Progressive multifocal leukoencephalopathy in Zambia is caused by JC virus with prototype regulatory region

Eugene Mubanga, Atiyah Patel, Omar K. Siddiqi, Barbara A. Hanson, Xin Dang, Shabir Lakhi, Gina Mulundu, Noemi Bender, Igor J. Koralnik*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

There are only few documented cases of progressive multifocal leukoencephalopathy (PML) in Africa. Whether this is caused by a lack of JC virus (JCV) spread or alteration in the JCV genome is unknown. We characterized the clinical presentation, laboratory findings, and JCV regulatory region (RR) pattern of the first documented PML cases in Zambia as well as JCV seroprevalence among HIV+ and HIV Zambians. We identified PML patients with positive JCV DNA PCR in their cerebrospinal fluid (CSF) among subjects enrolled in an ongoing tuberculous meningitis study from 2014 to 2016 in Lusaka. JCV regulatory region was further characterized by duplex PCR in patients’ urine and CSF. Of 440 HIV+ patients, 14 (3%) had detectable JCV DNA in their CSF (age 18–50; CD4+ T cells counts 15–155 × 106/μl) vs 0/60 HIV patients. The main clinical manifestations included altered mental status and impaired consciousness consistent with advanced PML. While prototype JCV was identified by duplex PCR assay in the CSF samples of all 14 PML patients, only archetype JCV was detected in their urine. All PML Zambian patients tested were seropositive for JCV compared to 46% in a control group of HIV+ and HIV Zambian patients without PML. PML occurs among HIV-infected individuals in Zambia and is caused by CNS infection with prototype JCV, while archetype JCV strains are present in their urine. JCV seroprevalence is comparable in Zambia and the USA, and PML should be included in the differential diagnosis of immunosuppressed individuals presenting with neurological dysfunction in Zambia.

Original languageEnglish (US)
Pages (from-to)475-479
Number of pages5
JournalJournal of neurovirology
Volume25
Issue number4
DOIs
StatePublished - Aug 1 2019

Keywords

  • JCV
  • Progressive multifocal leukoencephalopathy
  • Regulatory region
  • Zambia

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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  • Cite this

    Mubanga, E., Patel, A., Siddiqi, O. K., Hanson, B. A., Dang, X., Lakhi, S., Mulundu, G., Bender, N., & Koralnik, I. J. (2019). Progressive multifocal leukoencephalopathy in Zambia is caused by JC virus with prototype regulatory region. Journal of neurovirology, 25(4), 475-479. https://doi.org/10.1007/s13365-019-00746-x