By Jonathan Briggs
Clinical laboratories routinely identify pathogenic microorganisms and test them for susceptibility to drugs, but not every laboratory can quickly, easily, and efficiently perform any test at any time. Infectious disease can be especially tricky to diagnose because the bugs responsible are constantly mutating. It’s not unusual for a lab to come across something that defies immediate classification or is difficult to pin down. Lyme disease, nicknamed “the great imitator,” would certainly be counted among the more difficult diseases to diagnose.
In 1999, the Centers for Disease Control documented more than 16,000 cases of Lyme disease, which is caused by the spirochete Borrelia burgdorferi (Bb). The most common insect-borne infectious disease in North America, Lyme Disease is a significant public health concern.
Humans are infected with this bacterium via tick bites. Both the clinical and laboratory diagnosis of Lyme disease can be difficult. Although clinical presentation can include characteristic symptoms such as a bulls-eye rash, many symptoms are non-specific such as malaise, fever and joint pain. The incubation period can range from three to 30 days, and some patients are asymptomatic. Complicating things further still is the fact that although Bb often can be cultured from skin lesion samples (nearly 80 percent of the time), the procedure requires the use of modified Barbour-Stoenner-Kelly medium and extended culture observation.
Even molecular tests have problems pinpointing primary diagnosis of Lyme disease because they are not specific for active disease, not standardized and not sensitive enough. In addition, turnaround time on results is slow. That’s why CDC recommends that the primary diagnosis of Lyme disease be made clinically and then supported with a two-step serologic ELISA or IFA test followed by Western blot. Serologic tests are not used alone because antibodies to the bacteria can remain in the blood for years, even in patients who have been treated for the infection.
Unfortunately, the difficulty in diagnosing Lyme disease is a health concern because quick treatment of early-stage Lyme disease has been tied to good outcomes. As a defense, physicians in areas where the disease is endemic often treat patients prophylactically if they suspect infection. This protocol has led to a controversy because of the potential side effects from high-dose antibiotic chemotherapy and the high cost of such treatment. Fortunately, several new tests on the market are targeted at helping physicians and their patients out of this jam.
Just in time for Lyme season, an innovative Lyme disease test has been cleared by the Food & Drug Administration. Immunetics of Cambridge, Mass., recently launched its C6 B. burgdorferi (Lyme) ELISA kit which detects human antibodies specific to B. burgdorferi. The test, based on the C6 peptide, has been shown to dramatically reduce the number of false positive results, while increasing the sensitivity of Lyme disease detection in both early and late stages.
The test does not yield false positive results on the 300,000 to 400,000 individuals who have been vaccinated with the Lymerix vaccine (recombinant OspA vaccine against Lyme disease, manufactured by GlaxoSmithKline Biologicals). False positive results are a problem with many screening tests on the market. In addition, the C6 test detects infection in European strains of the Lyme disease pathogen. These advantages should help physicians diagnose and rule out the disease more quickly, with less re-testing.
Manufactured by Immunetics, the C6 B. burgdorferi (Lyme) ELISA antibody testing is now offered only by Specialty Laboratories in Santa Monica, Calif.
More difficult to diagnose than other infectious organisms
Specialty’s Lyme disease test is highly specific and effective early in the disease course. “Normally with IgG or an IgM, you can’t tell if the patient is really infected or how long ago the infection occurred. Although with an IgM you can tell a little bit better. Bb infection sometimes goes into a chronic persistent phase. It’s not like most bugs where you have an acute infection and the patient recovers and manages to clear the bug either by antibiotics or naturally. Bb tends to stay in the circulation which is why it’s more difficult to diagnose than other infectious organisms,” said Meeta Patnaik, M.D., a vice president of research and development at Specialty Labs.
“In contrast to other tests for Lyme disease, C6 is a peptide-based test that is specific to Lyme disease. C6 protein is only expressed in the active phase of the infection. If you see the C6, it means the organism is multiplying within the patient, so you have a bacteremia,” continued Patnaik.
First CLIA-waived Lyme tests hits the market
Given the importance of a swift diagnosis for Lyme disease patients, the recent announcement by Wampole Laboratories of Cranbury, N.J., that it had launched the first CLIA-waived test for Lyme disease was welcome news for the laboratory and physician community. The CLIA waiver allows for testing in doctors’ offices and point-of-care settings, which previously were not permitted to perform the test based on licensing requirement. “The major advantage of this test is the rapid results,” said Raymond Dattwyler, M.D., professor of medicine at SUNY Stony Brook, director of the Lyme Disease Center and chief of the Division of Allergy and Immunology. “With three to seven days for an ELISA and another three to seven for a confirmatory Western blot, it could take a week to two weeks for diagnosis,” he added. With results in 20 minutes, a faster diagnosis of Lyme disease can mean earlier antibiotic treatment and potentially better clinical outcomes for infected patients. As with all first-step Lyme tests, positive results must be confirmed with a Western blot performed in a clinical laboratory.
The Wampole PreVue B. burgdorferi Antibody Detection Assay is a single-use, rapid test for the qualitative presumptive (first step) detection of IgG and IgM antibodies to B. burgdorferi in whole blood (CLIA waived) or human serum. Test results are read at 20 minutes with some positive results appearing in less than two minutes. Total hands-on time is approximately one minute. The assay features unique recombinant antigens rather than the whole-cell B. burgdorferi preparations used in many laboratory tests. The Wampole assay demonstrated excellent performance in comparison to Western blot and an ELISA on a CDC Lyme disease stratified panel (95.2% agreement for Wampole PreVue versus 78.6% for Western blot and 85.7% for ELISA).
With Lyme disease endemic to the Northeast and large pockets of the Midwest and West Coast, the arrival of these rapid and highly sensitive diagnostic tests is good news for those fighting on the front lines against this insidious infectious “imitator” disease.
Jonathan Briggs is a freelance writer based on Tijeras, N.M.
