What is the concern that has been raised about West Nile virus (WNV) testing?
The Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), and state health departments are investigating an increase in false-positive test results obtained with a commercially-available West Nile virus immunoglobulin M capture enzyme-linked immunosorbent assay (WNV IgM capture ELISA). Inverness Medical (Princeton, NJ) has voluntarily recalled two lots of their PanBio WNV IgM capture ELISA kit. One lot (#07262) was only distributed in Canada. The other lot (#08118) was distributed from July-September 2008 to four laboratories in the United States. One of the laboratories that used the kit receives specimens from healthcare providers and hospitals throughout the country.
What is meant by a “false positive” WNV test?
A “false positive” is when an initial test suggests that a person does have a West Nile infection, but a more specific test (confirmatory test) indicates that the person does not actually have the infection. Confirmatory testing has always been recommended but is not always done.
How does “WNV testing” work?
Laboratory tests for West Nile virus look for the presence of specific antibodies produced by the body against the virus. This is different from looking for the presence of the virus itself. The virus may be present at only very low levels in the blood stream and only for a limited time.
Antibody testing is used for many infectious diseases. The most commonly used WNV laboratory test measures antibodies that are produced very early in the infected person. These antibodies, called IgM antibodies, can be measured in blood or cerebrospinal fluid (CSF), which is the fluid surrounding the brain and spinal cord.
What type of testing is available?
The FDA has cleared four commercially-available test kits, from different manufacturers, for detection of WNV IgM antibodies. These four kits are used in many commercial laboratories in the United States. According to the package inserts, each of these kits is indicated for use on serum to aid in the presumptive laboratory diagnosis of WNV infection in patients with clinical symptoms of meningitis or encephalitis. The package inserts also state that all positive results obtained with any of the commercially-available WNV test kits should be confirmed through additional testing at a state health department laboratory or CDC. Public health practitioners, healthcare providers and clinical laboratories are reminded to consider these factors when ordering WNV tests and interpreting the results.
In addition to commercially-available testing, WNV testing can be performed in most state health departments. Further testing is available at the Diagnostic and Reference Laboratory in the Arboviral Diseases Branch at CDC for specimens with discordant results or that require additional confirmation.
What is the scope of this problem with WNV testing?
Based on the investigation to date, this increase in false-positive results appears to be limited to the two lots of the PanBio kit that were used between July and September of this year. The test kits from the lots in question have been recalled by the manufacturer and should no longer be in use. In addition, no subsequent lots of this test kit have been released. However, CDC and FDA will continue to monitor and evaluate any additional reports of false-positive tests that may have resulted from previous lots or other kits.
What should a health care provider do if they received a positive WNV test result on a patient this summer (July-September 2008)?
Hospitals or healthcare providers who submitted specimens that tested positive between July and September 2008 using the recalled PanBio kit will be notified by the testing laboratories working in conjunction with the state and local health departments. If the original specimen is still available, it will be retested at a state public health laboratory or CDC using a different WNV IgM assay. Healthcare providers will be notified of the results. If the original specimen is not available, health departments will work with healthcare providers to decide if a new serum specimen should be obtained for WNV testing. For additional information on specimens affected by this commercial test recall, please contact your state health department.
What should a patient do if they received a WNV diagnosis this summer (July-September 2008)?
There are four commercially-available kits in use in the U.S., and only one is affected by this recall. Therefore, most people who received a positive WNV diagnosis will be unaffected by this recall. Health care providers will be notified if their patients tested positive with the recalled kit. If you are concerned about your positive test results you should contact your health care provider.
How will this problem with false-positive results affect people who were diagnosed with West Nile virus disease?
If a person had a false-positive test result for West Nile virus disease, this may have resulted in the incorrect diagnosis and failure to consider other possible causes of their illness.
There is no specific treatment for West Nile virus disease. So it is unlikely that people would have received unnecessary treatment due to these false-positive test results.
Patients with West Nile virus disease may experience prolonged symptoms. However, if a patient is still experiencing symptoms, additional evaluation and alternative diagnoses may need to be considered. These patients should work with their health care provider to determine if there may be another cause for their illness and if subsequent testing is warranted.
How will this problem with false-positive results affect West Nile human case reporting?
As the investigation proceeds, the provisional number of WNV disease cases reported to CDC will be adjusted as needed.