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 RSV infection led to AOM in sOP than non-otitis prone (NOP) children that correlated with diminished total RSV-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 NP colonization and AOM than NOP children and they had defects in antigen presenting cells.

Nasopharyngeal polymicrobial colonization during health, viral upper respiratory infection and upper respiratory bacterial infection

“…Whenever the children were diagnosed as having AOM, tympanocentesis was performed and MEF samples were collected to confirm the clinical diagnosis. When a child experienced 3 episodes of AOM infections within a 6 month time span or 4 episodes of AOM infections in a 12 month time span they were designated as AOM infection-prone and because the diagnosis was confirmed by tympanocentesis-derived middle ear fluid culture we have termed these children stringently-defined otitis prone in our prior publication (20). Three bacterial pathogens ( Spn, NTHi and Mcat ) were identified by culture.…”

Pneumococcal whole-cell and protein-based vaccines: changing the paradigm

“…In fact, our published studies show that about 90% of otitis prone children have inadequate innate responses and diminished quantity and function of antibody generated to pneumococcal proteins, diminished memory B- and T-cell generation, and specific deficits in activation of B-cells and helper T-cells. [76] Many of these children also show an increased propensity to viral URI and fail to generate protective anti-viral antibody following infection[77] indicating broad immunologic defects. About 25% of otitis-prone children fail to produce immune responses when antigen is presented by injection of routine pediatric vaccines.…”

“…Over the past 10 years, we have studied a large population of children during their first 3 years of life who experience repeated pneumococcal infections in the middle ear, sinuses and lungs. [76,87] Our research has identified deficiencies in T and B cell immunity in response to pneumococcal infections. [88,89] The deficiencies resemble a neonatal immunity response, giving our group reason to propose a new type of immunodeficiency termed “Prolonged Neonatal-Like Immune Profile” (PNIP).…”

“…[88,89] The deficiencies resemble a neonatal immunity response, giving our group reason to propose a new type of immunodeficiency termed “Prolonged Neonatal-Like Immune Profile” (PNIP). [76] We have shown that young children with PNIP do not respond with protective antibody titers to PCVs. [90] Although this population of young children is small (<10% of all young children), they experience the highest burden of pneumococcal disease.…”

“…Our work suggests that specific pneumococcal proteins, such as PcpA, are more immunogenic than others in stimulating an immune response in PNIP young children when PCVs do not. [76,81,90] Currently, we are exploring novel adjuvants that facilitate immune responses in children especially prone to pneumococcal infections. Our early findings involving novel adjuvants have been encouraging.…”