Antibody detection tests for early diagnosis in tuberculous meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Microbiological confirmation is rare and treatment is often delayed. Early diagnosis and immediate initiation of treatment are essential for effective TBM control. A systematic review was performed in this study to assess the diagnostic accuracy of detecting antibodies against Mycobacterium tuberculosis in the cerebrospinal fluid (CSF), according to standard methods. Test performance was summarized using a bivariate random-effects meta-analysis. METHODS: Studies were identified by a search of the literature, up to July 25, 2015, in the EMBASE and MEDLINE databases via Ovid SP and PubMed. The Cochrane Library was also searched for original, peer-reviewed molecular epidemiology studies that reported the diagnosis of TBM based on antibody detection in the CSF. RESULTS: Thirty-six articles (58 studies) were identified. The sensitivity of antibody detection was 0.75 (95% confidence interval (CI) 0.66-0.82), specificity was 0.98 (95% CI 0.96-0.99), and the area under the receiver operating characteristic curve (AUROC) was 0.97 (95% CI 0.95-0.98). By subgroup analysis, the detection of anti-M37Ra was the highest (AUROC 0.99, 95% CI 0.98-1.00), followed by anti-antigen 5 (AUROC 0.99, 95% CI 0.97-0.99) and anti-M37Rv (AUROC 0.97, 95% CI 0.95-0.98). CONCLUSIONS: For the early diagnosis of TBM based on antibodies in the CSF, the detection of anti-M37Ra, anti-antigen 5, or anti-M37Rv provides the greatest sensitivity and specificity.

Changes in lymphocyte subsets in the peripheral blood of patients with active pulmonary tuberculosis.

The aim of this study was to determine the percentage of lymphocyte subsets in peripheral blood in patients with active tuberculosis. A total of 21 patients with active tuberculosis and 15 healthy volunteers were included in the study. T-lymphocyte subsets, B-lymphocytes (CD19(+) cells), natural killer (NK) cells and cells positive for costimulatory molecules CD28 and CD152 were evaluated using flow cytometry. Patients with tuberculosis had a significantly decreased percentage of CD3(+) and CD3(+)CD4(+) cells, and a significantly decreased ratio of CD3(+)CD4(+) to CD3(+)CD8(+) cells compared with healthy controls. In contrast, the percentage of B-cells (CD19(+) cells), CD3(+)CD8(+) cells, CD28(+) cells, CD152(+) cells, and subpopulations of CD4(+)CD152(+), CD8(+)CD152(+) and CD8(+)CD28(+) T-cells were all significantly increased compared with healthy controls. There were no statistically significant differences in the percentages of NK cells or CD4(+)CD28(+) cells between patients and controls. These results indicate that patients with active tuberculosis have altered lymphocyte homeostasis.

Fractals for multicyclic synthesis conditions of biopolymers. Examples of oligonucleotide synthesis measured by high-performance capillary electrophoresis and ion-exchange high-performance liquid chromatography.

We have developed models of patterns for nucleotide chain growth. These patterns are measurable by high-performance capillary electrophoresis and ion-exchange high-performance liquid chromatography in crude products of solid-phase synthesized 30mer and 65mer oligodeoxyribonucleotide target sequences N. We introduce mathematical methods for finding characteristic values d(o) and p(o) for constant chemical modes of growth as well as d and p for non-constant chemical modes of growth (d = probability of propagation, p = probability of termination). These methods are employed by presenting the accompanying computer software developed by us in C code, Mathematica R languages, and Fortran. Characteristic values of the parameters d, p, and the target nucleotide length N describe the complete composition of the crude product. From this we have developed the relation 2 - [N/(N - 1)]/Da, measurable(N,d) as a universal quantitative measure for multicyclic synthesis conditions (D, fractal dimension and similarity exponent, respectively). We use this mathematical treatment to compare the efficiency of oligodeoxyribonucleotide syntheses of different target length N on polymer support materials. Further, we analyze selected syntheses of short and long oligodeoxyribonucleotides as well as single-stranded DNA sequences by well-known empirical autocorrelation, fast Fourier transformation, and embedding dimension techniques.

Fractal dimension of error sequence dynamics in quantitative modeling of syntheses of short oligonucleotide and single-stranded DNA sequences.

Oligonucleotides are becoming more and more important in molecular biomedicine; for example, they are used as defined primers in polymerase chain reaction and as antisense oligonucleotides in gene therapy. In this paper, we model the dynamics of polymer-supported oligonucleotide synthesis to an inverse power law of driven multi-cycle synthesis on fixed starting sites. The mathematical model is employed by presenting the accompanying view of error sequences dynamics. This model is a practical one, and is applicable beyond oligonucleotide synthesis to dynamics of biological diversity. Computer simulations show that the polymer support synthesis of oligonucleotides and single-stranded DNA sequences in iterated cyclic format can be assumed as scale-invariant. This synthesis is quantitatively described by nonlinear equations. From these the fractal dimension Da (N,d) is derived as the growth term (N = number of target nucleotides, d = coupling probability function). Da(N,d) is directly measurable from oligonucleotide yields via high-performance liquid chromatography or capillary electrophoresis, and quantitative gel electrophoresis. Different oligonucleotide syntheses, including those with large-scale products can be directly compared with regard to error sequences dynamics. In addition, for short sequences the fractal dimension Da (N,d) is characteristic for the efficiency with which a polymer support of a given load allows oligonucleotide chain growth. We analyze the results of separations of crude oligonucleotide product from the synthesis of a 30 mer. Preliminary analysis of a 238 mer single-stranded DNA sequence is consistent with a simulated estimate of crude synthesis product, although the target sequence itself is not detectable. We characterize the oligonucleotide support syntheses by simulated and experimentally determined values of the fractal dimension Da (N,d0) within limitations (d0 = constant (average) coupling probability).