October 3, 2006
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”?