PCV7- and PCV10-Vaccinated Otitis-Prone Children in New Zealand Have Similar Pneumococcal and Haemophilus influenzae Densities in Their Nasopharynx and Middle Ear

Abstract

Otitis media (OM) is a major reason for antibiotic consumption and surgery in children. Nasopharyngeal carriage of otopathogens, Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi), is a prerequisite for development of OM, and increased nasopharyngeal otopathogen density correlates with disease onset. Vaccines can reduce or eliminate otopathogen carriage, as demonstrated for pneumococcal serotypes included in pneumococcal conjugate vaccines (PCV). The 10-valent PCV (PCV10) includes an NTHi carrier protein, and in 2011 superseded 7-valent PCV on the New Zealand Immunisation Program. Data are conflicting on whether PCV10 provides protection against NTHi carriage or disease. Assessing this in otitis-prone cohorts is important for OM prevention. We compared otopathogen density in the nasopharynx and middle ear of New Zealand PCV7-vaccinated and PCV10-vaccinated otitis-prone and non-otitis-prone children to determine PCV10 impact on NTHi and S. pneumoniae carriage. We applied qPCR to specimens collected from 217 PCV7-vaccinated children (147 otitis-prone and 70 non-otitis-prone) and 240 PCV10-vaccinated children (178 otitis-prone and 62 non-otitis-prone). After correcting for age and day-care attendance, no difference was observed between NTHi density in the nasopharynx of PCV7-vaccinated versus PCV10-vaccinated otitis-prone (p = 0.563) or non-otitis-prone (p = 0.513) children. In contrast, pneumococcal nasopharyngeal density was higher in PCV10-vaccinated otitis-prone children than PCV7-vaccinated otitis-prone children (p = 0.003). There was no difference in otopathogen density in middle ear effusion from PCV7-vaccinated versus PCV10-vaccinated otitis-prone children (NTHi p = 0.918; S. pneumoniae p = 0.415). When pneumococcal carriage was assessed by vaccine serotypes (VT) and non-vaccine serotypes (NVT), there was no difference in VT density (p = 0.546) or NVT density (p = 0.315) between all PCV7-vaccinated versus all PCV10-vaccinated children. In summary, PCV10 did not reduce NTHi density in the nasopharynx or middle ear, and was associated with increased pneumococcal nasopharyngeal density in otitis-prone children in New Zealand. Development of therapies that prevent or reduce otopathogen colonisation density in the nasopharynx are warranted to reduce the burden of OM.

Panel 8: Vaccines and immunology

“…Replacing PCV7 with PCV10 in New Zealand's national immunization program did not result in a decline in NTHi (or S. pneumoniae) prevalence [22]. Neither did it result in a decline in density [24] in the nasopharynx or middle ear of children undergoing tympanostomy tube insertion for recurrent AOM/OM with effusion (or in the nasopharynx of non-otitis-prone children). In contrast, a decreased prevalence of NTHi-infected ear discharge in PCV10-vaccinated Aboriginal children compared to PCV7-vaccinated Aboriginal children was observed when PCV10 was used in the Northern Territory of Australia from 2009 to 2011 [23].…”

Differences in Pneumococcal and Haemophilus influenzae Natural Antibody Development in Papua New Guinean Children in the First Year of Life

“…The swab media was enzymatically lysed and genomic DNA (gDNA) extracted as previously described ( 35 ). Quantitative (q)PCR was conducted using primers and probes specific for S. pneumoniae: lytA ( 36 ), and H. influenzae: fuc P and hpd 3 as described previously ( 37 , 38 ).…”

Pneumococcal Vaccines: Challenges and Prospects

“…Apart from IPD, non-invasive pneumococcal disease, such as acute otitis media (AOM) and community-acquired pneumonia (CAP) cause significant childhood and adult morbidity. A study by De Gier et al examined the effect of PCV10 and PCV13 on nasopharyngeal carriage of pneumococcus and non-typeable Haemophilus influenza (NTHi), which are a prerequisite for the development of AOM [4]. The authors found that PCV10 does not result in the reduction of NTHi carriage and is associated with higher pneumococcal carriage compared to PCV13.…”