Paediatric Infections Point-Of-Care

NCT ID: NCT03900091

Last Updated: 2020-12-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

351 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-04-01

Study Completion Date

2020-07-24

Brief Summary

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This study aims to identify the aetiology of childhood meningitis in Southwestern Uganda and develop and evaluate new methods for point-of-care diagnosis of childhood meningitis in a low-income setting. A prospective observational study including 600 children aged 0-12 years will be conducted during 1 year in Mbarara, Uganda. We estimate to recruit about 300 children with suspected meningitis (cases), and 300 with non-severe infection age-matched as controls.

Detailed Description

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The current gold standard for laboratory diagnostics of suspected childhood meningitis are microbiology culture of CSF and polymerase chain reaction (PCR). However, these methods are expensive, time-consuming, require dedicated facilities and trained professionals, that are often lacking in low-income health systems. Our team has developed a new vertical flow paper printed microarray method for rapid, inexpensive and multiplexed microbiology analysis of cerebrospinal fluid (CSF), with potential for point-of-care use in low-income settings. This study will evaluate the diagnostic accuracy of this newly developed paper printed microarray method.

The bioMérieux FilmArray® ME Panel is an existing multiplexed PCR based system for rapid microbiology analyses of CSF. Even though previous studies have reported good diagnostic accuracy of the FilmArray® system, the studies have mostly been focused on evaluating the system in high-income settings.

This study will do a field evaluation of the diagnostic performance and clinical usability of the FilmArray® ME Panel in a low-income setting in Mbarara, Uganda.

A study by Page et al, conducted 2009-2012 in Mbarara, Uganda, identified the most frequent pathogen causing childhood bacterial meningitis to be Streptococcus pneumoniae. This is also the case on a global level, with the addition of the bacteria Neisseria meningitidis and Haemophilus influenzae type B. However, the Page study did not find a single case of Neisseria meningitidis, which is in contrast to most other reports from low-, middle- and high-income countries. Furthermore, after the finalisation of the Page study, pneumococcal conjugate vaccines were introduced to the Ugandan childhood immunisation program. This study will identify the current aetiology of childhood meningitis and the impact of the pneumococcal conjugate vaccine, in Mbarara, Uganda, and also study the carriage and characteristics of Neisseria meningitis in children in the area.

Myxovirus resistance protein A (MxA) blood levels have been reported to be elevated in children with respiratory tract infections of viral aetiology, as compared to bacterial aetiology. Previous studies have also shown a higher abundance of MxA in viral encephalitis, however this only through histological analyses of post-mortem brain tissue samples.

This study aims to investigate the correlation of blood MxA levels in children with viral, bacterial and malarial meningitis in Mbarara, Uganda by analysing the protein profile and temporal dynamic in blood of children with severe and non-severe infection.

Conditions

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Meningitis Pediatric Infectious Diseases

Keywords

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Point of care Diagnostics Low-income countries Meningitis Pediatrics MxA FilmArray Low-cost diagnostics

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Cases with clinical meningitis

Patients aged 0-12 years with suspected CNS infection, at the pediatric clinics at Mbarara Regional Referral Hospital or Holy Innocents Children's Hospital, Mbarara, Uganda.

Multiplex PCR assay for meningitis

Intervention Type DIAGNOSTIC_TEST

CSF from cases to be analysed with a FilmArray ME Panel

Multiplex vertical flow microarrray assay for meningitis

Intervention Type DIAGNOSTIC_TEST

CSF from cases will also undergo analysis with a newly developed prototype for point-of-care diagnostic tool for CNS infections identification. The tool is a DNA-based vertical flow microarray technology printed on paper.

Profiling of blood proteins by multi-analyte Profiling technology

Intervention Type DIAGNOSTIC_TEST

Blood from cases and controls to be analysed using Luminex technology to identify protein profiles associated with severe and non-severe infection. Myxovirus protein A (MxA) will also be analysed by the Luminex assay, to associate MxA levels with severe/non-severe infection.

Typing and whole genome sequencing

Intervention Type OTHER

Pathogenic strains isolated from nasopharyngeal swabs from cases and controls will undergo whole genome sequencing (WGS) and typing .

Control subjects

Patients aged 0-12 years, visiting the outpatient pediatric clinics at Mbarara Regional Referral Hospital or Holy Innocents Children's Hospital, Mbarara, Uganda, with fever clinically considered non-severe.

Profiling of blood proteins by multi-analyte Profiling technology

Intervention Type DIAGNOSTIC_TEST

Blood from cases and controls to be analysed using Luminex technology to identify protein profiles associated with severe and non-severe infection. Myxovirus protein A (MxA) will also be analysed by the Luminex assay, to associate MxA levels with severe/non-severe infection.

Typing and whole genome sequencing

Intervention Type OTHER

Pathogenic strains isolated from nasopharyngeal swabs from cases and controls will undergo whole genome sequencing (WGS) and typing .

Interventions

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Multiplex PCR assay for meningitis

CSF from cases to be analysed with a FilmArray ME Panel

Intervention Type DIAGNOSTIC_TEST

Multiplex vertical flow microarrray assay for meningitis

CSF from cases will also undergo analysis with a newly developed prototype for point-of-care diagnostic tool for CNS infections identification. The tool is a DNA-based vertical flow microarray technology printed on paper.

Intervention Type DIAGNOSTIC_TEST

Profiling of blood proteins by multi-analyte Profiling technology

Blood from cases and controls to be analysed using Luminex technology to identify protein profiles associated with severe and non-severe infection. Myxovirus protein A (MxA) will also be analysed by the Luminex assay, to associate MxA levels with severe/non-severe infection.

Intervention Type DIAGNOSTIC_TEST

Typing and whole genome sequencing

Pathogenic strains isolated from nasopharyngeal swabs from cases and controls will undergo whole genome sequencing (WGS) and typing .

Intervention Type OTHER

Other Intervention Names

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Biomerieux FilmArray ME Panel Luminex Multi-Analyte Profiling (xMAP)

Eligibility Criteria

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Inclusion Criteria

* Children aged 0 months to 12 years of age, who
* meet the case or control definition criteria, and where
* informed consent is obtained from the parent or guardian

* No, insufficient or inappropriate CSF sample collection
Minimum Eligible Age

1 Day

Maximum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mbarara University of Science and Technology

OTHER

Sponsor Role collaborator

Science for Life Laboratory

UNKNOWN

Sponsor Role collaborator

Epicentre Mbarara Research Center

UNKNOWN

Sponsor Role collaborator

Stockholm South General Hospital

OTHER

Sponsor Role collaborator

Karolinska Institutet

OTHER

Sponsor Role lead

Responsible Party

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Tobias Alfvén

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Elias Kumbakumba, MD

Role: PRINCIPAL_INVESTIGATOR

Mbarara University of Science and Technology

Tobias Alfvén, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Locations

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Holy Innocents Children's Hospital

Mbarara, , Uganda

Site Status

Mbarara Regional Referral Hospital

Mbarara, , Uganda

Site Status

Countries

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Uganda

References

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Rasti R, Kumbakumba E, Nanjebe D, Mlotshwa P, Nassejje M, Mzee J, Businge S, Akankwasa G, Nyehangane D, Gantelius J, Boum Y 2nd, Martensson A, Mwanga-Amumpaire J, Alfven T, Gaudenzi G. Clinical utility of the FilmArray(R) meningitis/encephalitis panel in children with suspected central nervous system infection in a low-resource setting - a prospective study in Southwestern Uganda. BMC Infect Dis. 2025 Mar 22;25(1):396. doi: 10.1186/s12879-025-10732-w.

Reference Type DERIVED
PMID: 40121439 (View on PubMed)

Gaudenzi G, Kumbakumba E, Rasti R, Nanjebe D, Reu P, Nyehangane D, Martensson A, Nassejje M, Karlsson J, Mzee J, Nilsson P, Businge S, Loh E, Boum Ii Y, Andersson-Svahn H, Gantelius J, Mwanga-Amumpaire J, Alfven T. Point-of-Care Approaches for Meningitis Diagnosis in a Low-Resource Setting (Southwestern Uganda): Observational Cohort Study Protocol of the "PI-POC" Trial. JMIR Res Protoc. 2020 Nov 4;9(11):e21430. doi: 10.2196/21430.

Reference Type DERIVED
PMID: 33146628 (View on PubMed)

Other Identifiers

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2018/1676-31/1

Identifier Type: -

Identifier Source: org_study_id