October 3, 2006

Serial Testing of Health Care Workers for Tuberculosis Using

Interferon-γ AssayMadhukar Pai, et. al.

American Journal of Respiratory and Critical Care Medicine, 2006, (174): 349-355.

Discussion by:Anna Gushchin

Mentor: Dr. David Paterson

GHIG Journal Club

October 3, 2006

Acknowledgements

• Dr. David Paterson – University of Pittsburgh, Department of Medicine,

Division of Infectious Diseases.

• Dr. Anu Manandhar– Tilganga Eye Centre, Gaushala, Nepal.

• Dean Harvey– University of Pittsburgh, School of Medicine.

• You!

Outline

• Global TB Burden

• Current Diagnosis Methods

• Article Findings

• Discussion

Why TB?• Estimated 1/3 of the world is affected

– 9 million cases every year1.

• MMWR: March 24, 2006 (17,690 samples)– Multiple drug resistant TB

• MDR 20%

– Extensive drug resistant TB • XDR 2%

• How is this treated?– Isoniazid, rifampin, pyrazinamide, ethambutol,

streptomycin, cycloserine, capreomycin…

1) World Health Organization. Global Tuberculosis Control. Surveillance, Planning FinancingWHO Report 2005. Geneva.

(3,538)

(70)

Before Treating, Must Detect

• PPD – (Purified Protein Derivative)

– 0.1 mL injection– 48-72 hours later measure reaction

• Secondary confirmation may be necessary– 1-2 weeks apart

• US CDC recommendations:– HCW: Every year– High Risk: Every 6 months

Question

• Which country currently has the highest voluntarily reported rate of XDR (extremely drug-resistant) TB?

• 2002-2004 Latvia 21% XDR

•What % of the population in India is estimated to be infected?

• 40%

Serial Testing of Health Care Workers for Tuberculosis Using

Interferon-γ AssayMadhukar Pai, et. al.

American Journal of Respiratory and Critical Care Medicine, 2006, (174): 349-355.

Questions Asked:

• Is IFN-γ release assay (IGRA) comparable to the Tuberculin Skin Test (TST) aka PPD?

• Are there advantages to using one technology over another?

• Can it be used successfully in an underserved population with a high burden of infection?

1) Is IGRA comparable to TST?

• 353 medical and nursing students– 216 completed the study

• Tested twice (6 months apart)– QFT (QuantiFERON)– TST

• Analysis:– Concordant/discordant

The Technology

• IGRA:– Unaffected by BCG vaccination

– Single visit

– No booster effects

– Rapid test, 24 hours

– Uses whole blood

– Good detection of LTBI

– 98.2% Specificity

– 90% Sensitivity.

How do these tests work?

TSTHypersensitivity response

> Erythema

IGRA

Results!N=216

Statistics

Bottom line: compared the 4 subgroups for level of agreement (kappa coefficient)

Results+ve Conversion Conversion 2

TST 48 (22%) 14 (9.5%)

(10mm)

6 (4.1%)

(6mm)

QFT 38 (18%) 17 (11.6%)

>0.35IU/ml

11 (7.5%)

>0.70IU/ml

Agreement 96%, Kappa = 0.70

Conclusions

• IGRA shows promise for serial testing

• IGRA is comparable with TST

• Must interpret results judiciously – Determine the threshold points for positive and

negative results.

Study Strengths

TST• Same evaluator read

TST results from “blinded” calipers.

• Used same PPD preparation.

QFT• Internal positive and

negative controls.• Colorimetric test (read

by plate reader).

Limitations

• Small sample size

• BCG effect

• Isoniazid treatment in some*

• Not included other professionals

Limitations

• quantiFERON-TB Gold-in Tube: Cellestis– Refrigerated (2 year shelf life)– 44 test/kit ($748.00) – After initial costs: $17/patient

Lessons

• Testing people is difficult if they do not come in.

• Cannot test immunocompromised.

• People more likely to come for one appointment.

What do you think?

• Is this a technology that should be implemented in hospitals in ______?

• How to present evidence for a New technology without a “gold standard”?