On 2018 Feb 04, Sin Hang Lee commented:

The medical profession, including medical schools and hospitals, is now a part of the health care industry, and implementation of editorial policies of medical journals is commonly biased in favor of business interests. PubMed Commons has offered the only, albeit constrained, open forum to air dissenting research and opinions in science-based language. Discontinuation of PubMed Commons will silence any questioning of the industry-sponsored promotional publications indexed in PubMed.

On 2017 Jun 23, Samuel Shor commented:

Marzec, et al (1) described 5 cases of treated chronic Lyme disease that resulted in poor outcomes We are concerned about 3 conclusions: 1. Characterization of chronic Lyme disease as an invalid nebulous condition 2 “…..evidence that the recommended two-tiered serologic testing is actually more sensitive the longer B. burgdeorferi infection has been present” 3. “Studies have not shown that such treatments lead to substantial long-term improvements for patients.” We too are concerned about any individual whose outcomes represent complications to well-intentioned intervention. However, there is substantive support in the literature for the existence of 1. Chronic Lyme disease-Our perspective is that this represents the clinical manifestations of ongoing active infection by Borrelia burgdorferi (Bb) sensu latu complex in the setting of either chronic untreated or inadequately treated individuals. The lilkihood of undiagnosed acute Lyme is increased by the infrequency of patients recalling tick bites. In one study representing CDC criteria diagnosed Lyme disease, only 14% had that recollection. (2) Not all cases of acute Lyme are associated with an erythema (EM) rash. Over 15 years, 31% of the reported surveillance cases lacked an EM rash. (3) The ILADS guidelines (4) describe the Lyme post treatment "….persistence of B. burgdorferi in specific individuals and animal models." The 2012 Embers (5) nonhuman primate and 2014 Hodzic (6) murine studies provide evidence of persistence of Bb infection after MBC adequate courses of antimicrobials. Additional animal and human studies support this concept (7-10). We want to emphasize that other etiologies may be causal, but that a cohort of these patients likely have a perpetuation of chronic signs and symptoms due to an active Bb infection. 2. Sensitivity of two tiered testing in late Lyme: Based upon a 2008 study by Steere et al (11) “the sensitivity of 2-tier testing in patients with later manifestations of Lyme disease was 100%, and the specificity was 99%” Entrance criteria for late stage Lyme: “In all patients with neurologic, cardiac, or joint involvement, a serologic result positive for B. burgdorferi by ELISA and Western blot was required for case inclusion….” “Because the entrance criteria for the aforementioned analysis REQUIRED positive serologies … by definition, all patients with disseminated or persistent Lyme disease were required to have a positive serologic test result. It is disingenuous to define a condition by a positive test result and then state that the test has 100% sensitivity…” (12) By extension, the concept of seronegativity is well-documented in cases of chronic Lyme disease (13-15) In a study, patients with a positive culture and/or PCR results and active late Lyme disease, 63.5% were not two-tier positive. (16) A second study of pcr positive late Lyme patients found that 56.3% were seronegative. (17) 3. “Studies have not shown that such treatments lead to substantial long-term improvements for patients.” A number of studies discount this claim. In 2 of the 4 NIH supported prospective human trials by Fallon (18) and Krupp (19), sub-cohort analysis showed statistically significant benefit to retreatment. In the former study 37 patients who were suspected of having active neuroborreliosis, and were treated with 10 weeks of 2gms/day IV Ceftriaxone. Pain and physical functioning improved at 12 and was sustained at 24 weeks. The authors indicated that “these benefits were felt to be independent of carefully assessed placebo effects.” In the latter study 55 patients who were felt to have active infection by Bb, with persistent severe fatigue of 6 or more months received 28 days of IV Ceftriaxone. A significant improvement in fatigue was sustained at 6 months. Other prospective trials of prolonged antimicrobial treatment were employed that revealed statistically significant improved outcomes. (20-22) In summary, as unfortunate are the 5 cases reported by Marzec, it is this author’s belief that they should not be used to discount a real entity, chronic Lyme disease. Whether due to the lack of timely diagnosis or adequacy of intervention, the literature supports the concept of chronic active Bb infection. That the diagnostic sensitivity of the 2 tiered paradigm is flawed, and seronegative active Bb infection exists. That emphasis should be made to generate a careful differential diagnosis, proactive management with probiotics and careful monitoring in the selective utility of long term antibiotics. As such, these often disabled individuals will more readily have access to the care they deserve, with compassion and empathetic oversight. Samuel Shor, MD, FACP President ILADS [International Lyme and Associated Diseases Society] Associate Clinical Professor George Washington University Health Care Sciences 1. Marzec NS, 2017 2. Berger BW, 1989 3. Bacon RM, 2008 4. Cameron DJ, 2014 5. Embers ME, 2012 6. Hodzic E, 2014 7. Treib J, 1998 8. Steere AC, 1990 9. Dvoráková J, 2004 10. Berglund J, 2002 11. Steere AC, 2008 12. Stricker RB, 2008 13. Breier F, 2001 14. Dejmková H, 2002 15. Schutzer SE, 1990 16. Oksi J, 1995 17. Chmielewski T, 2003 18. Fallon BA, 2008 19. Krupp LB, 2003 20. Cameron D, 2008 21. Wahlberg P, 1994 22. Oksi J, 1998

On 2017 Jun 20, Sin Hang Lee commented:

Dear L Ide: I have stopped reading NEJM since its Publisher fired Dr. Jerome Kassirer as the editor in chief. If you have published an article in the NEJM against intravenous or prolonged antibiotic treatment of SBE cases, please list the reference here. Then I will try to read it. What is elispot anyway? Have you used it? I was talking about using borrelial gene sequencing to diagnose chronic Lyme disease. Please write more if you have any objections.

On 2017 Jun 19, L Ide commented:

Sin Hang Lee, please read the NEJM. Longterm antibiotics are rubbish. I hope you 're not in favor of the not evidence-based test elispot? Thank you Marzec et al. for your article.

On 2017 Jun 19, Sin Hang Lee commented:

Marzec and colleagues presented five “chronic Lyme disease” patients who did not benefit from additional antibiotic treatment when the diagnoses of “chronic Lyme disease” were made on the basis of clinical symptoms and signs (www.cdc.gov/lyme/diagnosistesting/) or by unvalidated tests. The authors have not presented evidence to show that chronic Lyme disease patients with borrelial spirochetemia proven by culture or by gene sequencing do not benefit from additional antibiotic treatment. In medicine, certain chronic infections, such as subacute bacterial endocarditis, may require intravenous or prolonged antibiotic treatment [1] in spite of its potential side effects.

The CDC should give the practitioners a case definition of Lyme disease, as for Ebola and Zika.

Conflicts of Interest: Sin Hang Lee, MD is the director of Milford Molecular Diagnostics Laboratory specialized in developing DNA sequencing-based diagnostic tests.

References 1. Hoen B. Epidemiology and antibiotic treatment of infective endocarditis: an update. Heart 2006 ;92 :1694-700. Review.

On 2017 Jun 18, Raphael Stricker commented:

Chronic Lyme Disease Treatment: Science versus Anecdotes.

Lorraine Johnson, Raphael B. Stricker, MD.

Lymedisease.org, PO Box 1352, Chico, CA 95927; ILADS, PO Box 341461, Bethesda, MD 20827

lorrainejohnson@outlook.com; rstricker@usmamed.com

The article by Marzec et al. published in MMWR purports to show the dangers of treatment in patients diagnosed with chronic Lyme disease (1). Recent reports from the Centers for Disease Control and Prevention (CDC) indicate that more than 300,000 new cases of Lyme disease are diagnosed each year in the USA (2). The MMWR article from the CDC describes five anecdotal cases of treatment complications in these patients while ignoring the significant morbidity related to denial of treatment for chronic Lyme disease (2,3). The resultant biased report raises scientific and ethical issues about the CDC's role in promoting the best care for patients with tickborne diseases.

The MMWR piece resulted from anecdotal reports gathered by Dr. Christina Nelson of the CDC. The article notes that the information was gathered because “clinicians and state health departments periodically contact CDC concerning patients who have acquired serious bacterial infections during treatments for chronic Lyme disease.” However, an ethics complaint filed against Dr. Nelson by the Lyme disease patient advocacy group LymeDisease.org suggests that these adverse event reports were in fact specifically solicited by Dr. Nelson via emails distributed in 2014 (4). Dr. Nelson asked clinicians from the Infectious Diseases Society of America (IDSA) to provide anecdotal evidence of harm to patients from intravenous antibiotic therapy related to Lyme disease, and she apparently offered coauthorship of her article as an incentive to describe these adverse events. She did not ask for consequences of failing to treat these patients, nor did she solicit commentary from practitioners who treat chronic Lyme disease according to the guidelines of the International Lyme and Associated Diseases Society (ILADS).

The risk of any medical treatment is extremely context-sensitive. A crucial question is whether the risks of treatment are warranted given the potential benefits, the availability of other treatment options, the severity of the patient's presentation, and the risk tolerance of the individual patient. By asking for an assessment of treatment risks only, Dr. Nelson is framing the issue in a manner that excludes the other half of the equation in a risk/benefit assessment. She is also ignoring an issue that is critical to patients who suffer a profoundly diminished quality of life due to their illness, namely the risk of not treating (5,6). Moreover, by failing to mention that these adverse event reports were rare and specifically solicited, she implies that these rare occurrences are a common concern. In reality, studies of the risks and benefits associated with intravenous antibiotic treatment for Lyme disease indicate that the risks of adverse events are no greater than the risks of intravenous therapy in other unrelated diseases (7,8).

By asking the question only of those on one side of the controversy, Dr. Nelson is further demonstrating favoritism and a lack of impartiality on the part of the CDC. Accordingly, Dr. Nelson's solicitation of anecdotal adverse events for case studies of Lyme disease is a highly inappropriate partisan act of favoritism toward the IDSA viewpoint at the expense of critical stakeholders - Lyme disease patients and their treating physicians - and an attack on the ILADS viewpoints.

References 1. Marzec NS, Nelson C, Waldron PR, et al. Serious bacterial infections acquired during treatment of patients given a diagnosis of chronic Lyme disease - United States. MMWR Morb Mortal Wkly Rep. 2017 Jun 16;66(23):607-609. 2. Stricker RB, Johnson L. Lyme disease: Call for a ‘‘Manhattan Project’’ to combat the epidemic. PLoS Pathog. 2014;10(1): e1003796. 3. Stricker RB, Fesler MC. Chronic Lyme disease: A working case definition. Chronic Dis Int. 2017; 4(1): 1025. 4. Leland DK. TOUCHED BY LYME: CDC ignores ethics, attacks “chronic Lyme”. Available at https://www.lymedisease.org/touchedbylyme-cdc-ignores-ethics/. Accessed June 16, 2017. 5. Johnson L, Aylward A, Stricker RB. Healthcare access and burden of care for patients with Lyme disease: a large United States survey. Health Policy. 2011;102: 64–71. 6. Johnson L, Wilcox S, Mankoff J, Stricker RB. Severity of chronic Lyme disease compared to other chronic conditions: a quality of life survey. Peer J. 2014;2:e322. 7. Stricker RB, Green CL, Savely VR, Chamallas SN, Johnson L. Safety of intravenous antibiotic therapy in patients referred for treatment of neurologic Lyme disease. Minerva Med. 2010;101:1–7. 8. Stricker RB, Delong AK, Green CL, et al. Benefit of intravenous antibiotic therapy in patients referred for treatment of neurologic Lyme disease. Int J Gen Med. 2011; 4: 639–646. Disclosure: RBS and LJ are members of the International Lyme and Associated Diseases Society (ILADS) and directors of LymeDisease.org. They have no financial or other conflicts to declare.

On 2017 Jun 18, Raphael Stricker commented:

Chronic Lyme Disease Treatment: Science versus Anecdotes.

Lorraine Johnson, Raphael B. Stricker, MD.

Lymedisease.org, PO Box 1352, Chico, CA 95927; ILADS, PO Box 341461, Bethesda, MD 20827

lorrainejohnson@outlook.com; rstricker@usmamed.com

The article by Marzec et al. published in MMWR purports to show the dangers of treatment in patients diagnosed with chronic Lyme disease (1). Recent reports from the Centers for Disease Control and Prevention (CDC) indicate that more than 300,000 new cases of Lyme disease are diagnosed each year in the USA (2). The MMWR article from the CDC describes five anecdotal cases of treatment complications in these patients while ignoring the significant morbidity related to denial of treatment for chronic Lyme disease (2,3). The resultant biased report raises scientific and ethical issues about the CDC's role in promoting the best care for patients with tickborne diseases.

The MMWR piece resulted from anecdotal reports gathered by Dr. Christina Nelson of the CDC. The article notes that the information was gathered because “clinicians and state health departments periodically contact CDC concerning patients who have acquired serious bacterial infections during treatments for chronic Lyme disease.” However, an ethics complaint filed against Dr. Nelson by the Lyme disease patient advocacy group LymeDisease.org suggests that these adverse event reports were in fact specifically solicited by Dr. Nelson via emails distributed in 2014 (4). Dr. Nelson asked clinicians from the Infectious Diseases Society of America (IDSA) to provide anecdotal evidence of harm to patients from intravenous antibiotic therapy related to Lyme disease, and she apparently offered coauthorship of her article as an incentive to describe these adverse events. She did not ask for consequences of failing to treat these patients, nor did she solicit commentary from practitioners who treat chronic Lyme disease according to the guidelines of the International Lyme and Associated Diseases Society (ILADS).

The risk of any medical treatment is extremely context-sensitive. A crucial question is whether the risks of treatment are warranted given the potential benefits, the availability of other treatment options, the severity of the patient's presentation, and the risk tolerance of the individual patient. By asking for an assessment of treatment risks only, Dr. Nelson is framing the issue in a manner that excludes the other half of the equation in a risk/benefit assessment. She is also ignoring an issue that is critical to patients who suffer a profoundly diminished quality of life due to their illness, namely the risk of not treating (5,6). Moreover, by failing to mention that these adverse event reports were rare and specifically solicited, she implies that these rare occurrences are a common concern. In reality, studies of the risks and benefits associated with intravenous antibiotic treatment for Lyme disease indicate that the risks of adverse events are no greater than the risks of intravenous therapy in other unrelated diseases (7,8).

By asking the question only of those on one side of the controversy, Dr. Nelson is further demonstrating favoritism and a lack of impartiality on the part of the CDC. Accordingly, Dr. Nelson's solicitation of anecdotal adverse events for case studies of Lyme disease is a highly inappropriate partisan act of favoritism toward the IDSA viewpoint at the expense of critical stakeholders - Lyme disease patients and their treating physicians - and an attack on the ILADS viewpoints.

References 1. Marzec NS, Nelson C, Waldron PR, et al. Serious bacterial infections acquired during treatment of patients given a diagnosis of chronic Lyme disease - United States. MMWR Morb Mortal Wkly Rep. 2017 Jun 16;66(23):607-609. 2. Stricker RB, Johnson L. Lyme disease: Call for a ‘‘Manhattan Project’’ to combat the epidemic. PLoS Pathog. 2014;10(1): e1003796. 3. Stricker RB, Fesler MC. Chronic Lyme disease: A working case definition. Chronic Dis Int. 2017; 4(1): 1025. 4. Leland DK. TOUCHED BY LYME: CDC ignores ethics, attacks “chronic Lyme”. Available at https://www.lymedisease.org/touchedbylyme-cdc-ignores-ethics/. Accessed June 16, 2017. 5. Johnson L, Aylward A, Stricker RB. Healthcare access and burden of care for patients with Lyme disease: a large United States survey. Health Policy. 2011;102: 64–71. 6. Johnson L, Wilcox S, Mankoff J, Stricker RB. Severity of chronic Lyme disease compared to other chronic conditions: a quality of life survey. Peer J. 2014;2:e322. 7. Stricker RB, Green CL, Savely VR, Chamallas SN, Johnson L. Safety of intravenous antibiotic therapy in patients referred for treatment of neurologic Lyme disease. Minerva Med. 2010;101:1–7. 8. Stricker RB, Delong AK, Green CL, et al. Benefit of intravenous antibiotic therapy in patients referred for treatment of neurologic Lyme disease. Int J Gen Med. 2011; 4: 639–646. Disclosure: RBS and LJ are members of the International Lyme and Associated Diseases Society (ILADS) and directors of LymeDisease.org. They have no financial or other conflicts to declare.

On 2017 Jun 19, Sin Hang Lee commented:

Marzec and colleagues presented five “chronic Lyme disease” patients who did not benefit from additional antibiotic treatment when the diagnoses of “chronic Lyme disease” were made on the basis of clinical symptoms and signs (www.cdc.gov/lyme/diagnosistesting/) or by unvalidated tests. The authors have not presented evidence to show that chronic Lyme disease patients with borrelial spirochetemia proven by culture or by gene sequencing do not benefit from additional antibiotic treatment. In medicine, certain chronic infections, such as subacute bacterial endocarditis, may require intravenous or prolonged antibiotic treatment [1] in spite of its potential side effects.

The CDC should give the practitioners a case definition of Lyme disease, as for Ebola and Zika.

Conflicts of Interest: Sin Hang Lee, MD is the director of Milford Molecular Diagnostics Laboratory specialized in developing DNA sequencing-based diagnostic tests.

References 1. Hoen B. Epidemiology and antibiotic treatment of infective endocarditis: an update. Heart 2006 ;92 :1694-700. Review.

On 2017 Jun 19, L Ide commented:

Sin Hang Lee, please read the NEJM. Longterm antibiotics are rubbish. I hope you 're not in favor of the not evidence-based test elispot? Thank you Marzec et al. for your article.

On 2017 Jun 20, Sin Hang Lee commented:

Dear L Ide: I have stopped reading NEJM since its Publisher fired Dr. Jerome Kassirer as the editor in chief. If you have published an article in the NEJM against intravenous or prolonged antibiotic treatment of SBE cases, please list the reference here. Then I will try to read it. What is elispot anyway? Have you used it? I was talking about using borrelial gene sequencing to diagnose chronic Lyme disease. Please write more if you have any objections.

On 2017 Jun 23, Samuel Shor commented:

Marzec, et al (1) described 5 cases of treated chronic Lyme disease that resulted in poor outcomes We are concerned about 3 conclusions: 1. Characterization of chronic Lyme disease as an invalid nebulous condition 2 “…..evidence that the recommended two-tiered serologic testing is actually more sensitive the longer B. burgdeorferi infection has been present” 3. “Studies have not shown that such treatments lead to substantial long-term improvements for patients.” We too are concerned about any individual whose outcomes represent complications to well-intentioned intervention. However, there is substantive support in the literature for the existence of 1. Chronic Lyme disease-Our perspective is that this represents the clinical manifestations of ongoing active infection by Borrelia burgdorferi (Bb) sensu latu complex in the setting of either chronic untreated or inadequately treated individuals. The lilkihood of undiagnosed acute Lyme is increased by the infrequency of patients recalling tick bites. In one study representing CDC criteria diagnosed Lyme disease, only 14% had that recollection. (2) Not all cases of acute Lyme are associated with an erythema (EM) rash. Over 15 years, 31% of the reported surveillance cases lacked an EM rash. (3) The ILADS guidelines (4) describe the Lyme post treatment "….persistence of B. burgdorferi in specific individuals and animal models." The 2012 Embers (5) nonhuman primate and 2014 Hodzic (6) murine studies provide evidence of persistence of Bb infection after MBC adequate courses of antimicrobials. Additional animal and human studies support this concept (7-10). We want to emphasize that other etiologies may be causal, but that a cohort of these patients likely have a perpetuation of chronic signs and symptoms due to an active Bb infection. 2. Sensitivity of two tiered testing in late Lyme: Based upon a 2008 study by Steere et al (11) “the sensitivity of 2-tier testing in patients with later manifestations of Lyme disease was 100%, and the specificity was 99%” Entrance criteria for late stage Lyme: “In all patients with neurologic, cardiac, or joint involvement, a serologic result positive for B. burgdorferi by ELISA and Western blot was required for case inclusion….” “Because the entrance criteria for the aforementioned analysis REQUIRED positive serologies … by definition, all patients with disseminated or persistent Lyme disease were required to have a positive serologic test result. It is disingenuous to define a condition by a positive test result and then state that the test has 100% sensitivity…” (12) By extension, the concept of seronegativity is well-documented in cases of chronic Lyme disease (13-15) In a study, patients with a positive culture and/or PCR results and active late Lyme disease, 63.5% were not two-tier positive. (16) A second study of pcr positive late Lyme patients found that 56.3% were seronegative. (17) 3. “Studies have not shown that such treatments lead to substantial long-term improvements for patients.” A number of studies discount this claim. In 2 of the 4 NIH supported prospective human trials by Fallon (18) and Krupp (19), sub-cohort analysis showed statistically significant benefit to retreatment. In the former study 37 patients who were suspected of having active neuroborreliosis, and were treated with 10 weeks of 2gms/day IV Ceftriaxone. Pain and physical functioning improved at 12 and was sustained at 24 weeks. The authors indicated that “these benefits were felt to be independent of carefully assessed placebo effects.” In the latter study 55 patients who were felt to have active infection by Bb, with persistent severe fatigue of 6 or more months received 28 days of IV Ceftriaxone. A significant improvement in fatigue was sustained at 6 months. Other prospective trials of prolonged antimicrobial treatment were employed that revealed statistically significant improved outcomes. (20-22) In summary, as unfortunate are the 5 cases reported by Marzec, it is this author’s belief that they should not be used to discount a real entity, chronic Lyme disease. Whether due to the lack of timely diagnosis or adequacy of intervention, the literature supports the concept of chronic active Bb infection. That the diagnostic sensitivity of the 2 tiered paradigm is flawed, and seronegative active Bb infection exists. That emphasis should be made to generate a careful differential diagnosis, proactive management with probiotics and careful monitoring in the selective utility of long term antibiotics. As such, these often disabled individuals will more readily have access to the care they deserve, with compassion and empathetic oversight. Samuel Shor, MD, FACP President ILADS [International Lyme and Associated Diseases Society] Associate Clinical Professor George Washington University Health Care Sciences 1. Marzec NS, 2017 2. Berger BW, 1989 3. Bacon RM, 2008 4. Cameron DJ, 2014 5. Embers ME, 2012 6. Hodzic E, 2014 7. Treib J, 1998 8. Steere AC, 1990 9. Dvoráková J, 2004 10. Berglund J, 2002 11. Steere AC, 2008 12. Stricker RB, 2008 13. Breier F, 2001 14. Dejmková H, 2002 15. Schutzer SE, 1990 16. Oksi J, 1995 17. Chmielewski T, 2003 18. Fallon BA, 2008 19. Krupp LB, 2003 20. Cameron D, 2008 21. Wahlberg P, 1994 22. Oksi J, 1998

On 2018 Feb 04, Sin Hang Lee commented:

The medical profession, including medical schools and hospitals, is now a part of the health care industry, and implementation of editorial policies of medical journals is commonly biased in favor of business interests. PubMed Commons has offered the only, albeit constrained, open forum to air dissenting research and opinions in science-based language. Discontinuation of PubMed Commons will silence any questioning of the industry-sponsored promotional publications indexed in PubMed.