On 2016 Dec 07, Raphael Stricker commented:

Serological Test Sensitivity in Late Lyme Disease.

Raphael B. Stricker, MD<br> Union Square Medical Associates San Francisco, CA rstricker@usmamed.com

Cook and Puri have written an excellent review of the sorry state of commercial two-tier testing for Lyme disease (1). Unfortunately the authors failed to address the myth of high serological test sensitivity in late Lyme disease.

In the review, Figure 4 and Table 7 show a mean two-tier serological test sensitivity of 87.3-95.8% for late Lyme arthritis, neuroborreliosis and Lyme carditis. However, this apparently high sensitivity is based on circular reasoning: in order for patients to be diagnosed with these late conditions, they were required to have clinical symptoms AND POSITIVE SEROLOGICAL TESTING. Then guess what, they had positive serological testing! This spurious circular reasoning invalidates the high sensitivity rate and should have been pointed out by the authors of the review.

As an example, the study by Bacon et al. (2) contains the following language: "For late disease, the case definition requires at least one late manifestation AND LABORATORY CONFIRMATION OF INFECTION, and therefore the possibility of selection bias toward reactive samples cannot be discounted" (emphasis added). Other studies of late Lyme disease using spurious circular reasoning to prove high sensitivity of two-tier serological testing have been discussed elsewhere (3-5).

In the ongoing controversy over Lyme disease, it is important to avoid propagation of myths about the tickborne illness, and insightful analysis of flawed reasoning is the best way to accomplish this goal.

References 1. Cook MJ, Puri BK. Commercial test kits for detection of Lyme borreliosis: a meta-analysis of test accuracy. Int J Gen Med 2016;9:427–40. 2. Bacon RM, Biggerstaff BJ, Schriefer ME, et al. Serodiagnosis of Lyme disease by kinetic enzyme-linked immunosorbent assay using recombinant VlsE1 or peptide antigens of Borrelia burgdorferi compared with 2-tiered testing using whole-cell lysates. J Infect Dis. 2003;187:1187–99. 3. Stricker RB, Johnson L. Serologic tests for Lyme disease: More smoke and mirrors. Clin Infect Dis. 2008;47:1111-2. 4. Stricker RB, Johnson L. Lyme disease: the next decade. Infect Drug Resist. 2011;4:1–9. 5. Stricker RB, Johnson L. Circular reasoning in CDC Lyme disease test review. Pubmed Commons comment on: Moore A, Nelson C, Molins C, Mead P, Schriefer M. Current guidelines, common clinical pitfalls, and future directions for laboratory diagnosis of Lyme disease, United States. Emerg Infect Dis. 2016;22:1169-77.

Disclosure: RBS is a member of the International Lyme and Associated Diseases Society (ILADS) and a director of LymeDisease.org. He has no financial or other conflicts to declare.

On 2016 Dec 07, Raphael Stricker commented:

Serological Test Sensitivity in Late Lyme Disease.

Raphael B. Stricker, MD<br> Union Square Medical Associates San Francisco, CA rstricker@usmamed.com

Cook and Puri have written an excellent review of the sorry state of commercial two-tier testing for Lyme disease (1). Unfortunately the authors failed to address the myth of high serological test sensitivity in late Lyme disease.

In the review, Figure 4 and Table 7 show a mean two-tier serological test sensitivity of 87.3-95.8% for late Lyme arthritis, neuroborreliosis and Lyme carditis. However, this apparently high sensitivity is based on circular reasoning: in order for patients to be diagnosed with these late conditions, they were required to have clinical symptoms AND POSITIVE SEROLOGICAL TESTING. Then guess what, they had positive serological testing! This spurious circular reasoning invalidates the high sensitivity rate and should have been pointed out by the authors of the review.

As an example, the study by Bacon et al. (2) contains the following language: "For late disease, the case definition requires at least one late manifestation AND LABORATORY CONFIRMATION OF INFECTION, and therefore the possibility of selection bias toward reactive samples cannot be discounted" (emphasis added). Other studies of late Lyme disease using spurious circular reasoning to prove high sensitivity of two-tier serological testing have been discussed elsewhere (3-5).

In the ongoing controversy over Lyme disease, it is important to avoid propagation of myths about the tickborne illness, and insightful analysis of flawed reasoning is the best way to accomplish this goal.

References 1. Cook MJ, Puri BK. Commercial test kits for detection of Lyme borreliosis: a meta-analysis of test accuracy. Int J Gen Med 2016;9:427–40. 2. Bacon RM, Biggerstaff BJ, Schriefer ME, et al. Serodiagnosis of Lyme disease by kinetic enzyme-linked immunosorbent assay using recombinant VlsE1 or peptide antigens of Borrelia burgdorferi compared with 2-tiered testing using whole-cell lysates. J Infect Dis. 2003;187:1187–99. 3. Stricker RB, Johnson L. Serologic tests for Lyme disease: More smoke and mirrors. Clin Infect Dis. 2008;47:1111-2. 4. Stricker RB, Johnson L. Lyme disease: the next decade. Infect Drug Resist. 2011;4:1–9. 5. Stricker RB, Johnson L. Circular reasoning in CDC Lyme disease test review. Pubmed Commons comment on: Moore A, Nelson C, Molins C, Mead P, Schriefer M. Current guidelines, common clinical pitfalls, and future directions for laboratory diagnosis of Lyme disease, United States. Emerg Infect Dis. 2016;22:1169-77.

Disclosure: RBS is a member of the International Lyme and Associated Diseases Society (ILADS) and a director of LymeDisease.org. He has no financial or other conflicts to declare.