BoDV-1 Infection in Children and Adolescents: A Systematic Review and Meta-Analysis

Abstract

Borna disease virus 1 (BoDV-1) can cause a severe human syndrome characterized by meningo-myeloencephalitis. The actual epidemiology of BoDV-1 remains disputed, and our study summarized prevalence data among children and adolescents (<18-year-old). Through systematic research on three databases (PubMed, EMBASE, MedRxiv), all studies, including seroprevalence rates for BoDV-1 antigens and specific antibodies, were retrieved, and their results were summarized. We identified a total of six studies for a total of 2692 subjects aged less than 18 years (351 subjects sampled for BoDV-1 antibodies and 2557 for antigens). A pooled seroprevalence of 6.09% (95% Confidence Interval [95% CI] 2.14 to 16.17) was eventually calculated for BoDV-1 targeting antibodies and 0.76% (95% CI 0.26 to 2.19) for BoDV-1 antigens. Both estimates were affected by substantial heterogeneity. Seroprevalence rates for BoDV-1 in children and adolescents suggested that a substantial circulation of the pathogen does occur, and as infants and adolescents have relatively scarce opportunities for being exposed to hosts and animal reservoirs, the potential role of unknown vectors cannot be ruled out.

Keywords: BoDV-1; Bornavirus; ELISA; meningo-myeloencephalitis; seroprevalence.

Figure A1

Correlation between sample size and prevalence rates for Bornavirus Disease Virus (BoDV) 1 targeting antibodies (a) and BoDV-1 antigens (b). No correlation was found in both cases (Spearman’s rho = −1.000, p = 0.083 for BoDV-1 antibodies, and Spearman’s ρ = 0.0247, and p = 0.941 for BoDV-1 antigens).

Figure 1

Flow chart for included studies.

Figure 2

Summary of risk of bias assessment according to the National Toxicology Program (NTP)’s Office of Health Assessment and Translation (OHAT) handbook and respective Risk of Bias (ROB) tool [60,61].

Figure 3

Forest plot for retrieved seroprevalence studies on antibodies targeting BoDV-1 infection in Italian Children [49,50,51,67]. A pooled seroprevalence of 6.09% (95% Confidence Interval [95% CI] 2.14 to 16.17) was calculated. Data were affected by substantial heterogeneity (τ² = 0.985; I² = 84.1%, 95% CI 60.0–93.7%; Q = 18.88; p < 0.001).

Figure 4

Forest plot for retrieved seroprevalence studies on BoDV-1 associated antigens in Italian Children and adolescents [51,67,68,69]. A pooled seroprevalence of 0.76% (95% Confidence Interval [95% CI] 0.26 to 2.19) was calculated. Data were affected by substantial heterogeneity (τ² = 2.280; I² = 87.9%, 95% CI 80.8–92.4% p < 0.001).

Figure 5

Radial plot (a) and funnel plot (b) for estimates on the prevalence of BoDV-1 antibodies. Asymmetry in both plots suggested a significant small study effect and substantial publication bias, which was rejected by Egger’s test (t = −1.42, p = 0.292).

Figure 6

Radial plot (a) and funnel plot (b) for estimates on the prevalence of BoDV-1 antigens. Asymmetry in both plots suggested a significant small study effect and substantial publication bias. The latter was also confirmed by Egger’s test (t = −4.42, p = 0.001).