Clinical trial NCT04923035: Paediatric Pneumococcal Pneumonia in Malaysia Prior to and During Pneumococcal Conjugate Vaccine (PCV) Implementation
Official title: Evaluating the Burden of Paediatric Pneumococcal Pneumonia in Malaysia Prior to and During Pneumococcal Conjugate Vaccine (PCV) Implementation
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Pneumonia, Pneumococcal
Pneumonia Childhood
Keywords: surveillance
polymerase chain reaction
whole-genome sequencing
pneumococcal urine antigen detection
correlation analysis
Lead sponsor: International Medical University
Sponsor class: OTHER
Collaborators: name: University of Malaya
name: Universiti Sains Malaysia
name: International Islamic University Malaysia
name: University of Southampton
name: Merck Sharp & Dohme LLC
First posted: 2021-06-11
Enrollment: 1010
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Nasopharyngeal (NP) pneumococcal carriages prevalence rate among young children
timeFrame: 24 months
Secondary outcomes:
measure: Streptococcus pneumoniae (SPN) detection in urine samples among young children
timeFrame: 24 months
Other outcomes:
Locations:
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
state: Federal Territory Of Kuala Lumpur
city: Kota Bharu
country: Malaysia
facility: Hospital Universiti Sains Malaysia
state: Kelantan
city: Kuantan
country: Malaysia
facility: Sultan Ahmad Shah Medical Centre @International Islamic University Malaysia
state: Pahang
Study officials:
affiliation: International Medical University
name: Lokman Hakim H Sulaiman, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.