Tuberculin skin testing underestimates a high prevalence of latent tuberculosis infection in hemodialysis patients.
BACKGROUND
Identification of latent Mycobacterium tuberculosis infection in hemodialysis patients is hampered by reduced sensitivity of the established tuberculin skin test. We investigated whether in vitro quantitation of purified protein derivative (PPD)-specific T cells using a rapid 6-hour assay may represent an alternative approach for detecting latent infection.


METHODS
One hundred and twenty-seven hemodialysis patients and 218 control patients (blood donors, health care workers, and control patients) were analyzed. Specific T cells toward PPD and early secretory antigenic target-6 (ESAT-6), a protein expressed in Mycobacterium tuberculosis but absent from M. bovis bacillus Calmette-Guerin (BCG) vaccine strains, were flow cytometrically quantified from whole blood, and results were compared with skin testing.


RESULTS
Compared to blood donors, a high proportion of both health care workers (48.6%) and hemodialysis patients (53.5%) had PPD-specific Th1-type CD4 T-cell reactivity with similar median frequencies of PPD-specific T cells (0.17%; 0.06-3.75% vs. 0.26%; 0.06-4.12%, respectively). In contrast, skin test reactivity was significantly reduced in hemodialysis patients. Whereas 85.7% of control patients with PPD reactivity in vitro were skin test-positive, the respective percentage among hemodialysis patients was 51.4% (P= 0.007). Among individuals with PPD reactivity in vitro, approximately 50% had T cells specific for ESAT-6.


CONCLUSIONS
Unlike the skin test, measurement of PPD reactivity by in vitro quantitation of PPD-specific T cells was unaffected by uremia-associated immunosuppression. This whole-blood assay may thus be a valuable alternative to skin testing, and detection of ESAT-6-specific T cells could moreover allow distinction of latent M. tuberculosis infection from BCG-induced reactivity to PPD. The assay is well suited for clinical use and may facilitate targeting of preventative therapy in high-risk individuals.
Sester
Martina
M
Medical Department IV, University of the Saarland, Homburg, Germany.
Sester
Urban
U
Clauer
Peter
P
Heine
Gunnar
G
Mack
Ulrich
U
Moll
Thomas
T
Sybrecht
Gerhard W
GW
Lalvani
Ajit
A
Köhler
Hans
H
D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D005188:False Negative Reactions; D005434:Flow Cytometry; D005858:Germany / Q000453:epidemiology; D006801:Humans; D016867:Immunocompromised Host; D007156:Immunologic Memory; D066298:In Vitro Techniques; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects*; D012680:Sensitivity and Specificity; D018417:Th1 Cells / Q000276:immunology; D014373:Tuberculin / Q000276:immunology; D014374:Tuberculin Test / Q000379:methods* / Q000706:statistics & numerical data; D014376:Tuberculosis / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D014373:Tuberculin