Analysis of serologic testing for diagnosis of LD

Topics with information and discussion about published studies related to Lyme disease and other tick-borne diseases.
Post Reply
RitaA
Posts: 2768
Joined: Thu 1 Jul 2010 8:33

Analysis of serologic testing for diagnosis of LD

Post by RitaA » Thu 6 Nov 2014 0:51

http://www.ncbi.nlm.nih.gov/pubmed/25351855
Curr Infect Dis Rep. 2014 Dec;16(12):450. doi: 10.1007/s11908-014-0450-9.

A concise critical analysis of serologic testing for the diagnosis of lyme disease.

DeBiasi RL.

Author information

Division of Pediatric Infectious Diseases, Children's National Health System, 111 Michigan Avenue, NW, West Wing 3.5, Suite 100, Washington, DC, 20010, USA

Abstract

Diagnostic testing for Lyme disease in the clinical setting primarily relies on assessment of serologic responses to infection, with the exception of the early localized phase of disease, in which the diagnosis must be made clinically, due to the recognized insensitivity of serologic testing at this phase of disease. For the diagnosis of early disseminated and late disease, the Centers for Disease Control and Prevention (CDC) recommends a two-tiered approach to testing consisting of initial IgM and IgG quantitative enzyme-linked immunosorbent assay (ELISA), followed by confirmation of all indeterminate or positive ELISA tests with separate IgG and IgM Western blots. This critical analysis addresses the sensitivity, specificity, and predictive value of serologic testing for Lyme disease in early localized, early disseminated, and late disease. Other testing modalities currently under evaluation are also discussed, including IgG vlsE C6 peptide ELISA, other two-tiered testing strategies, rapid diagnostics, and PCR. An understanding of the strengths and limitations of currently available testing for Lyme disease is critical for appropriate diagnosis.

PMID:
25351855
[PubMed]
If anyone reading this has access to the full article, even notes/highlights would be appreciated by the rest of us.

duncan
Posts: 1370
Joined: Wed 5 Sep 2012 18:48

Re: Analysis of serologic testing for diagnosis of LD

Post by duncan » Thu 6 Nov 2014 13:20

I second that request.

lou
Posts: 215
Joined: Fri 2 Nov 2007 0:41

Re: Analysis of serologic testing for diagnosis of LD

Post by lou » Thu 6 Nov 2014 18:19

When have we ever gotten an accurate report on lyme testing from any establishment author?

Here is a link. Scroll down to references list and click on it. You can see that Steere, Shapiro, and Wormser are cited most. That is a hint about the content of the rest of the article. So, seems fair to assume this is just more propaganda.

http://link.springer.com/article/10.100 ... 014-0450-9

duncan
Posts: 1370
Joined: Wed 5 Sep 2012 18:48

Re: Analysis of serologic testing for diagnosis of LD

Post by duncan » Thu 6 Nov 2014 18:29

Yes, and I noticed in her (DeBiasi's) vitae that she is an IDSA grant recipient. So, we are forwarned of potential bias. But I always like to get may hands on a good current compendium of diagnostics, and their characteristics. Maybe this will prove to be one. Maybe.

RitaA
Posts: 2768
Joined: Thu 1 Jul 2010 8:33

Re: Analysis of serologic testing for diagnosis of LD

Post by RitaA » Thu 6 Nov 2014 20:35

Hi folks,

I don't want to get my (or anyone else's) hopes up too high, however an article that Dr. DeBiasi co-authored in 2004 while working in the Department of Pediatrics (Division of Infectious Diseases and Neurology) at the University of Colorado Health Sciences Center has impressed me. Granted, I'm no infectious diseases expert or neuroscientist, so please do keep that in mind. ;)

http://www.ncbi.nlm.nih.gov/pubmed/15489354
Clin Microbiol Rev. 2004 Oct;17(4):903-25, table of contents.

Molecular methods for diagnosis of viral encephalitis.

Debiasi RL 1, Tyler KL.

Author information

1 Department of Pediatrics, Division of Infectious Diseases, University of Colorado Health Sciences Center, Box A036/B055, Denver, CO 80262, USA.

Abstract

Hundreds of viruses cause central nervous system (CNS) disease, including meningoencephalitis and postinfectious encephalomyelitis, in humans. The cerebrospinal fluid (CSF) is abnormal in >90% of cases; however, routine CSF studies only rarely lead to identification of a specific etiologic agent. Diagnosis of viral infections of the CNS has been revolutionized by the advent of new molecular diagnostic technologies to amplify viral nucleic acid from CSF, including PCR, nucleic acid sequence-based amplification, and branched-DNA assay. PCR is ideally suited for identifying fastidious organisms that may be difficult or impossible to culture and has been widely applied for detection of both DNA and RNA viruses in CSF. The technique can be performed rapidly and inexpensively and has become an integral component of diagnostic medical practice in the United States and other developed countries. In addition to its use for identification of etiologic agents of CNS disease in the clinical setting, PCR has also been used to quantitate viral load and monitor duration and adequacy of antiviral drug therapy. PCR has also been applied in the research setting to help discriminate active versus postinfectious immune-mediate [sic] disease, identify determinants of drug resistance, and investigate the etiology of neurologic disease of uncertain cause. This review discusses general principles of PCR and reverse transcription-PCR, including qualitative, quantitative, and multiplex techniques, with comment on issues of sensitivity, specificity, and positive and negative predictive values. The application of molecular diagnostic methods for diagnosis of specific infectious entities is reviewed in detail, including viruses for which PCR is of proven efficacy and is widely available, viruses for which PCR is less widely available or for which PCR has unproven sensitivity and specificity, and nonviral entities which can mimic viral CNS disease.

PMID:
15489354
[PubMed - indexed for MEDLINE]
PMCID:
PMC523566
Free PMC Article
The full article is here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC523566/

Although this article is primarily about viral central nervous disease, it contains a lot of information that I found rather interesting (although I admit to skimming over most of it). Since I wasn't initially able to cut and paste from the full article, please excuse any typos in the following snippets:
DISTINGUISHING ENCEPHALITIS FROM ENCEPHALOPATHY AND POSTINFECTIOIUS ENCEPHALITIS

Encephalitis versus Encephalopathy

From a neuropathological perspective, the cardinal difference between encephalitis and encephalopathy is the presence of inflammation. Patients with encephalopathy have focal or generalized dysfunction of neurons and supporting cells without inflammation and as a result are far less likely to have either fever or headache. The inflammatory response engendered by infection also typically results in both peripheral leukocytosis and CSF pleocytosis, both of which are absent in encephalopathy.

[snip]

Although encephalopathy usually results from non-infectious processes, it is important to recognize that some infectious agents induce CNS dysfunction in the absence of either direct invasion or induction of a postinfectious immune-mediated response. Viral culture and/or PCR is unlikely to be positive in cases of encephalopathy.

[snip]

GENERAL PRINCIPLES OF MOLECULAR DIAGNOSTIC METHODS AS APPLIED TO THE DIAGNOSIS OF CNS INFECTION

[snip]

Use of PCR in the Diagnosis of Infections Which Can Mimic Viral CNS Disease

[snip]

B. burgdorferi (Lyme disease)

Borrelia burgdorferi infection is associated with subacute and late CNS and peripheral nervous system complications, including cranial neuropathies, aseptic meningitis, and encephalitis. Serologic detection of intrathecal Lyme-specific IgM is routinely used as the diagnostic method of choice, but IgM may not be present at the time of clinical symptoms. Recently, the yield of PCR testing of CSF and urine specimens from 30 patients with neuroborreliosis was analyzed and compared to they [sic] yield obtained by serologic methods (142,143). The diagnostic sensitivities of PCR in CSF and urine samples were only 17 and 7%, respectively. Specific intrathecal antibody production was found in 90% of patients, and 87% showed elevated B. burgdorferi antibodies in serum, suggesting that measurement of specific intrathecal antibody synthesis was superior to CSF PCR for diagnosis of neuroborreliosis. However, in patients with a short duration of disease (<14 days), CSF PCR may be a useful diagnostic supplement. PCR of skin biopsy specimens is currently the most sensitive and specific test for the diagnosis of patients with electron microscopy, being superior to culture and serologic testing. Detection of spirochetal DNA in clinical samples by PCR may have a role in diagnosis but has not yet been standardized for routine diagnostic use (33).
Note: Since the article was published in 2004, it's understandable there is no mention of focus floating microscopy (FFM), which is showing great promise when it comes to analyzing skin biopsy specimens. There are a few references to FFM here on LNE, easily found using the search function and the search words "focus floating microscopy".

User avatar
ChronicLyme19
Posts: 564
Joined: Mon 11 Aug 2014 17:42
Location: NY, USA

Re: Analysis of serologic testing for diagnosis of LD

Post by ChronicLyme19 » Thu 6 Nov 2014 21:25

Diagnostic testing for Lyme disease in the clinical setting primarily relies on assessment of serologic responses to infection, with the exception of the early localized phase of disease, in which the diagnosis must be made clinically, due to the recognized insensitivity of serologic testing at this phase of disease.
I wish that statement also included the late stage insensitivity. I hope the UC Davis group continues their work on IgG suppression.
Half of what you are taught is incorrect, but which half? What if there's another half missing?

RitaA
Posts: 2768
Joined: Thu 1 Jul 2010 8:33

Re: Analysis of serologic testing for diagnosis of LD

Post by RitaA » Thu 6 Nov 2014 22:55

ChronicLyme19 wrote:
Diagnostic testing for Lyme disease in the clinical setting primarily relies on assessment of serologic responses to infection, with the exception of the early localized phase of disease, in which the diagnosis must be made clinically, due to the recognized insensitivity of serologic testing at this phase of disease.
I wish that statement also included the late stage insensitivity. I hope the UC Davis group continues their work on IgG suppression.
Me too, but I'm hoping that's just a reflection of the space limitation for any article abstract.

I think many of us are relying on the continued efforts of the UC Davis group when it comes to IgG suppression because this is obviously very important research that needs to be continued.

Although the "concise" part of the article title ("A concise critical analysis of serologic testing for the diagnosis of lyme disease") may limit the level of detail DeBiasi includes in her most recent article, I do hope she addresses the issue of insensitivity/seronegativity. The following sentence in her 2004 article gives me a tiny bit of hope:
The potential of generating false-negative PCR results is obviously of concern, as this may result in failure to treat or to complete treatment in patients who would benefit from treatment.
I sure hope the full article doesn't disappoint.

Post Reply