Lyme & the Bladder-
- From: "CaliforniaLyme" <CaliforniaLyme@xxxxxx>
- Date: 17 Jun 2005 12:37:30 -0700
1: J Urol. 1993 Jan;149(1):26-30. Related Articles, Links
Urinary dysfunction in Lyme disease.
Chancellor MB, McGinnis DE, Shenot PJ, Kiilholma P, Hirsch IH.
Department of Urology, Jefferson Medical College, Thomas Jefferson
University, Philadelphia, Pennsylvania.
Lyme disease, which is caused by the spirochete Borrelia burgdorferi,
is
associated with a variety of neurological sequelae. We describe 7
patients with
neuro-borreliosis who also had lower urinary tract dysfunction.
Urodynamic
evaluation revealed detrusor hyperreflexia in 5 patients and detrusor
areflexia in
2. Detrusor external sphincter dyssynergia was not noted on
electromyography
in any patient. We observed that the urinary tract may be involved in 2
respects in the course of Lyme disease: 1) voiding dysfunction may be
part of
neuro-borreliosis and 2) the spirochete may directly invade the urinary
tract. In 1
patient bladder infection by the Lyme spirochete was documented on
biopsy.
Neurological and urological symptoms in all patients were slow to
resolve and
convalescence was protracted. Relapses of active Lyme disease and
residual
neurological deficits were common. Urologists practicing in areas
endemic for Lyme
disease need to be aware of B. burgdorferi infection in the
differential
diagnosis of neurogenic bladder dysfunction. Conservative bladder
management
including clean intermittent catheterization guided by urodynamic
evaluation is
recommended.
Publication Types:
Case Reports
PMID: 8417211 [PubMed - indexed for MEDLINE]
1: Am J Pathol. 1992 Nov;141(5):1173-9. Related Articles, Links
Cystitis induced by infection with the Lyme disease spirochete,
Borrelia
burgdorferi, in mice.
Czub S, Duray PH, Thomas RE, Schwan TG.
Department of Health and Human Services, National Institutes of Health,
National Institute of Allergy and Infectious Diseases, Hamilton, MT
59840.
Previous studies have demonstrated that the urinary bladder is a
consistent
source for isolating the Lyme disease spirochete, Borrelia burgdorferi,
from
both experimentally infected and naturally exposed rodents. We examined
histopathologic changes in the urinary bladder of different types of
rodents
experimentally infected with Lyme spirochetes, including BALB/c mice
(Mus musculus),
nude mice (M. musculus), white-footed mice (Peromyscus leucopus), and
grasshopper mice (Onychomys leucogaster). Animals were inoculated
intraperitoneally,
subcutaneously, or intranasally with low-passaged spirochetes,
high-passaged
spirochetes, or phosphate-buffered saline. At various times after
inoculation,
animals were killed and approximately one-half of each urinary bladder
and kidney
were cultured separately in BSK-II medium while the other half of each
organ
was prepared for histologic examination. Spirochetes were cultured from
the
urinary bladder of all 35 mice inoculated with low-passaged spirochetes
while we
were unable to isolate spirochetes from any kidneys of the same mice.
The
pathologic changes observed most frequently in the urinary bladder of
the
infected mice were the presence of lymphoid aggregates, vascular
changes, including
an increase in the number of vessels and thickening of the vessel
walls, and
perivascular infiltrates. Our results demonstrate that nearly all
individuals
(93%) of the four types of mice examined had a cystitis associated with
spirochetal infection.
PMID: 1443051 [PubMed - indexed for MEDLINE]
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1: J Clin Microbiol. 1991 May;29(5):894-6. Related Articles, Links
Persistent cardiac and urinary tract infections with Borrelia
burgdorferi in
experimentally infected Syrian hamsters.
Goodman JL, Jurkovich P, Kodner C, Johnson RC.
Department of Medicine, University of Minnesota School of Medicine,
Minneapolis 55455.
The heart can be severely affected in humans with Lyme disease, causing
conduction defects and, rarely, heart failure. Although immunodeficient
and young
mice may develop cardiac lesions, cultivation of Borrelia burgdorferi
from
cardiac tissues of experimentally infected animals has not been
reported
previously. We infected Syrian hamsters with B. burgdorferi 297 and
found a marked
tropism of the spirochete for myocardial and urinary tract tissues.
Fifty-six of
57 hearts (98%) and 52 of 58 bladders (90%) were culture positive. The
cardiac
infection was persistent and could be documented in 21 of 22 hearts
(96%)
cultured from days 28 to 84 postinfection. The urinary tract was also a
site of
persistent infection in most animals, with 18 of 23 bladders (78%)
being culture
positive from days 28 to 84. The persistence of spirochetes was
specific for
the heart and bladder, as indicated by negative cultures of specimens
from the
liver and spleen, in which only 1 of 23 cultures was positive from days
28 to
84. Because of the high isolation rates, tropism, and persistence that
we
found for B. burgdorferi in the hamster heart and bladder, these sites
will be
useful and important for the cultivation of spirochetes in experimental
studies
that evaluate the efficacies both of candidate vaccines in preventing
infection and of antibiotics in eradicating organisms from privileged
sites. In
addition, the clear demonstration of persistent cardiac infection with
B.
burgdorferi may provide a useful model for studying the pathogenesis of
cardiac Lyme
disease.
PMID: 2056054 [PubMed - indexed for MEDLINE]
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1: J Clin Microbiol. 1988 May;26(5):893-5. Related Articles, Links
The urinary bladder, a consistent source of Borrelia burgdorferi in
experimentally infected white-footed mice (Peromyscus leucopus).
Schwan TG, Burgdorfer W, Schrumpf ME, Karstens RH.
Rocky Mountain Laboratories, National Institute of Allergy and
Infectious
Diseases, Hamilton, Montana 59840.
White-footed mice, Peromyscus leucopus, were experimentally infected in
the
laboratory with Borrelia burgdorferi, the causative agent of Lyme
disease.
After mice were infected by intraperitoneal or subcutaneous inoculation
or by tick
bite, attempts were made to culture spirochetes from the urinary
bladder,
spleen, kidney, blood, and urine. Spirochetes were most frequently
isolated from
the bladder (94%), followed by the kidney (75%), spleen (61%), and
blood
(13%). No spirochetes were isolated from the urine. Tissue sectioning
and
immunofluorescence staining of the urinary bladder demonstrated
spirochetes within the
bladder wall. The results demonstrate that cultivation of the urinary
bladder
is very effective at isolating B. burgdorferi from experimentally
infected
white-footed mice and that culturing this organ may be productive when
surveying
wild rodents for infection with this spirochete.
PMID: 3290239 [PubMed - indexed for MEDLINE]
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1: Vector Borne Zoonotic Dis. 2001 Spring;1(1):35-44. Related Articles,
Links
An analysis of spirochete load, strain, and pathology in a model of
tick-transmitted Lyme borreliosis.
Zeidner NS, Schneider BS, Dolan MC, Piesman J.
Division of Vector-Borne Infectious Diseases, National Center for
Infectious
Diseases, Centers for Disease Control and Prevention, Fort Collins, CO
80522,
USA. naz2@xxxxxxx
Four laboratory-grown, low-passage isolates of Borrelia burgdorferi
sensu
stricto, B31, JD-1, 910255, and N40, were incorporated into Ixodes
scapularis
ticks to examine the pathogenesis of these isolates in mice after tick
transmission. All isolates induced multifocal, lymphoid nodular
cystitis, subacute,
multifocal, necrotizing myocarditis, and a localized periostitis and
arthritis of
the femorotibial joint 6-18 weeks after tick infestation. In terms of
the
number of mice that demonstrated pathology in bladder, heart, and
joint, the
highest incidence of lesions occurred 12 weeks after tick bite.
Utilizing the
Taqman quantitative polymerase chain reaction (q-PCR) fluorogenic
detection
technology to amplify a conserved region of the flagellin gene, a trend
was
demonstrated between the number of spirochetes in tissue with duration
of pathology.
The q-PCR assay developed for this study was sensitive and could
reliably
measure as few as 1 to 10 spirochetes in the target tissues tested. A
higher
percentage of B31- and N40-infected mice (92 and 100%, respectively)
developed
myocarditis than JD-1- or 910255-infected mice (67 and 46%,
respectively) 12 weeks
after tick bite. The amount of spirochetal DNA that could be amplified
for
heart at this time point was not statistically different between
isolates,
indicating a difference in virulence between B31 and N40 relative to
JD-1 and 910225.
N40-infected mice demonstrated a significantly higher spirochete load
(an
average of 1.23 spirochetes/mg of tissue, p = 0.045) in femorotibial
joints 18
weeks after infection, with 60% of these mice maintaining lesions
compared with
those infected with B31 (13%), JD-1 (25%), or 910255 (50%), which
averaged
<0.5 spirochetes/mg of tissue. This mouse model of Lyme borreliosis,
including
the ability to monitor lesion development and spirochete load, can
facilitate
the testing of therapeutic regimens for the later stages of
tick-transmitted
Lyme disease and help investigate aspects of the immunopathogenesis of
lesion
development.
PMID: 12653134 [PubMed - indexed for MEDLINE]
1: Lancet. 1992 May 16;339(8803):1237-8. Related Articles, Links
Lyme cystitis and neurogenic bladder dysfunction.
Chancellor MB, McGinnis DE, Shenot PJ, Hirsch IH, Kiilholma PJ.
Publication Types:
Letter
PMID: 1349976 [PubMed - indexed for MEDLINE]
1: Lab Invest. 2000 Jul;80(7):1043-54. Related Articles, Links
Localization of Borrelia burgdorferi in the nervous system and other
organs
in a nonhuman primate model of lyme disease.
Cadavid D, O'Neill T, Schaefer H, Pachner AR.
Department of Neuroscience, University of Medicine and Dentistry of New
Jersey-New Jersey Medical School, Newark 07103, USA.
Lyme borreliosis is caused by infection with the spirochete Borrelia
burgdorferi. Nonhuman primates inoculated with the N40 strain of B.
burgdorferi
develop infection of multiple tissues, including the central (CNS) and
peripheral
nervous system. In immunocompetent nonhuman primates, spirochetes are
present in
low numbers in tissues. For this reason, it has been difficult to study
their
localization and changes in expression of surface proteins. To further
investigate this, we inoculated four immunosuppressed adult Macaca
mulatta with 1
million spirochetes of the N40 strain of B. burgdorferi, and compared
them with
three infected immunocompetent animals and two uninfected controls. The
brain,
spinal cord, peripheral nerves, skeletal muscle, heart, and bladder
were
obtained at necropsy 4 months later. The spirochetal tissue load was
first studied
by polymerase chain reaction (PCR)-ELISA of the outer surface protein A
(ospA) gene. Immunohistochemistry was used to study the localization
and numbers of
spirochetes in tissues and the expression of spirochetal proteins and
to
characterize the inflammatory response. Hematoxylin and eosin and
trichrome stains
were used to study inflammation and tissue injury. The results showed
that
the number of spirochetes was significantly higher in immunosuppressed
animals.
B. burgdorferi in the CNS localized to the leptomeninges, nerve roots,
and
dorsal root ganglia, but not to the parenchyma. Outside of the CNS, B.
burgdorferi localized to endoneurium and to connective tissues of
peripheral nerves,
skeletal muscle, heart, aorta, and bladder. Although ospA, ospB, ospC,
and
flagellin were present at the time of inoculation, only flagellin was
expressed by
spirochetes in tissues 4 months later. Significant inflammation
occurred only
in the heart, and only immunosuppressed animals had cardiac fiber
degeneration
and necrosis. Plasma cells were abundant in inflammatory foci of
steroid-treated animals. We concluded that B. burgdorferi has a tropism
for the meninges in
the CNS and for connective tissues elsewhere in the body.
PMID: 10908149 [PubMed - indexed for MEDLINE]
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1: Infect Immun. 1993 Nov;61(11):4777-84. Related Articles, Links
A guinea pig model for Lyme disease.
Sonnesyn SW, Manivel JC, Johnson RC, Goodman JL.
Department of Medicine, University of Minnesota School of Medicine,
Minneapolis 55455.
We report that outbred Hartley guinea pigs are susceptible to Borrelia
burgdorferi. We recovered spirochetes from 57 of 60 (95%) guinea pigs
inoculated
when < or = 3 months of age. In contrast, animals inoculated when > or
= 6 months
of age were resistant to infection as defined by recovery of organisms
at >
or = 4 weeks postinoculation. Infection was widely disseminated: B.
burgdorferi
was recovered from 83% of bladders, 64% of knee joints, 57% of hearts,
48% of
spleens, and 38% of spinal cords examined within 4 weeks of
inoculation.
Histopathologic changes were common in the heart (88%) (preferential
involvement
of perineural tissues near the annulus fibrosus) and bladder (76%) and
were
also noted in a minority of spinal cords (13%) and knee joints (9%).
Western
immunoblots demonstrated an immunoglobulin G response to B.
burgdorferi,
particularly to the 24-, 31- (OspA), 39-, and 41-kDa (flagellin)
antigens. Infection
was cleared from most tissues with the passage of time; spirochetes
were
recovered from 63% of tissues removed from guinea pigs at < or = 4
weeks after
inoculation but from only 32% at > or = 8 weeks postinoculation (P <
0.001). An
exception was the failure to clear spirochetes from infected knees, 90%
of which
were culture positive even when evaluated at > or = 8 weeks
postinoculation.
The guinea pig provides a new model useful for studying host-spirochete
interactions in Lyme disease.
PMID: 8406878 [PubMed - indexed for MEDLINE]
1: Zentralbl Bakteriol. 1998 May;287(4):347-61. Related Articles, Links
Detection of Borrelia burgdorferi in urine specimens from dogs by a
nested
polymerase chain reaction.
Bauerfeind R, Kreis U, Weiss R, Wieler LH, Baljer G.
Institut fur Hygiene und Infektionskrankheiten der Tiere,
Justus-Liebig-Universitat Giessen, Germany.
A nested PCR (nested flagellin PCR) carrying an internal E. coli DNA
control
was established and compared with an in-vitro culture method for the
detection
of Borrelia burgdorferi in urine specimens of dogs. The predicted
specific
amplicon of the flagellin gene fla was generated from all cultured
strains of B.
burgdorferi tested (comprising three European genospecies). In
contrast, all
13 strains of seven other flagellated bacterial species were negative.
The PCR
detection limit yielded 20 cells of B. burgdorferi per ml of
double-distilled
water and approx. 250 bacteria per ml of dog urine. Using the bacterial
culture method, urine specimens collected from 216 dogs in Germany were
all
diagnosed negative for spirochetes by in-vitro culture and dark-field
microscopy. In
contrast, DNA of B. burgdorferi was detected in 32 specimens (14.8%) by
PCR.
31 urine specimens (14.4%) showed inhibitory activity in the PCR assay.
However, 94 (44%) were inhibitory in the culture assay. The majority of
the
PCR-positive dogs exhibited major clinical symptoms which have not been
reported in the
course of B. burgdorferi infection previously, e.g. cystitis (14/32
dogs) or
prostatitis (5/32 dogs). Our results indicate that the analysis of
urine
specimens by the nested flagellin PCR is a highly valuable procedure
for the
diagnosis of B. burgdorferi infections in dogs.
PMID: 9638865 [PubMed - indexed for MEDLINE]
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1: Eur Urol. 2000 Apr;37(4):395-9. Related Articles, Links
The role of Borrelia burgdorferi in interstitial cystitis.
Haarala M, Kiiholma P, Nurmi M, Uksila J, Alanen A.
Obstetrics and Gynecology, University of Turku, Finland.
anna.alanen@xxxxxx
BACKGROUND/AIMS: Borrelia burgdorferi spirochete has been found both in
bladder biopsies and the urine of patients with Lyme disease (LD) as
well as in
experimental animals. The urological symptoms in borreliosis resemble
those of
interstitial cystitis (IC): frequency, urgency and nocturia. The aim of
this
studies is to find the role of B. burgdorferi in interstitial cystitis.
METHODS:
We studied antibodies against B. burgdorferi from serum samples of 50
IC
patients with two separate EIA tests. Patients with positive serology
in both tests
underwent cystoscopy and a bladder biopsy was taken. The presence of
borrelia
DNA was studied with borrelia-specific polymerase chain reaction (PCR),
and
with universal bacterial PCR. RESULTS: IgM class antibodies to B.
burgdorferi
were not found, but IgG antibodies were found in four samples (8%).
This was
higher than in the control material (2%). One patient's sample was
strongly
positive, whereas three samples were weakly positive. Bladder biopsies
taken from
the 4 patients were negative for borrelia DNA in both PCR tests. None
of the
seropositive patients had any symptoms consistent with LD. CONCLUSION:
These
results indicate that persistent infection of B. burgdorferi has no
role in the
etiology of IC. On the other hand a connection with a past borrelia
infection
and IC is not excluded.
Publication Types:
Clinical Trial
PMID: 10765068 [PubMed - indexed for MEDLINE]
1: J Wildl Dis. 1994 Jul;30(3):408-16. Related Articles, Links
Response of the meadow vole (Microtus pennsylvanicus) to experimental
inoculation with Borrelia burgdorferi.
Campbell GD, Barker IK, Johnson RP, Shewen PE, McEwen SA, Surgeoner GA.
Canadian Cooperative Wildlife Health Centre, Department of Pathology,
Ontario
Veterinary College, University of Guelph.
The response of the meadow vole (Microtus pennsylvanicus) to infection
by
experimental inoculation with Borrelia burgdorferi was evaluated.
Forty-two adult
voles were inoculated subcutaneously with 0.5 x 10(6) spirochetes. Sera
taken
during the 196 day trial were tested by indirect fluorescent antibody
(IFA)
assay for antibodies to B. burgdorferi. Tissues from animals which died
during
the trial, and from animals killed at 28, 112 and 196 days
post-inoculation
(DPI), respectively, were cultured in BSK-II medium for < or = 6 weeks.
They
also were examined histologically for lesions and the presence of
spirochetes.
All inoculated animals developed antibodies by 14 DPI and maintained
titers > or
= 1:10 for the duration of the trial. Spirochetes were isolated from
ears,
bladder, and spleen. Spirochetes also were identified by Bosma-Steiner
silver
stain or tissue IFA assay in sections of ears, bladder, kidney and
heart.
Infection as confirmed by re-isolation persisted for < or = 111 days.
No lesions
were identified in association with the presence of spirochetes. No
increase in
mortality was observed in inoculated animals compared with controls.
Sensitivity of the IFA test at a cut-off titer of 1:10 was 100% from >
or = 14 DPI, but
at 1:20 reached a maximum of 97%. Specificity at 1:10 was 84% and at
1:20 was
97%. Use of antiserum to Microtus immunoglobulin (Ig) in a
double-layered test
provided no significant advantages over use of a commercial
fluorescein-conjugated anti-mouse Ig in a single-layered IFA test.
PMID: 7933285 [PubMed - indexed for MEDLINE]
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