Federal health officials are investigating a laboratory test for West Nile virus (WNV) after the manufacturer recalled two lots in early October because of an increase in false-positives.
Inverness Medical, in Princeton, NJ, recalled two batches of the PanBio West Nile Virus kit, an immunoglobulin M capture enzyme-linked immunosorbent assay (IgM capture ELISA) test, on Oct. 8. In an Oct. 14 health advisory, the Centers for Disease Control and Prevention (CDC) announced that it had joined with FDA and state health departments to determine the extent of the problem.
The testing laboratories are working with the CDC and state and local health departments to notify hospitals and health care providers who submitted specimens that tested positive between July and September 2008 using the recalled kit. 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, according to the alert.
If the original specimen is not available, health departments will work with health care providers to decide if a new serum specimen should be obtained for further testing.
Of 1,108 total WVV reported to the CDC as of Oct. 14 of this year, 508 (46 percent) involved a neurological disease such as meningitis or encephalitis. An additional 561 patients (51 percent) were diagnosed with West Nile fever and the remaining patients had clinically unspecified symptoms. Twenty-two deaths have been reported this year. Last year there were 3,630 total cases reported to the CDC, including 124 fatalities.
The high proportion of neurological disease is attributed to surveillance reporting bias — serious cases are more likely to be reported than milder cases, the CDC noted. Population-based studies have indicated that less than 1 percent of patients infected by the virus, including asymptomatic cases, develop severe neuroinvasive disease.
Because the problem involved false-positives, and there is no treatment for WNV, the primary concern is the theoretical risk of misdiagnosis in patients with other infections for which treatment exists, such as herpes simplex, Kenneth L. Tyler, MD, the Reuler-Lewin Family Professor of Neurology at the University of Colorado at Denver and Health Sciences Center Division of Infectious Diseases, told Neurology Today in a telephone interview.
Although it is too late to conduct follow-up IgM [immunoglobulin M] antibody testing, concerned neurologists can order tests for West Nile IgG antibodies, he added. “IgM antibodies are transitory and are usually gone after two or three months, so these patients will now be IgM-negative, but they will have IgG antibodies if they have been exposed, indicating lifelong infection,” he explained.
The incident underscores the need for confirmative screening for patients with encephalitis and similar symptoms who test positive for West Nile and similar insect-borne diseases, Dr. Tyler said. “Problems like this remind us that diagnostic testing is never foolproof, and that inconsistent test results need further testing in a timely manner,” he said.
“Most doctors just check a box for a West Nile IgM antibody test, send a serum (or CSF) sample to a laboratory, and wait for the results to come back. Some hospitals have on-site facilities, but most use commercial labs. We're not usually aware of where the testing is done or what kits are being used, and there is a lot of variability in these kits. In this instance, only one batch was distributed in the US, so the impact was limited — but it is a reminder to all of us.”
ADVISORY ON FALSE-POSITIVES: WEST NILE VIRUS TESTING
- One testing lot (#07262) was distributed only in Canada, but the other (#08118) was distributed between July and September to four US laboratories, including ViroMed in Minnetonka, MN; Meritcare Health System, in Fargo, ND; the Pennsylvania Department of Health in Exton, PA; and Baylor University Medical Center in Dallas, TX.
- The CDC and the FDA will continue to monitor and evaluate any additional reports of false-positive tests that may have resulted from previous lots or other kits. No new lots of the PanBio assay kit have been released.
- Four West Nile virus (WNV) IgM ELISA kits are currently available in the US, each made by a different manufacturer. All are indicated for the “presumptive” diagnosis of WNV infection in patients with clinical symptoms of meningitis or encephalitis, and package inserts state that all positive results should be confirmed by additional testing.
- Most individuals who received a positive WNV diagnosis during the July-September.2008 period will be unaffected by the recall because only the two lots have recalled and there are four other commercially-available tests in wide use. Because there is no specific treatment for WNV, it is also unlikely that anyone would have received unnecessary treatment due to a false-positive result, according to the CDC.