPOT.TB and TST were significantly associated with history of prior TB infection. A positive result for T-SPOT.TB was significantly associated with contact with infectious TB and birth in a TB endemic country; no such association observed for TST. A positive TST was associated with BCG vaccination; no such association observed for T-SPOT.TB A negative TST was associated with being immunocompromised; no such association observed for T-SPOT.TB TSPOT.TB results were not impacted by age

22 TSpot.TB FDA approval document/pi (continued) Notes theoretical cross-reaction (false-positive test) with M. kansasii, M.szulgai, M. marinum, M. xenopi, M gordonae (latter two not mentioned in QFT-G IT PI). However, actual data obtained in a very small # of patients 12 with MAC (all negative with TSpot), 1 with xenopi (positive), 4 with gordonae (all positive), 1 with kansasii (positive). (note: no marinum..) The performance of this test has not been adequately evaluated with specimens from individuals younger than age 17 years, in pregnant women and in patients with hemophilia

23 Direct comparisons of QFT-G IT, TSpot.TB, and TST: meta-analysis Diel et al, Chest 2010 Evaluated comparative sensitivity in studies of subjects with active TB confirmed by culture and/or PCR and/or histologic evaluation, treated for <2 weeks Evaluated comparative specificity for LTBI in studies of subjects who were healthy, native residents of low-incidence countries without any previously known exposure to TB, irrespective of BCG vaccination status. Evaluated indeterminate rates (though no apparent distinction between indeterminates due to high background, vs low mitogen) Included studies that evaluated immunosuppressed subjects Note: cutoff for TSpot.TB+ was >6 spots in all included studies, which as discussed is different than FDA-approved version

24 Diel et al metaanalysis, cont Pooled sensitivities in active TB: TST: 69.9% QFT-G IT: 81%. Note that in studies done in developing countries, sensitivity was 74.3%, vs 84.5% in developed countries. (Is this difference due to HIV co-infection, malnutrition, or other factors?) TSpot.TB: 87.5%. Majority of studies done in developed countries; sensitivity in that subgroup was 88.5% Pooled specificities in low-risk subjects: QFT-G IT (5 studies): 99.2% TSpot.TB (3 studies): 86.3% Pooled rates of Indeterminates: QFT-G IT: 2.1%. In immunosuppressed subgroup: 4.4% TSpot.TB: 3.8%. In immunosuppressed subgroup: 6.1%

25 IGRA performance in specific groups of interest

26 e.g. contacts of active TB cases Overall consensus, IUATLD NAR meeting, Vancouver, 2007: overall both IGRAs performing well (and comparably) in contact investigations Tspot.TB and QFT-G (including IT version) results correlate better than TST results with exposure to MTB 1, 2 Direct comparison TSpot.TB vs QFT-IT vs TST, : both IGRAs appeared to indicate LTBI more accurately than TST, and IGRAs agreed well Suggests that IGRAs may be as or more sensitive than TST for recently acquired infection (in immunocompetent) (1 Richeldi, AJRCCM 2006; 2 Arend et al, AJRCCM 2007; 3 Diel et al, Chest 2009)

27 e.g. HIV Data mixed: can use IGRAs, but watch for indeterminates, particularly at low CD4 QFT-G IT: e.g. Brock et al, 2006, Denmark: % indeterminates correlated with low CD4 (24% in pts with CD4<100). ELISPOT assays 1 : overall perform better than TST. E.g. Dheda et al, 2005: T-Spot.TB in HIV-positive pts w/o other TB risk factors: technical performance independent of CD4 count. However, another study found more indeterminates with Tspot vs QFT-G (Stephan et al, 2008) Tspot may be more sensitive than QFT-G in this population (Mandalakas et al, 2008, small study in S. African patients) 1 Kimura et al 1999; Chapman et al, 2002; Carrara et al, 2004, Dheda et al 2005

28 HIV, continued Diagnosis of active TB in HIV+: QFT-G IT might be a sensitive tool for detection/prediction of active TB in HIV+ (Aichelburg et al, CID 2009), or NOT (Aabye et al, PLoSONE 2009) Cattamanchi et al, BMC ID 2010: TSpot.TB in 236 HIV+ active TB suspects in Uganda; mean CD4 of patients diagnosed with active TB by culture. 10% of subjects had insufficient mononuclear cell counts for TSpot assay. Of remainder: 25% had indeterminate results IGRA sensitivity was 73% Proportion of positive test results was similar across CD4 count strata **IGRA results did not meaningfully alter the probability of active TB in patients with negative sputum smears **If IGRA sensitivity might be lower in HIV+ subjects (vs immunocompetent) with active TB (recall also Diel metaanalysis), what does this mean re: sensitivity for LTBI?

29 Immunocompromised patients IGRAs (vs TST) do allow optimization of experimental conditions in vitro, e.g. incubation time or adjustment of cell numbers, allowing potential for higher sensitivity. However, studies are as usual limited by lack of gold standard for LTBI. Overall: IGRAs seem to work, but true sensitivity for LTBI unknown. In earlier studies, QFT-G had higher rate of indeterminates (low mitogen control) than TSpot.TB (Ferrara et al, AJRCCM 2005 (Italy); Piana et al, AJRCCM 2006 (Italy); Ferrara et al, Lancet 2006 (Italy)) More recent metaanalysis (Diel et al, 2010): rates of indeterminates (note: reason for indeterminate not defined) in immunosuppressed subgroups: QFT-G IT: 4.4% TSpot.TB: 6.1% Occasional case reports of IGRAs being used to help with Dx of active TB in TST-negative immunosuppressed patients Disturbing case report of person who was QFT-G negative before liver transplant AND in setting of post-transplant active (Cx-positive) pulmonary TB (Codeluppi et al, 2006)

30 e.g. health care workers (HCW): depends where you are and what question you ask. For example: Japan (Harada, 2006): QFT-G vs TST 95% s/p BCG. 93% TST>10mm, vs 10% +QFT-G. +QFT-G results were a/w LTBI risk factors, while +TST results were not. Rural India (Pai, 2005): QFT-IT vs TST 50% positive by either test, 31% by both Russia (Drobniewski, 2007): QFT-IT QFT-IT was positive in 8.7% of medical/non-medical students, 39.1% of all doctors/nurses, 46.9% of TB doctors and nurses Denmark (Soberg, 2007): QFT-G vs TST ID dept employees: 34% TST+, 1% QFT-G+. 89% of TST+ were BCGvaccinated. Urban US (Pollock, 2008): QFT-G In TST+ newly hired employees with increased risk of having LTBI (large PPD, residence in highly endemic area, recent or remote contact, conversion, CXR findings c/w old TB, patient care): 28% QFT-G+, 70% QFT-G- Many more.mostly descriptive (TST results vs IGRA results)

31 Patients approaching TNF-alpha blocker therapy The problem: many have underlying diseases or are on immunosuppressive medications which can compromise TST sensitivity. But how sensitive are the IGRAs in this group? Again, limited by lack of a gold standard. E.g. Laffitte et al, Br J Dermatol 2009; retrospective study of TST vs T-Spot.TB in 50 patients with psoriasis considering TNF-alpha blocker (in Switzerland) Positive TSpot was strongly a/w presumptive Dx of LTBI (by risk factors), while TST was not 20% of subjects had positive TST and negative TSpot and were NOT treated for LTBI; no reactivation detected with median f/u of 64 weeks (but note, small numbers overall) E.g. Diel et al, Pneumologie 2009 (German recommendations): due to expectation of false negative AND false positive TST in these patients, they recommend highly specific IGRA instead (but what about IGRA sensitivity??)

32 Children Lewinsohn, Lobato, and Jereb, Curr Opin Pediatrics 2010: Overall, performance of IGRAs equivalent or superior to that of the TST, but evidence supports usage of IGRAs in children aged 5 years or older only (insufficient evidence re: performance in younger kids, and sensitivity poorly defined in that group) In kids >5, IGRAs preferred over TST when specificity is paramount or when patients might not return for TST reading Kids <5: TST preferred E.g. Bianchi et al, Pediatr Infect Dis J 2009: QFT-G IT was positive in 15 of 16 (93.8%) children with active pulmonary TB Among IGRA+ children (excluding active TB), TST- were significantly younger than TST+ children (so could IGRA be more sensitive than TST in younger kids?)

33 Are CFP-10, ESAT-6, +/- TB7.7 sufficient for comprehensive detection of LTBI? Overall: in contact investigations, sensitivity of IGRA=TST, and IGRAs correlate better with TB exposure For active TB, sensitivity of IGRAs = or > to TST Could IGRAs be sensitive to recent/active infection, but not remote infection? (Pollock et al, ICHE 2008)

34 Relying on IGRAs for making clinical decisions: how much caution should we use at this point? if we base Tx decisions on IGRA results alone, many individuals with clinical risk factors historically considered suggestive of true LTBI will suddenly be exempt from treatment. Is this good or bad? AND, some of these risk factors have historically been associated with increased reactivation risk (e.g. PPD>15 mm, recent immigration from high risk country, various CXR findings) But can IGRAs actually distinguish those at higher reactivation risk? Should we only care about the IGRA+?

35 Studies of predictive value of IGRAs Hard to do studies of predictive value of positive IGRA for development of active TB typically, ethically would need to consider treatment of LTBI if IGRA+. E.g. Diel et al, AJRCCM 2008, Germany: evaluated rates of progression to active TB in close contacts (immunocompetent) within 2 years of contact screening. 11% of contacts were QFT-G IT+, vs 40% TST+ (>5 mm). 41 QFT-G IT+ subjects refused LTBI treatment; 6 (14.6%) developed active TB. 219 TST+ subjects refused treatment; 5 (2.3%) progressed to active TB. Concluded that QFT-G IT is a more accurate indicator of LTBI than the TST and provides at least the same sensitivity for detecting those who will progress to active TB. Vs. e.g. Kik et al, Eur Respir J 2009: looked at immigrants who were close contacts of smear + TB cases, all found to have TST >5 mm during contact investigation: followed for 2 years. PPV for progression to TB disease was comparable and LOW for QFT-G IT (2.8%), T-Spot TB (3.3%), TST>10 mm (3.1%), TST >15 mm (3.8%)

36 Predictive value of IGRAs, cont E.g. Hill et al, PLoS One 2008, The Gambia: risk of progression to active TB after positive ELISPOT (similar to TSpot) or TST in case contacts, over 2 year period. Noone got preventive therapy, per local guidelines. Rates of progression in ELISPOT+ was similar to rates in TST+. Because initial ELISPOT and TST were each positive in just over half of secondary cases, while 71% were initially positive by one or the other test, they concluded that positivity by either might be the best indication for preventive treatment. Note: there were clearly some NEW infections over study time period (discordant genotyping between index and secondary case isolates) so this really confuses this study. San Francisco IGRA experience--?? Not seeing spike in TB cases after switching to IGRA only for TB screening programs..

37 Our clinical response to all this data: We feel great about the IGRA+. We re just not sure what to do with all the IGRA- We don t assume (for now) that a negative IGRA rules out LTBI. Perhaps, in future, we can be confident that it does or, at least, that it rules out high baseline reactivation risk. Consider offering treatment to certain high-risk populations even with a negative IGRA result: 1. ***Patients with medical risk factors placing them at higher risk of TB reactivation if they do have LTBI, i.e. HIV, chronic oral steroid treatment, TNF-alpha blocker treatment, renal insufficiency, diabetes, some malignancies. 2. recent TB contact (debatable, given good IGRA performance in contact studies) 3. PPD conversion (>10 mm increase) in past 2 years (also debatable, given performance in contact studies) 3. Abnormal CXR potentially consistent with old TB in significant burden (e.g. large scar, nodule, after r/o with smear/culture)

38 FAQ: Do positive IGRA results turn negative with TB or LTBI treatment? Multiple studies on this topic: data mixed, but general consensus is NO, not reliably. E.g. local study: Pollock et al, ICHE 2009: HCW treated for LTBI with 9 months INH still had positive QFT-G after treatment. Suggested approach to this issue based on current data: IGRA results should not be used to assess the effectiveness of recent or remote treatment courses for TB/LTBI: many (if not most) individuals will continue to test positive after standard therapy Do not assume that an individual who reports prior TB/LTBI therapy but still tests positive by IGRA has not been appropriately treated in the past Neither providers nor patients should expect reliable changes in IGRA results after standard treatment

39 Serial testing with IGRAs Primarily relevant to HCW or other individuals requiring annual screening Multiple issues to think about: reproducibility of test results in a given individual tested repeatedly over time, without intervening exposures to TB appropriate definition of reversion/conversion optimal test cutoffs (e.g. initially raised by Pai et al, 2006,2009, India)

40 From QFT-G IT package insert: The magnitude of the measured IFN-g level cannot be correlated to stage or degree of infection, level of immune responsiveness, or likelihood for progression to active disease.

41 Reproducibility of IGRA results in serial testing E.g. Detjen et al, Clin Vaccine Immunol 2009: 27 S. African HCW, tested with QFT-G IT on day 1 (2 tests, by different operators) and day 3 (1 test). 6/27 had discordant results of some kind variability in the magnitude of IFN-gamma responses between assays performed for a given individual most variability seen in assays that were obtained from an individual on two different days. Conclusion: This intra-individual variability could influence interpretation of serial measurements E.g. Van Zyl-Smit, AJRCCM 2009: 26 S. African subjects; repeated IGRAs (T.SpotTB, QFT-G IT) 4x over 21D prior to TST (to assess within-patient variability), and then again on days 3,7,28, 84 post-tst (to assess for boosting of IGRA by TST). Pre-TST tests: 7/26 had spontaneous conversions/reversions (6 for TSpot, 1 for QFT-G IT). 95% of variability was 3-spot or 80% IFN-gamma response variation on either side of baseline values could be useful for interpreting conversions/reversions

42 Effect of TST on IGRA results QFT-G IT package insert: in U.S. specificity study (**individuals with no reported TB risk factors), a subset of subjects were retested 4-5 weeks after initial QFT-G IT/TST. Agreement between 2 QFT-G IT tests was 98.5% (out of 530 subjects, 5 went pos neg, and 3 went neg pos.) Van Zyl-Smit, AJRCCM 2009: 26 S. African subjects; after baseline IGRAs (T.SpotTB, QFT-G IT), repeated IGRAs on days 3,7,28, 84 post-tst (to assess for boosting of IGRA by TST). **Post-TST tests: 8 subjects boosted above defined baseline variability by day 7, but not day 3. 2 initially IGRA-negative subjects converted to IGRA-positive. Conclusion: safe to do QFT-G IT or TSpot within 3 days of performing TST (i.e. on day of TST read). Cohort as a whole showed some persistently elevated IFN-gamma responses up to day 84 after TST, though some individuals had returned to pre- TST levels by day 28.(So what are implications for long-term boosting effects, e.g. in those receiving annual testing?)

43 Effect of TST on IGRA, continued Review by van Zyl-Smit et al, PLoSOne 2009: 13 studies Studies used different TU for TST, different time points for IGRAs after TST, and varied re: initial TST/IGRA status of individuals 5 studies concluded boosting of IGRA by TST did NOT occur; in 4/5, earliest timepoint of repeat IGRA was 28 days-9 months after TST. In 5 th, IGRA was repeated only on day 3 after TST. 7 studies demonstrated TST-induced boosting of IGRA responses; in 5/7, repeat IGRA was done within 21 days after TST. Conclusions: Boosting more pronounced in IGRA-positive (i.e. sensitized) individuals, but also occurred in a smaller but not insignificant proportion of IGRA-negative subjects Time frame of repeat IGRA is key. TST appeared to affect IGRA responses only after 3 days, and may be issue particularly between days 7-28; boosting effect may apparently persist for up to 3 months and then wane, but evidence for this is weak.

44 Preliminary (unpublished) data from a 4-site (U.S.) collaborative study of serial IGRAs in HCW Longitudinal study of HCW undergoing routine testing for LTBI; overall low risk for TB acquisition at work 15% born in high-burden country 10% s/p BCG 0.4% HIV, 3% DM, 2% other immunocompromise Baseline 2-step TST, QFT-G IT, TSpot.TB IGRAs done BEFORE placement of 1 st TST Repeat all 3 tests at 6, 12, and 18 months Slides obtained from Dr. John Bernardo, BMC

45 Baseline Results in subjects with no prior (+) TST or LTBI treatment n = 2083 TST QFT* T-SPOT* Positive 43 (2.1) 76 (3.7) 108 (5.2) Negative 2040 (97.9) 2007 (96.3) 1907 (91.6) Borderline 68 (3.3) * p < compared to the TST (borderline T-Spots categorized as negative)

46 6 month Follow-up Conversion Reversion* TST 6 / 1503 (0.4) 11 / 21 (52.4) QFT-GIT 56 / 1516 (3.7) 28 / 56 (50) T-SPOT 52 / 1473 (3.3) 47 / 85 (55.3) Conversion = (-) baseline (+) 6 month Reversion = (+) baseline (-) 6month * Total Baseline Positive = 43 TST, 76 QFT-GIT, 108 T-SPOT

47 12 month Follow-up Conversion Reversion TST 1 / 362 (0.3) n/a QFT-GIT 9 / 384 (2.3) 7 / 11 (63.6) T-SPOT 3 / 356 (0.8) 10 / 16 (62.5) Conversion = (-) baseline (-) 6 month (+) 12 month Reversion = (-) baseline (+) 6month (-) 12 month

48 Some take-home points IGRAs should not be used alone to exclude the Dx of active TB In particular, sensitivity in question for extra-pulmonary TB 1 IGRAs cannot distinguish between active and latent TB IGRAs may remain positive even after appropriate treatment of active or latent TB. Sensitivity for diagnosis of LTBI is impossible to calculate, given absence of a gold standard for this Dx. Exercise caution when interpreting negative IGRA results in individuals with major risks for TB reactivation. A negative result must be considered with the individual s medical and historical data relevant to probability of M. tuberculosis infection and potential risk of progression to tuberculosis disease, particularly for individuals with impaired immune function. (QFT-G IT package insert, 2009) 1. Dewan et al, CID 2007

49 Some take-home points, cont. Specificity of IGRAs is very high, but occasionally you will see a patient with NO apparent TB risk factors and a positive IGRA result. Check absolute value to see if they are close to cutoff for positive would repeat, if negative repeat again as tie-breaker.. Again, consider who should be tested in the first place, and who shouldn t It is still not clear how well IGRAs will perform in serial testing situations (e.g. HCW) or what the true impact of TSTs on subsequent IGRAs actually is. Can we trust conversions if IGRAs are used for annual testing in relatively low risk settings? Would those conversions be stable if we waited 6 months and retested?

50 December, 2005: CDC guidelines for use of QFT-G CDC recommends that QFT-G may be used in all circumstances in which the TST is currently used, including contact investigations, evaluation of recent immigrants, and sequential-testing surveillance programs for infection control (e.g., those for healthcare workers). left open the possibility that "QFT-G sensitivity for LTBI might be less than that of the TST," while acknowledging that the lack of a confirmatory test would make this difficult to assess "each QFT-G result and its interpretation should be considered in conjunction with other epidemiologic, historic, physical, and diagnostic findings."

51 New CDC recs for use of IGRAs in development coming in 2010!!?? Likely to advocate broad use (including in annual testing), and use in place of TST, rather than as confirmatory test. My opinion: if we are going to make clinical decisions based on IGRA results, then we need to focus on estimating IGRA sensitivity/npv for LTBI and also potentially revisit the clinical guidelines regarding increased reactivation risk. What will we do with TST+/IGRA- individuals who: Have various forms of relative immunocompromise, or are going to become immunocompromised (e.g. by transplant, TNF-alpha blockers)? Are recent immigrants from endemic areas? Have CXR findings consistent with past TB (and which CXR findings, specifically, matter?)

52 MACET recommendations on use of IGRAs Recent contacts: IGRAs seem to perform well (good sensitivity and correlation with TB exposure); can use IGRA or TST Immunocompromised: two groups Pre-immunocompromisation (awaiting transplant, going on TNF-alpha blocker or steroids, etc): use both tests, Tx if either positive Already immunocompromised (including HIV): same recommendations

53 MACET recs 2008, cont. Recent immigrants: panel unable to reach consensus, as negative test does not appear to rule out LTBI, and some of this population could be recently infected. Clinical f/u after testing is optimal. HCW: same caveats as above. Agreed that either IGRA or TST could be used. Those with key reactivation risk factors who are IGRA negative should have clinical f/u if possible.

54 MACET recs 2008, continued Children: limited data, no recommendations (could update, given recent analyses suggesting good performance in kids>5) Low-risk individuals: given low pre-test probability, test results difficult to interpret. Best to NOT test with either IGRA or TST. Adults with recent BCG: IGRAs can be helpful given high specificity Active TB: can use IGRA to rule IN infection (either latent or active), but NOT to rule OUT active disease (given limits to sensitivity)

Evaluation and Treatment of TB Contacts Tyler, Texas April 11, 2014

Evaluation and Treatment of TB Contacts Tyler, Texas April 11, 2014 Evaluation and Treatment of TB Contacts Tyler, Texas April 11, 2014 Interferon Gamma Release Assays: Understanding the Test David Griffith, BA, MD April 11, 2014 David Griffith, BA, MD has the following

More information

TB Intensive Houston, Texas October 15-17, 2013

TB Intensive Houston, Texas October 15-17, 2013 TB Intensive Houston, Texas October 15-17, 2013 Interferon Gamma Release Assays (IGRA s) Lisa Armitige, MD, PhD October 16, 2013 Lisa Armitige, MD, PhD has the following disclosures to make: No conflict

More information

TB Intensive San Antonio, Texas November 11 14, 2014

TB Intensive San Antonio, Texas November 11 14, 2014 TB Intensive San Antonio, Texas November 11 14, 2014 Interferon Gamma Release Assays Lisa Armitige, MD, PhD November 12, 2014 Lisa Armitige, MD, PhD has the following disclosures to make: No conflict of

More information

Approaches to LTBI Diagnosis

Approaches to LTBI Diagnosis Approaches to LTBI Diagnosis Focus on LTBI October 8 th, 2018 Michelle Haas, M.D. Associate Director Denver Metro Tuberculosis Program Denver Public Health DISCLOSURES I have no disclosures or conflicts

More information

Technical Bulletin No. 172

Technical Bulletin No. 172 CPAL Central Pennsylvania Alliance Laboratory QuantiFERON -TB Gold Plus Assay Contact: J Matthew Groeller, MPA(HCM), MT(ASCP), 717-851-4516 Operations Manager, Clinical Pathology, CPAL Jennifer Thebo,

More information

TB Nurse Case Management San Antonio, Texas July 18 20, 2012

TB Nurse Case Management San Antonio, Texas July 18 20, 2012 TB Nurse Case Management San Antonio, Texas July 18 20, 2012 IGRA s and Their Use in TB Nurse NCM Lisa Armitige, MD, PhD July 18, 2012 Lisa Armitige, MD, PhD has the following disclosures to make: No conflict

More information

TB Intensive Tyler, Texas December 2-4, 2008

TB Intensive Tyler, Texas December 2-4, 2008 TB Intensive Tyler, Texas December 2-4, 2008 Interferon Gamma Releasing Assays: Diagnosing TB in the 21 st Century Peter Barnes, MD December 2, 2008 TOPICS Use of interferon-gamma release assays (IGRAs)

More information

TB Prevention Who and How to Screen

TB Prevention Who and How to Screen TB Prevention Who and How to Screen 4.8.07. IUATLD 1st Asia Pacific Region Conference 2007 Dr Cynthia Chee Dept of Respiratory Medicine / TB Control Unit Tan Tock Seng Hospital, Singapore Cycle of Infection

More information

Barbara J Seaworth MD Medical Director, Heartland National TB Center Professor, Internal Medicine and Infectious Disease UT Health Northeast

Barbara J Seaworth MD Medical Director, Heartland National TB Center Professor, Internal Medicine and Infectious Disease UT Health Northeast Practical Aspects for Using the Interferon Gamma Release Assay (IGRA) Test Live Webinar July 14, 2017 Barbara J Seaworth MD Medical Director, Heartland National TB Center Professor, Internal Medicine and

More information

Using Interferon Gamma Release Assays for Diagnosis of TB Infection

Using Interferon Gamma Release Assays for Diagnosis of TB Infection Learning Objectives Using Interferon Gamma Release Assays for Diagnosis of TB Infection 1. Describe available Interferon Gamma Release Assay tests for TB infection and how they work. 2. Understand interpretation

More information

Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection (LTBI) Lloyd Friedman, M.D. Milford Hospital Yale University

Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection (LTBI) Lloyd Friedman, M.D. Milford Hospital Yale University Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection (LTBI) Lloyd Friedman, M.D. Milford Hospital Yale University Tuberculosis Estimates USA World Infection 15,000,000 2,000,000,000

More information

Detecting latent tuberculosis using interferon gamma release assays (IGRA)

Detecting latent tuberculosis using interferon gamma release assays (IGRA) Detecting latent tuberculosis using interferon gamma release assays (IGRA) American Society for Microbiology June 2017 Edward Desmond, Ph.D., D (ABMM) San Lorenzo, CA Edward Desmond has no financial connections

More information

Mycobacterial Infections: What the Primary Provider Should Know about Tuberculosis

Mycobacterial Infections: What the Primary Provider Should Know about Tuberculosis Mycobacterial Infections: What the Primary Provider Should Know about Tuberculosis Henry F. Chambers, M.D Professor of Medicine, UCSF Topics for Discussion Epidemiology Diagnosis of active TB Screening

More information

Conflict of Interest Disclosures:

Conflict of Interest Disclosures: Mady Slater, M.D. Stanford University Medical Center Division of Infectious Diseases 04/23/14 WOEMA webinar Conflict of Interest Disclosures: I have no financial relationships with commercial entities

More information

Diagnosis and Medical Case Management of Latent TB. Bryan Rock, MD April 27, 2010

Diagnosis and Medical Case Management of Latent TB. Bryan Rock, MD April 27, 2010 TB Nurse Case Management Lisle, Illinois April 27-28, 28 2010 Diagnosis and Medical Case Management of Latent TB Infection Bryan Rock, MD April 27, 2010 DIAGNOSIS AND MANAGEMENT OF LATENT TUBERCULOSIS

More information

Peggy Leslie-Smith, RN

Peggy Leslie-Smith, RN Peggy Leslie-Smith, RN EMPLOYEE HEALTH DIRECTOR - AVERA TRAINING CONTENT 1. South Dakota Regulations 2. Iowa Regulations 3. Minnesota Regulations 4. Interferon Gamma Release Assay (IGRA)Testing 1 SOUTH

More information

Tuberculosis Update. Topics to be Addressed

Tuberculosis Update. Topics to be Addressed Tuberculosis Update Robert M. Jasmer, M.D. University of California, San Francisco TB Control Section, San Francisco Department of Public Health Topics to be Addressed TB in the USA Screening recommendations

More information

Interpretation of TST & IGRA results. Objectives

Interpretation of TST & IGRA results. Objectives Interpretation of TST & IGRA results Randall Reves, MD, MSc Volunteer Clinician Denver Metro TB Program and Division of Infectious Diseases, Department of Medicine University of Colorado Denver Objectives

More information

The Challenges and Pitfalls in Diagnosing or Misdiagnosing Tuberculosis: Are the Days of TB Skin Tests Over?

The Challenges and Pitfalls in Diagnosing or Misdiagnosing Tuberculosis: Are the Days of TB Skin Tests Over? The Challenges and Pitfalls in Diagnosing or Misdiagnosing Tuberculosis: Are the Days of TB Skin Tests Over? ROY F. CHEMALY, MD, MPH, FIDSA, FACP PROFESSOR OF MEDICINE DIRECTOR, INFECTION CONTROL SECTION

More information

Diagnosis Latent Tuberculosis. Disclosures. Case

Diagnosis Latent Tuberculosis. Disclosures. Case Diagnosis Latent Tuberculosis Neha Shah MD MPH Field Medical Officer Tuberculosis Control Branch California Department of Public Health Centers for Disease Control and Prevention September 2016 1 Disclosures

More information

Tuberculin Skin Test (TST) and Interferon-gamma Release Assays (IGRA)

Tuberculin Skin Test (TST) and Interferon-gamma Release Assays (IGRA) Tuberculin Skin Test (TST) and Interferon-gamma Release Assays (IGRA) April 2019 Bob Belknap M.D. Director, Denver Metro TB Program Disclosures No relevant financial relationships Objectives Be able to

More information

Contracts Carla Chee, MHS May 8, 2012

Contracts Carla Chee, MHS May 8, 2012 Moving Past the Basics of Tuberculosis Phoenix, Arizona May 8-10, 2012 Contracts Carla Chee, MHS May 8, 2012 Carla Chee, MHS has the following disclosures to make: No conflict of interests No relevant

More information

Screening for Tuberculosis Infection. Harlingen, TX. Linda Dooley, MD has the following disclosures to make:

Screening for Tuberculosis Infection. Harlingen, TX. Linda Dooley, MD has the following disclosures to make: TB Infection Diagnosis Recommendations Talk Developed by Lisa Y. Armitige, MD, PhD Medical Consultant, Heartland National TB Center Associate Professor Internal Medicine/Pediatrics/Infectious Disease UT

More information

Richard O Brien, Consultant, FIND 3 rd Global Symposium on IGRAs Waikoloa, Hawaii, 13 January 2012

Richard O Brien, Consultant, FIND 3 rd Global Symposium on IGRAs Waikoloa, Hawaii, 13 January 2012 Global l Applications of IGRAs Richard O Brien, Consultant, FIND 3 rd Global Symposium on IGRAs Waikoloa, Hawaii, 13 January 2012 Disclosure I have no personal financial conflicts of I have no personal

More information

Testing for TB. Bart Van Berckelaer Territory Manager Benelux. Subtitle

Testing for TB. Bart Van Berckelaer Territory Manager Benelux. Subtitle Testing for TB Bart Van Berckelaer Territory Manager Benelux Subtitle Agenda TB infection pathway TB immunisation Testing options Pre lab considerations of the whole blood ELISA test The T-SPOT.TB test

More information

Interferon Gamma Release Assay Testing for Latent Tuberculosis Infection: Physician Guidelines

Interferon Gamma Release Assay Testing for Latent Tuberculosis Infection: Physician Guidelines Interferon Gamma Release Assay Testing for Latent Tuberculosis Infection: Physician Guidelines Historically, Latent Tuberculosis Infection (LTBI) diagnosis was based on risk assessment, chest x-ray (CXR)

More information

What the Primary Physician Should Know about Tuberculosis. Topics for Discussion. Life Cycle of M. tuberculosis

What the Primary Physician Should Know about Tuberculosis. Topics for Discussion. Life Cycle of M. tuberculosis What the Primary Physician Should Know about Tuberculosis Henry F. Chambers, M.D Professor of Medicine, UCSF Topics for Discussion Microbiology Epidemiology Common disease presentations Diagnosis of active

More information

Didactic Series. Latent TB Infection in HIV Infection

Didactic Series. Latent TB Infection in HIV Infection Didactic Series Latent TB Infection in HIV Infection Jacqueline Peterson Tulsky, MD UCSF Positive Health Program at SFGH Medical Director, SF and North Coast AETC March 13, 2014 ACCREDITATION STATEMENT:

More information

Tuberculin Skin Test (TST) and Interferon-gamma Release Assays (IGRA)

Tuberculin Skin Test (TST) and Interferon-gamma Release Assays (IGRA) Tuberculin Skin Test (TST) and Interferon-gamma Release Assays (IGRA) April 2018 Bob Belknap M.D. Director, Denver Metro TB Program No Disclosures Objectives be able to describe: 1. Who should get tested

More information

Evidence-based use of the new diagnostic tools for TB-infection

Evidence-based use of the new diagnostic tools for TB-infection Evidence-based use of the new diagnostic tools for TB-infection Roland Diel, MD, MPH German Central Committee against Tuberculosis, Germany 20. Tuberkulose-Symposium in Münchenwiler, 24 th March 2011 1

More information

LTBI: Who to Test & When to Treat

LTBI: Who to Test & When to Treat LTBI: Who to Test & When to Treat TB Intensive May 10 th, 2016 David Horne, MD, MPH Harborview Medical Center University of Washington DISCLOSURES I have no disclosures or conflicts of interest to report

More information

What the Primary Physician Should Know about Tuberculosis. Topics for Discussion. Global Impact of TB

What the Primary Physician Should Know about Tuberculosis. Topics for Discussion. Global Impact of TB What the Primary Physician Should Know about Tuberculosis Henry F. Chambers, M.D Professor of Medicine, UCSF Topics for Discussion Epidemiology Common disease presentations Diagnosis of active TB Screening

More information

Testing & Treatment for TB Infection: Blood Tests, Skin Tests, Who to Screen & Who to Treat?

Testing & Treatment for TB Infection: Blood Tests, Skin Tests, Who to Screen & Who to Treat? NECHA 11/4/2016 Testing & Treatment for TB Infection: Blood Tests, Skin Tests, Who to Screen & Who to Treat? E. Jane Carter, M.D. Immediate Past President International Union Against TB and Lung Disease

More information

Category Description / Key Findings Publication

Category Description / Key Findings Publication PUBLICATIONS Selected T-SPOT.TB test publications, by area of interest, up to 31 th August 2016. Category Description / Key Findings Publication Background A useful primer on the evolution, administration

More information

AT HIGH RISK OF PROGRESSING TO ACTIVE TB? Senior Lecturer and Consultant Physician University Hospitals of Leicester UK

AT HIGH RISK OF PROGRESSING TO ACTIVE TB? Senior Lecturer and Consultant Physician University Hospitals of Leicester UK HOW WELL DO IGRAS PERFORM IN THE IDENTIFICATION OF PERSONS WHO ARE AT HIGH RISK OF PROGRESSING TO ACTIVE TB? Dr Pranab Haldar MD MRCP Senior Lecturer and Consultant Physician University Hospitals of Leicester

More information

Making the Diagnosis of Tuberculosis

Making the Diagnosis of Tuberculosis Making the Diagnosis of Tuberculosis Alfred Lardizabal, MD NJMS Global Tuberculosis Institute Testing for TB Infection Targeted Testing: Key Points Test only if plan for ensuring treatment De-emphasizes

More information

Identifying TB co-infection : new approaches?

Identifying TB co-infection : new approaches? Identifying TB co-infection : new approaches? Charoen Chuchottaworn MD. Senior Medical Advisor, Central Chest Institute of Thailand, Department of Medical Services, MoPH Primary tuberculosis Natural history

More information

TB Update: March 2012

TB Update: March 2012 TB Update: March 2012 David Schlossberg, MD, FACP Medical Director, TB Control Program Philadelphia Department of Public Health 1 TB Update: March 2012 IGRAs vs TST LTBI A New Regimen NAATs What is Their

More information

Let s Talk TB A Series on Tuberculosis, A Disease That Affects Over 2 Million Indians Every Year

Let s Talk TB A Series on Tuberculosis, A Disease That Affects Over 2 Million Indians Every Year A Series on Tuberculosis, A Disease That Affects Over 2 Million Indians Every Year Madhukar Pai, MD, PhD Author and Series Editor Camilla Rodrigues, MD co-author Abstract Most individuals who get exposed

More information

Latent Tuberculosis Infections Controversies in Diagnosis and Management Update 2016

Latent Tuberculosis Infections Controversies in Diagnosis and Management Update 2016 Latent Tuberculosis Infections Controversies in Diagnosis and Management Update 2016 Randy Culpepper, MD, MPH Deputy Heath Officer/Medical Director Frederick County Health Department March 16, 2016 2 No

More information

TB in Corrections Phoenix, Arizona

TB in Corrections Phoenix, Arizona TB in Corrections Phoenix, Arizona March 24, 2011 Treatment of Latent TB Infection Renuka Khurana MD, MPH March 24, 2011 Renuka Khurana, MD, MPH has the following disclosures to make: No conflict of interests

More information

Investigation of false-positive results by the QuantiFERON-TB Gold In-Tube assay

Investigation of false-positive results by the QuantiFERON-TB Gold In-Tube assay JCM Accepts, published online ahead of print on 11 July 2012 J. Clin. Microbiol. doi:10.1128/jcm.00730-12 Copyright 2012, American Society for Microbiology. All Rights Reserved. 1 2 Investigation of false-positive

More information

Targeted Testing and the Diagnosis of. Latent Tuberculosis. Infection and Tuberculosis Disease

Targeted Testing and the Diagnosis of. Latent Tuberculosis. Infection and Tuberculosis Disease Self-Study Study Modules on Tuberculosis Targeted Testing and the Diagnosis of Latent Tuberculosis Infection and Tuberculosis Disease 1 Module 3: Objectives At completion of this module, learners will

More information

Jeffrey R. Starke, M.D. has the following disclosures to make:

Jeffrey R. Starke, M.D. has the following disclosures to make: AAP 2018 Red Book Tuberculosis: IGRAs and Treatment of TB Infection Jeffrey R. Starke, M.D. May 31, 2018 AAP 2018 Red Book Childhood Tuberculosis: IGRAs and Treatment of TB Infection May 31, 2018 WEBINAR

More information

Latent TB Infection (LTBI)

Latent TB Infection (LTBI) Latent TB Infection (LTBI) Diagnosis & Treatment of Latent TB Infection (LTBI) Amee Patrawalla MD MPH Assistant Professor UMDNJ-New Jersey Medical School Infection with Mycobacterium tuberculosis without

More information

LTBI-Tuberculin skin test. T-Spot.TB Technology. QuantiFERON -TB Gold In Tube T-SPOT.TB ELISA ELISA

LTBI-Tuberculin skin test. T-Spot.TB Technology. QuantiFERON -TB Gold In Tube T-SPOT.TB ELISA ELISA LTBI-Tuberculin skin test QuantiFERON -TB Gold In Tube ELISA PPD ~200 antigens 3 ml blood ESAT-6 TB 7.7 16-24 hour incubation Nil Negative control PHA Positive control Andersen et al Lancet 2000;356:1099-1104

More information

Didactic Series. Latent TB Infection in HIV Infection

Didactic Series. Latent TB Infection in HIV Infection Didactic Series Latent TB Infection in HIV Infection Jacqueline Peterson Tulsky, MD UCSF Positive Health Program at SFGH Medical Director SF, North Coast and East Bay AETC January 8, 2015 ACCREDITATION

More information

Tuberculosis: Where Are We Now?

Tuberculosis: Where Are We Now? Tuberculosis: Where Are We Now? Amee Patrawalla MD MPH Rutgers - NJ Medical School Global TB Institute Rutgers, The State University of New Jersey Learning Objectives Understand the current epidemiologic

More information

Thorax Online First, published on December 8, 2009 as /thx

Thorax Online First, published on December 8, 2009 as /thx Thorax Online First, published on December 8, 2009 as 10.1136/thx.2009.119677 Title Page Cost effectiveness of the NICE guidelines for screening for latent tuberculosis infection: the Quantiferon-TB gold

More information

결핵노출접촉자감염관리 서울아산병원감염내과 김성한

결핵노출접촉자감염관리 서울아산병원감염내과 김성한 결핵노출접촉자감염관리 서울아산병원감염내과 김성한 TB incidence (2012) TB incidence South Korea 108 China 73 Taiwan 68 Portucal 26 Japan 19 Spain 14 US 3.6 * unit- per 100,000 population Adapted from WHO Adapted from WHO Emerg

More information

Understanding and Managing Latent TB Infection Arnold, Missouri October 5, 2010

Understanding and Managing Latent TB Infection Arnold, Missouri October 5, 2010 Understanding and Managing Latent TB Infection Arnold, Missouri October 5, 2010 What is Latent TB Infection (LTBI)? Traci Hadley, RN October 5, 2010 LTBI or TB Disease? Presented by : Traci Hadley, RN

More information

A Clinician s Perspective: Improving Rheumatology Patient Care Using the T-SPOT.TB Test

A Clinician s Perspective: Improving Rheumatology Patient Care Using the T-SPOT.TB Test A Clinician s Perspective: Improving Rheumatology Patient Care Using the T-SPOT.TB Test Solomon Forouzesh, MD, FACD, FACR Medical Director Arthritis Care & Treatment Center Clinical Associate Professor

More information

2016 OPAM Mid-Year Educational Conference, Sponsored by AOCOPM Sunday, March 13, 2016

2016 OPAM Mid-Year Educational Conference, Sponsored by AOCOPM Sunday, March 13, 2016 Learning Objectives Tuberculosis Case Discussions: Evaluation for Tuberculosis Infection Melissa C. Overman, DO, MPH, CHES, FAOCOPM Describe appropriate technique for TST placement, reading and interpretation

More information

Role of the Laboratory in TB Diagnosis and Management

Role of the Laboratory in TB Diagnosis and Management Role of the Laboratory in TB Diagnosis and Management Michael Pentella, Ph.D., D(ABMM), CIC Associate Director University Hygienic Lab Clinical Associate Professor, College of Public Health, University

More information

CHILDHOOD TUBERCULOSIS: NEW WRINKLES IN AN OLD DISEASE [FOR THE NON-TB EXPERT]

CHILDHOOD TUBERCULOSIS: NEW WRINKLES IN AN OLD DISEASE [FOR THE NON-TB EXPERT] CHILDHOOD TUBERCULOSIS: NEW WRINKLES IN AN OLD DISEASE [FOR THE NON-TB EXPERT] QUESTION: : Which children in the United States should get a tuberculin skin test? Do questionnaires really work? Jeffrey

More information

Diagnosis and Medical Management of TB Infection Lisa Y. Armitige, MD, PhD September 12, TB Nurse Case Management September 12 14, 2017

Diagnosis and Medical Management of TB Infection Lisa Y. Armitige, MD, PhD September 12, TB Nurse Case Management September 12 14, 2017 Diagnosis and Medical Management of TB Infection Lisa Y. Armitige, MD, PhD September 12, 2017 TB Nurse Case Management September 12 14, 2017 EXCELLENCE EXPERTISE INNOVATION Lisa Y. Armitige, MD, PhD has

More information

Review. Interferon- assays in the immunodiagnosis of tuberculosis: a systematic review. Interferon- assays for tuberculosis diagnosis

Review. Interferon- assays in the immunodiagnosis of tuberculosis: a systematic review. Interferon- assays for tuberculosis diagnosis Interferon- assays for tuberculosis diagnosis Review Interferon- assays in the immunodiagnosis of tuberculosis: a systematic review Madhukar Pai, Lee W Riley, and John M Colford Jr A major challenge in

More information

Laboratory Updates on IGRA Testing

Laboratory Updates on IGRA Testing Laboratory Updates on IGRA Testing Edward A. Graviss, PhD, MPH, FIDSA August 18, 2017 EXCELLENCE EXPERTISE INNOVATION Edward A. Graviss, PhD, MPH, FIDSA, has the following disclosures to make: No conflict

More information

ATS/CDC Guidelines for Treating Latent TB Infection

ATS/CDC Guidelines for Treating Latent TB Infection TB Intensive Tyler, Texas June 2-4, 2010 ATS/CDC Guidelines for Treating Latent TB Infection Timothy R. Aksamit, MD June 2, 2010 ATS/CDC Guidelines for Treating LTBI Tuberculosis Intensive University of

More information

The Most Widely Misunderstood Test of All

The Most Widely Misunderstood Test of All The Most Widely Misunderstood Test of All Lee B. Reichman, MD, MPH NJMS Global Tuberculosis Institute History of Treatment of Latent Tuberculosis Infection For more than 4 decades, treatment of persons

More information

ORIGINAL ARTICLE. Clinical evaluation of QuantiFERON TB-2G test for immunocompromised patients

ORIGINAL ARTICLE. Clinical evaluation of QuantiFERON TB-2G test for immunocompromised patients ERJ Express. Published on July 25, 2007 as doi: 10.1183/09031936.00040007 ORIGINAL ARTICLE Clinical evaluation of QuantiFERON TB-2G test for immunocompromised patients Yoshihiro Kobashi, Keiji Mouri, Yasushi

More information

Use of an Interferon- Release Assay To Diagnose Latent Tuberculosis Infection in Foreign-Born Patients*

Use of an Interferon- Release Assay To Diagnose Latent Tuberculosis Infection in Foreign-Born Patients* Original Research MYCOBACTERIAL DISEASE Use of an Interferon- Release Assay To Diagnose Latent Tuberculosis Infection in Foreign-Born Patients* Daniel Brodie, MD; David J. Lederer, MD, MS; Jade S. Gallardo,

More information

Is the QuantiFERON-TB Blood Assay a Good Replacement for the Tuberculin Skin Test in Tuberculosis Screening? A Pilot Study at Berkshire Medical Center

Is the QuantiFERON-TB Blood Assay a Good Replacement for the Tuberculin Skin Test in Tuberculosis Screening? A Pilot Study at Berkshire Medical Center Microbiology and Infectious Disease / QuantiFERON-TB Assay for TB Screening Is the QuantiFERON-TB Blood Assay a Good Replacement for the Tuberculin Skin Test in Tuberculosis Screening? A Pilot Study at

More information

Predictive Value of interferon-gamma release assays for incident active TB disease: A systematic review

Predictive Value of interferon-gamma release assays for incident active TB disease: A systematic review Predictive Value of interferon-gamma release assays for incident active TB disease: A systematic review Lele Rangaka University of Cape Town, South Africa mxrangaka@yahoo.co.uk 1 The 3 I s Isoniazid preventive

More information

ESCMID Online Lecture Library. by author

ESCMID Online Lecture Library. by author Tuberculosis prevention in immunodepressed patients M. Carmen Fariñas Álvarez Infectious Diseases.H.U.Marqués de Valdecilla University of Cantabria, Spain DISCLOSURES I have no potential conflicts with

More information

Tuberculosis Tools: A Clinical Update

Tuberculosis Tools: A Clinical Update Tuberculosis Tools: A Clinical Update CAPA Conference 2014 JoAnn Deasy, PA-C. MPH, DFAAPA jadeasy@sbcglobal.net Adjunct Faculty Touro PA Program Learning Objectives Outline the pathogenesis of active pulmonary

More information

QuantiFERON-TB Gold Plus

QuantiFERON-TB Gold Plus QuantiFERON-TB Gold Plus A New Interferon-γ Release Assay (IGRA) for the Indirect Detection of Mycobacterium tuberculosis HOT TOPIC / 2018 Presenter: Elitza S. Theel, PhD, D(ABMM) Director of Infectious

More information

Update on IGRA Predictive Value

Update on IGRA Predictive Value Update on IGRA Predictive Value Sandra Kik, PhD Molebogeng Rangaka, MD, PhD Madhukar Pai, MD, PhD McGill International TB Centre, McGill University University of Cape Town & London School of Hygiene and

More information

LATENT TUBERCULOSIS. Robert F. Tyree, MD

LATENT TUBERCULOSIS. Robert F. Tyree, MD LATENT TUBERCULOSIS Robert F. Tyree, MD 1 YK TB OFFICERS Ron Bowerman Elizabeth Roll Mien Chyi (Pediatrics) Cindi Mondesir (Pediatrics) The new guys: Philip Johnson Robert Tyree 2009 CDC TB CASE DEFINITION

More information

These recommendations will remain in effect until the national shortage of PPD solution has abated.

These recommendations will remain in effect until the national shortage of PPD solution has abated. Maryland Recommendations Regarding the National Shortage of Purified Protein Derivative (PPD) Solution; Attachment to Health Officer Memorandum National Shortages of Tubersol and Aplisol for TB Skin Testing;

More information

Revised Technical Instructions for Civil Surgeons. October 9, 2018

Revised Technical Instructions for Civil Surgeons. October 9, 2018 Revised Technical Instructions for Civil Surgeons October 9, 2018 Speakers Joanna Regan Centers for Disease Control and Prevention Shereen Katrak California Department of Public Health Pennan Barry California

More information

Self-Study Modules on Tuberculosis

Self-Study Modules on Tuberculosis Self-Study Modules on Tuberculosis Targe te d Te s ting and the Diagnosis of Latent Tuberculosis Infection and Tuberculosis Disease U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control

More information

The Origin of Swine Flu

The Origin of Swine Flu How the Heck Do You Diagnose Tuberculosis in Children, Anyway? Jeffrey R. Starke, M.D. Professor and Vice Chairman of Pediatrics Baylor College of Medicine Houston, Texas USA The Origin of Swine Flu MAIN

More information

Latent TB, TB and the Role of the Health Department

Latent TB, TB and the Role of the Health Department Latent TB, TB and the Role of the Health Department Elaine Darnall, RN, BSN, CIC TB Nurse Consultant Illinois Dept of Public Health March 21, 2018 Elaine Darnall has disclosed that there is no actual or

More information

Effect of prolonged incubation time on the results of the QuantiFERON TB Gold In-Tube assay for the diagnosis of latent tuberculosis infection

Effect of prolonged incubation time on the results of the QuantiFERON TB Gold In-Tube assay for the diagnosis of latent tuberculosis infection CVI Accepts, published online ahead of print on 3 July 2013 Clin. Vaccine Immunol. doi:10.1128/cvi.00290-13 Copyright 2013, American Society for Microbiology. All Rights Reserved. 1 2 3 Effect of prolonged

More information

Advanced Management of Patients with Tuberculosis Little Rock, Arkansas August 13 14, 2014

Advanced Management of Patients with Tuberculosis Little Rock, Arkansas August 13 14, 2014 Advanced Management of Patients with Tuberculosis Little Rock, Arkansas August 13 14, 2014 Tuberculosis Pathogenesis and Treatment of Latent TB Infection Lisa Armitige, MD, PhD August 13, 2014 Lisa Armitige,

More information

Latent Tuberculosis Infection (LTBI) Questions and Answers for Health Care Providers

Latent Tuberculosis Infection (LTBI) Questions and Answers for Health Care Providers Latent Tuberculosis Infection (LTBI) Questions and Answers for Health Care Providers Who Should Be Screened for Latent Tuberculosis Infection (LTBI)?... 2 What tests are used to screen for LTBI?... 2 How

More information

Tuberculosis and Diabetes Mellitus. Lana Kay Tyer, RN MSN WA State Department of Health TB Nurse Consultant

Tuberculosis and Diabetes Mellitus. Lana Kay Tyer, RN MSN WA State Department of Health TB Nurse Consultant Tuberculosis and Diabetes Mellitus Lana Kay Tyer, RN MSN WA State Department of Health TB Nurse Consultant Learning Objectives Understand the impact of uncontrolled diabetes mellitus (DM) on TB infection

More information

Report on WHO Policy Statements

Report on WHO Policy Statements Report on WHO Policy Statements Christopher Gilpin TB Diagnostics and Laboratory Strengthening Unit Secretariat, Global Laboratory Initiative Stop TB Department, WHO Geneva New Diagnostics Working Group

More information

Tuberculin Skin Testing

Tuberculin Skin Testing Understanding and Managing Latent TB Infection Arnold, Missouri October 5, 2010 Testing to TB Infection Using the TST Presented by Debra Howenstine, MD for Debbie Onofre, RN October 5, 2010 Tuberculin

More information

TB: Management in an era of multiple drug resistance. Bob Belknap M.D. Denver Public Health November 2012

TB: Management in an era of multiple drug resistance. Bob Belknap M.D. Denver Public Health November 2012 TB: Management in an era of multiple drug resistance Bob Belknap M.D. Denver Public Health November 2012 Objectives: 1. Explain the steps for diagnosing latent and active TB role of interferon-gamma release

More information

Advanced Concepts in Pediatric Tuberculosis

Advanced Concepts in Pediatric Tuberculosis Advanced Concepts in Pediatric Tuberculosis: Nizar F. Maraqa, MD, FPIDS Division of Pediatric Infectious Diseases & Immunology University of Florida College of Medicine - Jacksonville Advanced Concepts

More information

TB Skin Test Practicum Houston, Texas Region 6/5 South September 23, 2014

TB Skin Test Practicum Houston, Texas Region 6/5 South September 23, 2014 TB Skin Test Practicum Houston, Texas Region 6/5 South September 23, 2014 Catalina Navarro, BSN, RN has the following disclosures to make: No conflict of interests No relevant financial relationships with

More information

TB Intensive. San San Antonio, Texas. December 1-3, 2010

TB Intensive. San San Antonio, Texas. December 1-3, 2010 TB Intensive San Antonio, Texas December 1-3, 2010 ATS/CDC Guidelines for Treating Latent TB Infection Timothy Aksamit, MD; Mayo Clinic December 1, 2010 ATS/CDC Guidelines for Treating LTBI Tuberculosis

More information

Screening of HIV-Infected Patients with IGRAs for LTBI. Background. Tuberculosis is the most prevalent in the world.

Screening of HIV-Infected Patients with IGRAs for LTBI. Background. Tuberculosis is the most prevalent in the world. Screening of HIV-Infected Patients with IGRAs for LTBI Kentaro Sakashita, Akira Fujita, Shuji Hatakeyma Stay strong, Japan! Tokyo Metropolitan Tama Medical Center Department of Pulmonary Medicine Background

More information

Diagnosis and Medical Management of LTBI

Diagnosis and Medical Management of LTBI TB Nurse Case Management San Antonio, Texas December 8-10, 2009 Diagnosis and Medical Management of LTBI Barbara Seaworth, MD December 8, 2009 CLINICAL DIAGNOSIS AND MANAGEMENT OF LATENT TB INFECTION Barbara

More information

Within-Subject Variability of Mycobacterium tuberculosis-specific Gamma Interferon Responses in German Health Care Workers

Within-Subject Variability of Mycobacterium tuberculosis-specific Gamma Interferon Responses in German Health Care Workers CLINICAL AND VACCINE IMMUNOLOGY, July 2011, p. 1176 1182 Vol. 18, No. 7 1556-6811/11/$12.00 doi:10.1128/cvi.05058-11 Copyright 2011, American Society for Microbiology. All Rights Reserved. Within-Subject

More information

TUBERCULOSIS. Pathogenesis and Transmission

TUBERCULOSIS. Pathogenesis and Transmission TUBERCULOSIS Pathogenesis and Transmission TUBERCULOSIS Pathogenesis and Transmission Infection to Disease Diagnostic & Isolation Updates Treatment Updates Pathogenesis Droplet nuclei of 5µm or less are

More information

TB Intensive San Antonio, Texas

TB Intensive San Antonio, Texas TB Intensive San Antonio, Texas August 2, 2011 ATS/CDC Guidelines for Treating LTBI Timothy Aksamit, MD April 6, 2011 Timothy Aksamit, MD has the following disclosures to make: No conflict of interests

More information

Literature Overview. Health Economics. Experience with QuantiFERON -TB Gold. Cellestis Clinical Guide series

Literature Overview. Health Economics. Experience with QuantiFERON -TB Gold. Cellestis Clinical Guide series Literature Overview Experience with QuantiFERON -TB Gold Health Economics Cellestis Clinical Guide series 2008 www.cellestis.com This literature overview is intended to provide healthcare professionals

More information

TB Nurse Case Management Davenport, Iowa September 27 28, 2011

TB Nurse Case Management Davenport, Iowa September 27 28, 2011 TB Nurse Case Management Davenport, Iowa September 27 28, 2011 Role of the Laboratory in the TB Diagnosis and Management Michael Pentella, PhD, MS, SM(ASCP), CIC, D(ABMM) September 27, 2011 Michael Pentella,

More information

TUBERCULOSIS IN HEALTHCARE SETTINGS Diana M. Nilsen, MD, FCCP Director of Medical Affairs, Bureau of Tuberculosis Control New York City Department of

TUBERCULOSIS IN HEALTHCARE SETTINGS Diana M. Nilsen, MD, FCCP Director of Medical Affairs, Bureau of Tuberculosis Control New York City Department of TUBERCULOSIS IN HEALTHCARE SETTINGS Diana M. Nilsen, MD, FCCP Director of Medical Affairs, Bureau of Tuberculosis Control New York City Department of Health and Mental Hygiene TODAY S PRESENTATION Epidemiology

More information

Utility of PPD or IGRA to answer the age old question of "TB or not TB

Utility of PPD or IGRA to answer the age old question of TB or not TB Utility of PPD or IGRA to answer the age old question of "TB or not TB Thomas S. Alexander, Ph.D., D(ABMLI) Immunologist Summa Health alexandt@summahealth.org Yes, The reservation is in the name of Dr.

More information

Diagnostic challenges of active childhood TB in Tanzania. Michala Vaaben Rose, MD, Ph.D Department of Infectious Diseases, Hvidovre

Diagnostic challenges of active childhood TB in Tanzania. Michala Vaaben Rose, MD, Ph.D Department of Infectious Diseases, Hvidovre Diagnostic challenges of active childhood TB in Tanzania Michala Vaaben Rose, MD, Ph.D Department of Infectious Diseases, Hvidovre 1 Diagnosis of Childhood Tuberculosis Muheza hospital, TZ Hilleroedhospital.dk

More information

Dimitrios Vassilopoulos,* Stamatoula Tsikrika, Chrisoula Hatzara, Varvara Podia, Anna Kandili, Nikolaos Stamoulis, and Emilia Hadziyannis

Dimitrios Vassilopoulos,* Stamatoula Tsikrika, Chrisoula Hatzara, Varvara Podia, Anna Kandili, Nikolaos Stamoulis, and Emilia Hadziyannis CLINICAL AND VACCINE IMMUNOLOGY, Dec. 2011, p. 2102 2108 Vol. 18, No. 12 1556-6811/11/$12.00 doi:10.1128/cvi.05299-11 Copyright 2011, American Society for Microbiology. All Rights Reserved. Comparison

More information

Richard N. van Zyl-Smit 1, Rannakoe J. Lehloenya 1,2, Richard Meldau 1, Keertan Dheda 1,3,4. Introduction

Richard N. van Zyl-Smit 1, Rannakoe J. Lehloenya 1,2, Richard Meldau 1, Keertan Dheda 1,3,4. Introduction Original Article Impact of correcting the lymphocyte count to improve the sensitivity of TB antigen-specific peripheral blood-based quantitative T cell assays (T-SPOT. TB and QFT-GIT) Richard N. van Zyl-Smit

More information

10/3/2017. Updates in Tuberculosis. Global Tuberculosis, WHO 2015 report. Objectives. Disclosures. I have nothing to disclose

10/3/2017. Updates in Tuberculosis. Global Tuberculosis, WHO 2015 report. Objectives. Disclosures. I have nothing to disclose Disclosures Updates in Tuberculosis I have nothing to disclose Chris Keh, MD Assistant Clinical Professor, Division of Infectious Diseases, UCSF TB Controller, TB Prevention and Control Program, Population

More information

Preventing Tuberculosis (TB) Transmission in Ambulatory Surgery Centers. Heidi Behm, RN, MPH TB Controller HIV/STD/TB Program

Preventing Tuberculosis (TB) Transmission in Ambulatory Surgery Centers. Heidi Behm, RN, MPH TB Controller HIV/STD/TB Program Preventing Tuberculosis (TB) Transmission in Ambulatory Surgery Centers Heidi Behm, RN, MPH TB Controller HIV/STD/TB Program Topics of Discussion TB Overview Epidemiology of TB in Oregon Annual Facility

More information