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 Sep 21, Sin Hang Lee commented:

The narrative review titled “To test or not to test? Laboratory support for the diagnosis of Lyme borreliosis” by Dessau and colleagues[1] is a position paper of the authors. It is not a systematic review. A systemic review typically involves a detailed and comprehensive plan and search strategy derived a priori, with the goal of reducing bias by identifying, appraising, and synthesizing all relevant studies on a particular topic.[2] The gross biases in this position paper are:

1.Dessau and colleagues recognized “Lyme borreliosis (LB) is a tick-borne infection caused by Borrelia burgdorferi sensu lato.”, namely a bacterial infectious disease. However, the authors proposed using objective signs of clinical presentations to diagnose borreliosis[1], but failed to mention that the European Centre for Disease Prevention and Control requires detection of the pathogen’s nucleic acid in a clinical specimen and confirmation by DNA sequencing for diagnosis of any emerging infectious diseases, such as Ebola.[3] According to an official publication of the United States Centers for Disease Control and Prevention, the state of the art in diagnosing infectious diseases is by molecular approaches[4], in particular by 16S rRNA gene analysis for bacterial infectious diseases, such as anthrax.[5]

2.Dessau and colleagues stated that “clinicians are advised to avoid serological testing whenever the clinical symptoms are not indicative of LB according to the case definitions”. However, the case definitions which were written by some of the authors of the current position paper are “for reliable epidemiological studies and are of great value in clinical management[6]”, not for reliable diagnosis of Lyme borreliosis. In fact, in another recet review, two of the co-authors (Strle and Hovius) of the current narrative review stated on record that “Demonstration of borrelial infection by laboratory testing is required for reliable diagnosis of Lyme borreliosis, with the exception of erythema migrans.” [7] Therefore, at least two of the co-authors of this position paper[1] are advancing an agenda of managing clinical patients of Lyme borreliosis, an infectious disease, without a reliable diagnosis against their own beliefs.

3.The statement “Laboratory testing for antibodies to B. burgdorferi in serum is necessary for diagnosing suspected manifestations of LB such as Lyme carditis, borrelial lymphocytoma, Lyme arthritis, acrodermatitis chronica atrophicans and possibly other rare LB manifestations” while omitting direct DNA testing of blood for the diagnosis of spirochetemia is biased. At least two of the co-authors of this position paper knew and stated that the early stage of Lyme borreliosis infections “can be treated successfully with a 10–14 day course of antibiotics”, “serodiagnostic tests are insensitive during the first several weeks of infection” and if untreated “within days to weeks, the strains of B. burgdorferi in the United States commonly disseminate from the site of the tick bite to other regions of the body.”[7] Sensitive 16S rRNA gene analysis for the detection of Lyme borreliae in blood samples has been known since 1992.[8-12] Continued suppression of using direct DNA testing for the diagnosis of early Lyme borreliosis infections is no longer acceptable.

4.The authors of this position paper emphasized “an immune response with clinical findings, such as skin lesions, neurological signs, cardiac involvement (e.g. AV block), or arthritis involving the large joints”, but avoided mentioning that cardiac involvements may be due to myocarditis caused by spirochetes invading the myocardium.[13] The authors focused on management of the immune response in the cases of chronic Lyme neuroborreliosis because “there is no convincing evidence that B. burgdorferi produces any toxin.” It is well known that Treponema pallidum, the spirochetes causing neurosyphilis, also lacks a lipopolysaccharide endotoxin. However, it possesses abundant lipoproteins which induce inflammatory processes.[14] Would these authors recommend not to treat patients suffering from neurosyphilis with antibiotics?

In summary, this narrative review by Dessau and colleagues contains serious scientific biases and should not be used as materials to influence public health policy decisions or as guidelines to direct clinical practice.

References

[1] Dessau RB, van Dam AP, Fingerle V, Gray J, Hovius J, Hunfeld KP, Jaulhac B, Kahl O, Kristoferitsch W, Lindgren PE, Markowicz M, Mavin S, Ornstein K, Rupprecht T, Stanek G, Strle F. To test or not to test? Laboratory support for the diagnosis of Lyme borreliosis. Clin Microbiol Infect. 2017 Sep 5. pii: S1198-743X(17)30488-3.

[2] Uman LS. Systematic reviews and meta-analyses. J Can Acad Child Adolesc Psychiatry. 2011;20:57-9.

[3] http://ecdc.europa.eu/en/healthtopics/ebola_marburg_fevers/EVDcasedefinition/Pages/default.aspx

[4] CDC. State of the Art. Molecular Approaches to Diagnosing and Managing Infectious Diseases: Practicality and Costs https://wwwnc.cdc.gov/eid/article/7/2/70-0312_article

[5] Sacchi CT, et al. Sequencing of 16S rRNA gene: a rapid tool for identification of Bacillus anthracis. Emerg Infect Dis. 2002 Oct;8(10):1117-23.

[6] Stanek G, Fingerle V, Hunfeld KP, Jaulhac B, Kaiser R, Krause A, Kristoferitsch W, O'Connell S, Ornstein K, Strle F, Gray J. Lyme borreliosis: clinical case definitions for diagnosis and management in Europe. Clin Microbiol Infect. 2011;17:69-79.

[7] Steere AC, Strle F, Wormser GP, Hu LT, Branda JA, Hovius JW, Li X, Mead PS. Lyme borreliosis. Nat Rev Dis Primers. 2016 Dec 15;2:16090.

[8] Marconi RT Garon CF . Development of polymerase chain reaction primer sets for diagnosis of Lyme disease and for species-specific identification of Lyme disease isolates by 16S rRNA signature nucleotide analysis. J Clin Microbiol . 1992;30:2830–2834.

[9] Cyr TL, et al Improving the specificity of 16S rDNA–based polymerase chain reaction for detecting Borrelia burgdorferi sensu lato–causative agents of human Lyme disease. J Appl Microbiol . 2005;98:962–970.

[10] Santino I, et al. Detection of Borrelia burgdorferi sensu lato DNA by PCR in serum of patients with clinical symptoms of Lyme borreliosis. FEMS Microbiol Lett . 2008;283:30–35.

[11] Lee SH, et al. Early Lyme disease with spirochetemia - diagnosed by DNA sequencing. BMC Res Notes. 2010 Nov 1;3:273. doi: 10.1186/1756-0500-3-273.

[12] Lee SH, et al. DNA sequencing diagnosis of off-season spirochetemia with low bacterial density in Borrelia burgdorferi and Borrelia miyamotoi infections. Int J Mol Sci. 2014 Jun 25;15(7):11364-86.

[13] Muehlenbachs A, et al. Cardiac Tropism of Borrelia burgdorferi: An Autopsy Study of Sudden Cardiac Death Associated with Lyme Carditis. Am J Pathol. 2016;186:1195-205.

[14] https://www.ncbi.nlm.nih.gov/books/NBK7716/

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

On 2017 Sep 21, Sin Hang Lee commented:

The narrative review titled “To test or not to test? Laboratory support for the diagnosis of Lyme borreliosis” by Dessau and colleagues[1] is a position paper of the authors. It is not a systematic review. A systemic review typically involves a detailed and comprehensive plan and search strategy derived a priori, with the goal of reducing bias by identifying, appraising, and synthesizing all relevant studies on a particular topic.[2] The gross biases in this position paper are:

1.Dessau and colleagues recognized “Lyme borreliosis (LB) is a tick-borne infection caused by Borrelia burgdorferi sensu lato.”, namely a bacterial infectious disease. However, the authors proposed using objective signs of clinical presentations to diagnose borreliosis[1], but failed to mention that the European Centre for Disease Prevention and Control requires detection of the pathogen’s nucleic acid in a clinical specimen and confirmation by DNA sequencing for diagnosis of any emerging infectious diseases, such as Ebola.[3] According to an official publication of the United States Centers for Disease Control and Prevention, the state of the art in diagnosing infectious diseases is by molecular approaches[4], in particular by 16S rRNA gene analysis for bacterial infectious diseases, such as anthrax.[5]

2.Dessau and colleagues stated that “clinicians are advised to avoid serological testing whenever the clinical symptoms are not indicative of LB according to the case definitions”. However, the case definitions which were written by some of the authors of the current position paper are “for reliable epidemiological studies and are of great value in clinical management[6]”, not for reliable diagnosis of Lyme borreliosis. In fact, in another recet review, two of the co-authors (Strle and Hovius) of the current narrative review stated on record that “Demonstration of borrelial infection by laboratory testing is required for reliable diagnosis of Lyme borreliosis, with the exception of erythema migrans.” [7] Therefore, at least two of the co-authors of this position paper[1] are advancing an agenda of managing clinical patients of Lyme borreliosis, an infectious disease, without a reliable diagnosis against their own beliefs.

3.The statement “Laboratory testing for antibodies to B. burgdorferi in serum is necessary for diagnosing suspected manifestations of LB such as Lyme carditis, borrelial lymphocytoma, Lyme arthritis, acrodermatitis chronica atrophicans and possibly other rare LB manifestations” while omitting direct DNA testing of blood for the diagnosis of spirochetemia is biased. At least two of the co-authors of this position paper knew and stated that the early stage of Lyme borreliosis infections “can be treated successfully with a 10–14 day course of antibiotics”, “serodiagnostic tests are insensitive during the first several weeks of infection” and if untreated “within days to weeks, the strains of B. burgdorferi in the United States commonly disseminate from the site of the tick bite to other regions of the body.”[7] Sensitive 16S rRNA gene analysis for the detection of Lyme borreliae in blood samples has been known since 1992.[8-12] Continued suppression of using direct DNA testing for the diagnosis of early Lyme borreliosis infections is no longer acceptable.

4.The authors of this position paper emphasized “an immune response with clinical findings, such as skin lesions, neurological signs, cardiac involvement (e.g. AV block), or arthritis involving the large joints”, but avoided mentioning that cardiac involvements may be due to myocarditis caused by spirochetes invading the myocardium.[13] The authors focused on management of the immune response in the cases of chronic Lyme neuroborreliosis because “there is no convincing evidence that B. burgdorferi produces any toxin.” It is well known that Treponema pallidum, the spirochetes causing neurosyphilis, also lacks a lipopolysaccharide endotoxin. However, it possesses abundant lipoproteins which induce inflammatory processes.[14] Would these authors recommend not to treat patients suffering from neurosyphilis with antibiotics?

In summary, this narrative review by Dessau and colleagues contains serious scientific biases and should not be used as materials to influence public health policy decisions or as guidelines to direct clinical practice.

References

[1] Dessau RB, van Dam AP, Fingerle V, Gray J, Hovius J, Hunfeld KP, Jaulhac B, Kahl O, Kristoferitsch W, Lindgren PE, Markowicz M, Mavin S, Ornstein K, Rupprecht T, Stanek G, Strle F. To test or not to test? Laboratory support for the diagnosis of Lyme borreliosis. Clin Microbiol Infect. 2017 Sep 5. pii: S1198-743X(17)30488-3.

[2] Uman LS. Systematic reviews and meta-analyses. J Can Acad Child Adolesc Psychiatry. 2011;20:57-9.

[3] http://ecdc.europa.eu/en/healthtopics/ebola_marburg_fevers/EVDcasedefinition/Pages/default.aspx

[4] CDC. State of the Art. Molecular Approaches to Diagnosing and Managing Infectious Diseases: Practicality and Costs https://wwwnc.cdc.gov/eid/article/7/2/70-0312_article

[5] Sacchi CT, et al. Sequencing of 16S rRNA gene: a rapid tool for identification of Bacillus anthracis. Emerg Infect Dis. 2002 Oct;8(10):1117-23.

[6] Stanek G, Fingerle V, Hunfeld KP, Jaulhac B, Kaiser R, Krause A, Kristoferitsch W, O'Connell S, Ornstein K, Strle F, Gray J. Lyme borreliosis: clinical case definitions for diagnosis and management in Europe. Clin Microbiol Infect. 2011;17:69-79.

[7] Steere AC, Strle F, Wormser GP, Hu LT, Branda JA, Hovius JW, Li X, Mead PS. Lyme borreliosis. Nat Rev Dis Primers. 2016 Dec 15;2:16090.

[8] Marconi RT Garon CF . Development of polymerase chain reaction primer sets for diagnosis of Lyme disease and for species-specific identification of Lyme disease isolates by 16S rRNA signature nucleotide analysis. J Clin Microbiol . 1992;30:2830–2834.

[9] Cyr TL, et al Improving the specificity of 16S rDNA–based polymerase chain reaction for detecting Borrelia burgdorferi sensu lato–causative agents of human Lyme disease. J Appl Microbiol . 2005;98:962–970.

[10] Santino I, et al. Detection of Borrelia burgdorferi sensu lato DNA by PCR in serum of patients with clinical symptoms of Lyme borreliosis. FEMS Microbiol Lett . 2008;283:30–35.

[11] Lee SH, et al. Early Lyme disease with spirochetemia - diagnosed by DNA sequencing. BMC Res Notes. 2010 Nov 1;3:273. doi: 10.1186/1756-0500-3-273.

[12] Lee SH, et al. DNA sequencing diagnosis of off-season spirochetemia with low bacterial density in Borrelia burgdorferi and Borrelia miyamotoi infections. Int J Mol Sci. 2014 Jun 25;15(7):11364-86.

[13] Muehlenbachs A, et al. Cardiac Tropism of Borrelia burgdorferi: An Autopsy Study of Sudden Cardiac Death Associated with Lyme Carditis. Am J Pathol. 2016;186:1195-205.

[14] https://www.ncbi.nlm.nih.gov/books/NBK7716/

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

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.