Pneumococcal Carriage and Serotype Distribution in Children With Otitis Media in Malaysia. (OM)

The purpose of this research is to conduct a multi-center prospective surveillance study focusing upon pneumococcal carriage and serotype epidemiology in patients with otitis media (OM).The data generated will be crucial especially as baseline data for future assessments on the long-term impacts of pneumococcal conjugate vaccine 10 (PCV10) coverage, compared to that of pneumococcal conjugate vaccine 13 (PCV13) that is being used in the majority of other countries. Pneumococcal carriage in patients with OM and serotype distribution will be assessed, including changes in antibiotic resistance. With the establishment of sentinel surveillance in the country, we hope to provide detailed data on the epidemiology of OM in Malaysia; working towards the development of a national surveillance programme for the monitoring of OM burden in the country.

Study Overview

• Status: Recruiting
• Conditions: Otitis Media; Streptococcus Pneumonia

Detailed Description

Otitis media (OM) is a condition defined as an inflammation of the middle ear and is one of the most commonly diagnosed infections in children, especially amongst those aged below 5 years (1). By 3 years of age, approximately 80% of children have experienced at least one episode of acute otitis media (AOM) in developed countries. More than 700 million AOM cases are reported annually worldwide at an incidence rate of 10.8%, with Southeast Asia reporting a yearly incidence of 8.2% and disease burden varying substantially by geographical location (2). In Malaysia, based on data published from a population based survey (n=7,041) conducted by the Ministry of Health in 2005 (3),OM with effusion (OME) prevalence was found to be 2.9% amongst individuals all ages, of which 46.5% suffered from hearing loss. Amongst children, OME prevalence was 3.8% in those aged ≤17 years, 1.4% in 13-17 year olds and 2.3% in children ≤12 years of age. The survey also found that prevalence was higher in rural settings (3.2%) compared to urban settings (2.7%). These findings were in contrast to an earlier cross-sectional study based on 5 to 6 years olds from kindergartens in 1993 (n=1,097), where prevalence was 17.9% in the urban district of Kuala Lumpur compared to 9.5% in rural Kuala Selangor (4). AOM was found in Malaysia to have a negative impact on both parental and child quality of life (QoL), with significant indirect healthcare costs and thus substantial economic burden in the population (5).

Studies on the epidemiology of AOM, especially those reliant upon clinical diagnosis and following the uptake of pneumococcal conjugate vaccination (PCV) are few and far between. In Malaysia the prevalence of OME, as described above, has been reported although limited to specific settings and locations, with even fewer assessments on AOM prevalence. Immunisation programmes against Spn have an impact on carriage, and consequently the causative pathogen and infecting strains of Spn in OM infections. There has been a consistent observed association between PCV introduction and a decline of AOM infections caused by Spn. As Malaysia is one of the more recent countries to start the PCV National Immunisation Programme (NIP), this presents an excellent opportunity to begin surveillance on pneumococcal carriage and serotype distribution allowing for a detailed assessment of the epidemiology of OM in the country.

Specific Objectives

1. To determine the prevalence of Streptococcus pneumoniae (Spn) nasopharyngeal carriage among children 5 years of age and below with OM
2. To determine Spn serotypes in children diagnosed with OM

• Study Type: Observational
• Enrollment (Estimated): 360

Contacts and Locations

• Study Contact: Name: Nur Alia Johari, PhD; Phone Number: +60 12 234 5651; Email: NurAliaJohari@imu.edu.my
• Study Contact Backup: Name: Nurul Hanis Ramzi, PhD; Phone Number: +60 17 339 6532; Email: nurulhanis@imu.edu.my

Study Locations

• Malaysia
  • Pahang
    • Kuantan, Pahang, Malaysia, 57000
      • Recruiting
      • Sultan Ahmad Shah Medical Centre @International Islamic University Malaysia
      • Contact: Zamzil Amin Ash'ari, MBBS; Email: zamzilamin@iium.edu.my
      • Contact: Norhidayah Kamarudin, MBBS; Email: norhidayahkamarudin@iium.edu.my;
      • Principal Investigator: Ailin Razali, MBBS
      • Sub-Investigator: Zamzil Amin Ash'ari, MBBS
      • Sub-Investigator: Norhidayah Kamarudin, MBBS
  • Seri Kembangan
    • Serdang, Seri Kembangan, Malaysia, 43400
      • Recruiting
      • Universiti Putra Malaysia
      • Contact: Atiqah Farah Zakaria, MBBS; Email: atiqahfarah@gmail.com
      • Contact: Saraiza Abu Bakar, MBBS; Email: drsaraiza@yahoo.com
      • Principal Investigator: Atiqah Farah Zakaria, MBBS
      • Sub-Investigator: Saraiza Abu Bakar, MBBS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 5 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All children meeting the inclusion criteria, attending general practitioner clinics, the outpatient department or admitted as hospital inpatients in sentinel teaching hospital sites (International Islamic University Malaysia, Universiti Putra Malaysia and Hospital Serdang). Male and female patients from the three major ethnic groups (Malay, Chinese, and Indian) will be recruited from each sentinel site.

Description

Inclusion Criteria:

Children aged ≥3 months and <5 years with clinically diagnosed AOM/CSOM whose parent/legal authorized representative (LAR) is willing to give consent on his/her behalf and attending general practitioner clinics, the ear, nose and throat (ENT) outpatient's department or admitted as a hospital inpatient at hospital sites.

Exclusion Criteria:

Any child aged ≥3 months and <5 years old

• who does not meet the case definition
• whose parent/guardian does not give consent on his/her behalf.
• who had nasal surgery,
• who has chronic respiratory diseases (including asthma) and cardiac condition
• with tympanostomy tubes

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Otitis Media (OM) Case Group; Case definition: Acute otitis media (AOM)AOM will be diagnosed by pneumatic otoscopy by validated otoscopists, when children with acute onset of otalgia had tympanic membranes (TMs) that were:bulging or full; anda cloudy or purulent effusion was observed, or the TM was completely opacified; andTM mobility was reduced or absent; Otitis media with effusion (OME)Collection of fluid within the middle ear without signs of acute inflammation, fever or otorrhea. Otoscopic findings include:dull tympanic membrane (TM)retraction of TMfluid level or air bubbleTM colour changerestricted TM mobility with pneumatic otoscopy; Chronic suppurative otitis media (CSOM) Otoscopic findings: Perforated TM; Mucopurulent discharge

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of Streptococcus pneumoniae (Spn) nasopharyngeal (NP) carriage among young children with OM (AOM/OME/CSOM).	The absence/presence of nasopharyngeal pneumococcal carriage will be tested using standard bacteriological methods and Streptococcus Pneumoniae (SPN) isolates will be inoculated for DNA extraction and tested by polymerase chain reaction (PCR) for pneumococcal carriage detection.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serotype distribution of Streptococcus pneumoniae (Spn) among young children with OM (AOM/OME/CSOM).	Spn isolates will be sequenced using whole-genome sequencing (WGS) platform (Illumina, UK) to determine the infecting serotype(s) among children with OM. Serotype and sequence type will be derived from the genomic data using a pipeline to identify the serotype from Illumina WGS reads for given references and multilocus sequence type respectively.	12 months

Collaborators and Investigators

• Sponsor: International Medical University
• Collaborators: Merck Sharp & Dohme LLC; Universiti Putra Malaysia; University of Southampton; International Islamic University Malaysia; Hospital Serdang
• Investigators: Principal Investigator: Lokman Hakim Sulaiman, PhD, International Medical University

Publications and helpful links

General Publications

• Monasta L, Ronfani L, Marchetti F, Montico M, Vecchi Brumatti L, Bavcar A, Grasso D, Barbiero C, Tamburlini G. Burden of disease caused by otitis media: systematic review and global estimates. PLoS One. 2012;7(4):e36226. doi: 10.1371/journal.pone.0036226. Epub 2012 Apr 30.
• Mahadevan M, Navarro-Locsin G, Tan HK, Yamanaka N, Sonsuwan N, Wang PC, Dung NT, Restuti RD, Hashim SS, Vijayasekaran S. A review of the burden of disease due to otitis media in the Asia-Pacific. Int J Pediatr Otorhinolaryngol. 2012 May;76(5):623-35. doi: 10.1016/j.ijporl.2012.02.031. Epub 2012 Mar 8.
• Institute For Public Health. Findings of the National Hearing and Ear Disorders Survey. Malaysia: Institute For Public Health, National Instiutes of Health, Ministry of Health Malaysia; 2009.
• Saim A, Saim L, Saim S, Ruszymah BH, Sani A. Prevalence of otitis media with effusion amongst pre-school children in Malaysia. Int J Pediatr Otorhinolaryngol. 1997 Jul 18;41(1):21-8. doi: 10.1016/s0165-5876(97)00049-9.
• Crawford B, Hashim SS, Prepageran N, See GB, Meier G, Wada K, Coon C, Delgleize E, DeRosa M. Impact of Pediatric Acute Otitis Media on Child and Parental Quality of Life and Associated Productivity Loss in Malaysia: A Prospective Observational Study. Drugs Real World Outcomes. 2017 Mar;4(1):21-31. doi: 10.1007/s40801-016-0099-9.

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2023
• Primary Completion (Estimated): April 5, 2024
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: June 19, 2022
• First Submitted That Met QC Criteria: June 19, 2022
• First Posted (Actual): June 23, 2022

Study Record Updates

• Last Update Posted (Actual): August 7, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia; Lung Diseases; Otorhinolaryngologic Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Ear Diseases; Pneumonia, Bacterial; Pneumococcal Infections; Pneumonia, Pneumococcal; Otitis; Otitis Media
• Other Study ID Numbers: MISP #61353

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No