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An experimental new test holds great promise for diagnosing Lyme disease soon after infection, well before current tests are able to detect infection.
A “next-generation sequencing” technique called RNA-seq found distinctive patterns in patients with Lyme disease.
There are a couple of technical words to know, bolded below. Don’t let the big words scare you—there are good explanations from Carolyn Elya and a weird, funny YouTube clip by DRdoubleB (Brett Baskovich) here:
A transcriptome shows the pattern of messenger RNA (mRNA) genetic material that a cell uses in directing production of a protein. This next-generation sequencing looks at the patterns of the transcriptome, called a gene expression signature.
This technique—still in development—can be used for “precision medicine” to rapidly diagnose a large array of infectious diseases, something we are currently incapable of doing. In fact, Charles Chiu, MD, PhD, an associate professor of laboratory medicine at University of California San Francisco (UCSF) and lead investigator for the study, used this technique last year to diagnose an unusual form of encephalitis due to leptospirosis (a water-borne bacterial infection) in an immunocompromised 14 year old boy.
Current sorry state of Lyme disease diagnosis and treatment
Lyme disease is exploding across the country. The CDC now estimates the true incidence may be 300,000 cases per year, 10x higher than the actual number of cases reported.
Diagnosing Lyme can be very difficult. The telltale bull’s eye rash (erythema migrans) is absent in 20-30%. Sometimes the rash is mistaken for an allergic reaction or local skin infection (see photos of my early Lyme in "Ticked Off").
The standard “2-tier” test done by health departments and commercial labs is based on an antibody response to infection, which can take weeks after a bite or the rash. Who wants to wait weeks for a possible diagnosis? And the single dose of Doxycycline recommended as prophylaxis after a tick bite is enough to foul up the antibody response.
If Lyme is untreated and goes on to disseminate, 90% of patients will have a positive Elisa antibody titer. That’s terrific—unless you’re one of the 10% who remains undiagnosed. Even with treatment, 10 to 20% of patients report persistent symptoms lasting months to years. We don’t know how to diagnose or treat these patients. The cost of our failure and these patients' ongoing symptoms? In the U.S., Lyme disease adds between $712 million and $1.3 billion a year to healthcare costs--or nearly $3,000 per patient.
Research is lagging behind that devoted to other illnesses.
Surveillance is poor, with state health departments not even doing tick prevalence studies, let alone routinely looking for pathogens. Through special surveillance done by the military, we know prevalence of Lyme is increasing, as is the presence of coinfections with other pathogens including Anaplasma and the parasite Babesia.
As Lyme advocate Lonnie Marcum (@LonnieRhea) tweeted this week in frustration:
Not a single Zika transmission in US & @WhiteHouse gives $1.8billion. What about Lyme with ~300,000 per year? #Help https://t.co/BJBcS49qQA
— Lonnie R Marcum, PT (@LonnieRhea) February 11, 2016
Why next-gen test could be critical for Lyme
This study looked at blood samples from 29 patients before and after a traditional three-week course of antibiotics. Not only did the researchers find that the characteristic Lyme gene signatures persisted despite the antibiotic treatment, some of the transcriptome differences were still present 6 months later. At this stage, half of the patients had fully recovered; 13 had persistent symptoms. Yet despite the marked contrast in how the two groups of patients were feeling, there were not corresponding differences in the transcriptome. The other striking finding was that the patterns had 31-60% in common with immune-mediated diseases.
Dr. John Aucott, assistant professor of medicine at the Johns Hopkins University School of Medicine and a senior investigator on the study, concluded, "To our knowledge, this study is the first to document changes in gene expression occurring even after a bacterial infection has been treated with appropriate antibiotics.”
Aucott also shared perspective on another new assay in early development, just reported at the AAAS meeting, with me. The collaborators—from the National Institute of Standards and Technology (NIST), Institute for Bioscience and Biotechnology Research, and Johns Hopkins showed that they could detect minuscule amounts of a membrane protein (ospA) from the Borrelia burgdorferi (Lyme) bacteria in the blood of patients. In one of the three pilot patients tested, this technique detected the bacteria 3 weeks before it could be confirmed by standard antibody testing.
I beg to differ with the CDC about the value of standard 2-tier testing, based on my clinical experience. There are no routinely available diagnostic tests to readily and accurately diagnose Lyme, let alone panels that might help us diagnose related cryptic (mysterious) infections like Ehrlichia or Babesia.
The gene expression signature of early Lyme disease could be distinguished from other infectious causes, which would be extraordinarily helpful. The findings in the past year of new B. miyamotoi in California (not detected by standard testing) and the B. mayonii I reported last week emphasizes the urgency of developing accurate diagnostic tests.
While these two tests are likely several years away from being commercially available, I wanted to share my excitement over having some tangibly good news in the Lyme wars.
