Urine Pneumococcal Antigen Project

NCT ID: NCT07181200

Last Updated: 2025-09-18

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 350 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-10-31
• Study Completion Date: 2027-08-31

Brief Summary

Background:Pneumonia caused by the bacteria Streptococcus pneumoniae is a leading cause of death among children under five years of age, especially in sub-Saharan Africa. Accurate diagnosis remains challenging due to the need for invasive procedures to obtain samples for culture-based diagnostic tests, which are not very sensitive for detecting S.pneumoniae, particularly after antibiotic use.

Serotype-specific urinary antigen detection (ssUAD) assays are a promising, non-invasive alternative for the surveillance and diagnosis of pneumococcal disease. Importantly, they can identify different serotypes of S.pneumoniae, which is crucial for monitoring vaccine impact. However, the ability of the ssUAD to identify invasive disease due to S.pneumoniae has not been studied in children in sub-Saharan Africa, where high rates of asymptomatic carriage may affect diagnostic accuracy.

Aim:

The overall aim of this study is to evaluate the performance of the ssUAD test to detect pneumococcal carriage, and distinguish it from invasive disease, among children under five years old in Blantyre, Malawi.

Methods:This study will test 350 existing urine samples that have already been collected from children as part of the NP Resistome study (Protocol V 5.0, LSTM reference 24-076), including healthy children in the community, children with pneumonia in the community, and children hospitalised with pneumonia. Participants of the NP Resistome study will be recruited from Ndirande Health Centre (NHC), Gateway Primary Care Centre (GPCC) and Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi. Aliquots from each urine sample will be tested using the ssUAD in the UK, as the assay is not currently available in Malawi. Urinary detection of pneumococcal serotypes will be compared with both culture-based and metagenomic sequencing results from nasopharyngeal swab samples taken as part of the main study.

Detailed Description

Study type: This is a nested case-control sub-study within the multi-site, observational NP Resistome study (COMREC reference P.10/24-1200).

Background:

Pneumococcal pneumonia is a leading cause of morbidity and mortality among children under five, especially in sub-Saharan Africa. Accurate diagnosis remains a challenge due to the need for invasive specimen collection and poor sensitivity of standard culture-based diagnostic tests, particularly after antibiotic use. Serotype-specific urinary antigen detection (ssUAD) offers a promising, non-invasive alternative for serotype surveillance and diagnosis of pneumococcal disease. Serotype-specific identification provided by ssUAD is crucial for monitoring the impact of vaccines and informing public health interventions. The ssUAD test is a Luminex-based urine antigen capture assay developed by the UK Health Security Agency (UKHSA) that targets 24 pneumococcal serotypes, with good sensitivity and specificity among adults with community-acquired pneumonia in the UK. Further investigation is required to determine its ability/utility to identify invasive disease among children, particularly in settings like sub-Saharan Africa, where high rates of asymptomatic carriage may affect diagnostic accuracy.

Broad Objective: To evaluate the performance of the ssUAD test in detecting pneumococcal carriage and distinguishing it from invasive disease among children under five years old in Blantyre, Malawi.

Specific Objectives:

1. To determine the prevalence of serotype-specific pneumococcal antigens in urine among children under five years of age with pneumonia compared to their healthy counterparts.

2. To characterise the association between the detection of serotype-specific antigens in urine and nasopharyngeal pneumococcal carriage among children.

3. To define revised ssUAD thresholds that may distinguish pneumococcal carriage from disease, to support field evaluations and inform diagnostic and surveillance strategies in Malawi and similar settings.

Methodology: We will test 350 existing urine samples that have already been collected from children as part of the NP Resistome study (Protocol v5.0 COMREC reference P.10/24-1200), including healthy children in the community, children with pneumonia in the community, and children hospitalised with pneumonia at the time of recruitment. Participants of the NP Resistome study will be recruited from Ndirande Health Centre (NHC), Gateway Primary Care Centre (GPCC), and Queen Elizabeth Central Hospital(QECH) in Blantyre, Malawi. Urine samples will be aliquoted into 1.8 mL cryotubes and stored at -80°C at Malawi Liverpool Wellcome Research Programme (MLW) laboratory in Malawi. Aliquots from each urine sample will be tested using the ssUAD in the UK, as the assay is not currently available in Malawi. However, we are working towards developing and evaluating the assay locally as part of future implementation efforts. Urinary detection of pneumococcal serotypes will be compared with both culture-based and metagenomic sequencing results from nasopharyngeal swab (NPS) samples taken as part of the main study.

Expected results and dissemination: This sub-study will generate key data on the prevalence of pneumococcal serotype-specific urinary antigens in children with pneumonia and healthy controls. It will improve understanding of ssUAD performance as a surveillance tool in this setting, help distinguish antigenuria due to carriage from disease, and refine diagnostic thresholds for use in high-carriage and disease-burden settings. Study findings will inform surveillance, pneumonia diagnostics, and vaccine impact assessments in LMICs. Results will be shared with COMREC, the Blantyre District Health Office, at scientific conferences, both local and international, and in peer-reviewed publications.

Conditions

Pneumonia; Pneumonia - Bacterial

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Healthy community

Healthy children living in Ndirande community, aged between 12 and 24 months at recruitment.

No interventions assigned to this group

Community pneumonia

Children aged between 12 and 24 months who have presented to Ndirande Health Centre with a pneumonia clinical syndrome (based on the WHO definition of fever, cough, tachypnoea and dyspnoea) for which they are prescribed antibiotic therapy.

No interventions assigned to this group

Hospital pneumonia - first admission

Children aged between 12 and 24 months who have been admitted to Queen Elizabeth Central Hospital for the first time with a pneumonia clinical syndrome (based on the WHO definition of fever, cough, tachypnoea and dyspnoea) for which they are prescribed antibiotic therapy.

No interventions assigned to this group

Hospital pneumonia - re-admission

Children aged between 12 and 24 months who have been re-admitted to Queen Elizabeth Central Hospital with a pneumonia clinical syndrome (based on the WHO definition of fever, cough, tachypnoea and dyspnoea) for which they are prescribed antibiotic therapy, within 3 months of a previous hospitalisation with pneumonia.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Child aged between12-24 months.

• Child aged between12-24 months.
• Presence of all of the following symptoms: fever, cough, difficulty in breathing and fast breathing.
• Participant has been prescribed antibiotics for treatment of a lower respiratory tract infection on this presentation.

• Child aged between 12-24 months.
• Presence of all of the following symptoms: fever, cough, difficulty in breathing and fast breathing.
• Participant has been prescribed antibiotics for treatment of a lower respiratory tract infection on this presentation.

• Child aged between12-24 months.
• Presence of all of the following symptoms: fever, cough, difficulty in breathing and fast breathing.
• Participant has been prescribed antibiotics for treatment of a lower respiratory tract infection on this presentation.
• Hospital admission to ANY hospital with a lower respiratory tract infection within the past 3 months.

Exclusion Criteria

• Presence of any of the following symptoms: fever, cough, difficulty in breathing or fast breathing.
• Currently taking long-term antibiotic prophylaxis, TB treatment or immunosuppressive medications.
• Diagnosis of an immunosuppressive illness, including HIV infection.
• Hospital admission within the past six months.

• Severe anaemia, with a recorded haemoglobin level < 70 grams per Litre.
• Currently taking long-term antibiotic prophylaxis, TB treatment or immunosuppressive medications.
• Diagnosis of an immunosuppressive illness, including HIV infection.
• Hospital admission within the past six months.

• Severe anaemia, with a recorded haemoglobin level < 70 grams per Litre.
• Currently taking long-term antibiotic prophylaxis, TB treatment or immunosuppressive medications.
• Diagnosis of an immunosuppressive illness, including HIV infection.
• Hospital admission within the past six months.

• Severe anaemia, with a recorded haemoglobin level < 70 grams per Litre.
• Currently taking long-term antibiotic prophylaxis, TB treatment or immunosuppressive medications.
• Diagnosis of an immunosuppressive illness, including HIV infection.

• Minimum Eligible Age: 12 Months
• Maximum Eligible Age: 24 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Malawi Liverpool Wellcome Programme

OTHER

Sponsor Role: collaborator

Liverpool School of Tropical Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brenda Kwambana-Adams, PhD

Role: PRINCIPAL_INVESTIGATOR

LSTM

Central Contacts

Charles B Nkhata, Pre-MSc

Role: CONTACT

cbnkhata@mlw.mw

+265990557781

Brenda Kwambana-Adams, PhD

Role: CONTACT

bkwambana@mlw.mw

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

P.0725-1685

Identifier Type: -

Identifier Source: org_study_id