On March 16, 2007, the US Food and Drug Administration approved a laboratory test that quickly detects the most common type of viral meningitis in the US. Just hours after symptoms develop, the Xpert EV Test can identify an enteroviral (EV) infection, the cause of about 90% of viral meningitis cases. At present, such rapid testing for the detection of enterovirus is performed by tests that have been validated by individual laboratories. Currently, meningitis cases are diagnosed by analyzing cerebrospinal fluid (CSF) for cell count and types of cells present (differential), protein, glucose and by examining and culturing the CSF for bacteria. Results from the Xpert EV test when used in combination with these other diagnostic tests will help to distinguish bacterial from viral meningitis.

Determining whether the cause of meningitis is viral rather than bacterial helps physicians quickly pursue the right course of treatment and relieves some of the anxiety for patients and their families. A person with a viral infection will not need the strong antibiotics used to treat bacterial meningitis, a severe and potentially life-threatening condition. If the viral infection is mild, the person also may avoid hospitalization and unnecessary treatment.

When bacteria have infected the CSF surrounding the spinal cord and brain, rapid administration of antibiotics is required. The bacterial infection can lead to irreversible brain damage, hearing loss, and even death. Bacterial meningitis can be deadly in as little as two days, but confirming that the infection is or is not bacterial can take two to three days or even longer. Some of the diagnostics take up to a week. The new test provides a valuable answer for planning appropriate treatment.

A Starting Point in Rapid Testing
The new test can detect enterovirus RNA in the cerebrospinal fluid in 2.5 hours. The test - a molecular analysis using a reverse transcription–polymerase chain reaction - is both highly sensitive (96.3%) and specific (97.2%). However, since bacterial meningitis can have serious consequences and cannot afford to be misdiagnosed, the physician still must order a variety of other diagnostic tests. The Xpert EV test, like other rapid molecular tests, does not definitively rule out other causes of meningitis, including bacterial, mycobacteria, other viruses, and fungus, notes the manufacturer. In addition to conducting additional tests on the CSF (see below), tests are done on samples of blood, urine, and other body sites (e.g., throat culture). Looking at brain waves via an electroencephalogram (EEG) and computer-generated images using computed tomography (CT) or magnetic resonance imaging (MRI) are also typical.

Diagnosing Meningitis
The following tests of cerebrospinal fluid are typically used when meningitis is suspected:

CSF Gram stain

CSF bacterial culture

CSF glucose

CSF blood glucose ratio

CSF total protein concentration

CSF leukocyte (white blood cell) count and differential

The new test may be of particular value in emergency rooms where most cases of enteroviral meningitis are seen. Many hospitals do not have a molecular pathology lab open around the clock and can use this test, explains a director of pediatric infectious diseases for a children’s hospital interviewed by the physician news service MedPageToday. This automated test, which must be run on a multipurpose instrument sold by the test maker, offers the convenience of getting results 24 hours a day, 7 days a week. Patients and their healthcare providers can know the results while they are still in the emergency room. However, since the test was just recently approved by the FDA, relatively few laboratories have the equipment and the test may not be widely available yet.

The test’s accuracy was confirmed in a study using 255 patient samples from six medical institutions, notes the FDA. In the trial, 96% of those receiving positive results from the test had viral meningitis and 97% of those testing negative did not have viral meningitis. The FDA has cleared the test for marketing as an in vitro diagnostic.

Sources
S1
Cepheid Xpert EV (product brochure). On the Internet: http://www.cepheid.com/Sites/cepheid/content.cfm?id=252. Accessed 10 Apr 2007.

S2
Healthcare Sales and Marketing Network News (source Cepheid). 19 March 2007. Cepheid’s Xpert EV test for enteroviral meningitis, run on the GeneXpert platform, receives FDA clearance. On the Internet: http://salesandmarketingnetwork.com/news_release.php?ID=2017057. Accessed 10 Apr 2007.

S3
Lusky K. July 2004. Not Mayo? No matter—small labs go molecular. CAP Today. On the Internet: http://www.cap.org/apps/docs/cap_today/feature_stories/0704MolecLab.html. Accessed 10 Apr 2007.

S4
National Institute of Neurological Disorders and Stroke. Apr 2004 (updated 19 Mar 2007). Meningitis and Encephalitis Fact Sheet. NIH Pub. No. 04-4840. On the Internet: http://www.ninds.nih.gov/disorders/encephalitis_meningitis. Accessed 10 Apr 2007.

S5
Peck P. 19 Mar 2007. FDA okays quicker viral meningitis test. On the Internet: http://www.medpagetoday.com/tbprint.cfm?tbid=5276&topicid=190. Accessed 10 Apr 2007.

S6
US Food and Drug Administration. 16 Mar 2007. FDA clears rapid test for meningitis (press release). On the Internet: http://www.fda.gov/vvs/topics/NEWS/2007/NEW01588.html. Accessed 2 Apr 2007.