Vol. 17, No. 36

1. Provided by Leslie Edwards Reger, Division of Outbreak Investigation, Maryland Department of Health and Mental Hygiene.

From September 25, 1998 to October 2, 1998 six outbreaks were reported to the Maryland Department of Health and Mental Hygiene. From longterm care facilities: Two outbreaks of influenza-like illness: One outbreak of gastroenteritis of unknown etiology. Other Foodborne outbreaks: Two outbreaks of food service facility-associated gastroenteritis of unknown etiology. One outbreak of viral conjunctivitis in a daycare center

2. The Johns Hopkins Hospital. Information provided by Dr. Angelique Wolf, Department of Pathology.

Case Report: A 27 year old HIV positive man with a recent CD4 count of 4 and viral load 150,000 was brought by his family directly to the ER after being released from prison for evaluation of altered mental status, mutism, generalized weakness, and incontinence. Prior to the patient's four week incarceration, he was noted to have increasing difficulty with speech and a progressive decrease in functioning at home noted by his mother. During his incarceration, the patient was treated for otitis media. It is unclear whether the patient had been taking his regimen of antivirals and prophylactic antibiotics over the last few months. Upon evaluation in the ER, the patient was afebrile. He was alert, able to follow simple commands and answer some questions nonverbally. While the neurologic exam was nonfocal, a profound decrease in muscle strength was appreciated diffusely. Laboratory values included a white blood cell count of 5.8 with a differential of 18% bands, 54% polymorphonuclear cells, 15% lymphocytes, and 3% monocytes. A lumbar puncture revealed a glucose of 50, a protein of 37, no WBCs and mononuclear cells only on a cytospin. No organisms were seen on a Gram stain of the cerebrospinal fluid (CSF) and there was no evidence of Cryptococcal antigen. Serology was negative for cryptococcal antigen, as well as Toxoplasma and CMV antibodies. A head CT showed minimally enlarged ventricles, diffuse cerebral atrophy and diffuse white matter changes in the frontal lobes. MRI confirmed an abnormally increased T2 signal without evidence of enhancement throughout the white matter of the frontal lobes and extending into the corpus callosum and the left temporal lobe. Blood and CSF cultures were pending. Given the above clinical history and radiologic findings, a PCR based test for the detection of JC virus in the CSF was ordered and the result was positive.

Organism: JC virus (JCV) is classified in the genus Polyomavirus of the family Papovaviridae because of its icosahedral capsid symmetry, particle size (40 nm), and physical and genetic makeup of its DNA genome. JCV is a double-stranded, circular, supercoiled, non-enveloped DNA virus. JCV has the ability to hemagglutinate human type O erythrocytes. Capsid proteins VP1, VP2, and VP3 are assembled in the nucleus to form virion particles. VP1 is the external protein used for attachment to a presumed glycoprotein cell receptor and is responsible for the virion's ability to hemagglutinate.

Clinical Manifestations: Diseases associated with the polyomaviruses, JCV and BK virus (BKV), occur mostly in immunocompromised adults, suggesting a reactivation of a latent infection. Based on seroepidemiologic studies, the population in general appears to be susceptible to human polyomavirus infections. Serum conversion occurs between the ages of 5 and 8 in almost 80% of the population worldwide. JCV is the etiologic agent linked with progressive multifocal leukoencephalopathy (PML), a severe subacute demyelinating disease of the central nervous system. The virus lytically infects the oligodendrocyte, the myelin-producing cell in the white matter of the brain. PML is a rare complication of immunosuppressive treatment, but the general epidemiology of PML has paralleled that of AIDS. The classic clinical triad of the disorder (dementia, hemiparesis, hemianopia) develops insidiously and death usually follows within 9 months.

Laboratory Diagnosis: Brain biopsy remains the definitive diagnostic procedure. Of the non-invasive procedures, viral culture of the CSF for JCV is often unsuccessful and serology is generally not helpful in the diagnosis of acute infections, since most people have been previously exposed. Molecular techniques based on DNA amplification are becoming increasingly important in the diagnosis of PML and several methods have been developed in order to demonstrate JCV sequences in CSF.

A diagnostic PCR test for JCV in the CSF is now available in the Molecular Microbiology Laboratory of the JHH Microbiology Division. JCV DNA is extracted from the CSF, then amplified using primers specific to the VP1 structural gene of JCV as described by McGuire(4). The 183 bp PCR product is detected by agarose gel electrophoresis and Southern blot analysis. The analytical sensitivity is 10 copies of plasmid DNA containing the JCV genome. The test requires 0.5 cc of CSF and is performed on Thursdays at 9:00 a.m. with results available at 4:00 p.m. the following day. The detection of JCV in CSF using PCR provides a non-invasive, rapid, sensitive and specific alternative laboratory test to aid in the diagnosis of PML.

Treatment: The nucleoside analogue cytosine aribinoside (ARA-C) has been used in treatment for PML with equivocal results. ARA-C has been reported to be effective in combination with alpha-interferon. There have also been reports documenting clinical improvement in AIDS patients being treated with zidovudine alone.