Register below for our weekly Letter from the Editor to receive the latest Clinical Lab news and insights.
Email
By Emily Hayes, LabPulse.com editor in chief

April 22, 2019 -- The demographics of tick-borne Lyme disease in the U.S. have been changing, with more testing and diagnoses in states that traditionally have had a low incidence of the infection, according to a study of blood-based testing by researchers from Massachusetts General Hospital (MGH) and Quest Diagnostics.

Lyme disease is most often caused by the bacterium Borrelia burgdorferi, which is transmitted by tick bites to humans. Delays in diagnosis may result in the spread of infection to the joints, heart, and nervous system.

The U.S. Centers for Disease Control and Prevention (CDC) advises that a diagnosis of Lyme disease may be made through the evaluation of patient symptoms and the characteristic rash the disease produces. Laboratory testing is helpful if used correctly and performed with validated methods, according to the CDC guidance. In the case of lab tests, a screening enzyme immunoassay (EIA) may be done and followed up with an immunoglobulin M (IgM)/immunoglobulin G (IgG) western blot (WB) as needed for confirmation.

But the number of cases of Lyme disease being reporting to the CDC -- more than 36,000 confirmed and probable cases in 2016 -- significantly lags data from commercial reference labs, which put the number of infected individuals at 244,000 to 444,000 per year. This suggests that there could be "significant underreporting" of Lyme disease, according to a team led by MGH pathologist Elizabeth Lee-Lewandrowski, PhD, and Quest Diagnostics Senior Medical Director Dr. Harvey Kaufman.

Lee-Lewandrowski and Kaufman decided to investigate trends in Lyme disease testing at the Quest Diagnostics lab at MGH. They tracked all EIA and IgM/IgG WB blood-based testing for Lyme disease caused by B. burgdorferi at the Quest lab over seven years (2010 to 2016), analyzing results by state and nationwide.

Lee-Lewandrowski initiated the study and Quest performed data mining and assisted with editing a manuscript about the results, which was published in the American Journal of Clinical Pathology on April 15.

Testing is more accurate earlier in the infection, and because the study was performed at a reference laboratory, which is often used to confirm equivocal cases done at outside facilities, a limitation of the analysis is that it may have been enriched for positive WB results, the authors acknowledged.

Rate of positive tests highest at end of study period

Out of almost 5.3 million tests for Lyme disease in 4.2 million patients (almost all had one to three tests each) over the entire period, 11.3% were positive, and cases were reported in all 50 U.S. states and the District of Columbia. The study volume was similar between 2010 and 2016, and there were no changes in testing recommendations during the period analyzed.

The percentage that was positive, however, fluctuated (see table). In 2010, 10.5% of tests were positive, and the highest positivity rates were in 2015 and 2016, at 11.7% and 13.3%, respectively. The increases reported in the last two years of the study were statistically significant, the authors noted.

Lyme disease test results at Quest lab, U.S. 2010-2016
Year Tests performed Positive tests (n) Positivity rate
2010 770,946 81,096 10.5%
2011 767,869 86,908 11.3%
2012 768,976 85,954 11.2%
2013 738,935 79,890 10.8%
2014 723,410 74,398 10.3%
2015 730,349 85,227 11.7%
2016 755,151 100,327 13.3%
Total 5,255,636 593,800 11.3%
Source: American Journal of Clinical Pathology.

They suggested that as with other studies of data from commercial reference laboratories, the Quest data indicate that the number of cases in the U.S. reported by the CDC is, indeed, an underestimation. According to the CDC, there were 26,203 confirmed and 10,225 probable cases in 2016.

However, the authors acknowledged limitations of their own data.

"In some cases, reference laboratories perform only the WB confirmation, as the screening serology may be performed by the referring practice or institution," they wrote. "For these and many other reasons, we do not believe it is reasonable to use our data to estimate national infection rates."

Another limitation is that the data were from one reference laboratory that had variable market share across the U.S. And diagnoses made on the basis of clinical signs and symptoms without a laboratory test were not included.

Similar to what the CDC has reported, the researchers found that most cases (85.3%) were concentrated in 14 states: Connecticut, New York, Wisconsin, Massachusetts, Rhode Island, Pennsylvania, Minnesota, New Hampshire, Maine, Vermont, Maryland, New Jersey, Delaware, and Virginia.

"After normalizing for total population, Connecticut had the highest rate of testing, with approximately 130 tests per thousand people," the authors wrote. "In contrast, 37 states had fewer than 10 tests per thousand people."

The number of tests done in New York was actually lower in 2016 than in 2010 (about 148,602 versus 190,931), but the positivity rate was similar for those years.

The investigators also flagged significant increases in testing and positivity rates over time in states that have historically had low rates of Lyme disease, such as Texas, Florida, and California.

"In Maryland, the test volume dropped from 42,645 to 30,303," they wrote. "In contrast, Texas saw a significant increase in test volume (8,856 to 13,505) and an increase in the percentage of positive tests, from 7.7% to 12.1%."

The volume of tests done in California rose from 772 to 3,002 between 2010 and 2016, and the positivity rate increased from 4.5% to 10.8%.

"Trends in some states with low testing and positivity rates are challenging to evaluate," the group noted. "In these states with low rates of test positivity, there may be an opportunity to improve utilization management through physician education, order entry alerts, gatekeeping, or other means. Also, in these states, the number of positive cases that may have resulted from travel to endemic areas should be investigated."

As would be expected, more tests were performed in the summertime than in the winter.

"In our data, the total test volume varied from 279,810 tests (February) to 624,752 (July) (2.2-fold) and the number of positive tests from 28,900 to 91,240 (3.2-fold)," the authors wrote. "The rate of positivity varied from 8.95% (May) to 14.6% (July). Particularly surprising was the number of tests and rate of positivity during the winter months."

The data show that the demographics of Lyme disease are changing across the country -- certain states such as California and Texas traditionally had a low incidence of Lyme disease, but in recent years infection has become more common, Lee-Lewandrowski commented by email to LabPulse.com.

"Collectively the data demonstrates a public health problem impacting most of the United States," she said. "Ongoing monitoring at the national level will be important. Also, physicians from states that have a low incidence of [Lyme disease] will need to be educated about the clinical presentation, diagnosis, and treatment of [Lyme disease]."

Massachusetts General Hospital and Stanford University are holding a meeting on emerging research and the diagnosis and treatment of Lyme disease and tick-borne illness over the weekend of September 14-15. The joint meeting will be held at the Li Ka Shing Center in Stanford, CA.


Copyright © 2019 LabPulse.com

Last Updated np 5/14/2019 1:37:40 PM