NIH awards $3M grant for new LD test

[RitaA]

http://investor.opko.com/releasedetail. ... eID=891076

January 13, 2015

OPKO Claros1 Analyzer Selected for Development of a Rapid Lyme Disease Test Under Immuno Technologies NIH Grant

MIAMI & MEMPHIS, Tenn.--(BUSINESS WIRE)-- OPKO Health, Inc. (NYSE:OPK) and Immuno Technologies, Inc. today announced that the National Institutes of Health (NIH) has awarded a $3 million grant to develop a rapid diagnostic test for Lyme disease. The Phase II Small Business Innovation Research (SBIR) grant was issued to Immuno Technologies working in collaboration with OPKO Diagnostics, LLC and Columbia University in the City of New York. The goal of the grant is to develop a rapid diagnostic test based upon novel antigens that increase the specificity and sensitivity of the current laboratory assays and improve discrimination between early and late stage disease using OPKO's Claros®1 in office analyzer. Combinations of these antigens have already been successfully demonstrated on OPKO's microfluidic cassettes for the detection of Lyme disease using challenge panels from patients.

There's more to read in the press release.

[Lorima]

Here's a paper on diagnostics by Gomes-Solecki:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752154/

Clin Immunol. 2009 Sep;132(3):393-400. doi: 10.1016/j.clim.2009.05.017. Epub 2009 Jul 2.
Comprehensive seroprofiling of sixteen B. burgdorferi OspC: implications for Lyme disease diagnostics design.
Ivanova L1, Christova I, Neves V, Aroso M, Meirelles L, Brisson D, Gomes-Solecki M.
Author information
1Department of Molecular Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

Abstract
Early diagnosis of Lyme disease (LD) is critical to successful treatment. However, current serodiagnostic tests do not reliably detect antibodies during early infection. OspC induces a potent early immune response and is also one of the most diverse proteins in the Borrelia proteome. Yet, at least 70% of the amino acid sequence is conserved among all 21 known OspC types. We performed a series of comprehensive seroprofiling studies to select the OspC types that have the most cross-reactive immunodominant epitopes. We found that proteins belonging to seven OspC types detect antibodies from all three infected host species regardless of the OspC genotype of the infecting strain. Although no one OspC type identifies all seropositive human samples, combinations of as few as two OspC proteins identified all patients that had anti-OspC antibodies.
PMID: 19576856 [PubMed - indexed for MEDLINE] PMCID: PMC2752154 Free PMC Article

OspC is band 22-25 on the western blot.

It sounds reasonable; and there is more than one cautionary mention that this one set of antigens would only be useful when combined with others, and that by itself it gives 13% false negatives:

snip
As with all serodiagnostic assays, caution should be used given that up to 13% of samples, with proven anti-B. burgdorferi antibodies from three different hosts, did not react to any of the 16 OspC tested. This highlights a source of false-negative results that could indirectly lead to the increase in the incidence of late Lyme disease.
snip

The bad news is, at least in this particular paper, there is only a focus on early LD, and all the tested samples were prescreened and were positive for C6. So there is no claim that this test will help with diagnosing late LD (though I suppose it might), nor that patients who don't mount a good, early antibody response to C6, will be detectable by screening with this antigen. In other words, immunocompromised patients won't be detected (something true of all serological assays).

I'm not complaining about this; just because it leaves some problems unsolved, doesn't mean the final product won't be useful. Just pointing out the limitations, of which the authors seem cognizant, and which they are not trying to hide.

[ChronicLyme19]

The bad news is, at least in this particular paper, there is only a focus on early LD, and all the tested samples were prescreened and were positive for C6. So there is no claim that this test will help with diagnosing late LD (though I suppose it might), nor that patients who don't mount a good, early antibody response to C6, will be detectable by screening with this antigen. In other words, immunocompromised patients won't be detected (something true of all serological assays).

I'm not complaining about this; just because it leaves some problems unsolved, doesn't mean the final product won't be useful. Just pointing out the limitations, of which the authors seem cognizant, and which they are not trying to hide.

I agree. If you don't get tested soon enough, you are still up the creek without a paddle. Maybe it'll just have to be two approaches, one super sensitive antigen based test for early, and then an improved culture for us late stagers?

[migs]

Well I hold out hope that it is a real improvement and that interpretation is not perversed or neutered by the CDC.

I am a patient that is ruled a false positive because I produced IGM positive results only after being sick for years. I wonder how a new test might or might not recognize my case and the others in my boat.

Even if only good in early detection it would be a HUGE improvement. My first ELISA, about 2 weeks post tick attachment and about one week post bullseye, was interpreted as negative. I might still be where I am now in the sense of relapsing infection but the immediate diagnosis would have been big for me by saving frustration and anger. I wouldn't have had to listen to so many doctors inform me that we don't have Lyme carrying ticks on Vancouver Island. Some of them even checked with a local ID doc, who is an "expert" in Lyme Disease and he assured them I had something else. A good early test would really open some eyes, even if those patients who didn't recognize the tick and/or bullseye are still foresaken.

[ChronicLyme19]

I am a patient that is ruled a false positive because I produced IGM positive results only after being sick for years. I wonder how a new test might or might not recognize my case and the others in my boat.

Well, yes and no. Yes, it would have saved some cases like us who had known tick/bites or rashes. But if you had a case like mine and were given a round of doxycycline before testing positive prophylactically, and it returned when you stopped the abx, it only would have helped if you got to a doctor who also knows that Lyme can persist post abx treatment. But usually, the ones who don't understand partial positive WBs or Igenex positives are the same ones who think you can't have lyme after you've been given a round of doxycycline.

An early accurate test would have given ME the knowledge I had Lyme two years sooner, but I'm pretty sure I still would have been bounced around a bit before getting retreated. Would it have been a shorter time to retreatment? I sure hope so, and maybe I wouldn't have gotten so ill. I guess I'm being very pessimistic, but my guess is even armed with a full positive, most docs were taught that Lyme can't exist past one round of doxycycline and wouldn't recognize it, or even worse just call it a post treatment syndrome in all cases (yes, you can have permanent damage post Lyme treatment, but I'm talking about the subset of patients like me that still benefits from abx after the first course).