"Disease Fingerprints” Identifies Common Infections in Children

Traditionally, investigators have looked for clues to an infection by tracking down the virus or bacteria causing it. But that does not always work because the bacteria or virus may not be present in the blood or other easily accessible area.
Scientists at University of Texas (UT) Southwestern, Children's Medical Center Dallas (TX, USA) and the Baylor Institute for Immunology Research came up with a different approach: Analyzing the telltale fingerprints a disease leaves behind on cells involved in the immune response, and using that information to get a composite sketch of the infectious agent.
We are genetically programmed to respond differently to different infections. We have developed the tools to understand that, said Dr. Octavio Ramilo, professor of pediatrics at UT Southwestern and lead author of a study appearing in the March 2007 edition of the journal Blood. Infectious diseases are the number one cause of death in the world. So we hope this eventually can be used not only to diagnose, but also to understand the prognosis and how the body is responding to therapy, he added.
Different viruses and bacteria trigger the activation of very specific genes that code for proteins called receptors in leukocytes, the white blood cells that help the body fight infections. Scientists surmised that if they looked at the leukocytes, they could detect the specific pattern of receptors--similar to a disease fingerprint--and be able to identify which infection was present. The process identifying such biosignatures is called gene expression profiling, which is done using microarray analysis.
RNA was extracted from a drop of blood and placed on a special gene chip called a microarray, which contains probes for the whole human genome and measures which genes are turned on or off.
Gene expression patterns were examined in leukocytes from 29 children known to have one of four common infections: flu (influenza A); staph (Staphylococcus aureus); strep (Streptococcus pneumoniae); or E coli (Escherichia coli). Thirty-five genes were analyzed that help distinguish infections and identified infectious agents with better-than-average success rates. Doctors were able to distinguish between the influenza, E coli, and strep infections in 95% of cases. A different set of genes distinguished E coli from staph infections with 85% accuracy. Further investigation demonstrated clear distinction between viral and bacterial pneumonias.
The next step will be to study whether the microarray analysis can be applied in a more challenging clinical setting, such as an emergency room (ER). "When a child comes in with a fever to the ER, we want to see if we can predict who just has a virus and can go home, and who has to be admitted and put into the intensive care unit and treated with antibiotics. That's our goal, said Dr. Ramilo. This is just the first step. But it establishes a basis for us to do that.
Pediatricians understand that this could change the way we do things, said Dr. Ramilo. It could also prove useful for identifying previously unknown illnesses or biologic weapons. Even if we don't know which pathogen it is, we still can tell which family or which group it's in, so if someone engineers a virus that has never been seen, we will have hints that it's close to something that is known, he said. Further studies may eventually help doctors track the progression of a disease and help assess the risks for complications.


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