Incidence and Risk Factors for Varicella-Zoster Virus-Associated Central Nervous System Infections: A Nationwide Swedish Retrospective Case-Control Study

Abstract

The determinants of varicella-zoster virus (VZV)-associated central nervous system (CNS) infection have not been fully elucidated. This study aimed to investigate the incidence and risk factors, including immunosuppression, for different manifestations of VZV-associated CNS infection. Patient registers were used to include adults diagnosed with VZV-associated CNS infections between 2010 and 2019 in Sweden. Nationwide registers covering specialized care, and regional registers covering primary care, were used. Controls without a VZV diagnosis during the study period were matched by age and sex. Risk factors were calculated using multivariable logistic regression. A total of 1488 adult cases with VZV-associated CNS infection were identified, yielding an incidence of 1.92/100 000 person-years, which increased over the study period. Meningitis was the most frequent (45%), followed by encephalitis (38%), and Ramsay Hunt syndrome (17%). The highest incidence was observed in individuals over 70 years of age (4.15/100 000 person-years), in whom encephalitis was most common. Statistically significant risk factors for VZV-associated CNS infection were HIV, hematological cancer, treatment with specific immunosuppressants or glucocorticoids, chronic obstructive pulmonary disease, diabetes, solid cancer, stroke, and congestive heart failure. Encephalitis was associated with older age, more immunosuppressive conditions, and more comorbidities than other manifestations. In conclusion, VZV is a common cause of adult viral CNS infection, for which elderly individuals with immunosuppressive or comorbid conditions are at the highest risk. The strongest risk factors found were HIV, hematological cancer, and treatment with specific immunosuppressants or high-dose glucocorticoids.

Keywords: central nervous system (CNS); encephalitis; epidemiology; immunosuppression; varicella‐zoster virus (VZV).

Figure 1

Line plots showing incidences of VZV‐associated CNS infections per 100 000 person‐years in adults (≥ 18 years old). (A) Yearly incidences of VZV‐associated CNS infections 2010–2019. (B) Average incidences in different age strata: ages 18–29, 30–49, 50–69, and 70 and older. Four cases with RHS were identified exclusively by primary healthcare. Primary healthcare registers cover 39% of total population, therefore four cases represent 4/0.39 ≈ 10 cases for the calculation of national incidence. CNS, central nervous system; RHS, Ramsay Hunt syndrome; VZV, varicella‐zoster virus.