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The Trouble with Lyme Tests

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.

What To Do After a Tick Bite

Tick bites are common in New England.  In many cases, there is value in taking 200 mg of Doxycycline within 72 hours of discovering a tick on your body.  Here is a useful three minute video produced by the Centers for Disease Control that will answer most of your questions on this topic.

 

 

 

Tick-borne illness expert, Nantucket's Dr. Timothy Lepore demystifies Lyme disease.

Tick-borne illness expert Dr. Timothy Lepore demystifies Lyme disease.

 

This was a good article in Nantucket's "N" magazine (August 2019)

When it comes to island treasures, there is the Great Point Lighthouse, the Old Mill, the Nantucket Whaling Museum—and Dr. Timothy Lepore. An enduring icon on Nantucket, Lepore was the subject of a critically acclaimed book titled Island Practice and has earned a following on the island like no other doctor. Beyond Nantucket, Lepore has developed a national reputation for his expertise in Lyme disease and other tick-borne illnesses. Patients suffering from these diseases venture from all over the world to see him. N Magazine sat down with Lepore to help demystify the confusion around Lyme disease, how it is treated, how serious an illness it is and ways in which it could be managed or eradicated on Nantucket.

N MAGAZINE: What is Lyme disease?

LEPORE: Lyme disease is an infection with a spirochete [a type of bacterium] of which the vector is the tick and the reservoir [or carrier] is probably the white-footed mouse, deer mouse and vole. That’s what Lyme disease is. Now, Lyme disease has a series of several different stages.

Link to full article.

Dr, Lepore with giant Nantucket tick

How to Reduce Tick Rick

Ticks are wide-spread in the Northeast.

This helpful and informative brochure is on the Williams College website. 

 

 

Human Granulocytic Anaplasmosis (HGA)

This valuable reference is available Full Text.

Human Granulocytic Anaplasmosis
Johan S. Bakken, MD, PhD^a and J. Stephen Dumler, MD
^{Infect Dis Clin North Am. 2015 Jun; 29(2): 341–355.}

Human granulocytic anaplasmosis (HGA), a deer tick transmitted rickettsial infection caused by Anaplasma phagocytophilum, is a common cause of undifferentiated fever in the Northeast and Upper Midwest U.S. Patients are often initially diagnosed with a mild viral infection, and illness readily resolves in most cases. However, as many as 3% may develop life threatening complications and nearly 1% die from the infection. A history of tick bite and a high degree of clinical suspicion thus warrant consideration for doxycycline treatment in both adults and children, even in the absence of known tick bite, a negative blood film examination, or pending results of specific A. phagocytophilum diagnostic tests such as paired serology or PCR on acute phase blood. Antibody tests and titers should not be used to monitor active infection as detectable antibodies can remain present for years. Moreover, persistent infection has never been reported. While co-infections with Borrelia burgdorferi and Babesia microti occur, there is little evidence to suggest synergism of disease or a role for A. phagocytophilum in chronic illness. Preventive measures include avoiding tick-infested areas, use of tick repellents, and careful searches of skin to remove attached ticks; no vaccine is available.

 

Baffling Borrelia

Bullying Borrelia: When the Culture of Science is Under Attack
Paul G. Auwaerter, MD (by invitation) and Michael T. Melia, MD
Trans Am Clin Climatol Assoc. 2012; 123: 79–90.

Full Text.  PubMed Central

Although Lyme disease responds to short courses of antibiotics, tick-borne Borrelia burgdorferi has been advanced by some as a frequent explanation for medically unexplained symptoms such as continual fatigue, musculoskeletal pains, and subjective neurocognitive dysfunction. Often called “chronic Lyme disease” by adherents of this philosophy, it is loosely defined, and practitioners liberally prescribe nostrums, including prolonged antimicrobial therapies, in a belief that this eradicates suspected infection. Perhaps due to the lack of supportive data, proponents of this theory have developed their own meetings, literature, activist groups, and substantial internet activities to advance their views. Forces motivating this movement are explored, as are tactics used to advance non-scientific ideas that have included legal action and garnering legislative endorsement. While neither logical nor evidence-based, “chronic Lyme disease” harnesses corrosive energies that taint modern medicine and society.

Tick Talk

Recently, we found a tick on the shoulder of an 84 yo man who was being seen for an unrelated problem.  A picture was taken through a dermatoscope.

It is clear to me that tick identification is complicated.

There is a helpful video on Tick Identification produced by the University of Maine.  It may be helpful to send the tick to a state lab for definitive identification.  This 30 second video (also from the State of Maine) describes tick removal and where to send the bugger for identification.

With regards to the tick pictured above, I am not certain if this is a deer tick or a dog tick.   I will follow patient and share his office visit with his primary care physician.

Lyme Disease Foundation

"The best private organization-based site that can be recommended to patients for education on Lyme disease is that of the American Lyme Disease Foundation."*  This is a valuable resource for patients with Lyme Disease and also their health care providers.  Lyme Disease has become a controversial topic.  If you want to stick with "science" the ALDF is a good place to start.

*Quote taken from:

Clin Infect Dis. 2002 Aug 15;35(4):451-64. Epub 2002 Jul 19.

Effective retrieval of Lyme disease information on the Web.

Sood SK.

Pediatric Infectious Diseases, Schneider Children's Hospital at North Shore, Manhasset, NY, USA.

Abstract:

The spirochetal infection Lyme disease, although now usually easily diagnosed and treated, has acquired an aura of ambiguity for many laypersons and medical professionals. The existence of controversy makes it difficult for infectious diseases physicians and scientists to readily obtain accurate information on Lyme disease by casually browsing the World Wide Web. Informative and current Web sites on the diagnosis, epidemiology, treatment, and prevention of Lyme disease can be found on-line, as can clear images of its clinical variants and of ticks. There are a handful of on-line resources on the biology of Borrelia and ticks, which can be tapped by the research community. These Web sites are described in the present article.

Lyme Tick Geography

This important article which appeared on the NPR Blog "Shots" is worth reading.  Especially if you reside in the Northeast, the Mid-Atlantic states, the upper Midwest and other endemic areas:

"Tick Tally Reveals Lyme Disease Risk."

 

Babesiosis

"A potentially serious infection caused by tick bites has gained a foothold on the East Coast, particularly in the Lower Hudson Valley and in coastal areas of the Northeast.

The condition, called babesiosis, is a malariua-like illness that results from infection with Babesia microti, a parasite that lives in red blood cells and is carried by deer ticks. Though far less common than Lyme disease, babesiosis can be fatal, particularly in people with compromised immune systems.

So. In addition to Lyme Dissease, one can contract Ehrlichiosis and Babesiosis from tick bites.  The NT Times had a reasonably good introduction to babesiosis in the June 21 issue:  "Once Rare, Infestion Spreads By Tick Bites."  We will post something on Ehrlichiosis soon.

For more on Babesiosis see:  eMedicine.com (although you may need to register for a free account.