Ten-Year Study of the Stringently Defined Otitis-prone Child in Rochester, NY

Abstract

This review summarizes a prospective, longitudinal 10-year study in Rochester, NY, with virtually every clinically diagnosed acute otitis media (AOM) confirmed by bacterial culture of middle ear fluid. Children experiencing 3 episodes within 6 months or 4 episodes in 12 months were considered stringently defined otitis prone (sOP). We found stringent diagnosis compared with clinical diagnosis reduced the frequency of children meeting the OP definition from 27% to 6% resulting in 14.8% and 2.4% receiving tympanostomy tubes, respectively. Significantly more often respiratory syncytial virus infection led to AOM in sOP than non-otitis-prone children that correlated with diminished total respiratory syncytial virus-specific serum IgG. sOP children produced low levels of antibody to Streptococcus pneumoniae and Haemophilus influenzae candidate vaccine protein antigens and to routine pediatric vaccines. sOP children generated significantly fewer memory B cells, functional and memory T cells to otopathogens following nasopharyngeal colonization and AOM than non-otitis-prone children and they had defects in antigen-presenting cells.

Figure 1. AOM-Free Rates

Kaplan–Meier estimates of proportion children with AOM as they age in the Intervention, Legacy and Community groups.

Figure 2. PET-Free Rates

Kaplan–Meier estimates of proportion children receiving tympanostomy tubes as they age in the Intervention, Legacy and Community groups.

Figure 3. B-cell, T-cell and APC Responses

Recognition of infecting agent by antigen presenting cells (APC) and subsequent interaction with T-cells. Activation of B-cells result in antibody production and long-lived memory B-cells. Activation of CD4⁺ T-cells via MHCII pathway produces Th1, Th2 or Th17 depending on the cytokine stimulation. Recognition of infecting agent via the MHCI pathway activates cytotoxic CD8⁺ T-cells that directly attack the infecting cell.

Figure 4

Antibody levels to Spn antigens in non-otitis prone (NOP) and otitis prone (sOP) children, age 6–24 months. Significant difference for all five antigens except for LytB (p<0.07), comparing relative rise in IgG serum antibody between 6 to 24 months was found in NOP children while the difference was not significant in sOP children. Therefore must confirm potential effectiveness of candidate vaccine proteins in this immunologically different and vulnerable population.

Figure 5

During nasopharyngeal colonization with Spn or Spn-caused AOM, infection prone (sOP) children develop a lower percentage of memory B-cells to Spn antigens PhtD, LytB, PcpA, PhtE and Ply than NOP children. *(p<0.05)