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New Test: Detecting Lyme With “Footprints” of Bacteria

New study shows that detection of Borrelia prophages, equated as “footprints” of Borrelia, can be used to identify the bacteria due to the close correlation between them and the exact prophages found in each Borrelia host. Evidence presented in this study shows that prophages can be released outside the bacterial cell following stressors such as antibiotic use and are easier to detect than the bacteria itself. 

Testing for prophages rather than the bacteria in blood samples, when bacteria may not be present or present in very low numbers, yields a higher chance of detection. The study further states that this test can be developed not only as a diagnostic marker for accurate identification of Lyme disease, but also to differentiate Lyme disease from related infections and coinfections such as relapsing fever.  

Read full article here. 

Read more LDA articles on Lyme testing here.




HHS Request for Information (RFI): Diagnostic Testing for Lyme

As part of the LymeX public-private partnership between Health & Human Services (HHS) and the Cohen Foundation, HHS has published an RFI in the Federal Register, 2.11.21 that seeks information on the current state of the science and technology to accelerate “innovative solutions” for Lyme disease diagnosis.

The RFI contains a series of questions it encourages responders to answer including the types of technologies being developed, any emerging technologies that could be used to characterized stages of Lyme, what sample type optimum for a detection test, and challenges in clinical practice.

Responses need to be submitted no later than 5:00 PM ET, March 15, 2021.

See the Federal Register for all details:
Request for Information (RFI): Accelerating Innovation in Diagnostic Testing for Lyme Disease

See LDA website: HHS, Steven & Alexandra Cohen Foundation Announce “LymeX” Partnership




Current Lyme Disease Testing Problems

Elizabeth Maloney, MD, explains current Lyme disease testing issues, including the ELISA and Western Blot, sensitivity and specificity of the testing, and the problems associated with the two-tier testing recommended by the CDC. It begins with the general characteristics of diagnostic testing

The Summary states: “Serologic testing for Lyme is inaccurate. While the inadequate sensitivity of ELISA and Western blot tests is the primary problem, imprecision and the lack of clinical validity contribute to the poor performance of two-tier testing in clinical settings. Although the high specificity of the CDC two-tier strategy works well for epidemiologic purposes, the testing sequence reduces the overall sensitivity, thereby limiting its clinical effectiveness. While positive results on two-tier testing in an untreated patient who has symptoms of Lyme disease would confirm the clinical diagnosis (and it would be a mistake to label such results as “false positives”), negative results do not rule out Lyme disease.”

See full article by Elizabeth Maloney, MD here:  Applying Basic Concepts in Laboratory Testing to Serologic Testing for Lyme Disease

See International Lyme & Associated Diseases (ILADS) Controversy & Challenges Page – Issues with Diagnosis & Diagnostics

Lyme disease testing problems by Elizabeth Maloney, MD
ELISA Test: The original whole cell sonicate test




Study Shows Increase of Non-Lyme Tick-Borne Diseases

A study by Elizabeth Lee-Lewandrowski, PhD, MPH, et al, published in The American Journal of Clinical Pathology from the Department of Pathology, Massachusetts General Hospital and Harvard Medical School, evaluated trends in non-Lyme disease tick-borne disease (NLTBI) blood testing at Quest Diagnostics laboratory located in New Jersey.

The study took place over the course of seven years and included polymerase chain reaction (PCR) and serological tests. Testing data from Quest Diagnostics were analyzed both nationally and at the state level from 2010 through 2016.

The study showed that:

  • testing and positivity for most NLTBIs increased dramatically over the course of the study,
  • testing criteria was not as stringent as required for public health reporting, but the study showed that the number of positive cases generally exceeds those reported by the Centers for Disease Control and Prevention (CDC),
  • frequency of NLTBI in US is seasonal but testing activity and positive test results are present throughout all months of the year, and
  • positive results for NLTBI testing originated primarily from a limited number of states, signifying a geographic concentration and distribution.

The study shows a significant increase in the number of reported cases of many NLTBI from 2004 to 2016, including a 6.6-fold (875 to 5,750) increase in anaplasmosis and ehrlichiosis combined. It also uncovered a significant underreporting of Lyme disease and Q fever to the CDC. Since reporting for tick-borne illnesses (TBI) generally use the same reporting system as Lyme disease,  the researchers indicate the possibility that underreporting also occurs for other TBI.

The study outlines laboratory-developed tests (LDTs) that have not been cleared by the US Food and Drug Administration (FDA) but have been approved by Clinical Laboratory Improvement Amendments (CLIA) regulations.

Said LDA President Pat Smith, “Although the findings are not surprising to many in the Lyme community, it is imperative that we have this data to support the increases in many of these non-Lyme tick-borne diseases. Increased awareness will result in medical professionals being more likely to consider other tick-borne diseases in people who have been bitten by ticks.” 

See entire AJCP article here.




CDC Recommends New Lyme Disease Tests Cleared by FDA

The CDC formally recommends several new serologic assay testing methods recently cleared by the FDA. The Lyme disease serologic assays, which utilize a sensitive enzyme immunoassay (EIA) for detecting pathogens, were cleared by the FDA on July 29th, 2019 and have since been determined to be acceptable alternatives for the serologic diagnosis of Lyme disease by the CDC. Serologic assays that utilize EIA rather than western immunoblot assay in a two-test format can be used in place of the western immunoblot assay as the second tier of testing.

In 1994 the CDC and FDA met with several other government health organizations for the Second National Conference on Serologic Diagnosis of Lyme Disease. The consensus reached was a recommendation for a two-test methodology which uses an EIA or immunofluorescence assay as a first test, followed by a western immunoblot assay for specimens yielding positive or equivocal results (cdc.gov). At the time, it was determined that evaluation of any new serologic assays would include blind testing against a comprehensive challenge panel, and that new assays should only be recommended if their specificity, sensitivity, and precision equaled or surpassed the performance of tests used in the recommended two-test procedure (cdc.gov).

Clearance by FDA of the new Lyme disease assays indicates that test performance has been evaluated and is “substantially equivalent to or better than” a legally marketed predicate test (cdc.gov).

According to LDA President Pat Smith, “Although it has been the hope of the Lyme community to have a new Lyme test cleared, it was always with the proviso that new technology needed to be used in test development. With the current two-tier system, which was first implemented in 1994, a positive or equivocal ELISA test is followed by the Western blot. This method is considered to be about 50% accurate by many, although treating physicians feel the Western blot is perhaps the most significant element of the current Lyme testing protocol.”

“The new two-tier testing system for Lyme disease, the ZEUS ELISA, is now being offered as an alternative to the existing testing protocol. Because ZEUS lacks a Western blot and is not a new technology, it is difficult for many to fathom how this new paradigm, that has been cleared by the FDA as ‘substantially equivalent’ to the existing testing with 50% accuracy, will improve the diagnosis of Lyme disease.”

Click here to see the CDC’s recommendation of the new serologic assay testing.




Two-Tier Testing for Lyme Disease: How it Evolved

 

Dr. Kenneth Liegner, MD

Kenneth Liegner, MD

Internal & Critical Care Medicine, Private Practice, Pawling, NY; author, In the Crucible of Chronic Lyme Disease: Collected Writings & Associated Materials

The Two-tier method of testing is used in the Lyme Disease Surveillance Criteria developed and adopted by the Council of State & Territorial Epidemiologists and used by the Centers for Disease Control and Prevention (CDC).This entails a screening test (e.g., Lyme E.L.I.S.A. – Enzyme Linked Immuno-Sorbent Assay) in which a positive or borderline result is followed by a Western blot for confirmation.  This protocol was specifically intended strictly for epidemiologic purposes (e.g. to track numbers of cases in a given geographic region and to track the spread of the disease in to other geographic regions).

This type of schema was originally utilized with quite satisfactory results for the H.I.V./A.I.D.S. epidemic.  It worked well because the screening test was some 95% sensitive.

It is widely recognized that the screening test for Lyme disease is at best some 50% sensitive.  As a result, persons who may have Lyme disease are often missed since Western blot (which may show important clues or even conclusive evidence of infection) is not done, per CDC advice.  As a result, individuals may go months, years, or decades without diagnosis or treatment and may become progressively (and sometimes irreversibly) damaged.

Compounding the situation, many physicians, health plans, vertically integrated health care systems and insurers misuse the Two-tier Testing schema as the sole criterion for a diagnosis of Lyme disease, despite CDC’s ‘lip-service’ that the diagnosis of Lyme disease is a clinical diagnosis with supportive data from the laboratory.

The Two-tier Testing schema was brought forth as a result of the Second National Conference on Lyme disease testing under the auspices of the Association of State and Territorial Public Health Laboratory Directors (ASPHLD), the state health department, the National Committee for Clinical Laboratory Standards (NCCLS), Council of State & Territorial Epidemiologists (CSTE), CDC, NIH, and FDA in Dearborn, Michigan in 1995.  Ostensibly the result of a ‘consensus’, actually this was forced through against the objections of many of the scientists, physicians and laboratorians who had been convened there.  It was made to appear as though it had been a ‘consensus’ whereas this was not the case (1). No minority report was accepted.

Clinicians often mistakenly believe that a negative screening test for Lyme disease ‘rules out’ Lyme disease.  Due to the mischief that has resulted from this situation, the states of Virginia and Maryland have passed legislation requiring physicians to advise patients, in writing, that a negative screening test does NOT rule out Lyme disease.

Direct detection methods that do not depend on antibody methods have been developed for Lyme disease.  One methodology, PCR (polymerase chain reaction), is accepted widely for the diagnosis of virtually all infectious diseases, but inexplicably, its use for the diagnosis of Lyme disease by detecting its DNA, is officially discouraged by CDC for the clinical diagnosis of Lyme disease.  This method would allow for early diagnosis before diagnostic antibody levels can be mounted and also for the disease at any stage, including for persons who are seronegative.  Although the method is not as sensitive as one would like (due to the low density of the DNA of the Lyme organism in bodily fluids), it remains at present the only well validated method of direct detection that is readily available to clinicians and could be more widely utilized.

(1 )Conflicts of Interest in Lyme Disease: Laboratory Testing, Vaccination, and Treatment Guidelines. Special Report. Lyme Disease Association, Inc. 2001.




New Research & Testing, Lyme Book, $$ for Researchers Available, Awareness Activities

LDA NEWS & UPDATES 
March 2018
FDA Approves Tests to Screen Blood supply for Babesia
The U.S. Food and Drug Administration (FDA) has approved the first tests to screen human plasma and whole blood samples for the Babesia parasite species, Babesia Microti (B. Microti), the main species that causes infection in the United States.
DoD TBD Research Program Announces Funding Opportunities for Researchers
The Department of Defense Tick-Borne Disease Research Program (TBDRP) is announcing its anticipated funding opportunities for fiscal year 2018 for researchers. Since there is a current Continuing Resolution, the Defense Appropriations bill has not been passed yet, so funds have not been appropriated for the DoD TBDRP. This is a preannouncement to allow researchers time to plan ideas for submission to the anticipated FY18 funding opportunities.
Mary Beth Pfeiffer Releases Lyme Book
Announcing the publication Mary Beth Pfeiffer’s book – Lyme: The First Epidemic of Climate Change which documents the human contribution to the dangerous spread of Lyme disease to dozens of countries and multitudes of people. Pfeiffer is known for her dedicated coverage over the years with the Poughkeepsie Journal — covering Lyme, TBD’s and the decades of controversy that has left patients without insurance coverage and life saving treatment options.
New Publications from LDA-Funded Research
The LDA provided funding to Alfredo Angeles-Boza, University of Connecticut, whose work with colleagues translated into three new publications which provide information that could benefit Lyme patients.
May Lyme Disease Awareness Events
May is Lyme Disease Awareness Month! These events, which sometimes start in March, help educate the public and raise funds for Lyme research. Click our calendar icon below to view events hosted by LDA’s partners, members of LDAnet, LDA’s umbrella organization. Keep checking back for new events. Click below for two conferences, each supported by an education grant from the LDA: In April, the 4th Annual Midcoast Lyme Disease Support & Education Conference at the Augusta Civic Center (Maine); and in May, the Colorado Tick-Borne Disease Awareness Association – Lyme & Other Tick-Borne Diseases: 3rd Rocky Mountain Forum. LDA also provided an education grant for Lyme Society, Inc.1st Annual Lyme and Tick-Borne Disease Conference – in May, Staten Island, NY.
Post Your State Lyme Awareness Proclamations Here
Many states and counties have taken steps to raise awareness regarding Lyme and tick-borne diseases. Declaring “May Lyme Awareness Month” is one move to help remind people spring is here, ticks are out, prevention & proper education are your best tools to staying healthy.
Proclamations are issued by governors and resolutions are adopted by the legislature.
Click here to add a picture of your state or county proclamation/resolution so we can include it on our annual list.
888-366-6611 Toll Free Hot Line



FDA Approves Tests to Screen Blood Supply for Babesia

Scope2The U.S. Food and Drug Administration (FDA) has approved the first tests to screen human plasma and whole blood samples for the Babesia parasite species, Babesia Microti (B. Microti), the main species that causes infection in the United States. Babesia parasites are transmitted by Ixodes scapularis ticks, also known as blacklegged or deer ticks but can also be transmitted by transfusion of blood or blood components collected from an infected donor. These new tests will be performed on human donor samples, which includes volunteer donors of whole blood and blood components, as well as living organ and tissue donors.

The approval was granted to Oxford Immunotec, Inc. for the Imugen Babesia microti Arrayed Fluorescent Immunoassay (AFIA) to detect antibodies to B. Microti in human plasma samples, and the Imugen Babesia microti Nucleic Acid Test (NAT) to detect B. Microti DNA in human whole blood samples. Both tests can only be performed at the Norwood, Massachusetts facility of Oxford Immunotec, Inc.

Studies performed by the manufacturer and previous investigational use of Babesia donor testing in endemic areas have shown these tests are effective in screening donors for B. microti infection.

As noted in the FDA news release: “The U.S. Centers for Disease Control and Prevention (CDC) warns that for certain people, especially those with a weak immune system, it [B.microti infection/babesiosis] can be a severe, life-threatening disease and that while bloodborne transmission of babesiosis is thought to be uncommon, it is the most frequently reported transfusion-transmitted parasitic infection in the U.S. and remains an important concern.”

Click here for FDA News Release




Labs Develop New Tick-Borne Diseases Tests

Igenex Labs, Palo Alto, CA has announced the development of three new tests, two for Lyme disease and one for tick-borne relapsing fever (TBRF).

According to Igenex, the new Lyme ImmunoBlot IgM & IgG has better specificity compared to the traditional Western Blot, 98% for IgM and 98.7 for IgG, and is 90.9% sensitive with well-defined samples. It has better sensitivity because it is designed to detect antibodies to major B. burgdorferi sensu lato specific antigens from North America and European strains: B. burgdorferi B31, B. burgdorferi 297, B. californiensis, B. mayonii, B. afzelii, B. garinii, B. spielmanii, B. valaisiana.

The Lyme IGXSpot is an Enzyme-Linked ImmunoSpot (ELISPOT) assay that detects human T cells reactive to B. burgdorferi specific antigens in vitro. ELISPOT is a widely used method for detecting and monitoring cellular immune responses to specific antigens. It detects specific T-cell responses soon after B. burgdorferi infection, when antibodies to the organisms are not detectable or late in the disease, when the levels of antibodies are very low, so combined with Lyme ImmunoBlot tests, patient’s full spectrum of immune response to infection & disease stage is available. The Lab also notes it is especially useful to seronegative patients.

The TBRF ImmunoBlot is designed to detect antibodies to specific antigens of tick-borne relapsing fever Borrelia in human serum– antibodies to B. hermsii, B. miyamotoi, B. turicatae and B. coriaceae. Based on in-house studies, these blots detect antibodies to North American, European and Australian strains of TBRF Borrelia in patient serum samples. The specificity of the TBRF ImmunoBlot is 94% and 98% for IgM and IgG respectively, according to the lab.

Coppe Labs, Waukesha, WI has announced the development of commercial tests for Powassan virus, an emerging virus transmitted by the same deer tick that transmits Lyme disease bacteria. A direct PCR test and indirect serologic tests are now available. Doctors now have access to these tests for patients, especially those in known areas for Powassan exposure

This test is important because clinical research has shown that the Powassan virus can be transmitted to humans within 15 minutes of a tick-bite and can be fatal in 10% or more of cases. Those who survive can be left with debilitating neurologic conditions. There are currently no specific treatments for Powassan, palliative care is administered.

More details can be found on the IGeneX and Coppe Labs websites.




Emerging Tests for Lyme Disease

Published on August 14, 2017 (6th segment)
Panelists Peter L. Salgo, MD; Robert C. Bransfield, MD, DLFAPA; Leonard Sigal, MD; Samuel Shor, MD, FACP; and Patricia V. Smith discuss emerging laboratory tests for detecting Lyme disease and the ways in which these technologies may offer diagnostic improvements. Click here for transcript of the video on Contagion® website

Published on August 14, 2017 (6th segment)
Panelists Peter L. Salgo, MD; Robert C. Bransfield, MD, DLFAPA; Leonard Sigal, MD; Samuel Shor, MD, FACP; and Patricia V. Smith discuss emerging laboratory tests for detecting Lyme disease and the ways in which these technologies may offer diagnostic improvements.

Click here for transcript of the video on Contagion® website

Full list of interview segments