A comparative study of two different methods for the detection of latent tuberculosis in HIV-positive individuals in Chile.

OBJECTIVE: To compare the performance of two tests for diagnosing latent tuberculosis (TB) infection in the HIV-positive population in Chile, in order to better identify the subjects who might benefit from TB chemoprophylaxis. DESIGN: This was a cross-sectional study among individuals attending three HIV outpatient clinics in Santiago, tested with a 2-TU purified protein derivative, QuantiFERON((R))-TB Gold 'in-tube' (QFT-G), and a chest X-ray. RESULTS: A total of 116 subjects were enrolled in the study, having a mean CD4 count of 393cells/microl (range 100-977). The tuberculin skin text (TST; 5mm cutoff) and QFT-G results were positive in 10.9% and 14.8% of the individuals, respectively, with moderate agreement between both tests (kappa=0.59). A history of both known TB exposure (odds ratio (OR) 3.46, 95% confidence interval (CI) 1.02-11.22) and past TB (OR 4.31, 95% CI 1.13-15.5) were associated with a positive QFT-G result. Only past TB was significantly associated with a positive TST result (OR 6.63, 95% CI 1.62-26.3). Among the subjects with TST<5mm, 8.2% were positive by QFT-G test. These individuals had a lower mean CD4 cell count than those detected positive by both tests (328cells/microl and 560cells/microl, respectively, p=0.03). CONCLUSIONS: In this population of HIV-infected individuals, QFT-G and TST showed an acceptable level of agreement, although QFT-G appears less affected by more advanced immunosuppression.

Redefining the facilitated transport of mannose in human cells: absence of a glucose-insensitive, high-affinity facilitated mannose transport system.

Current evidence suggests that extracellular mannose can be transported intracellularly and utilized for glycoprotein synthesis; however, the identity and the functional characteristics of the transporters of mannose are controversial. Although the glucose transporters are capable of transporting mannose, it has been postulated that the entry of mannose in mammalian cells is mediated by a transporter that is insensitive to glucose [Panneerselvam, K., and Freeze, H. (1996) J. Biol. Chem. 271, 9417-9421] or by a transporter induced by cell treatment with metformin [Shang, J., and Lehrman, M. A. (2004) J. Biol. Chem. 279, 9703-9712]. We performed a detailed analysis of the uptake of mannose in normal human erythrocytes and in leukemia cell line HL-60. Short uptake assays allowed the identification of a single functional activity involved in mannose uptake in both cell types, with a K(m) for transport of 6 mM. Transport was inhibited in a competitive manner by classical glucose transporter substrates. Similarly, the glucose transporter inhibitors cytochalasin B, genistein, and myricetin inhibited mannose transport by 100%. Using long uptake experiments, we identified a second, high-affinity component associated with the intracellular trapping of mannose in the HL-60 cells that is not directly involved in the transport of mannose via the glucose transporters. Thus, the transport of mannose via glucose transporters is a process which is kinetically and biologically separable from its intracellular trapping. A general survey of human cells revealed that mannose uptake was entirely blocked by concentrations of cytochalasin B that obliterates the activity of the glucose transporters. The transport and inhibition data demonstrate that extracellular mannose, whose physiological concentration is in the micromolar range, enters cells in the presence of physiological concentrations of glucose. Overall, our data indicate that transport through the glucose transporter is the main mechanism by which human cells acquire mannose.