Evaluation of a new hepatitis B virus surface antigen rapid test with improved sensitivity.

A new rapid immunochromatographic assay based on the signal amplification system (SAS) has been developed by Diagnostics for the Real World (Europe) Ltd. for the detection of hepatitis B virus surface antigen (HBsAg) in plasma or serum specimens. The SAS format features enhanced sensitivity as a result of an increased binding valence of the detector molecules. We have now evaluated the performance of the new HBsAg rapid test (DRW-HBsAg) in comparison with a well-established commercial rapid test (Determine HBsAg; previously from Abbott Laboratories; now from Inverness Medical Innovations) and with a CE-marked enzyme immunoassay (EIA) (Hepanostika HBsAg Ultra; BioMérieux) as the gold standard. Testing of serially diluted in-house HBsAg-positive samples, the World Health Organization standard, and sensitivity and reference panels yielded an analytical sensitivity for the DRW test of 0.2 to 0.8 IU/ml across HBsAg serotypes. Evaluation with eight commercially available seroconversion panels showed that the DRW-HBsAg test detected HBsAg an average of 6.1 days (range, 3 to 8 days) earlier than the Determine assay (P = 0.0078). Test sensitivity was also examined with two low-titer HBsAg EIA-positive panels in Beijing, China. Whereas 100% of these samples were detected by the DRW-HBsAg test, only 15.0% (P < 0.0001) and 87.3% (P < 0.0001), respectively, were detected by the Determine HBsAg test. The performance of the DRW-HBsAg test was further evaluated with samples determined to be HBsAg positive or negative by the EIA in Conakry, Guinea, and Beijing, China. No significant difference in sensitivity between the DRW and Determine tests was apparent with the HBsAg EIA-reactive samples from Guinea (96.7% versus 94.4%, respectively) or China (99.46 versus 98.92%, respectively). The specificity of the Determine HBsAg test was slightly higher than that of DRW-HBsAg test (100 versus 99.2%, respectively) with samples from EIA-negative blood donors in China. In conclusion, the new DRW HBsAg rapid test is more sensitive than the Determine HBsAg test and is suitable for diagnostic and blood screening in resource-limited settings.

Development of a large-scale chemogenomics database to improve drug candidate selection and to understand mechanisms of chemical toxicity and action.

Successful drug discovery requires accurate decision making in order to advance the best candidates from initial lead identification to final approval. Chemogenomics, the use of genomic tools in pharmacology and toxicology, offers a promising enhancement to traditional methods of target identification/validation, lead identification, efficacy evaluation, and toxicity assessment. To realize the value of chemogenomics information, a contextual database is needed to relate the physiological outcomes induced by diverse compounds to the gene expression patterns measured in the same animals. Massively parallel gene expression characterization coupled with traditional assessments of drug candidates provides additional, important mechanistic information, and therefore a means to increase the accuracy of critical decisions. A large-scale chemogenomics database developed from in vivo treated rats provides the context and supporting data to enhance and accelerate accurate interpretation of mechanisms of toxicity and pharmacology of chemicals and drugs. To date, approximately 600 different compounds, including more than 400 FDA approved drugs, 60 drugs approved in Europe and Japan, 25 withdrawn drugs, and 100 toxicants, have been profiled in up to 7 different tissues of rats (representing over 3200 different drug-dose-time-tissue combinations). Accomplishing this task required evaluating and improving a number of in vivo and microarray protocols, including over 80 rigorous quality control steps. The utility of pairing clinical pathology assessments with gene expression data is illustrated using three anti-neoplastic drugs: carmustine, methotrexate, and thioguanine, which had similar effects on the blood compartment, but diverse effects on hepatotoxicity. We will demonstrate that gene expression events monitored in the liver can be used to predict pathological events occurring in that tissue as well as in hematopoietic tissues.