quantiferon-tb gold ® : practical applications
DESCRIPTION
QuantiFERON-TB Gold ® : Practical Applications. L. Masae Kawamura M.D. Director, San Francisco TB Control Section, Department of Public Health Francis J. Curry National TB Center. Diagnosis of tuberculosis infection. QuantiFERON Blood Test (QFT). TB Skin Test (TST). - PowerPoint PPT PresentationTRANSCRIPT
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QuantiFERON-TB Gold®:Practical Applications
L. Masae Kawamura M.D.Director, San Francisco TB Control
Section, Department of Public HealthFrancis J. Curry National TB Center
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Diagnosis of tuberculosis infection
TB Skin Test (TST) QuantiFERON Blood Test(QFT)
“..the greatest needs in the United States are new diagnostic tools for the more accurate identification of individuals who are truly infected and who are also at risk of developing tuberculosis”
US Institute of Medicine Report,“Ending Neglect”; 2000
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Problems with TST…Poor inter-reader reliability
9 mm (negative) vs. 10mm (positive)?False-positives/specificity
NTM infection Prior BCG
Poor positive-predictive value in low prevalence populations (like US)
Cost/time of patient visits Unread tests
Sensitivity? Reaction wanes over time Lack of gold standard
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Program Implications of a More Specific Blood-Based TB Test
• ↓Societal costs and public safety: Elimination of unnecessary CXRs, evaluation and treatment
Program efficiency: More results means targeting efforts on “positives” instead of on retesting individuals who fail to show up for TST readings (homeless, jails, employee testing)
Public confidence : Reliable and specific results• New surveillance capabilities: laboratory-based
targeted testing
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SF QFT Guidelines/Philosophy• QFT: Acceptable alternative to TST in all patients
• In contacts, use in same fashion as TST —Follow-up test needed at 8-12 weeks
• TB Suspects: Use QFT in conjunction with TST to maximize diagnostic yield in suspects and highest risk patients (especially immunocompromised patients and contacts under age 5)
• Don’t “confirm” TST unless it will change patient management
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Programmatic use of QFT-G in San Francisco
• Targeted testing —Homeless and IDUs (high rates of TB, HIV
and ongoing transmission) Rationale: poor TST return rates
-New immigrants and refugees (high infection prevalence) Rationale: BCG-induced, false positive TSTs
• Contact investigation• Prioritizing TB suspects for outreach• Surveillance: Homeless shelters, Newcomers
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Current implementation
• Limited use: 15 sites — public health clinics and community clinics targeting newcomers, homeless and IDUs (methadone clinics)
• Non-health department requests: must be approved by “gate keeper”
Planned expansion: 2006-2007 • Access to all HD providers when automation is
available• Unresolved: private provider demand for QFT
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Number of New Patients Evaluated Monthly by QFT-TB & QFT-G,
San Francisco, Nov. 2003 - Feb. 2006
0100200300400500600
Nov
Jan '0
4Mar
May Jul
Sept
Nov
Jan '0
5Mar
May Jul
Sept
Nov
Jan '0
6
Num
ber
QFT-TB n=4574
QFT-G n=6124
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TB testing by Quantiferon-TB Gold by clinic typeSan Francisco, Mar. 2005 – Feb. 2006
Result
Homelessn=3594 (%)
TB Clinicn=693 (%)
Methadone n=546 (%)
Immigrantn= 626 (%)
HIVn=154 (%)
Positive 221 (6) 182 (26) 21 (4) 72 (12) 4 (3)
Negative 3168 (88) 463 (66) 494 (90) 490 (78) 142 (92)
Indetermin. 118 (3) 32 (5) 26 (5) 58 (9) 5 (3)
Not Tested 87 (2) 16 (2) 5 (1) 6 (1) 3 (2)
*2 clinic types not listed: refugee clinic (n=147) & community clinics (n=399)
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QFT-G Test Results by Age Category March 2005 – February 2006
0%
20%
40%
60%
80%
100%
<5 5 to 14 15 to24
25 to44
45 to64
65 to84
Perc
ent
IndeterminateNegativePositive (%) (3) (1) (6) (7) (12)
(31)
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TB Infection Prevalence by Testand Clinic Type
Homeless TB Clinic Methadone Immigrant
TST(2001-2003)
26% >50% 10% 37%
QFT-1 (11/04-2/05)
17 %n=1848
48 %n=292
18 %n=346
37 % n=344
QFT-Gold (3/05-2/06)
Decline in positive rate from TST
6 %n=3594
77%
26 %N=693
48%
4 %n=546
60%
12 %n=626
66%
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Preliminary HIV results from SF AIDS Clinic
3/1/06 and 5/31/06Why they were anxious to switch: TST return rate <50%
# samples submitted: 44Results: 93%Results w/o indeterminates: 86%
Indeterminate: 3 (7%) Not Tested: 3 (7%) Positive: 1 (2%) Negative: 37 (84%)
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Wisconsin Shelter TST Results
January 2004 – March 2005• 268 TSTs were given
– 152 people returned (56%)– 14 were positive (9%)
Data provided by the Wisconsin Division of Public Health
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QFT shift:Wisconsin Shelter testing April – December 2005
• 306 QFT-TB Gold (95% initial results)– 31 positives (10%)
• 5 people previously documented negative TST• 4 people known TST positives• 12 people previously in other shelters within one
year– 259 negative (85%)
• 17 people previously documented positive TST– 17 indeterminate (5%)
• 7 people retested — 1 positive• Multiple medical and immunity problems
Data provided by the Wisconsin Division of Public Health
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QFT and Contact Investigation
Expect maximum benefit:• Populations with poor return rates (homeless and hotel dwellers)• F.B. with high background prevalence of LTBI and BCG vaccination
Example: SF low-cost hotel drug-resistance investigation• Prior QFT results easy to track down in database• 9/31 converters found! (6 QFT conversions and 1 case found)
4 negative TSTs → positive QFT2 negative QFTs → positive QFT3 negative TSTs → positive TST
Example: XDR investigation involving F.B. contacts (88% FB, ½ with prior +TST)1 out of 25 contacts with positive QFT (Is QFT weeding out remote infection?)…..stay tuned!
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Don’t use QFT-G to “rule out” TB!TB Suspects: 37/242 had culture-confirmed tuberculosis
(3/2/05-12/31/05)
• QFT-G sensitivity: 64% (TST sensitivity = 88%)• Very poor performance in extrapulmonary TB (14%
sensitivity 1/7 cases)
Conclusion: low sensitivity and poor correlation to published studies
Note: No cases were missed due to a negative QFT result
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TST is not perfect either …
• 282 B notifications reported 3/1/05 to 4/3/06• 217 with either QFT-G or TST• QFT-G – 84/164 positive = 51.8% positive rate
73 B1 - 40 positive = 55.8%• 91 B2 - 45 positive = 49.5%• TST - 38/53 positive = 71.6% positive rate
32 B1 - 21 positive = 65.6%21 B2 - 17 positive = 81.0%
• 11 cases identified with either QFT or TSTQFT- /TST + : 2 cases potentially missed by QFT QFT+ /TST - : 2 cases potentially missed by TST
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Estimated Costs in High Usage Setting
Commercial Kit
QFT-G QFT-GIn-tube
QFT-GIn-tube
T-SPOT
Assay type ELISA ELISA ELISA ELISPOT
Lab Automation
partial partial Full Partial
TOTAL ($) 29.22 26.74 25.09 57.79
Costs include facility space, equipment, consumables and staff timeTST cost estimated (Medicare) $12-14 per patient tested
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Remaining issues…
• Interpretation of discordant TST and QFT results• Management of indeterminate results• QFT-G thresholds set for higher specificity… has it
sacrificed too much sensitivity?• Serial testing: no long-term data on conversions,
reversions, management of changing results and evidence-based thresholds for conversion
• Unknown dynamics of T-cell responses during and after treatment for LTBI and active treatment
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Is the TST still useful? Of course!• When there is no phlebotomy expertise or
patient is a “difficult stick “E.g., very young children and some IDUs
• When TB screening opportunities are limited (e.g., contact investigation, jail screening)Until 12-hour laboratory submission time eliminated or access to blood-based testing becomes widespread and 24/7, PPD may be more practical
• When maximizing sensitivity in suspects, immunocompromised, and young children
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Conclusions• QFT-G is highly specific!!! It will result in a significantly lower
number of positive results compared to QFT-TB and TST• While this is disconcerting, there is no evidence to date that
cases are being missed • Long-term studies are needed to study discordants, QFT-G
negative contacts and high-risk children• Blood-based TB testing is a superior surveillance tool with
more believable results• Training lab personnel is much easier than the training
countless providers of a whole city • QFT-G is most useful in nonadherent and BCG-vaccinated
populations • NEVER USE A QFT TO RULE OUT DISEASE… it’s a tool,
not a panacea!
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QFT-Gold: Clinical Applications
• The distraught mother….Feisty 4 year-old Chinese adoptee with history of 2 BCGs and 12mm TST result.
QFT-1: conditionally positiveQFT-Gold: negative
• The BCG-vaccinated baby…MDR newborn contact to smear+ mother. BCG given X2. TST at 4 months negativeResults at 6 months QFT-1: conditionally positive QFT-Gold: negative
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QFT-Gold: Clinical Applications• The nonbeliever: “I’m TST positive because of BCG!”
French-born HIV researcher with documented BCG X3 returns from a 10-day trip in Africa (worked in HIV clinic). Refuses LTBI treatment.-PPD 20mm -QFT-Gold positive
• Other potential uses: Solving disputes-Waxing and waning TST results in serial testing -Funny-looking TST results -“Well, it might be swollen and it sure is red!”-Referred patient: “I think they read my skin test wrong.”
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Acknowledgments: Puneet Dewan, M.D.,
SF TB Control staff, SFDPH laboratory (Sally Liska, Ernest Wong),
SF community clinics
Tanya Oemig RM(NRM)TB Program Director
Wisconsin Division of Public Health