Early spread of Borrelia burgdorferi into mammal tissues:

Pubmed search for:
Borreli*+early+AND+(spread+OR+dissemin*)
Borreli*+(isolat*+OR+cult*+OR+PCR+OR+microscop*)+AND+early
Borreli*+(isolat*+OR+cult*+OR+PCR+OR+microscop*)+AND+late

A few selected citations:

Kornblatt AN, Steere AC, Brownstein DG.
Infection in rabbits with the Lyme disease spirochete.
Yale J Biol Med. 1984 Jul-Aug;57(4):613-6.

Spirochetemia occurs within two weeks post-inoculation.
 
Barthold SW, Moody KD, Terwilliger GA, Jacoby RO, Steere AC.
An animal model for Lyme arthritis.
Ann N Y Acad Sci. 1988;539:264-73.

Abstract:
Spirochetes were isolated from blood, liver, kidney, spleen, brain, and joints of inoculated rats.
Arthritis, associated with the presence of spirochetes, developed in multiple joints by day 14 and persisted through day 90 after inoculation.”
  
Johnson SE, Swaminathan B, Moore P, Broome CV, Parvin M.
Borrelia burgdorferi: survival in experimentally infected human blood processed for transfusion.
J Infect Dis. 1990 Aug;162(2):557-9.

The isolation of Borrelia burgdorferi from blood raises the possibility of bloodborne transmission of Lyme borreliosis through transfusions.
To assess this possibility, the ability of B. burgdorferi to survive in human blood processed for transfusion was studied. Human blood was inoculated with B. burgdorferi type strain B-31 (ATCC 35210) at 0.2, 20, or 2000 viable cells/ml, processed by conventional blood banking procedures, stored at 4 degrees C, and cultured for B. burgdorferi at 12, 23, 36, and 48 days of storage.
After processing, most B. burgdorferi were found in the packed cell fraction.
At inoculum levels of 20 or 2000 viable cells/ml, B. burgdorferi survived in processed blood through 48 days of storage at 4 degrees C.
B. burgdorferi was isolated from packed cells after 36 days of storage at 4 degrees C even when the initial inoculum level was as low as 0.2 cells/ml.
The data demonstrate that B. burgdorferi can survive the blood processing procedures normally applied to transfused blood in the USA.
Since hematogenous spread of the spirochete seems to occur early in the illness, primarily in symptomatic patients, the risk of transfusion-associated Lyme disease may be small.
However, the possibility of survival of B. burgdorferi under blood banking conditions warrants a heightened awareness of this potential problem.

Schmid GP.
Epidemiology and clinical similarities of human spirochetal diseases.
Rev Infect Dis. 1989 Sep-Oct;11 Suppl 6:S1460-9. Review.

Lyme disease, first identified in 1975, is the most recently recognized of the seven human spirochetal diseases; the evolving clinical picture of Lyme disease indicates it shares many features with the other diseases.
These similarities are striking in view of the diverse epidemiology of the seven diseases, which are caused by Treponema species (spread by human-to-human contact) or Leptospira or Borrelia species (zoonoses). These similarities include the following:
(1) skin or mucous membrane as portal of entry;
(2) spirochetemia early in the course of disease, with wide dissemination through tissue and body fluid; and
(3) one or more subsequent stages of disease, often with intervening latent periods.
Lyme disease shares with many spirochetal diseases a tropism for skin and neurologic and cardiovascular manifestations, whereas chronic arthritis is unique to Lyme disease.
These similarities and dissimilarities offer opportunities to discover which properties unique to the pathogenic spirochetes are responsible for clinical manifestations and suggest that certain clinical features of patients with spirochetal diseases other than Lyme disease may someday be recognized in patients with Lyme disease.

Luft BJ, Steinman CR, Neimark HC, Muralidhar B, Rush T, Finkel MF, Kunkel M, Dattwyler RJ.
Invasion of the central nervous system by Borrelia burgdorferi in acute disseminated infection.
JAMA 1992 Mar 11; 267(10): 1364-7    

OBJECTIVE--To determine central nervous system (CNS) involvement in acutely disseminated Borrelia burgdorferi infection by measurement of borrelia-specific DNA using the polymerase chain-reaction (PCR) assay and to compare the results of this with standard serological tests.
DESIGN--Prospective study with laboratory investigators blinded to clinical data.
SETTING--Multicenter office practice with a central reference laboratory.
PATIENTS--Cerebrospinal fluid (CSF) was collected from 12 patients with acute disseminated Lyme borreliosis with less than 2 weeks of active disease. The normal control specimens came from 16 patients whose CSF samples had been sent to the clinical laboratory for tests unrelated to the present study.
MAIN OUTCOME MEASURES--Clinical evidence of disease and laboratory abnormalities.
RESULTS--Eight of the 12 patients (four of six with multiple areas of erythema migrans and four of six with cranial neuritis without erythema migrans) had B burgdorferi-specific DNA in their CSF. Among the 12 patients studied, nine had acute cranial neuritis and six had multiple erythema migrans lesions.
Just four of the eight who were found to have spirochetal DNA in their CSF had complaints suggestive of CNS infection.
In three of the PCR-positive CSF samples, no other abnormalities were noted. None of 16 samples from controls were positive in the PCR assay.
CONCLUSION--B burgdorferi can invade the CNS early in the course of infection.
Careful consideration should be given to choosing antibiotics that achieve adequate CSF levels in patients with disseminated infection.

Erratum in:
JAMA 1992 Aug 19;268(7):872
Comment in:
JAMA. 1992 Aug 19;268(7):872; discussion 873."    "order erratum

Excerpts:
Our findings demonstrate that B. burgdorferi can disseminate to CNS very early in the course of infection with little or no clinical evidence of CNS involvement.  Acute primary and secondary infections due to Treponema pallidum are also associated with a high rate of early dissemination to the CNS.  Although the full range of late CNS manifestations of Lyme Borreliosis remains controversial and ill defined, as in syphilis, the presence of CNS infection could have serious long-term consequences ...........
Among four patients with chronic  Lyme arthritis, B. burgdorferi was found in the CSF on one patient with relapsing arthritis. This patient had no clinical evidence of CNS involvement and no intrathecal antibody production. 
This raises the possibility that the CNS may act as a sanctuary for B. burgdorferi, protecting it from the action of systemic antibiotics and immunity and thereby allowing it to reseed the periphery intermittently.  This finding is especially important when considering the appropriate treatment of the chronic phase of this disease and whether the use of oral antibiotics alone, as suggested by some for chronic arthritis, is appropriate.
 
Galbe JL, Guy E, Zapatero JM, Peerschke EI, Benach JL.
Vascular clearance of Borrelia burgdorferi in rats.
Microb Pathog. 1993 Mar;14(3):187-201.

Radiolabeled Borrelia burgdorferi, the etiologic agent of Lyme disease, injected intravenously into rats are cleared from the vasculature within 1 h of injection.
One low passage isolate showed trafficking between the circulation and possibly the vessel walls for the first 2 h after injection.
All strains used were resistant to the effects of normal and heat-inactivated rat serum.
During the first 2 h after injection, B. burgdorferi can be visualized in, and recovered from, the platelet-rich plasma.
B. burgdorferi can adhere to both human and rat platelets in in vitro assays, but an in vivo association with these cells was not apparent.
Similarly, none of the strains of B. burgdorferi used induced platelet aggregation.
Removal from the circulation into the organs was measured in perfused rats by polymerase chain reaction and autoradiography and in non-perfused rats by organ cultures.
These organisms invade organs (heart, kidneys, bladder, liver, spleen, brain) within 1-6 h after injection.
Invasion of organs occurred in an apparent random manner; a large amount of radiolabel but no live organisms was excreted in the urine during the first 24 h, suggesting degradation of the inoculum.

Wormser GP, McKenna D, Carlin J, Nadelman RB, Cavaliere LF, Holmgren D, Byrne DW, Nowakowski J.  (fri PDF)
Brief communication: hematogenous dissemination in early Lyme disease.
Ann Intern Med. 2005 May 3;142(9):751-5. Summary for patients in: Ann Intern Med. 2005 May 3;142(9):I48.

BACKGROUND: Bloodstream invasion in Lyme disease has been difficult to study because until recently blood culture methods were too insensitive to detect spirochetemia.
OBJECTIVE: To evaluate the clinical and laboratory features of spirochetemic patients.
DESIGN: Cross-sectional study.
SETTING: Lyme Disease Diagnostic Center in Valhalla, New York, 1997 to 2002.
PATIENTS: 213 untreated adults with erythema migrans.
INTERVENTION: Blood culture for Borrelia burgdorferi.
MEASUREMENTS: Symptom scores and selected laboratory measures.
RESULTS: Spirochetemia was found in 93 (43.7%) patients. Spirochetemic patients were more often symptomatic (89.2% vs. 74.2%; P = 0.006) and more often had multiple erythema migrans lesions (41.9% vs. 15.0%; P < 0.001) than patients without spirochetemia.
However, 8 (22.9%) of the 35 asymptomatic patients with a single skin lesion nevertheless had a positive blood culture.
Risk for spirochetemia was present the day the patient noticed the lesion and continued for more than 2 weeks.
LIMITATIONS: Long-term outcome data were not available.
CONCLUSIONS: The high rate, early onset, and prolonged duration of risk for spirochetemia explain why untreated patients with erythema migrans are at risk for dissemination of B. burgdorferi to anatomic sites beyond the lesion site. Differences in the strain of the infecting spirochete, as well as host factors, may be important determinants of hematogenous dissemination.

“All but 2 of the patients satisfied the Lyme disease surveillance definition of the Centers for Disease Control and Prevention (8); these 2 exceptions had an erythema migrans lesion less than 5 cm in diameter.
Patients were excluded if they had received an antimicrobial agent effective for the treatment of Lyme disease within 2 weeks preceding the study (9).
Nineteen (8.9%) of the patients were included in our previous study (1). …
Spirochetemia was not associated with duration of erythema migrans (P > 0.2) or the size of the erythema migrans lesion (P = 0.18), both for the entire study sample (Figure) and separately for those with a single erythema migrans lesion and those with multiple lesions. The oldest lesion associated with spirochetemia was of 33 days’ duration.”

Comment:
The design of this study, enrolling patient already displaying EM, does not allow any evaluation of the risk of hematogenous spread of Borrelia occurring BEFORE the development of EM; somebody should try to culture blood from people having been bitten by a proven Borrelia infected tick!