 |
|
Neurological Involvement in Acute Q Fever
A Report of 29 Cases and Review of the Literature
Emmanuelle Bernit, MD;
Jean Pouget, MD;
François Janbon, MD;
Hervé Dutronc, MD;
Philippe Martinez, MD;
Philippe Brouqui, MD, PhD;
Didier Raoult, MD, PhD
Arch Intern Med. 2002;162:693-700.
ABSTRACT
| |
Background Q fever is characterized by its clinical polymorphism; neurological
involvement has occasionally been described. In the course of acute Q fever,
neurological manifestations may include aseptic meningitis, encephalitis or
encephalomyelitis, and peripheral neuropathy.
Objective To review and evaluate cases of acute Q fever with neurological symptoms
diagnosed in our laboratory.
Methods A total of 1269 acute Q fever cases were recorded from January 1985
to January 2000 in our laboratory and were reviewed for neurological complications.
Patients were considered to have acute Q fever when serological procedures
showed Coxiella burnetii phase II titers of 1:200
or higher for IgG and 1:50 or higher for IgM. Those patients who underwent
a lumbar puncture for cerebrospinal fluid analysis or who had abnormal neurological
symptoms were selected for this study. We describe the clinical, epidemiological,
and biological features of these cases. We also review the literature and
compare our cases with those previously reported.
Results Among the 45 patients selected, 14 were excluded because they had normal
cerebrospinal fluid and no neurological symptoms. Two were excluded because
there were no clinical or epidemiological data. Three major clinical syndromes
were observed: meningoencephalitis or encephalitis in 17 cases; meningitis
in 8; and myelitis and peripheral neuropathy in 4. Encephalitic signs were
not specific, but behavior or psychiatric disturbances were common.
Conclusions Q fever should be included in the differential diagnosis of acute neurological
disease in a patient with a fever. Serological testing should be performed
in cases of meningoencephalitis, lymphocytic meningitis, and peripheral neuropathy,
including Guillain-Barré syndrome and myelitis.
INTRODUCTION
Q FEVER IS A worldwide zoonosis caused by Coxiella
burnetii, a strictly intracellular organism living in the phagolysosomes
of the host cell. Throughout the world, the most common reservoirs for C burnetii are cattle, sheep, and goats.1
Infection in animals is not usually apparent, but the organism is found in
urine, feces, milk, and the afterbirth or aborted products of infected animals.2 Pets have also been involved, mainly cats but also
dogs.3 Moreover, as C burnetii can be transported by the wind, a substantial proportion of patients
have reported no direct contact with animals.4
Human infection occurs following inhalation of contaminated aerosols or ingestion
of raw milk or fresh goat cheese. A percutaneous route and vertical transmission
from mother to child have also been documented.
A main characteristic of C burnetii infection
is clinical polymorphism. Q fever is commonly categorized into acute and chronic
forms, and the clinical manifestations, serological profiles, and treatments
for the 2 forms are different. Half of acute cases are asymptomatic. The most
common clinical syndromes of acute fever are a self-limited febrile illness,
a flulike syndrome, or pneumonia.2 Granulomatous
hepatitis may occur in association with an increase in liver enzyme levels.
Cases of prolonged fever, febrile eruption, myocarditis, and pericarditis
have also been reported. While the involvement of the central nervous system
(CNS) due to embolism from an infected valve during chronic Q fever endocarditis
is common,5 neurological symptoms in acute
Q fever have been reported less frequently, and their incidence is probably
underestimated. To our knowledge, only 17 well-documented cases of meningoencephalitis,6-22
2 of Guillain-Barré syndrome,23-24
4 of peripheral neuritis,25-26
and 6 of aseptic meningitis have been reported.26-29
Neurological manifestations described in the course of the acute disease include
aseptic meningitis, encephalitis or encephalomyelitis, toxic confusional states,
extrapyramidal signs, dementia, behavioral disturbances, and multiple cranial
nerve involvement.30 Our laboratory has recently
reported the clinical and epidemiological features of 1614 cases of acute
and chronic Q fever, including neurological involvement in cases of acute
infection, without detailing cases reported or comparing them with cases from
the literature.31
We report herein 29 cases of Q fever with diverse neurological symptoms
from a series of patients diagnosed in our laboratory between January 1985
and January 2000, including 5 previously reported cases of meningoencephalitis.32 The prevalence of neurological complications during
acute Q fever was calculated. Neurological manifestations associated with
chronic Q fever were excluded. We also reviewed the literature for all cases
of acute Q fever with neurological involvement, and their epidemiological
and clinical features were compared with our cases.
PATIENTS AND METHODS
PATIENT CHARACTERISTICS
Our laboratory is the French National Reference Center for Rickettsial
Diseases in Marseille, France, which receives 9000 samples annually from France
and other countries. A total of 1614 Q fever cases were recorded from January
1985 to January 2000 (1269 acute and 345 chronic infections); for most of
these, clinical information was available. Case records of patients with acute
Q fever were reviewed for neurological complications. Patients with meningitis
(cerebrospinal fluid [CSF] pleocytosis), encephalitic and/or medullar involvement,
and/or peripheral neuropathy were selected for this study. A headache was
considered a neurological symptom when it was severe enough to prompt a lumbar
puncture. However, of the cases where a lumbar puncture was performed, we
eliminated those where CSF was normal (cell count, <5/µL; protein
level, <0.5 g/L; and CSF glucose level, half the blood glucose level) and
there were no neurological symptoms. Exposure factors, age, sex, presence
of immunodepression, clinical presentation (occurrence of fever, pneumonia,
or hepatitis), and biological data such as increased erythrocyte sedimentation
rate (>20 mm/h), elevated liver enzyme levels (>40 IU/L, which is twice the
upper normal value), and thrombocytopenia (platelet count, <130 x
109/L) were studied.
DIAGNOSTIC PROCEDURES
Titers of IgG, IgM, and IgA antibodies in serum samples from each patient
were estimated by using the indirect immunofluorescent antibody test as previously
described.33 Serum IgG antibodies were systematically
removed before titration of IgA and IgM to avoid rheumatoid factor interference
(RF Absorbent, Dade Behring GmbH, Marburg, Germany). Patients were considered
to have acute Q fever when serological procedures showed a C burnetii phase II titer of 1:200 or higher for IgG and 1:50 or higher
for IgM.33
Blood-CSF barrier permeability was evaluated by the albumin quotient
(plasma albumin level divided by the CSF albumin level; an index of 0.0075
was considered the normal upper limit value).9 Coxiella burnetii antibody levels were estimated in CSF
by immunofluorescence, and intrathecal synthesis of immunoglobulin was evaluated
by IgG index (the ratio of CSF antibody titer divided by serum antibody titer
to CSF albumin level divided by serum albumin); a ratio higher than 0.8 was
considered suggestive of intrathecal synthesis.9
Blood and CSF samples (when available) were inoculated onto human fibroblasts
grown on a coverslip within a shell vial as previously described.34 After 7 days of incubation at 37°C, cultured
bacteria were detected by using the direct immunofluorescence test incorporating
rabbit monoclonal antibody to C burnetii.35
DNA was extracted from CSF and/or blood samples by using the QiAmp Tissue
kit and the QiAmp Blood kit (QIAGEN GmbH, Hilden, Germany) according to the
manufacturer's instructions. These extracts were used as templates in polymerase
chain reaction amplifications as previously described.36
REVIEW OF THE LITERATURE
We reviewed the English- and French-language literature on MEDLINE for
all cases of Q fever with neurological complications from 1946 to 2000 using
the following keywords: acute Q fever; Coxiella burnetii; neurological involvement; meningoencephalitis; encephalitis; meningitis,
Guillain-Barré syndrome; neuritis; and myelitis.
RESULTS
Between January 1985 and January 2000, the diagnosis of acute Q fever
was confirmed in 1269 patients. Forty-five patients (3.5%) with acute Q fever
had a headache, meningeal syndrome, and/or abnormal encephalitic or myelitis
signs. Among these, 14 patients with normal CSF were excluded from the study
and were considered to have meningeal irritation. We were not able to obtain
epidemiological or clinical information for 2 patients, and these 2 were therefore
also excluded.
All patients had significant titers of antibodies against C burnetii phase II antigens, and none had serological evidence of
chronic Q fever. Among the 10 patients tested for the presence of specific
CSF antibodies, 6 tested positive (with significant levels of CSF IgG >1:200
by immunofluorescence), and 1 of these also had IgM antibodies. The albumin
quotient showed a damaged blood-CSF barrier in 5 cases. The IgG index was
above 0.8 for 3 patients, but 2 had a damaged blood-CSF barrier. Thus, the
IgG index was suggestive of intrathecal synthesis of C burnetii antibodies in only 1 case. Attempts to isolate C burnetii from blood in 2 cases and from CSF in 5 cases where CSF
was abnormal were unsuccessful. Molecular detection in CSF produced negative
results in the 3 cases where it was carried out. Bacterial cultures of blood
and CSF (including for Mycobacteria) were negative,
and attempts to isolate herpesvirus and enterovirus failed. The serological
assay findings for Brucella, Leptospira, Salmonella, Borrelia burgdorferi, human immunodeficiency virus, herpesvirus, and enterovirus were negative.
Epidemiological, clinical, and biological data for the reported cases
are summarized in Table 1, Table 2, Table 3, and Table 4). Among the 29 patients, 22 were male and 7 were female (male/female sex ratio,
3.1). The mean age was 46.5 ± 20.6 years (range, 7-83 years). No immunocompromised
situation was noted. Fourteen patients had a strong epidemiological risk of
Q fever because they were in close contact with goats or goat products. Several
exposure factors were identified: living in rural areas in 13 of 25 cases;
profession (farmer, veterinarian, or shepherd) in 6 of 26 cases; contact with
farm animals, specifically goats, or parturient cats in 13 of 23 cases; and
ingestion of raw milk or farm goat cheese in 4 of 13 cases.
|
|
|
|
Table 1. Epidemiological, Clinical, and Biological Data of Patients
With Q Fever Meningoencephalitis From Present Study*
|
|
|
|
|
|
|
Table 2. Epidemiological, Clinical, and Biological Data of Patients
With Q Fever Meningoencephalitis Found in Literature Review*
|
|
|
|
|
|
|
Table 3. Patients With Polyradiculoneuritis, Peripheral Neuritis, and
Myelitis During Acute Q Fever*
|
|
|
|
|
|
|
Table 4. Patients With Meningitis During Acute Q Fever*
|
|
|
Clinically, 26 patients were febrile and 12 had myalgia or arthralgia.
Nine of the 27 patients had a flulike syndrome, and 3 had pneumonia. Platelet
counts were low in 6 cases, and the erythrocyte sedimentation rate was abnormal
in 17. There were abnormalities of liver function tests in 8 cases. As for
prognosis of the 29 patients, 2 with meningoencephalitis died (Table 1, patients 10 and 11): an 83-year-old woman and a 70-year-old
man. Both had severe and diffuse encephalitic signs, and in patient II the
findings of a computed tomography (CT) brain scan were normal. Patient 10
was treated with clavunalic acid–amoxicillin and patient 11 with rifampin.
Neurological sequelae were noted in 4 of 29 patients (Table 1, patients 12, 14, and 17; Table 3, patient 1). These consisted of a palsy of nerve VI in 1
case, a central vestibular vertigo in 1, a pyramidal syndrome in 1, and a
bilateral facial palsy in 1. Two of these patients were treated with doxycycline,
1 with rifampin, and 1 with ciprofloxacin. Twenty-three patients recovered
within days or weeks (maximum of 3 months). The course of clinical symptoms
showed that, as in patients 1 and 2, neurological aggravation periods lasted
from a few hours to a few days, alternating with complete or partial recovery
periods. Recovery seemed to occur regardless of treatment. Treatments included
erythromycin (2 cases), ampicillin (3 cases), doxycycline (10 cases), pefloxacin
(3 cases), and rifampin (5 cases).
Three major syndromes were observed: meningoencephalitis or encephalitis
in 17 patients, meningitis in 8, and myelitis and polyradiculoneuritis or
peripheral neuritis in 4. Among those patients with meningoencephalitis (Table 1, patients 1-17), encephalitic symptoms
varied. Symptoms included abnormalities of behavior or psychiatric problems
(6/17; 35%), confusion and/or somnolence (12/17; 71%), seizures (5/17; 29%),
and focal neurological deficit (11/17; 765%). Cerebrospinal fluid was abnormal
in 12 cases, with pleocytosis characterized by a predominance of lymphocytes
in the CSF in 11 cases and an increased protein level in 1. The glucose level
was normal in all cases.
Computed tomography brain scans were abnormal in 3 (21%) of 14 cases,
with nonspecific diffuse brain edemas in 2 cases and pseudonecrotic edemas
in the right temporal area in the third case. Magnetic resonance imaging (MRI)
confirmed on these 2 patients diffuse cerebral edemas. In another case, a
CT brain scan was normal, but a brain MRI demonstrated bilateral periventricular
edemas (Figure 1). The electroencephalogram
carried out in 16 cases revealed abnormalities in 13. These included diffuse
encephalitic involvement with right temporal theta ( ) waves or postseizure
waves.
|
|
|
|
Bilateral periventricular edemas in a T2-weighted magnetic resonance
brain image in a patient with meningoencephalitis, psychiatric symptoms, and
focal deficit (aphasia).
|
|
|
Two patients had myelitis (Table 3, patients 2 and 4) with a motor weakness and sensory loss in the
limbs, although CSF was normal. In one case, medullar MRI was performed but
was normal. One patient had Guillain-Barré syndrome (Table 3, patient 1) with a bulbar involvement. An increased protein
level without pleocytosis was evident in the CSF. One patient (Table 3, patient 3) had only ocular involvement with a third right
cranial nerve palsy; no lumbar puncture was done.
Eight patients (Table 4,
patients 1-8) had only meningitis with pleocytosis, which was characterized
by a predominance of lymphocytes in 6 cases and an increased protein level
in the other 2. The glucose level was normal in all cases.
COMMENT
In this study, we report neurological manifestations that include a
headache severe enough to prompt a lumbar puncture to rule out meningitis
in 3.5% of hospitalized acute Q fever cases22, 25-26,28-29,37-38
(Table 5). When we excluded patients
who had only a headache and normal CSF, the prevalence of neurological symptoms
in acute Q fever was 2.2%. In a review of acute Q fever in California, Clark
et al26 reported signs of diffuse meningeal
irritation and stupor in 5% of cases (Table
5). The prevalence of neurological manifestations in acute Q fever
varies considerably. Reviewing 188 cases of Q fever in Australia, Derrick37 describes a single case of cerebral involvement (paresis
and areflexia of the extremities) (Table
5). Reilly et al,25 in a series of
103 patients with Q fever in Plymouth, England (46 acute infections, 5 chronic
infections, and 52 past infections), reported an astounding 22% incidence
of neurological complications in acute infections (Table 5). Clark et al26 found disorientation
and confusion (and occasionally encephalitic apathy) in 7% of patients. Exposure
factors were rarely available in previously reported cases, but the prevalence
of clinical and epidemiological conditions associated with neurological involvement
and reported by our team in the retrospective analysis on acute Q fever suggests
that neurological involvement in acute Q fever is not linked with predisposing
conditions but with strong environmental exposure.31
|
|
|
|
Table 5. Prevalence of Neurological Involvement in the Present Study
and Previous Series*
|
|
|
The neurological symptoms of the 34 patients with meningoencephalitis
and/or encephalitis reported herein and from the literature (Table 1 and Table 2)
were nonspecific. Behavioral abnormalities were common (9 patients; 26%),
and Schwartz19 reported a case of manic psychosis.
Furthermore, other signs of CNS involvement have been found as an extrapyramidal
neurological syndrome simulating Parkinson disease (case 3220),
Millard-Gubler syndrome,18 cerebellar syndrome,6, 20 and pyramidal syndrome.39
A variety of neuro-ocular findings have been reported in cases of Q fever
encephalitis. Shaked and Samra13 describe bilateral
lateral rectus muscle palsy and optic neuritis with a normal CT of the head.
In addition, Schuil et al15 describe bilateral
optic neuritis in a farmer who presented with loss of vision in his right
eye and painful eye movements; a CT scan showed bilateral optic nerve thickening.
In another case, Miller Fisher syndrome was reported with bilateral paralysis
of the sixth cranial nerves and with upgaze and mild bilateral ptosis11; findings of a CT head scan and lumbar puncture were
normal. In the 33 cases where the CSF was examined (Table 1 and Table 2),6-21
cells were present in 23 cases (70%); cell counts ranged from 19/µL
to 1600/µL. In all but 1 case, these were predominantly mononuclear
cells. The glucose level was low in only 1 patient. The protein level was
increased in 11. Findings of neuroradiological examinations were rarely abnormal
and were not specific. Six (18%) of the 34 meningoencephalitis cases had neuroradiological
abnormalities evidenced on brain imaging (Table 1 and Table 2).
In 1 case, there was a decreased absorption coefficient in the subcortical
white matter of both hemispheres on CT scan.6
Magnetic resonance imaging carried out in this case showed increased signal
intensity on T2-weighted images in the right cerebellar hemisphere. The electroencephalogram
was often abnormal (85% of cases; n = 23) when this investigation was carried
out (Table 1 and Table 2). It showed a nonspecific involvement of the CNS.
With respect to myelitis, polyradiculoneuritis, and peripheral neuropathy,
we herein report 3 cases of Guillain-Barré syndrome (Table 3), which has been reported only twice before. In 1960,23 a 61-year-old woman had bilateral optic neuritis
and sensory and motor peripheral neuropathy with paraesthesia of her legs
and arms; she was treated with chloramphenicol and had no sequelae.23 Another case of Guillain-Barré syndrome was
reported in a 42-year-old woman24 with facial
diplegia and loss of proximal motor coordination of the lower limbs. In our
study, there was 1 case of peripheral neuropathy with palsy of the third right
nerve (Table 3, case 3). Among
103 cases of Q fever reported by Reilly et al,25
there was 1 case of lower-limb peripheral neuropathy (wasted and flaccid)
with paraesthesia in a 32-year-old man with jaundice and hepatosplenomegaly.
The CSF findings were normal. There was minimal leg weakness after 1 year
of follow-up. Clark et al26 reported altered
reflexes in 2 of 180 patients. We herein report 2 cases of myelitis (Table 3), but no cases of isolated myelitis
have previously been reported in the literature (Table 5).
Severe headache associated with a meningeal syndrome is the most common
neurological manifestation in Q fever.26 Findings
on CSF examination are usually described as normal in Q fever infection. In
the present study, CSF was normal in 14 (34%) of 41 cases. We have herein
reported 8 cases of aseptic meningitis (Table 4). In Spelman's study,28 examination
of the CSF revealed mild pleocytosis in 2 of 26 cases of lumbar puncture and
an elevated protein level in 14 of the 26 cases (Table 5). In the studies of Reilly et al25
and Derrick,37 there was no reported case of
meningitis (Table 5). In the 180-patient
series reported by Clark et al,26 stiffness
of the back or neck severe enough to suggest meningeal irritation was observed
in 9 patients (5%). Of 5 lumbar punctures performed, 1 resulted in an abnormal
CSF finding. During an outbreak of Q fever among American and British troops
in Italy during World War II, lumbar punctures were performed in 3 cases because
of neck stiffness, but the CSF was normal in all 3 cases.38
In a report of C burnetii occurrences in the northwest
of England and North Wales between 1965 and 1967, among 10 patients with headache,
neck stiffness, and pyrexia, only 1 had meningitis.29
Leng-Levy et al27 reported 2 cases of acute
Q fever with meningitis. In total, to the best of our knowledge, 6 cases of
acute Q fever with meningitis have been reported.
As for prognosis, in most instances the neurological involvement is
mild. However, in the Plymouth series,25 6
of the 45 patients with acute Q fever had residual neurological impairment,
including motor weakness, recurrent meningismus, blurred vision, residual
paresthesia, and sensory loss involving the left leg. In our 34 encephalitis
cases, recovery was complete for 22 patients within days or weeks (3 months
at the most); there were no long-term relapses, and neurological sequelae
were found in 7 cases (21%). There were 2 cases of peripheral neuritis with
neurological impairment. No deaths have been reported prior to this work.
Recovery seems to take place regardless of treatment. Although many cases
of Q fever infection will resolve without antimicrobial therapy, doxycycline
(200 mg daily) is the recommended treatment. It has also been suggested, because
of the possible CSF passage of C burnetii, that fluoroquinolones
be used in cases associated with meningeal involvement because of the good
CSF concentration of these compounds.40 Other
antibiotics such as erythromycin, chloramphenicol, co-trimoxazole, and ceftriaxone
have been reported effective in the treatment of acute Q fever.41-43
The type of treatment in our series does not seem to be correlated with the
presence of neurological sequelae.
With respect to physiopathology, the mechanism by which infection with C burnetii may cause symptoms attributable to the CNS is
not known. Coxiella burnetii has been identified
by immunofluorescence in brain capillary endothelial cells,44
and other mechanisms of injury of Q fever on CNS have been suggested such
as that mediated by circulating immune complexes,45
which are detected in acute infection. Robbins and Ragan38
succeeded in isolating C burnetii from the CSF of
1 patient and in guinea pigs after serial passages. Our attempts to isolate C burnetii from CSF in 5 cases in which the CSF was abnormal
were always unsuccessful. The case reported by Sawaishi et al6
is the first in which C burnetii has been isolated
and detected by polymerase chain reaction in CSF. Pathological findings of
the brain in a patient who died of Q fever pneumonia46
showed small perivascular hemorrhages with capillary endothelial swelling
and a few capillary thrombi. No perivascular infiltrate was noted, but Giemsa
staining demonstrated coccoid and bacillary rickettsial forms inside neuroglial
cells as well as extracellularly.
Our data show that individuals with specific occupational exposure are
at a significantly higher risk of neurological involvement than are other
patients with acute Q fever.31 This could mean
that individuals in specific occupations are exposed to strains of C burnetii that have a greater pathological potential for the neurological
system. Or it could mean that these individuals are exposed more frequently,
and the neurological involvement results from multiple exposure and reinfection.
Indeed, the clinical manifestations in these occupationally exposed individuals
were different from those of others: these occupationally exposed patients
had hepatitis and pneumonia less frequently and a worse prognosis even though
they were not older or more frequently immunocompromised. Therefore, we consider
that neurological manifestations characterize a distinct clinical entity.
In conclusion, neurological signs are prevalent in acute Q fever. Patients
with CNS involvement do not demonstrate differences in predisposing conditions,
but more frequently have occupational exposure to goats than patients with
acute Q fever but no neurological involvement. There are 3 major neurological
entities associated with Q fever: (1) meningoencephalitis or encephalitis;
(2) lymphocytic meningitis (both of these entities have already been described)
and (3) peripheral neuropathy (myelitis, polyradiculoneuritis, or peripheral
neuritis, which have been less frequently identified). The outcome of all
3 of these entities may be severe. Two deaths occurred in our series, and
residual neurological impairment may be permanent in 4 other cases. Q fever
should be included in the differential diagnosis of acute neurological disease,
and serological testing should be performed in all cases of meningoencephalitis,
meningitis, and peripheral neuropathy because Q fever requires specific antibiotic
treatment. Moreover, systematic screening for Q fever may explain some previously
undiagnosed cases of acute neurological disease.
AUTHOR INFORMATION
Accepted for publication July 30, 2001.
We wish to thank J. R. Birtle, PhD, for his revision of the English
manuscript.
Corresponding author: Didier Raoult, MD, PhD, Unité des Rickettsies,
Centre National de la Recherche Scientifique, UPRESA 6020 IFR 48, Faculté
de Médecine, Université de la Méditerranée, 27
Boulevard Jean Moulin, 13385 Marseille CEDEX 05, France (e-mail: Didier.Raoult{at}univ.mrs.fr).
From Unité des Rickettsies, Centre National de la Recherche
Scientifique (Drs Bernit, Brouqui, and Raoult) and Service de Neurologie,
Hôpital de La Timone (Dr Pouget), Marseille, France; Service de Maladies
Infectieuses, Hôpital Gui de Chauliac, Montpellier, France (Dr Janbon);
Service de Maladies Infectieuses, Hôpital Pellegrin-Tripode, Bordeaux,
France (Dr Dutronc); and Service de Neurologie, Hôpital de Rangueil,
Toulouse, France (Dr Martinez).
REFERENCES
| |
1. Fishbein DB, Raoult D. A cluster of Coxiella burnetti infections
associated with exposure to vaccinated goats and their unpasteurized dairy
products. Am J Trop Med Hyg. 1992;47:35-40.
2. Raoult D, Marrie TJ. Q fever. Clin Infect Dis. 1995;20:489-496.
ISI
| PUBMED
3. Marrie TJ, Raoult D. Q fever: a review and issues for the next century. Int J Antimicrob Agents. 1997;8:145-161.
4. Tissot-Dupont H, Torres S, Nezri M, Raoult D. Hyperendemic focus of Q fever related to sheep and wind. Am J Epidemiol. 1999;150:67-74.
FREE FULL TEXT
5. Raoult D, Razza A, Marrie TJ. Q fever endocarditis and other forms of chronic Q fever. In: Marrie TJ, ed. Q Fever: The Disease.
Boca Raton, Fla: CRC Press; 1991:179-199.
6. Sawaishi Y, Takahashi I, Hirayama Y, et al. Acute cerebellitis caused by Coxiella burnetii. Ann Neurol. 1999;45:124-127.
FULL TEXT
|
ISI
| PUBMED
7. Scully RE, Mark EJ, McNeely WF, Ebeling SH, Phillips LD. Weekly clinicopathological exercises. N Engl J Med. 1998;338:112-119.
FREE FULL TEXT
8. Ferrante MA, Dolan MJ. Q fever meningoencephalitis in a soldier returning from the Persian
Gulf War. Clin Infect Dis. 1993;16:489-496.
ISI
| PUBMED
9. Guerrero M, Gutierrez J, Carnero C, Gonzalez-Maldonado R, Maroto C. Acute meningoencephalitis as the sole manifestation of Q fever. Eur J Clin Microbiol Infect Dis. 1993;12:35-37.
FULL TEXT
|
ISI
| PUBMED
10. Casalino E, Clair B, Kalo T, Gykas A, Vachon F. Méningo-encéphalite grave au cours d'une infection aiguë
à Coxiella burnetii. Ann Med Interne (Paris). 1992;143:70-71.
PUBMED
11. Diaz Ortuno A, Maeztu C, Munoz JA, Reigadas R, Rodriguez T, Valdes M. Miller Fisher syndrome associated with Q fever. J Neurol Neurosurg Psychiatry. 1990;53:615-616.
ABSTRACT
12. Cameron DA, Freedman AR, Wansbrough-Jones MH. Q fever encephalitis. J Infect. 1990;20:159-162.
FULL TEXT
|
ISI
| PUBMED
13. Shaked Y, Samra Y. Q fever meningoencephalitis associated with bilateral abducens nerve
paralysis, bilateral optic neuritis and abnormal cerebrospinal fluid findings. Infection. 1989;17:394-395.
FULL TEXT
|
ISI
| PUBMED
14. Marrie TJ. Pneumonia and meningoencephalitis due to Coxiella
burnetii. J Infect. 1985;11:59-61.
FULL TEXT
|
ISI
| PUBMED
15. Schuil J, Richardus JH, Baarsma GS, Schaap GJ. Q fever as a possible cause of bilateral optic neuritis. Br J Ophthalmol. 1985;69:580-583.
FREE FULL TEXT
16. Brooks RG, Licitra CM, Peacock MG. Encephalitis caused by Coxiella burnetii. Ann Neurol. 1986;20:91-93.
FULL TEXT
|
ISI
| PUBMED
17. Gomez-Aranda F, Pachon Diaz J, Romero Acebal M, Lopez Cortes L, Navarro Rodriguez A, Maestre Moreno J. Computed tomographic brain scan findings in Q fever encephalitis. Neuroradiology. 1984;26:329-332.
ISI
| PUBMED
18. Haegy JM, Laplatte G. La fièvre Q, une pathologie méconnue: a propos de 2 observations
de formes graves de fièvre Q. J Med Strasbourg. 1983;14:21-24.
19. Schwartz RB. Manic psychosis in connection with Q-fever. Br J Psychiatry. 1974;124:140-143.
ISI
| PUBMED
20. Decourt J, De Gennes JL, Drosdowsky M. Fièvre Q compliquée d'encéphalite à forme
cérébelleuse. Bull Mem Soc Med Hopital Paris. 1961;77:312-315.
21. Gallagher WH. Q fever. JAMA. 1961;177:187-189.
22. Powell O. "Q" fever: clinical features in 72 cases. Aust Ann Med. 1960;9:214-223.
23. Alajouanine T, Lhermitte F, Clay R, Corbin J. Polyradiculonévrite avec dissociation albumino-cytologique au
décours d'une fièvre Q. Bull Mem Soc Med Hopital Paris. 1960;9-10:329-331.
24. Bernard E, Carles M, Laffont C, Durant J, Dellamonica P. Guillain-Barré syndrome associated with acute Q fever. Eur J Clin Microbiol Infect Dis. 1994;13:658-659.
FULL TEXT
|
ISI
| PUBMED
25. Reilly S, Northwood JL, Caul EO. Q fever in Plymouth, 1972-88: a review with particular reference to
neurological manifestations. Epidemiol Infect. 1990;105:391-408.
PUBMED
26. Clark WH, Lenette EH, Railback OC, Romer MS. Q fever in California: clinical features in one hundred eighty cases. Arch Intern Med. 1951;88:155-161.
FULL TEXT
27. Leng-Levy MMJ, David Causse J, Serre A, Biessy P. Deux cas de germe meningée de fièvre Q observés
dans le Sud Ouest. J Med Bordeaux. 1958;130:591-596.
28. Spelman DW. Q fever: a study of 111 consecutive cases. Med J Aust. 1982;1:547-553.
ISI
| PUBMED
29. Pennington JH, Poole PM, Smith HJR. The occurrence of Coxiella burnetii in northwestern
England and North Wales. J Hyg (Lond). 1969;67:125-133.
30. Marrie TJ, Raoult D. Rickettsial infections of the central nervous system. Semin Neurol. 1992;12:213-224.
ISI
| PUBMED
31. Raoult D, Tissot-Dupont H, Foucault C, et al. Q fever 1985-1998: clinical and epidemiologic features of 1,383 infections. Medicine (Baltimore). 2000;79:109-123.
FULL TEXT
| PUBMED
32. Drancourt M, Raoult D, Xeridat B, Milandre L, Nesri M, Dano P. Q fever meningoencephalitis in five patients. Eur J Epidemiol. 1991;7:134-138.
ISI
| PUBMED
33. Tissot-Dupont H, Thirion X, Raoult D. Q fever serology: cutoff determination for microimmunofluorescence. Clin Diag Lab Immunol. 1994;1:189-196.
FREE FULL TEXT
34. Raoult D, Vestris G, Enea M. Isolation of 16 strains of Coxiella burnetii
from patients by using a sensitive centrifugation cell culture system and
establishment of strains in HEL cells. J Clin Microbiol. 1990;28:2482-2484.
FREE FULL TEXT
35. Raoult D, Laurent JC, Mutillod M. Monoclonal antibodies to Coxiella burnetii
for antigenic detection in cell cultures and in paraffin embedded tissues. Am J Clin Pathol. 1994;101:318-320.
ISI
| PUBMED
36. Stein A, Raoult D. Detection of Coxiella burnetii by DNA amplification
using polymerase chain reaction. J Clin Microbiol. 1992;30:2462-2466.
FREE FULL TEXT
37. Derrick EH. "Q" fever, a new fever entity: clinical features, diagnosis and laboratory
investigation. Rev Infect Dis. 1983;5:790-800.
ISI
| PUBMED
38. Robbins FC, Ragan CA. Q fever in the Mediterranean area: report of its occurence in allied
troops, I: clinical features of the disease. 15 Med Gen Lab. 1946:6-21.
39. Ladurner G, Stunzner D, Lechner H, Sixl W. Q-fever meningoencephalitis: case report. Nervenarzt. 1976;46:274-275.
ISI
| PUBMED
40. Raoult D. Treatment of Q fever. Antimicrob Agents Chemother. 1993;37:1733-1736.
FREE FULL TEXT
41. Perez-del-Molino A, Aguado JM, Riancho JA, Sampredo I, Matorras P, Gonzales-Macias J. Erythromycin and the treatment of Coxiella burnetii pneumonia. J Antimicrob Chemother. 1991;28:455-459.
FREE FULL TEXT
42. Torres H, Raoult D. In vitro activities of ceftriaxone and fusidic acid against 13 isolates
of Coxiella burnetii determined using the shell vial
assay. Antimicrob Agents Chemother. 1993;37:491-494.
|
