On 2014 Sep 10, David J Volkman commented:

Despite the isolation of borrelia in two tick vectors throughout the Southeast, the CDC stubbornly insists there is no borreliosis there. A letter to the NEJM addressing the CDC’s flawed diagnostic criteria was rejected in ’12.

The Emperor’s Rash

Reports that Lyme disease (LD) is concentrated in two areas in the US (1) promulgate a myth. As in the “Emperor’s New Clothes” fairy tale people ignore contradictory evidence-based observations. Many individuals nationally remain undiagnosed with LD, a treatable bacterial infection. Several rationales have been proposed to deny the presence of LD in areas like the South, e.g., bactericidal lizard complement, I. scapularis ticks don’t bite Southerners, positive tests must be false positives because LD doesn’t occur there, idiopathic Southern Tick Associated Rash Illness with a characteristic LD rash is not LD, because borrelia cannot be cultured. Opinions have been substituted for evidence-based studies. Notwithstanding the observation of seronegative Lyme disease published in this journal in 1988 (2) seronegative LD is dismissed by claims that there is “no scientific evidence” that there can be infection without anti-borrelia antibodies (3). Similarly, despite molecular and microbiological evidence to the contrary (4) there are still published denials that persistent borreliosis exists (3). The CDC only acknowledges LD cases from areas in which LD has been previously reported and requires that a positive antibody test react in a Western Blot with 5-10 borrelia proteins (so called 2-tier test). Using these revised criteria LD cases in Georgia plummeted from 715 cases in 1989 to only 10 in 2010. The 5 weeks it often takes for antibody production to be detectable further impede diagnosis. Different borrelia strains elicit antibodies that may react poorly with the single Long Island B31 tested. Whole Cell Sonicate (WCS) used in most commercial assays. A new assay (C6) is based on two small peptides that has few B31 antigenic determinants and is less sensitive than WCS. Positive blood tests or PCR assays are dismissed as “false positives” if they are not from designated LD areas although the incidence of predicted false positive IgG antibody or nested PCR assays is <1%. The distinction between the surveillance classification and clinical diagnosis has become blurred. A caveat I inserted in the CDC’s “Surveillance Definition” of LD in 1989 explicitly cautioned that this restrictive definition was only to be used for surveillance and was “NOT appropriate for clinical diagnosis” (4) (CDC’s emphasis); this caution was inexplicably removed in 2008. Even employing imperfect technology based on antibodies binding to the single LI strain and requiring Western Blot confirmation, >70% of cases are currently detected. By simply abjuring unsupported geographic requirements we can diagnose >90% of infections with an ELISA WCS assay; thousands of additional patients can be treated by abandoning unsupported assumptions about false positives, geographic prerequisites, and 2-tier confirmation.

1. Diuk-Wasser MA, Hoen AG, Cislo P, Brinkerhoff R, Hamer SA, Rowland M, Cortinas R, Vourc’h G, Melton F, Hickling GJ, Tsao JI, Bunikis J, Barbour AG, Kitron U, Piesman J, Fish D. Am J Trop Med Hyg, 86, 2012, pp. 320–327.

2. Dattwyler RJ, Volkman,DJ, Luft,BJ, Halperin JJ, Thomas J, and Golightly MG. Seronegative late Lyme borreliosis: Dissociation of Borrelia burgdorferi specific T and B lymphocyte responses following early antibiotic therapy. N Engl J Med, 319: 1441-1446, 1988.

3. Feder HM Jr, Johnson BJ, O'Connell S, Shapiro ED, Steere AC, Wormser GP; A critical appraisal of "chronic Lyme disease". N Engl J Med. 2007;357:1422-30. Letters: 2008;358:1084.

4. Hodzic E, Feng S, Holden K, Freet KJ, Barthold SW. Persistence of Borrelia burgdorferi following antibiotic treatment in mice. Antimicrob Agents Chemother 2008; 52:1728-36.

5. Centers for Disease Control and Prevention. Case Definitions for Infectious Conditions Under Public Health Surveillance. MMWR, 1997;46(RR-10):1-55.

On 2014 Sep 10, David J Volkman commented:

Despite the isolation of borrelia in two tick vectors throughout the Southeast, the CDC stubbornly insists there is no borreliosis there. A letter to the NEJM addressing the CDC’s flawed diagnostic criteria was rejected in ’12.

The Emperor’s Rash

Reports that Lyme disease (LD) is concentrated in two areas in the US (1) promulgate a myth. As in the “Emperor’s New Clothes” fairy tale people ignore contradictory evidence-based observations. Many individuals nationally remain undiagnosed with LD, a treatable bacterial infection. Several rationales have been proposed to deny the presence of LD in areas like the South, e.g., bactericidal lizard complement, I. scapularis ticks don’t bite Southerners, positive tests must be false positives because LD doesn’t occur there, idiopathic Southern Tick Associated Rash Illness with a characteristic LD rash is not LD, because borrelia cannot be cultured. Opinions have been substituted for evidence-based studies. Notwithstanding the observation of seronegative Lyme disease published in this journal in 1988 (2) seronegative LD is dismissed by claims that there is “no scientific evidence” that there can be infection without anti-borrelia antibodies (3). Similarly, despite molecular and microbiological evidence to the contrary (4) there are still published denials that persistent borreliosis exists (3). The CDC only acknowledges LD cases from areas in which LD has been previously reported and requires that a positive antibody test react in a Western Blot with 5-10 borrelia proteins (so called 2-tier test). Using these revised criteria LD cases in Georgia plummeted from 715 cases in 1989 to only 10 in 2010. The 5 weeks it often takes for antibody production to be detectable further impede diagnosis. Different borrelia strains elicit antibodies that may react poorly with the single Long Island B31 tested. Whole Cell Sonicate (WCS) used in most commercial assays. A new assay (C6) is based on two small peptides that has few B31 antigenic determinants and is less sensitive than WCS. Positive blood tests or PCR assays are dismissed as “false positives” if they are not from designated LD areas although the incidence of predicted false positive IgG antibody or nested PCR assays is <1%. The distinction between the surveillance classification and clinical diagnosis has become blurred. A caveat I inserted in the CDC’s “Surveillance Definition” of LD in 1989 explicitly cautioned that this restrictive definition was only to be used for surveillance and was “NOT appropriate for clinical diagnosis” (4) (CDC’s emphasis); this caution was inexplicably removed in 2008. Even employing imperfect technology based on antibodies binding to the single LI strain and requiring Western Blot confirmation, >70% of cases are currently detected. By simply abjuring unsupported geographic requirements we can diagnose >90% of infections with an ELISA WCS assay; thousands of additional patients can be treated by abandoning unsupported assumptions about false positives, geographic prerequisites, and 2-tier confirmation.

1. Diuk-Wasser MA, Hoen AG, Cislo P, Brinkerhoff R, Hamer SA, Rowland M, Cortinas R, Vourc’h G, Melton F, Hickling GJ, Tsao JI, Bunikis J, Barbour AG, Kitron U, Piesman J, Fish D. Am J Trop Med Hyg, 86, 2012, pp. 320–327.

2. Dattwyler RJ, Volkman,DJ, Luft,BJ, Halperin JJ, Thomas J, and Golightly MG. Seronegative late Lyme borreliosis: Dissociation of Borrelia burgdorferi specific T and B lymphocyte responses following early antibiotic therapy. N Engl J Med, 319: 1441-1446, 1988.

3. Feder HM Jr, Johnson BJ, O'Connell S, Shapiro ED, Steere AC, Wormser GP; A critical appraisal of "chronic Lyme disease". N Engl J Med. 2007;357:1422-30. Letters: 2008;358:1084.

4. Hodzic E, Feng S, Holden K, Freet KJ, Barthold SW. Persistence of Borrelia burgdorferi following antibiotic treatment in mice. Antimicrob Agents Chemother 2008; 52:1728-36.

5. Centers for Disease Control and Prevention. Case Definitions for Infectious Conditions Under Public Health Surveillance. MMWR, 1997;46(RR-10):1-55.