Characteristics and long-term prognosis of Danish residents with a positive intrathecal antibody index test for herpes simplex virus or varicella-zoster virus compared with individuals with a positive cerebrospinal fluid PCR: a nationwide cohort study

Isabella L. Platz*, Malte M. Tetens, Ram Dessau, Svend Ellermann-Eriksen, Nanna S. Andersen, Veronika Vorobieva Solholm Jensen, Christian Østergaard, Jacob Bodilsen, Kirstine Kobberøe Søgaard, Jette Bangsborg, Alex Christian Yde Nielsen, Jens Kjølseth Møller, Anne Mette Lebech, Lars Haukali Omland, Niels Obel

*Corresponding author for this work

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Abstract

Objectives: We compared characteristics and outcomes of individuals who in the cerebrospinal fluid (CSF) were positive for herpes simplex virus (HSV) or varicella-zoster virus (VZV)-intrathecal antibody index test ([AI]-positive) vs. individuals who were PCR-positive for HSV type 1 (HSV1), type 2 (HSV2), and for VZV. Methods: Nationwide cohort study of all Danish residents with positive CSF-AI or -PCR for HSV or VZV (1995–2021). We calculated short- and long-term risks as age-, sex-, and comorbidity-adjusted odds ratios (aOR), adjusted hazard ratios (aHR), and absolute risk differences with 95% CIs. Results: Compared with individuals with positive PCR for HSV1 (n = 321), HSV2 (n = 497), and VZV (n = 1054), individuals with a positive AI for HSV (n = 177) and VZV (n = 219) had CSF pleocytosis less frequently (leucocyte count >10/μL: HSV-AI: 39%, VZV-AI: 52%, HSV1-PCR: 81%, HSV2-PCR: 92%, VZV-PCR: 83%), and were less frequently diagnosed with central nervous system infection ([aOR {95%CI}]: HSV-AI vs. HSV1-PCR: [0.1 {0.1, 0.2}], HSV-AI vs. HSV2-PCR: [0.1 {0.0, 0.1}], VZV-AI vs. VZV-PCR: [0.2 {0.2, 0.3}]). Individuals with a positive HSV-AI or VZV-AI had increased risk of demyelinating disease ([aOR {95%CI}; aHR {95%CI}]: HSV-AI vs. HSV1-PCR: [4.6 {0.9, 24.5}; aHR not applicable], HSV-AI vs. HSV2-PCR: [10.4 {2.3, 45.9}; 12.4 {2.3, 66.0}], VZV-AI vs. VZV-PCR: [aOR not applicable; 10.3 {1.8, 58.8}]). Disability pension was less frequent among HSV-AI than HSV1-PCR cohort members (5-year risk difference: −23.6%, 95%CI: −35.2, −11.8), and more frequent among VZV-AI than VZV-PCR cohort members (5-year risk difference: 16.8%, 95%CI: 5.0, 28.7). Discussion: AI-positive individuals differ from PCR-positive individuals in several aspects. AI appears unspecific for current central nervous system infections.

Original languageEnglish
JournalClinical Microbiology and Infection
Volume30
Issue number2
Pages (from-to)240-246
ISSN1198-743X
DOIs
Publication statusPublished - Feb 2024

Bibliographical note

Publisher Copyright:
© 2023 The Author(s)

Keywords

  • Central nervous system infections
  • Herpes simplex viruses
  • Intrathecal antibody index
  • PCR
  • Varicella-zoster virus
  • Denmark/epidemiology
  • Prognosis
  • Humans
  • Polymerase Chain Reaction
  • Herpesvirus 3, Human/genetics
  • Herpesvirus 1, Human/genetics
  • Cohort Studies

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