Pneumococcal Carriage, Serotypes, and Antibiotic Resistance in Malaysian Children: A Multi-Centre Study (MY-PNEUMO2)

Nasopharyngeal Carriage, Serotype Distribution, and Antimicrobial Resistance Profile of Streptococcus Pneumoniae in Malaysian Children: A Prospective Multi-Centre Study

The goal of this observational study is to determine the prevalence, serotype distribution, and antimicrobial resistance patterns of nasopharyngeal carriage of Streptococcus pneumoniae in Malaysian children aged ≤5 years following the implementation of pneumococcal conjugate vaccines (PCVs). The study focuses on healthy and mildly symptomatic male and female children aged 0-60 months recruited from urban and semi-urban settings in Kuala Lumpur, Selangor, and Negeri Sembilan.

The main questions it aims to answer are:

1. What is the overall and age-specific prevalence of nasopharyngeal pneumococcal carriage among children aged ≤5 years in Malaysia?
2. What are the circulating serotypes and antimicrobial resistance (AMR) profiles of pneumococcal isolates, and how are they associated with vaccination status and PCV valency coverage?

Researchers will compare carriage prevalence, serotype distribution (vaccine-type vs non-vaccine-type), and antimicrobial resistance patterns across different states, vaccination statuses, and socioeconomic backgrounds to determine differences in transmission dynamics and potential serotype replacement patterns.

Participants will:

1. Undergo a nasopharyngeal swab collection for pneumococcal detection.
2. Provide demographic and vaccination history information through a standardised case report form completed with parental/guardian consent.
3. Have their samples analysed using bacterial culture, antimicrobial susceptibility testing, and whole-genome sequencing (WGS) for serotyping and resistance profiling.

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Carriage of Streptococcus Pneumoniae

Detailed Description

Nasopharyngeal colonisation with Streptococcus pneumoniae (Spn) is common in children under five and serves as a reservoir for transmission, a precursor to disease, and an indicator of circulating serotypes within communities. While often asymptomatic, pneumococcal carriage contributes to the development of respiratory tract infections and the spread of antimicrobial resistance (AMR) (1-3). In Malaysia, pneumonia remains the third leading principal cause of death among children under five (4), and pneumococcal carriage is central to its pathogenesis. Spn is one of the primary bacterial agents responsible for childhood pneumonia and other serious infections, including otitis media, bacteremia, and meningitis (5). However, prior to causing disease, S. pneumoniae typically colonises the nasopharynx, particularly in young children, making nasopharyngeal carriage a key epidemiological marker for disease risk, serotype circulation, and transmission dynamics (6,7).

The background of this study is rooted in the recent evolution of Malaysia's National Immunisation Programme (NIP). While pneumococcal conjugate vaccines (PCVs) have been available in the private sector for years, the Malaysian government officially introduced the vaccine into the NIP in December 2020, initially using the 10-valent vaccine (PCV10) before transitioning to the 13-valent version (PCV13) in 2023. This transition created a unique epidemiological landscape where different cohorts of children have received different vaccine formulations. Current surveillance in Malaysia has largely focused on invasive disease cases in hospital settings, leaving a significant "data gap" regarding how the vaccine is affecting the general population of children who carry the bacteria. Understanding this community carriage is essential because it reveals "serotype replacement"-a phenomenon where non-vaccine strains emerge to fill the ecological niche left by the strains targeted by the vaccine. Furthermore, the rising threat of antimicrobial resistance (AMR) in S. pneumoniae complicates treatment, as many strains are becoming less sensitive to common antibiotics like penicillin and erythromycin.

The primary objective of this prospective, multi-centre, cross-sectional study is to establish a comprehensive baseline of pneumococcal carriage, serotype distribution, and antimicrobial resistance patterns among Malaysian children aged five years and below. By adopting a prospective cross-sectional design, the research aims to determine the point prevalence of carriage in both healthy and mildly symptomatic children across a specific temporal snapshot. Utilizing advanced laboratory techniques, the study intends to identify which specific serotypes are circulating in the community and evaluate the extent to which current vaccines (PCV13) cover these strains. Additionally, the study seeks to map the AMR profiles of these isolates to understand how resistance genes are distributed across different serotypes and geographic locations. A secondary but vital objective is to compare these findings across different urban and semi-urban settings in Kuala Lumpur, Selangor, and Negeri Sembilan to identify socioeconomic or regional variations in transmission.

To achieve these goals, the study will recruit 600 children from diverse settings, including daycare centers and outpatient clinics, ensuring the data reflects the community rather than just the sickest patients in hospitals. Each participant will undergo a nasopharyngeal swab collection, and a standardized case report form will be used to record their demographic details and precise vaccination history. The collected samples will undergo rigorous analysis at the IMU Central Laboratory, employing both traditional bacterial culture and state-of-the-art Whole-Genome Sequencing (WGS). WGS allows for high-resolution serotyping and the detection of specific resistance markers, providing a level of detail that traditional methods cannot reach. By linking the genomic data of the bacteria with the vaccination status of the children within this prospective framework, the study will provide the evidence-based insights necessary for health authorities to decide on future strategies, such as the potential implementation of higher-valent vaccines like PCV15 or PCV20.

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

• Study Contact: Name: Nurul Hanis Ramzi; Phone Number: +60173396532; Email: nurulhanis@imu.edu.my
• Study Contact Backup: Name: Erwin Khoo Jiayuan; Phone Number: +60123678175; Email: jiayuan_khoo@imu.edu.my

Study Locations

• Malaysia
  • Kuala Lumpur
    • Kuala Lumpur, Kuala Lumpur, Malaysia, 58100
      • Recruiting
      • KMI Taman Desa Medical Centre
      • Contact: Lim Menq Keong; Phone Number: +60176044995; Email: mktor17@gmail.com
      • Principal Investigator: Lim Menq Keong
  • Negeri Sembilan
    • Seremban, Negeri Sembilan, Malaysia, 70300
      • Recruiting
      • Hospital Tuanku Jaafar
      • Contact: David Ng Chun-Ern; Phone Number: +60178806188; Email: davidngce@gmail.com
      • Principal Investigator: David Ng Chun-Ern
    • Seremban, Negeri Sembilan, Malaysia, 70200
      • Recruiting
      • CMH Specialist Hospital
      • Contact: Chew Joling; Phone Number: +60126563661; Email: cjoling17@gmail.com
      • Principal Investigator: Chew Joling
  • Selangor
    • Shah Alam, Selangor, Malaysia, 40000
      • Recruiting
      • Avisena Women's & Children Specialist Hospital
      • Contact: Tan Eng Kian, MBBS; Phone Number: +60122839516; Email: ektan369@gmail.com
      • Principal Investigator: Tan Eng Kian

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

All children meeting the inclusion criteria, attending GP clinics, the outpatient department or admitted as hospital inpatients in sentinel teaching hospital sites. 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 ≤5 years (0-60 months)
• Hemodynamically stable at the time of sampling
• Parent/guardian provides written informed consent
• Resident in Malaysia for at least 3 months prior to enrolment

Exclusion Criteria:

• Current or recent antibiotic use within the last 30 days
• Known to have an immunodeficiency or currently on chemotherapy, or post-transplant recipients or on high-dose steroids (defined as >20mg/day or 2mg/kg/day of Prednisolone for 2 weeks or more)
• Has nasal surgery
• Refusal of consent by parent or guardian

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Pneumococcal Carriage Group; A single cohort of 600 children aged 0 to 60 months (≤5 years) recruited from urban and semi-urban community settings in Kuala Lumpur, Selangor, and Negeri Sembilan. This group includes healthy children and those with mild, self-limiting symptoms attending daycare centres, outpatient paediatric clinics, and community healthcare facilities. All participants will undergo a one-time nasopharyngeal swab collection to determine the prevalence, serotype distribution, and antimicrobial resistance patterns of Streptococcus pneumoniae carriage.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of Streptococcus pneumoniae (Spn) nasopharyngeal carriage among children aged ≤5 years.	The presence or absence of nasopharyngeal pneumococcal carriage will be determined using standard bacteriological culture methods. Confirmed S. pneumoniae isolates will be processed for DNA extraction, and the prevalence will be calculated as the proportion of children carrying the bacteria within the total sampled population of 600.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serotype distribution and Antimicrobial Resistance (AMR) profiles of Streptococcus pneumoniae (Spn) isolates	Spn isolates will be sequenced using a Whole-Genome Sequencing (WGS) platform (Illumina) to determine the circulating serotypes and sequence types (MLST). The genomic data will also be analyzed to identify resistance genes and susceptibility patterns. This will allow for an assessment of vaccine-type (VT) versus non-vaccine-type (NVT) distribution and the coverage provided by PCV13, PCV15, and PCV20.	18 months

Collaborators and Investigators

• Sponsor: IMU University, Malaysia
• Investigators: Principal Investigator: Nurul Hanis Ramzi, IMU University, Malaysia

Publications and helpful links

General Publications

• Adegbola RA, DeAntonio R, Hill PC, Roca A, Usuf E, Hoet B, Greenwood BM. Carriage of Streptococcus pneumoniae and other respiratory bacterial pathogens in low and lower-middle income countries: a systematic review and meta-analysis. PLoS One. 2014 Aug 1;9(8):e103293. doi: 10.1371/journal.pone.0103293. eCollection 2014.
• Bogaert D, van Belkum A, Sluijter M, Luijendijk A, de Groot R, Rumke HC, Verbrugh HA, Hermans PW. Colonisation by Streptococcus pneumoniae and Staphylococcus aureus in healthy children. Lancet. 2004 Jun 5;363(9424):1871-2. doi: 10.1016/S0140-6736(04)16357-5.
• Zakiyah N, Insani WN, Suwantika AA, van der Schans J, Postma MJ. Pneumococcal Vaccination for Children in Asian Countries: A Systematic Review of Economic Evaluation Studies. Vaccines (Basel). 2020 Jul 30;8(3):426. doi: 10.3390/vaccines8030426.
• Sallam M, Abbadi J, Natsheh A, Ababneh NA, Mahafzah A, Ozkaya Sahin G. Trends in Antimicrobial Drug Resistance of Streptococcus pneumoniae Isolates at Jordan University Hospital (2000(-)2018). Antibiotics (Basel). 2019 Apr 12;8(2):41. doi: 10.3390/antibiotics8020041.
• Siira L, Vestrheim DF, Winje BA, Caugant DA, Steens A. Antimicrobial susceptibility and clonality of Streptococcus pneumoniae isolates recovered from invasive disease cases during a period with changes in pneumococcal childhood vaccination, Norway, 2004-2016. Vaccine. 2020 Jul 22;38(34):5454-5463. doi: 10.1016/j.vaccine.2020.06.040. Epub 2020 Jun 30.
• Aspa J, Rajas O, de Castro FR. Pneumococcal antimicrobial resistance: therapeutic strategy and management in community-acquired pneumonia. Expert Opin Pharmacother. 2008 Feb;9(2):229-41. doi: 10.1517/14656566.9.2.229.

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: April 16, 2026
• First Submitted That Met QC Criteria: April 16, 2026
• First Posted (Actual): April 22, 2026

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Streptococcus pneumoniae; nasopharyngeal carriage
• Other Study ID Numbers: 4.12/JCM-322/2025; 100064489 (Other Grant/Funding Number: Pfizer)

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