igras in practice: the san francisco health department experience jennifer grinsdale, mph program...

IGRAs in Practice: IGRAs in Practice:

The San Francisco Health The San Francisco Health Department ExperienceDepartment Experience

Jennifer Grinsdale, MPHJennifer Grinsdale, MPHProgram Manager/EpidemiologistProgram Manager/Epidemiologist

Acting DirectorActing Director

Tuberculosis Control SectionTuberculosis Control Section

San Francisco Department of Public HealthSan Francisco Department of Public Health

Setting for QFT Implementation: Setting for QFT Implementation: San FranciscoSan Francisco

• 49 square miles • Population ~805,000• 35% foreign born • 27,000 living with AIDS• >6,000 homeless (1,500 in shelter)• 18,000+ injection drug users

(22% HIV+)• ~55,000 jail bookings each year

Setting for QFT Implementation:Setting for QFT Implementation:TB Morbidity, 1980-2011TB Morbidity, 1980-2011

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1980 1983 1986 1989 1992 1995 1998 2001 2004 2007 2010

HIV co-infected Cases All Cases

QFT Implemented in 2003

Setting for QFT Implementation:Setting for QFT Implementation:Case Finding MethodsCase Finding Methods

PassivePassive Hospital and MD referral of suspectsHospital and MD referral of suspects

ActiveActive Immigration screeningImmigration screening Contact InvestigationContact Investigation Targeted testingTargeted testing

• 2005-2009: 30% of cases found through active TB 2005-2009: 30% of cases found through active TB screeningscreening

• Targeted testing yields 3x more cases than CI and Targeted testing yields 3x more cases than CI and immigration screening combined (2009: 27 of 37 immigration screening combined (2009: 27 of 37 cases from TT)cases from TT)

Setting for QFT Implementation:Setting for QFT Implementation:Targeted Testing ModelTargeted Testing Model

Community-Based12 Primary Care Health Centers

10 DPH-Affiliated Partners

7 Fee-for Service Clinics

6 Youth Clinics

Most screen for TB using TST (and now QFT) and refer to TB clinic for evaluation and LTBI treatment

2001-2003: Implementation2001-2003: ImplementationWhy switch to QFT?Why switch to QFT?

Better test Better test • Reduce the number of false positives• No quality control of >10,000 TSTs/yr at community sites• Low confidence in the TST by providers caring foreign-born

because of BCG vaccination• A less subjective test is better and safer for the public

Operational advantagesOperational advantages• Results for every patient – eliminate wasted effort• Reduce unnecessary CXR and MD evaluation of false

positives• Improved documentation, surveillance & communication

‘‘Use it or lose it’ timeUse it or lose it’ time• FDA approved in 2001 but no one was using it • It was time to try something new

Program Implications: Our Hopes…Program Implications: Our Hopes…

New surveillance capabilities:New surveillance capabilities: • Citywide laboratory-based surveillance for LTBI

through the public health lab

More efficient:More efficient: • Eliminate unnecessary CXRs, evaluation and

treatment • More results means targeting efforts on “positives”

instead of on retesting individuals who fail to show up for TST readings (homeless, jails, employee testing)

Behave as “expected”:Behave as “expected”:• Increase patient and provider confidence with more Increase patient and provider confidence with more

reliable and specific resultsreliable and specific results

Program Implications: Our Fears…Program Implications: Our Fears…

Feasibility and Acceptability:Feasibility and Acceptability:• Blood-based testing might not be feasible or

acceptable to the lab, patients and providers• Moving cost of screening from the program to the

lab

Sensitivity:Sensitivity:• No gold standard for LTBI• Missed diagnosis of active disease

Risk of Progression in QFT positives:Risk of Progression in QFT positives:• Would we identify the “right” patients for LTBI

treatment?

We took the leap…

Is QFT feasible and acceptable?Can QFT be used as a LTBI surveillance tool?Is QFT programmatically more efficient than

TST?Does QFT behave as expected (more specific

than TST)?Is QFT more sensitive in diagnosing active

TB?Does QFT correctly identify patients who will

progress to disease?

QFT ChecklistQFT Checklist

QFT-1st Generation: 2003-2005• During the first 18 months QFT was implemented at

6 clinics (including TB clinic)

• QFT results were available to the TB program for 92% of persons tested

• Indeterminate results were uncommon (2%)

• Phlebotomy refusal/failure was uncommon

• A valid result was obtained for 99% of homeless clients (88% with TST prior to QFT implementation)

• IGRA implementation cost the health care system in San Francisco approximately $33.89 per patient tested – 83% of that by the lab

Dewan et al. BMC Infectious Diseases 2006, 6:47

QFT-TB n=4,574

QFT-G n=23,529

QFT Tests Performed By Month, QFT Tests Performed By Month, November 2003 – December 2011November 2003 – December 2011

QFT-GIT n=34,806

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2004 2005 2006 2007 2008 2009 2010 2011

QFT Results by Clinic Type QFT Results by Clinic Type March 2005 – December 2011March 2005 – December 2011

Homeless TB ClinicMethadon

eImmigrant/ Refugee

HIVCommuni

tyAll

Positive Gold In-tube

734 (7)629 (7)

942 (22)2293 (23)

51 (3)128 (5)

392 (14)882 (23)

24 (3)20 (5)

349 (10)1340 (14)

2603 (11)5292 (15)

Negative Gold In-tube

8646 (89)8033 (92)

3177 (73)7186 (74)

1514 (93)2129 (92)

2235 (80)2920 (76)

800 (93)359 (93)

3531 (84)8249 (85)

19903 (85)

28876 (83)

Indeterm. Gold In-tube

352 (4) 114 (1)

217 (5)249 (3)

62 (4)67 (3)

157 (6)39 (1)

39 (5)6 (2)

196 (5)163 (2)

1023 (4)638 (2)

Total Tests Gold In-tube

97328776

43369728

16272324

27843841

863385

41879752

2352934806

TB Infection Prevalence By Test TB Infection Prevalence By Test Version and Clinic TypeVersion and Clinic Type

Homeless TB Clinic Methadone Immigrant

TST(2001-2003)

26% >50% 10% 37%

QFT-1 (11/03-2/05) 17% 48% 18% 37%

QFT-gold (3/05-2/09) 7% 22% 3% 14%

QFT-gold IT (1/08-12/11) 7% 23% 5% 23%

Decline in positive rate from TST

73% >54% 50% 38%

QFT and Contact InvestigationQFT and Contact InvestigationMarch 2005 – December 2007March 2005 – December 2007

TST QFT-G

Contacts tested 650 641

Fully evaluated * 361 (56%) 410 (64%)

Cases found 5 (1%) 8 (2%)

Infection prevalence* 141 (39%) 120 (29%)

Initiation of LTBI * treatment

100/139 (72%) 105/118 (89%)

Completion of treatment among those who started

73/100 (73%) 83/105 (79%)

Completion of treatment among those infected *

73/139 (53%) 83/118 (70%)

J. Grinsdale, et al. IJTLD, 2011.*P<0.05

Role of QFT in Diagnosing Active TB Role of QFT in Diagnosing Active TB

• Adding quantitative QFT-G results significantly improved clinical prediction model performance in reclassifying suspects as low, intermediate, and high risk of active disease• Odds of active tuberculosis increased by 7% for each

doubling of interferon-γ level

• Quantitative results did not significantly improve appropriate risk reclassification beyond that provided by SF clinician assessment of risk

• Not better than subjective clinical assessment but better than using objective risk criteria alone

J. Metcalf et al, AJRCCM 2010




TB? Does QFT correctly identify patients who will



QFT Results by Age Group and Test QFT Results by Age Group and Test VersionVersion

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Positive Negative Indeterminate

Pediatric TST/QFT Discordance by Pediatric TST/QFT Discordance by Age and BCG or Foreign-born StatusAge and BCG or Foreign-born Status

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28.0

71.0

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91.0

72.0

29.0

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< 5 BCG or FB > 5 BCG or FB < 5 No BCG > 5 No BCG

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Age Group and BCG/FB Status

Concordant

Discordant

CI Infection Rates by ExposureCI Infection Rates by Exposure

QFT-G*QFT-G* TSTTST QFT-G*QFT-G* TSTTST

Index Smear + 88/384 (23%)

113/439 (26%)

70/233 (30%)

92/164 (56%)

Index Smear-/ Culture +

37/257 (14%)

47/211 (22%)

25/125 (20%)

42/88 (48%)

QFT-G*QFT-G* TST*TST* QFT-G*QFT-G* TSTTST

Household 82/267 (31%)

95/253(38%)

76/207(37%)

84/149(56%)

Non-household 43/374 (12%)

65/397 (16%)

19/150(13%)

50/103(49%)

All ContactsAll Contacts Foreign-Born Foreign-Born ContactsContacts

J. Grinsdale, et al. IJTLD, 2011.

*P<0.05




TB? Does QFT correctly identify patients who will



Culture Confirmed TB: Culture Confirmed TB: TST and QFT SensitivityTST and QFT Sensitivity

Test type Test type SensitivitySensitivity

(n=321)(n=321)ConcordanceConcordance

TST+TST+ 83.6% (112/134) -

QFT-G+QFT-G+ 73.3% (137/187) -

QFT-G+ or TST+QFT-G+ or TST+ 91.1% ( 92/101) 69%

Test typeTest type SensitivitySensitivity

(n=383)(n=383)ConcordanceConcordance

TST+TST+ 82.2% (134/163)82.2% (134/163) --

QFT-IT+QFT-IT+ 76.4% (168/220)76.4% (168/220) --

QFT-IT+ or TST+QFT-IT+ or TST+ 91% (134/145)91% (134/145) 68.3% 68.3%



than TST)?X Is QFT more sensitive in diagnosing active




Pediatric QFT Screening Outcomes Pediatric QFT Screening Outcomes (Preliminary)(Preliminary)

• 1,087 children followed for a median of 3.6 years (>4000 person-years of follow-up)

• No one developed active TB• 979 untreated QFT-negative or

indeterminate children • 47 children <2 yrs• 214 children ages 2-4• 55 children <5 with TST+/QFT- results

Adult QFT Screening Outcomes Adult QFT Screening Outcomes (Preliminary)(Preliminary)

“Quick and Dirty” analysis suggests:• QFT-positives

• Active TB develops “quickly” when LTBI is untreated, usually within 2 years

• Most were new arrivers or contacts

• QFT-negatives• Active TB develops ”later” (>2-10 years) • Most were contacts to multiple cases in large

outbreaks where ongoing opportunities for infection couldn’t be ruled out - screened early in the investigation but not again after new cases were diagnosed



than TST)?X Is QFT more sensitive in diagnosing active




QFT: The Test of Choice for San QFT: The Test of Choice for San FranciscoFrancisco

PERFORMANCE• Single step to get results• Higher specificity and reliability of results

SURVEILLANCE • Superior to TST• Strengthen our partnership with the PHL

CONTACT INVESTIGATION• IGRA preferred by investigators• Better evaluation and treatment outcomes• Results correlate to intensity of exposure

TARGETED TESTING• Screening BCG vaccinated populations

• Significantly decreased the number of referrals to the TB Clinic and LTBI treatment

• Made mandatory shelter clearance screening possible

PEDIATRIC• No cases missed• Negative predictive value excellent at >24 months

follow up• Phlebotomy is more difficult but parents continue to

want QFT results because of its higher specificity and avoidance of unnecessary treatment

QFT: The Test of Choice for San QFT: The Test of Choice for San FranciscoFrancisco

The Keys to Our Success… The Keys to Our Success…

• Targeted the patient and provider population who would most benefit from the test (e.g., Community clinics, refugees, shelter clients)

• Developed political will through education

• Partnerships with laboratory and providers

• Resource assessment and development• Communication, communication,

communication

Regarding QFT-G…..Regarding QFT-G…..

This has been the single biggest This has been the single biggest advance in delivering healthcare to advance in delivering healthcare to people who are homeless in my 20 people who are homeless in my 20 years of doing healthcareyears of doing healthcare. Barry ZevinBarry ZevinSan Francisco homeless healthcare providerSan Francisco homeless healthcare provider

May 5, 2008May 5, 2008

CDC Recommends New Blood Test CDC Recommends New Blood Test for TB – Associated Press, 2005for TB – Associated Press, 2005

"This is one of the first TB advancements made since the discovery of antibiotics. … This is a huge deal," said Jennifer Grinsdale, an epidemiologist with the San Francisco Department of Public Health.

In San Francisco, QFT is a HUGE DEAL!

igras in practice: the san francisco health department experience jennifer grinsdale, mph program...

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