Paediatric Pneumococcal Pneumonia in Malaysia Prior to and During Pneumococcal Conjugate Vaccine (PCV) Implementation (MSIP PCV)

Evaluating the Burden of Paediatric Pneumococcal Pneumonia in Malaysia Prior to and During Pneumococcal Conjugate Vaccine (PCV) Implementation

The purpose of this research is to provide baseline surveillance of pneumonia in young children in Malaysia before and during the implementation of the pneumococcal conjugate vaccine (PCV). Pneumonia is a respiratory infection that can cause mild to life-threatening disease among all age groups but is the leading infectious cause of death among children globally. The most common cause of pneumonia is infection with a bacteria called Streptococcus pneumoniae, also known as pneumococcus. Hence, immunisation with a pneumococcal vaccine is an effective way to prevent pneumonia. In Malaysia, pneumococcal vaccination under the National Immunisation Programme (NIP) for children has since commenced in December 2020, comprising of 3 doses at four, six and 15 months. The routine use of PCV in children will contribute to reducing the burden of pneumococcal infections in the country, especially severe infections. The ongoing COVID-19 pandemic may also have implications on the pneumococcal serotype and clinical presentation of infections in the community.

Study Overview

• Status: Active, not recruiting
• Conditions: Pneumonia, Pneumococcal; Pneumonia Childhood

Detailed Description

This study will be a multi-centre prospective case-control study and the recruitment of clinically diagnosed pneumonia patients and healthy controls aged 5 years and below will be conducted at the three university hospitals; University Malaya Medical Centre (UMMC), Sultan Ahmad Shah Medical Centre@International Islamic University Malaysia (SASMEC@IIUM) and Hospital University Sains Malaysia (HUSM). Subject recruitment and sample collection will be carried out for 24 months. Informed consent and general questionnaire will be administrated by the on-site researchers. Clinical samples will be taken according to approved protocol and local policy to include nasopharyngeal (NP) swab and urine sample. NP swab in a transport medium will be store at -80°C before shipment to the International Medical University (IMU) Advanced Microbiology Collaborative Research Laboratory (AMCRL) in Kuala Lumpur for polymerase chain reaction (PCR) analysis. The data obtained may provide crucial data to support policy decisions on pneumococcal vaccination.

. Specific Objectives

1. To determine the prevalence of Streptococcus pneumoniae (SPN) nasopharyngeal (NP) carriage among children 5 years of age and below with pneumonia and invasive pneumonia disease (IPD) using polymerase chain reaction (PCR) analysis.
2. To determine SPN serotypes in young children during the coronavirus disease 2019 (COVID-19) pandemic by whole-genome sequencing analysis.
3. To identify potential changes in clinical presentation and severity of pneumococcal infection in young children during the COVID-19 pandemic.
4. To evaluate the correlations between SPN serotypes detected in NP carriage and urine sample from the same individual/child.
5. To estimate sensitivity and specificity for SPN serotypes detection in urine among children with pneumonia and IPD.

• Study Type: Observational
• Enrollment (Actual): 1010

Contacts and Locations

• Study Contact: Name: Nurul Hanis Ramzi, PhD; Phone Number: +60173396532; Email: nurulhanis@imu.edu.my
• Study Contact Backup: Name: Nur Alia Johari, PhD; Phone Number: +60 12-234 5651; Email: NurAliaJohari@imu.edu.my

Study Locations

• Malaysia
  • Federal Territory Of Kuala Lumpur
    • Kuala Lumpur, Federal Territory Of Kuala Lumpur, Malaysia, 57000
      • University Malaya Medical Centre
  • Kelantan
    • Kota Bharu, Kelantan, Malaysia, 16150
      • Hospital Universiti Sains Malaysia
  • Pahang
    • Kuantan, Pahang, Malaysia, 57000
      • Sultan Ahmad Shah Medical Centre @International Islamic University Malaysia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 5 years (Child)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

This is a prospective case-control study in which all children aged 5 years and below with clinically diagnosed community-acquired pneumonia and healthy controls will be recruited at three study sites. As per assumptions of 95% confidence interval (CI), 80% power and detectable odds ratio (OR) of 1.5, The investigators estimate 164 cases and 164 healthy controls per each sentinel hospital site. Thus, the investigators aim to recruit a total of 500 confirmed pneumonia cases and 500 healthy controls for this study.

Description

Inclusion Criteria:

- Any child aged 5 years and below who meets the case and control definition and whose parent/legal authorized representative (LAR) is willing to give consent on his/her behalf.

Exclusion Criteria:

• who does not meet the case and control definition
• whose parent/guardian does not give consent on his/her behalf
• who has nasal surgery

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Case; Children aged 5 years and below with clinically diagnosed pneumonia and attending the outpatient's department or admitted as a hospital inpatient at three sentinel sites. Pneumonia. Suspected pneumonia cases will be identified by a family physician or paediatrician based on medical history and clinical symptoms. Pneumonia is defined as (WHO Fact Sheet 2019) patient with history of: cough and/or; difficulty/rapid breathing and/or; intercostal recession,; with or without fever. and supported by chest x-ray findings.
Control; Healthy children aged 5 years and below without any intercurrent respiratory illness and who is in good health as determined by a brief medical history and/or clinical judgement of the investigator whose parent/LAR is willing and able to give informed consent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nasopharyngeal (NP) pneumococcal carriages prevalence rate among young children	The absence/presence of nasopharyngeal pneumococcal carriages will be tested using standard bacteriological methods and Streptococcus Pneumoniae (SPN) isolates will be inoculated for DNA extraction and further tested by polymerase chain reaction (PCR) for pneumococcal carriage detection.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Streptococcus pneumoniae (SPN) detection in urine samples among young children	To evaluate the correlations between SPN isolates detected in NP carriage and urine sample from the same individual/child.	24 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• La Vincente SF, von Mollendorf C, Ulziibayar M, Satzke C, Dashtseren L, Fox KK, Dunne EM, Nguyen CD, de Campo J, de Campo M, Thomson H, Surenkhand G, Demberelsuren S, Bujinlkham S, Do LAH, Narangerel D, Cherian T, Mungun T, Mulholland EK. Evaluation of a phased pneumococcal conjugate vaccine introduction in Mongolia using enhanced pneumonia surveillance and community carriage surveys: a study protocol for a prospective observational study and lessons learned. BMC Public Health. 2019 Mar 21;19(1):333. doi: 10.1186/s12889-019-6639-y.
• Adetifa IMO, Adamu AL, Karani A, Waithaka M, Odeyemi KA, Okoromah CAN, Bello MM, Abubakar IS, Inem V, Scott JAG. Nasopharyngeal Pneumococcal Carriage in Nigeria: a two-site, population-based survey. Sci Rep. 2018 Feb 22;8(1):3509. doi: 10.1038/s41598-018-21837-5.

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2021
• Primary Completion (Actual): August 29, 2023
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: June 1, 2021
• First Submitted That Met QC Criteria: June 10, 2021
• First Posted (Actual): June 11, 2021

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: correlation analysis; surveillance; polymerase chain reaction; whole-genome sequencing; pneumococcal urine antigen detection
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumonia, Bacterial; Pneumococcal Infections; Pneumonia; Pneumonia, Pneumococcal
• Other Study ID Numbers: MISP #60200

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