The impact of HIV infection and CD4 cell count on the performance of an interferon gamma release assay in patients with pulmonary tuberculosis
Department of Infectious Diseases, University of Copenhagen, Righospitalet, Copenhagen, Denmark; Unit for Infectious Diseases Q, Universityof Copenhagen, Herlev Hospital, Herlev, Denmark; National Institute for Medical Research, Mwanza Medical Research Center, Mwanza, Tanzania; Zonal Tuberculosis Reference Laboratory, Bugando Medical Centre, Mwanza, Tanzania; Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Frederiksberg, Denmark; National Institute for Medical Research, Muhimbili Medical Research Center, Dar Es Salaam, Tanzania
Background: The performance of the tuberculosis specific Interferon Gamma Release Assays (IGRAs) has not been sufficiently documented in tuberculosis- and HIV-endemic settings. This study evaluated the sensitivity of the QuantiFERON TB-Gold In-Tube (QFT-IT) in patients with culture confirmed pulmonary tuberculosis (PTB) in a TB- and HIV-endemic population and the effect of HIV-infection and CD4 cell count on test performance. Methodology/Principal Findings: 161 patients with sputum culture confirmed PTB were subjected to HIV- and QFT-IT testing and measurement of CD4 cell count. The QFT-IT was positive in 74% (119/161; 95% CI: 67-81%). Sensitivity was higher in HIV-negative (75/93) than in HIV-positive (44/68) patients (81% vs. 65%, p = 0.02) and increased with CD4 cell count in HIV-positive patients (test for trend p = 0.03). 23 patients (14%) had an indeterminate result and this proportion decreased with increasing CD4 cell count in HIV-positive patients (test for trend p = 0.03). Low CD4 cell count (<300 cells/μl) did not account for all QFT-IT indeterminate nor all negative results. Sensitivity when excluding indeterminate results was 86% (95% CI: 81-92%) and did not differ between HIV-negative and HIV-positive patients (88 vs. 83%, p = 0.39). Conclusions/Significance: Sensitivity of the QFT-IT for diagnosing active PTB infection was reasonable when excluding indeterminate results and in HIV-negative patients. However, since the test missed more than 10% of patients, its potential as a rule-out test for active TB disease is limited. Furthermore, test performance is impaired by low CD4 cell count in HIV-positive patients and possibly by other factors as well in both HIV-positive and HIV-negative patients. This might limit the potential of the test in populations where HIV-infection is prevalent. © 2009 Aabye et al.
gamma interferon; gamma interferon; adult; article; CD4 lymphocyte count; cell culture; controlled study; cytokine release; disease association; endemic disease; female; human; human cell; Human immunodeficiency virus infection; immunoassay; lung tuberculosis; major clinical study; male; performance measurement system; sensitivity analysis; analytical equipment; biochemistry; blood; CD4+ T lymphocyte; Human immunodeficiency virus infection; lung tuberculosis; metabolism; methodology; prevalence; sensitivity and specificity; sputum; Tanzania; Adult; Biochemistry; CD4-Positive T-Lymphocytes; Female; HIV Infections; HIV Seropositivity; Humans; Interferon-gamma; Male; Prevalence; Reagent Kits, Diagnostic; Sensitivity and Specificity; Sputum; Tanzania; Tuberculosis, Pulmonary