Analysis of JC virus DNA in NPSLE patients treated with different immunomodulatory agents.

OBJECTIVE: The objective of this report is to assess the presence and viral load of JC polyomavirus (JCV) DNA in cerebrospinal fluid (CSF) and plasma from neuropsychiatric systemic lupus erythematosus (NPSLE) patients in comparison to controls and to investigate if different types of immunosuppressive treatments were correlated to detection and viral load of JCV DNA in SLE. BACKGROUND: Reactivation of a latent JCV infection with subsequent development of the fatal disease progressive multifocal leukoencephalopathy (PML) has become an increasing problem in patients with autoimmune diseases treated with newer immunosuppressants. Accumulating data point out that SLE patients are at particular risk for PML compared to patients with other rheumatic diseases. METHODS: CSF samples (n = 69) and plasma samples (n = 51) from 71 SLE patients and 58 controls (53 CSF samples and 50 plasma samples) with other non-inflammatory neurological disease (OND) were analyzed for JCV DNA with a quantitative PCR method. RESULTS: All CSF and plasma samples from NPSLE patients and controls were negative for JCV DNA. CONCLUSION: JCV DNA was absent in CSF and plasma in NPSLE patients and controls and consequently we were not able to identify any correlation between the occurrence of JCV DNA and type of immunosuppressive medication.

[The first case of rabies in Sweden in 26 years. Inform travellers abroad about risks and treatment following suspected infection]. / Första rabiesfallet i Sverige på 26 år. Informera utlandsresenärer om risker och behandling efter misstänkt smitta.

In June 2000, a case of rabies was diagnosed in Stockholm. The patient, a 19-year-old woman, had been bitten by a dog in Thailand three months earlier. She was admitted with a 2-day history of pain and paresthesia at the exposure site (right arm), along with anxiety. Her neurological symptoms progressed, and during the following week she developed the typical signs of furious rabies. Despite intensive care, her condition deteriorated continuously, and she died 18 days after onset of symptoms. The diagnosis was not considered until five days after admission to the hospital. A saliva sample was obtained and the diagnosis confirmed by virus isolation in mouse neuroblastoma cells. Although Sweden is free of rabies, the diagnosis should be considered in patients with encephalitis after having visited a rabies endemic area. Tourists must be informed of the vital importance of post-exposure prophylaxis after suspected infection.

BK virus as the cause of meningoencephalitis, retinitis and nephritis in a patient with AIDS.

BACKGROUND: The two widely spread human polyomaviruses, BK virus (BKV) and JC virus (JCV) establish latency in the urinary tract, and can be reactivated in AIDS. JCV might cause progressive multifocal leucoencephalopathy, but although up to 60% of AIDS patients excrete BKV in the urine there have been few reports of BKV-related renal and/or neurological disease in AIDS. OBJECTIVE: To report on an AIDS patient with progressive renal and neurological symptoms involving the retina. DESIGN: Case report. SETTING: Venhälsan, Söder Hospital, Stockholm, Sweden. METHODS: The brain, eye tissue, cerebrospinal fluid, urine and peripheral blood mononuclear cells were analysed by nested PCR for polyoma-virus DNA. Macroscopical and microscopical examination were performed of the kidney and brain post mortem. Immunohistochemical stainings for the two BKV proteins, the VP1 and the agnoprotein, were performed on autopsy material and virus infected tissue culture cells. RESULTS: BKV could be demonstrated in the brain, cerebrospinal fluid, eye tissues, kidneys and peripheral blood mononuclear cells. CONCLUSION: During 6 years, approximately 400 cerebrospinal fluid samples from immunosuppressed individuals with neurological symptoms have been investigated by PCR for the presence of polyomaviruses. BKV DNA has, so far, only been found in the case reported here. Although reports of BKV infections in the nervous system are rare, there is now evidence for its occurrence in immunocompromised patients and the diagnosis should be considered in such patients with neurological symptoms and signs of renal disease. The diagnosis is simple to verify and is important to establish.

Identification of BK virus in a patient with acquired immune deficiency syndrome and bilateral atypical retinitis.

OBJECTIVE: To report the clinical and histopathologic characteristics of BK virus (BKV) retinitis. DESIGN: Case report. TESTING: The clinical features of bilateral retinitis in a 29-year-old homosexual white male with the acquired immune deficiency syndrome (AIDS) included focal, mottled fundus pigmentation, and haloes, as documented by fundus photography. After death of the patient, the left eye was studied by light microscopic and immunohistochemical examination. The nested polymerase chain reaction (PCR) was used to detect viral deoxyribonucleic acid (DNA) in the right eye and other nonocular tissues. The specificity was then confirmed by restriction enzyme analysis. RESULTS: The retina of the left eye showed focal necrosis and contained cells with intranuclear staining for the BKV VP1 protein. In the right eye, BKV DNA was detected in the retina and other tissues by nested PCR. Autopsy showed that BKV infection was also present in the brain, kidneys, and peripheral blood mononuclear cells. CONCLUSIONS: A number of pathogens may cause retinitis in patients with AIDS. The authors have shown that BKV should be included among those pathogens and that some clinical features may suggest the presence of BKV retinitis.

Detection of JC virus in cerebrospinal fluid (CSF) samples from patients with progressive multifocal leukoencephalopathy but not in CSF samples from patients with herpes simplex encephalitis, enteroviral meningitis, or multiple sclerosis.

JC virus (JCV) DNA was detected in cerebrospinal fluid (CSF) samples from patients with progressive multifocal leukoencephalopathy (PML) but not in CSF samples from patients with herpes simplex encephalitis, enteroviral meningitis, or multiple sclerosis. This suggests that inflammatory processes in the brain do not necessarily reactivate JCV, which further supports the proposal that the presence of JCV DNA in the CSF is diagnostic for PML.

Polymerase chain reaction for detection of JC virus DNA in cerebrospinal fluid: a quality control study. European Union Concerted Action on Viral Meningitis and Encephalitis.

The sensitivity and specificity of PCR of CSF for the diagnosis of progressive multifocal leuko encephalopathy is estimated at 75 and 98.5%, respectively. However, inter-laboratory and inter-technique variations have been shown to produce wide variations. A 10-fold dilution series of JC virus in cerebrospinal fluid was prepared and circulated for 'blind' evaluation in laboratories participating in a European Union Concerted Action on Virus Meningitis and Encephalitis. Six of seven laboratories returned results with sensitivity of between 10 and 1 JCV DNA copy equivalents per 10 microl of CSF, one laboratory detected 10(5) copies per 10 microl of CSF. These results demonstrate the feasibility of using virus diluted in CSF for comparison of PCR techniques, and that the range of sensitivity of JCV PCR in proficient laboratories is between 10 and 1 copy equivalents per 10 microl of CSF.

Analysis of PCR as a tool for detection of JC virus DNA in cerebrospinal fluid for diagnosis of progressive multifocal leukoencephalopathy.

Two polyomaviruses, JC virus (JCV) and BK virus (BKV), affect humans. JCV is the causative agent of progressive multifocal leukoencephalopathy (PML), and detection of JCV in the central nervous system (CNS) is a prerequisite for confirmation of the disease. BKV is generally not associated with neurological disease, but involvement of BKV in patients with CNS disorders has been reported. In the present study polyomavirus DNA was detected by a nested PCR at a sensitivity corresponding to the detection of 10 copies of JCV DNA in 10 microliters of cerebrospinal fluid (CSF). CSF samples from 212 patients with neurological symptoms and immunodeficiencies were investigated for the presence of polyomavirus DNA. Of 128 human immunodeficiency virus (HIV)-infected patients, 14 (11%) had JCV DNA in their CSF, and all 14 patients had clinical PML. BKV DNA was detected in one HIV-infected patient with neurological symptoms not compatible with PML. Among 84 HIV-negative patients, 6 (7%) had detectable JCV DNA in their CSF, confirming PML in patients with clinical conditions of T-cell lymphoma, chronic lymphatic leukemia, status postliver transplantation, congenital immunodeficiency, sarcoidosis, and immunodeficiency of unknown origin. The specificity of the PCR was confirmed by a clinical follow-up study which showed full agreement between the detection of JCV DNA in CSF and clinically manifest PML. The described PCR is a rapid, reproducible, and easily performed assay.

No association of JC virus with Alzheimer's disease or astrocytomas.

OBJECTIVES: To investigate if JC virus (JCV) can be involved in the pathogenesis of Alzheimer's disease (AD) and astrocytomas. STUDY DESIGN: A nested polymerase chain reaction (PCR) was used for the detection of JCV DNA in autopsy brain material (cerebral white matter) and cerebrospinal fluid (CSF) specimens from patients with AD and age-matched control patients without neurological diseases, together with biopsies from patients with astrocytomas (grades 3 and 4). Brain autopsy material from AIDS patients with progressive multifocal leukoencephalopathy (PML) was examined as positive control material. RESULTS: JCV DNA was detected by PCR in only one of the 17 brain autopsies from patients with AD, but in none of the 26 control patients without neurological diseases and in none of the 5 astrocytoma biopsies. JCV DNA was, however, detected in the brain material from two patients with PML. CONCLUSION: Our results show that JCV infection does not seem to be directly involved in the pathology of AD or in the development of astrocytomas. In addition, since no viral DNA was detected in CSF specimens from 43 patients without PML (17 with AD and 26 elderly controls), our results suggest that the finding of JCV DNA in CSF correlates to PML.

Nested PCR for detection of BK virus and JC virus DNA.

BACKGROUND: A nested polymerase chain reaction (PCR) was developed to detect BK virus (BKV) and JC virus (JCV) DNA sequences. The unique clevage site for BamHI restriction enzyme was located in the JCV amplimer and cleavage was used to differentiate between BKV and JCV. STUDY DESIGN: Twenty-three urine specimens from 17 bone marrow recipients with haemorrhagic cystitis and one liver transplant patient were tested for the presence of BKV and JCV DNA. Four brain tissue specimens (paraffin embedded brain tissues and a fresh frozen brain biopsy) and 5 cerebrospinal fluids from 3 AIDS patients and one liver transplant patient, all with progressive multifocal leukoencephalopathy (PML), were also examined by PCR. RESULTS: The sensitivity of the PCR was 10 genomes for each virus. BKV DNA was detected in 15 urine specimens from 12 bone marrow transplant patients. JCV DNA was detected in 4 cerebrospinal fluids and 4 brain tissues from patients with PML. CONCLUSION: Our results show that the nested PCR is a sensitive and rapid assay that can be used for diagnosis of BKV and JCV infections. The cerebrospinal fluid appears to be a suitable material for diagnosis of JC virus reactivation in the brain.

Nested PCR for detection of BK virus and JC virus DNA.

BACKGROUND: A nested polymerase chain reaction (PCR) was developed to detect BK virus (BKV) and JC virus (JCV) DNA sequences. The unique clevage site for BamHI restriction enzyme was located in teh JCV amplimer and cleavage was used to differentiate between BKV and JCV. STUDY DESIGN: Twenty-three urine specimens from 17 bone marrow recipients with haemorrhagic cystitis and one liver transplant patient were tested for the presence of BKV and JCV DNA. Four brain tissue specimens (paraffin embedded brain tissues and a fresh frozen brain biopsy) and 5 cerebrospinal fluids from 3 AIDS patients and one liver transplant patient, all with progressive multifocal leukoencephalopathy (PML), were also examined by PCR. RESULTS: The sensitivity of the PCR was 10 genomes for each virus. BKV DNA was detected in 15 urine specimens from 12 bone marrow transplant patients. JCV DNA was detected in 4 cerebrospinal fluids and 4 brain tissues from patients with PML. CONCLUSION: Our results show that the nested PCR is a sensitive and rapid assay that can be used for diagnosis of BKV and JCV infections.