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Developing a Prospective Gestational Lyme Disease Study

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Borrelia burgdorferi

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2742))

Abstract

Lyme disease in pregnancy is understudied. The few available reports of Borrelia infection during pregnancy collecting clinical outcomes, with or without confirmed fetal infection both in utero and neonatal, are limited to case reports and small series. Population-based studies are not available. We propose a prospective study of Borrelia infection during pregnancy based in obstetrical practices in both endemic and nonendemic areas, with long term follow-up of pregnancy outcomes and development assessment of offspring infected or exposed to Borrelia in utero using current serological, microscopic, culture, and molecular techniques. In addition to detection of Borrelia burgdorferi sensu stricto, additional Borrelia species and other pathogens known to be transmitted by ticks will be tested. Serial biospecimens including maternal and cord blood, maternal peripheral blood mononuclear cells and urine, and, when clinically indicated, amniotic fluid, chorionic villi, intrauterine cord blood, will be collected with clinical data, imaging, and for infections treatment medications. Offspring will be followed until age 5 years with annual developmental assessments to assess pregnancy outcomes. The study will require parallel development of a biorepository with strategies for management, data security and data sharing. A public-private partnership will be required to support the study.

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References

  1. Burn L, Vyse A, Pilz A et al (2023) Incidence of Lyme Borreliosis in Europe: a systematic review (2005-2020). Vector Borne Zoonotic Dis 23(4):172–194. https://doi.org/10.1089/vbz.2022.0070

    Article  PubMed  PubMed Central  Google Scholar 

  2. https://www.cdc.gov/lyme/datasurveillance/index.html. Accessed 15 June 2023

  3. DeLong A, Hsu M, Kotsoris H (2019) Estimation of cumulative number of post-treatment Lyme disease cases in the US, 2016 and 2020. BMC Public Health 19(1):352. https://doi.org/10.1186/s12889-019-6681-9

    Article  PubMed  PubMed Central  Google Scholar 

  4. Lambert JS (2020) An overview of tickborne infections in pregnancy and outcomes in the newborn: the need for prospective studies. Front Med (Lausanne) 7:72. https://doi.org/10.3389/fmed.2020.00072

    Article  PubMed  Google Scholar 

  5. https://www.prnewswire.com/news-releases/update-for-patients-and-practitioners-the-icd-11-and-lyme-borreliosis-301488697.html. Accessed 15 June 2023

  6. Leavey K, MacKenzie RK, Faber S et al (2022) Lyme Borreliosis in pregnancy and associations with parent and offspring health outcomes: an international cross-sectional survey. Front Med (Lausanne) 9:1022766. https://doi.org/10.3389/fmed.2022.1022766

    Article  PubMed  Google Scholar 

  7. Maraspin V, Lusa L, Blejec T et al (2020) Course and outcome of erythema migrans in pregnant women. J Clin Med 9(8):2364. https://doi.org/10.3390/jcm9082364

    Article  PubMed  PubMed Central  Google Scholar 

  8. Lakos A, Solymosi N (2010) Maternal Lyme Borreliosis and pregnancy outcome. Int J Infect Dis 14(6):e494–e498. https://doi.org/10.1016/j.ijid.2009.07.019

    Article  PubMed  Google Scholar 

  9. Johnson RC, Hyde FW, Rumpel CM (1984) Taxonomy of the Lyme disease spirochetes. Yale J Biol Med 57(4):529–537

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Tilly K, Rosa PA, Stewart PE (2008) Biology of infection with Borrelia burgdorferi. Infect Dis Clin N Am 22(2):217-34:v. https://doi.org/10.1016/j.idc.2007.12.013

    Article  Google Scholar 

  11. Barbour AG, Hayes SF (1986) Biology of Borrelia species. Microbiol Rev 50(4):381–400. https://doi.org/10.1128/mr.50.4.381-400.1986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Pritt BS, Mead PS, Johnson DKH et al (2016) Identification of a novel pathogenic Borrelia species causing Lyme Borreliosis with unusually high spirochaetaemia: a descriptive study. Lancet Infect Dis 16(5):556–564. https://doi.org/10.1016/S1473-3099(15)00464-8

  13. Xu G, Luo CY, Ribbe F et al (2021) Borrelia miyamotoi in human-biting ticks, United States, 2013-2019. Emerg Infect Dis 27(12):3193–3195. https://doi.org/10.3201/eid2712.204646

    Article  PubMed  PubMed Central  Google Scholar 

  14. Brummitt SI, Kjemtrup AM, Harvey DJ et al (2020) Borrelia burgdorferi and Borrelia miyamotoi seroprevalence in California blood donors. PLoS One 15(12):e0243950. https://doi.org/10.1371/journal.pone.0243950

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Burde J, Bloch EM, Kelly JR et al (2023) Human Borrelia miyamotoi infection in North America. Pathogens 12(4):553. https://doi.org/10.3390/pathogens12040553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Krause PJ, Narasimhan S, Wormser GP, Tick Borne Diseases Group et al (2014) Borrelia miyamotoi sensu lato seroreactivity and seroprevalence in the northeastern United States. Emerg Infect Dis 20(7):1183–1190. https://doi.org/10.3201/eid2007.131587

  17. Sabin AP, Scholze BP, Lovrich SD et al (2023) Clinical evaluation of a Borrelia modified two-tiered testing (MTTT) shows increased early sensitivity for Borrelia burgdorferi but not other endemic Borrelia species in a high incidence region for Lyme disease in Wisconsin. Diagn Microbiol Infect Dis 105(1):115837. https://doi.org/10.1016/j.diagmicrobio.2022.115837

    Article  CAS  PubMed  Google Scholar 

  18. Smith RP Jr, Muzaffar SB, Lavers J et al (2006) Borrelia garinii in seabird ticks (Ixodes uriae), Atlantic Coast, North America. Emerg Infect Dis 12(12):1909–1912. https://doi.org/10.3201/eid1212.060448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Baggs EM, Stack SH, Finney-Crawley JR et al (2011) Peromyscus maniculatus, a possible reservoir host of Borrelia garinii from the Gannet Islands off Newfoundland and Labrador. J Parasitol 97(5):792–794. https://doi.org/10.1645/GE-2548.1

    Article  PubMed  Google Scholar 

  20. Rudenko N, Golovchenko M, Horak A et al (2023) Genomic confirmation of Borrelia garinii, United States. Emerg Infect Dis 29(1):64–69. https://doi.org/10.3201/eid2901.220930

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lantos PM, Rumbaugh J, Bockenstedt LK et al (2021) Clinical practice guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis, and treatment of Lyme disease. Arthritis Rheumatol 73(1):12–20. https://doi.org/10.1002/art.41562

    Article  PubMed  Google Scholar 

  22. Steere AC (1989) Lyme disease. N Engl J Med 321(9):586–596. https://doi.org/10.1056/NEJM198908313210906

    Article  CAS  PubMed  Google Scholar 

  23. Council of State and Territorial Epidemiologists. Modification of Lyme disease case definition. 2021 21-ID-05 (https://www.cste.org/page/PositionStatements), chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://cdn.ymaws.com/www.cste.org/resource/resmgr/ps/ps2021/21-ID-05_Lyme_Disease.pdf. Accessed 19 June 2023

  24. Centers for Diseases Control and Prevention (2022) Tickborne diseases of the United States: a reference manual for healthcare providers. Sixth edn. https://www.cdc.gov/ticks/tickbornediseases/index.html. Accessed 19 June 2023

  25. Waddell LA, Greig J, Lindsay LR et al (2018) A systematic review on the impact of gestational Lyme disease in humans on the fetus and newborn. PLoS One 13(11):e0207067. https://doi.org/10.1371/journal.pone.0207067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. National Notifiable Diseases Surveillance System (NNDSS) (2018) Syphilis (Treponema pallidum) case definition. https://ndc.services.cdc.gov/case-definitions/syphilis-2018/

  27. Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission. Recommendation for the use of antiretroviral drugs during pregnancy and interventions to reduce perinatal HIV transmission in the United States. Department of Health and Human Services. Available at https://clinicalinfo.hiv.gov/en/guidelines/perinatal. Accessed 19 June 2023

  28. Association of State and Territorial Public Health Laboratory Directors (1994) Proceedings of the second national conference on serologic diagnosis of Lyme disease: October 27–29, 1994. Conference publication. Association of State and Territorial Public Health Laboratory Directors, Washington, DC

    Google Scholar 

  29. FDA clears new indications for existing Lyme Disease tests that may help streamline diagnoses [press release]. US Food & Drug Administration, Washington, DC, 29 Jul 2019. Accessed at https://www.fda.gov/news-events/press-announcements/fda-clears-new-indications-existing-lyme-disease-tests-may-help-streamline-diagnoses

  30. Mead P, Petersen J, Hinckley A (2019) Updated CDC recommendation for serologic diagnosis of Lyme disease. MMWR Morb Mortal Wkly Rep 68(32):703

    Article  PubMed  PubMed Central  Google Scholar 

  31. Association of Public Health Laboratories. Suggested reporting language, interpretation and guidance regarding Lyme disease serologic test results. Silver Spring, May 2021. Accessed at https://www.aphl.org/aboutAPHL/publications/Documents/ID-2021-Lyme-Disease-Serologic-Testing-Reporting.pdf

  32. Niewiesk S (2014) Maternal antibodies: clinical significance, mechanism of interference with immune responses, and possible vaccination strategies. Front Immunol 5:446. https://doi.org/10.3389/fimmu.2014.00446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Aguero-Rosenfeld ME, Nowakowski J, McKenna DF et al (1993) Serodiagnosis in early Lyme disease. J Clin Microbiol 31(12):3090–3095. https://doi.org/10.1128/jcm.31.12.3090-3095.1993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Aguero-Rosenfeld ME, Nowakowski J, Bittker S et al (1996) Evolution of the serologic response to Borrelia burgdorferi in treated patients with culture-confirmed erythema migrans. J Clin Microbiol 34(1):1–9. https://doi.org/10.1128/jcm.34.1.1-9.1996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Steere AC, McHugh G, Damle N et al (2008) Prospective study of serologic tests for Lyme disease. Clin Infect Dis 47(2):188–195. https://doi.org/10.1086/589242

    Article  PubMed  Google Scholar 

  36. Steere AC, Grodzicki RL, Kornblatt AN et al (1983) The spirochetal etiology of Lyme disease. N Engl J Med 308(13):733–740. https://doi.org/10.1056/NEJM198303313081301

    Article  CAS  PubMed  Google Scholar 

  37. Szer IS, Taylor E, Steere AC (1991) The long-term course of Lyme Arthritis in children. N Engl J Med 325(3):159–163. https://doi.org/10.1056/NEJM199107183250304

  38. Kalish RA, McHugh G, Granquist J et al (2001) Persistence of immunoglobulin M or immunoglobulin G antibody responses to Borrelia burgdorferi 10-20 years after active Lyme disease. Clin Infect Dis 33(6):780–785. https://doi.org/10.1086/322669

    Article  CAS  PubMed  Google Scholar 

  39. Kannian P, McHugh G, Johnson BJ et al (2007) Antibody responses to Borrelia burgdorferi in patients with antibiotic-refractory, antibiotic-responsive, or non-antibiotic-treated Lyme Arthritis. Arthritis Rheum 56(12):4216–4225. https://doi.org/10.1002/art.23135

  40. Glatz M, Golestani M, Kerl H et al (2006) Clinical relevance of different IgG and IgM serum antibody responses to Borrelia burgdorferi after antibiotic therapy for erythema migrans: long-term follow-up study of 113 patients. Arch Dermatol 142(7):862–868. https://doi.org/10.1001/archderm.142.7.862

    Article  CAS  PubMed  Google Scholar 

  41. Aguero-Rosenfeld ME, Wang G, Schwartz I et al (2005) Diagnosis of Lyme Borreliosis. Clin Microbiol Rev 18(3):484–509. https://doi.org/10.1128/CMR.18.3.484-509.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Alexander JM, Cox SM (1995) Lyme disease and pregnancy. Infect Dis Obstet Gynecol 3(6):256–261. https://doi.org/10.1155/S1064744995000755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Trevisan G, Ruscio M, di Meo N et al (2022) Case report: Lyme Borreliosis and pregnancy – our experience. Front Med (Lausanne) 9:816868. https://doi.org/10.3389/fmed.2022.816868

    Article  PubMed  Google Scholar 

  44. World Health Organization, Malaria Parasite Counting. file:///Users/stanleynaides/Downloads/WHO-HTM-GMP-MM-SOP-2016.09-eng.pdf. Accessed 19 June 2023

    Google Scholar 

  45. Sapi E, Pabbati N, Datar A et al (2013) Improved culture conditions for the growth and detection of Borrelia from human serum. Int J Med Sci 10(4):362–376. https://doi.org/10.7150/ijms.5698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Stupica D, Lusa L, Maraspin V et al (2015) Correlation of culture positivity, PCR positivity, and burden of Borrelia burgdorferi sensu lato in skin samples of erythema migrans patients with clinical findings. PLoS One 10(9):e0136600. https://doi.org/10.1371/journal.pone.0136600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Fraser CM, Casjens S, Huang WM et al (1997) Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature 390(6660):580–586. https://doi.org/10.1038/37551

    Article  CAS  PubMed  Google Scholar 

  48. Casjens S, Palmer N, van Vugt R et al (2000) A bacterial genome in flux: the twelve linear and nine circular extrachromosomal DNAs in an infectious isolate of the Lyme disease spirochete Borrelia burgdorferi. Mol Microbiol 35(3):490–516. https://doi.org/10.1046/j.1365-2958.2000.01698.x

    Article  CAS  PubMed  Google Scholar 

  49. Dumler JS (2001) Molecular diagnosis of Lyme disease: review and meta-analysis. Mol Diagn 6(1):1–11. https://doi.org/10.1054/modi.2001.21898

    Article  CAS  PubMed  Google Scholar 

  50. Liveris D, Schwartz I, McKenna D et al (2012) Comparison of five diagnostic modalities for direct detection of Borrelia burgdorferi in patients with early Lyme disease. Diagn Microbiol Infect Dis 73(3):243–245. https://doi.org/10.1016/j.diagmicrobio.2012.03.026

    Article  PubMed  PubMed Central  Google Scholar 

  51. Das S, Hammond-McKibben D, Guralski D et al (2020) Development of a sensitive molecular diagnostic assay for detecting Borrelia burgdorferi DNA from the blood of Lyme disease patients by digital PCR. PLoS One 15(11):e0235372. https://doi.org/10.1371/journal.pone.0235372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Leth TA, Joensen SM, Bek-Thomsen M et al (2022) Establishment of a digital PCR method for detection of Borrelia burgdorferi sensu lato complex DNA in cerebrospinal fluid. Sci Rep 12(1):19991. https://doi.org/10.1038/s41598-022-24041-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Yang J, Guan G, Niu Q et al (2013) Development and application of a loop-mediated isothermal amplification assay for rapid detection of Borrelia burgdorferi s. l. in ticks. Transbound Emerg Dis 60(3):238–244. https://doi.org/10.1111/j.1865-1682.2012.01335.x

    Article  CAS  PubMed  Google Scholar 

  54. Lager M, Faller M, Wilhelmsson P et al (2017) Molecular detection of Borrelia burgdorferi sensu lato – an analytical comparison of real-time PCR protocols from five different Scandinavian laboratories. PLoS One 12(9):e0185434. https://doi.org/10.1371/journal.pone.0185434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Pícha D, Moravcová L, Vaňousová D et al (2014) DNA persistence after treatment of Lyme borreliosis. Folia Microbiol (Praha) 59(2):115–125. https://doi.org/10.1007/s12223-013-0272-4

    Article  CAS  PubMed  Google Scholar 

  56. Krause PJ, Auwaerter PG, Bannuru RR et al (2021) Clinical practice guidelines by the Infectious Diseases Society of America (IDSA): 2020 guideline on diagnosis and management of Babesiosis. Clin Infect Dis 72(2):185–189. https://doi.org/10.1093/cid/ciab050

    Article  PubMed  Google Scholar 

  57. Buchan BW, Jobe DA, Mashock M et al (2019) Evaluation of a novel multiplex high-definition PCR assay for detection of tick-borne pathogens in whole-blood specimens. J Clin Microbiol 57(11):e00513–e00519. https://doi.org/10.1128/JCM.00513-19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Shakir SM, Mansfield CR, Hays ED et al (2020) Evaluation of a novel high-definition PCR multiplex assay for simultaneous detection of tick-borne pathogens in human clinical specimens. J Clin Microbiol 58(3):e01655–e01619. https://doi.org/10.1128/JCM.01655-19

    Article  PubMed  PubMed Central  Google Scholar 

  59. Pach JJ, Zubair AS, Traner C et al (2021) Powassan meningoencephalitis: a case report highlighting diagnosis and management. Cureus 13(7):e16592. https://doi.org/10.7759/cureus.16592

    Article  PubMed  PubMed Central  Google Scholar 

  60. Singh A, Yeh CJ, Boone Blanchard S (2017) Ages and stages questionnaire: a global screening scale. Bol Med Hosp Infant Mex 74(1):5–12. https://doi.org/10.1016/j.bmhimx.2016.07.008

    Article  PubMed  Google Scholar 

  61. Schonhaut L, Armijo I, Schönstedt M et al (2013) Validity of the ages and stages questionnaires in term and preterm infants. Pediatrics 131(5):e1468–e1474. https://doi.org/10.1542/peds.2012-3313

    Article  PubMed  Google Scholar 

  62. (DP™-4) Developmental Profile-4. https://www.wpspublish.com/dp-4-developmental-profile-4.html?gclid=CjwKCAjw-b-kBhB-EiwA4fvKrMGYBaFrG2fXDZZtq98OUyRwS3BC9W-ZeSfG5FgO26UylVF9kMMbhoClloQAvD_BwE&hsa_acc=6243382947&hsa_ad=466818335208&hsa_cam=1687564787&hsa_grp=97202719802&hsa_kw=developmental+profile+4&hsa_mt=e&hsa_net=adwords&hsa_src=g&hsa_tgt=kwd-877101473704&hsa_ver=3&utm_campaign=Search+%7C+Child+Clinical&utm_medium=ppc&utm_source=adwords&utm_term=developmental+profile+4

  63. D’Arcy E, Wallace K, Chamberlain A et al (2022) Content validation of common measures of functioning for young children against the international classification of functioning, disability and health and code and core Sets relevant to neurodevelopmental conditions. Autism 26(4):928–939. https://doi.org/10.1177/13623613211036809

    Article  PubMed  Google Scholar 

  64. Firestein MR, Shuffrey LC, Hu Y et al (2023) Assessment of neurodevelopment in infants with and without exposure to asymptomatic or mild maternal SARS-CoV-2 infection during pregnancy. JAMA Netw Open 6(4):e237396. https://doi.org/10.1001/jamanetworkopen.2023.7396

    Article  PubMed  PubMed Central  Google Scholar 

  65. Gallagher SL, Sullivan et al (2011) Chapter 30: Kaufman assessment battery for children, second edition. In: Davis A (ed) Handbook of pediatric neuropsychology. Springer, New York, pp 343–352. ISBN 978-0-8261-0629-2

    Google Scholar 

  66. ADNI. Alzheimer’s disease neuroimaging initiative. https://adni.loni.usc.edu/. Accessed 20 Jul 2023

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Authors and Affiliations

  1. Laboratory Corporation of America Holdings (Labcorp), Burlington, NC, USA

    Graham McLennan, Suzanne E. Dale, Laura Gillim, Vivian Weinblatt, Robert Wallerstein & Stanley J. Naides

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  1. Graham McLennan
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  2. Suzanne E. Dale
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  3. Laura Gillim
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  4. Vivian Weinblatt
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  5. Robert Wallerstein
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  6. Stanley J. Naides
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Correspondence to Stanley J. Naides .

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  1. Tezted Ltd, Jyväskylä, Finland

    Leona Gilbert

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McLennan, G., Dale, S.E., Gillim, L., Weinblatt, V., Wallerstein, R., Naides, S.J. (2024). Developing a Prospective Gestational Lyme Disease Study. In: Gilbert, L. (eds) Borrelia burgdorferi. Methods in Molecular Biology, vol 2742. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3561-2_18

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  • DOI: https://doi.org/10.1007/978-1-0716-3561-2_18

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