In light of pneumococcal vaccination programmes, is otitis media evolving to have a different natural history?
Acute otitis media (AOM) is a major public health problem in children worldwide, as it is the leading bacterial infection and first cause of antibiotics prescription in children in many countries [1]. Since the advent of the pneumococcal vaccine, the bacteriology of AOM has shifted globally from a primary pneumococcal disease to a nontypeable Haemophilus influenzae (NTHi) dominant condition.
Both streptococcus pneumoniae and NTHi are common respiratory pathogens that cause otitis media (OM). When AOM presented as a primary pneumococcal disease, it frequently manifested as systemic and invasive – as observed when a complicated infection would trigger symptoms of intracranial complications, such as meningitis [2]. Recent improvements in AOM prevention have shifted the bacteriology of AOM to an NTHi-dominant condition, which tends to associate with more local, non-invasive infections. This conceptual shift from ‘disease’ to ‘condition’ implies that there have been improvements in manageability and consequences of AOM. There have been efforts to mitigate and control Streptococcus pneumoniae by means of vaccination. S. pneumonia tends to be a more invasive bacterial pathogen than NTHi, particularly strains such as 1, 5, 7F, 14, 19A, 19F and 23F. These serotypes are increasingly covered as the Prevnar vaccine coverage continues to evolve (as seen from PCV7 to PCV13 to now PCV20).
In observation of PCV7 with respect to serotypic changes in S. pneumoniae, PCV7 proved 60% efficient against vaccine-serotype pneumococcal OM. Strains have virtually disappeared from middle ear fluid of vaccinated children with AOM. Overall prevention by PCV7 was 6–7%, which is a major improvement from an initial suggestion that it was inefficient and not recommended for AOM (Table1) [3].
While the public health improvements are significant, vaccine coverage is not an end-all solution, as AOM and its consequences still remain among the most common diagnoses in childhood. Accordingly with these improvements in AOM, symptoms of acute mastoiditis (AM) and meningitis with respect to AOM have declined in countries with high PCV13 coverage. For example, a study in Swedish children found that the incidence of AM in children under two years old decreased by 60% after the introduction of PCV in 2006 [4]. A different study of hospitalisation due to mastoiditis in Swedish children showed a significant decrease by 61–68% (from 2008–2016). Similar findings held true for bacterial meningitis, with a significant decrease in hospitalisations.
"Since the advent of the pneumococcal vaccine, the bacteriology of AOM has shifted globally from a primary pneumococcal disease to a nontypeable Haemophilus influenzae dominant condition"
NTHI as a respiratory commensal organism is strongly associated with mucogenesis, goblet cell metaplasia, mucous secretion and even biofilm formation in the middle ear. A function of goblet cells is to produce mucin glycoproteins, which come together in a protective mucus layer via mucogenesis. Mucogenesis activates DNA instructions to generate mucin proteins, which then triggers general mucin production. Mucin production is not inherently consequential, but the under and overproduction of it can trigger negative outcomes. NTHi has been well proven to drive middle ear mucosal thickening in mice models. In turn, it is has also widely been shown that NTHi activates inflammation and mucin expression in vitro and in animal models of OM.
A classic animal study from 1997 greatly highlighted this fact, showing how the middle ear mucosa of NTHi-infected rat ears had vigorous goblet cell activity, without the same finding after pneumococcal infection [5]. Other animal studies have also observed that NTHi promotes the middle ear’s squamous epithelium changes with increased goblet cell concentration and submucosal mucus glands. Moreover, the NTHi is associated with increases in mucins MUC5B and neutrophil extracellular traps – a host component of bacterial biofilm matrices. In the context of immature eustachian tube function, these thick DNA and mucin-laden effusions may overwhelm the capacity for clearance from the middle ear, resulting in conductive hearing loss and likelihood of tympanostomy tube needed. To this point, microbiome studies from fluid obtained at tympanostomy tube placement show distinct associations between Haemophilus speciation (not pneumococcal) and mucin presence in middle ear fluid, along with fluid viscosity and conductive hearing loss.
Taken together, these findings support a larger postulation that AOM has shifted to becoming a less invasive or severe pneumococcal disease, while being associated with an increasing incidence of chronic otitis media with mucoid effusions. Ostensibly, the rate of tympanostomy tube placement to treat mucoid COME may be increasing in the post-pneumococcal vaccine era. After the Covid-19 pandemic, epidemiological findings support that tympanostomy tube insertions without adenoidectomy surged nearly 10% [6]. The long-term prevalence of tympanostomy tube placement in regions of the globe with high vaccination rates remains to be determined.
In conclusion, given the success of pneumococcal vaccination efforts in reducing AOM invasiveness, future studies could focus on modulating mucoid responses to NTHi to reduce the surgical need in children for COME.
References
1. Jamal A, Alsabea A, Tarakmeh M, Safar A. Etiology, Diagnosis, Complications, and Management of Acute Otitis Media in Children. Cureus 2022;14(8):e28019.
2. Picard C et al, Puel A, Bustamante J. Primary immunodeficiencies associated with pneumococcal disease. Curr Opin Allergy Clin Immunol 2003;3(6):451–9.
3. Marra LP, Sartori AL, Martinez-Silveira MS, et al. Effectiveness of Pneumococcal Vaccines on Otitis Media in Children: A Systematic Review. Value Health 2022;25(6):1042–56.
4. Arebro Julia, Bennet R, Eriksson M, Granath A. The complexity of acute mastoiditis in Swedish children. Int J Pediatr Otorhinolaryngol 2025;193:112346.
5. Magnuson K, Hermansson A, Melhus A, Hellström S. The tympanic membrane and middle ear mucosa during non-typeable Haemophilus influenzae and Haemophilus influenzae type b acute otitis media: a study in the rat. Acta oto-laryngol 1997;117(3):396–405.
6. Dedhia K, Maltenfort M, Briddell J, et al. Temporal Trends in and Patient Characteristics Associated with Surgery for Otitis Media. Laryngoscope 2025;135(5):1821–9.
Declaration of competing interests: DP has participated in the Solo+ Tympanostomy tube VENTY trial clinical events committee; a trial sponsored by Karl Storz.
Diego Preciado will present on this topic at CEORL-HNS 2026 in Gothenburg, Sweden, in April. For further information visit https://www.ceorlhnscongress.org
