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First Otitis Media and Pneumococcal Conjugate Vaccine Serotypes in Infants

Dagan, Ron, MD; Pelton, Stephen, MD; Bakaletz, Lauren, PhD; Cohen, Robert, MD

The Pediatric Infectious Disease Journal: December 2018 - Volume 37 - Issue 12 - p e351–e352
doi: 10.1097/INF.0000000000002030
Letters to the Editor
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Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Boston University School of Medicine, Boston, MA

Center for Microbial Pathogenesis, The Research Institute at Nationwide Children’s Hospital, Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH

Université Paris Est, IMRB-GRC GEMINI, Unité Court Séjour, Petits Nourrissons, Centre Hospitalier Intercommunal de Créteil, France

R.D. has received grants/research support from MSD and Pfizer; has been a scientific consultant for MeMed, MSD and Pfizer; and has served as a speaker for Pfizer. L.B. has received grants/research support from GSK. S.P. has received investigator-initiated research grants and/or honorarium for participation in advisory board meeting or symposiums from Pfizer, GSKbio, Merck Vaccines, Sanofi and Cempra. R.C. has received grants/research support from GSK, Nestlé, Novartis, Pfizer and Sanofi-Pasteur-MSD; has been a scientific consultant for GSK, Novartis and Pfizer; and has served as a speaker for GSK, Novartis, Pfizer and Sanofi-Pasteur-MSD.

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To the Editors,

We read with interest the article by Palmu et al.1 The trigger for their study was our recent review and hypothesis-generating article, suggesting that widespread vaccination with pneumococcal conjugate vaccines (PCVs) can prevent early otitis media (OM) episode caused by vaccine-serotype (VT) pneumococci, resulting in a reduction of acute OM incidence and subsequent complex OM (recurrent/nonresponsive OM and chronic OM with effusion).2 While much of acute OM is caused by Streptococcus pneumoniae, complex OM is caused predominantly by nontypeable Haemophilus influenzae, often in combination with other otopathogens. Hence, our hypothesis that reduction of early-onset pneumococcal OM may prevent later sequelae, including those caused by other bacteria such as nontypeable Haemophilus influenzae.

The prevalence of VT-pneumococcal OM is higher during early-onset OM (<6 months) than at any other age.2 Data by Palmu demonstrate that early-onset VT episodes were by far the most common of all pneumococcal OM episodes: 40/48 (83%) were caused by PCV7 + 6A serotypes and 42/48 (87.5%) were caused by PCV13 serotypes. Similarly, of all middle ear fluid (MEF) pneumococcal isolates, 50% were PCV7 + 6A serotypes and 52.5% were PCV13 serotypes.

In the pivotal study by the Finnish Group,3 a trend toward early efficacy of PCV7 against OM was seen. After 1 and 2 doses (cases occurring before 4 months of age), efficacy against PCV7 serotypes was 21% and 43%, respectively (however, these figures did not reach significance). After dose 3, it reached 57%.

Because children <6 months of age are only partially vaccinated at best, the most crucial early protection against VT-OM in the PCV era is achieved through reduction of VT carriage in the community (indirect [herd] protection), augmenting the direct benefits of PCV. Our conclusion was, therefore, that by reducing early-onset OM, PCVs can greatly impact on the sequelae rates of early-onset OM, namely complex OM, the main drivers of OM-related burden in the community.

It appears that Palmu et al interpreted our publication to imply that VT early-onset OM was exclusively associated with increased risk of complex OM compared with early-onset OM by other pathogens. However, what we stated is that the reduction of overall early-onset OM is associated with reduced complex OM. Actually, Palmu’s data support our conclusions; early-onset OM episodes (predominated by VT pneumococci) were the only factor associated with recurrence, as shown in their Table 1 and Figure. The impressive reduction of ventilation-tube placement afforded by PCV7 reported in the FinOM study3,4 further confirms our conclusions because ventilation-tube placement is indicated for chronic OM with effusion, rarely associated with VTs. The only plausible explanation is the effect of PCV7 on VT episodes (most prevalent in early-onset OM), preventing subsequent sequelae.

We agree with Palmu that the impact of PCV on OM cannot be fully explained by the prevention of early-onset VT episodes. As they state, the sustained VT antibody persistence and the development of indirect protection also contribute to protection against OM, including primary prevention of cases beyond 6 months of age. However, given that VT are most prevalent below 6 months of age, any additional PCV impact, not because of early OM reduction, is potentially of lesser overall impact on the development of sequelae.

Ron Dagan, MD

Faculty of Health Sciences

Ben-Gurion University of the Negev

Beer-Sheva, Israel

Stephen Pelton, MD

Boston University School of Medicine

Boston, MA

Lauren Bakaletz, PhD

Center for Microbial Pathogenesis

The Research Institute at Nationwide Children’s Hospital

Department of Pediatrics

The Ohio State University College of Medicine

Columbus, OH

Robert Cohen, MD

Université Paris Est, IMRB-GRC GEMINI

Unité Court Séjour, Petits Nourrissons

Centre Hospitalier Intercommunal de Créteil

France

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REFERENCES

1. Palmu A, Lahdenkari M. Early vaccine-type pneumococcal acute otitis media does not predispose to subsequent otitis when compared to early acute otitis media due to other bacterial etiology. Pediatr Infect Dis J. 2018;37:592–594.
2. Dagan R, Pelton S, Bakaletz L, et al. Prevention of early episodes of otitis media by pneumococcal vaccines might reduce progression to complex disease. Lancet Infect Dis. 2016;16:480–492.
3. Eskola J, Kilpi T, Palmu A, et al; Finnish Otitis Media Study Group. Efficacy of a pneumococcal conjugate vaccine against acute otitis media. N Engl J Med. 2001;344:403–409.
4. Sarasoja I, Jokinen J, Lahdenkari M, et al. Long-term effect of pneumococcal conjugate vaccines on tympanostomy tube placements. Pediatr Infect Dis J. 2013;32:517–520.
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