Measuring genomic response to infection leads to earlier, accurate diagnoses
Duke researchers are looking to genomic technologies – not the isolation of bacteria or viruses – to quickly detect and diagnose infectious diseases such as the flu and staph.
Two studies appearing online Jan. 9, 2013, both in the journal PLOS ONE, show how a pattern of genomic information among infected individuals can be used to accurately pinpoint the cause of infection.
"Traditional diagnostic tests for infectious diseases rely on detecting the specific illness-causing pathogens. So you only find what you're looking for," said Geoffrey Ginsburg, M.D., PhD, a senior author on both studies and director of genomic medicine at the Duke Institute for Genome Sciences & Policy and professor of medicine.
Identifying the culprit pathogen guides the selection of treatment for sick patients; however, these traditional tests for infectious diseases can take several days and have varying levels of accuracy.
"Given that humans already have robust systems that recognize and try to ward off infectious organisms, can we harness the systems' response to distinguish between pathogens?" Ginsburg asked.
The body's reaction to infection, or host response, can be measured using genome-wide technologies that analyze human genes responding to the infection. Scientists can use the resulting "genomic signatures" to classify and diagnose infectious diseases based on the host response, without needing to test for a specific pathogen. The approach is especially appealing for detecting influenza since a genomic signature could identify new flu strains, which emerge frequently but may not be detected with existing diagnostic tests.
"The 2009 H1N1 flu pandemic highlighted the limitations of traditional pathogen-based testing," said Christopher W. Woods, M.D., MPH, associate professor of medicine, pathology, and global health at Duke and the flu study's lead author. "A test that could identify individuals exposed to the flu before the onset of symptoms would be an important and useful tool for guiding treatment decisions, especially with limited antiviral medications."
Woods and his colleagues set out to develop a test using two strains of flu. They inoculated 41 participants with either the H1N1 or H3N2 virus, and analyzed their blood samples to gauge the host response using a variety of genome-wide technologies.
The host response for the two different strains was similar, and was combined into a single genomic signature dubbed the Influenza Factor. The Influenza Factor distinguished people as infected or uninfected with flu with 94 percent accuracy, and could be used to test for multiple strains.
In addition, researchers detected the Influenza Factor before participants fully developed flu symptoms, as early as 29 hours after exposure to the virus and approximately 40 hours before the development of peak symptoms.
An early flu diagnosis could have several far-reaching benefits. Sick individuals could make the decision to stay home and rest, potentially limiting the illness's severity and transmission. In addition, they could begin taking antiviral medications, which are most effective when taken early.
The researchers also tested the Influenza Factor in a real-world setting with naturally acquired disease: the Duke University Hospital emergency department. They analyzed blood samples in 36 patients with confirmed cases of H1N1 flu during the 2009 pandemic; the Influenza Factor distinguished between H1N1-infected and non-infected individuals with 92 percent accuracy.
In a second study using a similar approach, researchers at Duke found a genomic factor for diagnosing Staphylococcus aureus, or staph, a common bacterial infection. As with flu tests, conventional methods of diagnosing staph involve culturing for the specific pathogen, which leaves room for error and often takes too long.
"Our current bacterial identification techniques rely on isolating the organism by culture. Although time-tested, cultures are slow, on average taking several days," said study author Vance G. Fowler, M.D., MHS, professor of medicine and infectious disease specialist at Duke. "During this time, clinicians are forced to make educated guesses as to how to treat patients, often over-treating with a broad cocktail of powerful antibiotics.
"These antibiotics can breed resistance, and may also be costly and have side effects. Reducing the time to diagnosis, which would allow the use of more tailored antibiotics, would help doctors make better treatment decisions sooner."
Duke researchers studied mice infected with staph or E. coli bacteria to measure the host response to infection. A genomic signature, derived from an analysis of blood samples, distinguished staph-infected mice from those infected with E. coli and those uninfected with 95 percent accuracy.
Researchers then studied blood samples from adult patients with bacterial infections who came to the Duke University Hospital emergency department. Using the patients' gene expression, researchers differentiated those with staph from those with no infection with 97 percent accuracy. The results were also replicated in pediatric patients, with the genomic signature helping to accurately diagnose staph infections around 95 percent of the time.
"This study demonstrates that the host response to bacterial infection can be harnessed as a potential diagnostic strategy, reducing the time required to establish a diagnosis and avoiding using unnecessary antibiotics," said Fowler.
The long-term goal of this research is to develop new diagnostic tools that use host gene expression patterns to quickly identify a patient's infection.
"These studies demonstrate that analysis of genomic factors show promise for early detection and accurately diagnosing the flu and staph," said Ginsburg. "Additional work is underway to develop more practical means of using these tests in a clinical setting."
Journal reference: PLoS ONE
Provided by Duke University Medical Center
- Genomic signature in blood identifies underlying viral infection Aug 06, 2009 | not rated yet | 0
- Early test for a killer of the sickest Mar 03, 2010 | not rated yet | 0
- Researchers find wide gap in immune responses of people exposed to the flu Aug 25, 2011 | not rated yet | 0
- Blood signatures to diagnose infection Sep 07, 2010 | not rated yet | 0
- 2009 H1N1 pandemic flu more damaging to lungs, opens opportunities for bacterial infection Sep 19, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
Bacteria resistant to the antibiotic colistin are also commonly resistant to antimicrobial substances made by the human body, according to a study in mBio, the online open-access journal of the American Society for Microb ...
Diseases, Conditions, Syndromes 2 hours ago | 5 / 5 (1) | 0
(AP)—Federal investigators probing the hantavirus outbreak blamed for three deaths at Yosemite National Park recommend that design changes to tent cabins and other lodging run by private concessionaires first be reviewed ...
Diseases, Conditions, Syndromes 8 hours ago | not rated yet | 0
A new diagnostic test for a worm infection that can lead to severe enlargement and deformities of the legs and genitals is far more sensitive than the currently used test, according to results of a field ...
Diseases, Conditions, Syndromes 8 hours ago | not rated yet | 0 |
A Saudi man who had contracted the coronavirus has died, raising the death toll in the kingdom from the SARS-like virus to 16, the health ministry announced on Monday on its Internet website.
Diseases, Conditions, Syndromes 10 hours ago | not rated yet | 0
A new "telerehabilitation" approach lets physical therapists assess patients with low back pain (LBP) over the Internet, with good accuracy compared with face-to-face examinations, reports a study in the May 15 issue of Sp ...
Diseases, Conditions, Syndromes 10 hours ago | not rated yet | 0
Early-life exposure to traffic-related air pollution was significantly associated with higher hyperactivity scores at age 7, according to new research from the University of Cincinnati (UC) and Cincinnati Children's Hospital ...
2 hours ago | not rated yet | 0 |
(Medical Xpress)—A research team, led by Jeremy Barr, a biology post-doctoral fellow, unveils a new immune system that protects humans and animals from infection.
7 hours ago | 4.5 / 5 (11) | 3 |
New research suggests that a compound abundant in the Mediterranean diet takes away cancer cells' "superpower" to escape death. By altering a very specific step in gene regulation, this compound essentially re-educates cancer ...
10 hours ago | 4.8 / 5 (11) | 2 |
Researchers have pinpointed a catalytic trigger for the onset of Alzheimer's disease – when the fundamental structure of a protein molecule changes to cause a chain reaction that leads to the death of neurons ...
11 hours ago | 5 / 5 (3) | 0 |
Salamanders' immune systems are key to their remarkable ability to regrow limbs, and could also underpin their ability to regenerate spinal cords, brain tissue and even parts of their hearts, scientists have ...
11 hours ago | 4.8 / 5 (6) | 2 |
Turns out, that old "practice makes perfect" adage may be overblown. New research led by Michigan State University's Zach Hambrick finds that a copious amount of practice is not enough to explain why people ...
8 hours ago | 3.3 / 5 (10) | 0 |