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

Study Overview
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Brief Summary
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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.

Detailed Description
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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 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. To determine SPN serotypes in young children during the coronavirus disease 2019 (COVID-19) pandemic by whole-genome sequencing analysis. To identify potential changes in clinical presentation and severity of pneumococcal infection in young children during the COVID-19 pandemic. To evaluate the correlations between SPN serotypes detected in NP carriage and urine sample from the same individual/child. To estimate sensitivity and specificity for SPN serotypes detection in urine among children with pneumonia and IPD.

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

Conditions
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Pneumonia, Pneumococcal, Pneumonia Childhood

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Case<br>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<br>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?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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surveillance, polymerase chain reaction, whole-genome sequencing, pneumococcal urine antigen detection, correlation analysis