October 2012, 12:121,
Open Access This content is freely available online to anyone, anywhere at any time.
Date: 15 Oct 2012
Characteristics of progressive multifocal leukoencephalopathy clarified through internet-assisted laboratory surveillance in Japan
Progressive multifocal leukoencephalopathy (PML), a rare but fatal demyelinating disease caused by JC virus (JCV), occurs mainly in immunocompromised patients. As PML develops in individuals with various underlying disorders sporadically and infrequently, a nationwide survey of PML is difficult. This study was conducted to elucidate the characteristics of PML in Japan through an internet-assisted laboratory surveillance program.
A diagnostic support system for PML was established using a real-time PCR assay of JCV DNA in cerebrospinal fluid (CSF), and requests for testing were received from clinicians via specialized websites. Medical histories of patients were collected through standardized questionnaires, and a database of CSF JCV loads and clinical information was created and analyzed.
For 4 years from April 2007 to March 2011, CSF specimens from 419 patients were tested. Forty-eight individuals were found positive for JCV DNA in their CSF and were diagnosed with PML. PML primarily occurred not only in HIV-positive patients (33.3%) but also in patients with hematologic disorders after receiving stem cell transplantation, chemotherapy, and/or immunosuppressive treatment (39.6%). The frequencies of PML cases among the subjects in these two categories were 20.3% and 23.5%, respectively. Although no significant features were observed with respect to CSF JCV loads in PML patients with an HIV infection or hematologic disorder, males were predominant in both groups (100% and 89.5%, respectively). The proportion of PML cases with autoimmune disorders (6.3%) or solid-organ transplants (2.1%) was smaller than those with HIV infection or hematologic disorders, probably due to the limited availability of therapeutic monoclonal antibodies and transplantation from brain dead donors.
The results suggest that the internet-assisted laboratory surveillance program might be a useful strategy for collecting precise real-time information on PML on a national level. The current database provides important background information for the diagnosis and treatment of patients with risk factors for PML.
Garvey L, Winston A, Walsh J, Post F, Porter K, Gazzard B, Fisher M, Leen C, Pillay D, Hill T, Johnson M, Gilson R, Anderson J, Easterbrook P, Bansi L, Orkin C, Ainsworth J, Palfreeman A, Gompels M, Phillips AN, Sabin CA: Antiretroviral therapy CNS penetration and HIV-1-associated CNS disease. Neurology 2011, 76:693–700.PubMedCrossRef
Garvey L, Winston A, Walsh J, Post F, Porter K, Gazzard B, Fisher M, Leen C, Pillay D, Hill T, Johnson M, Gilson R, Anderson J, Easterbrook P, Bansi L, Orkin C, Ainsworth J, Phillips AN, Sabin CA: HIV-associated central nervous system diseases in the recent combination antiretroviral therapy era. Eur J Neurol 2011, 18:527–534.PubMedCrossRef
Engsig FN, Hansen AB, Omland LH, Kronborg G, Gerstoft J, Laursen AL, Pedersen C, Mogensen CB, Nielsen L, Obel N: Incidence, clinical presentation, and outcome of progressive multifocal leukoencephalopathy in HIV-infected patients during the highly active antiretroviral therapy era: a nationwide cohort study. J Infect Dis 2009, 199:77–83.PubMedCrossRef
Falco V, Olmo M, del Saz SV, Guelar A, Santos JR, Gutierrez M, Colomer D, Deig E, Mateo G, Montero M, Pedrol E, Podzamczer D, Domingo P, Llibre JM: Influence of HAART on the clinical course of HIV-1-infected patients with progressive multifocal leukoencephalopathy: results of an observational multicenter study. J Acquir Immune Defic Syndr 2008, 49:26–31.PubMedCrossRef
Kongsiriwattanakul S, Suankratay C: Central nervous system infections in HIV-infected patients hospitalized at King Chulalongkorn Memorial Hospital. J Med Assoc Thai 2011, 94:551–558.PubMed
Carson KR, Evens AM, Richey EA, Habermann TM, Focosi D, Seymour JF, Laubach J, Bawn SD, Gordon LI, Winter JN, Furman RR, Vose JM, Zelenetz AD, Mamtani R, Raisch DW, Dorshimer GW, Rosen ST, Muro K, Gottardi-Littell NR, Talley RL, Sartor O, Green D, Major EO, Bennett CL: Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the research on adverse drug events and reports project. Blood 2009, 113:4834–4840.PubMedCrossRef
Nakamichi K, Kurane I, Saijo M: Evaluation of a quantitative real-time PCR assay for the detection of JC polyomavirus DNA in cerebrospinal fluid without nucleic acid extraction. Jpn J Infect Dis 2011, 64:211–216.PubMed
Howley PM, Rentier-Delrue F, Heilman CA, Law MF, Chowdhury K, Israel MA, Takemoto KK: Cloned human polyomavirus JC DNA can transform human amnion cells. J Virol 1980, 36:878–882.PubMed
Benjamini Y, Hochberg Y: Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc 1995, 57:289–300.
UNAIDS: Global report: UNAIDS report on the global AIDS epidemic 2010. [Annex 1 - HIV and AIDs estimates and data, 2009 and 2001] [ http://www.unaids.org/documents/20101123_GlobalReport_Annexes1_em.pdf].
- Characteristics of progressive multifocal leukoencephalopathy clarified through internet-assisted laboratory surveillance in Japan
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
- Online Date
- October 2012
- Online ISSN
- BioMed Central
- Additional Links
- Cerebrospinal fluid
- JC virus
- Progressive multifocal leukoencephalopathy
- Author Affiliations
- 1. Department of Virology 1, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan
- 2. Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113-8519, Japan
- 3. Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Ishikawa, Kanazawa, 920-8640, Japan
- 4. Division of Neurology, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Bunkyo-ku, Tokyo, 113-8677, Japan
- 5. Department of Ecosocial System Engineering, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Kofu, Yamanashi, 400-8511, Japan