The investigators seek to conduct a prospective, longitudinal study to identify the dynamic changes in nasopharyngeal (NP) colonization patterns and acute otitis media (AOM) etiology involving antibiotic-resistant Streptococcus pneumoniae (Spn) and Haemophilus influenzae (Hflu).

The investigator's proposed study design involves 2 cohorts. Cohort 1: Collection of middle ear fluid(MEF), NP samples and blood at onset of AOM from otitis prone children and those who have AOM antibiotic treatment failure since these children more frequently harbor antibiotic resistant strains. Children will then be followed prospectively thereafter, collecting NP samples at pre-determined time points when the children are healthy (see cohort 2) and MEF, NP samples and blood if subsequent AOM infections occur. Cohort 2: Healthy children from whom we will prospectively collect NP samplings and blood at any of 7 pre-determined time points (age 6, 9, 12, 15, 18, 24, and/or 30-36 months old as they occur within the study time-frame) to assess commensal carriage of Spn and Hflu. MEF will be obtained from the participants at any AOM occurring, including the first and any subsequent AOM infection. Concurrently detailed demographic, vaccination, epidemiologic and risk factor data known to influence AOM epidemiology will be collected, providing scientific rigor.

Viral respiratory infections will be another focus during this project. The investigators will characterize dynamic changes in patterns of viral co-infections at onset of AOM including the common respiratory viruses RSV A, B, influenza A, B, parainfluenzae virus type 3, rhinovirus, enterovirus, human metapneumovirus, human bocavirus, adenovirus B, C and SARS-CoV-2. The studies will involve viral identification, evaluation of viral/bacterial (otopathogen) interactions and mucosal and systemic immune responses.

The investigators have identified multiple deficiencies in innate and adaptive immunity among young children who are AOM prone and introduced the term "prolonged neonatal-like immune profile (PNIP) because of striking similarities that resemble neonatal immunity. Another focus of this project will be to expand understanding of the central immune deficiencies of APM prone children using blood samples.

A a serum correlate of protection has been defined to predict the effectiveness of pneumococcal conjugate vaccines using blood samples linked to occurrence of NP colonization and AOM events in recent past work. Blood will be used to continue this work.

Inclusion Criteria:

• Male or female subject age 6 to 12 months + 30 days at the time of enrollment when healthy or up to 36 months old + 30 days with an ear infection.
• Subject has received full (3 dose) infant series of PCV.
• Parent/legal guardian must be able and willing to bring subject to all study visits

Exclusion Criteria:

• Any major illness/condition that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in the study.
• Participation in another investigational or interventional trial within the 28-day period before enrollment and during the conduct of the study. Participation in observational studies is permitted.