“In the current situation, even in an endemic area like Connecticut, the first doctor a Lyme patient sees is an emergency room physician” – Dr. Sin Hang Lee at the 2017 ILADS conference in Paris, Europe
Introduction
Lyme disease belongs in the same health threat category as AIDS and cancer, while it is far more prevalent than Zika. With over 300,000 new cases annually in the USA alone, the incidence of Lyme is now six times the AIDS epidemic and it is twice as prevalent as breast cancer.
Early detection and treatment of Lyme disease is of utmost importance, but it is well known that typical antibodies are not detectable for 4-6 weeks after infection. The lack of diagnostic tests for early Lyme disease has caused untold pain and suffering worldwide as delayed diagnosis and treatment often leads to “chronic Lyme disease” or “Post Treatment Lyme Disease Syndrome”. The current situation has been framed as a human rights abuse on a global scale.
For decades, the reliability of Lyme diagnostics has been subject to critique. A few doses of doxycycline prescribed will almost guarantee a negative two tier serology test. Historically an indirect way of proving the causative pathogen for Lyme Borreliose (LB) has been used, since direct diagnostics such as microscopy, PCR and DNA testing were lacking. The current two-tier serological test system (with ELISA and Western Blot) seem to have many false-negative results. A recent meta-analysis showed that the number of false-negatives are over 500 times higher than with the two-tier testing on HIV.
Recently Dr. Becker, director of the Association of Public Health Laboratories, publicly admitted that “Lyme disease presently cannot be diagnosed based solely on a laboratory test because the tests still aren’t good enough.”
Fortunately, medical technology has evolved during the last three decades. DNA sequencing produces no false-positives and can measure the presence of the Borrelia beyond a reasonable doubt. This method works even with low bacterial density in the blood, provided that specific precautions are taken.
According to Dr. Lee, director of Milford Molecular Diagnostics, Connecticut, the CDC should launch a national competitive proficiency test program. The goal of this program should be to select the laboratory methods which can detect low density of borrelial spirochetes in whole blood samples for patient management. He had tried to work with them to achieve that goal.
Attempt at cooperation
On the Change.org petition of Carl Tuttle, the history of this effort is well described: Dr. Lee and David Shearer originally contacted the CDC for collaboration. Marty Schriefer of the CDC agreed to assist. Schriefer sent archived sera from the CDC’s Lyme disease repository for testing using Dr. Lee’s lab developed PCR/sequencing test in a CLIA-certified laboratory.
In 2013 the CDC provided 52 blind-coded archived serum samples – including 12 from post treatment and 20 pretreatment clinically suspect Lyme disease patients – and 20 negative serum samples to Milford Molecular Diagnostics.
These samples were provided for the purpose of evaluating the accuracy of a new diagnostic test for Lyme disease by Nested PCR and DNA Sequencing.
Dr. Lee’s technology uncovered a novel Borrelia in one of the serum samples tied to a patient in the Hudson Valley, who had been previously treated for neurologic Lyme disease (DNA sequence deposited in GenBank under accession number KM052618). Dr. Lee also found Borrelia miyamotoi in one of the CDC’s Lyme disease serum samples.
As a result, Dr. Lee informed the CDC that the nested PCR/16S rRNA sequence analysis has been shown to be an effective testing platform for accurate diagnosis of Lyme borreliosis at the spirochetemic stages of the infection, even for some chronic Lyme disease patients.
This is a serious problem and clearly identifies that there is no accountability at the CDC. It would appear that the serum repository for Lyme disease has many problems and that samples may also be wrongly coded.
Using these samples to determine the validity of future test kits is highly questionable, whereas nested PCR and Sequencing through Milford Molecular Diagnostics can detect different strains of bacteria causing Lyme borreliosis with as few as 25 bacteria per mL of blood.
According to Dr. Lee, at a Telecom conference on Friday October 25, 2013 among Dr. Schriefer and Dr. Molins of the CDC, Dr. Shearer and Dr. Lee, the CDC agreed to organize a national study program to further evaluate and promote new diagnostic tests and encouraged researchers to develop direct test methods, including the 16S rRNA sequence analysis technology.
Based on this agreement a research protocol was initially drafted by Dr. Lee and Dr. Shearer, and submitted on December 19, 2013 to Dr. Molins and Dr. Schriefer for their review. Dr. Schriefer indeed had reviewed, commented and edited the protocol and returned the edited copy to Dr. Shearer for revision on December 26, 2013. Dr. Lee and Dr. Shearer returned the protocol revised according to Dr. Schriefer’s recommendations in January 2014 to be finalized and implemented.
The CDC commitment to the national study abruptly stopped with no reasons given. However, it appears the CDC is focusing on developing their own newly patented test rather than supporting a group of innovators that compete with the CDC patents.
But not only the project itself was ended. When Dr. Lee published his findings, Detection of Borreliae in Archived Sera from Patients with Clinically Suspect Lyme Disease, all communication with the CDC suddenly stopped. In the meantime, CDC developed a novel test based on metabolite detection.
As with serology, such a test is an indirect test, and does not directly detect the bacterium. In an open PubMed comment Dr. Lee characterized the metabolite measurement as “an unproven technology” which “has deviated from the classic teachings of diagnostic microbiology”.
The current law suit
The current legal case is unprecedented and complex. Due to “sovereign anti-trust immunity” to protect the US government from claims by its own people, the current claim against the CDC is a long and difficult process. According to the Federal Tort Claims Act, one can only sue the government or its employees for damage by submitting an SF-95 form with supportive documents for money compensation only.
Through the law firm of Moore Leonhardt & Associates LLC, Dr. Sin Lee of Milford Molecular Diagnostics has now submitted the SF-95 form with documents to support the $57 million damage claimed, based on a complaint of 16 pages and a file of Exhibits of 376 pages. This amount of $57 million is 10% of the annual Lyme testing dollar volume charged to the insurance companies by 7 large commercial laboratories in the United States.
The CDC is accused of violation of the antitrust law in suppressing a direct testing method to diagnose an emerging infectious disease (Lyme borreliosis), which the CDC itself has called the ‘fastest growing vector borne disease in the USA’.
One of the purposes of the current lawsuit is to make the Exhibits public, so that Lyme disease patients can ask their lawyer to use the Exhibits to file their own SF-95 form for damages due to delayed diagnosis.
If he wins his case, Dr. Lee intends to donate the money to a non-profit organization to set up nested PCR/16S rRNA sequence diagnostic laboratories in hospitals located in Lyme disease-endemic areas so that all Lyme patients can be diagnosed early within a few days of first symptomatic presentation and receive timely and proper treatment.
These diagnostic centers will further improve the sensitivity of the PCR procedure so that a very low density of spirochetemia in chronic Lyme patients can be diagnosed for further appropriate management. He also hopes that the insurance companies will pay for these tests, which should cost no more than the WB tests.
How to set up proper Lyme diagnostics?
In a letter to Jane Philpott, Federal Minister of Health of Canada, hand-delivered on August 22 2017, Dr. Lee explains how easy and cost-effective it would be to set up proper nationwide Lyme testing:
- Establish one National Lyme Disease Diagnostic Laboratory with Sanger sequencing facilities. The equipment costs less than US $300,000. This Lab also serves as an educational and training center.
- Set up 10 local PCR laboratories attached to the existent laboratories of regional hospitals located in Lyme disease endemic areas. Each of these laboratories will be equipped with one high speed micro-centrifuge to collect circulating spirochetes from platelet-rich plasma samples from suspected Lyme disease patients. The additional thermocycler, micro-centrifuge and PCR setup may cost about $15,000 at each site.
- The DNA extracted from the pellet of the platelet-rich plasma will be amplified with comprehensive genus-specific borrelial nested PCR primers for 16S rRNA gene detection at the local laboratories.
- The PCR results should be available within 2-3 working days after the patient’s visit. The PCR positive results are very accurate in the diagnosis of Lyme borreliosis for initiating timely treatment.
- The positive PCR amplicons will be sent to the national Lyme diagnostic laboratory for Sanger sequencing final validation.
In a reply to Dr. Becker, Dr. Lee also wrote that “the excuses commonly used to suppress using and development of direct DNA tests for the diagnosis of Lyme borreliosis include potential sample cross contamination, false identification of target DNA and lack of sensitivity. However, these are technical issues which can be overcome by good laboratory practices.”
He made this proposal for a national proficiency test project in the USA to advance the diagnostics in this area, which you can find here. However, he does not believe that anything will happen in the USA due to the financial stakes in keeping the current situation as it is.
A precedent?
Since Dr. Lee is not a Lyme patient nor a victim of delayed diagnosis himself, he cannot claim damage as a patient. So he can only sue the government for damage to his business (in terms of dollars).
Both American Lyme patients and Medical Doctors are also able to use a SF-95 claims form, within two years since the date when CDC’s suppression of using an available 16S rRNA sequence analysis as a reliable direct test method for diagnosis of early Lyme borreliosis was made public, namely on July 20, 2017. It could achieve two things: individual compensation and collective financial pressure to show that the CDC suppression of direct testing has led to delayed diagnosis of Lyme disease or missed diagnosis of Lyme disease, and the resulting devastating effects on public health, loss of income, expenses, general quality of life and a gross violation of basic human rights.
It is however not easy to sue the CDC, the European version ECDC or the Health Department of your national government, such as the RIVM in the Netherlands. You could be facing a long battle as – due to sovereign immunity protection – you may not be able to sue government employees. In the USA the exception is under Federal Tort Claims Act via the SF-95 form. You may need a lawyer to do this properly.
One cannot file a case in court until the Complaint is cleared with the federal agency (CDC) and the OIG. This means waiting for six months, if they do not rule. This is called “exhausting administrative remedies”. This legal option has been used so little by either patients or doctors that there are hardly any lawyers who are specialised in filing these claims.
As history of social revolution has shown over and over again, all effective action once started with a single try. As Dr. Lee puts it: “We have tried everything: reasoning, petitions, complaining, pleading. It’s time to change course. However, I am a lone wolf with one meagre voice. If a thousand patients are filing 1000 SF-forms, each demanding $1 million damage due to suppression of early diagnostics, the judge may think differently. Even if I lose the case and the patients win $100,000 per case, the CDC would have to change its Lyme policy. Someone has to try and we are given the opportunity now.”
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