On 2014 Sep 09, David J Volkman commented:

The following letter was sent to the NEJM and rejected after internal review after one day.

Under-diagnosis of Lyme Borreliosis It was recently estimated that of the more than 300,000 annual borrelia infections (Lyme disease (LD)) in the US, the CDC reports only 30,000 (1). The two-tier serology criterion recommended by the CDC, derived from the 1994 Dearborn Conference (2), requires 5-10 antibody reactivities to confirm a case, resulting in many positive Lyme disease (LD) titers with fewer reactivities being ignored and untreated. In contrast, a single reactivity against a crude flagella antigen or a positive IgG ELISA against a whole cell borrelia sonicate (WCS) is often sufficient to detect new infection (3). In 1999 Felz reported 22/22 people with an erythema migrans rash in Georgia and South Carolina, areas the CDC insist is devoid of LD, had IgG antibody against the flagella (3). The WCS from the inexpensive, widely available B31 Long Island borrelia isolate has enough ubiquitous p41 flagella epitopes to detect borrelia infections across the US, Europe, and China (4). As shown in Table 1 specific antibodies may take more than 5 weeks to develop and if assayed too early may be absent. Table 1 shows the serology of a woman with a negative LD serology hospitalized with a diagnosis of aseptic meningitis. A week after discharge she had a highly positive ELISA, a strong anti-41 kd IgG band, and 3 IgM bands. She was treated with 4 weeks of oral doxycycline, recovered fully, and remains well 2 years later. Anti-borrelia antibodies can take 5 weeks to develop and may have reactivity only to the p41 flagella; obtained too early or requiring restrictive criteria, serology may be falsely reported as negative. Since Congress is considering closer oversight of FDA approved LD testing (5); it is imperative testing becomes evidence-based, sensitive, and reflects biomedical reality. The CDC’s current 20 year old criteria for LD testing leave many infected people with spurious false negative tests, undiagnosed, and untreated.   Table 1: Serologic Response to EM

Date IgG/IgM EIA IgG bands IgM bands

Early June noted 5 mm light brown bump on thigh June 27 negative none none negative July 8 5.49* P41 + p23,39,41 + IgM positive/WB negative < 5 bands

August 1 month 100mg BID PO doxycycline Next year 4.79 p41, p23 + none negative

• relative optical density (1.00 = 3 Standard Deviations greater than mean of negative controls)
• present

References 1. Kuehn BM. CDC Estimates 300000 US Cases of Lyme Disease Annually. JAMA.18, 2013. 310, 1110.

1. CDC (1995) Recommendations for test performance and interpretation from the second national conference on serologic diagnosis of Lyme disease. Morbidity and Mortality Weekly Report 44, 590–591.

2. Felz MW, Chandler FW Jr, Oliver JH Jr, Rahn DW, Schriefer ME. Solitary erythema migrans in Georgia and South Carolina. Arch Dermatol. 1999; 135:1317-26.

3. Chao LL, Chen YJ, Shih CM. First isolation and molecular identification of Borrelia burgdorferi sensu stricto andBorrelia afzelii from skin biopsies of patients in Taiwan. Int J Infect Dis. 2011 Mar; 15:e182-7.

4. Nelson C, Hojvat S, Johnson B, Petersen J, Schriefer M, Beard CB, Petersen L, Mead P. Concerns regarding a new culture method for Borrelia burgdorferi not approved for the diagnosis of Lyme disease. Centers for Disease Control and Prevention (CDC). MMWR Mor

On 2014 Sep 09, David J Volkman commented:

The following letter was sent to the NEJM and rejected after internal review after one day.

Under-diagnosis of Lyme Borreliosis It was recently estimated that of the more than 300,000 annual borrelia infections (Lyme disease (LD)) in the US, the CDC reports only 30,000 (1). The two-tier serology criterion recommended by the CDC, derived from the 1994 Dearborn Conference (2), requires 5-10 antibody reactivities to confirm a case, resulting in many positive Lyme disease (LD) titers with fewer reactivities being ignored and untreated. In contrast, a single reactivity against a crude flagella antigen or a positive IgG ELISA against a whole cell borrelia sonicate (WCS) is often sufficient to detect new infection (3). In 1999 Felz reported 22/22 people with an erythema migrans rash in Georgia and South Carolina, areas the CDC insist is devoid of LD, had IgG antibody against the flagella (3). The WCS from the inexpensive, widely available B31 Long Island borrelia isolate has enough ubiquitous p41 flagella epitopes to detect borrelia infections across the US, Europe, and China (4). As shown in Table 1 specific antibodies may take more than 5 weeks to develop and if assayed too early may be absent. Table 1 shows the serology of a woman with a negative LD serology hospitalized with a diagnosis of aseptic meningitis. A week after discharge she had a highly positive ELISA, a strong anti-41 kd IgG band, and 3 IgM bands. She was treated with 4 weeks of oral doxycycline, recovered fully, and remains well 2 years later. Anti-borrelia antibodies can take 5 weeks to develop and may have reactivity only to the p41 flagella; obtained too early or requiring restrictive criteria, serology may be falsely reported as negative. Since Congress is considering closer oversight of FDA approved LD testing (5); it is imperative testing becomes evidence-based, sensitive, and reflects biomedical reality. The CDC’s current 20 year old criteria for LD testing leave many infected people with spurious false negative tests, undiagnosed, and untreated.   Table 1: Serologic Response to EM

Date IgG/IgM EIA IgG bands IgM bands

Early June noted 5 mm light brown bump on thigh June 27 negative none none negative July 8 5.49* P41 + p23,39,41 + IgM positive/WB negative < 5 bands

August 1 month 100mg BID PO doxycycline Next year 4.79 p41, p23 + none negative

• relative optical density (1.00 = 3 Standard Deviations greater than mean of negative controls)
• present

References 1. Kuehn BM. CDC Estimates 300000 US Cases of Lyme Disease Annually. JAMA.18, 2013. 310, 1110.

1. CDC (1995) Recommendations for test performance and interpretation from the second national conference on serologic diagnosis of Lyme disease. Morbidity and Mortality Weekly Report 44, 590–591.

2. Felz MW, Chandler FW Jr, Oliver JH Jr, Rahn DW, Schriefer ME. Solitary erythema migrans in Georgia and South Carolina. Arch Dermatol. 1999; 135:1317-26.

3. Chao LL, Chen YJ, Shih CM. First isolation and molecular identification of Borrelia burgdorferi sensu stricto andBorrelia afzelii from skin biopsies of patients in Taiwan. Int J Infect Dis. 2011 Mar; 15:e182-7.

4. Nelson C, Hojvat S, Johnson B, Petersen J, Schriefer M, Beard CB, Petersen L, Mead P. Concerns regarding a new culture method for Borrelia burgdorferi not approved for the diagnosis of Lyme disease. Centers for Disease Control and Prevention (CDC). MMWR Mor