Comorbid conditions as risk factors for West Nile neuroinvasive disease in Ontario, Canada: a population-based cohort study

Abstract

West Nile neuroinvasive disease (WNND) is a severe neurological illness that can result from West Nile virus (WNV) infection, with long-term disability and death being common outcomes. Although WNV arrived in North America over two decades ago, risk factors for WNND are still being explored. The objective of this study was to identify WNND comorbid risk factors in the Ontario population using a retrospective, population-based cohort design. Incident WNV infections from laboratory records between 1 January 2002 – 31 December 2012 were individually-linked to health administrative databases to ascertain WNND outcomes and comorbid risk factors. WNND incidence was compared among individuals with and without comorbidities using risk ratios (RR) calculated with log binomial regression. Three hundred and forty-five individuals developed WNND (18.3%) out of 1884 WNV infections. West Nile encephalitis was driving most associations with comorbidities. Immunocompromised (aRR 2.61 [95% CI 1.23–4.53]) and male sex (aRR 1.32 [95% CI 1.00–1.76]) were risk factors for encephalitis, in addition to age, for which each 1-year increase was associated with a 2% (aRR 1.02 [95% CI 1.02–1.03]) relative increase in risk. Our results suggest that individuals living with comorbidities are at higher risk for WNND, in particular encephalitis, following WNV infection.

Atypical presentation of West Nile encephalitis

“…Although difficult to interpret, motor disturbances, especially asthenia of the upper limbs, are considered typical of the forms of WNV encephalitis (24). Furthermore, advanced age is considered to be a major risk factor for the development of WNVinduced neuroinvasive disease, in particular encephalitis (25).…”

Inflammatory Response Associated with West Nile Neuroinvasive Disease: A Systematic Review

“…Patients aged over 65 years have a risk 16 times higher than younger individuals of developing severe disease, and those over 70 years of age with WNND have a risk of death 30–45 times higher than younger patients [ 10 , 11 ]. Other risk factors for neuroinvasive disease include the male sex (odds ratio [OR] = 1.3–1.6 for neuroinvasive disease) and various immunocompromising conditions (e.g., diabetes) [ 9 , 12 , 13 ]. As for other infections, immunologic and genetic determinants of severe WNV disease start to be considered [ 14 , 15 ].…”

Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients

“…The seroprevalence of IgG or IgM against this virus is similar in all age groups (Mostashari et al, 2001;Tsai et al, 1998), but the risk of severe disease, particularly neuroinvasive disease, is about 16 times higher in those over 65 yr than in younger individuals (Carson et al, 2012), and the risk of death is about 30-45 times higher in those over 70 yr of age than in younger individuals (Kopel et al, 2011;Lindsey et al, 2012). Being male also increases the risk of neuroinvasive disease, albeit to a lesser extent (odds ratio [OR] = 1.3-1.6; Sutinen et al, 2022). Some comorbid conditions and immunosuppression also lead to a modest increase in the risk of neuroinvasive disease and death Murray et al, 2006;Murray et al, 2009;Sutinen et al, 2022).…”

“…Being male also increases the risk of neuroinvasive disease, albeit to a lesser extent (odds ratio [OR] = 1.3-1.6; Sutinen et al, 2022). Some comorbid conditions and immunosuppression also lead to a modest increase in the risk of neuroinvasive disease and death Murray et al, 2006;Murray et al, 2009;Sutinen et al, 2022).…”