Critical Needs and Gaps in Understanding Prevention, Amelioration, and Resolution of Lyme and Other Tick-Borne Diseases The Short-Term and Long-Term Outcomes: Workshop Report (2011) / Chapter Skim
Currently Skimming:
7 Diagnostics and Diagnosis
7 Diagnostics and Diagnosis
Pages 125-154
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 125... ...
Diagnostics provide a cluster of objective measures directed toward identifying the cause of a disease. After scientists discover the causative agent of an emerging infectious disease, such as Borrelia burgdorferi or Ehrlichia chaffeensis, they develop, evaluate, and refine diagnostic tests over time.
|
From page 126... ...
However, researchers are just beginning to understand the difference between immune responses to antigens expressed in vivo and antibodies detected using antigens from B burgdorferi cultured in vitro.
|
From page 127... ...
For example, the European Borrelia garinii is more neuroinvasive, which means that it is more often present in the cerebrospinal fluid, where it can be detected in culture. The second technique for directly detecting Borrelia in patients is PCR, which amplifies specific sequences of spirochete DNA in samples of skin, synovial fluid, or blood.
|
From page 128... ...
The IgM immunoblot should be used only within the first 4 weeks of illness, while the IgG immunoblot can be used at any stage in Lyme disease. If patients test positive on the ELISA but negative on the Western blot, they are considered not to have specific antibodies against B
|
From page 129... ...
Clinicians sometimes order tests on patients with a low probability of infection, making the results difficult to interpret. In the diagnostic laboratory, education and training are also important for laboratorians as individual interpretation of the test often results in over-reading of the Western blots, in particular IgM immunoblots.
|
From page 130... ...
More recently, great progress has been made following the development of PCR and other nucleic acid amplification techniques for detection of pathogens in blood and other tissues. Most types of diagnostic tests used to diagnose Lyme disease are also used to diagnose other tick-borne infections, including rickettsial diseases, ehrlichioses, and anaplasmosis.
|
From page 131... ...
As with the diagnostic tests for Borrelia burgdorferi, the presence of IgM antibodies can be detected 5 to 7 days after the onset of symptoms, but the specificity of these tests is low. They produce false positives as other bacterial, viral, and parasitic infections can cross-react with the antigens.
|
From page 132... ...
Promising preliminary results have been observed with rabbit and dog sera and a few human samples available for testing. In conclusion, Olano noted that despite advances in antigen-capturing systems, detection technologies, automation, and nucleic acid amplification techniques, commercially available tests for the diagnosis of human
|
From page 133... ...
. However, a more recent study using a combination of CD56 and CD16 surface markers in conjunction with CD3 markers showed that natural killer cell counts did not differ between postLyme disease patients and healthy controls or patients who had recovered from Lyme disease after treatment (Marques et al., 2009)
|
From page 134... ...
These conditions are frequently referred to as "central sensitivity" syndromes. Thus, to understand the persistent symptoms of post-treatment Lyme disease, there is a need to understand the commonalities between these symptoms and those associated with central sensitivity syndromes.
|
From page 135... ...
In these cases, it appears that augmentation of central nervous system pain processing accounts for the persistent experience of pain. Another common symptom in central sensitivity syndromes is fatigue, which is thought to have a peripheral or central origin.
|
From page 136... ...
Biomarker research in central sensitivity syndromes could be highly pertinent to patients with persistent symptoms after treatment for Lyme disease. A recent study showed a decrease in natural killer cell cytotoxicity, and three different measures of CD26 -- an antigen located on cellular surfaces associated with immune regulation -- accurately discriminated chronic fatigue syndrome patients from controls (Fletcher et al., 2010)
|
From page 137... ...
and flat diurnal variation (Crofford et al., 2004; Dedert et al., 2004; Weissbecker et al., 2006) were observed in people with central sensitivity syndromes.
|
From page 138... ...
The fact that cortisol levels are correlated with momentary pain in fibromyalgia patients also suggests that the pain may be causing the autonomic nervous system dysfunction, rather than vice versa. Finally, people with baseline hypo- or hyperactivity of these stress response systems may be more likely to develop central sensitivity syndromes after exposure to stressors, including even routine events such as cessation of exercise or restrictions on sleep.
|
From page 139... ...
In summary, research suggests that • Although depression is common among people with post-Lyme dis ease, it does not explain the symptoms nor predict which patients with active Borrelia burgdorferi infection will later develop post Lyme disease. These individuals could have a genetic vulnerability to central sensitivity syndromes, which might offer a productive approach to better identify those at risk.
|
From page 140... ...
Aguero-Rosenfeld noted that in very well-characterized Lyme disease patients, IgM positivity remained up to a year or more after a patient was well. She noted that IgM antibody-validated diagnostic criteria were restricted to acute Lyme disease in the first month of illness.
|
From page 141... ...
, the clinician cannot easily attribute the patient's symptoms to Lyme disease. A second difficulty arises in distinguishing the array of symptoms from those associated with other multisymptom illnesses such as chronic fatigue syndrome (CFS)
|
From page 142... ...
Brian A Fallon, M.D., M.P.H., Columbia University Medical Center and the New York State Psychiatric Institute Helping patients with chronic persistent symptoms requires understanding who the patient is, the chief complaint, the history of this person's disease, and the history of treatment.
|
From page 143... ...
Turning to the literature pertaining to patients with chronic persistent symptoms, Fallon noted a number of areas need additional research. A European study compared patients with neurologic Lyme disease to those with erythema migrans, 3 years later, and found that 50 percent of those with neuroborreliosis experienced persistent symptoms versus 16 percent of the EM patients (Vrethem et al., 2002)
|
From page 144... ...
Cerebrospinal fluid findings across four studies of patients with persistent symptoms following Lyme borreliosis showed elevated protein in 25.8 percent, 7.3 percent, and 12.1 percent of the patients, respectively (Klemper et al., 2001; Krupp et al., 2003; Fallon et al., 2008)
|
From page 145... ...
of patients with chronic, persistent symptoms had elevated levels of anti-neural antibodies, indicating there is an abnormally activated immunological process at work in some of these patients with chronic symptoms. A summary of the possible explanations for chronic, persistent symptoms in patients following treatment for Lyme disease includes: persistent infection in some patients; reinfection from a later tick bite; reactivation of a latent, dormant infection; widely distributed effects from a small amount of physiologically active but attenuated spirochetes; or post-infectious phenomena, such as spirochete-triggered immune abnormalities, neurotransmitter/receptor changes, or damage from prior infection.
|
From page 146... ...
. The physical presentation of ehrlichiosis has a large differential diagnosis, including a significant overlap with Rocky Mountain spotted fever (Buckingham et al., 2007)
|
From page 147... ...
The clinical challenge is compounded by the short incubation period of the TBDs. Antibody testing is not useful in the acute management of Rocky Mountain spotted fever or human monocytic ehrlichiosis.
|
From page 148... ...
Thirtynine percent of patients ultimately considered to have Lyme disease do not meet the Centers for Disease Control and Prevention (CDC) criteria, and approximately 40 percent had negative Lyme disease serology and an acute viral-like illness without objective findings.
|
From page 149... ...
This reinforces the challenges that clinicians face in the diagnosis and treatment of patients with chronic persistent symptoms following Lyme borreliosis. In treating such patients, it is important to ensure that a thorough history and physical exam are conducted and that they have received sufficiently long courses of the appropriate doses and types of antibiotics.
|
From page 150... ...
With respect to the experience and impact of Lyme disease and chronic persistent symptoms in children, Jacobs emphasized how difficult it is to have to tell concerned parents that there is simply no solid information about the long-term effects and impact of the disease on the child. A participant observed that it seems as if the numbers of children experiencing symptoms and being diagnosed with illnesses such as fibromyalgia or chronic fatigue syndrome have risen since the last generation and asked whether schools could be surveyed to obtain information on the school-age population and the kind of symptoms and difficulties they are experiencing.
|
From page 151... ...
Donta noted that there are changes in the severity of symptoms experienced by women not only with Lyme disease but also with various chronic conditions, such as chronic fatigue syndrome, as hormone levels fluctuate. In addition there is a gender difference in Lyme disease, perhaps related to the presence of estrogen and progesterone receptors in glial and neural cells.
|
From page 152... ...
developing and applying new technology for serological assays to close the gap between bench and bedside using microfluidic technology, automation, and nanotechnology to achieve accurate, fast, and inexpensive diagnostic tests; and (3) consensus building to establish criteria for clinical phases of disease in children and adults, possibly describing necessary and sufficient criteria for arriving at common nomenclature, such as in systemic lupus erythematosus, chronic fatigue syndrome, and fibromyalgia, among others.
|
From page 153... ...
Samples of whole blood and cerebrospinal fluid, tissue biopsies, and other specimens would allow scientists to validate the use of PCR for amplifying nucleic acids and to identify and validate novel methods of detecting tick-borne pathogens. The recently sequenced genomes of different strains of B
|
From page 154... ...
Good biomarkers for post-Lyme disease are not yet available. However, conceptualizing the disease as having roots in central nervous system dysfunction could help chart the way.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.