As Lyme disease becomes an increasingly challenging public health threat across the Northeast, a growing number of tests for the vexing ailment may be misdiagnosing patients when telling them that they have – or don’t have – the tick-borne illness.

An exemption in federal regulations allows many labs to offer Lyme tests without proof that they accurately identify the disease, leaving anxious patients and their doctors to decide which tests to believe.

“There are desperately ill people looking for an answer. But there are so many companies using (unproven tests) … you can’t trust them,’’ said Andrew Onderdonk, a professor of pathology at Harvard Medical School who was diagnosed with Lyme disease in 2012 using a federally recommended test.

Cases of Lyme Disease from 2001-2011 (Source: CDC)

While the loophole in US Food and Drug Administration regulations affects a wide variety of tests, it has particular significance with Lyme disease because controversy exists over its diagnosis, treatment and how long the illness can last. Thousands of sick people believe they have a chronic form of the illness that can evade antibiotics and last years, but medical establishment doctors often dismiss this idea of long-term Lyme.

Over the past two decades, the issue has become deeply divisive and bitter – and the regulation exemption fuels polarization on the issue of Lyme treatment.

Ailing patients are increasingly forced to negotiate between the parallel medical worlds of doctors who use only federally recommended Lyme tests that may not catch the disease early on and “Lyme literate” doctors who may diagnose them with chronic Lyme, often by using these alternative tests. Most insurers do not cover these tests – which range from $100 to more than $1,000 – forcing patients to swallow the cost.

Federally recommended tests identify about 300,000 new cases of Lyme each year in the United States – more than three-quarters in the Northeast. In addition, medical authorities say, many other people are diagnosed with alternative tests that may be inaccurate, leading to unnecessary, inappropriate and costly treatment.

At least seven labs in the U.S. have been denied permission to offer Lyme tests over the past decade in New York, according to state records obtained by the New England Center for Investigative Reporting.  The state is the only one that performs a rigorous review of tests to ensure they identify what they claim to before they can be offered there.

The labs include a Pennsylvania company that has failed to follow through on a promise to deliver independent validation studies of its test and a Wisconsin lab whose owner who was once involved in a malaria research fraud case. Officials at both labs say they stand by their tests.

The U.S. Centers for Disease Control and Prevention has become so concerned about queries from public health officials, doctors and patients regarding questionable Lyme tests – especially the Pennsylvania lab’s – that it issued a warning in May for doctors and the public to avoid tests that are not recommended by the federal agency.

An estimated 3.4 million Lyme tests are conducted in the U.S. each year largely using federally recommended tests at a cost of about $492 million, according to a recent CDC study. But that doesn’t include unproven tests, and it’s unclear exactly how many are being used because they do not have to register with the FDA, and not all testing companies seek the stringent approval of New York.

At least tens of thousands of these alternative tests are probably performed each year, NECIR estimates based on interviews with the CDC and two of the labs that offer tests rejected by New York.


A Loophole Creates A Market

The federal test exemption dates back to the 1970s when the FDA began regulating diagnostic tests but exempted what was then a small group of relatively simple tests developed, manufactured and performed all in a single lab – for example, in a hospital. Many of the tests were low-risk, variations of common tests, or designed for rare diseases and could not be validated well in studies.

The exemption has since become a market incentive for companies that produce thousands of FDA-exempt diagnostic tests, from prenatal screening to identification of genetic mutations known to increase the risk of cancer.

The FDA announced its intention to regulate these tests in 2010, but has been opposed by many laboratories that argue their facilities are already well regulated and the new rules would be cost-prohibitive, take too much time and stifle innovation that can help patients. While many of these tests do go through robust and independent validation, not all do, making it challenging for doctors and the public to distinguish between the two.

Indeed, thousands of sick people rely on the unproven Lyme tests, in part, because when the results provide a diagnosis, patients then have a hope of a treatment and cure. Many say they feel better once on medication, which is further validation for them that they were diagnosed correctly.

“I did not test positive using the CDC method,’’ said Allen Bargfrede, 39, an associate professor of music business at Berklee College of Music in Boston who contracted Lyme last summer while in Europe. He remembers a tick bite and a subsequent bulls-eye rash. He forgot about it until he came back to Boston and became severely ill with cognitive problems, overwhelming fatigue and other symptoms that CDC-recommended tests did not show to be Lyme. Bargfrede ultimately received a positive diagnosis of Lyme overseas with a test that is not recommended by the CDC. One year later, he is recovering with the aid of antibiotics.

“If there was better testing for Lyme, I could have avoided six months off from work,’’ he said.

Deer ticks, which can be as small as poppy seeds, are often hard to detect (Lauren Owens/NECIR)

Lyme is one of the Northeast’s most insidious public health threats. Deer ticks no bigger than a poppy seed can latch onto people during outdoor activities. The parasites, while feeding on a host’s blood, can transfer the Lyme bacteria and other disease-causing pathogens. Early Lyme symptoms can mimic those of the flu and, untreated, the disease can cause arthritis, among other ailments.

The CDC-recommended method is far from perfect: It can miss the disease more often than it catches it in its early stages, although its accuracy improves greatly as the disease progresses. It can also tell people they are positive even after the disease is gone, acknowledge federal health officials. Yet despite the limitations, they say a test has not come along yet that has proven to perform better. So, they still recommend the tests in addition to a doctor’s judgment based on symptoms and whether the person lives in a tick-prone area.

 “What needs to be done are longitudinal studies and blinded samples from a third party with no vested interest,’’ says Sam Donta, a physician and consultant at Falmouth Hospital who specializes in Lyme disease. He says the CDC test is far too strict and omits valid cases of Lyme. But he’s unwilling to use tests that are not validated. “We need something unbiased.”


Thousands of Questionable Tests

When people notice a tick bite or get sick in the summer in a Lyme-prone area, many will call their doctor. If a telltale bulls-eye rash is present, a doctor will often assume Lyme and prescribe antibiotics without testing.

Two-Tiered Testing Diagram (Source: CDC)

But not everyone gets or notices the rash, so most mainstream doctors turn to the CDC-recommended test. The two-step process first looks for increased antibodies in the blood that react to the Lyme bacteria. But because someone can test positive and not have the disease, a second test, known as a “Western Blot” is performed to more accurately identify antibodies specific to the Lyme bacteria.

While the CDC has specific guidelines to interpret the results to identify Lyme, some labs interpret them far more liberally. IGeneX Inc., for example, a Palo Alto, Calif. lab that performs more than 20,000 Lyme tests a year, uses different interpretation criteria for the Western Blot. On its website, the lab also offers others, such as a urine test, that is not recommended by the CDC. IGeneX was rejected by New York three times for Lyme tests in the past decade for not having enough documentation to prove the tests worked. The lab did not respond to requests for comment.

Other labs use different means to test for Lyme. Advanced Laboratory Services Inc. outside Philadelphia, for example, says it can detect and grow the bacteria that cause Lyme, a method most Lyme researchers have never been able to reliably do. The lab has conducted more than 4,000 tests but now does less than 50 a week, according to officials there.


The facility has come under sustained criticism by scientists and regulators since its test went on the market in 2011. New York rejected it in 2012 because, the state concluded, there was no proof it worked, and inspectors who visited the facility uncovered “broad substandard” laboratory practices, including an employee not wearing protective gear and a lack of lab supervision. A federal scientist last year also published a critical study about the company’s methods, raising contamination concerns.

“The obligation of a clinical laboratory is to properly validate their test before offering it to the public for sale,’’ said Barbara Johnson, a CDC scientist who wrote the critical study and is dubious that the Advanced Laboratory Services test works.

Advanced Laboratory Services officials publicly pledged after the CDC study to respond to it and deliver outside validation studies by the end of April. The lab has still not done so. Company spokeswoman Jen Hoefner said in an e-mail that validation studies were delayed but will still be conducted. “We have ample data to discredit” the federal scientist, she wrote, “and we hope to have this information published shortly.” She also said a study related to the test’s performance will be published soon in a scientific journal.

Philip M. Tierno, a New York University Langone Medical Center clinical professor of microbiology and pathology, has spoken out in favor of the Advanced Laboratory Services test in a media account and on the lab’s website in recent months.

“I have seen the culture and evidence of (the Lyme bacteria),” Tierno said in an NECIR interview.

Rejected Lyme Tests (Source: NY State Department of Health)

But the accounts did not state, nor did Tierno initially acknowledge to NECIR, that he is a former employee of Advanced Laboratory Services, at one time running its bacteriology lab. The 2012 New York state lab inspection report took special note of Tierno, saying he was “not cognizant of what strategies or analysis was used” for the Lyme detection method.

Tierno said he was newly hired at the time of the New York state inspection and that he is no longer paid by the company. After the NECIR interview, the words “outside consultant” were inserted into his identification on his comments on the lab website.

Another lab – Pharmasan Labs. Inc., in Wisconsin – has been unable to offer its test in New York in part because of validation problems. Its test, rejected by the state last year, uses a new method to detect an immune response to Lyme.

Gottfried Kellermann, founder of Pharmasan and its sister company, NeuroScience Inc., said he plans to resubmit the rejected test to New York.

“It is a very (accurate) diagnostic test,’’ said Kellermann, who defended his test as misunderstood by authorities.

Kellermann is a German national with a 1992 felony conviction for his part in a conspiracy to defraud the federal government out of $750,000 related to malaria research.

In May, the FBI raided Kellermann’s NeuroScience offices. Kellermann’s lawyer, Henry M. Helgen III said the company believes the raid to be related to Medicare billing problems from a former employee who the company successfully sued for fraud. An FBI spokesman could not confirm the reason for the raid because it is an active case.

Not All Alternative Tests Are Bad

Of course, not all tests rejected by the state of New York are problematic, cautioned state officials. While tests may be rejected when developers fail to prove their validity, said Michael P. Ryan, director of the Division of Laboratory Quality Certification for the New York State Department of Health, those tests can be resubmitted as better data becomes available.

Some doctors say that while they know of the controversy around alternative tests they use, they choose a particular one because they trust the scientists involved who created it. Chris Foley, a medical doctor at Minnesota Natural Medicine in Vadnais Heights, Minn. says he has ordered more than 100 Advanced Laboratory Services tests because, combined with his Lyme expertise, “it helps me with difficult cases to decide if it’s persistent Lyme.”

Still, many doctors say they can only abide by the scientific method, which requires evidence, such as reproducible results by an independent party in peer-reviewed literature, that a test does what it says it will.

Fredric Silverblatt, a doctor who runs a Lyme clinic southern Rhode Island said he often sees patients who have been on antibiotics for years without tangible results and who have tested negative on CDC-recommended tests. In those cases, he questions if they really have the disease.

One way to resolve the controversy, he said, is “to better understand how the body reacts to Lyme.”
With that, will come clarity on how people are affected and better tests.

NECIR interns Amanda Ostuni, Carl Mueller, Michael Bottari, and Jack Cohen assisted with the research for this story.

Photography by Lauren Owens.