Abstract
Moraxella catarrhalis (Mcat) is a prominent mucosal pathogen causing acute otitis media (AOM). We studied Mcat nasopharyngeal (NP) colonization, AOM frequency and mucosal antibody responses to four vaccine candidate Mcat proteins: outer membrane protein (OMP) CD, oligopeptide permease (Opp) A, hemagglutinin (Hag), and Pilin A clade 2 (PilA2) from stringently defined otitis prone (sOP) children, who experience the greatest burden of disease, compared to non-otitis prone (NOP) children. sOP children had higher NP colonization of Mcat (30 vs. 22%, P = 0.0003) and Mcat-caused AOM rates (49 vs. 24%, P < 0.0001) than NOP children. Natural acquisition of mucosal antibodies to Mcat proteins OMP CD (IgG, P < 0.0001), OppA (IgG, P = 0.018), Hag (IgG and IgA, both P < 0.0001), and PilA2 (IgA, P < 0.0001) was lower in sOP than NOP children. Higher levels of mucosal IgG to Hag (P = 0.039) and PilA2 (P = 0.0076), and IgA to OMP CD (P = 0.010), OppA (P = 0.030), and PilA2 (P = 0.043) were associated with lower carriage of Mcat in NOP but not sOP children. Higher levels of mucosal IgG to OMP CD (P = 0.0070) and Hag (P = 0.0003), and IgA to Hag (P = 0.0067) at asymptomatic colonization than those at onset of AOM were associated with significantly lower rate of Mcat NP colonization progressing to AOM in NOP compared to sOP children (3 vs. 26%, P < 0.0001). In conclusion, sOP children had a diminished mucosal antibody response to Mcat proteins, which was associated with higher frequencies of asymptomatic NP colonization and NP colonization progressing to Mcat-caused AOM. Enhancing Mcat antigen-specific mucosal immune responses to levels higher than achieved by natural exposure will be necessary to prevent AOM in sOP children.
Highlights
Acute otitis media (AOM) is the most common infectious disease among children to cause parents to seek medical care for their child and receive antibiotics
Moraxella catarrhalis (Mcat) NP colonization rates were consistently higher in stringently defined otitis prone (sOP) vs. non-otitis prone (NOP) children: 33 vs. 27% at age 6 months, 31 vs. 25% at age 9 months, 34 vs. 26% at age 12 months, 26 vs. 23% at age 15 months, 26 vs. 23% at age 18 months, 36 vs. 22% at age 24 months (P = 0.010), 23 vs. 11% at age 30–36 months (P = 0.006), and overall 30 vs. 22% at age 6–36 months old (P = 0.0003, Figure 1A)
We found that sOP children displayed more frequent AOMs and asymptomatic NP colonizations caused by Mcat than NOP children, which is consistent with our prior observations on Mcat as well as otopathogens Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi) [24]
Summary
Acute otitis media (AOM) is the most common infectious disease among children to cause parents to seek medical care for their child and receive antibiotics. Moraxella catarrhalis (Mcat) has been ranked as the third most common cause of AOM after Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi) in children [1]. Our recent studies on the prevalence of otopathogens show that Mcat has overtaken Spn and NTHi to become the most frequent cause of episodic and recurrent AOM in children [2]. Mcat was recently identified as the most common otopathogen in Finish children [3]. AOM often recurs and poses a high burden on the quality of life of children, the health care system and the economy worldwide [4]
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