Case Report

Received: May 12, 2000

Am J Nephrol 2001;21:66–68
Accepted: November 8, 2000

Neurobrucellosis – A Rare Complication

of Renal Transplantation
Bedri Yousif Jeff Nelson
Clinical Medical Services Department, Saudi Aramco-Dhahran Health Center, Saudi Aramco Medical Services
Organization, Dhahran, Saudi Arabia

Key Words Introduction

Kidney transplantation W Brucellosis W Nervous system
diseases
Abstract
Brucellosis is an intracellular bacterial infection con-
tracted by consuming raw milk or by contact with
infected cattle. Neurobrucellosis is a rather rare manifes-
tation of brucellosis and has protean clinical presenta-
tions characterized by meningoencephalitis, myelitis,
myelopathies, subarachnoid hemorrhage and psychiat-
ric manifestations. A depressed immune status is be-
lieved to be a risk factor for developing neurobrucellosis.
We report a case of neurobrucellosis in a patient 13 years
after a cadaveric renal transplantation. Even though a
Brucella organism was not isolated from body fluids she
satisfied other criteria for establishing the diagnosis.
Treatment with doxycycline and rifampin led to a clinical
cure as well as to marked improvement in the Brucella
titer.
Copyright © 2001 S. Karger AG, Basel
Since the successful introduction of renal transplanta-
tion as a viable therapeutic option, thousands of people
have enjoyed a quality of life far superior to one on dialy-
sis. This was, of course, made possible by the ever-
improving immunosuppressive agents now available in
clinical practice. However, any such drug remains a dou-
ble-edged sword. Too much may cause severe immuno-
suppression with its accompanying consequences, while
too little raises the specter of renal allograft rejection.
Infections in solid organ transplantation have been
artificially, albeit conveniently, classified according to the
relationship to the time of transplant [1]. Brucellosis is a
bacterial infection acquired from consuming raw milk or
its products or from contact with infected cattle. Brucella
is an intracellular bacteria whose elimination from the
body, like other intracellular pathogens, requires an effec-
tive orchestration of monocyte macrophages and T-cell
function and various cytokines. CNS infection by Brucel-
la is rare and is mostly seen in those with decreased
immune resistance [2].
To our knowledge, there is no reported case of neuro-
brucellosis in a renal transplant patient. We report a
patient with whom neurobrucellosis was diagnosed 13
years after a cadaveric renal transplantation.

© 2001 S. Karger AG, Basel Dr. B. Yousif

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 Case Report
A 56-year-old Saudi woman underwent a cadaveric renal trans-
plantation in Houston, Tex., in 1983. The degree of tissue match is
not available to us. She was placed on triple immunosuppressive
therapy, consisting of cyclosporine, azathioprine and prednisone.
Twelve years later, in October 1995, the patient was hospitalized at a
local teaching Hospital in Riyadh because of fever and loss of con-
sciousness. Mycobacterium tuberculosis was isolated from her CSF
and she was treated with antituberculous medication for 1 year. In
lieu of prednisone, the patient received 4 mg of dexamethasone
daily.
In September 1996, the patient was admitted to Saudi Aramco-
Dhahran Health Center because of confusion. Review of her medica-
tions revealed that she had been inadvertently taking 20 mg of dexa-
methasone daily. Probable steroid-induced confusion was diagnosed.
She improved following a decrease in her dexamethasone dose to
4 mg daily and was discharged home. Her antituberculous medica-
tions had been discontinued after a year-long therapy. This com-
prised INH 300 mg q.d. rifampin 600 mg q.d., pyrazinamide 1.5 g
q.d. and pyridoxine 50 mg q.d.
Two weeks later she was seen in the renal clinic, where she was
found to have vesicular lesions on the medial aspect of her right
thigh. Several of the lesions had scabbed. The patient was not placed
on parenteral antiviral medication as there was no evidence of sys-
temic involvement. Ten days later she was readmitted with fever,
decreased level of consciousness, volume depletion and metabolic
acidosis. Her usual serum creatinine of 2.7 mg/dl had gone up to
6 mg/dl. Following blood and urine cultures and negative brain CT
scan, the patient was started on ceftriaxone and vancomycin. She
also received cautious intravenous hydration. A spinal tap was per-
formed the next day and this showed lymphocytic pleocytosis, ele-
vated protein and normal glucose levels. The CSF specimen was also
sent for routine, fungal, viral and TB cultures. Gram stain and India
ink were performed on the specimen and were negative. Her antitu-
berculous medications were continued. Because of the possibility of
herpes encephalitis, acyclovir, adjusted to her level of renal function,
was started. An EEG was not consistent with the diagnosis of herpet-
ic encephalitis. A serological test for herpes was also negative.
The patient remained febrile and in a coma for over 10 days.
Amphotericin was added to her antimicrobial therapy. A serum Bru-
cella titer was obtained and came back positive at 1/320. A presump-
tive diagnosis of neurobrucellosis was entertained and treatment
with doxycycline 100 mg p.o. b.i.d. and rifampin 600 mg p.o. q.d.
was initiated and continued for a total of 6 weeks. All other antimi-
crobials were discontinued. The patient’s level of consciousness grad-
ually improved. Three weeks later she was fully awake and a repeat
serum Brucella titer was 1/80. Her serum creatinine also returned to
her baseline value of 2.7 mg/dl. At no time during her ordeal did she
require dialytic support and the rest of her immunosuppressive med-
ication consisting of cyclosporine (Neoral) 125 mg p.m. b.i.d. and
azathioprime 50 mg q.d. remained unchanged.
Her family consistently denied any knowledge of the patient con-
suming raw milk or products made of raw milk or of any contact with
cattle during the last 25 years, however, they did admit that these
were common practices for the family in the past.
Neurobrucellosis
Discussion
Brucellosis is an intracellular bacterial infection that
localizes in different parts of the body (spleen, brain, heart
and bones) and is characterized by undulant fever, endo-
carditis, arthritis and osteomyelitis [3]. On the basis of her
clinical response and Brucella serology, we believe that
our patient had neurobrucellosis. This entity is known to
have a protean clinical manifestation. Meningoencephali-
tis, myelitis and myelopathies, subarachnoid hemorrhage
and psychiatric disorders are some described manifesta-
tions [2].
Our failure to isolate the Brucella organism from CSF
or blood does not rule out this diagnosis. The following
criteria, modified from Spink [4, 5], were recommended
by Larbrisseau in chronic brucellosis where isolation of
the organism is difficult: (1) history of exposure to the dis-
ease; (2) objective and subjective evidence of illness;
(3) presence of Brucella agglutinin, especially if the titer
exceeds 1/100, and (4) unequivocal and rapid improve-
ment in clinical condition and Brucella agglutinin titer
after specific therapy. Our patient fulfilled all these crite-
ria.
The serological diagnosis in our laboratory is per-
formed by hemagglutination using polyvalent antibody
against B. abortus, B. melitensis and B. suis. It measures
both IgM and IgG antibodies. The latter is believed to cor-
relate best with active disease [6]. This distinction in our
case is rather inconsequential as we were able to demon-
strate a falling titer with significant clinical improvement.
Skin lesions are rare in brucellosis [3]. Evanescent rash,
ulcers, abscesses, papules and erythema nodosum have
been reported. Even though there is no virological confir-
mation of the skin lesion in our patient, it appeared clini-
cally to be a herpetic lesion limited to a dermatome. This
goes along with the marked cytotoxic T-lymphocyte-defi-
cient states induced by profound immunosuppression.
What is intriguing is whether the presumptive diagnosis
of so-called steroid-induced confusion was, in retrospect,
a manifestation of neurobrucellosis.
Neurobrucellosis is a rare manifestation of Brucella
infection, even more so in a transplant patient. In one
study, the incidence of neurobrucellosis was believed to
be about 6% of all brucellosis cases admitted to that insti-
tution [7]. The authors were quick to add that this inci-
dence was probably too high as there could have been
numerous cases where medical advice was never sought.
Brucella, like a number of other intracellular pathogens,
evade the phagocytic action of macrophages by various
mechanisms [8]. A more recent finding is the in vitro
Am J Nephrol 2001;21:66–68 67
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identification of a protein suppressor factor secreted by
Brucella following its phagocytosis by macrophages. This
inhibits macrophages from synthesizing TNF-· and al-
lows Brucella to establish long-term residence [9]. TNF-·
is a key cytokine in the control of infectious processes. It
increases the bactericidal activity of macrophages in an
autocrine fashion [10]. In concert with IL-12, it stimulates
NK cells to produce gamma interferon and this enhances
nonspecific immunity [11]. It also plays an important role
in triggering a specific immunity against intracellular
pathogens [12]. We speculate that the intense immuno-
suppression our patient was exposed to, through inadver-
tent use of high doses of dexamethasone, could have led to
recrudescent brucellosis by altering the cytokine milieu,
Glucocorticoid has been found to modulate several cyto-
kine and growth factors (i.e. IL-1, IL-3, IL-4, IL-6), insu-
lin-like growth factor, TNF, IFN-Á, IL-8, RANTES and
MCAF, as well as some of their receptors [13, 14].
Finally, this case report illustrates that while neurobru-
cellosis is an unusual manifestation of brucellosis, one
needs to consider it in the differential diagnoses when pre-
sented with a patient from a region with endemic brucel-
losis who has fluctuating levels of consciousness and pro-
found immunosuppression, despite an apparently nega-
tive history of exposure.
Acknowledgements
The authors wish to acknowledge the use of Saudi Aramco Medi-
cal Services Organization facilities for the data and study which
resulted in this paper. The authors were employed by Saudi Aramco
during the time the study was conducted and the paper written.

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