The Infectious Aetiology of Otitis Media in Young Children Nikki Mills Paed ENT Consultant, Starship Emma Best Paed Inf Dis Consultant, Starship Tony Walls Paed Inf Dis Consultant, Canterbury Starship CHILDREN’S HEALTH

Disclosure Statement This is investigator led research with funding from: Glaxo-Smith Kline (GSK) & an Auckland District Health Board Research Grant The Researchers have not received any personal funding or salary from GSK

Otitis Media In New Zealand Gold Coast Starting point in 2010 Significant burden of disease in NZ Paucity of NZ specific data for Otitis Media New Zealand 2,220kms

OMIVI Study Otitis Media Infectious aetiology & Vaccination Impact - Prospective descriptive study < 3 y olds - Nasopharyngeal flora - Bacteria present in middle ear fluid - Impact of pneumococcal vaccination change: Phase 1 – 2011: Cohort PCV7 (2008) Phase 2 – 2014: Cohort PHiD-CV (Dec 2011) - Interest in the impact of PHiD-CV on H.inf NZ has a high incidence of ear disease, particularly in our Maori and Pacific Island population NZ’s only study on microbiology was done 17 years ago PCV 7 cohort with changing pneumococcal vaccination schedule Synflorix is a 10-valent pneumococcal vaccination using a protein carrier (Protein D) that has been shown to have an immunogenic effect against Haemophilus The 7 valent conjugated pneumococcal vaccination was introduced in 2008, with a change to Synflorix – the 10 valent vaccination at the end of last year With synflorix we are particularly interested in the potential benefit for H influenzae in the context of middle ear disease So we aimed to perform a prospective descriptive study of our population We were interested in collecting baseline data for potential comparison with co-hort of PCV10 immunised children We wanted to identify the bacteria present in the nasopharynx of children with and without ear disease and identify the bacteria present in the middle ear at the time of grommet insertion Our plan to repeat the study in 3 years with a cohort who have been vaccinated with Synflorix

Pneumococcal Serotyping OMIVI Study Phase 1: 2011: 462 participants Phase 2: 2014: 473 participants Phase 1 : 325 Phase 1 : 137 Grommet patients Comparison group RAOM & OME No sig history ear disease Questionnaire & Nasopharyngeal Swab Middle ear samples < 3 y olds Phase 2 : 319 Phase 2 : 154 Pneumococcal Serotyping PCR Culture

OMIVI Phase 1 & 2 Papers 2014 2016

Pneumococcal Serotyping OMIVI Study Phase 1: 462 participants Phase 2: 473 participants Phase 1 : 325 Phase 1 : 137 Grommet patients Comparison group RAOM & OME No sig history ear disease Questionnaire & Nasopharyngeal Swab Middle ear samples < 3 y olds Phase 2 : 319 Phase 2 : 319 Phase 2 : 154 PCR for Respiratory Viruses Nasopharyngeal Swab Middle ear samples Pneumococcal Serotyping PCR Culture

Otitis Media Infectious Aetiology Study < 3 y old: RAOM &/or OME Grommet insertion Fluid present one or both ears n = 217 Questionnaire & Nasopharyngeal Swab Middle ear samples PCV10 vaccinated cohort < 3 y old RAOM &/or OME Grommet insertion N = 319 Bilateral Dry Ears N = 102 Fluid present one or both ears N = 217 Questionnaire Nasopharyngeal Swab N = 217 Middle ear samples n = 376 Viral PCR Bacterial PCR Bacterial Culture Pneumococcal Serotyping

3 Study Centres Recruitment: 7 months: 1 May – 30 Nov 2014 (winter) 77% of all <3 year olds receiving grommets 2 in Auckland Auckland pop 1.4 million Christchurch pop 400,000 Recruitment over 6 months in the winter period Many of you may be aware of the devastating earthquake in Christchurch in February last year It is a real tribute to them that they were able to still participate in the study 1 in Christchurch

Questionnaire Otitis Media Risk Factors Demographics Vaccination data: National Immunisation Register Birth weight & gestation Breast feeding Reflux Smoking in house Day care attendance Overcrowding Atopic symptoms Ear Disease history: symptoms, freq, treatment General Medical history Antibiotic History ......

Demographics N = 217 Questionnaire Data Average Age 20 months Age range 7 – 35.7 months Gender Male 68%: Female 32% Ethnicity Maori 24% European 52% Pacific 15% Other 9% Day care attendance: 76% Family History of OME: 51% Antibiotic in last 4 weeks: 52% Questionnaire Data

Exposures and Viral detection univariate analyses (odds ratios for binary covariates and t-tests for continuous) as well as multivariate logistic regression No variables correlated with the presence of virus in middle ear fluid or the nasopharynx

Indication for Surgery Both AOM & OME 28% RAOM 42% OME 30% N = 217

Nasopharyngeal Samples: Bacterial Culture N = 217 % In Grommet group – H inf most common organism Moraxella most common NP organism in Comparison Group Both Haemophilus & Pnuemococcus had higher rates of carriage in the Grommet group – which was statistically significant

Nasopharyngeal Samples: Bacterial Culture N = 217 60% positive for 2 or 3 otopathogens % In Grommet group – H inf most common organism Moraxella most common NP organism in Comparison Group Both Haemophilus & Pnuemococcus had higher rates of carriage in the Grommet group – which was statistically significant

Nasopharyngeal Samples: Viral PCR n = 217 % In Grommet group – H inf most common organism Moraxella most common NP organism in Comparison Group Both Haemophilus & Pnuemococcus had higher rates of carriage in the Grommet group – which was statistically significant

Nasopharyngeal Samples: Bacterial Culture & Viral PCR n = 217 Negative Viral only Bacterial only % Bacterial & Viral In Grommet group – H inf most common organism Moraxella most common NP organism in Comparison Group Both Haemophilus & Pnuemococcus had higher rates of carriage in the Grommet group – which was statistically significant No significant correlation between any specific bacteria & virus

Middle ear findings Serous Dry 13% 18% Purulent 12% 57% Mucoid Grommet patients n = 217 Number of ears 434 Middle ear samples 376 Patients with unilateral effusions 58 (27%) 159 (73%) Serous Dry 13% 18% Purulent 12% 57% Mucoid

Bacterial & Viral PCR Middle Ear Fluid (n = 376) Virus only 28% 33% 20% 19%

Middle Ear Samples: n = 376 Microbiology: Bacterial Culture % of Samples

Middle Ear Samples: n = 376 Microbiology: Bacterial Culture vs PCR % of Samples

Middle Ear Samples: Viral PCR n = 376 % of Samples

Viral PCR: Nasopharynx vs MEF %

Conclusions Young children in NZ with ear disease: Detection of bacteria & viruses in the nasopharynx is high H.influenzae is the dominant bacteria in NP & MEF Rhinovirus is the dominant virus in NP & MEF Supportive evidence for mixed aetiology of otitis media Nasopharynx +ve: Viruses and bacteria in 68% Middle ear fluid +ve: Bacterial PCR 39% Viral PCR in 42% PCR for both Bacteria & Viruses in 19% Multivariate analyses did not identify significant correlations between pathogens or exposures

OMIVI Research Team Infectious Diseases Consultants ENT Consultants: Emma Best (ADHB) Tony Walls (CDHB) David Murdoch (CDHB) ENT Consultants: Nikki Mills (ADHB) Murali Mahadevan (ADHB) Colin Barber (ADHB) Michel Neeff (ADHB) Colin Brown (ADHB) Lesley Salkeld (ADHB & CMDHB) Zahoor Ahmad (CMDHB) Mel Souter (CDHB) Microbiology: Scientific Officer Trevor Anderson Research Nurses: Debby Sandow (ADHB) Eileen Andreas (ADHB) Miriam Logan (ADHB) Mandy Retter (CMDHB) Kirstin Davey (CMDHB Raewyn Wright (CDHB) Louise Burgess(CDHB) Research Assistant Shamini Mahadevan A+ Research Trust: Genevieve Morris Boris Mauwa (Accountant) Statistician: Cameron Walker (UoAuck)

Thanks Under 3 year old New Zealander