A study of the John Cunningham Virus (JCV) seroprevalence among Zambian adults presenting with “meningoencephalitis” to the University Teaching Hospital, Lusaka, Zambia

Abstract

Background: The John Cunningham virus (JCV) is an opportunistic virus which leads to the development of progressive multifocal leukoencephalopathy (PML), which is a lytic infection of oligodendrocytes of the central nervous system in immunosuppressed patients. Infection with the JCV occurs in childhood and the virus remains quiescent in the body, activating during immunosuppression. Exposure to the virus can be detected by testing for JC virus specific antibodies in an ELISA test. Our aim was to determine the JCV seroprevalence and factors associated with its positivity among Zambian adults presenting to the University Teaching Hospital (UTH) with suspected meningoencephalitis and to assess the JCV ELISA test as a possible tool for PML risk stratification.

Methodology: This was a cross sectional nested study in the TB meningitis in Zambia (TMZ) study which looked at improving ways of TB diagnosis in patients with meningoencephalitis. It included adults 18 years and older who presented with suspected meningoencephalitis and had undergone a lumbar puncture as part of their evaluation. 50 HIV positive and 50 HIV negative patients were selected from the parent study and underwent testing for JCV serology. PML cases were also recruited from the parent study based on clinical features, confirmed by JCV DNA PCR of CSF.

Results: Final analysis for JCV seroprevalence was done in 96 patients and noted to be 46% (95% CI, 35.62 – 56.31). The JCV seroprevalence in the HIV positive group was 40.82% and in the HIV negative group was 51.06 % but there was no statistical difference (p-value 0.31). None of the other factors studied had any impact on the JCV seroprevalence such as age, gender, clinical presentation, CD4 count and co-morbid TB meningitis (TBM) diagnosis. There was a bimodal distribution of age associated with JCV seropositivity; with one peak occurring in the 18 to 20 years age group and the second peak occurring in the 55 to 60 years age group. 14 (3.2%) confirmed PML cases, based on clinical features and JCV DNA CSF positive, were all JCV seropositive and HIV positive with advanced immunosuppression (CD4<200/mm³). Memory impairment was associated with a 6 fold increased likelihood of having PML in advanced HIV disease with JCV seropositive patients which further, increased to over 20 fold after adjusting for age , gender and TBM diagnosis. After adjusting for other variables TBM was associated with an 87% less likelihood of having PML (p-value 0.03). Female gender was associated with increased risk of having PML (p-value 0.02) and a younger age was protective for PML (p-value 0.03).

Conclusion: The prevalence of anti-JCV antibodies in patients with suspected CNS infection (meningoencephalitis) was 46%. Anti- JCV antibody prevalence did not differ significantly by age, gender, HIV status or CD4 count. Memory impairment in JCV seropositive, advanced HIV disease patients with meningoencephalitis was the most important variable associated with having PML.

Keywords: John Cunningham Virus (JCV), Progressive Multifocal Leukoencephalopathy (PML), seropositive