Evaluation of Antigens for Development of a Serological Test for Human African Trypanosomiasis.

Background: Control and elimination of human African trypanosomiasis (HAT) can be accelerated through the use of diagnostic tests that are more accurate and easier to deploy. The goal of this work was to evaluate the immuno-reactivity of antigens and identify candidates to be considered for development of a simple serological test for the detection of Trypanosoma brucei gambiense or T. b.

Systematic reference sample generation for multiplexed serological assays.

Quality controls of serological assays have to contain defined amounts of human antibodies specific for the targeted antigen. A prevailing issue for array-based antigen assays is that dozens of antigens are targeted within the same assay. Commonly different patient sera are combined and optimal pools are empirically identified.

Validation of Mycobacterium tuberculosis Rv1681 protein as a diagnostic marker of active pulmonary tuberculosis.

The development of an accurate antigen detection assay for the diagnosis of active tuberculosis (TB) would represent a major clinical advance. Here, we demonstrate that the Mycobacterium tuberculosis Rv1681 protein is a biomarker for active TB with potential diagnostic utility. We initially identified, by mass spectroscopy, peptides from the Rv1681 protein in urine specimens from 4 patients with untreated active TB.

Proteome-scale antibody responses and outcome of Mycobacterium tuberculosis infection in nonhuman primates and in tuberculosis patients.

Background: Biomarkers of progression from latent Mycobacterium tuberculosis infection to active tuberculosis are needed. We assessed correlations between infection outcome and antibody responses in macaques and humans by high-throughput, proteome-scale serological studies.

Methods: Mycobacterium tuberculosis proteome microarrays were probed with serial sera from macaques representing various infection outcomes and with single-point human sera from tuberculosis suspects.

Discerning trends in multiplex immunoassay technology with potential for resource-limited settings.

Background: In the search for more powerful tools for diagnoses of endemic diseases in resource-limited settings, we have been analyzing technologies with potential applicability. Increasingly, the process focuses on readily accessible bodily fluids combined with increasingly powerful multiplex capabilities to unambiguously diagnose a condition without resorting to reliance on a sophisticated reference laboratory. Although these technological advances may well have important implications for the sensitive and specific detection of disease, to date their clinical utility has not been demonstrated, especially in resource-limited settings.

Mycolic acids as diagnostic markers for tuberculosis case detection in humans and drug efficacy in mice.

Mycolic acids are attractive diagnostic markers for tuberculosis (TB) infection because they are bacteria-derived, contain information about bacterial species, modulate host-pathogen interactions and are chemically inert. Here, we present a novel approach based on mass spectrometry. Quantification of specific precursor → fragment transitions of approximately 2000 individual mycolic acids (MAs) resulted in high analytical sensitivity and specificity.

Single-molecule detection on a protein-array assay platform for the exposure of a tuberculosis antigen.

Based on a single-molecule sensitive fluorescence-linked immunosorbent assay, an analytical platform for the detection of lipoarabinomannan (LAM), a lipopolysaccharide marker of tuberculosis, was established that is about 3 orders of magnitude more sensitive than comparable current ELISA assays. No amplification step was required. Also, no particular sample preparation had to be done.

Dynamic antibody responses to the Mycobacterium tuberculosis proteome.

Considerable effort has been directed toward controlling tuberculosis, which kills almost two million people yearly. High on the research agenda is the discovery of biomarkers of active tuberculosis (TB) for diagnosis and for monitoring treatment outcome. Rational biomarker discovery requires understanding host-pathogen interactions leading to biomarker expression.

A decline in hepatitis B virus surface antigen (hbsag) predicts clearance, but does not correlate with quantitative hbeag or HBV DNA levels.

Background: The elimination of hepatitis B virus surface antigen (HBsAg) is the final goal of hepatitis B treatment, but is rarely achieved. As quantitative assays for HBsAg recently became available, we have investigated whether quantitative HBsAg measurements can substitute for hepatitis B virus (HBV) DNA quantification in treatment monitoring.

Methods: Within this study, 23 liver transplant patients and 18 heart transplant recipients were retrospectively analysed.

Third Santorini conference pharmacogenomics workshop report: "Pharmacogenomics at the crossroads: what else than good science will be needed for the field to become part of Personalized Medicine?".

This workshop discussed the use of pharmacogenomics knowledge in clinical practice. It was organized in three sections: educational needs, definition of industry as a potential trigger, and regulatory aspects. Regarding pharmacogenomics education, it appears that this is truly lacking, except for patients, who are becoming increasingly educated thanks to the media.

HBsAg level at time of liver transplantation determines HBsAg decrease and anti-HBs increase and affects HBV DNA decrease during early immunoglobulin administration.

Background/aims: Administration of hepatitis B immunoglobulin (HBIG) initially after liver transplantation of hepatitis B patients is considered important to prevent reinfection reliably. However, dosing schedules differ considerably between centers. We measured HBsAg, anti-HBs and HBV DNA kinetics to create a rational basis for dosing schemes.

Cholesterol levels linked to abnormal plasma thiol concentrations and thiol/disulfide redox status in hyperlipidemic subjects.

Treatment of hyperlipidemic patients with the thiol compound N-acetylcysteine (NAC) was previously shown to cause a significant dose-related increase in the high-density lipoprotein (HDL)-cholesterol serum level, suggesting the possibility that its disease-related decrease may result from a diminished thiol concentration and/or thiol/disulfide redox status (REDST) in the plasma. We therefore investigated plasma thiol levels and REDST in normo-/hyperlipidemic subjects with and without coronary heart disease (CHD). The thiol level, REDST, and amino acid concentrations in the plasma and intracellular REDST of peripheral blood mononuclear cells (PBMC) have been determined in 62 normo- and hyperlipidemic subjects.

Multicenter study of the LCx HIV RNA quantitative assay--a new competitive reverse transcriptase-PCR which targets pol genomic region of HIV-1 for the measurement of type B, non-type B and group O HIV-1 RNA.

Performance characteristics of the Abbott LCx HIV RNA Quantitative Assay (LCx HIV) were established in a multicenter study comparing it with the manual (Amplicor v1.5) and automated (Cobas) ultra-sensitive Roche Amplicor HIV-1 Monitor v1.5, the Bayer Quantiplex HIV RNA 3.