January 12, 2018

Tick-Borne Disease Lab Tests

Ticks can transmit a wide variety of diseases to humans, and determining which one a patient may have can be difficult for doctors, particularly if no distinguishing symptoms are present.

Certain clues can sometimes help narrow down options—for example, knowing if a patient has recently spent time in a region where a specific tick-borne disease is prevalent. Also, knowing the species of the tick that has bitten a patient can help isolate the types of diseases it can transmit. However, many patients that are ultimately diagnosed with one or more tick-borne diseases don’t even recall being bitten by a tick. Plus, early symptoms of many tick-borne diseases are often very similar, while others, such as Lyme disease and Tick-borne Relapsing Fever, can also present symptoms that mimic numerous other illnesses that range from the flu to ALS, Alzheimer’s disease, MS and rheumatoid arthritis.

As a result of these challenges, lab tests are often essential in determining or confirming diagnosis of a tick-borne illness. The following article highlights some potential tests your doctor may prescribe if he or she suspects one or more of the following tick-borne illness.

The most widely known testing protocol for Lyme disease involves a two-tier process aimed at identifying specific antibodies in a patient’s blood that typically develop to fight off the Lyme disease bacteria (Borrelia). Established by the Centers for Disease Control and Prevention (CDC) in 1994, this process comprises the following steps:

    • Tier One:1https://www.cdc.gov/lyme/diagnosistesting/labtest/twostep/eia/index.htmlA patient’s blood sample is tested using one of two testing methods: the enzyme immunoassay (EIA) or immunofluorescence assay (IFA) test. Of these two options, the EIA test is used by most diagnostic labs; of the various types of EIA tests that exist, only two are validated and FDA approved: the ELISA (enzyme-linked immunosorbent assay) and the ELFA (enzyme-linked fluorescent immunoassay), with the ELISA test appearing to be the most commonly used.
      • What It Measures: The ELISA test is designed to detect and measure specific antibodies within the blood that indicate the presence of the Lyme disease bacteria, B. burgdorferi.
      • Possible Concerns:
        • False Positives: The EIA test is designed to be highly sensitive, so that nearly everyone with Lyme disease will test positive. However, the test can also produce positive results if a patient has various other diseases-including syphilis, autoimmune disorders such as lupus, Tick-borne Relapsing Fever (TBRF) and Anaplasmosis.
        • False Negatives: Another concern with this type of test is that antibodies may not yet have had time to develop if the test is conducted too soon following the initial tick bite. False negatives can also result in patients due to coinfection, another illness or in immunocompromised patients.
    • Tier Two: If the first test is negative, the CDC recommends that no further tests be conducted for Lyme disease. However, if the test is positive or has indeterminate results, the CDC recommends that a second test be performed to confirm diagnosis. Most labs use the Western blot test for this second step.
      • What It Measures:The Western blot is designed to detect specific classes of antibodies that target different molecules, or antigens, that are part of the B. burgdorferi bacteria. The specific antibodies it identifies are IgM and IgG. The test produces a series of “bands” that look similar to a bar code. Each band represents antibodies that align to a different component of the Lyme disease bacterium. A combination of specific bands must be present to indicate a positive result for Lyme disease.
      • Possible Concerns:IgM antibodies appear early in the disease, making it possible to identify Lyme disease within the first few weeks of infection. However, relying on the presence of IgM antibodies alone can result in false-positive test results due to cross reactivity of viral antibodies to some of the Borrelia antigens. In contrast, the presence of IgG antibodies can be a more reliable; however, it can take up to six weeks to develop a high enough titer, or concentration of antibodies, for the test to be positive.

According to the CDC, the ELISA and the Western blot tests must both be positive for a patient to be considered Lyme disease-positive. However, both of these tests are indirect methods of diagnosis-meaning, they do not detect the actual Lyme disease bacterium. Instead, they look for reactions within the patient’s body to the presence of that pathogen. As noted above, timing and other factors could influence a patient’s ability to produce these antibodies. What’s more, recent studies reveal that many of the test kits are only designed to identify a few species of B. burgdorferi , which means infections caused by more recently discovered Borrelia species such as B. mayonii, could be missed. In-fact according to a recent report published in January 2017, the overall sensitivity of the FDA-approved two-tier test for B. burgdorferi was only 53.7 percent.2“Analysis Shows Standalone Lyme Testing is Highly Inaccurate,” LymeSci, Jan. 13, 2017. https://www.lymedisease.org/lyme-sci-testing/

Newer, more precise and advanced tests are available through a few laboratories certified by the Clinical Laboratory Improvement Amendments (CLIA). These tests do not require FDA clearance. This include newly developed Lyme immunoblots that detect all the common species of B. burgdorferi sensu lato (including B. mayonii) in the United States and Europe. Patients may wish to discuss these options with their doctors to determine if the potential for earlier detection and greater accuracy outweighs potentially higher out-of-pocket costs. These tests include, but are not limited to, the following:

    • Polymerase Chain Reaction (PCR) Assays: These tests are used to detect the actual presence of the Lyme-disease bacteria by amplifying the specific DNA sequence of the pathogen within the blood, urine, cerebral spinal fluid (CSF) or tissue samples. A Lyme multiplex PCR assay can be used to amplify several DNA sequences, or genes, that are specific to the Borrelia bacteria that cause Lyme disease. This multipronged approach can save time and cost for patients while enhancing result specificity and accuracy.
    • Immunoblot Assays: More sensitive and specific immunoblot tests can help clinicians identify disease earlier and more reliably. These qualitative tests allow clinicians to visualize antibodies on a membrane strip, which can lead to earlier disease detection and diagnosis. IGeneX recently developed more-advanced and -inclusive Lyme ImmunoBlot assays that test for most species of B. burgdorferi. The specificity of these new tests is 98 percent for IgM antibodies and 98.7 percent for IgG antibodies, both of which are significantly higher than the FDA-approved Western blot test. They can also detect antibodies for a broader range of bacteria species, including both North American and European strains, as well as the newly discovered B. mayonii. Higher test sensitivity can also lead to earlier detection of specific antibodies. The IGeneX ImmunoBlot IgM, for example, can reveal the presence of IgM antibodies as early as a week after a tick bite and will continue to remain positive for eight weeks or longer after a bite.
    • T-Cell Test: When a patient has a Borrelia infection, the body will naturally develop both B-cell-mediated humoral immunity and T-cell immunity. Specific T-cell based tests have recently been developed, including the Lyme IGXSpot, to detect antigen-specific T cell response to B. burgdorferi. These tests are very useful in detecting the disease very early on when antibodies have not yet developed as well as when the levels are very low, which may occur in later-stage infections.
    • Culture Test: A culture confirmation test is not used widely because it is difficult to culture Borrelia from blood samples. Only one laboratory offers Borrelia culture confirmation test.
Symptoms of TBRF and Lyme disease are often very similar, therefore more comprehensive tests that can detect and differentiate the two diseases are critical.

The TBRF IgM and IgG Immunoblot tests offered by IGeneX are designed to detect antibodies to specific antigens of TBRF Borrelia that are commonly found in the United States and Europe-specifically, B. hermsii, B. miyamotoi, B. turicatae, and B. coriaceae.

Additional tests that are currently available to diagnose TBRF include PCR tests for detecting Relapsing Fever Borrelia, including B. miyamotoi, DNA.

Babesiosis is a parasitic disease that is similar to malaria and is caused by Babesia. Babesia infect red blood cells. In the United States, the most common species of Babesia that infect humans are Babesia microti and B. duncani. Infections of B. microti have been reported throughout the United States, whereas B. duncani infections occur primarily on the West Coast.

Although microscopy of giemsa stained blood smear is considered the gold standard of diagnostic tests for malaria and babesia, it is not used very often because it is difficult to detect the parasites in the smear. Therefore, antibody detection tests such as the indirect fluorescent antibody test (IFA) are generally used for diagnosis.

All patients suspected of babesiosis should be tested by B. microti IFA tests. In addition, if a patient has been exposed to infected ticks on the West Coast, he or she should also be tested by B. duncani IFA test. Other advanced tests to consider include a PCR test, to detect Babesia-specific DNA in whole blood, and Babesia fluorescent in-situ hybridization (FISH) assay, which enables the qualitative detection of ribosomal RNA in any and all Babesia parasites in a patient’s blood smear.

Bartonellosis is a tick-borne disease caused by Bartonella bacteria. The disease can take different forms, depending on the strain of Bartonella bacteria. Cat-scratch disease, caused by B. henselae, is the most common.

Several advanced lab tests are currently available to diagnose Bartonella, including the Bartonella IFA, which can detect antibodies to B. henselae and B. quintana antigens in patient blood; Bartonella PCR, which can detect Bartonella-specific DNA and B. henselae-specific DNA in whole blood or spinal fluid; and the Bartonella FISH assay, which enables the qualitative detection of ribosomal RNA of the Bartonella in a blood sample. Bartonella culture tests used to confirm an infection from a patient’s blood sample are difficult to perform and therefore are not commonly used. Only one laboratory, in fact, offers a Bartonella culture confirmation test.

Ehrlichiosis is a bacterial infection of the white blood cells that is caused by the Ehrlichia. Five species of Ehrlichia can infect humans, although Ehrlichia chaffeensis and Ehrlichia ewingii are the most common.

Some basic blood-test results can help support suspicions of Ehrlichiosis, including a low white-blood-cell count, a low platelet count, and abnormal liver function.3https://www.mayoclinic.org/diseases-conditions/ehrlichiosis/diagnosis-treatment/drc-20372147

More advanced lab tests that can provide more precise diagnosis of the disease include a PCR test to identify Ehrlichia-specific DNA, and IFA tests to detect antibodies to the Ehrlichia antigens in the blood.

Anaplasmosis, similar to Ehrlichiosis is caused by the bacterium Anaplasma phagocytophilum. Currently, an IFA test to detect antibodies to the A. phagocytophilum antigens in the blood and a PCR test to identify specific A. phagocytophilum DNA are most often used to diagnose this disease.
Rickettsiosis, which is caused by the bacteria of the genus Rickettsia, has two main branches: typhus and spotted fever. Within the spotted fever branch, Rocky Mountain spotted fever is the best known and most deadly form of rickettsiosis. Both IFA and PCR tests can be used to detect Rickettsia in patients.

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