Lyme borreliosis and tick-bome encephalitis 
Case report 
CONCOMITANT INFECTION WITH 
TICK-BORNE ENCEPHALITIS VIRUS 
AND BORRELIA BURGDORFERI 
J. Cimperman, F. Strle, V. Maraspin-Čarman, S. Lotrič-Furlan, 
E. Ružič-Sabljic and T. Avšič-Župan 
SUMMARY 
We hereby describe two patients, one from the south-eastern part and the other from the northern part 
of Slovenia, where both tick-borne encephalitis (TBE) and Lyme borreliosis are endemic. Both patients 
showed severe meningoencephalitic signs; one with a two-phase course of disease without a tick bite and the 
other with a single-phase course of disease with tick bite. High levels of serum antibodies for TBE virus and 
presence of borrelial antibodies in the serum and in the cerebrospinal fluid were detected, locally synthesized 
borrelial antibodies in the cerebrospinal fluid were demonstrated as well. After the treatment with ceftriaxone 
the state of both patients remarkably improved. The first patient complained of intermittent headache, 
arthralgias and fatigue 6 months after leaving the hospital. The described cases suggest a possibility of a 
concomitant infections with TBE virus and B. burgdorferi in patients living in the endemic areas where Ixodes 
ticks might be infested with TBE virus and B. burgdorferi. 
KEY WORDS: 
Lyme borreliosis, tick-bome encephalitis, concomitant infection 
INTRODUCTION 
The causative spirochete of Lyme borreliosis (LB), 
B. burgdorferi and Plavi virus of the ARBO group B 
are both transferred by the same tick Ixodes ricinus 
in the same area of Slovenia (1,2,3). LB can affect 
the skin, joints, heart and the nervous system. 
Neurologic manifestations may include peripheral 
neuritis, cranial neuritis, encephalopathy and me-
ningoencephalitis ( 4,5). Late manifestations of LB 
acta dennatovenerologica A.P.A. Vol 3, 94, No 1/2 
can be prevented by appropriate treatment of early 
infection. 
The majority of the subjects infected by tick-borne 
encephalitis (TBE) virus most probably never develops 
the disease (3,6). The course of TBE in the Central 
Europe is milder compared to other areas of -the 
Eastern Europe and Asia (7). Paralysis can be 
observed in 7% of the patients, death rate is low -
121 
Lyme borreliosis and tick-bome encephalitis 
less than 1 % (8, 9), No specific treatment is available, 
but the disease can be prevented by immunization 
(10). 
METHODS 
Like ali the patients with meningitis admitted to 
the Clinic of Infectious Diseases Ljubljana, both 
patients presented in this report underwent the 
following tests: basic blood tests, urine tests, and 
routine cerebrospinal fluid (CSF) parameters (concen-
tration of total proteins, glucose and number of 
cells). Using radia! immune diffusion method the 
concentrations of albumin, IgA, IgG and IgM were 
measured in both - the serum and the CSF. Borrelial 
IgM and IgG antibody titers were determined in 
the serum and CSF with the IFA without absorption 
(11). B. burgdorferi serotype 2 strain PKo was used 
as an antigen. Serum antibody titers of 1 : 256 and 
CSF antibody titers of 1 : 8 were considered as 
positive. 
Intrathecal production of borrelial antibodies was 
calculated with commonly used formulas (12, 13, 
14). Serum TBE virus antibodies were determined 
with two methods: complement fixation test (CF) 
using antigen manufactured by BEHRING - 4-fold 
increase of the titers was considered as significant 
and enzyme immunoassay (ELISA) manufactured by 
IMMUNO (IMMUNOZYM FSME - IgG and 
IMMUNOZYM FSME-IgM) following a two-step 
"sandwich" system. 
Patients were tested for syphilis (VDRL, FTA-
ABS). Both patients underwent the ECG and EEG 
examination. 
CASE REPORTS 
Case 1: MD, female, 50 yrs 
Prior to admission to our clinic the patient enjoyed 
good health with the exception of mild cervicalgia. 
During the last three years she was not aware of 
having been bitten by a tick or an insect, she did 
not notice erythema migrans (EM). The first signs 
of disease appeared in the middle of May 1991, 
with fever up to 38°C, general feeling of discomfort 
and headache. After 3 days the fever abated the 
headache disappeared and she was feeling better. 5 
days later her condition deteriorated, the fever rose 
to 39°C, and severe headache and vomiting appeared. 
Upon admission to our clinic in the beginning of 
June 1991 the patient was febrile - 38.6°C, somnolent, 
with expressed meningeal signs. The results of basic 
122 
laboratory tests were within normal limits, except 
ESR which amounted to 30 mm/h, whereas the C-
reactive protein (CRP) was negative. Antibody titers 
in the serum and CSF are demonstrated in the 
table l. Serologic tests for syphilis were negative. 
ECG was normal, EEG abnormal with arrhythmic, 
slow and sharp waves diffusely. 
During the first day the patient was treated with 
analgesics and anti-edematous drugs. On the fifth 
day ceftriaxone 2 g daily was introduced for 14 
days. After two days of antibiotic treatment the 
patient became afebrile, her psychic state became 
normal, but severe tremor of the tongue appeared. 
Within the next 5 days the patient had no headache 
and her general feeling was improved. She left the 
hospital after 20 days; tremor of the tongue persisted. 
At the examination 6 months after leaving the 
hospital she complained of intermittent headache, 
arthralgias of the large joints and fatigue. 2 years 
later EEG was stili moderately abnormal with slow 
activity in the left frontotempornl region. 
Borrelial serologic tests performed after leaving 
hospital remained negative. 
Case 2: MF, male, 39 yrs 
26 years before admittance to our hospital the 
patient was treated for osteomyelitis of the left leg. 
At the end of May 1993, he was bitten by a tick. 
There was no EM. In the middle of June 1993 
dizziness, overall discomfort, fever up to 40°C, 
somnolence, tremor and disturbed speech appeared. 
Headache did not occur. 
Upon admission the patient was febrile - 38.5°C, 
somnolent, with severe tremor of the tongue and 
hands, bilateral conjunctivitis, and prominent meningeal 
signs. 
Laboratory findings demonstrated increased ESR 
(37 mm/h), C-reactive protein 23.7 mg/1. Antibody 
titers of the serum and CSF are shown in the table 
. l. Serologic tests for syphilis were negative. 
ECG was within the normal limits, EEG abnormal 
with sharper activity over the temporal regions, 
which was more expressed on the right side. 
On the third day of hospitalization the patient 
became excited and disoriented. He was moved to 
the intensive care unit. An anti-edematous treatment 
was introduced. On the seventh day the fever dropped, 
the borrelial serology was positive. Ceftriaxone 2 g 
i.v. daily was introduced. Within a few days the 
patient's psychical state improved, and after 14 days 
of antibiotic .treatment his psychical state was normal. 
At examination at the beginning of August 1993 
acta dermatovenerologica A.P.A. Vol 3, 94, No 1/2 
Table 1 
Parameter 
Serum 
Glucose (nmol/1) 
Albumin (g/1) 
IgM (g/1) 
IgG (g/1) 
TBE IgG 
(ELISA) 
TBE IgM 
(ELISA) 
TBE CF 
BB** IgM 
(IFA) 
BB IgG 
(IFA) 
CSF 
Cells (106/1) 
Neutrophils (106/1) 
Lymphocytes (106/1) 
Glucose (mmol/1) 
Tota! proteins (g/1) 
IgM (mg/1) 
IgG (mg/1) 
Albumin (mg/1) 
BBigM 
(IFA) 
BB IgG 
(IFA) 
BB IgM 
index••• 
BB IgG 
index*** 
Albumin 
quotient**** 
• Optical density 
• • B. Burgdorferi 
• • • BB IgG index 
Lyme bo"eliosis and tick-bome encephalitis 
Patient 1 
on admittance 
4.4 
48.2 
4.52 
13.4 
slightly pos 
(60VIEU/ml) 
highly pos 
(OD* 2.871) 
1:32 
1:128 
neg 
165 
11 
154 
3.4 
0.58 
7.25 
60.5 
329 
1:8 
38.99 
0.0083 
TBE tick-borne encephalitis 
BB IgG (CSF) 
4 weeks later 
1:128 
neg 
neg 
BB IgG (serum) 
IgG (CSF) IgG (aerum) 
•••• Albumin (CSF): Albumin (serum) (norm = 0.0033 - 0.0059) 
Patient 2 
on admittance 4 weeks later 
5.3 
35.8 
1.93 
10.3 
pos 
( > 260VIEU/ml) 
highly pos 
(OD* 1.698) 
1:8 
1:64 
1:256 
139 
11 
128 
2.5 
0.73 
4 
50 
310 
1:32 
25.75 
0.0086 
(norm.= 1) 
1:512 
neg 
1 :512 
acta dennatovenerologica A.P.A. Vol 3, 94, No 1/2 123 
Lyme borreliosis and tick-bome encephalitis 
the patient was feeling well, had no headache, but 
complained of intermittent pain in the neck. 
COMMENT 
At least twci cases of concomitant infection with 
TBE virus and B. burgdorferi can be found in the 
literature. 
The first report describes a patient in whom a 
multiple peripheral paresis occurred in the left leg 
3 weeks after the onset of neurological symptoms 
and after recovering from encephalitis (14). 
The second report describes a patient who died 
one month after the disease was noted. The autopsy 
revealed necrotising encephalitis and myelitis with 
the involvement of dorsal root ganglion, presumably 
the main damage was caused by TBE virus (15). 
In our cases of concomitant infection, TBE virus 
infection was verified with highly positive serologic 
tests for TBE virus. The diagnosis of neuroborreliosis 
was established on the basis of positive serologic 
findings in the serum and in CSF, and on the basis 
of calculated values for borrelial antibodies production 
in CSF. The beginning of the disease was severe in 
both patients including meningoencephalitic signs. 
TBE virus may cause meningitis or infection of 
the gray matter of central nervous system ( encephalitis 
and encephalomyelitis) associated with brain edema 
(16). The course of the disease suggests that the 
beginning of the disease in the first patient was 
caused by TBE virus, further disturbances most 
probably resulted from borrelial infection. 
The course of the disease in the second patient 
suggests that the disease might have been caused by 
TBE virus or B. burgdorferi. However, the treatment 
with ceftriaxone resulted in significantly improved 
state of the patient. 
CONCLUSION 
In patients with meningoencephalitis coming from 
the TBE and LB endemic regions the possibility of 
concomitant infection should be suspected. 
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AUTHORS' ADDRESSES 
Jože Cimperman, MD, Department of lnfections Diseases 
University Medica! Centre, Japljeva 2, 61000 Ljubljana, Slovenia 
Franc Strle, MD, PhD, professor at infectious diseases, same address 
Vera Maraspin-Čarman, MD, same address 
Stanka Lotrič-Furlan, MD Mr se, same address 
Eva Ružic-Sabljic, MD, Mr Se, Institute for Microbiology, Zaloška 4 
Medica! Faculty, 61000 Ljubljana, Slovenia 
Tatjana Avšič-Župan, MD, PhD, same address 
acta dermatovenerologica A.P.A. Vol 3, 94, No 1 /2 125