Antecedentes: La enfermedad de Lyme (LD) es una infección transmitida por las garrapatas y causadapor la Borrelia burgdorferi sensulato. El enfoque terapéutico actual de esta enfermedad se limita a los antibióticos. Sin embargo, tras su administración, alrededor del 20% de los pacientes experimentan un retraso en la aparición de la enfermedad manifestando síntomas persistentes.
Métodos: Para determinar un enfoque adecuado que ayude a reducir esta cifra, hemos examinado la eficacia de una composición de compuestos polifenólicos (baicaleína, luteolina y ácido rosmarínico) con ácidos grasos (monolaurina y ácido cis-2-decenoico), y yodo/algas en un modelo animal con enfermedad de Lyme y en voluntarios.
Resultados: Los resultados mostraron que 4 semanas de ingesta dietética de esta composición redujeron la carga de espiroquetas en los tejidos de los animales en aproximadamente un 75%. Los parámetros sanguíneos básicos y diferenciales no mostraron diferencias significativas entre los animales de control y los alimentados con esta composición. Asimismo, los marcadores de toxicidad hepática y renal no se modificaron y la apoptosis no se observó. Las citoquinas inflamatorias relevantes, como la IL-6, la IL-17, el TNF-a y el INF-. estaban elevadas en los animales infectados pero se normalizaron en los animales infectados y tratados. Un pequeño estudio observacional reveló que tras la administración de esta composición a 17 voluntarios tres veces al día durante 6 meses, el 67,4% de los voluntarios con LD tardía o persistente, y no receptivos a la aplicación previa de antibióticos, respondieron positivamente, en términos de estado energético así como en el bienestar físico y psicológico a la suplementación con esta composición, mientras que el 17,7% tuvo una ligera mejoría y el 17,7% no respondió.
Referencias:
1. Shapiro Lyme disease. N Engl J Med 2014; 370: 1724–1731.
2. Stricker RB and Johnson Lyme disease: the next decade. Infect Drug Resist 2011; 4: 1–9.
3. Anderson JF, Magnarelli LA, Burgdorfer W,
et al. Spirochetes in Ixodes dammini and mammals from Connecticut. Am J Trop Med Hyg 1983; 32: 818–824.
4. Dryden MW and Hodgkins E. Vector-borne diseases in pets: the stealth health threat. Compend Contin Educ Vet 2010; 32: E1–E4.
5. Centers for Disease Control and Lyme disease website, http://www.cdc.gov/lyme/. (2014, accessed 13 September 2014)
6. Robinson S. Lyme disease in Maine: a comparison of NEDSS surveillance data and Maine health data organization hospital discharge data. Online J Public Health Inform 2014; 5: e231.
7. Strle F, Wormser GP, Mead P, et al. Gender disparity between cutaneous and non-cutaneous manifestations of Lyme borreliosis. PLoS One 2013; 8:
8. Murray TS and Shapiro ED. Lyme disease. Clin Lab Med 2010; 30: 311–328.
9. Arvikar SA and Steere Diagnosis and treatment of Lyme arthritis. Infect Dis Clin North Am 2015; 29: 269–280.
10. Steere AC, Sikand VK, Schoen RT, et al. Asymptomatic infection with Borrelia Clin Infec Dis 2003; 37: 528–532.
11. Klempner MS, Baker PJ, Shapiro ED, et al. Treatment trials for post-Lyme disease symptoms revisited. Am J Med 2013; 126: 665–669.
12. Fallon BA, Keilp JG, Corbera KM, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology 2008; 70: 992–1003.
13. Brorson O and Brorson SH. Grapefruit seed extract is a powerful in vitro agent against motile and cystic forms of Borrelia burgdorferi sensu lato. Infection 2007; 35: 206–208.
14. Goc A, Niedzwiecki A and Rath M. In vitro evaluation of antibacterial activity of phytochemicals and micronutrients against
Borrelia burgdorferi and Borrelia garinii. J Appl Microbiol 2015; 119: 1561–1572.
15. Goc A and Rath M. The anti-borreliae efficacy of phytochemicals and micronutrients: an update. Ther Adv Infec Dis 2016; 3: 75–82.
16. Theophilus PA, Victoria MJ, Socarras KM, et al. Effectiveness of Stevia Rebaudiana whole leaf extract against the various morphological forms of Borrelia burgdorferi in vitro. Eur J Microbiol Immunol 2015; 5: 268–280.
17. Goc A, Niedzwiecki A and Rath M. Synergistic anti-borreliae efficacy of a composition of naturally-occurring compounds: an in vitro study. J Nutr Biol 2019; 5: 350–363.
18. Labandeira-Rey M and Skare Decreased infectivity in Borrelia burgdorferi strain B31 is associated with loss of linear plasmid 25 or 28-1. Infect Immun 2001; 69: 446–455.
19. Van Laar TA, Hole C, Rajasekhar Karna SL, et al. Statins reduce spirochetal burden and modulate immune responses in the C3H/HeN mouse model of Lyme disease. Microbes Infect 2016; 18: 430–435.
20. Han WK, Bailly V, Abichandani R, et al. Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int 2002; 62: 237–244.
21. Lavrik IN, Golks A and Krammer PH. Caspases: pharmacological manipulation of cell death.
J Clin Invest 2005; 115: 2665–2672.
22. Gordon S, Hamann J, Lin HH, et al. F4/80 and the related adhesion-GPCRs. Eur J Immunol 2011; 41: 2472–2476.
23. Stricker RB and Fesler Chronic Lyme disease: a working case definition. Am J Infect Dis 2018; 14: 1–44.
24. Feng J, Auwaerter PG and Zhang Y. Drug combinations against Borrelia burgdorferi persisters in vitro: eradication achieved by using daptomycin, cefoperazone and doxycycline. PLoS One 2015; 10: e0117207.
25. Forsberg P, Ernerudh J, Ekerfelt C, et al. The outer surface proteins of Lyme disease borrelia spirochetes stimulate T cells to secrete interferon- gamma (IFN-gamma): diagnostic and pathogenic Clin Exp Immunol 1995; 101: 453–460.
26. Pahl A, Kühlbrandt U, Brune K, et al. Quantitative detection of Borrelia burgdorferi by real-time J Clin Microbiol 1999; 37: 1958–1963.
27. Yang L, Weis JH, Eichwald E, et al. Heritable susceptibility to severe Borrelia burgdorferi- induced arthritis is dominant and is associated with persistence of large numbers of spirochetes in tissues. Infect Immun 1994; 62: 492–500.
28. Wu Q, Liu Z, Wang J, et al. Pathogenic analysis of Borrelia garinii strain SZ isolated from northeastern China. Parasit Vectors 2013; 6: 177–183.
29. Strother KO, Hodzic E, Barthold SW, et al. Infection of mice with Lyme disease spirochetes constitutively producing outer surface proteins A and B. Infec Immun 2007; 75: 2786–2794.
30. Iyer R, Mukherjee P, Wang K, et al. Detection of Borrelia burgdorferi nucleic acids after antibiotic treatment does not confirm J Clin Microbiol 2013; 51: 857–862.
31. Hodzic E, Feng S, Holden K, et al. Persistence of Borrelia burgdorferi following antibiotic treatment in Antimicrob Agents Chemother 2008; 52: 1728–1736.
32. Bradley JF, Johnson RC and Goodman JL. The persistence of spirochetal nucleic acids in active Lyme arthritis. Ann Int Med 1994; 120: 487–489.
33. Giambartolomei GH, Dennis VA, Lasater BL, et al. Induction of pro- and anti-inflammatory cytokines by Borrelia burgdorferi lipoproteins in monocytes is mediated by Infect Immun 1999; 67: 140–147.
34. Yang LM, Ma Y, Schoenfeld R, et al. Evidence for lymphocyte-B mitogen activity in Borrelia burgdorferi-infected Infect Immun 1992; 60: 3033–3041.
35. Tai KF, Ma Y and Weis JJ. Normal human B lymphocytes and mononuclear cells respond to the mitogenic and cytokine-stimulatory activities of Borrelia burgdorferi and its lipoprotein OspA. Infect Immun 1994; 62: 520–528.
36. Berende A, Oosting M, Kullberg BJ, et al. Activation of innate host defense mechanisms by Eur Cytokine Netw 2010; 21: 7–18.
37. Liang FT, Brown EL, Wang T, et al. Protective niche for Borrelia burgdorferi to evade humoral Am J Pathol 2004; 165: 977–985.
38. Priem S, Burmester GR, Kamradt T, et al. Detection of Borrelia burgdorferi by polymerase chain reaction in synovial membrane, but not in synovial fluid from patients with persisting Lyme arthritis after antibiotic therapy. Ann Rheum Dis 1998; 57: 118–121.
39. Kvasnicka HM, Thiele J and Ahmadi T. Bone marrow manifestation of Lyme disease (Lyme Borreliosis). Br J Haematol 2003; 120:
40. Berndtson K. Review of evidence for immune evasion and persistent infection in Lyme disease. Int J Gen Med 2013; 6: 291–306.
41. Bockenstedt LK, Mao J, Hodzi E, et al. Detection of attenuated, non-infectious spirochetes after antibiotic treatment of Borrelia burgdorferi- infected J Infect Dis 2002; 186:
1430–1437.
42. Preac-Mursic V, Pfister HW, Wilske B, et al. Survival of Borrelia burgdorferi in antibiotically treated patients with Lyme Infection 1989; 17: 355–359.
43. Schmidli J, Hunziker T, Moesli P, et al. Cultivation of Borrelia burgdorferi from joint fluid three months after treatment of facial palsy due to Lyme J Infect Dis 1988; 158: 905–906.
44. Straubinger RK, Summers BA, Chang YF, et al. Persistence of Borrelia burgdorferi in experimentally infected dogs after antibiotic
treatment. J Clin Microbiol 1997; 35: 111–116.
45. Embers ME, Barthold SW, Borda JT, et al. Persistence of Borrelia burgdorferi in rhesus macaques following antibiotic treatment of disseminated PloS One 2012; 7: e29914.
46. Kadam P, Gregory NA, Zelger B, et al. Delayed onset of the Jarisch-Herxheimer reaction in doxycycline-treated disease: a case report and review of its histopathology and implications
for pathogenesis. Am J Dermatopathol 2015; 37: e68–e74.
47. Marques A, Telford SR, Turk SP, et al. Xenodiagnosis to detect Borrelia burgdorferi infection: a first-in-human study. Clin Infec Dis 2014; 58: 937–945.
48. Bockenstedt LK, Gonzalez DG, Haberman AM, et al. Spirochete antigens persist near cartilage after murine Lyme borreliosis J Clin Invest 2012; 122: 2652–2660.
49. Krupp LB, Hyman LG, Grimson R, et al. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology 2003; 60: 1923–1930.
50. Straubinger RK, Straubinger AF, Summers BA, et al. Status of Borrelia burgdorferi infection after antibiotic treatment and the effects of corticosteroids: an experimental J Infect Dis 2002; 181: 1069–1081.
51. Straubinger PCR-Based quantification of Borrelia burgdorferi organisms in canine tissues over a 500-day post-infection period. J Clin Microbiol 2000; 38: 2191–2199.
(Descarga pdf de 1,36 MB)
