Diagnostics & Imaging Week Contributing Writer
And D&IW

LONDON – A cheap, simple and accurate dipstick test for active tuberculosis could be available for use in the field within a few years, researchers have predicted. The test would employ antibodies to detect combinations of proteins that have been shown to be present in the serum of people suffering from active tuberculosis, but not in healthy controls.

Sanjeev Krishna, professor of molecular parasitology and medicine at the Centre for Infection at St. George's Hospital at the University of London, said: "This work provides a fresh approach to an ancient problem. I think it is going to be very exciting to make this work in clinics where a test for tuberculosis is desperately needed. The next stage will be to use the biomarkers we have identified to develop a cheap, accurate and rapid diagnostic test that can be used easily and quickly out in the field."

The research – by Delmiro Fernandez-Reyes of the division of parasitology at the Medical Research Council's National Institute for Medical Research (NIMR) in London, with Dan Agranoff, also of St. George's Hospital, and Krishna and their colleagues – is published in Sept. 16 issue of The Lancet. The title of the paper is "Identification of diagnostic markers for tuberculosis by proteomic fingerprinting of serum."

The paper describes how the team has been able to identify a complex signature of biomarkers, such as proteins and enzymes, in the serum of people who have tuberculosis. They did that using a type of mass spectrometer called a surface-enhanced laser desorption and ionization time-of-flight spectrometer SELDI).

Tuberculosis is often diagnosed by examination of sputum using a microscope, a method that is accurate in only 40% to 60% of cases. Culturing sputum for presence of Mycobacterium tuberculosis is a more reliable method of diagnosis but can take up to 6 weeks to give a result.

Clinicians throughout the world would therefore welcome a reliable test that could give immediate results in order to start treatment immediately.

Krishna, Fernandez-Reyes and their colleagues decided to find out if they could apply the concept of "proteomic fingerprinting" to assist in the development of new tests for tuberculosis. The idea is that certain diseases will cause unique and distinctive configurations of proteins to circulate in the blood.

The researchers compared the mass spectrometry "signature" of serum from 179 patients known to have tuberculosis with that of serum from 170 controls. Many of the controls had inflammatory conditions with clinical features that can overlap with those of tuberculosis.

Analysis of the complex patterns generated, coupled with statistical methods, allowed the team to identify a specific signature associated with tuberculosis infection. The use of the signature made it possible to distinguish between serum from people with tuberculosis and that from controls with 94 percent accuracy. The sensitivity of the test was 93.5 percent, and the specificity was 94.9 percent.

Further study made it possible to identify some of the proteins responsible for some parts of the signature.

Writing in The Lancet, the authors said: "Although SELDI technology can provide a diagnostic test for tuberculosis that makes no previous assumptions about the identities of proteins constituting an informative signature, cost and complexity preclude its general use. We therefore identified two of the 20 most discriminatory proteins to demonstrate the possibility of implementing more conventional diagnostic assays that are adaptable for field use."

Fernandez-Reyes said: "Our work opens the door to further research into translating these findings to fast and reliable methods of detecting active tuberculosis infection that could have a major impact in global health. We currently apply similar approaches to malaria diagnosis. We are increasing the number of biomarkers selected from the signature to improve the accuracy of the rapid test."

AD market demand set to triple

An aging population and improved rates of diagnosis will be the main drivers of the European Alzheimer's disease (AD) therapeutics market, according to a new report from Frost & Sullivan (F&S; London). The high levels of unmet patient need, combined with increasing patient awareness, are set to further expand market revenues, it said.

F&S puts Europe's Alzheimer's disease therapeutics market earnings at $1.39 billion in 2005, estimating that this sector will balloon to $3.75 billion in 2012.

"The key reason for positive growth trends in the market are high prevalence of AD in the elderly, coupled with increasing disease awareness amongst patients and physicians leading to a spurt in diagnosis rates," said Sumanth Kambhammettu, F&S research analyst. "With no existing effective therapies in the market, a variety of research approaches are on trial for the elusive wonder drug that can halt, slow or stop the progression of the disease."

Disease awareness campaigns and physician training will further boost diagnosis rates and promote overall expansion. Moreover, strategic alliances and competitive benchmarking will be catalysts for success, he said.

Market barriers he pointed to include reimbursement, competition from parallel imports and lower-priced generics. Spiralling healthcare costs in most European nations have resulted in stringent cost containment measures.

"The National Institute of Clinical Excellence's recent recommendations on Alzheimer's therapeutics in the United Kingdom have garnered all-round criticism," said Kambhammettu. "However, with several European countries also likely to demand greater evidence regarding clinical advantages and cost-benefit studies, there is significant pressure on market participants to, on the one hand, develop genuinely innovative drugs and on the other, price these products competitively."

Ibis T5000 biosensor introduced

At the 9th International Conference in Genomics and Proteomics of Human Pathogens in London, Bruker Daltonics (Billerica, Massachusetts) and Isis Pharmaceuticals (Carlsbad, California) reported European introduction of the Ibis T5000 biosensor system for the identification and characterization of microorganisms.

The Ibis T5000 system is an automated biosensor for healthcare research, enabling the analysis of viruses, bacteria, and fungi without the need for microbial culturing or genome sequencing steps. The Ibis T5000 relies on technology and applications developed by Ibis Biosciences, a division of Isis, incorporating Bruker Daltonics' micrOTOF ESI TOF mass spectrometer.

Following the report of a manufacturing/distribution agreement between Isis and Bruker earlier this year, the companies have taken step towards commercialization of the Ibis T5000 biosensor system by entering the European markets. Ready-to-use consumable assay kits will be available for applications such as pan-influenza surveillance and detection of sources of hospital-associated infections, including methicillin-resistant Staph. aureus (MRSA) strains.

Applications will also enable in-depth characterization of bacterial strain types, antibiotic resistance profiles and virulence markers. The Ibis T5000 is currently designated for Research Use Only.

Michael Treble, president of the Ibis Biosciences division and vice president of Isis, said that the Ibis T5000 biosensor "has the potential to revolutionize infectious microorganism detection. And we're especially pleased that our partner, Bruker Daltonics, will be manufacturing, installing and servicing the Ibis T5000 instruments."

Wolfgang Pusch, assistant vice president for clinical research solutions at Bruker, said: "The Ibis T5000 biosensor system analyzes the DNA of infectious disease microorganisms, and is an ideal complement to Bruker Daltonics' existing MALDI BioTyper platform for microorganism identification based on protein signatures. With the Ibis T5000 we further expand the scope of our products in microbiology."

Isis says that it commercialized the world's first antisense drug and that it has 15 drugs in development.

Bruker BioSciences is the parent company of Bruker AXS Bruker Daltonics and Bruker Optics.