Clinical assessment and improved diagnosis of bocavirus-induced wheezing in children, Finland

Abstract

Human bocavirus (HBoV) is a widespread respiratory virus. To improve diagnostic methods, we conducted immunoglobulin (Ig) G and IgM enzyme immunoassays with recombinant virus-like particles of HBoV as antigen. Acute-phase and follow-up serum samples from 258 wheezing children and single serum samples from 115 healthy adults in Finland were examined. Our assays had a sensitivity of 97% and a specificity of 99.5%. Of adults, 96% had immunity; none had an acute infection. Of 48 children with serologically diagnosed acute HBoV infections, 45 were viremic and 35 had virus in nasopharyngeal aspirates (NPAs). Of 39 HBoV NPA PCR-positive children co-infected with another virus, 64% had a serologically verified HBoV infection. HBoV caused illness of longer duration than rhinovirus and of equal severity to that of respiratory syncytial virus. Among children with bronchiolitis, >25% had acute HBoV infections. Accurate HBoV diagnosis requires serologic analysis or PCR of serum; PCR of NPAs alone is insufficient.

Figure 1

Recombinant human bocavirus virus protein 2 virus-like particles. Scale bar = 100 nm.

Figure 2

Scatter plots of individual absorbance values at 492 nm (A₄₉₂) of immunoglobulin (Ig) G (×) and IgM (red dots) against human bocavirus (HBoV) in enzyme immunoassays (EIAs) for acute-phase (I), convalescence-phase (II), and 5-year follow-up (III) serum samples from wheezing children and single serum samples from young healthy adults, Finland. The 45 children with confirmed acute HBoV infections (by viremia and serodiagnosis) were divided into 3 groups according to the degree of acuteness (very acute, acute, and subacute) on the basis of findings in I and II serum samples. Very acute, I sample seronegative but II sample IgM positive (n = 12); acute, I sample IgM positive but IgG showed seroconversion (n = 20); subacute, IgG positive with a diagnostic increase or constant level in I and II samples, IgM positive (n = 13). Also shown are results for children without viremia or serodiagnosis (nonacute [for only the first 45 children with seropositive samples]), and young healthy adults (n = 115). EIA cutoffs are indicated by a blue line (IgG; 0.188) or a red line (IgM; 0.167). Dots below the cutoff lines indicate samples with absorbance values less than the negative cutoff values (i.e., IgM­– and IgG– results).