Urine Pneumococcal Antigen Project

Официальное название

Accelerating the Development of an Extended-specificity Multiplex Urine Immunoassay for the Diagnosis and Serotyping of Pneumococcal Pneumonia in High Carriage and Disease Burden Settings Like Malawi

Обзор

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.

Подробное описание

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.

Первичные конечные точки

• Serotype specific urinary pneumococcal antigen detection [Срок оценки: At the time of recruitment/participant enrolment.]

Вторичные конечные точки (1)

• Nasopharyngeal pneumococcal carriage [Срок оценки: At time of recruitment/enrolment.]

Критерии участия

Inclusion criteria for healthy children in the community

• Child aged between12-24 months.

Exclusion criteria for healthy children in the community

• 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.

Inclusion criteria for children with pneumonia in the community

• 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.

Exclusion criteria for children with pneumonia in the community

• 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.

Inclusion criteria for children hospitalised with pneumonia

• 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.

Exclusion criteria for children hospitalised with pneumonia

• 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.

Inclusion criteria for children re-hospitalised with pneumonia

• 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 for children re-hospitalised with pneumonia

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07181200 · P.0725-1685

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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