False-negative Results for Lyme disease
False-negative results for Lyme disease tests can occur, but their frequency varies based on several factors. False negatives could happen in around 20-30% of cases, especially in the early stages of infection.
Early Stage: During the first few weeks after infection, the body's immune response may not have produced detectable levels of antibodies yet, leading to false negatives.
Test Type: The standard two-tier testing approach (ELISA followed by Western blot) has varying sensitivity and specificity, affecting the likelihood of false negatives. 3.
Test Quality: Variations in test quality and laboratory procedures can impact accuracy.
References:
False Negative
Hofmann H. Lyme borreliosis--problems of serological diagnosis
. Infection. 1996 Nov-Dec;24(6):470-2.
Abstract
As long as test procedures are not standardized, the serological results of IgM- and IgG-antibodies in Lyme borreliosis must be interpreted with caution and always in the context of clinical signs and symptoms. False negative results occur primarily during the first weeks of infection. In erythema migrans of less than 4 weeks' duration, 50% of patients are seronegative even with newly designed ELISAs. At this early stage of the infection the therapeutic decision has to be established on the basis of clinical criteria. Frequently IgM- and/or IgG-antibodies develop during antibiotic therapy. After 4 weeks' duration 80% of patients have elevated borrelial antibodies detectable with recently developed ELISAs. Positive and borderline results should be confirmed by Western blot. False positive results, particularly slightly elevated IgM, may occur in a variety of other diseases. Another problem is the persistence of Borrelia-specific IgM antibodies after therapy. Serological follow-up can only be carried out with the same methods in the same laboratory. Retreatment should be considered if IgM antibodies are increasing significantly and new symptoms are occurring.
False Positive
V Seriburi 1 , N Ndukwe, Z Chang, M E Cox, G P Wormser High frequency of false positive IgM immunoblots for Borrelia burgdorferi in clinical practice
. Clin Microbiol Infect. 2012 Dec;18(12):1236-40.
Abstract
Although it is known that two-tier serologic testing for Lyme disease may be associated with false positive results on the IgM immunoblot, this problem has never been systematically studied in the clinical practice setting. In a retrospective investigation of patients referred to the private adult practice of an Infectious Diseases physician for possible for Lyme disease, 50 of 182 patients (27.5%, 95% CI: 21.1-34.6) were found to have a false positive IgM immunoblot. 78.0% of these patients had received unnecessary antibiotic therapy. False positive results were not restricted to any single commercial laboratory. Research on alternative testing strategies that eliminate the IgM immunoblot entirely is warranted.
Overview
Jonas Bunikis 1 , Alan G Barbour. Laboratory testing for suspected Lyme disease. Med Clin North Am 2002 Mar;86(2):311-40.
Abstract: Detection of antibodies to B. burgdorferi is the most practical and common approach for laboratory work-up of a case of suspected Lyme disease. Serologic assays fall short of 100% sensitivity and specificity, however, and examination of a single specimen in time does not discriminate between previous and ongoing infection. Because of a background false positivity even among healthy populations of nonendemic regions, serologic testing is recommended only when there is at least a one in five chance, in the physician's estimation, that the patient has active Lyme disease. The pretest likelihood of the disease is determined by the physician in the context of epidemiologic and clinical facts of the case. This estimate can serve to reassure patients who are at low risk of B. burgdorferi infection but are seeking a Lyme test for complaints of a more nonspecific nature. Although new subunit serologic assays based on recombinant proteins are becoming available commercially, the longstanding two-test approach, in which a positive or indeterminate result with a standardized, sensitive ELISA test is followed by verification with a more specific Western blot assay, still provides the physician with a reasonably accurate and reliable assessment of the presence of antibodies to B. burgdorferi. More recent challenges for serologic testing are seropositivity in the population as the result of immunization with the Lyme disease vaccine and the emergence of new Borrelia species that cause Lyme disease-like illnesses.